Therapeutic compounds and related methods of use

Abstract

Methods of treating disorders using compounds that modulate striatal-enriched tyrosine phosphatase (STEP), such as those of formula (III), and composition thereof are described herein. Exemplary disorders include schizophrenia and cognitive deficit. ##STR00001##

Claims

1. A compound of formula (III): ##STR03371## or a salt thereof, wherein: A is N; L is NR.sup.6; one of X.sup.1, X.sup.2, X.sup.3, X.sup.4 and X.sup.5 is N and the others are CH; m is 1; n is 0 or 1; R.sup.1 is hydrogen, C.sub.1C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, alkoxyalkyl, hydroxyalkyl, imidazolyl, furylalkyl, pyridylalkyl, phenylalkyl, oxazolylalkyl, thienylalkyl, thiazolidinyl, isoindolyl, C(O)R.sup.e, dihydroindenyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.3-C.sub.8 cycloalkylalkyl, piperidyl, morpholinyl, pyrrolidinyl, azetidinyl or piperazinyl, each of which is optionally substituted with 1-3 R.sup.7; R.sup.2 is phenyl, naphthyl, benzofuryl, indazolyl, benzothienyl, pyridyl, pyrimidinyl, dihydrobenzodioxinyl, benzodioxolyl, benzoimidazolyl, isoxazolyl, pyrazolyl, indolinyl or benzisoxazolyl, each of which is substituted with 1-5 R.sup.9; each R.sup.3 or R.sup.4 is independently hydrogen, C.sub.1-C.sub.8 alkyl, halo, haloalkyl or OR.sup.d; R.sup.6 is hydrogen or C.sub.1-C.sub.8 alkyl; each R.sup.7 and R.sup.9 is independently C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, oxo, CN, NO.sub.2, C(O)OR.sup.a, C(O)NR.sup.bR.sup.b, NR.sup.bR.sup.b, OR.sup.d, C(O)R.sup.e or S(O).sub.qR.sup.f, each of which is optionally substituted with 1-3 R.sup.12; R.sup.12 is independently C.sub.1-C.sub.8 alkyl, oxo, halo, haloalkyl, CN, C(O)NR.sup.bR.sup.bor C(O)R.sup.e, each of which is optionally substituted with 1-3 R.sup.13; R.sup.13 is independently C.sub.1-C.sub.8 alkyl, halo or pyrrolidinyl; and each R.sup.a, R.sup.b, R.sup.b, R.sup.c, R.sup.c, R.sup.d, R.sup.d, R.sup.e and R.sup.f is independently hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.3-C.sub.8 cycloalkyl, pyrrolidinyl, piperidyl, morpholinyl, piperazinyl, tetrahydropyranyl, phenylalkyl, alkoxyalkyl, morpholinylalkyl, oxazolidinylalkyl, imidazolylalkyl, tetrahydropyranylalkyl, pyridylalkyl, pyrazolylalkyl, tetrazolylalkyl, thiazolylalkyl, pyrrolylalkyl, benzoxazolylalkyl, indazolylalkyl, dihydrobenzoxazinylalkyl, tetrahydrofurylalkyl, tetrahydrofuryl, alkylaminoalkyl, dialkylaminoalkyl or phenyl.

2. The compound according to claim 1 represented by general formula (III) or a salt thereof, wherein: R.sup.3 is hydrogen, C.sub.1-C.sub.8 alkyl, halo, haloalkyl, or OR.sup.d; R.sup.4 is hydrogen, C.sub.1-C.sub.8 alkyl, halo, or OR.sup.d; R.sup.7 is C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, oxo, C(O)NR.sup.bR.sup.b or OR.sup.d each of which is optionally substituted with 1-3 R.sup.12; and R.sup.9 is C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, CN, NO.sub.2, C(O)NR.sup.bR.sup.b, C(O)OR.sup.a , NR.sup.bR.sup.b, OR.sup.d, C(O)R.sup.e or S(O).sub.gR.sup.f, each of which is optionally substituted with 1-3 R.sup.12.

3. The compound according to claim 2 represented by general formula (III) or a salt thereof, wherein: R.sup.7 is C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, oxo, C(O)OR.sup.a, C(O)NR.sup.bR.sup.b or OR.sup.d; R.sup.9 is C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, CN, NO.sub.2, C(O)NR.sup.bR.sup.b, C(O)OR.sup.a , NR.sup.bR.sup.b, OR.sup.d, C(O)R.sup.e or S(O).sub.qR.sup.f.

4. The compound according to claim 3 represented by general formula (III) or a salt thereof, wherein: R.sup.2 is phenyl, which is optionally substituted with 1-5 R.sup.9; and each R.sup.a, R.sup.b, R.sup.b, R.sup.c, R.sup.c, R.sup.d, R.sup.d, R.sup.e and R.sup.f is independently hydrogen, C.sub.1-C.sub.8 alkyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, alkoxyalkyl, morpholinylalkyl, tetrahydropyranylalkyl, pyridylalkyl, thiazolylalkyl, pyrrolylalkyl, tetrahydrofuryl, tetrahydrofurylalkyl, alkylaminoalkyl or phenyl.

5. The compound according to claim 4 represented by general formula (III) or a salt thereof, wherein: n is O; R.sup.1 is hydrogen, C.sub.1-C.sub.8 alkyl or pyridylalkyl, each of which is optionally substituted with 1-3 R.sup.7; R.sup.7 is C.sub.1-C.sub.8 alkyl or halo; R.sup.9 is C.sub.1-C.sub.8 alkyl, phenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, CN, NO.sub.2, C(O)NR.sup.bR.sup.b, C(O)OR.sup.a , NR.sup.bR.sup.b, OR.sup.d, C(O)R.sup.e or S(O).sub.qR.sup.f; and each R.sup.a, R.sup.b, R.sup.b, R.sup.c, R.sup.c, R.sup.d, R.sup.d, R.sup.e and R.sup.f is independently hydrogen, C.sub.1-C.sub.8 alkyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, alkoxyalkyl, morpholinylalkyl, tetrahydropyranylalkyl, pyridylalkyl, thiazolylalkyl, pyrrolylalkyl or tetrahydrofurylalkyl.

6. The compound according to claim 5 represented by general formula (III) or a salt thereof, wherein: R.sup.9 is halo or OR.sup.d, and R.sup.d is C.sub.1-C.sub.8 alkyl.

7. The compound according to claim 1 or a salt thereof, wherein the compound of formula (III) is a compound selected from the group consisting of ##STR03372## ##STR03373## ##STR03374## ##STR03375##

8. A pharmaceutical composition comprising the compound according to claim 1 or a salt thereof as an active ingredient and a pharmaceutically acceptable carrier.

Description

DETAILED DESCRIPTION

(1) A compound or composition described herein can be used, e.g., in a method of treating schizophrenia or cognitive deficit. Many of the compounds described herein modulate STEP activity and can be used, e.g., to reduce or inhibit STEP activity, e.g., in a subject.

(2) Definitions

(3) The term acyl refers to an alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl, or heteroarylcarbonyl substituent, any of which may be further substituted (e.g., by one or more substituents).

(4) The term alkenyl refers to a straight or branched hydrocarbon chain containing 2-12 carbon atoms (unless otherwise noted) and having one or more double bonds. Examples of alkenyl groups include, but are not limited to, allyl, propenyl, 2-butenyl, 3-hexenyl and 3-octenyl groups. One of the double bond carbons may optionally be the point of attachment of the alkenyl substituent.

(5) The term alkenylene refers to a divalent alkenyl, e.g. CHCH, CH.sub.2CHCH, and CHCHCH.sub.2.

(6) The term alkynyl refers to a straight or branched hydrocarbon chain containing 2-12 carbon atoms (unless otherwise noted) and characterized in having one or more triple bonds. Examples of alkynyl groups include, but are not limited to, ethynyl, propargyl, and 3-hexynyl. One of the triple bond carbons may optionally be the point of attachment of the alkynyl substituent.

(7) The term alkynylene refers to a divalent alkynyl, e.g. CHCH, CH.sub.2CHCH, and CHCHCH.sub.2.

(8) The terms alkoxyl or alkoxy as used herein refers to an alkyl group, as defined below, having an oxygen radical attached thereto. Representative alkoxy groups include methoxy, ethoxy, propyloxy, tert-butoxy and the like. The term alkoxyalkyl refers to an alkyl in which one or more hydrogen atoms are replaced by an alkoxy group.

(9) An ether is two hydrocarbons covalently linked by an oxygen.

(10) The term alkyl refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, and branched-chain alkyl groups. In preferred embodiments, a straight chain or branched chain alkyl has 12 or fewer carbon atoms in its backbone (unless otherwise noted) e.g., from 1-12, 1-8, 1-6, or 1-4. Exemplary alkyl moieties include methyl, ethyl, propyl (e.g., n-propyl or isopropyl), butyl (e.g., n-butyl, isobutyl or t-butyl), pentyl (e.g., n-pentyl, isopentyl or pentan-3-yl), hexyl and hepty.

(11) The term alkylene refers to a divalent alkyl, e.g., CH.sub.2, CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2CH.sub.2.

(12) The term alkoxylene refers to an alkylene wherein a CH.sub.2 is substituted with an oxygen. For example, an aryl alkoxylene refers to a group with an alkylene attached to an aryl group through an oxygen, an optionally substituted heteroaryl alkoxylene refers to a group with an alkylene attached to an heteroaryl group through an oxygen.

(13) The term amino refers to NH.sub.2.

(14) The term aminoalkyl refers to an alkyl in which one or more hydrogen atoms are replaced by an amino group.

(15) The terms alkylamino and dialkylamino refer to NH(alkyl) and N(alkyl).sub.2 radicals respectively.

(16) The term aralkylamino or arylalkylamino refers to a NH(aralkyl) radical. The term alkylaminoalkyl refers to a (alkyl)NH-alkyl-radical; the term dialkylaminoalkyl refers to an (alkyl).sub.2N-alkyl-radical.

(17) The term amido refers to a NHC(O) or C(O)NH.sub.2 substituent.

(18) The term aryl refers to a 6-carbon monocyclic, 10-carbon bicyclic, or 14-carbon tricyclic aromatic ring system wherein 0, 1, 2, 3, or 4 atoms of each ring may be substituted by a substituent. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl and the like. The term arylalkyl or aralkyl refers to alkyl substituted with an aryl. Exemplary aralkyls include but are not limited to benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 9-fluorenyl, benzhydryl, phenethyl, and trityl groups. The term arylalkenyl refers to an alkenyl substituted with an aryl. The term arylalkynyl refers to an alkynyl substituted with an aryl. Terms such as arylC.sub.2-C.sub.6alkyl are to be read as a further limitation on the size of the alkyl group. The term arylalkoxy refers to an alkoxy substituted with aryl. The term arylenyl refers to a divalent aryl (i.e., Ar).

(19) The terms cycloalkyl or cyclyl as employed herein include saturated and partially unsaturated cyclic hydrocarbon groups having 3 to 12 carbons, preferably 3 to 8 carbons, and more preferably 3 to 6 carbons, wherein the cycloalkyl group may be optionally substituted. Exemplary cyclyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Cyclyl moieties also include both bridged and fused ring systems. Cyclyl groups also include those that are fused to additional ring systems, which may be saturated or unsaturated. A cyclyl group may thus be a bicyclic group in which one ring is saturated or partially unsaturated and the other is fully unsaturated (e.g., indanyl).

(20) The term cyclylalkyl as used herein, refers to an alkyl group substituted with a cyclyl group. Cyclylalkyl includes groups in which more than one hydrogen atom of an alkyl group has been replaced by a cyclyl group.

(21) The term cycloalkylalkyl as used herein, refers to an alkyl group substituted with a cycloalkyl group.

(22) The term halo or halogen refers to any radical of fluorine, chlorine, bromine or iodine.

(23) The term haloalkyl refers to an alkyl group that may have any number of hydrogens available on the group replaced with a halogen atom. Representative haloalkyl groups include but are not limited to: CH.sub.2Cl, CH.sub.2ClCF.sub.3, CHBr.sub.2, CF.sub.3, CH.sub.2F, CHF.sub.2, and CH.sub.2CF.sub.3. The term fluoroalkyl refers to an alkyl group that may have any number of hydrogens available on the group replaced with a fluorine atom. Representative fluoroalkyl groups include but are not limited to: CH.sub.2F, CH.sub.2FCF.sub.3, CHF.sub.2 and CF.sub.3. The term haloalkoxy refers to an alkoxy group that may have any number of hydrogen atoms available on the alkyl group replaced with a halogen atom. Representative haloalkoxy groups include but are not limited to: OCH.sub.2Cl, OCH.sub.2ClCF.sub.3, OCHBr.sub.2, OCHF.sub.2 or OCF.sub.3. The term fluoroalkoxy refers to an alkoxy group that may have any number of hydrogens available on the group replaced with a fluorine atom. Representative fluoroalkoxy groups include but are not limited to: OCH.sub.2F, OCH.sub.2FCF.sub.3, OCHF.sub.2 or OCF.sub.3.

(24) The term heteroatom as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur, phosphorus and silicon. A heteroatom may be present in any oxidation state (e.g., any oxidized form of nitrogen, sulfur, phosphorus or silicon) and any charged state (e.g., the quaternized form of any basic nitrogen), and includes a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR.sup.+ (as in N-substituted pyrrolidinyl).

(25) The term heteroaryl refers to an aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S (e.g., carbon atoms and 1-3, 1-6, or 1-9 heteroatoms of N, O, or S if monocyclic, bicyclic, or tricyclic, respectively), wherein 0, 1, 2, 3, or 4 atoms of each ring may be substituted by a substituent. Examples of heteroaryl groups include pyridyl, furyl or furanyl, imidazolyl, benzimidazolyl, pyrimidinyl, thiophenyl or thienyl, quinolinyl, indolyl, thiazolyl, oxazolyl and the like. The term heteroarylalkyl or the term heteroaralkyl refers to an alkyl substituted with a heteroaryl. The term heteroarylalkenyl refers to an alkenyl substituted with a heteroaryl. The term heteroarylalkynyl refers to an alkynyl substituted with a heteroaryl. The term heteroarylalkoxy refers to an alkoxy substituted with heteroaryl.

(26) The term heteroaryl refers to a group having 5 to 14 ring atoms, preferably 5, 6, 9, or 10 ring atoms; having 6, 10, or 14 electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. A heteroaryl group may be mono-, bi-, tri-, or polycyclic, preferably mono-, bi-, or tricyclic, more preferably mono- or bicyclic. When a heteroaryl is substituted by a hydroxy group, it also includes its corresponding tautomer. The term heteroaryl, as used herein, also includes groups in which a heteroaromatic ring is fused to one or more aryl rings. Nonlimiting examples of heteroaryl groups include thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. The term heteroaryl may be used interchangeably with the terms heteroaryl ring, heteroaryl group, or heteroaromatic, any of which terms include rings that are optionally substituted. A ring nitrogen atom of a heteroaryl may be oxidized to form the corresponding N-oxide compound. A nonlimiting example of such a heteroaryl having an oxidized ring nitrogen atom is N-oxopyridyl.

(27) The term heteroarylalkyl or heteroaralkyl refers to an alkyl group substituted by a heteroaryl. Heteroaralkyl includes groups in which more than one hydrogen atom has been replaced by a heteroaryl group.

(28) As used herein, the terms heterocycle, heterocyclyl and heterocyclic ring are used interchangeably and refer to a stable 3- to 8-membered monocyclic or 7-10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term nitrogen includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2/y-pyrrolyl), NH (as in pyrrolidinyl), or NR.sup.+ (as in N-substituted pyrrolidinyl). A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, piperidinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and thiomorpholinyl. A heterocyclyl group may be mono-, bi-, tri-, or polycyclic, preferably mono-, bi-, or tricyclic, more preferably mono- or bicyclic. Additionally, a heterocyclic ring also includes groups in which the heterocyclyl ring is fused to one or more aryl, heteroaryl or cyclyl rings. A ring nitrogen atom of a heterocyclic ring also may be oxidized to form the corresponding N-hydroxy compound.

(29) The term heterocyclylalkyl refers to an alkyl group substituted by a heterocyclyl. Heterocyclylalkyl includes groups in which more than one hydrogen atom has been replaced by a heterocyclyl group.

(30) The terms hetaralkyl and heteroaralkyl, as used herein, refers to an alkyl group substituted with a heteroaryl group. Examplary heteroaralkyl groups include but are not limited to methylpyridyl or methylpyrimidyl.

(31) The term heterocyclyl or heterocyclylalkyl refers to a nonaromatic 5-8 membered monocyclic, 5-12 membered bicyclic, or 11-14 membered tricyclic ring system having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S (e.g., carbon atoms and 1-3, 1-6, or 1-9 heteroatoms of N, O, or S if monocyclic, bicyclic, or tricyclic, respectively), wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent. Examples of heterocyclyl groups include piperazinyl, pyrrolidinyl, dioxanyl, morpholinyl, tetrahydrofuranyl, and include both bridged and fused ring systems. The term heterocyclylalkyl refers to an alkyl substituted with a heterocyclyl.

(32) The term heterocyclylalkyl, as used herein, refers to an alkyl group substituted with a heterocycle group.

(33) The term heteroalkyl, as used herein, refers to a saturate or unsaturated, straight or branched chain aliphatic group, wherein one or more of the carbon atoms in the chain are independently replaced by a heteroatom. Exemplary hetero atoms include O, S, and N.

(34) In the case of aralkyl, heteroaralkyl, cyclylalkyl, heterocyclylalkyl etc., groups described as optionally substituted, it is intended that either or both aryl, heteroaryl, cyclyl, heterocyclyl and alkyl moieties may be independently optionally substituted or unsubstituted.

(35) The term hydroxyalkyl refers to an alkyl in which one or more hydrogen atoms are replaced by a hydroxy group.

(36) The term oxo refers to an oxygen atom (O), which forms a carbonyl when attached to carbon, an N-oxide when attached to nitrogen, and a sulfoxide or sulfone when attached to sulfur.

(37) The term thioalkyl as used herein refers to an S(alkyl) group, where the point of attachment is through the sulfur atom and the alkyl group is as defined above.

(38) The term thiono or thioxo refers to a sulfur atom (S), which forms a thioketone when attached to carbon.

(39) The term substituted refers to moieties having substituents replacing a hydrogen on one or more carbons of the backbone. It will be understood that substitution or substituted with includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term substituted is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms.

(40) The term substituent refers to a group substituted on a moiety described herein. Any atom on any substituent can be substituted. Substituents can include any substituents described herein. Examplary substituents include, without limitation, alkyl (e.g., C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12 straight or branched chain alkyl), cycloalkyl, haloalkyl (e.g., perfluoroalkyl such as CF.sub.3), aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, alkenyl, alkynyl, cycloalkenyl, heterocycloalkenyl, alkoxy, haloalkoxy (e.g., perfluoroalkoxy such as OCF.sub.3), halo, hydroxy, carboxy, carboxylate, cyano, nitro, amino, alkylamino, SO.sub.3H, sulfate, phosphate, methylenedioxy (OCH.sub.2O wherein oxygens are attached to vicinal atoms), ethylenedioxy, oxo, thioxo (e.g., CS), imino (alkyl, aryl, aralkyl), S(O).sub.nalkyl (where n is 0-2), S(O).sub.n aryl (where n is 0-2), S(O).sub.n heteroaryl (where n is 0-2), S(O).sub.n heterocyclyl (where n is 0-2), amine (mono-, di-, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, and combinations thereof), ester (alkyl, aralkyl, heteroaralkyl, aryl, heteroaryl), amide (mono-, di-, alkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, and combinations thereof), sulfonamide (mono-, di-, alkyl, aralkyl, heteroaralkyl, and combinations thereof). In one aspect, the substituents on a group are independently any one single, or any subset of the aforementioned substituents. In another aspect, a substituent may itself be substituted with any one of the above substituents.

(41) As used herein, the phrase optionally substituted is used interchangeably with the phrase substituted or unsubstituted. In general, the term substituted, whether preceded by the term optionally or not, means that a hydrogen radical of the designated moiety is replaced with the radical of a specified substituent, provided that the substitution results in a stable or chemically feasible compound. The term substitutable, when used in reference to a designated atom, means that attached to the atom is a hydrogen radical, which hydrogen atom can be replaced with the radical of a suitable substituent. Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds.

(42) As used herein, the term optionally substituted means substituted or unsubstituted.

(43) As used herein, the term partially unsaturated refers to a moiety that includes at least one double or triple bond between atoms. The term partially unsaturated encompasses rings, e.g., having one or more sites of unsaturation, but that are not completely unsaturated so as to be aryl or heteroaryl.

(44) The term chiral refers to molecules which have the property of non-superimposability of the mirror image partner, while the term achiral refers to molecules which are superimposable on their mirror image partner. With respect to the nomenclature of a chiral center, terms R and S configuration are as defined by the IUPAC Recommendations. The term enantiomers refers to two stereoisomers of a compound which are non-superimposable mirror images of one another. An equimolar mixture of two enantiomers is called a racemic mixture or a racemate. The term isomers or stereoisomers refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. For example, isomers include cis- and trans-isomers, E- and Z-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, racemic mixtures thereof, and other mixtures thereof. The term diastereomers refers to stereoisomers with two or more centers of dissymmetry and whose molecules are not mirror images of one another.

(45) The term administration or administering includes routes of introducing the compounds, or a composition thereof, of the invention to a subject to perform their intended function. Examples of routes of administration that may be used include injection (subcutaneous, intravenous, parenterally, intraperitoneally, intrathecal), oral, inhalation, rectal and transdermal. The pharmaceutical compositions may be given by forms suitable for each administration route. For example, these compositions are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administration is preferred. The injection can be bolus or can be continuous infusion. Depending on the route of administration, a compound described herein can be coated with or disposed in a selected material to protect it from natural conditions which may detrimentally affect its ability to perform its intended function. A compound or composition described herein can be administered alone, or in conjunction with either another agent as described above or with a pharmaceutically-acceptable carrier, or both. A compound or composition described herein can be administered prior to the administration of the other agent, simultaneously with the agent, or after the administration of the agent. Furthermore, a compound described herein can also be administered in a pro-drug form which is converted into its active metabolite, or more active metabolite in vivo.

(46) The language biological activities of a compound described herein includes all activities elicited by a compound described herein in a responsive subject or cell. It includes genomic and non-genomic activities elicited by these compounds.

(47) The terms inhibit and inhibitor as used herein means an agent that measurably slows or stops the production of STriatal-Enriched tyrosine Phosphatase (STEP), or decreases or inactivates STEP, or interferes with STEP-mediated biological pathways. Inhibitors of STEP include compounds of the invention, e.g., compounds of Formulas (I), (II), or (III). A compound can be evaluated to determine if it is an inhibitor by measuring either directly or indirectly the activity of STEP in the presence of the compound suspected to inhibit STEP. Exemplary methods of measure STEP inhibition are described in the EXAMPLES herein.

(48) An effective amount or an amount effective refers to an amount of the compound or composition which is effective, upon single or multiple dose administrations to a subject and for periods of time necessary, in treating a cell, or curing, alleviating, relieving or improving a symptom of a disorder, e.g., a disorder described herein. An effective amount of a compound described herein may vary according to factors such as the disease state, age, and weight of the subject, and the ability of a compound described herein to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. An effective amount is also one in which any toxic or detrimental effects (e.g., side effects) of a compound described herein are outweighed by the therapeutically beneficial effects. The term effective amount includes an amount effective, at dosages and for periods of time necessary, to achieve the desired result, e.g., modulate or regulate protein tyrosine phosphatases, e.g., STEP, in a subject and/or treat a disorder described herein such as a protein tyrosine phosphatase related disorder. Exemplary disorders include those related to cognition, learning and memory, neurogenesis. An effective amount may also affect neuronal plasticity, pain perception, mood and anxiety, and neuroendocrine regulation.

(49) An effective amount of a compound described herein may vary according to factors such as the disease state, age, and weight of the subject, and the ability of a compound described herein to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. An effective amount is also one in which any toxic or detrimental effects (e.g., side effects) of a compound described herein are outweighed by the therapeutically beneficial effects.

(50) A therapeutically effective amount of a compound described herein (i.e., an effective dosage) may range from about 0.001 to 50 mg/kg body weight, preferably about 0.01 to 40 mg/kg body weight, more preferably about 0.1 to 35 mg/kg body weight, still more preferably about 1 to 30 mg/kg, and even more preferably about 10 to 30 mg/kg. The skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a compound described herein can include a single treatment or, preferably, can include a series of treatments. In one example, a subject is treated with a compound described herein in the range of between about 0.1 to 20 mg/kg body weight, one time per week for between about 1 to 10 weeks, preferably between 2 to 8 weeks, more preferably between about 3 to 7 weeks, and even more preferably for about 4, 5, or 6 weeks. It will also be appreciated that the effective dosage of a compound described herein used for treatment may increase or decrease over the course of a particular treatment.

(51) As used herein, an amount of a compound effective to prevent a disorder, or a prophylactically effective amount of the compound refers to an amount effective, upon single- or multiple-dose administration to the subject, in preventing or delaying the occurrence of the onset or recurrence of a disorder or a symptom of the disorder.

(52) The language improved biological properties refers to any activity inherent in a compound described herein that enhances its effectiveness in vivo. In a preferred embodiment, this term refers to any qualitative or quantitative improved therapeutic property of a compound described herein, such as reduced off-target effects.

(53) The term modulate refers to an increase or decrease, e.g., in the activity of an enzyme in response to exposure to a compound or composition described herein, e.g., the activation or inhibition of STEP, in at least a sub-population of cells in a subject such that a desired end result is achieved (e.g., a therapeutic result). In some embodiments, a compound as described herein inhibits a target described herein, e.g., STEP. In some embodiments, a compound as described herein is activates a target described herein, e.g., STEP.

(54) As used herein, the term subject is intended to include human and non-human animals. Exemplary human subjects include a human patient having a disorder, e.g., a disorder described herein, or a normal subject. The term non-human animals includes all vertebrates, e.g., non-mammals (such as chickens, amphibians, reptiles) and mammals, such as non-human primates, domesticated and/or agriculturally useful animals, e.g., sheep, dog, cat, cow, pig, etc.

(55) As used herein, the term treat or treating is defined as applying or administering a compound or composition, alone or in combination with a second compound or composition, to a subject, e.g., a patient, or applying or administering the compound or composition to an isolated tissue or cell, e.g., cell line, from a subject, e.g., a patient, who has a disorder (e.g., a disorder as described herein), a symptom of a disorder, or a predisposition toward a disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the disorder, one or more symptoms of the disorder or the predisposition toward the disorder (e.g., to prevent at least one symptom of the disorder or to delay onset of at least one symptom of the disorder).

(56) The phrases parenteral administration and administered parenterally as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

(57) The term prodrug or pro-drug includes compounds with moieties that can be metabolized in vivo. Generally, the prodrugs are metabolized in vivo by esterases or by other mechanisms to active drugs. Examples of prodrugs and their uses are well known in the art (See, e.g., Berge et al. (1977) Pharmaceutical Salts, J. Pharm. Sci. 66:1-19). The prodrugs can be prepared in situ during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent. Hydroxyl groups can be converted into esters via treatment with a carboxylic acid. Examples of prodrug moieties include substituted and unsubstituted, branch or unbranched lower alkyl ester moieties, (e.g., propionoic acid esters), lower alkenyl esters, di-lower alkyl-amino lower-alkyl esters (e.g., dimethylaminoethyl ester), acylamino lower alkyl esters (e.g., acetyloxymethyl ester), acyloxy lower alkyl esters (e.g., pivaloyloxymethyl ester), aryl esters (phenyl ester), aryl-lower alkyl esters (e.g., benzyl ester), substituted (e.g., with methyl, halo, or methoxy substituents) aryl and aryl-lower alkyl esters, amides, lower-alkyl amides, di-lower alkyl amides, and hydroxy amides. Preferred prodrug moieties are propionoic acid esters and acyl esters. Prodrugs which are converted to active forms through other mechanisms in vivo are also included.

(58) The language a prophylactically effective amount of a compound refers to an amount of a compound described herein any formula herein or otherwise described herein which is effective, upon single or multiple dose administration to the patient, in preventing or treating a disease or condition.

(59) The language reduced off-target effects is intended to include a reduction in any undesired side effect elicited by a compound described herein when administered in vivo. In some embodiments, a compound described herein has little to no cardio and/or pulmonary toxicity (e.g., when administered to a subject). In some embodiments, a compound described herein has little to no hallucinogenic activity (e.g., when administered to a subject).

(60) The term selective means a greater activity against a first target. In some embodiments a compound has a selectivity of at least 1.25-fold, at least 1.5 fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 10-fold or at least 100-fold greater towards a first target relative to a second target. In some embodiments, a compound described herein, e.g., a compound of Formulas (I), (II), or (III) is selective toward STEP relative to one or more other protein tyrosine phosphatases.

(61) The term subject includes organisms which are capable of suffering from a serotonin-receptor-related disorder or who could otherwise benefit from the administration of a compound described herein of the invention, such as human and non-human animals. Preferred humans include human patients suffering from or prone to suffering from a serotonin-related disorder or associated state, as described herein. The term non-human animals of the invention includes all vertebrates, e.g., mammals, e.g., rodents, e.g., mice, and non-mammals, such as non-human primates, e.g., sheep, dog, cow, chickens, amphibians, reptiles, etc.

(62) The phrases systemic administration, administered systemically, peripheral administration and administered peripherally as used herein mean the administration of a compound described herein(s), drug or other material, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

(63) Compounds

(64) The compounds described herein can be used for a variety of purposes, e.g., therapeutic purposes. Many of the compounds modulate STEP activity and can be used, for example to inhibit STEP, e.g., in a subject.

(65) Exemplary compounds include a compound of formula (I):

(66) ##STR00129##

(67) wherein A, B, E, L, X, Z, R.sup.1, R.sup.2, R.sup.3, m, n and p are as defined above in the section relating to compound of Formula (I). In preferred embodiments, L is NH, B is aryl (e.g., phenyl) that may be optionally substituted, E is aryl (e.g., phenyl), A is N, X is CH and Z is N.

(68) Exemplary compounds include a compound of formula (II):

(69) ##STR00130##

(70) wherein A, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, R.sup.1, R.sup.2, R.sup.3, n and p are as defined above in the section relating to compound of Formula (II).

(71) Exemplary compounds include a compound of formula (III):

(72) ##STR00131##

(73) wherein A, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, R.sup.1, R.sup.2, R.sup.3, R.sup.4, m, and n are as defined above in the section relating to compound of Formula (III).

(74) Exemplary compounds include a compound of formula (IV):

(75) ##STR00132##

(76) wherein A, B, E, L, X, Z, R.sup.1, R.sup.2, R.sup.3, m, n and p are as defined above in the section relating to compound of Formula (IV). In preferred embodiments, L is NH, B is aryl (e.g., phenyl) that may be optionally substituted, E is aryl (e.g., phenyl), A is N, X is CH and Z is N.

(77) Exemplary compounds include a compound of formula (V):

(78) ##STR00133##

(79) wherein A, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, R.sup.1, R.sup.2, R.sup.3, n and p are as defined above in the section relating to compound of Formula (V).

(80) Exemplary compounds include a compound of formula (VI):

(81) ##STR00134##

(82) wherein A, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, R.sup.1, R.sup.2, R.sup.3, R.sup.4, m, and n are as defined above in the section relating to compound of Formula (VI).

(83) The present invention includes compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, the replacement of a carbon by a .sup.13C- or .sup.14C-enriched carbon, or the replacement of a fluorine by a .sup.19F-enriched fluorine are within the scope of this invention. Such compounds are useful, for example, as analytical tools or probes in biological assays, or as bioactive agents.

(84) In the compounds of the present invention, any atom not specifically designated as a particular isotope is meant to represent any stable isotope of that atom unless otherwise stated (e.g., hydrogen, .sup.2H or deuterium and .sup.3H or tritium). The formulas described herein may or may not indicate whether atoms at certain positions are isotopically enriched. When a structural formula is silent with respect to whether a particular position is isotopically enriched, it is to be understood that the isotopes at that particular position are present in natural abundance or, that the particular position is isotopically enriched with one or more naturally occuring stable isotopes. For example, the formula CH.sub.2 represents the following possible structures: CH.sub.2, CHD or CD.sub.2-.

(85) The variable D is defined as deuterium.

(86) The terms compound or compounds, when referring to a compound of this invention or a compound described herein, refers to a collection of molecules having an identical chemical structure, except that there may be isotopic variation among the constituent atoms of the molecules. Thus, it will be clear to those of skill in the art that a compound represented by a particular chemical structure containing indicated hydrogen atoms will contain lesser amounts of isotopologues having deuterium atoms at one or more of the designated hydrogen positions in that structure. Alternatively, a compound represented by a particular chemical structure containing indicated deuterium atoms will contain lesser amounts of isotopologues having hydrogen atoms at one or more of the designated deuterium positions in that structure. The relative amount of such isotopologues in a compound of this invention will depend on a number of factors including isotopic purity of deuterated reagents used to make the compound and the efficiency of incorporation of deuterium in the various synthetic steps used to prepare the compound. The relative amount of such isotopologues in total will be less than 55% of the compound. In other embodiments, the relative amount of such isotopologues in total will be less than 50%, less than 45%, less than 40%, less than 35%, less than 35%, less than 15%, less than 10%, less than 5%, less than 1% or less than 0.5% of the compound.

(87) The term isotopologue refers to a species that differs from a specific compound of this invention only in the isotopic composition thereof. Isotopologues can differ in the level of isotopic enrichment at one or more positions and/or in the position(s) of isotopic enrichment.

(88) The compounds of this invention may contain one or more asymmetric centers and thus occur as racemates and racemic mixtures, single enantiomers, individual diastereomers and diastereomeric mixtures. Described herein are enantiomerically enriched compounds (e.g., a compound resolved to an enantiomeric excess of 60%, 70%, 80%, 85%, 90%, 95%, 99% or greater). All such isomeric forms of these compounds are expressly included in the present invention. The compounds of this invention may also contain linkages (e.g., carbon-carbon bonds) or substituents that can restrict bond rotation, e.g. restriction resulting from the presence of a ring or double bond. Accordingly, all cis/trans and E/Z isomers are expressly included in the present invention. The compounds of this invention may also be represented in multiple tautomeric forms, in such instances, the invention expressly includes all tautomeric forms of the compounds described herein, even though only a single tautomeric form may be represented (e.g., alkylation of a ring system may result in alkylation at multiple sites, the invention expressly includes all such reaction products). All such isomeric forms of such compounds are expressly included in the present invention. All crystal forms of the compounds described herein are expressly included in the present invention.

(89) Naturally occurring or synthetic isomers can be separated in several ways known in the art. Methods for separating a racemic mixture of two enantiomers include chromatography using a chiral stationary phase (see, e.g., Chiral Liquid Chromatography, W. J. Lough, Ed. Chapman and Hall, New York (1989)). Enantiomers can also be separated by classical resolution techniques. For example, formation of diastereomeric salts and fractional crystallization can be used to separate enantiomers. For the separation of enantiomers of carboxylic acids, the diastereomeric salts can be formed by addition of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, and the like. Alternatively, diastereomeric esters can be formed with enantiomerically pure chiral alcohols such as menthol, followed by separation of the diastereomeric esters and hydrolysis to yield the free, enantiomerically enriched carboxylic acid. For separation of the optical isomers of amino compounds, addition of chiral carboxylic or sulfonic acids, such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid can result in formation of the diastereomeric salts. For example a compound can be resolved to an enantiomeric excess (e.g., 60%, 70%, 80%, 85%, 90%, 95%, 99% or greater) via formation of diasteromeric salts, e.g. with a chiral base, e.g., (+) or () -methylbenzylamine, or via high performance liquid chromatography using a chiral column. In some embodiments a product is purified directly on a chiral column to provide enantiomerically enriched compound.

(90) Combinations of substituents and variables envisioned by this invention are only those that result in the formation of stable compounds. The term stable, as used herein, refers to compounds which possess stability sufficient to allow manufacture and which maintains the integrity of the compound for a sufficient period of time to be useful for the purposes detailed herein (e.g., therapeutic administration to a subject).

(91) Compounds of formulas (I), (II), (III), (IV), (V), and (VI) are described herein, for example as provided in the summary above. Exemplary compounds are shown in Tables 1-30 in the Examples section.

(92) Synthetic Methods

(93) A compound described herein may be prepared via a variety of synthetic methods. Representative syntheses are shown in the Examples section.

(94) As can be appreciated by the skilled artisan, further methods of synthesizing the compounds of the formulae herein will be evident to those of ordinary skill in the art. Additionally, the various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing the compounds described herein are known in the art and include, for example, those such as described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995), and subsequent editions thereof.

(95) Additionally, the compounds disclosed herein can be prepared on a solid support. The term solid support refers a material to which a compound is attached to facilitate identification, isolation, purification, or chemical reaction selectivity of the compound. Such materials are known in the art and include, for example, beads, pellets, disks, fibers, gels, or particles such as cellulose beads, pore-glass beads, silica gels, polystyrene beads optionally cross-linked with divinylbenzene and optionally grafted with polyethylene glycol, poly-acrylamide beads, latex beads, dimethylacrylamide beads optionally cross-linked with N,N-bis-acryloyl ethylene diamine, glass particles coated with hydrophobic polymer, and material having a rigid or semi-rigid surface. The solid supports optionally have functional groups such as amino, hydroxy, carboxy, or halo groups, (see, Obrecht, D. and Villalgrodo, J. M., Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries, Pergamon-Elsevier Science Limited (1998)), and include those useful in techniques such as the split and pool or parallel synthesis techniques, solid-phase and solution-phase techniques, and encoding techniques (see, for example, Czarnik, A. W., Curr. Opin. Chem. Bio., (1997) 1, 60).

(96) A compound described herein may be modified by appending appropriate functionalities to enhance selective biological properties. Such modifications are known in the art and include those which increase biological penetration into a given biological compartment (e.g., brain, blood, lymphatic system, central nervous system), increase oral availability, increase solubility to allow administration by injection, alter metabolism and alter rate of excretion.

(97) Included herein are pharmaceutically acceptable derivatives or prodrugs of the compounds described herein. A pharmaceutically acceptable derivative or prodrug means any pharmaceutically acceptable salt, ester, salt of an ester, or other derivative of a compound of this invention (for example an imidate ester of an amide), which, upon administration to a recipient, is capable of providing (directly or indirectly) a compound described herein. Particularly favored derivatives and prodrugs are those that increase the bioavailability of the compounds of this invention when such compounds are administered to a mammal (e.g., by allowing an orally administered compound to be more readily absorbed into the blood) or which enhance delivery of the parent compound to a biological compartment (e.g., the brain or lymphatic system) relative to the parent species. In an exemplary embodiment, the prodrug is a derivative including a group that enhances aqueous solubility or active transport through the gut membrane is appended to the structure of formulae described herein. In another exemplary embodiment, the prodrug is suitable for treatment or prevention of those diseases and conditions that require the drug molecule to cross the blood brain barrier. In a preferred embodiment, the prodrug enters the brain, where it is converted into the active form of the drug molecule.

(98) Pharmaceutically acceptable salts of the compounds of this invention include those derived from pharmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acid salts include acetate, adipate, benzoate, benzenesulfonate, butyrate, citrate, digluconate, dodecylsulfate, formate, fumarate, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, palmoate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, tartrate, tosylate and undecanoate. Salts derived from appropriate bases include alkali metal (e.g., sodium), alkaline earth metal (e.g., magnesium), ammonium and N-(alkyl).sub.4.sup.+ salts. This invention also envisions the quaternization of any basic nitrogen-containing groups of the compounds disclosed herein. Water or oil-soluble or dispersible products may be obtained by such quaternization.

(99) Evaluating Compounds

(100) A variety of methods can be used to evaluate a compound for ability to modulate STEP activity. Evaluation methods include in vitro assays (e.g., enzyme-based assays), in vitro cell-based signaling assays, and in vivo methods (e.g., testing in animal models). The evaluation methods can evaluate binding activity, phosphatase activity, or an activity downstream of STEP, such as the activity of ERK.

(101) For example, a compound described herein may be evaluated using a fluorescence-based phosphatase assay. A phosphate-containing reagent may be used in the assay which, upon dephosphorylation by a phosphatase, generates a fluorescent product that may be detected using a fluorometer or fluorescence plate reader. Data may be expressed as percentage (%) inhibition of enzyme activity. For compounds showing enzymatic activation, data may be represented as percentage of inhibition but with negative values.

(102) Compositions and Routes of Administration

(103) The invention also provides a pharmaceutical composition, comprising an effective amount of a compound described herein (e.g., a compound capable of treating or preventing a condition as described herein, e.g., a compound of any formula herein or otherwise described herein) and a pharmaceutically acceptable carrier.

(104) The compositions delineated herein include the compounds delineated herein (e.g., a compound described herein), as well as additional therapeutic agents if present, in amounts effective for achieving a modulation of disease or disease symptoms, including those described herein.

(105) The term pharmaceutically acceptable carrier or adjuvant refers to a carrier or adjuvant that may be administered to a patient, together with a compound of this invention, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the compound.

(106) Pharmaceutically acceptable carriers, adjuvants and vehicles that may be used in the pharmaceutical compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d--tocopherol polyethylene glycol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tweens or other similar polymeric delivery matrices, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Cyclodextrins such as -, -, and -cyclodextrin, or chemically modified derivatives such as hydroxyalkylcyclodextrins, including 2- and 3-hydroxypropyl--cyclodextrins, or other solubilized derivatives may also be advantageously used to enhance delivery of compounds of the formulae described herein.

(107) The pharmaceutical compositions of this invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir, preferably by oral administration or administration by injection. The pharmaceutical compositions of this invention may contain any conventional non-toxic pharmaceutically-acceptable carriers, adjuvants or vehicles. In some cases, the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases or buffers to enhance the stability of the formulated compound or its delivery form. The term parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.

(108) The pharmaceutical compositions may be in the form of a sterile injectable preparation, for example, as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are mannitol, water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents which are commonly used in the formulation of pharmaceutically acceptable dosage forms such as emulsions and or suspensions. Other commonly used surfactants such as Tweens or Spans and/or other similar emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation.

(109) The pharmaceutical compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, emulsions and aqueous suspensions, dispersions and solutions. In the case of tablets for oral use, carriers which are commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions and/or emulsions are administered orally, the active ingredient may be suspended or dissolved in an oily phase is combined with emulsifying and/or suspending agents. If desired, certain sweetening and/or flavoring and/or coloring agents may be added.

(110) The pharmaceutical compositions of this invention may also be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound of this invention with a suitable non-irritating excipient which is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components. Such materials include, but are not limited to, cocoa butter, beeswax and polyethylene glycols.

(111) Topical administration of the pharmaceutical compositions of this invention is useful when the desired treatment involves areas or organs readily accessible by topical application. For application topically to the skin, the pharmaceutical composition should be formulated with a suitable ointment containing the active components suspended or dissolved in a carrier. Carriers for topical administration of the compounds of this invention include, but are not limited to, mineral oil, liquid petroleum, white petroleum, propylene glycol, polyoxyethylene polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutical composition can be formulated with a suitable lotion or cream containing the active compound suspended or dissolved in a carrier with suitable emulsifying agents. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. The pharmaceutical compositions of this invention may also be topically applied to the lower intestinal tract by rectal suppository formulation or in a suitable enema formulation. Topically-transdermal patches are also included in this invention.

(112) The pharmaceutical compositions of this invention may be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art.

(113) When the compositions of this invention comprise a combination of a compound of the formulae described herein and one or more additional therapeutic agents, both the compound and the additional agent should be present at dosage levels of between about 1 to 100%, and more preferably between about 5 to 95% of the dosage normally administered in a monotherapy regimen. The additional agents may be administered separately, as part of a multiple dose regimen, from the compounds of this invention. Alternatively, those agents may be part of a single dosage form, mixed together with the compounds of this invention in a single composition.

(114) The compounds described herein can, for example, be administered by injection, intravenously, intraarterially, subdermally, intraperitoneally, intramuscularly, or subcutaneously; or orally, buccally, nasally, transmucosally, topically, in an ophthalmic preparation, or by inhalation, with a dosage ranging from about 0.5 to about 100 mg/kg of body weight, alternatively dosages between 1 mg and 1000 mg/dose, every 4 to 120 hours, or according to the requirements of the particular drug. The methods herein contemplate administration of an effective amount of compound or compound composition to achieve the desired or stated effect. Typically, the pharmaceutical compositions of this invention will be administered from about 1 to about 6 times per day or alternatively, as a continuous infusion. Such administration can be used as a chronic or acute therapy. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. A typical preparation will contain from about 5% to about 95% active compound (w/w). Alternatively, such preparations contain from about 20% to about 80% active compound.

(115) Lower or higher doses than those recited above may be required. Specific dosage and treatment regimens for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the disease, condition or symptoms, the patient's disposition to the disease, condition or symptoms, and the judgment of the treating physician.

(116) Upon improvement of a patient's condition, a maintenance dose of a compound, composition or combination of this invention may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level. Patients may, however, require intermittent treatment on a long-term basis upon any recurrence of disease symptoms.

(117) Methods of Treatment

(118) The compounds and compositions described herein can be administered to cells in culture, e.g. in vitro or ex vivo, or to a subject, e.g., in vivo, to treat, prevent, and/or diagnose a variety of disorders, including those described herein below.

(119) The compounds and compositions described herein can be administered to a subject, for example using a method described herein, who is suffering from a disorder described herein, e.g., a disorder that would benefit from the modulation of STEP (e.g., activating or inhibiting STEP). The compounds and compositions described herein can be administered to a subject, for example using a method described herein, who is at risk for a disorder described herein, e.g., a disorder that would benefit from the modulation of STEP (e.g., activating or inhibiting STEP).

(120) Inhibitors of STEP may increase phosphorylation of an NMDA-R. Thus, in some embodiments, a compound described herein, e.g., a compound that inhibits STEP, may be useful for treating a disorder in which increasing phosphorylation of an NMDA-R would be beneficial.

(121) Inhibitors of STEP may activate an ERK1 or ERK2 kinase, for example, in the CNS. Thus, in some embodiments, a compound described herein, e.g., a compound that inhibits STEP, may be useful for treating a disorder in which activate an ERK1 or ERK2 kinase would be beneficial.

(122) Compounds described herein may be useful in treating a variety of disorders, including disorders of the CNS. Exemplary disorders include schizophrenia, schizoaffective disorders, major depression, bipolar disorder, cognitive deficit, mild cognitive impairment (MCI), Alzheimer's disease (AD), attention-deficit/hyperactivity disorder (ADHD), dementia, generalized anxiety disorders, panic disorders, obsessive-compulsive disorders, phobias, post-traumatic stress syndrome, anorexia nervosa, drug addiction, ischemic stroke, head trauma or brain injury, Huntington's disease, Parkinson's disease, spinocerebellar degeneration, motor neuron diseases, epilepsy, neuropathic pain, chronic pain, neuropathies, autism and autistic disorders.

(123) Compounds described herein may be useful for treating or preventing central nervous system disorders selected from the group consisting of schizophrenia; refractory, intractable or chronic schizophrenia; emotional disturbance; psychotic disorder; mood disorder; bipolar I type disorder; bipolar II type disorder; depression; endogenous depression; major depression; melancholy and refractory depression; dysthymic disorder; cyclothymic disorder; panic attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatization disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; sexual desire disorder; sexual arousal disorder; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorder; adjustment disorder; alcohol abuse; alcohol intoxication; drug addiction; stimulant intoxication; narcotism; anhedonia; iatrogenic anhedonia; anhedonia of a psychic or mental cause; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment caused by Alzheimer's disease; Parkinson's disease and associated neurodegenerative diseases; cognitive impairment of schizophrenia; cognitive impairment caused by refractory, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain (ache); mental retardation; autism disorder (autism); Tourette's disorder; tic disorder; attention-deficit/hyperactivity disorder; conduct disorder; and Down's syndrome.

(124) Compounds described herein may be useful for treating or preventing disorders selected from schizophrenia, schizoaffective disorder, bipolar disorder, manic-depressive disorder, psychosis, mood and anxiety disorders, mania, drug or substance addiction, cognition disorders, learning disabilities, learning and memory disorders, aging and neurologic disorders associated with or linked with cognitive impairments; mild cognitive impairments (MCI), Alzheimer's disease, Alzheimer-related cognition disorders, Huntington's disease, Parkinson's disease, CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), amnesia, Wernicke-Korsakoff syndrome, Korsakoff syndrome, mild traumatic head injury (MBTI), traumatic head injury (TBI), fragile X syndrome, stroke, attention-deficit and hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), loss of concentration, autism, cerebral palsy, encephalopathy, and narcolepsy. The disorder may affect learning and memory, neurogenesis, neuronal plasticity, pain perception, mood and anxiety, or neuroendocrine regulation. The disorder may be a cognitive deficit disorder. The disorder may involve pain perception or neuroendocrine regulation.

(125) Schizophrenia

(126) In some embodiments, a compound or composition described herein can be used in the treatment of schizophrenia. Schizophrenia is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality. Distortions in perception may affect all five senses, including sight, hearing, taste, smell and touch, but most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational dysfunction. Onset of symptoms typically occurs in young adulthood, with approximately 0.4-0.6% of the population affected. Diagnosis is based on the patient's self-reported experiences and observed behavior.

(127) The disorder is thought to mainly affect cognition, but it also usually contributes to chronic problems with behavior and emotion. People with schizophrenia are likely to have additional (comorbid) conditions, including major depression and anxiety disorders. Social problems, such as long-term unemployment, poverty and homelessness, are common. Furthermore, the average life expectancy of people with the disorder is 10 to 12 years less than those without, due to increased physical health problems and a higher suicide rate.

(128) The Diagnostic and Statistical Manual of Mental Disorders (DSM) contains five sub-classifications of schizophrenia. These include Paranoid type (where delusions and hallucinations are present but thought disorder, disorganized behavior, and affective flattening are absent); Disorganized type (also known as hebephrenic schizophrenia, where thought disorder and flat affect are present together); Catatonic type (the subject may be almost immobile or exhibit agitated, purposeless movement; symptoms can include catatonic stupor and waxy flexibility); Undifferentiated type (psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic types have not been met); and Residual type (where positive symptoms are present at a low intensity only).

(129) The International Statistical Classification of Diseases and Related Health Problems (10th Revision) defines two additional subtypes. These include Post-schizophrenic depression (a depressive episode arising in the aftermath of a schizophrenic illness where some low-level schizophrenic symptoms may still be present); and Simple schizophrenia (insidious and progressive development of prominent negative symptoms with no history of psychotic episodes.)

(130) An agent for the treatment of schizophrenia may improve so-called positive symptoms in the acute period of schizophrenia such as hallucinations, delusions, excitations and the like. An agent for treating schizophrenia may also improve so-called negative symptoms that are observed in the chronic period of schizophrenia such as apathy, emotional depression, hyposychosis and the like.

(131) Schizoaffective Disorder

(132) Schizoaffective disorder is a psychiatric diagnosis that describes a mental disorder characterized by recurring episodes of elevated or depressed mood, or simultaneously elevated and depressed mood that alternate or occur together with distortions in perception. The perceptual distortion component of the disorder, called psychosis, may affect all five senses, including sight, hearing, taste, smell and touch, but most commonly manifest as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social and occupational dysfunction. The elevated, depressed or simultaneously elevated and depressed mood episode components of the disorder, called mood disorder, are broadly recognized as depressive and bipolar types of the illness; the division is based on whether the individual has ever had a manic, hypomanic or mixed episode. Onset of symptoms usually begins in early adulthood and is rarely diagnosed in childhood (prior to age 13). The lifetime prevalence of the disorder is uncertain (due to studies using varying diagnostic criteria), although it is generally agreed to be less than 1 percent, and possibly in the range of 0.5 to 0.8 percent. Diagnosis is based on the patient's self-reported experiences and observed behavior. No laboratory test for schizoaffective disorder currently exists. As a group, people with schizoaffective disorder have a more favorable prognosis than people with schizophrenia, but a worse prognosis than those with mood disorders.

(133) The disorder is thought to mainly affect cognition and emotion, but it also usually contributes to ongoing problems with behavior and motivation. People with schizoaffective disorder are likely to have additional (comorbid) conditions, including anxiety disorders and substance abuse. Social problems, such as long-term unemployment, poverty and homelessness, are common. Furthermore, the average life expectancy of people with the disorder is shorter than those without the disorder, due to increased physical health problems and a higher suicide rate.

(134) Cognitive Deficit

(135) Treatment using a compound or composition described herein may improve a cognitive deficit associated with a cognition-related disorder. Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance. The term may describe deficits in global intellectual performance, such as mental retardation, it may describe specific deficits in cognitive abilities (learning disorders, dyslexia), or it may describe drug-induced cognitive/memory impairment, such as that seen with alcohol and the benzodiazepines. Cognitive deficits may be congenital or caused by environmental factors such as brain injuries, neurological disorders, or mental illness.

(136) Exemplary cognition-related disorders (e.g., cognitive dysfunction) include, without limitation, mild cognitive impairment (MCI), dementia, delirium, amnestic disorder, Alzheimer's disease, Parkinson's disease and Huntington's disease; memory disorders including memory deficits associated with depression, senile dementia, dementia of Alzheimer's disease; cognitive deficits or cognitive dysfunction associated with neurological conditions including, for example, Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease, depression, schizophrenia and other psychotic disorders such as paranoia and manic-depressive illness; cognitive dysfunction in schizophrenia; disorders of attention and learning such as attention deficit disorders (e.g., attention deficit hyperactivity disorder (ADHD)) and dyslexia; cognitive dysfunction associated with developmental disorders such as Down's syndrome and Fragile X syndrome; loss of executive function; loss of learned information; vascular dementia; schizophrenia; cognitive decline; a neurodegenerative disorder; and other dementias, for example, dementia due to HIV disease, head trauma, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, or due to multiple etiologies. Cognition-related disorders also include, without limitation, cognitive dysfunction associated with MCI and dementias such as Lewy Body, vascular, and post stroke dementias. Cognitive dysfunction associated with surgical procedures, traumatic brain injury or stroke may also be treated in accordance with the embodiments described herein.

(137) Major Depression

(138) Major depression (also known as clinical depression, major depressive disorder, unipolar depression, or unipolar disorder) is a mental disorder characterized by a pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Types of Major depressive disorder include, e.g., Atypical depression, Melancholic depression, Psychotic depression, Catatonic depression, Postpartum depression, and Seasonal affective disorder.

(139) Bipolar Disorder

(140) Bipolar disorder, also known as manic depressive disorder, manic depressive psychosis, manic depression or bipolar affective disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if milder, hypomania. Individuals who experience manic episodes also commonly experience depressive episodes or symptoms, or mixed episodes in which features of both mania and depression are present at the same time. These episodes are usually separated by periods of normal mood, but in some individuals, depression and mania may rapidly alternate, known as rapid cycling. Extreme manic episodes can sometimes lead to psychotic symptoms such as delusions and hallucinations. The disorder has been subdivided into bipolar I, bipolar II, cyclothymia, and other types, based on the nature and severity of mood episodes experienced; the range is often described as the bipolar spectrum.

(141) Anxiety Disorders

(142) Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Current psychiatric diagnostic criteria recognize a wide variety of anxiety disorders. Recent surveys have found that as many as 18% of Americans may be affected by one or more of them.

(143) Generalized anxiety disorder is a common chronic disorder characterized by long-lasting anxiety that is not focused on any one object or situation. Those suffering from generalized anxiety experience non-specific persistent fear and worry and become overly concerned with everyday matters. Generalized anxiety disorder is the most common anxiety disorder to affect older adults.

(144) In panic disorder, a person suffers from brief attacks of intense terror and apprehension, often marked by trembling, shaking, confusion, dizziness, nausea, difficulty breathing. These panic attacks, defined by the APA as fear or discomfort that abruptly arises and peaks in less than ten minutes, can last for several hours and can be triggered by stress, fear, or even exercise; although the specific cause is not always apparent. In addition to recurrent unexpected panic attacks, a diagnosis of panic disorder also requires that said attacks have chronic consequences: either worry over the attacks' potential implications, persistent fear of future attacks, or significant changes in behavior related to the attacks. Accordingly, those suffering from panic disorder experience symptoms even outside of specific panic episodes. Often, normal changes in heartbeat are noticed by a panic sufferer, leading them to think something is wrong with their heart or they are about to have another panic attack. In some cases, a heightened awareness (hypervigilance) of body functioning occurs during panic attacks, wherein any perceived physiological change is interpreted as a possible life threatening illness (i.e. extreme hypochondriasis).

(145) Obsessive compulsive disorder is a type of anxiety disorder primarily characterized by repetitive obsessions (distressing, persistent, and intrusive thoughts or images) and compulsions (urges to perform specific acts or rituals). The OCD thought pattern may be likened to superstitions insofar as it involves a belief in a causative relationship where, in reality, one does not exist. Often the process is entirely illogical; for example, the compulsion of walking in a certain pattern may be employed to alleviate the obsession of impending harm. And in many cases, the compulsion is entirely inexplicable, simply an urge to complete a ritual triggered by nervousness. In a minority of cases, sufferers of OCD may only experience obsessions, with no overt compulsions; a much smaller number of sufferers experience only compulsions.

(146) The single largest category of anxiety disorders is that of Phobia, which includes all cases in which fear and anxiety is triggered by a specific stimulus or situation. Sufferers typically anticipate terrifying consequences from encountering the object of their fear, which can be anything from an animal to a location to a bodily fluid.

(147) Post-traumatic stress disorder or PTSD is an anxiety disorder which results from a traumatic experience. Post-traumatic stress can result from an extreme situation, such as combat, rape, hostage situations, or even serious accident. It can also result from long term (chronic) exposure to a severe stressor, for example soldiers who endure individual battles but cannot cope with continuous combat. Common symptoms include flashbacks, avoidant behaviors, and depression.

(148) Combination Therapies

(149) In some embodiments, the subject is being treated with an additional therapeutic agent. Such additional agents include atypical antipsychotics such as aripiprazole, clozapine, ziprasidone, risperidone, quetiapine, olanzapine, amisulpride, asenapine, iloperidone, melperone, paliperidone, perospirone, sertindole and sulpiride; and typical antipsychotics such as haloperidol, molindone, loxapine, thioridazine, molindone, thiothixene, pimozide, fluphenazine, trifluoperazine, mesoridazine, chlorprothixene, chlorpromazine, perphenazine, triflupromazine and zuclopenthixol.

(150) Clinical Outcomes

(151) In some embodiments, treatment with a compound or composition described herein, for example, using a method described herein, improves one or more clinical outcomes. For example, in some embodiments, treatment with a compound or composition described herein may improve cognitive function. Elements of cognitive function include memory, orientation, attention, reasoning, language and praxis.

(152) In some embodiments, clinical outcomes may be assessed using known methods. One such method is the Brief Psychiatric Rating Scale (BPRS), a multi-item inventory of general psychopathology traditionally used to evaluate the effects of drug treatment in schizophrenia. The BPRS psychosis cluster (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) is considered a particularly useful subset for assessing actively psychotic schizophrenic patients.

(153) In some embodiments, clinical outcomes may be assessed using the 7-point Clinical Global Impression (CGI) rating scale, a commonly used measure of symptom severity, treatment response and the efficacy of treatments. The CGI reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient.

(154) In some embodiments, clinical outcomes may be assessed using the 30-item Positive and Negative Symptoms Scale (PANSS). The name refers to the two types of symptoms in schizophrenia, as defined by the American Psychiatric Association: positive symptoms, which refer to an excess or distortion of normal functions (e.g. hallucinations and delusions), and negative symptoms, which represent a dimunition or loss of normal functions.

(155) In some embodiments, clinical outcomes may be assessed using the Scale for Assessing Negative Symptoms (SANS). SANS assesses five symptom complexes to obtain clinical ratings of negative symptoms in patients with schizophrenia. They are: affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. Assessments are conducted on a six-point scale.

(156) The invention is further illustrated by the following examples which are intended to illustrate but not limit the scope of the invention.

EXAMPLES

(157) Abbreviations

(158) DCM: Dichloromethane EA, EtOAc or AcOEt: Ethyl acetate PE: Petroleum ether DIPEA: Diisopropylethylamine TEA: Triethylamine rt: Room temperature SOCl.sub.2: Thionyl chloride POCl.sub.3: Phosphorous oxychloride THF: Tetrahydrofuran NaOAc: Sodium acetate MeOH: Methanol i-AmOH: Isoamyl alcohol NaH: Sodium hydride NaBH.sub.3CN: Sodium cyanoborohydride n-BuLi: n-Butyl lithium LHMDS: Lithium bis(trimethylsilyl)amide LDA: Lithium diisopropylamide i-PrOH: Isopropyl alcohol Na.sub.2SO.sub.4: Sodium sulfate Mg.sub.2SO.sub.4: Magnesium sulfate MeCN: Acetonitrile NaOH: Sodium hydroxide EtOH: Ethanol CuI: Copper(I) iodide Pd(PPh.sub.3).sub.2Cl.sub.2: trans-Dichlorobis(triphenylphosphine)palladium(II) MsCl: Methanesulfonyl chloride BINAM: [1,1-Binaphthalene]-2,2-diamine Xphos: 2-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl Sphos: 2-Dicyclohexylphosphino-2,6-dimethoxybiphenyl DavePhos: 2-(Dicyclohexylphosphino)-2-(N,N-dimethylamino)biphenyl Cs.sub.2CO.sub.3: Cesium carbonate K.sub.2CO.sub.3: Potassium carbonate Mwave or W or mW: Microwave t-BuOH: tert-Butanol K.sub.3PO.sub.4: Potassium phosphate Pd(APhos).sub.2Cl.sub.2:Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloro palladium(II) Pd(PPh.sub.3).sub.4: Tetrakis(triphenylphosphine)palladium (O) Pd(dppf).sub.2Cl.sub.2: Dichloro[1,1-bis(diphenylphosphino)ferrocene]palladium(II) PdOAc: Palladium(II) acetate Pd.sub.2dba.sub.3: Tris(dibenzylideneacetone)dipalladium (O) Pd-118: Dichloro[1,1-bis(di-t-butylphosphino)ferrocene]palladium(II) Xantphos: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene BINAP: ()-2,2-Bis(diphenylphosphino)-1,1-binaphthalene EDCI: 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide HOBt: Hydroxybenzotriazole NH.sub.4OH: Ammonium hydroxide H.sub.2O: Water Pd/C: Palladium on carbon DMF: N,N-Dimethylformamide KOCN: Potassium cyanate WSC-HCl or WSCDI: Water Soluble Carbodiimide hydrochloride HATU: O-(7-Azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate HBTU: O-(Benzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate Py-Brop: Bromotripyrrolidinophosphonium hexafluorophosphate BOP: Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluoro phosphate DBU: diaza(1,3)bicyclo[5.4.0]undecene DMSO: Dimethyl sulfoxide LCMS: Liquid chromatography mass spectrometry HPLC: High performance liquid chromatography DMA: N,N-dimethylacetamide h: hour TLC: Thin layer chromatography TFA: Trifluoroacetic acid Et.sub.3N: Triethylamine DIPEA: N,N-Diisopropylethylamine O.N: Overnight TBSO: tert-Butyldimethylsilyloxy DME: Dimethyl ether NMP: 1-methyl-2-pyrrolidinone PS-BEMP: 2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine supported on Polystyrene PBr.sub.3: Phosphorus tribromide NaOtBu: Sodium tert-butoxide KI: Potassium iodide PPh.sub.3: Triphenylphosphine NMM: N-Methylmorpholine HCHO: Formaldehyde PG: Protecting group ISCO: Teledyne ISCO purification systems BINAM: 1,1-binaphthyl-2,2-diamine.
General Experimental:

(159) All exemplified target compounds are fully analyzed and characterized (TLC, LCMS, .sup.1H-NMR) prior to submission for biological evaluation. Thin-layer chromatography was carried out on native silica 254F plates. Visualization was accomplished with ultraviolet or phosphomolybdic acid. .sup.1H-NMR spectra were recorded on multiple NMR spectrometers, either on 400 MHz on a Avance III 400 Ultra shield-plus TM digital Spectrometer or on 300 MHz using a Varian Mercury 300Plus Spectrometer, designated by 400 MHz or 300 MHz, respectively. .sup.1H-NMR spectra were also recorded on a Bruker Spectrospin 300 MHz Spectrometer at 300.13 MHz in DMSO-d6 with TMS as an internal standard and will be designated as Bruker 300 Hz. NMR assignments are based on a combination of the .sup.1H, .sup.13C, .sup.1HCOSY, HMBC and HMQC spectra. Coupling constants are given in hertz (Hz). Anhydrous methylene chloride, tetrahydrofuran, and dimethylformamide were obtained by distillation, and other materials are reagent grade.

(160) LC-MS Methods are Listed Here:

(161) Method A: Mobile phase: A=0.1% TFA/H.sub.2O, B=0.01% TFA/MeCN; Gradient: B=5%-95% in 1.5 min; Flow rate: 2.0 mL/min; Column: sunfire-C.sub.18, 504.6 mm, 3.5 um; Method B: Mobile phase: A=10 mM NH.sub.4HCO.sub.3/H.sub.2O, B=MeCN; Gradient: B=5%-95% in 1.5 min; Flow rate: 2.0 mL/min; Column: Xbridge-C.sub.18, 504.6 mm, 3.5 um; Method C: Mobile phase: A=10 mM ammonium formate/H.sub.2O/4.9% MeCN, B=MeCN; Gradient: B=5%-100% in 2.0 min; Flow rate: 2.5 mL/min; Column: Atlantis T3 3 uM 4.630 mm Method D: Mobile phase: A=0.1% formic acid/H.sub.2O/4.9% MeCN, B=MeCN; Gradient: B=5%-100% in 2.0 min; Flow rate: 2.5 mL/min; Column: Atlantis T3 3 uM 4.630 mm Method E: Mobile phase: A=0.05% TFA/H.sub.2O, B=0.05% TFA/MeCN; Gradient: B=5%-100% in 3.0 min; Flow rate: 0.8 mL/min; Column: CAPCELL PAK C18 (Shiseido, UG120, 3 mM, 2.0 mm I.D.50 mm)
Representative Conditions of PREP-HPLC are Listed Here: PREP-HPLC Condition A (Basic Mobile Phase): Instrument: Gilson 281 Mobile Phase: A=0.01% NH.sub.4HCO.sub.3/H.sub.2O, B=MeCN Flow Rate: 40.0 mL/min Column: AGT Venusil XBP C.sub.18, 10.0 um, 30 mm100 mm
PREP-HPLC Condition B (Basic Mobile Phase): Instrument: Gilson 281 Mobile Phase: A=NH.sub.3H.sub.2O, 10 mmol/L, B=MeCN Flow Rate: 40.0 mL/min Column: Waters X-Bridge, 5.0 um, 30 mm150 mm
PREP-HPLC Condition C (Basic Mobile Phase): Instrument: Gilson 281 Mobile Phase: A=0.01% NH.sub.4HCO.sub.3/H.sub.2O, B=MeCN Flow Rate: 30.0 mL/min Column: Shimadzu PRC-ODS, 10.0 um, 20 mm250 mm Gradient: B=xx %-yy % 0.0 to 8.0 min yy %-95% 8.0 to 8.2 min 95%-95% 8.2 to 11.0 min
The following table shows the relationship of representative value (xx %-yy %) of gradient and retention time on LC-MS of corresponding compound. 25%-30% 0.5-1.0 min 30%-50% 1.0-1.5 min 50%-70% 1.5-1.75 min 70%-90% 1.7-2.0 min
PREP-HPLC Condition D: Instrument: Waters 600 pump, Waters 2996, Photodiode Array Detector, Waters Micromass ZQ, Gilson 215 Liquid Handler. Mobile Phase: A=0.05% TFA/H.sub.2O, B=MeCN Flow Rate: 36.0 mL/min Column: Shiseido CAPCELL PAK C18, UG120, 5 uM, 20 mm I.D.50 mm Gradient: B=5%-100% 0.0 to 4.0 min

(162) ##STR00135##

(163) ##STR00136##

(164) Method A: 2-Nitro-5-propoxy-benzamide (i-a) A mixture of 2-nitro-5-propoxy-benzoic acid (1.97 g, 8.75 mmol) and DMF (0.1 mL) in SOCl.sub.2 (20 mL) was stirred at 65 C. for 2 h. After the reaction was completed, the mixture was cooled to room temperature. SOCl.sub.2 was removed in vacuo and the residue was dissolved in anhydrous CH.sub.2Cl.sub.2 (10 mL), which was added to NH.sub.3H.sub.2O (28%) dropwise. After 1 h, the precipitate was collected and dried in vacuo to give 1.68 g of i-a as a yellow solid (85.2%). LCMS m/z=208.1 (M-16), 225.1 (M+1) (Method B) (retention time=1.88 min)

(165) Method B: 2-Amino-5-propoxy-benzamide (ii-a) To a mixture of 2-nitro-5-propoxy-benzamide (1.20 g, 5.36 mmol) in MeOHH.sub.2O (v/v, 3:1, 60 mL) was added NH.sub.4Cl (2.84 g, 53.6 mmol) and Fe (2.99 g, 53.6 mmol). The resulting mixture was stirred at 60 C. for 3 h. After the reaction was completed, the mixture was cooled to room temperature and the iron was filtered off. The filtrate was concentrated to 15 mL and the formed precipitate was collected and dried in vacuo to give 1.02 g of ii-a as a pale yellow solid (98%). LCMS m/z=178.1 (M-16), 195.1 (M+1) (Method B) (retention time=1.46 min)

(166) ##STR00137##

(167) Method I: 2-Amino-4-chlorobenzamide (ii-b) To a mixture of 2-amino-4-chlorobenzoic acid (3.42 g, 20 mmol) in DMF (45 mL) was added HOBt (2.70 g, 20 mmol). After stirring for 10 min, EDC hydrogen chloride (3.82 g, 20 mmol) was added to the mixture. The resulted mixture was stirred at room temperature for 2 h. NH.sub.4OH (28%, 5 mL) was added at 0 C. with vigorous stirring. After addition, the mixture was stirred at room temperature for another 2 h. The reaction mixture was added to water (200 mL) dropwise with stirring, then a precipitate formed. The precipitate was collected and dried in vacuo to give 2.98 g of ii-b as a grey solid (87.6% yield). LCMS m/z=171.0 (M+1), 173.0 (M+3) (Method B) (retention time=1.39 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 7.27 (d, J=9.6 Hz, 1H), 6.68 (d, J=2.4 Hz, 1H), 6.60 (dd, J=8.4, 2.0 Hz, 1H), 5.50-5.82 (m, 4H).

(168) ##STR00138##
Method F for Chlorinating Conditions F1: POCl.sub.3/N,N-dimethylbenzeneamine F2: SOCl.sub.2/DMF/80 C. F3: SOCl.sub.2 (4-8 equiv.)/DMF/DCM/rt-40 C. F4: Phenylphosphinic dichloride/80-120 C. F5: POCl.sub.3/ F6: POCl.sub.3/Toluene/100 C. F7: PBr.sub.3/CH.sub.2Cl.sub.2/DMF/60 C.
Method G for Coupling Conditions G1: i-PrOH/85-100 C. G2: THF/reflux G3: i-AmOH/100-130 C. G4: MeOH/microwave/150 C. G5: i-AmOH/microwave/150 C. G6: THF/Et.sub.3N/reflux G7: THFH.sub.2O/NaOAc/rt-60 C. G8: NaH/THF G9: n-BuLi/THF G10: LHMDS/THF G11: LDA/THF G12: K.sub.2CO.sub.3/DMF/60 C. G13: Cs.sub.2CO.sub.3/DMA/80 C. G14: NaOtBu/DMF/Microwave/100 C.
Method J for Coupling Conditions J1: Pd(PPh.sub.3).sub.4/t-BuOK/Dioxane J2: Pd.sub.2(dba).sub.3/Xantphos/Cs.sub.2CO.sub.3/Dioxane

(169) ##STR00139## ##STR00140##

(170) Method C: N-(2-Carbamoyl-4-propoxy-phenyl)-nicotinamide (iii-a) To a solution of 2-amino-5-propoxy-benzamide (760 mg, 3.91 mmol) in THF (15 mL) and Et.sub.3N (1 mL) was added nicotinoyl chloride (607 mg, 4.30 mmol) in anhydrous THF (15 mL) dropwise. The resulting mixture was stirred at room temperature for 3 h. After the reaction was completed, the volatiles were removed. The residue was washed with H.sub.2O (10 mL). The pH was adjusted to approximately 5 by adding dilute HCl (2N in water). The resulting solid was collected and dried in vacuo to give 1.00 g of iii-a as a pale yellow solid (89.0%). LCMS m/z=300.1 (M+1) (Method B) (retention time=1.60 min)

(171) Method D: 2-benzamido-5-methoxy-3-methylbenzamide (iii-b) A 50 mL round-bottom flask was charged with nicotinic acid (41 mg, 0.33 mmol, 1.0 eq.), 2-amino-5-methoxy-3-methylbenzamide (60 mg, 0.33 mmol, 1.0 eq.) and HBTU (190 mg, 0.50 mmol, 1.5 eq), which were suspended in 4 mL of DMF. DIPEA (86 mg, 0.66 mmol, 2.0 eq.) was added dropwise at room temperature and the reaction mixture was stirred overnight. The reaction mixture was added to water (10 mL) dropwise with stirring. The mixture was extracted with ethyl acetate. The ethyl acetate was evaporated and 55 mg of the orange solid (58.5% yield) was obtained. LCMS m/z=286.1 (M+1) (Method B) (retention time=1.24 min)

(172) Method E: 6-Propoxy-2-pyridin-3-yl-1H-quinazolin-4-one (iv-a) A mixture of N-(2-carbamoyl-4-propoxy-phenyl)-nicotinamide (980 mg, 3.27 mmol) in EtOH (20 mL) was treated with NaOH (654 mg, 16.37 mmol). The resulting mixture was stirred at room temperature for 18 h. After the reaction was completed, the volatiles were removed in vacuo. The residue was partitioned between H.sub.2O (50 mL) and ethyl acetate (50 mL). The aqueous layer was neutralized to pH 7 by slowly adding aq. citric acid and then a precipitate formed. The precipitate was collected and dried to give 1.00 g of iv-a as a grey solid (quantitative yield). LCMS m/z=282.1 (M+1) (Method B) (retention time=1.60 min)

(173) Method F1: 4-Chloro-6-propoxy-2-pyridin-3-yl-quinazoline (v-a)

(174) (This method is representative of method F1, F2, F3 and F4. These three methods can be implemented in a similar way except for substitution of the appropriate chlorinating reagent, solvent and temperature) To a mixture of 6-propoxy-2-pyridin-3-yl-1H-quinazolin-4-one (1.00 g, 3.56 mmol) in POCl.sub.3 (10 mL) was added N,N-dimethylaniline (0.1 mL). The resulting mixture was stirred at 120 C. for 2 h. After the reaction was completed, POCl.sub.3 was removed in vacuo, and the residue was added to ice-water slowly. The pH was adjusted to around 7 by slowly adding NaHCO.sub.3 (sat.) at 0 C. The resultant solid was collected and purified by chromatography on silica gel eluted with petroleum ether/ethyl acetate (v/v=4:1 to 1:1) to give 580 mg of v-a as a pale yellow solid (54.7%).

(175) Method F5: 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (v-c) In a sealed tube, phosphorus oxychloride (11 mL, 120 mmol) was added to 6-methoxy-2-(pyridin-3-yl)quinazolin-4(3H)-one (2.70 g, 10.66 mmol). The mixture was refluxed at 120 C. for 12 h. After cooling, the remaining phosphorus oxychloride was removed in vacuo to leave a tan solid. This residue was added to an ice-water mixture (100 mL) with cooling and allowed to stir. The pH of the suspension was adjusted to about pH 9 via dropwise addition of 28% ammonium hydroxide, and stirring was continued for 30 mins. The resulting solid was filtered to give the desired product as a tan solid (2.55 g, 9.39 mmol, 88%). LC-MS m/z=272.0 (M+1) (retention time=2.05).sup.1H NMR (300 MHz, DMSO) 9.55 (s, 1H), 8.81-8.64 (m, 2H), 8.09 (d, J=9.2 Hz, 1H), 7.78 (dd, J=9.2, 2.8 Hz, 1H), 7.61 (dd, J=7.9, 4.8 Hz, 1H), 7.49 (d, J=2.5 Hz, 1H), 4.00 (s, 3H).

(176) Method F6: 6-Bromo-4-chloro-8-fluoro-2-(pyridin-3-yl)quinazoline (v-d) To a suspension of 6-bromo-8-fluoro-2-(pyridin-3-yl)quinazolin-4-ol (6.16 g, 0.0192 mol) in toluene (60 mL) was added phosphorus oxychloride (5.30 ml, 0.0579 mol) at room temperature. The mixture was refluxed for 3 h. The solvent was evaporated and water was added to the residue under cooling conditions. The suspension was stirred at room temperature for 30 min, the resulting precipitate was filtered and dried to give the title compound (6.5 g, quantitative). .sup.1H NMR (400 MHz, DMSO) 9.58 (d, J=1.6 Hz, 1H), 8.82 (dd, J=4.7, 1.5 Hz, 1H), 8.80-8.75 (m, 1H), 8.37 (dd, J=9.7, 1.9 Hz, 1H), 8.34-8.29 (m, 1H), 7.67 (dd, J=7.8, 4.6 Hz, 1H).

(177) Method F7: 4-Bromo-6-methoxy-2-(pyridin-3-yl)quinazoline (v-e) To a sealed tube containing 6-methoxy-2-(pyridin-3-yl)quinazolin-4(3H)-one (1.30 g, 5.13 mmol) in dichloromethane (20 mL) was added 1 M phosphorus tribromide in dichloromethane (10.3 mL, 10.3 mmol) and DMF (2 mL). The reaction mixture was heated at 60 C. for 4 h. After cooling, excess dichloromethane was evaporated leaving a tan residue. This solid was added to an ice-water mixture (100 mL) with cooling and allowed to stir. The pH of the suspension was adjusted to about pH 9 via dropwise addition of 28% ammonium hydroxide, and stirring was continued for 30 mins. The resulting solid was filtered to give the desired product as a tan solid (1.49 g, 4.71 mmol, 92%). LC-MS m/z=318.3 (M+2) (retention time=2.19).

(178) Method G1: 2-(6-Propoxy-2-pyridin-3-yl-quinazolin-4-ylamino)-benzamide (vi-a)

(179) (This method is representative of method G1, G2, and G3. These three methods can be implemented in a similar way except for substitution of the appropriate solvent and temperature) A mixture of 4-chloro-6-propoxy-2-(pyridin-3-yl)quinazoline (90 mg, 0.3 mmol) and 2-aminobenzamide (52 mg, 0.4 mmol) in i-PrOH (5 mL) was stirred at 85 C. for 18 h. The yellow precipitate was collected and washed with i-PrOH (10 mL). The solid was suspended in water (10 mL) and NH.sub.3H.sub.2O (1 mL) was added. After filtration the solid was dried in vacuo to afford 31.0 mg of vi-a as a white solid (30.8%). LCMS m/z=400.1 (M+1) (Method B) (retention time=1.96 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.59 (d, J=2.0 Hz, 1H), 9.58 (d, J=7.6 Hz, 1H), 8.69-8.74 (m, 2H), 8.48 (s, 1H), 7.97 (d, J=6.8 Hz, 2H), 7.90 (d, J=8.8 Hz 1H), 7.74 (t, J=7.6 Hz, 1H), 7.56-7.61 (m, 3H), 7.20 (t, J=7.2 Hz, 1H), 4.16 (t, J=6.4 Hz, 2H), 1.86 (dd, J=14.0, 6.8 Hz, 2H), 1.07 (t, J=7.2 Hz, 3H).

(180) Method G8: 2-(6-ethoxy-2-(pyridin-3-yl)quinazolin-4-yloxy)benzamide (vii-a)

(181) (The method G8 is representative of method G6, G7, G9, G10 and G11. These six methods can be implemented in a similar way except for substitution of the appropriate base, solvent and temperature) To a 2.5 dram reaction vial was first added sodium hydride 60% (0.028 g, 0.700 mmol) and salicylamide (0.072 g, 0.525 mmol) in DMF (2 mL). The mixture was allowed to stir at room temperature for 1 h. Then, 4-chloro-6-ethoxy-2-(pyridin-3-yl)quinazoline (0.100 g, 0.350 mmol) was added to the mixture, and the reaction was allowed to proceed at room temperature overnight. LC-MS analysis of the crude mixture showed about 85% of product formed and 10% remaining starting material. Water (30 mL) was added to the mixture, and the product was extracted with chloroform (315 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered, and concentrated. The crude product was purified via ISCO (silica gel, 97.5:2.5 CH.sub.2Cl.sub.2/MeOH; 12 g column) to afford 13.9 mg of the desired product as a white solid (10.3%) LCMS m/z=387 (M+1) (Method C) (retention time=2.05 min). .sup.1H NMR (300 MHz, DMSO) 11.47 (s, 2H), 9.39 (s, 1H), 8.66 (d, J=2.8 Hz, 1H), 8.56-8.47 (m, 1H), 8.01-7.90 (m, 2H), 7.69-7.55 (m, 2H), 7.55-7.40 (m, 2H), 7.05 (t, J=7.5 Hz, 1H), 6.97 (d, J=8.2 Hz, 1H), 4.23 (q, J=6.9 Hz, 2H), 1.44 (t, J=6.9 Hz, 3H).

(182) Method G13: 4-(4-chlorophenyl)-N-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-yl)thiazol-2-amine (vi-c) (The method G13 is representative of method G12 also. This method can be implemented in a similar way except for substitution of the appropriate base, solvent and temperature) To a suspension of 4-chloro-6-methoxy-2-(pyridine-3-yl)quinazoline (645.2 mg, 2.375 mmol) and 2-amino-4-(4-chlorophenyl)thiazole (1050 mg, 4.98 mmol) in DMA (40 mL) was added Cs.sub.2CO.sub.3 (2430 mg, 7.46 mmol) at room temperature. The mixture was stirred at 80 C. for 9.5 h. Water was added and a precipitate formed which was collected by filtration and washed with H.sub.2O. Recrystallization from acetone/DMF/methanol gave 383.6 mg of the product in a 36% yield as yellow solid, >98% purity by .sup.1H NMR). .sup.1H NMR (400 MHz DMSO-d.sub.6) 12.52 (s, 1H), 9.78 (d, J=1.56 Hz, 1H), 8.91-8.88 (m, 1H), 8.74 (dd, J=4.74, 1.60 Hz, 1H), 8.33 (brs, 1H), 8.06 (d, J=8.56 Hz, 2H), 7.93 (d, J=9.08 hz, 1H), 7.89 (s, 1H), 7.66-7.59 (m, 2H), 7.55 (d, J=8.56 Hz, 2H), 4.01 (s, 3H).

(183) Method G14: 4-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-1H-pyrazole-5-carboxamide, 2HCl (vi-d) The method G14 is representative of method G4 and G5 also. This method can be implemented in a similar way except for substitution of the appropriate solvent and adjustment of the temperature) To a microwave vial containing 4-bromo-6-methoxy-2-(pyridin-3-yl)quinazoline (150.0 mg, 0.47 mmol) in DMF (2 mL) was added 4-amino-1H-pyrazole-5-carboxamide (66.0 mg, 0.52 mmol) and sodium tert-butoxide (50 mg, 0.52 mmol). The reaction mixture was heated at 100 C. for 15 mins by microwave irradiation. Water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (550 mL). The crude material was purified via ISCO (silica, 12 g column, 93% CH.sub.2Cl.sub.2-7% MeOH-0.1% NH.sub.4OH) giving the product as a yellow solid. The free base was then converted to the HCl salt to yield the final product as an orange solid (59.8 mg, 0.14 mmol, 22%). LC-MS m/z=362.4 (M+1) (retention time=1.57) .sup.1H NMR (300 MHz, DMSO) 11.28 (s, 1H), 9.62 (d, J=1.7 Hz, 1H), 9.17 (d, J=7.8 Hz, 1H), 8.93 (dd, J=5.2, 1.3 Hz, 1H), 8.60 (s, 1H), 8.05 (s, 1H), 8.03-7.94 (m, 2H), 7.77 (s, 1H), 7.64 (dd, J=9.2, 2.5 Hz 1H), 7.40 (d, J=2.6 Hz, 1H), 3.97 (s, 3H).

(184) Method J1: 1-(6-Methoxy-2-(pyridin-3-yl)quinazolin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (vi-b) To a 50-mL two-neck round bottom flask equipped with a reflux condenser was added a mixture of 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (50 mg, 0.18 mmol, 1 eq.) and 1H-benzo[d]imidazol-2(3H)-one (27 mg, 0.21 mmol, 1.1 eq.) in 5 mL of dry 1,4-dioxane. Pd(PPh.sub.3).sub.4 (10.6 mg, 0.009 mmol, 0.05 eq) and t-BuOK (41 mg, 0.36 mmol, 2 eq.) were added. The resulting mixture was stirred at 100 C. under N.sub.2 atmosphere overnight. After cooling, 20 mL of methanol was added. The mixture was filtered, the filtrate was concentrated in vacuo and then was purified with chromatography on silica gel (ethyl acetate/petroleum ether from 1:4 to 1:2) to give the crude product, which was further purified with reverse phase HPLC to afford 4.8 mg of vi-e as a pale yellow solid (7%). MS m/z=370.1 (M+1) (Method B) (retention time=1.680 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 11.51 (s, 1H), 8.78 (d, J=8.0 Hz, 2H), 8.17 (d, J=9.2 Hz, 1H), 7.80 (dd, J=9.2, 2.8 Hz, 1H), 7.70-7.64 (m, 1H), 7.46 (d, J=2.8 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 7.20 (d, J=4.0 Hz, 2H), 7.16-7.08 (m, 1H), 3.89 (s, 3H).

(185) Method J2: 6-methoxy-N-(pyridin-2-yl)-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (vi-e) To a suspension of 4-chloro-6-methoxy-2-(pyridine-3-yl)quinazoline (600 mg, 2.208 mmol) in dioxane (40 mL) under N.sub.2, was added tris(dibenzylideneacetone)dipalladium(O) (103.1 mg, 0.113 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (132.2 mg, 0.228 mmol) and cesium carbonate (1.1289 g, 3.46 mmol) at room temperature. 2-Aminopyridine (229 mg, 2.43 mmol) was added and the mixture was stirred at 100 C. for 2 h 30 min Water was added and then a precipitate formed. The solid was collected and washed with water. The solid was dissolved in CH.sub.2Cl.sub.2. Purification was carried out using NH-silica gel to give the free base (649.3 mg). The free base was converted to the HCl salt by dissolving the compound in CH.sub.2Cl.sub.2/MeOH and 1.5 ml of 4N HCl in ethyl acetate was added and then a precipitate formed. The solid was collected and dried in vacuo (at 40 degrees on and 60 degrees for ca. 3 h) and then washed with methanol. The resulting solid was dried in vacuo at 60 degrees to give 682 mg of the desired product as the HCl salt in a 77% yield as a pale yellow solid. .sup.1H NMR (DMSO-d.sub.6) 11.14 (brs, 1H), 9.58 (s, 1H), 9.13 (dd, J=7.96 Hz, 1H), 8.93 (d, J=5.24 Hz, 1H), 8.54 (d, J=4.72 Hz, 1H), 8.48 (d, J=8.32 Hz, 1H), 8.28 (brs, 1H), 8.09 (brt, J=7.16 Hz, 1H), 8.02-7.96 (m, 2H), 7.65 (dd, J=8.80, 2.48 Hz, 1H), 7.34 (brt, J=6.52 Hz, 1H), 4.01 (s, 3H). The 1H of 2HCl was not observed.

(186) Method J3: N-(Biphenyl-4-yl)-6-methoxy-2-(pyridin-3-yl)quinazolin-4-amine hydrochloride (vi-f) To a suspension of N-(4-bromophenyl)-6-methoxy-2-(pyridin-3-yl)quinazolin-4-amine (548.7 mg, 1.347 mmol) and phenylboronic acid (270 mg, 2.21 mmol) in dioxane/H.sub.2O (2/1) (30 mL) under N.sub.2 was added Na.sub.2CO.sub.3 (485 mg, 4.58 mmol) and tetrakis(triphenylphosphine) palladium(O) (78 mg, 0.067 mmol) at room temperature. The mixture was stirred at 100 C. for 1 h. Water was added and then a precipitate formed. The solid was dissolved in methanol/acetone at 60 C. The solution was filtrated through Celite to remove any extra palladium. The filtrate was concentrated down to give 493.4 mg of a solid residue in. The solid was added to CH.sub.2Cl.sub.2 followed by addition of 4N HCl in ethyl acetate (0.4 mL) at room temperature to form the HCl salt. The mixture was stirred at room temperature and the resulting solid was filtered and dried in vacuo to give 435.2 mg and a yield of 73% as the HCl salt. .sup.1H NMR (DMSO-d6) 10.24 (br, 1H), 9.54 (s, 1H), 8.92 (d, J=7.52 Hz, 1H), 8.82 (d, J=3.96 Hz, 1H), 8.10 (d, J=2.44 Hz, 1H), 8.03 (d, J=8.68 Hz, 2H), 7.92 (d, J=9.08 Hz, 1H), 7.84 (d, J=8.68 Hz, 2H), 7.81 (m, 1H), 7.77-7.75 (m, 2H), 7.62 (dd, J=9.08, 2.44 Hz, 1H), 7.50 (m, 2H), 7.38 (m, 1H), 4.01 (s, 3H). The 1H of HCl was not observed.

(187) The compounds in the following table were prepared in a manner analogous to that described in Scheme 1 and 5 (prepared according to method procedure A-J as designated).

(188) TABLE-US-00001 TABLE 1 Molecular .sup.1H-NMR Number Product Salt type Mass .sup.1H-NMR Solvent LCMS LCMS Protocol Purity percent Method for Coupling 1 399.45 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.59 (d, J = 2.0 Hz, 1 H), 9.58 (d, J = 7.6 Hz, 1H), 8.69-8.74 (m, 2H), 8.48 (s, 1H), 7.97 (d, J = 6.8 Hz, 2H), 7.90 (d, J = 8.8 Hz 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.56- 7.61 (m, 3H), 7.20 (t, J = 7.2 Hz, 1H), 4.16 (t, J = 6.4 Hz, 2H), 1.86 (dd, J = 7.2, 6.8 Hz, 2H), 1.07 (t, J = 7.2 Hz, 3H). DMSO 400.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 2 HCl 398.46 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.20 (s, 1 H), 9.79 (s, 1 H), 9.02-9.08 (m, 2H), 8.87 (d, J = 3.2 Hz, 1 H), 8.53 (s, 1 H), 8.34 (d, J = 8.0 Hz, 1 H), 8.19 (d, J = 6.8 Hz, 1 H), 7.74-7.99 (m, 5H), 7.28 (t, J = 7.6 Hz, 1H), 4.92 (d, J = 4.0 Hz, 2H), 2.87 (d, J = 3.2 Hz, 6H). DMSO 399.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 3 HCl 424.50 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.07 (s, 1H), 9.64 (d, J = 1.6 Hz, 1H), 9.15 (d, J = 8.0 Hz, 1 H), 8.78 (ddd, J = 8.0, 4.0, 2.4 Hz, 1H), 8.73 (dd, J = 4.4, 1.2 Hz, 1H), 8.49 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.92-7.69 (m, 3H), 7.67-7.74 (m, 2H), 7.62 (dd, J = 8.0, 4.8 Hz, 1 H), 7.22 (t, J = 7.6 Hz, 1H), 4.29 (s, 2H), 2.61 (brs, 4H), 1.70 (brs, 4H). DMSO 425.2 (M +1) Method B (NH4HCO3) 95 Method C, G1 4 422.43 1H-NMR (400 MHz, DMSO-d.sub.6): 9.87 (s, 1H), 9.52 (s, 1H), 8.67 (d, J = 5.6 Hz, 1H), 7.99 (d, J = 2.4 Hz, 1H), 7.94 (s, 1 H), 7.86 (d, J = 9.2 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.50-7.58 (m, 3H), 7.30 (t, J = 34.0 Hz, 1 H), 7.00 (dd, J = 8.4, 2.0 Hz, 1H), 4.16 (t, J = 6.4 Hz, 2H), 1.86 (dd, J = 7.2, 6.4 Hz, 2H), 1.07 (t, J = 7.2 Hz, 3H). DMSO 423.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 5 HCl 408.86 1H-NMR (400 MHz, DMSO-d.sub.6): 10.28 (s, 1 H), 9.48 (s, 1 H), 8.93 (d, J = 8.4 Hz, 1H), 8.85 (d, J = 4.4 Hz, 1H), 8.18 (dd, J = 7.6, 2.4 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H), 7.85-7.93 (m, 3H), 7.62 (dd, J = 8.8, 6.4 Hz, 1 H), 7.55 (t, J = 8.8 Hz, 1 H), 4.17 (t, J = 6.4 Hz, 3H), 1.86 (dd, J = 7.6, 6.4 Hz, 2H), 1.06 (t, J = 7.6 Hz, 3H). DMSO 409.1, 411.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 6 425.31 1H-NMR (400 MHz, DMSO-d.sub.6): 9.93 (s, 1 H), 9.51 (s, 1 H), 8.68-8.71 (m, 2H), 8.16 (d, J = 2.4 Hz, 1 H), 7.94 (d, J = 2.0 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 1 H), 7.56- 7.60 (m, 2H), 7.37 (s, 1 H), 4.14 (t, J = 6.4 Hz, 2H), 1.84 (dd, J = 10.4 Hz, 7.2 Hz, 2H), 1.07 (t, J = 7.6 Hz, 3H). DMSO 425.0, 427.0 (M +1) Method B (NH4HCO3) 95 Method C, G1 7 392.4 1H-NMR (400 MHz, DMSO-d.sub.6): 10.06 (s, 1 H), 9.49 (s, 1 H), 8.77-8.81 (m, 2H), 8.09 (ddd, J = 10.0, 7.6, 2.4 Hz, 1H), 7.88 (d, J = 9.2 Hz, 1 H), 7.69-7.74 (m, 2H), 7.54-7.61 (m, 2H), 4.15 (t, J = 6.4 Hz, 2H), 1.86 (dd, J = 14.0, 7.6 Hz, 2H), 1.06 (t, J = 7.2 Hz, 3H). DMSO 393.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 8 425.31 1H-NMR (400 MHz, DMSO-d.sub.6): 10.05 (s, 1 H), 9.51 (s, 1 H), 8.75-8.80 (m, 2H), 8.34 (d, J = 2.4 Hz, 1 H), 7.96-8.00 (m, 2H), 7.88 (d, J = 9.2 Hz, 1 H), 7.68-7.75 (m, 2H), 7.59 (dd, J = 9.2, 2.8 Hz, 1H), 4.15 (t, J = 6.4 Hz, 2H), 1.86 (dd, J = 7.2, 6.8 Hz, 2H), 1.06 (t, J = 7.6 Hz, 3H). DMSO 425.0, 427.0 (M +1) Method B (NH4HCO3) 95 Method C, G1 9 415.44 1H-NMR (400 MHz, DMSO-d.sub.6): 13.03 (s, 1H), 9.59 (d, J = 1.2 Hz, 1H), 9.15 (d, J = 8.4 Hz, 1 H), 8.69-8.74 (m, 2H), 8.49 (s, 1H), 7.96-8.06 (m, 2H), 7.90 (d, J = 9.2 Hz, 1H), 7.56-7.63 (m, 3H), 7.20 (t, J = 8.0 Hz, 1 H), 4.31 (t, J = 4.0 Hz, 2H), 3.79 (t, J = 4.8 Hz, 2H), 3.31 (s, 3H). DMSO 416.0 (M +1) Method B (NH4HCO3) 95 Method C, G1 10 0 438.43 1H-NMR (400 MHz, DMSO-d.sub.6): 9.86 (s, 1H), 9.53 (s, 1H), 8.66-8.68 (m, 2H), 8.02 (d, J = 2.8 Hz, 1 H), 7.95 (t, J = 2.0 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.79 (d, J DMSO 439.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 11 HCl 424.86 1H-NMR (400 MHz, DMSO-d.sub.6): 10.27 (s, 1 H), 9.48 (s, 1 H), 8.93 (d, J = 8.4 Hz, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.19 (dd, J = 6.8, 2.4 Hz, 1H), 8.10 (d, J = 2.4 Hz, 1H), 7.85-7.93 (m, 3H), 7.64 (dd, J = 9.2, 6.8 Hz, 1H), 7.55 (t, J = 8.8 Hz, 1H), 4.34 (t, J = 4.4 Hz, 2H), 3.78 (t, J = 4.4 Hz, 2H), 3.31 (s, 3H). DMSO 425.1, 427.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 12 397.43 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.07 (s, 1H), 9.50 (s, 1H), 8.78 (dd, J = 17.6, 7.6 Hz, 1H), 8.39 (s, 1H), 8.26 (dd, J = 8.0, 2.0 Hz, 1 H), 8.02 (d, J = 2.0 Hz, 1 H), 7.90 (d, J = 9.2 Hz, 1 H), 7.61-7.73 (m, 4H), 4.34 (t, J = 4.8 Hz, 2H), 3.79 (t, J = 4.4 Hz, 2H), 3.35 (s, 3H). DMSO 398.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 13 408.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.86 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.67 (dd, J = 4.8. 1.6 Hz, 1H), 8.64 (dt, J = 8.0, 1.6 Hz, 1H). 8.12 (ddd, J = 13.2, 7.2, 2.4 Hz, 1H), 7.98 (d, J = 2.8 Hz, 1H), 7.86 (d, J = 9.2, 1H), 7.69-7.72 (m, 1H), 7.52-7.60 (m, 3H), 4.31 (t, J = 4.0 Hz, 2H), 3.76-3.80 (m, 2H), 3.37 (s, 3H). DMSO 409.1 (M +1) Method B (NH4HCO3) 95 Method C, G1 14 441.31 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.90 (s, 1H), 9.52 (d, J = 1.2 Hz, 1H), 8.64-8.68 (m, 1H), 8.37 (d, J = 2.8 Hz, 1H), 7.98 (d, J = 2.4 Hz, 1H), 7.96 (dd, J = 10.6, 2.4 Hz, 1H), 7.86 (d, J = 9.2 Hz, 1H), 7.74 (d, J = 9.2 Hz, 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.55 (dd, J = 8.0, 4.8 Hz, 1H), 4.31 (t, J = 4.08 Hz, 2H). 3.78 (t, J = 4.4 Hz, 2H), 3.37 (s, 3H). DMSO 441.0, 443.0 (M + 1) 221.9 (M/2 + 1) Method A (TFA) 95 Method C, G1 15 441.31 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.93 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.66-8.70 (m, 2H), 8.18 (s, 1H), 8.17 (s, 1H), 7.99 (d, J = 2.4 Hz, 1H). 7.89 (d, J = 8.8 Hz, 1H), 7.61 (dd, J = 8.8, 2.4 Hz, 1H), 7.56 (dd, J = 7.6, 4.8 Hz, 1H), 7.39 (t, J = 2.0 Hz, 1H), 4.33 (t, J = 4.8 Hz, 2H). 3.79 (t, J = 4.4 Hz, 2H). 3.37 (s, 3H). DMSO 441.0, 443.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 16 HCl 375.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.34 (s, 1H), 9.53 (d, J = 1.2 Hz, 1H), 9.16 (d, J = 1.2 Hz, 1H), 8.74 (dd, J = 4.0, 1.6 Hz, 1H), 8.66-8.69 (m, 2H), 8.20-8.28 (m, 2H), 8.00 (d, J = 8.4 Hz, 1H), 7.89-7.93 (m, 1H), 7.55-7.61 (m, 2H). DMSO 376.0, 378.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 17 393.8 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.37 (s, 1H), 9.54 (d, J = 1.6 Hz; 1H), 9.09 (s, 1H), 8.69 (d, J = 10.0 Hz, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.23-8.27 (m, 2H), 8.11 (s, 1H), 8.78 (s, 2H), 7.50-7.58 (m, 3H). DMSO 394.1, 396.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 18 HCl 394.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.81 (s, 1H), 9.48 (d, J = 0.8 Hz; 1H), 9.28 (cL J = 0.8 Hz, 1H), 8.69 (d, J = 10.0 Hz, 1H), 8.68 (d; J = 8.0 Hz, 1H), 8.23-8.27 (m, 2H), 8.11 (s, 1H), 8.78 (s, 2H), 7.50- 7.58 (m, 3H). DMSO 395.0, 397.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 19 422.38 1H-NMR (400 MHz, DMSO-d.sub.6): 10.11 (brs, 1H), 9.48 (s, 1H), 8.79 (d, J = 4.8 Hz, 1H), 8.83 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 8.02 (d, J = 2.4 Hz, 1H), 7.88-7.90 (m, 1H), 1.77(d, J = 8.0 Hz, 1H), 7.52-7.62 (m, 3H), 4.27 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H). DMSO 423.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 20 0 HCl 408.81 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.73 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 9.32 (d, J = 1.6 Hz, 1 H), 9.01 (d, J = 4.8 Hz, 1H), 8.91 (d, J = 5.2 Hz, 1H), 8.39 (dd, J = 8.4, 1.6 Hz, 1H), 8.17 (dd, J = 6.8, 2.0 Hz, 1 H), 8.01 (d, J = 8.8 Hz, 1H), 7.90- 7.95 (m, 2H), 7.55 (t, J = 9.2 Hz, 1H), 3.98 (s, 3H). DMSO 409.1, 411.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 21 399.45 .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 12.94 (s, 1H), 9.56 (s, 1H), 9.14 (d, J = 8.0 Hz, 1H), 8.83-8.66 (m, 2H), 8.48 (s, 1H), 8.06-7.91 (m, 2H), 7.76-7.58 (m, 2H), 7.35 (s, 1H), 7.27 (d, J = 2.0 Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 4.15 (q; J = 6.8 Hz, 2H), 2.64 (s, 3H), 1.43 (t, J = 6.8 Hz, 1H). DMSO 400.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 22 440.42 .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 9.84 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H)t 8.73-8.60 (m, 2H), 8.14 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 2.4 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.53 (dd, J = 7.6, 4.8 Hz, 1H), 7.45 (d, J = 1.6 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 4.23 (q, J = 6.8 Hz, 2H), 2.70 (s, 3H), 1.44 (t, J = 6.8 Hz, 3H) DMSO 440.9 (M + 1) Method A (TFA) 95 Method D, G1 23 405.81 .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 10.08 (s, 1H), 9.42 (s, 1H); 8.68 (d, J = 3.6 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 8.15 (dd, J = 6.8, 2.4 Hz, 1H), 8.04 (s, 1 H), 7.93-7.78 (m, 1H), 7.54 (td, J = 8.3, 6.9 Hz, 2H), 4.08 (s, 3H) DMSO 406.1, 408.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 24 493.92 .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 10.00 (s, 1H), 9.49-9.51 (m, 1H), 8.62-8.70 (m; 2H), 8.21 (dd, J = 6.8. 2.8 Hz, 1H), 8.03 (s, 1H), 7.87-7.91 (m, 1H), 7.75 (s, 1H), 7.53-7.59 (m, 2H), 4.02 (s, 3H), 3.64-3.73 (m, 4H), 3.49-3.58 (m, 2H). 3.14-3.22 (m, 2H). DMSO 494.1, 496.1 (M + 1) Method B (NH4HCO4) 95 Method C, G1 25 TFA 369.38 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.51 (s, 1H). 878 (d, J = 8.0 Hz, 2H). 8.17 (d, J = 9.2 Hz, 1H). 7.80 (dd, J = 9.2. 2.8 Hz, 1H). 7.70-7.64 (m, 1H). 7.46 (d, J = 2.8 Hz, 1H). 7.41 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 4.0 Hz, 2H), 7.16-7.08 (m, 1H). 3.89 (s, 3H). DMSO 370.1 (M + 1) Method B (NH4HCO3) 95 Method C, J1 26 408.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.87 (s, 1H). 8.53 (dd, J = 4.7, 1.5 Hz, 1H), 8.23 (d, J = 6.8 Hz, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.8 (t, J = 2.1 Hz, 1H). 7.84 (d, J = 9.1 Hz, 1H), 7.73 (dd, J = 8.2, 1.2 Hz, 1H), 7.58 (dd, J = 9.1, 2.6 Hz, 1H), 7.41- 7.25 (m, 3H), 7.24 (t, J = 74.0 Hz, 1H), 6.96 (dd, J = 8.0, 2.2 Hz, 1H), 3.99 (s, 3H), 2.75 (s, 3H). DMSO 409.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 27 385.42 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.09 (s, 1H), 9.08 (d, J = 7.8 Hz, 1H), 8.55 (dd, J = 4.8, 1.6 Hz, 1H), 8.49 (s, 1H), 8.22 (dd, J = 7.8, 1.7 Hz, 1H), 8.01 (s, 1H), 7.95 (dd, J = 7.9, 1.2 Hz, 1H), 7.87 (d, J = 9.6 Hz, 1 H), 7.66-7.58 (m, 3H), 7.40 (dd, J = 7.7, 4.8 Hz, 1H), 7.15 (dd, J = 11.5, 4.4 Hz, 1H). 3.99 (s, 3H), 2.77 (s, 3H). DMSO 386.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 28 394.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.10 (S, 1H). 8.63 (d, J = 4.1 Hz, 1H), 8.43 (d, J = 7.6 Hz, 1H), 8.15 (dd, J = 6.8, 2.5 Hz, 1H), 8.03 (d, J = 2.3 Hz, 1H), 7.88-7.78 (m, 2H). 7.58 (ddd, J = 12.5. 8.3, 4.1 Hz, 2H), 7.49 (t, J = 9.1 Hz, 1H), 3.99 (s, 3H). 2.80 (s, 3H). DMSO 395.1, 397.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 29 HCl 440.5 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.19 (s, 1H), 11.12-10.93 (m, 1H), 9.83 (d, J = 1.5 Hz, 1H), 9.21 (d, J = 7.8 Hz, 1H), 9.01 (d, J = 7.8 Hz, 1H), 8.93-8.89 (m, 1H), 8.53 (s, 1H), 8.36 (dd, J = 11.8, 7.9 Hz, 2H), 8.02-7.73 (m, 6H), 7.29 (d, J = 8.02 Hz, 1H), 5.01 (s, 2H), 3.95-3.81 (m, 4H), , 3.37 (s, 4H). DMSO 441.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 30 0 HCl 449.91 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.05 (s, 1H), 9.56 (s, 1H). 8.73-8.66 (m, 2H). 8.47 (d, J = 8.1 Hz, 1H), 8.28 (dd, J = 6.8, 2.5 Hz, 1H), 7.99-7.90 (m, 2H). 7.67-7.50 (m, 3H). 4.16 (s, 2H), 3.62 (s, 4H), 2.53 (s, 4H). DMSO 450.1, 452.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 31 400.33 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.47 (d, J = 2.0 Hz, 2H), 8.70 (dd, J = 4.8. 1.6 Hz, 1H), 8.65-8.59 (m, 1 H), 8.06 (s, 1H), 7.91 (dt, J = 8.1, 6.0 Hz, 1H), 7.82 (dd, J = 8.2, 1.2 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (t, J = 8.2 Hz, 1H), 7.51 (ddd, J = 20.0, 10.0, 6.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 1H). DMSO 401.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 32 HCl 368.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.53 (d, J = 11.3 Hz, 1H), 9.44 (d, J = 1.2 Hz, 1H), 8.84-8.79 (m, 2H), 8.09 (dd, J = 6.8, 2.6 Hz, 1H), 7.97-7.89 (m, 1H), 7.85-7.75 (m, 3H), 7.57- 7.47 (m, 2H). DMSO 369.1, 371.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 33 HCl 359.36 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.21 (d, J = 12.1 Hz, 1H), 9.53 (d, J = 1.2 Hz, 1H), 8.99 (d, J = 8.1 Hz, 1H), 8.89 (d, J = 4.2 Hz, 1H), 8.71 (d, J = 7.9 Hz, 1H), 8.35 (s, 1H), 7.97-7.76 (m, 5H), 7.72- 7.65 (m, 1H), 7.50 (dd, J = 12.1. 7.5 Hz, 1H), 7.29 (t, J = 7.1 Hz, 1H). DMSO 360.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 34 382.34 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.49 (d, J = 1.8 Hz, 1H), 9.42 (s, 1H), 8.71 (dd, J = 4.6, 1.3 Hz, 1H), 8.65 (d, J = 7.8 Hz, 1H), 7.90 (dd, J = 15.8, 9.7 Hz, 2H), 7.73 (dd, J = 19.0, 8.26 Hz, 2H), 7.56- 7.12 (m, 4H), 7.04 (dd, J = 8.2, 1.8 Hz, 1H). DMSO 383.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 35 HCl 400.33 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.43 (s, 1H), 9.52 (s, 1H), 8.89 (d, J = 8.2 Hz, 1H), 8.85 (d, J = 4.2 Hz, 1H), 8.78 (dd, J = 9.2. 5.9 Hz, 1H), 8.09 (s, 1H), 7.95 (dd, J = 8.2, 1.2 Hz, 1H), 7.80 (dd, J = 7.9, 5.2 Hz, 1H), 7.72-7.58 (m, 3H), 7.21 (d, J = 8.4 Hz, 1H). DMSO 401.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 36 HCl 405.84 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.74- 10.48 (m, 1H), 9.36 (d, J = 1.6 Hz, 1H), 8.95 (d, J = 8.2 Hz, 1H), 8.89-8.85 (m, 1H), 8.06 (d, J = 1.7 Hz, 1H), 8.02 (d, J = 9.15 Hz; 1H), 7.93-7.86 (m, 2H), 7.73- 7.63 (m, 3H), 7.60-7.52 (m, 2H), 3.98 (s, 3H). DMSO 406.1, 408.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 37 HCl 359.36 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 9.00 (dd, J = 15.4, 8.2 Hz, 2H), 8.86 (d, J = 4.13 Hz, 1H), 8.52 (s, 1H), 8.04-7.94 (m, 3H), 7.86-7.70 (m, 4H), 7.26 (dd, J = 11.2, 4.2 Hz, 1H). DMSO 360.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 38 HCl 368.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.22 (s, 1H), 9.52 (s, 1H), 8.73 (d, J = 3.6 Hz, 1H), 8.69 (td, J = 8.0, 1.8 Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.25 (dd, J = 6.8, 2.6 Hz, 1H), 7.91 (ddd, J = 9.0, 4.2. 2.6 Hz, 1H), 7.79 (dd, J = 9.8, 7.9 Hz, 1H), 7.67 (dd, J = 8.2, 5.2 Hz, 1H), 7.61-7.53 (m, 2H). DMSO 369.0, 371.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 39 HCl 400.33 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.52 (d, J = 1.4 Hz, 1H), 9.04 (d, J = 8.0 Hz; 1H), 8.92 (dd, J = 5.2, 1.2 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 8.07 (s, 1H), 7.97 (d, J = 1.2 Hz, 2H), 7.86-7.80 (m, 1H), 7.74-7.68 (m, 1 H), 7.62 (t J = 8.2 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H). DMSO 401.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 40 0 360.34 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.68 (d, J = 1.6 Hz, 1H), 8.82 (td, J = 7.9, 1.8 Hz, 1H), 8.71 (dd, J = 4.6, 1.6 Hz, 1H), 8.22 (d, J = 8.2 Hz, 1H), 7.87 (dd, J = 7.8, 1.9 Hz, 1H), 7.73 (dd, J = 9.2, 7.8 Hz, 1H), 7.59 (dt, J = 8.1, 5.0 Hz, 2H), 7.21-7.15 (m, 1H), 6.66 (d, J = 8.2 Hz, 1H), 6.54 (t, J = 7.4 Hz, 1H). DMSO 360.9 (M + 1), 382.9 (M + 23) Method B (NH4HCO3) 95 Method C, G1 41 380.08 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.56 (brs, 1H), 9.62 (d, J = 1.2 Hz, 1H), 9.05 (d, J = 8.4 Hz, 1H), 9.00 (dd, J = 1.6, 4.8 Hz, 1H), 8.71 (d, J = 9.2 Hz, 1H), 8.31 (dd, J = 2.0, 7.2 Hz, 1H), 8.02-7.99 (m, 2H), 7.66 (t, J = 9.2 Hz, 1H), 7.54 (s, 1H), 7.50 (dd, J = 2.4, 9.2 Hz, 1H), 4.11 (s, 3H). DMSO 381.1, 383.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 42 476.67 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.40 (s, 1H), 9.51 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 8.88 (d, J = 4.8 Hz, 1H), 8.40 (d, J = 8.8 Hz, 1H)S 8.35 (d, J = 1.6 Hz, 1H), 8.20 (dd; J = 4.4, 6.8 Hz, 1H), 8.04 (dd, J = 7.2, 8.8 Hz, 1H), 7.93-7.86 (m, 2H), 7.35 (t, J = 9.2 Hz, 1H). DMSO 477.0, 499.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 43 429.67 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.46 (s, 1H), 9.49 (s, 1 H), 8.95 (d, J = 8.1 Hz, 1H), 8.89 (d, J = 4.97 Hz, 1H), 8.60 (d, J = 8.9 Hz, 1H), 8.19 (dd, J = 6.8, 2.6 Hz, 1H), 8.14 (d, J = 1.9 Hz, 1H), 7.96-7.83 (m, 3H), 7.53 (t, J = 9.0 Hz, 1H). DMSO 429.0, 430.9, 433.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 44 HCl 385.42 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.05 (s, 1H), 9.44 (d, J = 1.7 Hz, 1H), 9.16- 8.91 (m, 2H), 8.03-7.89 (m, 3H), 7.88- 7.82 (m, 1H), 7.75-7.68 (m, 1H), 7.67- 7.60 (m, 2H), 7.25 (t, J = 7.6 Hz, 1H), 4.00 (s, 3H), 2.74 (s, 3H). DMSO 386.0 (M + 1) 193.4 (M/2 + 1) Method A (TFA) 95 Method C, G1 45 HCl 408.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.37- 10.12 (m, 1H), 9.35 (d, J = 1.8 Hz, 1H), 8.95 (dd, J = 4.6, 3.4 Hz, 1H), 8.09 (d, J = 2.3 Hz, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.87 (s, 1H), 7.84-7.74 (m, 2H), 7.62 (dd, J = 9.1, 2.6 Hz, 1 H), 7.54 (t, J = 8.2 Hz, 1H), 7.32 (t, J = 74.0 Hz, 1H), 7.05 (dd, J = 8.3; 1.9 Hz, 1H), 4.00 (s, 3H), 2.72 (s, 3H). DMSO 409.0 (M + 1) 205.0 (M/2 + 1) Method A (TFA) 95 Method C, G1 46 HCl 394.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.27 (brs, 1H), 9.32 (d, J = 1.7 Hz, 1H), 8.93 (d, J = 7.5 Hz, 1H), 8.19 (dd, J = 6.8, 2.5 Hz, 1H), 8.07 (d, J = 2.3 Hz, 1H), 7.88- 7.92 (m, 2H), 7.84 (d, J = 8.1 Hz, 1H), 7.62 (dd; J = 9.2, 2.5 Hz, 1H), 7.54 (t, J = 9.1 Hz, 1H), 4.00 (s, 3H), 2.72 (s, 3H). DMSO 395.0, 397.0 (M + 1) 197.8, 198.8 (M/2 + 1) Method A (TFA) 95 Method C, G1 47 HCl 378.37 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.58- 10.30 (m, 1H), 9.32 (d, J = 1.9 Hz, 1H), 9.04 (d, J = 7.9 Hz, 1H), 8.17-8.04 (m, 2H), 7.95 (d, J = 9.0 Hz, 2H), 7.73-7.66 (m, 1H), 7.63 (dd, J = 9.2, 2.6 Hz, 1H), 7.60-7.50 (m, 1H), 4.01 (s, 3H), 2.76 (s, 3H). DMSO 379.0 (M + 1) 190.0 (M/2 + 1) Method A (TFA) 95 Method C, G1 48 HCl 411.28 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.29 (s, 1H), 9.33 (d, J = 1.7 Hz, 1H), 9.04- 8.89 (m, 1H), 8.31 (d, J = 2.4 Hz, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.97 (dd, J = 8.8, 2.5 Hz, 1H), 7.91 (d, J = 9.1 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.62 (dd, J = 9.1, 2.5 Hz, 1H), 4.00 (s; 3H), 2.73 (s, 3H). DMSO 411.0, 413.0 (M + 1) 205.0, 206.9 (M/2 + 1) Method A (TFA) 95 Method C, G1 49 411.28 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.30 (s, 1H), 9.31 (d, J = 1.5 Hz, 1H), 8.94 (d, J = 7.3 Hz, 1H), 8.13 (d, J = 1.7 Hz, 2H), 8.07 (d, J = 2.3 Hz, 1H), 7.90 (d, J = 9.2 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.61 (dd, J = 9.1, 2.6 Hz, 1H), 7.41 (d, J = 1.7 Hz, 1H), 4.00 (s, 3H), 2.72 (s, 3H). DMSO 411.0, 413.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 50 0 HCl 389.84 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.09 (s, 1H), 9.38 (s, 1H), 9.16 (d, J = 8.4 Hz, 1H), 8.83 (d, J = 8.3 Hz, 1H), 8.50 (s, 1H), 8.20 (d, J = 8.8 Hz, 1H), 8.05-7.99 (m, 2H), 7.97 (d, J = 7.9 Hz, 1H), 7.92 (s, 1H), 7.81 (dd, J = 8.8, 2.0 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 2.82 (s, 3H). DMSO 390.1, 392.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 51 HCl 412.82 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.49 (s, 1H), 9.35 (d, J = 1.7 Hz, 1H), 9.08 (dd, J = 8.3, 1.5 Hz, 1H), 8.75 (d, J = 9.0 Hz, 1H), 8.02 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.87 (s, 1H), 7.80 (dd, J = 9.0, 2.0 Hz, 2H), 7.53 (t, J = 8.2 Hz, 1H), 7.31 (t, J = 74.0 Hz, 1 H), 7.06 (dd, J = 8.1, 2.0 Hz, 1H), 2.79 (s, 3H). DMSO 413.0, 415.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 52 399.25 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.49 (S, 1H), 9.32 (d, J = 1.7 Hz, 1H), 9.00 (d, J = 8.4 Hz, 1H), 8.69 (d, J = 8.9 Hz, 1H), 8.20 (dd, J = 6.8, 2.6 Hz, 1 H), 8.00 (d, J = 2.1 Hz, 1H), 7.96-7.86 (m, 2H), 7.80 (dd, J = 8.9, 2.1 Hz, 1H), 7.53 (t, J = 9.1 Hz, 1H), 2.76 (s, 3H). DMSO 399.0, 401.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 53 HCl 382.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.55 (s, 1H), 9.32 (d, J = 1.7 Hz, 1H), 9.07 (dd, J = 8.2, 1.2 Hz, 1H), 8.73 (d, J = 8.9 Hz, 1H), 8.08 (ddd, J = 13.0, 7.5, 2.6 Hz, 1H), 8.00 (dd, J = 8.9, 5.2 Hz, 2H), 7.80 (dd, J = 8.9. 2.1 Hz, 1H), 7.71 (dd, J = 6.1, 2.9 Hz, 1H), 7.54 (dd, J = 19.7, 9.2 Hz, 1H), 2.78 (s, 3H) DMSO 383.0, 385.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 54 HCl 415.7 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.63 (s, 1H), 9.30 (d, J = 1.7 Hz, 1H), 9.07 (dd, J = 8.3, 1.8 Hz, 1H), 8.75 (d, J = 9.0 Hz, 1H), 8.29 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 2.1 Hz, 1H), 7.96 (dd, J = 8.9, 2.5 Hz, 1H), 7.77 (dd, J = 8.9, 2.1 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 2.81 (s, 3H). DMSO 415.0, 417.0, 419.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 55 HCl 415.7 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.54 (s, 1H), 9.32 (s, 1H), 9.01 (dd, J = 8.0. 1.8 Hz, 1H), 8.72 (d, J = 9.0 Hz, 1H), 8.11 (d, J = 1.8 Hz, 2H), 8.01 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 8.5 Hz, 1H), 7.80 (dd, J = 8.9. 2.0 Hz, 1 H), 2.78 (s, 3H). DMSO 415.0, 417.0, 419.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 56 379.36 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.16 (s, 1H), 9.47 (s, 1H), 8.79 (dd, J = 8.9. 7.1 Hz, 2H), 7.91 (s? 1H), 7.84-7.77 (m, 2H), 7.76-7.68 (m, 1H), 7.56 (d, J = 2.1 Hz, 1H), 7.51 (t, J = 8.2 Hz, 1H), 7.39 (dd, J = 8.9, 2.2 Hzr 1H), 7.29 (t, J = 74.0 Hz, 1H), 7.00 (dd, J = 8.1, 2.1 Hz, 1H), 4.23 (bis, 2H). DMSO 380.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 57 HCl 463.48 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.43- 10.20 (m, 2H), 9.72 (s, 1H), 8.89-8.67 (m, 3H), 8.29-8.21 (m, 1H), 7.97 (s, 1H), 7.87-7.80 (m, 1H), 7.81-7.73 (m, 1H), 7.63-7.46 (m, 2H), 7.30 (t, J = 74.0 Hz, 1H), 7.08-6.98 (m, 1H), 5.00 (s, 2H), 4.05-3.65 (m, 4H), 3.39-3.36 (m, 4H). DMSO 464.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 58 HCl 399.45 .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 12.53 (s, 1H), 9.30 (d, J = 1.6 Hz, 1H), 9.03- 8.96 (m, 1H), 8.94-8.88 (m, 1H), 8.71 (d, J = 8.4 Hz, 1H), 7.91-7.83 (m, 3H), 7.67-7.55 (m, 3H), 7.25 (t, J = 7.2 Hz, 1H), 3.98 (s, 3H), 2.80-2.74 (m, 6H). DMSO 400.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 59 HCl 389.38 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.27 (s, 1H), 9.23 (s, 1H), 8.98 (d, J = 5.2 Hz, 1H), 8.91 (d, J = 8.0 Hz, 1H), 8.54 (dd, J = 12.0, 2.6 Hz, 1H), 8.48 (s, 1H), 8.07 (dd, J = 8.0, 5.6 Hz, 1H), 7.97-7.93 (m, 2H), 7.66 (d, J = 9.0 Hz, 1H), 7.37 (dd, J = 9.0, 2.4 Hz, 1H), 7.13 (d, J = 2.0 Hz, 1H), 6.91 (dt, J = 8.4. 2.G Hz, 1 H), 3.80 (s, 3H). DMSO 390.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 60 00 415.70 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.13 (s, 1H), 9.48 (s, 1H), 8.87 (dd, J = 14.0, 6.2 Hz, 2H), 8.54 (d, J = 1.7 Hz, 1H), 8.10 (d, J = 1.8 Hz, 2H), 7.89-7.78 (m, 2H), 7.37 (t, J = 1.8 Hz, 1H), 2.70 (s, 3H). DMSO 414.9, 416.9, 419.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 61 01 415.70 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.10 (s, 1H), 9.44 (s, 1 H), 8.86 (d, J = 7.8 Hz, 1H), 8.79 (d, J = 4.5 Hz, 1H), 8.50 (d, J = 1.7 Hz, 1H), 8.23 (d, J = 2.4 Hz, 1H), 7.89 (dd, J = 8.8, 2.4 Hz, 1H), 7.83- 7.71 (m, 2H), 7.62 (d, J = 8.8 Hz, 1H), 2.62 (s, 3H) DMSO 414.9, 416.9, 418.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 62 02 412.82 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): : 10.02 (s, 1H), 9.58 (d, J = 1.8 Hz, 1H), 8.76- 8.67 (m, 2H), 8.59 (d, J = 1.8 Hz, 1H), 7.96 (s, 1H), 7.82 (d, J = 6.6 Hz, 2H), 7.54 (ddd, J = 16.4, 10.0, 6.4 Hz, 2H), 7.30 (t, J = 74.0 Hz, 1H), 7.01 (dd, J = 8.0, 2.0 Hz, 1H), 2.74 (s, 3H). DMSO 413.0, 415.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 63 03 389.84 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.15 (s, 1H), 9.58 (s, 1H), 9.03 (d, J = 0.8 Hz, 1H), 8.78-8.84 (m, 2H), 8.50 (s, 1H), 7.95-8.03 (m, 3H), 7.80 (s, 1H), 7.70- 7.74 (m, 2H), 7.23 (d, J = 7.2 Hz, 1H), 2.70 (s, 3H). DMSO 391.0, 392.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 64 04 371.82 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.31 (s, 1H); 9.48 (d, J = 1.2 Hz, 1H), 9.01 (d, J = 8.4 Hz, 1H), 8.90 (d, J = 4.0 Hz, 1H), 8.61 (d, J = 1.6 Hz, 1H), 8.33 (s, 1H), 8.27 (dd, J = 6.0, 2.0 Hz, 1H), 7.95- 7.63 (m, 3H), 2.70 (s, 3H). DMSO 372.0 373.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 65 05 476.67 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.28 (s, 1H), 9.46 (d, J = 1.2 Hz, 1H), 9.01 (d, J = 1.2 Hz, 1H), 8.83 (dd, J = 8.4. 1.6 Hz, 2H), 8.19-8.14 (m, 2H), 7.89-7.49 (m, 2H). DMSO 476.9, 478.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 66 06 399.25 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.03 (s, 1H), 8.54 (s, 1 H), 871-8.67 (m, 2H)S 8.53 (s, 1H), 8.26 (dd, J = 6.8 Hz, 2.4 Hz, 1H), 7.83 (s, 1H), 7.58-7.52 (m, 2H), 2.72 (s, 3H). DMSO 399.0, 401.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 67 07 382.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.04 (s, 1H), 9.51 (d, J = 1.2 Hz, 1H), 8.72- 8.69 (m, 2H), 8.53 (d, J = 2.0 Hz, 1H), 8.08 (ddd, J = 9.2, 7.6, 2.4 Hz, 1H), 7.79- 7.48 (m, 4H), 2.69 (s, 3H). DMSO 383.0, 385.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 68 08 HCl 399.45 .sup.1H-NMR (400 MHz, DMSO-d6): 13.02 (S, 1H), 9.59 (s, 1H), 9.09 (d, J = 8.0 Hz, 1H), 8.96 (d, J = 8.4 Hz, 1H), 8.91 (d, J = 4.61 Hz, 1 H), 8.48 (s, 1H), 7.97 (dd, J = 8.0, 2.8 Hz, 4H), 7.72 (t, J = 7.6 Hz, 1H), 7.64-7.61 (m, 2H), 7.26 (t, J = 7.6 Hz, 1H), 4.88-4.82 (m, 1H), 1.43 (d, J = 6.0 Hz, 6H). DMSO 400.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 69 09 HCl 422.43 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.63 (s, 1H), 9.51 (s, 1 H), 9.09 (d, J = 7.6 Hz, 1H), 8.91 (d, J = 7.6 Hz, 1H), 8.23 (s, 1H), 8.03-7.97 (m, 1H), 7.83-7.80 (m, 2H), 7.64 (dd, J = 9.2, 2.4 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.32 (t, J = 74.0 Hz, 1H), 7.08 (d, J = 7.4 Hz, 1H), 5.02-4.97 (m, 1H), 1.39 (d, J = 6.0 Hz, 6H). DMSO 423.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 70 0 HCl 408.86 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.61 (s, 1H), 9.48 (s, 1 H), 9.05 (d, J = 7.2 Hz, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.19- 8.15 (m, 2H); 8.01-7.92 (m, 3H), 7.63- 7.53 (m, 2H), 5.01-4.94 (m, 1H), 1.39 (d, J = 6.0 Hz, 6H). DMSO 409.1, 411.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 71 HCl 425.31 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.92 (s, 1H), 9.52 (d, J = 1.2 Hz, 1H), 8.70-8.66 (m, 2H), 8.17 (d, J = 1.6 Hz, 2H), 7.98 (d, J = 2.4 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.60-7.56 (m, 2H), 7.39 (t, J = 1.8 Hz, 1H), 4.94-4.88 (m, 1H), 1.39 (d, J = 6.0 Hz, 6H). DMSO 424.9, 426.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 72 HCl 392.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.28 (s, 1H), 9.49 (d, J = 1.2 Hz, 1H), 8.93 (d, J = 8.0 Hz, 1H), 8.86-8.84 (m, 1H), 8.10-8.05 (m, 2H), 7.93-7.85 (m, 2H), 7.71-7.69 (m, 2H), 7.61-7.52 (m, 1H), 4.97-4.91 (m, 1H), 1.39 (d, J = 6.0 Hz, 6H). DMSO 393.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 73 HCl 385.42 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.03 (s, 1H), 9.53 (d, J = 1.2 Hz, 1H), 9.10 (d, J = 8.4 Hz, 1H), 8.93-8.90 (m, 2H), 8.49 (s, 1H), 8.01-7.91 (m, 4H), 7.69 (t, J = 7.6 Hz, 1H), 7.59-7.54 (m, 2H), 7.24 (t, J = 7.6 Hz, 1H), 4.21 (q, J = 6.8 Hz, 2H), 1.46 (t, J = 6.9 Hz, 3H). DMSO 386.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 74 HCl 367.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.35 (s, 1H), 9.49 (s, 1 H), 8.95 (d, J = 7.6 Hz, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.37 (s, 1H), 8.28 (d, J = 7.6 Hz, 1H), 8.08 (s, 1H), 7.94-7.85 (m, 2H), 7.73-7.60 (m, 3H), 4.28 (q, J = 6.8 Hz, 2H), 1.46 (t, J = 6.8 Hz, 3H). DMSO 368.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 75 HCl 394.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.64 (s, 1H), 9.44 (s, 1 H), 8.99 (d, J = 8.4 Hz, 1H), 8.91 (d, J = 4.4 Hz, 1H), 8.17 (d, J = 3.2 Hz, 2H), 7.59-7.50 (m, 2H), 4.26 (q, J = 6.8 Hz, 2H), 1.44 (t, J = 6.8 Hz, 3H). DMSO 395.1 397.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 76 HCl 411.28 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.48 (s, 1H), 9.47 (s, 1H), 9.02 (d, J = 7.6 Hz, 1H), 8.91 (d, J = 4.4 Hz, 1H), 8.28 (d, J = 1.6 Hz, 1H), 8.13 (s, 1H), 8.01-7.91 (m, 3H), 7.72 (d, J = 8.8 Hz, 1H), 7.59-7.57 (m, 1H), 4.26 (q, J = 6.8 Hz, 2H), 1.44 (t, J = 6.8 Hz, 3H). DMSO 411.0 413.0 415.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 77 HCl 411.28 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 9.48 (s, 1 H), 8.93 (d, J = 8.0 Hz, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.14 (s, 2H), 8.05 (d, J = 1.6 Hz, 1H), 7.92-7.85 (m, 2H), 7.61 (dd, J = 9.1, 1.8 Hz, 1H), 7.41 (s, 1H), 4.26 (q, J = 6.8 Hz, 2H), 1.45 (t, J = 6.8 Hz, 3H). DMSO 411.0 413.0 415.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 78 HCl 378.37 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.39 (s, 1H), 9.49 (s, 1 H), 8.98 (d, J = 8.0 Hz, 1H), 8.88 (d J = 4.8 Hz, 1H), 8.11-8.05 (m, 2H), 7.95-7.91 (m, 2H), 7.72-7.52 (m, 3H), 4.28 (q, J = 6.8 Hz, 2H), 1.45 (t, J = 6.8 Hz, 3H). DMSO 379.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 79 HCl 429.47 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.99 (s, 1H), 9.59 (d, J = 1.6 Hz, 1H), 9.14 (d, J = 7.6 Hz, 1H), 8.75-8.69 (m, 2H), 8.48 (s, 1H), 7.99-7.96 (m, 2H), 7.90 (d, J = 8.8 Hz,, 1H), 7.76-7.72 (m, 1H), 7.61-7.56 (m, 3H), 7.22-7.19 (m, 1H), 4.24 (t, J = 6.0 Hz, 2H), 3.56 (t, J = 6.0 Hz, 2H), 3.28 (s, 3H), 2.11-2.04 (m, 2H). DMSO 430.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 80 0 HCl 380.80 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.67 (s, 1H), 9.18 (d, J = 2.0 Hz, 1H), 8.90 (d, J = 8.4 Hz, 1H), 8.66 (dd, J = 8.8, 2.4 Hz, 1H), 8.35 (d, J = 8.4 Hz, 1H), 8.14-8.08 (m, 2H), 7.90-7.81 (m, 2H), 7.62 (t, J = 9.2 Hz, 1H), 7.09 (d, J = 8.8 Hz, 1H), 3.98 (s, 3H). DMSO 380.9, 382.9 (M + 1) Method A (TFA) 95 Method C, G1 81 HCl 394.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.81 (s, 1H), 9.49 (d, J = 1.2 Hz, 1H), 9.28 (d, J = 0.8 Hz, 1H), 9.15 (d, J = 8.0 Hz, 1H), 9.02 (d, J = 5.2 Hz, 1H), 8.37-8.34 (m, 1H), 8.12-8.09 (m, 2H), 8.01 (d, J = 8.4 Hz, 1H), 7.95-7.91 (m, 1 H), 7.53 (t, J = 9.0 Hz, 1H). DMSO 395.0, 397.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 82 385.39 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (d, J = 1.6 Hz, 1H), 9.13 (s, 1H), 8.80-8.75 (m, 2H), 8.21 (d, J = 9.2 Hz, 1H), 7.97- 7.94 (m, 1H), 7.82 (dd, J = 9.2, 2.8 Hz, 1H), 7.73 (dd, J = 9.2, 2.4 Hz, 1 H), 7.64- 7.61 (m, 1H), 7.38-7.32 (m, 2H), 4.18 (q, J = 6.8 Hz, 2H), 3.19 (t, J = 7.0 Hz, 3H). DMSO 386.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G10 83 HCl 426.39 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.43 (s, 1H), 9.49 (d, J = 1.6 Hz, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.89 (dd, J = 9.2. 1.6 Hz, 1H), 8.13 (d, J = 2.4 Hz, 1H), 8.05 (s, 1H), 7.97-7.89 (m, 3H), 7.65-7.61 (m, 2H), 7.23 (d, J = 8.4 Hz, 1H), 4.29 (q, J = 6.8 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H). DMSO 427.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 84 426.47 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.00 (s, 1H), 9.55 (s, 1H), 9.12 (d, J = 8.0 Hz, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.84 (d, J = 8.4 Hz, 1H), 8.11-8.09 (m, 1H), 8.02- 7.99 (m, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.82-7.11 (m, 1H), 7.65 (s, 1H), 7.62- 7.59 (m, 1H), 7.30 (t, J = 7.2, Hz, 1H), 5.06-5.03 (m, 1H), 2.15-2.09 (m, 2H), 1.86-1.74 (m, 4H), 1.68-1.65 (m, 2H). DMSO 427.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 85 375.81 .sup.1H-NMR (400 MHz, DMSO-d6): 13.09 (s, 1H), 9.58 (s, 1H), 9.12 (d, J = 8.4 Hz, 1H), 8.94 (d, J = 4.4 Hz, 1H), 8.88 (d, J = 8.4 Hz, 1H), 8.50 (s, 1H), 8.25 (s, 1H), 8.01-7.96 (m, 5H), 7.71 (t, J = 8.0 Hz, 1H), 7.27 (t, J = 8.0 Hz, 1H). DMSO 376.0, 378.0 (M + 1) 397.9 (M + 23) 188.4 (M/2 + 1) Method A (TFA) 95 Method C, G10 86 398.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.10 (s, 1H), 9.54 (s, 1H), 8.78 (s, 1H), 8.71- 8 67 (m, ?H) 7 96 (s, 1H), 7 91 (d, = 8.0 Hz, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.56-7.51 (m, 2H), 7.30 (t, J = 74.0 Hz, 1H), 7.01 (dd, J = 2.0. 8.0 Hz, 1H). DMSO 399.0, 401.0 (M + 1) 199.9, 200.8 (M/2 + 1) Method A (TFA) 95 Method C, G1 87 443.7 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.09 (s, 1H), 9.39 (s, 1H), 8.93 (d, J = 8.4 Hz, 1H), 8.90 (d, J = 5.6 Hz, 1H), 8.62 (d, J = 1.6 Hz, 1H), 8.11 (dd, J = 6.8, 2.4 Hz, 1H), 7.95-7.91 (m, 1H), 7.89-7.85 (m, 1H), 7.80 (s, 1H), 7.45 (t, J = 8.8 Hz, 1H), 2.66 (s, 3H). DMSO 443.0, 445.0, 447.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 98 Method C, G1 88 401.42 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.19 (S, 1H), 9.43 (d J = 8.0 Hz, 1H), 8.53 (s, 1H), 8.31 (dd, J = 4.8, 1.6 Hz, 1H), 8.26 (dd, J = 1.6, 7.2 Hz, 1H), 8.03 (s, 1H), 7.96-7.89 (m, 1H), 7.86 (d, J = 9.2 Hz, 1H), 7.65-7.54 (m, 3H), 7.18-7.12 (mT 2H), 4.02 (s, 3H); 3.98 (s, 3H). DMSO 402.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 89 410.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.79 (s, 1H), 8.52 (dd, J = 2.4, 7.2 Hz, 1H), 8.28 (dd, J = 5.6, 2.4 Hz, 1H), 8.12 (dd, J = 2.4. 5.2 Hz, 1H), 7.98-7.94 (m, 2H), 7.82 (d, J = 9.2 Hz, 1H), 7.56 (dd, J = 9.2, 2.8 Hz, 1H), 7.47 (t, J = 9.2 Hz, 1H), 7.14-7.1 I (m, IH), 4.00 (s, 3H), 3.99 (s, 3H). DMSO 411.1, 413.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 90 0 415.44 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.03 (s, 1H); 9.21 (d, J = 2.2 Hz, 1H), 9.16 (d, J = 7.9 Hz, 1H), 8.67 (dd, J = 8.7, 2.4 Hz, 1H), 8.50 (s, 1H), 8.02 (s, 1H), 7.99- 7.93 (m, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.78-7.72 (m, 1H), 7.56 (dd, J = 11.2. 2.1 Hz, 2H), 7.19(t, J = 7.2 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 4.24 (q, J = 6.9 Hz, 2H), 3.96 (s, 3H), 1.46 (t, J = 6.9 Hz, 3H). DMSO 416.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method D, G1 91 HCl 405.84 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.28 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 9.31 (d, J = 2.1 Hz, 1H), 8.90 (d, J = 8.3 Hz, 1H), 8.83 (dd, J = 5.0, 1.4 Hz, 1H), 8.58 (s, 1H), 8.12 (ss 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.82 (dd, J = 7.9, 5.0 Hz, 1H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.54 (d, J = 2.5 Hz, 1H), 7.30 (dd, J = 8.5. 2.2 Hz, 1 H), 3.98 (s, 3H). DMSO 406.0, 408.0 (M + 1) Method A (TFA) 95 Method C, G2 92 429.47 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.99 (s, 1H), 9.21 (d, J = 2.0 Hz, 1H), 9.14 (d, J = 8.4 Hz, 1H), 8.67 (dd, J = 8.7, 2.3 Hz, 1H), 8.49 (s, 1H), 8.05-7.90 (m, 2H), 7.85 (d, J = 9.0 Hz, 1H), 7.75 (t, J = 7.2 Hz, 1H), 7.67-7.47 (m, 2H), 7.20 (t, J = 7.5 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 4.15 (t, J = 6.3 Hz, 2H), 3.96 (s, 3H), 1.07 (t, J = 7.4 Hz, 3H), 1.86 (dd, J = 14.0, 6.7 Hz, 2H). DMSO 430.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method D, G1 93 HCl 389.38 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.34 (s, 1H), 9.52 (d, J = 1.7 Hz, 1H), 8.99 (d, J = 7.8 Hz, 1H), 8.85 (dd, J = 5.2, 1.3 Hz, 1H), 8.22 (d, J = 8.1 Hz, 1H), 8.11-8.00 (m, 2H), 7.95 (d J = 9.1 Hz, 1H), 7.87 (dd, J = 7.9, 5.3 Hz, 1H), 7.77-7.59 (m, 3H), 7.27-7.16 (m, 1H), 3.99 (s, 3H). DMSO 390.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G3 94 436.29 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.62 (s, 1H), 9.17 (s, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.76 (d, J = 4.0 Hz, 1H), 8.26-8.07 (m, 3H), 7.83 (dd, J = 9.1, 2.5 Hz, 1H), 7.63 (dd, J = 7.5. 5.0 Hz, 1H), 7.36 (d, J = 2.4 Hz, 1H), 4.18 (q, J = 6.8 Hz, 2H), 1.39 (t, J = 6.9 Hz, 3H). DMSO 436.1, 438.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G10 95 405.84 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.93 (s, 1H), 9.58 (s, 1H), 9.16 (d, J = 9.0 Hz, 1H), 8.70-8.74 (m, 2H), 8.59 (s, 1H), 8.13 (s, 1H), 8.05 (d, J = 2.3 Hz, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.82 (dd, J = 8.9, 2.1 Hz, 1H), 7.65-7.49 (m, 3H), 3.98 (s, 3H). DMSO 406.1, 408.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G3 96 429.67 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.45 (s, 1H), 9.47 (s, 1H), 9.02-8.92 (m, 3H), 8.18-8.16 (m, 1H), 8.06-8.04 (m, 1H), 7.96-7.84 (m, 3H), 7.54-7.50 (m, 1H). DMSO 429.9, 431.0, 433.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 97 398.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.25 (s, 1H), 9.58 (s, 1H), 8.85-8.76 (m, 2H), 8.60 (d, J = 7.2 Hz, 1H), 8.12-8.10 (m, 1H), 7.92 (s, 1H), 7.83-7.80 (m, 1H), 7.71-7.64 (m, 2H), 7.56-7.52 (m, 1H), 7.30 (t, J = 74.0 Hz, 1 H), 7.05-7.03 (m, 1H). DMSO 399.0, 401.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 98 385.22 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.50 (s, 1 H), 9.04 (d, J = 8.0 Hz, 1H), 8.93 (d, J = 5.2 Hz, 2H), 8.64 (d, J = 8.8 Hz, 1H), 8.20-8.18 (m, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.97-7.92 (m, 2H), 7.68-7.64 (m, 1H), 7.53 (t, J = 9.2 Hz, 1H). DMSO 385.0, 386.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 99 401.68 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.42 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 8.96 (d, J = 4.0 Hz, 1H), 8.88-8.87 (m, 1H), 8.61 (d, J = 7.6 Hz, 1H), 8.32 (d, J = 2.4 Hz, 1H), 8.14-8.12 (m, 1H), 7.99-7.95 (m, 1H), 7.88 (dd, J = 8.0, 5.2 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.70-7.67 (m, 1H). DMSO 400.9, 402.9, 404.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 100 0 368.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.51 (d, J = 1.2 Hz, 1H), 9.04 (d, J = 8.0 Hz, 1H), 8.92 (d, J = 5.6 Hz, 1H), 8.65 (d, J = 8.0 Hz, 1 H), 8.11-8.05 (m, 2H), 7.97 (dd, J = 8.0, 4.0 Hz, 1H), 7.75- 7.73 (m, 1H), 7.66 (t, J = 8.0 Hz; 1H), 7.58-7.51 (m, 1H). DMSO 369.0, 371.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 101 375.09 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.18 (s, 1H), 9.61 (s, 1 H), 9.02 (d, J = 8.4 Hz, 1H), 8.93 (d, J = 8.4 Hz, 1H), 8.83 (d, J = 4.0 Hz, 1H), 8.52 (s, 1H), 8.16-8.08 (m, 2H), 7.98-7.94 (m, 2H), 7.80-7.67 (m, 3H), 7.26 (t, J = 7.6 Hz, 1H). DMSO 376.0, 378.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 102 401.68 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.49 (d, J = 2.0 Hz, 1H), 9.00- 8.98 (m, 1H), 8.91 (dd, J = 5.2, 1.6 Hz, 1H), 8.64-8.62 (m, 1H), 8.12-8.09 (m, 3H), 7.94 (dd, J = 8.0, 5.2 Hz, 1 H), 7.67 (t, J = 8.0 Hz, 1H), 7.41 (t, J = 2.0 Hz, 1H). DMSO 400.9, 402.9, 404.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 103 434.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.17 (d, J = 1.2 Hz, 1H), 9.51 (s, 1H), 8.71- 8.62 (m, 3H), 8.25-8.22 (m, 1H), 8.04- 8.00 (m, 1 H), 7.92-7.87 (m, 2H), 7.58- 7.53 (m, 2H). DMSO 435.1, 437.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 104 448.35 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.16 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H), 8.72- 8.68 (m, 3H), 8.05 (d, J = 9.2 Hz, 1H), 7.92-7.95 (m, 2H), 7.80 (dd, J = 8.0, 1.2 Hz, 1 H), 7.57-7.53 (m, 2H), 7.31 (t, J = 74.4 Hz, 1 H), 7.03 (dd, J = 8.0, 1.2 Hz, 1H). DMSO 449.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 105 425.36 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.24 (s, 1H), 9.59 (s, 1H), 9.06 (d, J = 8.0 Hz, 1H), 8.74-8.73 (m, 2H), 8.54 (s, 1H), 8.10-7.91 (m, 5H), 7.77-7.73 (m, 1H), 7.61-7.58 (m, 1H), 7.26 (t, J = 7.6 Hz, 1H). DMSO 426.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 106 448.35 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 8.76 (d, J = 9.1 Hz, 1H), 8.74-8.67 (m, 2H), 7.94 (t, J = 2.0 Hz, 1H), 7.82-7.78 (m, J = 10.3 Hz, 2H), 7.68 (dd, J = 9.0, 1.8 Hz, 1H), 7.59-7.50 (m, 2H), 7.30 (t, J = 74.0 Hz, 1H), 7.03 (dd, J = 8.2, 2.2 Hz, 1H). DMSO 449.0 (M + 1) 225.0 (M/2 + 1) Method A (TFA) 95 Method C, G1 107 425.36 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.17 (s, 1H), 9.59 (s, 1H), 9.04 (d, J = 8.0 Hz, 1H), 8.74-8.70 (m, 2H), 8.51 (s, 1H), 8.30 (d, J = 9.0 Hz, 1H), 8.02-7.90 (m, 2H), 7.86-7.69 (m, 3H), 7.65-7.56 (m, 1H), 7.25 (t, J = 9.8 Hz, 1H). DMSO 426.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 108 434.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.26 (s, 1H), 9.52 (s, 1 H), 8.81-8.59 (m, 3H), 8.24 (dd, J = 6.9, 2.5 Hz, 1H), 7.89- 7.52 (m, 1H), 7.79 (s, 1H), 7.70 (d, J = 9.1 Hz, 1H), 7.65-7.50 (m, 2H). DMSO 435.0, 437.0 (M + 1) 218.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 109 455.39 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.35 (s, 1H), 9.58 (s, 1H), 9.27 (s, 1H), 8.83- 8.70 (m, 2H), 8.62 (s, 1H), 8.18 (s, 1H), 8.11 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.68-7.58 (m, 2H), 7.54 (d, J = 2.5 Hz, 1H), 7.19 (dd, J = 8.4, 2.17 Hz, 1H), 3.98 (s, 3H). DMSO 456.0 (M + 1) 228.5 (M/2 + 1) Method A (TFA) 95 Method C, J1 110 0 425.48 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.08 (s, 1H), 9.59 (s, 1H), 9.07 (d J = 7.6 Hz, 1H), 9.02 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 4.0 Hz, 1 H), 8.50 (s, 1H), 7.92-7.99 (m, 4H), 7.73 (t, J = 7.6 Hz, 1H), 7.59-7.60 (m, 2H), 7.25 (t, J = 7.6 Hz, 1H), 2.12- 2.15 (m, 2H), 5.02-5.03 (m, 1H), 1.67- 1.86 (m, 6H). DMSO 426.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 111 448.46 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.26 (S, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.95(d, J = 7.2 Hz, 1H), 8.55 (d, J = 4.4 Hz, 1H), 8.08 (s, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 9.6 Hz, 2H), 7.79 (d, J = 8.8 Hz, 1H), 7.60-7.63 (m, 1 H), 7.55 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 74.0 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 5.14 (s, 1H), 2.03-2.09 (m, 2H), 1.61-1.81 (m, 6H). DMSO 449.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 112 434.89 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.47 (s, 1 H), 8.97 (d, J = 7.6 Hz, 1H), 8.89 (d, J = 4.4 Hz, 1H), 8.16-8.19 (m, 1H), 7.53-7.61 (m, 2H), 8.10 (s, 1H), 7.90-7.96 (m, 3H), 5.15 (s, 1H), 2.09-2.10 (m, 2H), 1.67-1.78 (m, 6H). DMSO 435.0, 437.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 113 451.35 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 9.49 (s, 1H), 8.85 (d, J = 7.6 Hz, 1H), 8.80 (d, J = 4.0 Hz, 1H), 8.32 (s, 1H), 8.03 (s, 1H), 7.97-7.99 (m, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.77-7.79 (m, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.55-7.58 (m, 1H), 5.13 (s, 1H), 2.08 (d, J = 8.4 Hz, 2H), 1.79 (d, J = 9.6 Hz, 4H). DMSO 451.0, 453.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 114 418.44 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.24 (s, 1H), 9.49 (s, 1 H), 8.92 (d, J = 8.0 Hz, 1H), 8.40 (d, J = 6.4 Hz, 1H), 8.04-8.11 (m; 2H), 7.92 (d, J = 9.2 Hz, 1H), 7.84- 7.91 (m, 1H), 7.69-7.71 (m, 1H), 7.52- 7.61 (m, 2H), 5.13 (s, 1H), 2.06-2.11 (m, 2H), 1.65-1.81 (m, 6H). DMSO 419.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 115 407.47 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.70 (s, 1H), 9.45 (s, 1H), 8.98 (d, J = 6.8 Hz, 1H), 8.89 (d, J = 6.0 Hz, 1H), 8.37 (s, 1H), 8.32 (d, J = 6.8 Hz, 1H), 8.18 (s, 1H), 7.93 (t, J = 9.2 Hz, 2H), 7.70 (t, J = 7.2 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 5.18 (s, 1H), 2.09 (s, 2H), 1.77 (m, 4H), 1.66 (m, 2H). DMSO 408.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 116 401.68 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.81 (s, 1H), 9.47 (s, 1H), 8.71 (d, J = 6.4 Hz, 1H), 8.62 (d, J = 7.6 Hz, 1H), 8.26 (s, 1H), 7.88 (t, J = 7.2 Hz, 3H), 7.75-7.73 (m, 2H), 7.57-7.56 (m, 1H). DMSO 401.0, 403.0 405.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 117 368.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74(s, 1H), 9.45 (d, J = 1.2 Hz, 1H), 8.70 (dd, J = 4.4. 1.6 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.04-8.00 (m, 1H), 7.88-7.85 (m, 2H), 7.74 (dd, J = 8.4, 1.6 Hz, 1H), 7.65- 7.63 (m, 1H), 7.57- 7.56 (m, 2H). DMSO 369.1, 371.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 118 436.34 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.33 (s, 1H), 8.87-8.20 (m, 2H), 8.27 (d, J = 1.6 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.90-7.72 (m, 3H), 7.39-7.36 (m, 2H), 3.44 (brs, 4H), 2.05 (brs, 4H). DMSO 435.9, 437.9, 439.8 (M + 1) Method B (NH4HCO3) 95 Method C, G1 119 403.43 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.38 (s, 1H), 9.43 (d, J = 1.2 Hz, 1H), 8.85- 8.80 (m, 2H), 8.07-8.05 (m, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.81 (t, J = 6.8 Hz, 1H), 7.69-7.67 (m, 1H), 7.58-7.83 (m, 1H), 7.43-7.41 (m, 2H), 3.45 (brs, 4H), 2.06 (brs, 4H). DMSO 403.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 120 0 368.77 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.28 (s, 1H), 9.49 (s, 1 H), 8.77-8.87 (m, 3H), 8.06-8.12 (m, 1H), 7.90-7.95 (m, 2H), 7.78-7.81 (m, 1H), 7.57-7.73 (m, 1H), 7.53 (dd, J = 19.6 Hz, 9.2 Hz, 1H). DMSO 369.0, 371.1 (M + 1) Method A (TFA) 95 Method C, G1 121 401.68 1H-NMR (400 MHz, DMSO-d6): 10.37 (s, 1H), 9.52 (s, 1H), 8.95 (d, J = 3.2 Hz, 1H), 8.87 (m, 1H), 8.81 (s, 1H), 8.32 (d, J = 2.0 Hz, 1H), 7.95-7.99 (m, 3H), 7.87- 7.89 (m, 1H), 7.72 (d, J = 8.8 Hz, 1H). DMSO 401.0, 403.0, 405.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 122 385.22 1H-NMR (400 MHz, DMSO-d6): 10.09 (s, 1H), 9.50 (s, 1H), 8.69 (s, 2H), 8.64 (d, J = 8.0 Hz, 1H), 8.26 (dd, J = 10.6 Hz, 1.8 Hz, 1H), 7.89-7.90 (m, 3H), 7.51- 7.57 (m, 2H). DMSO 385.0, 387.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 123 357.8 1H-NMR (400 MHz, DMSO-d6): 10.25 (s, 1 H), 9.52 (s, 1 H), 8.67-8.76 (m, 3H), 8.44 (s, 1H), 8.27 (m, 1H), 7.96 (s, 2H), 7.66-7.69 (m, 2H), 7.57-7.59 (m, 1H). DMSO 358.0 (M + 1) Method A (TFA) 95 Method C, G1 124 411.86 1H-NMR (400 MHz, DMSO-d6): 10.53 (s, 1H), 9.54 (s, 1H), 9.08 (d, J = 8.4 Hz, 1H), 8.94-8.90 (m, 2H), 8.15 (d, J = 8.4 Hz, 2H), 8.00-7.93 (m, 5H), 7.39 (s, 2H). DMSO 412.0, 414.0 (M + 1) Method A (TFA) 95 Method C, G1 125 411.86 1H-NMR (400 MHz, DMSO-d6): 10.64 (s, 1H), 9.54 (s, 1H), 9.22 (s, 1H), 8.92- 8.98 (m, 2H), 8.70 (s, 1H), 8.10 (s, 1H), 8.03-8.05 (m, 1H), 7.95 (s, 2H), 7.69 (s, 2H), 7.53 (s, 2H). DMSO 412.0, 414.0 (M + 1) Method A (TFA) 95 Method C, G1 126 364.35 1H-NMR (400 MHz, DMSO-d6): 10.65 (s, 1H), 9.47 (s, 1H), 9.02 (d, J = 7.6 Hz, 1H), 8.92 (s, 1H), 8.21 (s, 1H), 8.08- 8.10 (m, 1 H), 7.95-7.97 (m, 2H), 7.74- 7.75 (m, 1H), 7.54-7.62 (m, 2H), 4.00 (s, 3H). DMSO 364.1 (M + 1) 183.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 127 397.26 1H-NMR (400 MHz, DMSO-d6): 10.56 (s, 1H), 9.48 (s, 1 H), 9.02 (d, J = 8.0 Hz, 1H), 8.91-8.92 (m, 1H), 8.28 (d, J = 2.4 Hz, 1H), 8.16-8.17 (m, 1H), 7.92-8.03 (m, 3H), 7.72 (d, J = 8.8 Hz, 1H), 7.58- 7.61 (m, 1H), 4.00 (s, 3H). DMSO 397.0, 399.0 (M + 1), 200.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 128 407.45 1H-NMR (400 MHz, DMSO-d6): 10.32 (s, 1H), 9.55 (s, 1H), 8.92-8.84 (m, 2H), 8.16-8.09 (m, 3H), 7.95-7.89 (m, 3H), 7.83-7.79 (m, 1 H), 7.62-7.58 (m, 1H), 7.36 (s, 2H), 3.40 (s, 3H). DMSO 408.1 (M + 1) Method A (TFA) 95 Method C, G1 129 362.81 1H-NMR (400 MHz, DMSO-d6): 10.06 (s, 1H), 9.51 (s, 1 H), 8.82-8.85 (m, 2H), 8.10-8.11 (m, 1H), 8.05 (d . J = 2.0 Hz, 1H), 7.98-7.93 (m, 2H), 7.75-7.77 (m, 1H), 7.59-7.61 (m, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.27-7.28 (m, 1H), 3.99 (s, 3H). DMSO 363.0, 365.0 (M + 1), 182.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 130 0 380.8 1H-NMR (300 MHz, DMSO-d6): 10.02 (s, 1H), 9.50 (s, 1H), 7.78-8.79 (m, 2H), 8.19-8.24 (m, 1H), 7.86-8.00 (m, 3H), 7.52-7.70 (m, 3H), 3.98 (s, 3H). DMSO 381.1, 383.1 (M + 1), 191.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 131 371.39 1H-NMR (300 MHz, DMSO-d6): 13.08 (s, 1H), 9.59 (s, 1 H), 9.07 (d, J = 8.1 Hz, 1H), 8.96(d, J = 8.1 Hz, 1H), 8.83 (d, J = 3.9 Hz, 1 H), 8.49(s, 1H), 7.89-7.99 (m, 3H), 7.80-7.84 (m, 1H), 7.72 (t, J = 7.8 Hz, 1 H), 7.60-7.63 (m, 2H), 7.23 (t, J = 7.5 Hz, 1H), 3.98 (s, 3H). DMSO 371.9 (M + 1) Method A (TFA) 95 Method C, G1 132 362.81 1H-NMR (400 MHz, DMSO-d6): 10.12 (s, 1H), 9.28 (s, 1H), 8.69 (d, J = 4.0 Hz, 1H), 8.59 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 2.8 Hz, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.68-7.70 (m, 2H), 7.57-7.63 (m, 2H), 7.48-7.53 (m, 1 H), 7.40-7.44 (m, 1 H), 3.86 (s, 3H). DMSO 363.0, 365.1 (M + 1), 182.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 133 348.35 1H-NMR (400 MHz, DMSO-d6): 9.46 (s, 1H), 9.11 (s, 1H), 8.79-8.76 (m, 2H), 8.00-7.94 (m, 1H), 7.83-7.73 (m, 3H), 7.62-7.48 (m, 3H), 3.00 (s, 3H). DMSO 349.1 (M + 1), 175.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 134 381.26 1H-NMR (400 MHz, DMSO-d6): 9.48 (s, 1H), 9.13 (s, 1H), 8.75-8.77 (m, 2H), 8.18 (s, 1H), 7.72-7.85 (m, 5H), 7.49- 7.50 (m, 1H), 3.00 (s, 3H). DMSO 381.0, 383.0, 385.0 (M + 1) Method A (TFA) 95 Method C, G1 135 364.8 1H-NMR (400 MHz, DMSO-d6): 9.43 (m, 2H), 8.94-8.89 (m, 2H), 8.08-8.06 (m, 1H), 7.92-7.81 (m, 4H), 7.57-7.53 (m, 2H)T 3.03 (s, 3H). DMSO 365.0, 367.0 (M + 1), 183.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 136 337.38 1H-NMR (400 MHz, DMSO-d6): 9.52- 9.44 (m, 2H), 8.98 (d, J = 8.0 Hz, 1H), 8.92 (d, J = 4.4 Hz, 1 H), 8.36-8.19 (m, 2H), 8.02-7.84 (m, 3H), 7.73-7.69 (m, 2H), 7.55 (d, J = 6.8 Hz, 1H), 3.04 (s, 3H). DMSO 338.1 (M + 1), 169.6 (M/2 + 1) Method A (TFA) 95 Method C, G1 137 364.35 1H-NMR (400 MHz, DMSO-d6): 9.97 (s, 1H), 9.51 (s, 1H), 8.69-8.66 (m, 2H), 8.16-8.08 (m, 2H), 7.75-7.73 (m, 1 H), 7.61-7.53 (m, 3H), 7.40 (d, J = 7.6 Hz, 1H), 4.01 (s, 3H). DMSO 183.1 (M/2 + 1) 365.1 (M + 1) Method A (TFA) 95 Method C, G1 138 397.26 1H-NMR (400 MHz, DMSO-d6): 10.01 (s, 1 H), 9.53 (s, 1H), 8.67-8.70 (m, 2H), 8.41 (d, J = 2.4 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 1H), 7.95-7.99 (m, 1H), 7.73 (d, J = 8.8 Hz, 1 H), 7.56-7.63 (m, 2H), 7.42 (d, J = 8.4 Hz, 1H), 4.02 (s, 3H). DMSO 397.0, 399.0 (M + 1) Method A (TFA) 95 Method C, G1 139 380.8 1H-NMR (400 MHz, DMSO-d6): 10.21 (S, 1H), 9.48 (s, 1 H), 8.99 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 4.8 Hz, 1H), 8.15-8.22 (m, 2H), 7.92-7.95 (m, 2H), 7.62 (t, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.8 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 4.02 (s, 3H). DMSO 191.1 (M/2 + 1) 381.1, 383.1 (M + 1) Method A (TFA) 95 Method C, G1 140 0 401.68 1H-NMR (400 MHz, DMSO-d6): 10.11 (S, 1H), 8.50 (m, 1H), 8.63-8.70 (m, 3H), 8.14 (d, J = 2.0 Hz, 2H), 7.92 (m, 2H), 7.57 (m, 1H), 7.38 (t, J = 1.6 Hz, 1H). DMSO 401.0, 403.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 141 348.35 1H-NMR (400 MHz, DMSO-d6): 9.46 (s, 1 H), 9.11 (s, 1 H), 8.76-8.70 (m, 2H), 7.95-7.99 (m, 1H), 7.78-7.60 (m, 3H), 7.54-7 .44 (m: 3H), 3.00 (s, 3H). DMSO 175.1 (M/2 + 1) 349.1 (M + 1) Method A (TFA) 95 Method C, G1 142 397.26 1H-NMR (400 MHz, DMSO-d6): 10.30 (s, 1H), 8.39 (s, 1H), 8.83 (s, 2H), 8.03- 8.12 (m, 3H), 7.79-7.81 (m, 2H), 7.50- 7.51 (m, 1H), 7.32 (s, 1H), 3.96 (s, 3H). DMSO 397.0, 399.0, 401.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 143 452.34 1H-NMR (400 MHz, DMSO-d6): 9.86 (s, 1H), 9.51 (s, 1H), 8.65-8.66 (m, 2H), 8.34-8.35 (m, 1H), 7.95-7.96 (m, 1 H), 7.72-7.80 (m, 4H), 7.54 (m, 1H), 3.84 (m, 4H), 3.56 (m, 4H). DMSO 452.1, 454.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 144 435.88 1H-NMR (400 MHz, DMSO-d6): 9.83 (s, 1H), 9.49 (s, 1 H), 8.62-8.65 (m, 2H), 8.21-8.23 (m, 1H), 7.89-7.91 (m, 1H), 7.78-7.81 (m, 1H), 7.72-7.73 (m, 2H), 7.51-7.54 (m, 2H), 3.84 (t, J = 4.0 Hz, 4H), 3.36 (m, 4H). DMSO 436.1, 438.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 145 419.43 1H-NMR (400 MHz, DMSO-d6): 10.50 (s, 1 H), 9.45 (s, 1 H), 8.83-8.90 (m, 2H), 8.06-8.08 (m, 1H), 7.70-7.93 (m, 5H), 7.56 (dd, J = 19.6, 9.6 Hz, 1H), 3.82- 3.83 (m, 4H), 3.39-3.41 (m, 4H). DMSO 420.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 146 408.46 1H-NMR (400 MHz, DMSO-d6): 10.54 (s, 1H), 9.44 (s, 1H), 8.90 (d, J = 8.0 Hz, 1H), 8.84 (d, J = 4.4 Hz, 1H), 8.34 (s, 1H), 8.27 (d, J = 7.2 Hz, 1H), 7.67-7.92 (m, 6H), 3.82-3.83 (m, 4H), 3.39-3.40 (m, 4H). DMSO 409.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 147 452.34 1H-NMR (400 MHz, DMSO-d6): 10.42 (s, 1 H), 9.42 (s, 1 H), 8.85-8.87 (m, 2H), 8.11 (s, 2H), 7.73-7.88 (m, 4H), 7.38 (s, 1H), 3.82-3.83 (m, 4H), 3.39-3.40 (m, 4H). DMSO 452.1, 454.1, 456.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 148 426.47 1H-NMR (400 MHz, DMSO-d6): 12.93 (s, 1H), 9.57 (m, 1H), 9.12 (d, J = 8.4 Hz, 1H), 8.68-8.72 (m, 2H), 8.56 (s, 1H), 8.02 (d, J = 6.8 Hz, 1H), 7.96 (s, 1H), 7.72-7.84 (m, 3H), 7.56-7.57 (m, 1 H), 7.40 (m, 1H), 7.19 (t, J = 8.0 Hz, 1H), 3.84 (t, J = 4.4 Hz, 4H), 3.35 (t, J = 4.4 Hz, 4H). DMSO 427.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 149 393.84 1H-NMR (400 MHz, DMSO-d6): 9.71 (s, 1 H), 9.48 (s, 1 H), 8.62-8.63 (m, 2H): 8.23 (m, 1H), 7.92 (m, 1H), 7.77 (d, J = 9.6 Hz, 1H), 7.51-7.56 (m, 3H), 7.42 (m, 1H), 3.12 (s, 6H). DMSO 394.1, 396.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 150 0 377.39 1H-NMR (400 MHz, DMSO-d6): 9.72 (s, 1H), 9.48 (m, 1H), 8.60-8.63 (m, 2H), 8.08-8.14 (m, 1H), 7.77 (d, J = 9.2 Hz, 1H), 7.69-7.71 (m, 1 H), 7.50-7.57 (m, 3H), 7.42-7.43 (m, 1H), 3.12 (s, 6H). DMSO 378.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 151 410.3 1H-NMR (400 MHz, DMSO-d6): 9.72 (s, 1H), 9.49 (s, 1 H), 8.60-8.64 (m, 2H), 8.17 (s, 2H), 7.76 (d, J = 8.8 Hz, 1H), 7.51-7.53 (m, 2H), 7.37 (s, 1H), 7.32 (s, 1H), 3.11 (s, 6H). DMSO 410.1, 412.0, 414.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 152 410.3 1H-NMR (400 MHz, DMSO-d6): 10.44 (s, 1 H), 9.45 (s, 1 H), 8.83-8.91 (m, 2H), 8.26-8.27 (m, 1H), 7.72-7.99 (m, 4H), 7.57-7.61 (m, 2H), 3.14(s, 6H). DMSO 410.1, 412.1, 414.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 153 366.42 1H-NMR (400 MHz, DMSO-d6): 9.82 (s, 1H), 9.48 (s, 1H), 8.55-8.64 (rn, 2H), 8.41 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 9.6 Hz, 1H), 7.69 (t, J = 8.0 Hz, 1H), 7.50-7.61 (m, 3H), 7.43 (m, 1H), 3.12(s, 6H). DMSO 367.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 154 435.23 1H-NMR (400 MHz, DMSO-d6): 10.57 (s, 1H), 9.53 (s, 1 H), 8.86-8.94 (m, 3H), 8.32-8.33 (m, 1H), 8.21 (s, 1H), 7.97- 8.01 (m, 2H), 7.84-7.88 (m, 1H), 7.73 (d, J = 8.8 Hz, 1H). DMSO 435.1, 437.1, 439.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 155 402.32 1H-NMR (400 MHz, DMSO-d6): 10.32 (S, 1H), 9.51-9.52 (m, 1H), 8.65-8.78 (m, 3H), 8.19 (s, 1H), 8.11 (m, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.71 (m, 1H), 7.55- 7.59 (m, 2H). DMSO 403.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 156 435.23 1H-NMR (400 MHz, DMSO-d6): 10.65 (s, 1H), 9.46(s, 1H), 8.88-8.97 (m, 3H): 8.17 (S, 1H), 8.10-8.11 (m, 2H), 7.97 (s, 1H), 7.95 (s, 1H), 7.39 (s, 1H). DMSO 435.1, 437.0, 439.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 157 418.77 1H-NMR (400 MHz, DMSO-d6): 10.62 (s, 1H), 9.52 (s, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.88-8.90 (m, 2H), 8.20-8.23 (m, 2H), 8.01 (d, J = 8.0 Hz, 1H), 7.92-7.95 (m, 2H), 7.54 (t, J = 9.2 Hz, 1H). DMSO 419.1, 421.1 (M + 1) Method B (NH4HCO3) 95 Method C, G 158 409.36 1H-NMR (400 MHz, DMSO-d6): 13.24 (S, 1H), 9.56 (s, 1H), 9.10 (d, J = 8.4 Hz, 1H), 8.96 (s, 1H), 8.87 (d, J = 8.0 Hz, 1H), 8.54 (s, 1H), 8.33 (d, J = 8.8 Hz, 1H), 8.18 (s, 1H), 7.95-8.01 (m, 4H), 7.70 (t, J = 7.6 Hz, 1 H), 7.27 (t, J = 7.2 Hz, 1H). DMSO 410.1 (M + 1) Method B (NH4HCO3) 95 Method C, G 159 391.35 1H-NMR (400 MHz, DMSO-d6): 10.82 (s, 1H), 8.50 (s, 1H), 9.04 (d, J = 8.0 Hz, 1H), 8.96 (d, J = 8.8 Hz, 2H), 8.37 (s, 1H), 8.30-8.28 (m, 1H), 8.21 (s, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.68-7.69 (m, 2H). DMSO 392.2 (M + 1) Method B (NH4HCO3) 95 Method C, G 160 00 450.34 1H-NMR (400 MHz, DMSO-d6): 10.40 (s, 1H), 9.54-9.55 (m, 1H). 8.82-8.84 (m, 1H), 8.67-8.73 (m, 2H). 8.16-8.21 (m, 2H), 7.93-8.00 (m, 2H), 7.54-7.64 (m, 2H), 7.21 (d, J = 8.0 Hz, 1H). DMSO 451.1 (M + 1) Method B (NH4HCO3) 95 Method C, G 161 01 416.78 1H-NMR (400 MHz, DMSO-d6): 10.10 (s, 1H), 9.49 (s, 1 H), 8.62-8.72 (m, 3H). 8.13 (s, 1 H), 7.88-7.92 (m, 3H), 7.51- 7.60 (m, 2H), 7.14-7.16 (m, 1H). DMSO 417.1, 419.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 162 02 375.81 1H-NMR (400 MHz, DMSO-d6): 13.13 (s, 1H), 9.53 (s, 1H), 9.01 (d, J = 8.0 Hz, 1H), 8.68-8.72 (m, 2H). 8.50 (s, 1H). 8.10 (d, J = 8.8, 1H), 7.88-7.97 (m, 3H). 7.70-7.72 (m, 2H), 7.57-7.59 (m, 1 H), 7.22 (t, J = 7.6, 1H). DMSO 376.0, 378.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 163 03 376.8 1H-NMR (400 MHz, DMSO-d6): 12.07 (s, 1H). 9.56 (s, 1H), 8.84 (d, J = 8.4 Hz, 1H), 8.71-8.73 (m, 2H). 8.34 (s, 1H), 7.96-8.09(m, 3H). 7.59-7.80 (m, 2H), 7.29 (t, J = 7.2 Hz, 1 H). DMSO 377.0, 379.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 164 04 394.37 1H-NMR (400 MHz, DMSO-d6): 9.90 (s, 1H). 9.53 (s, 1H), 8.67 (d, J = 5.2 Hz, 2H). 7.99 (d, J = 2.4 Hz, 1H). 7.94 (m, 1H). 7.87 (d, J = 9.2 Hz, 1H). 7.80 (d, J = 8.4 Hz, 1H). 7.49-7.59 (m, 3H). 7.31 (t, J = 74.0 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 3.99 (s, 3H). DMSO 395.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 165 05 HCl 458.51 1H-NMR (400 MHz, DMSO-d6): 9.42 (s, 1H), 8.98 (d, J = 8.4 Hz, 1H), 8.68- 8.71 (m, 2H), 7.94 (d, J = 7.6 Hz, 1H), 7.70 (t, J = 8.0 Hz, 1H), 7.57 (t, J = 5.6 Hz, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.19 (t, J = 7.2 Hz, 1H), 4.52 (s, 2H), 4.00 (s, 3H), 3.63 (s, 2H), 2.89 (s, 6H). DMSO 459.1 (M + 1) 230.2 (M/2 + 1) Method A (TFA) 95 Method C, G1 166 06 467.92 1H-NMR (400 MHz, DMSO-d6): 9.71 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.62- 8.67 (m, 2H), 8.20 (dd, J = 6.8, 2.4 Hz, 1H), 7.86-7.89 (m, 2H), 7.51-7.55 (m, 2H), 7.31 (s, 1H), 4.24 (t, J = 6.0 Hz, 2H), 3.98 (s, 3H), 2.77 (t, J = 5.6 Hz, 2H), 2.29 (s, 6H). DMSO 468.1 (M + 1) 234.6 (M/2 + 1) Method B (NH4HCO3) 95 Method C, G1 167 07 HCl 428.82 1H-NMR (400 MHz, DMSO-d6): 10.41 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.98 (d, J = 8.4 Hz, 1H), 8.88 (dd, J = 5.2, 1.6 Hz, 1H), 8.13 (d, J = 2.8 Hz, 1H), 8.00 (t, J = 2.0 Hz, 1H), 7.89-7.95 (m, 3H), 7.62 (dd, J = 9.2. 3.2 Hz, 1H), 7.36 (t, J = 73.6 Hz, 1H), 7.16 (d, J = 2.0 Hz, 1H), 4.01 (s, 3H). DMSO 429.1, 431.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 168 08 385.42 1H-NMR (400 MHz, DMSO-d6): 13.03 (s, 1H), 9.62 (d, J = 1.6 Hz, 1H), 9.20 (d, J = 8.4 Hz, 1H), 8.74-8.77 (m, 1H), 8.70 (dd, J = 4.4, 1.6 Hz, 1H), 8.48 (s, 1H), 7.96-7.99 (m, 2H), 7.72-7.76 (m, 1H), 7.57-7.60 (m, 1H), 7.47 (m, 1H), 7.41 (m, 1H), 7.17-7.21 (m, 1H), 3.95 (s, 3H), 2.72 (s, 3H). DMSO 386.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 169 09 HCl 368.77 1H-NMR (400 MHz, DMSO-d6): 10.31 (s, 1H), 9.47 (s, 1H), 8.86-8.93 (m, 2H), 8.54 (dd, J = 10.0. 2.8 Hz, 1H), 8.21 (dd, J = 6.8, 2.4 Hz, 1H), 7.82-8.00 (m, 4H), 7.52 (t, J = 9.2 Hz, 1H). DMSO 369.0, 371.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 170 0 HCl 400.33 1H-NMR (400 MHz, DMSO-d6): 10.35 (s, 1H), 9.53 (s, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 4.0 Hz, 1H), 8.60 (dd, J = 10.4, 3.2 Hz, 1H), 7.97-8.09 (m, 3H), 7.88-7.92 (m, 2H), 7.62 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H). DMSO 401.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 171 359.36 1H-NMR (400 MHz, DMSO-d6): 13.06 (s, 1H), 9.58 (s, 1H), 9.07 (d, J = 8.4 Hz, 1H), 8.72 (d, J = 5.6 Hz, 2H), 8.52 (s, 1H), 7.96-8.02 (m, 3H), 7.83-7.87 (m, 2H), 7.74 (t, J = 8.0 Hz, 1H), 7.59 (t, J = 6.0 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H). DMSO 360.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 172 HCl 382.34 1H-NMR (400 MHz, DMSO-d6): 10.30 (s, 1H), 9.53 (d, J = 1.2 Hz, 1H), 8.98 (d, J = 8.0 Hz, 1H), 8.88 (d, J = 4.4 Hz, 1H), 8.62 (dd, J = 10.0, 2.8 Hz, 1H), 8.01- 8.05 (m, 1 H), 7.84-7.92 (m, 4H), 7.50- 7.56 (m, 1H), 7.32 (t, J = 74.0 Hz, 1H), 7.03 (dd, J = 8.0, 2.0 Hz, 1H). DMSO 383.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 173 348.35 1H-NMR (400 MHz, DMSO-d6): 10.09 (s, 1 H), 9.51 (s, 1 H), 8.79-8.76 (m, 2H), 8.38 (s, 1 H), 8.16-8.11 (m, 1H), 7.86- 7.66 (m, 4H), 7.59-7.50 (m, 1H), 2.57 (s, 3H). DMSO 349.1 (M + 1), 175.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 174 364.8 1 H-NMR (300 Hz, CD30D): 9.50 (d, J = 1.2 Hz, 1H), 9.14 (d, J = 8.4 Hz, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.35 (s, 1H), 8.09-7.99 (m, 2H), 7.93 (s, 2H), 7.78- 7.73 (m, 1H), 7.39 (t, J = 9.0 Hz, 1H), 2.64 (s, 3H). CD3OD 365.1, 367.1 (M + 1) Method A (TFA) 95 Method C, G1 175 381.26 1H-NMR (400 MHz, DMSO-d6): 10.13 (S, 1H), 9.51 (s, 1H), 8.84-8.79 (m, 2H), 8.36-8.34 (m, 2H), 7.96 (dd, J = 8.8. 2.5 Hz, 1H), 7.85-7.70 (m, 4H), 2.55 (s, 3H). DMSO 381.0, 383.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 176 346.81 1 H-NMR (300 Hz, CD3OD): 9.48 (d, J = 1.2 Hz, 1H), 8.99-8.95 (m, 1H), 8.82- 8.80 (m, 1H), 8.30-8.29 (m, 1H), 7.90- 7.81 (m, 5H), 7.52-7.46 (m, 2H), 2.62 (s, 3H). CD3OD 347.0, 349.1 (M + 1) Method A (TFA) 95 Method C, G1 177 346.81 1 H-NMR (400 MHz, DMSO-d6): 10.12 (s, 1H), 9.52 (s, 1 H), 8.84-8.78 (m, 2H), 8.42 (s, 1H), 8.16-8.15 (m, 1H), 7.94- 7.91 (m, 1H): 7.85 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.75-7.71 (m, 1H), 7.50 (t, J = 8.1 Hz, 1 H), 7.27-7.23 (m, 1H), 2.56 (s, 3H). DMSO 347.1, 349.1 (M + 1) Method A (TFA) 95 Method C, G1 178 380.37 1H-NMR (400 MHz, DMSO-d6): 10.60 (S, 1H), 9.50 (d, J = 2.1 Hz, 1H), 9.00 (d, J = 8.1 Hz, 1H), 8.90 (dd, J = 5.1, 1.2 Hz, 1H), 8.55 (s, 1H), 8.43 (s, 1H), 8.25 (d, J = 7.8 Hz, 1H), 7.96-7.90 (m, 2H), 7.84 (d, J = 8.1 Hz, 1H), 7.27 (t, J = 8.2 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 2.62 (s, 3H). DMSO 381.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 179 414.81 1H-NMR (400 MHz, DMSO-d6): 10.59 (s, 1H), 9.50 (s, 1H), 9.02 (d, J = 8.4 Hz, 1H), 8.92 (d, J = 5.2 Hz, 1H), 8.59 (d, J = 2.8 Hz, 1H), 8.54 (s, 1H), 8.34 (dd, J = 8.6. 2.6 Hz, 1H), 7.96-7.90 (m, 2H), 7.81 (d, J = 8.8 Hz, 2H), 2.56 (s, 3H). DMSO 415.1, 417.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 180 0 401.37 1H-NMR (400 MHz, DMSO-d6): 13.91 (s, 1H), 10.38 (s, 1H), 9.59 (s, 1H), 8.79- 8.76 (m, 1H), 8.73 (d, J = 4.8 Hz, 1H), 8.61 (d, J = 2.4 Hz, 1H), 8.44 (s, 1H), 8.33 (dd, J = 9.0. 2.6 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.81 (dd, J = 8.4, 1.2 Hz, 1H), 7.60- 7.57 (m, 1H), 2.58 (s, 3H). DMSO 402.0 (M + 1) Method A (TFA) 95 Method C, G1 181 381.26 1H-NMR (400 MHz, DMSO-d6): 10.40 (s, 1H), 9.47 (s, 1H), 8.98 (d, J = 7.5 Hz, 1H), 8.91 (d, J = 4.5 Hz, 1H), 8.48 (s, 1H), 8.12 (d, J = 2.1 Hz, 2H), 7.97-7.93 (m, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.40 (s, 1H), 2.55 (s, 3H). DMSO 381.0, 383.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 182 390.82 1H-NMR (400 MHz, DMSO-d6): 12.25 (S, 1H), 9.54 (s, 1H), 9.25 (s, 1 H), 8.84- 8.80 (m, 2H), 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 9.2 Hz, 1H), 7.77-7.75 (m, 1H), 7.29 (d, J = 8.4 Hz, 1H), 2.56 (s, 3H). DMSO 391.1, 393.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 183 366.34 1 H-NMR (400 MHz, DMSO-d6): 9.98 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.69 (dd, J = 4.8, 1.6 Hz, 1H), 8.66-8.63 (m, 1H), 8.30 (s, 1H), 7.99-7.95 (m, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.76 (dd, J = 8.6. 1.4 Hz, 1H), 7.58-7.55 (m, 1H), 2.55 (s, 3H). DMSO 367.1 (M + 1), 184.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 184 415.7 1H-NMR (400 MHz, DMSO-d6): 10.09 (s, 1H), 9.51 (s, 1 H), 8.75-8.72 (m, 2H), 8.38 (s, 2H), 8.32 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.66- 7.64 (m, 1H), 2.55 (s, 3H). DMSO 414.8, 416.8 (M + 1) Method B (NH4HCO3) 95 Method C, G1 185 354.4 1H-NMR (400 MHz, DMSO-d6): 10.26 (s, 1H), 9.56 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 8.81 (d, J = 4.0 Hz, 1H), 8.65 (s, 1H), 8.48 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1 H), 7.88-7.88 (m, 3H), 7.65 (t, J = 7.6 Hz, 1H), 2.65 (s, 3H), 2.58 (s, 3H). DMSO 355.1 (M + 1), 178.1 (M/2 + 1) Method A (TFA) 95 Method C, G1 186 356.38 1H-NMR (400 MHz, DMSO-d6): 12.18 (s, 1H), 9.57 (s, 1H), 9.07 (d, J = 8.4 Hz, 1H), 8.71 (d, J = 5.6 Hz, 2H), 8.10 (d, J = 8.0 Hz, 1 H), 7.99 (s, 1H), 7.86-7.76 (m, 3H), 7.58 (t, J = 6.2 Hz, 1H), 7.23 (t, J = 7.4 Hz, 1H), 2.55 (s, 3H). DMSO 357.1 (M + 1) Method A (TFA) 95 Method C, G1 187 337.38 1 H-NMR (400 MHz, DMSO-d6): 10.10 (s, 1H), 9.51 (s, 1H), 8.65-8.70 (m, 2H), 8.45 (s, 1H), 8.38 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.8 Hz, 1 H), 7.62 (d, J = 7.2 Hz, 1 H), 7.54-7.57 (m, 1H), 2.56 (s, 3H). DMSO 338.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 188 355.39 1H-NMR (400 MHz, DMSO-d6): 13.11 (s, 1H), 9.61 (s, 1H), 9.09 (d, J = 8.8 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.81 (s, 1H), 8.50 (S, 1H), 8.01-7.98 (m, 2H), 7.96 (dd, J = 7.8, 1.0 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.78-7.72 (m, 3H), 7.23 (t,J = 7.4 Hz, 1H), 2.56 (s, 3H). DMSO 356.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 189 385.42 1H-NMR (400 MHz, DMSO-d6): 12.62 (s, 1H), 9.58 (s, 1H), 9.03 (d, J = 8.4 Hz, 1H), 8.92 (d, J = 4.0 Hz, 1 H), 8.74-8.69 (m, 2H), 7.92-7.87 (m, 2H), 7.72 (t, J = 7.6 Hz, 1H), 7.66-7.56 (m, 3H), 7.23 (t, J = 7.6 Hz, 1H), 4.00 (s, 3H), 2.84 (d, J = 4.4 Hz, 3H). DMSO 386.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 190 0 461.51 1H-NMR (400 MHz, DMSO-d6): 12.40 (S, 1H), 9.57 (d, J = 1.2 Hz, 1H), 9.48 (t, J = 6.0 Hz, 1H), 8.89 (d, J = 8.8 Hz, 1H), 8.73-8.68 (m, 2H), 7.96 (dd, J = 8.0. 1.2 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.76-7.72 (m, 1H), 7.61-7.55 (m, 3H), 7.34-7.20 (m, 6H), 4.52 (d, J = 5.6 Hz, 2H), 3.93 (s, 3H). DMSO 462.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 191 368.77 1H NMR (300 MHz, DMSO-d6): 10.32 (s, 1H), 9.55-9.45 (m, 1H), 8.93-8.76 (m, 2H), 8.63 (d, J = 8.9 Hz, 1H), 8.10 (ddd, J = 13.2, 7.5, 2.6 Hz, 1H), 7.97 (d, J = 2.1 Hz, 1H), 7.80-7.67 (m, 3H)T 7.62-7.49 (m, 1H). DMSO 369.0, 371.0 (M + 1) Method B (NH4HCO3) 97 Method C, G1 192 401.68 1H NMR (300 MHz, DMSO-d6): 10.38 (s, 1H), 9.58-9.43 (m, 1H), 8.90-8.79 (m, 2H), 8.65 (d, J = 9.0 Hz, 1H), 8.33 (d, J = 2.4 Hz, 1H), 8.01-7.90 (m, 2H), 7.82-7.68 (m, 3H). DMSO 401.0, 403.0, 405.0 (M + 1) Method B (NH4HCO3) 97 Method C, G1 193 367.23 1H NMR (300 MHz, DMSO-d6): 10.19 (S, 1H), 9.53 (d, J = 2.1 Hz, 1H), 8.78- 8.56 (m, 3H), 8.17 (t, J = 2.0 Hz, 1H), 7.96 (d, J = 2.1 Hz, 1H), 7.93-7.85 (m, 1H), 7.75 (dd, J = 8.9, 2.2 Hz, 1H), 7.58 (ddd, J = 8.0. 4.8, 0.7 Hz, 1H), 7.51 (t, J = 8.1 Hz, 1H), 7.26 (ddd, J = 8.0, 2.0, 0.8 Hz, 1H). DMSO 367.0, 369.0 (M + 1) Method B (NH4HCO3) 98 Method C, G1 194 376.80 1H NMR (300 MHz, DMSO-d6): 13.11 (s, 1H), 10.27 (s, 1H), 9.58 (d, J = 2.1 Hz, 1H), 8.87-8.62 (m, 4H), 8.21-8.10 (m, 1H), 7.96 (d, J = 2.1 Hz, 1H), 7.82- 7.68 (m, 2H), 7.64-7.53 (m, 2H). DMSO 377.0, 379.0 (M + 1) Method A (TFA) 95 Method C, G1 195 401.68 1H NMR (300 MHz, DMSO-d6): 10.32 (s, 1H), 9.52-9.49 (m, 1H), 8.85-8.73 (m, 2H), 8.61 (d, J = 9.0 Hz, 1H), 8.18- 8.08 (m, 2H), 7.99-7.95 (m, 1H), 7.77 (dd, J = 8.9, 2.2 Hz, 1H), 7.71 (dd, J = 7.8, 5.0 Hz, 1H), 7.42-7.39 (m, 1H). DMSO 401.0, 403.0, 405.0 (M + 1) Method B (NH4HCO3) 97 Method C, G1 196 386.76 1H-NMR (300 MHz, DMSO-d6): 10.43 (s, 1H), 9.49 (d, J = 1.9 Hz, 1H), 8.95- 8.82 (m, 2H), 8.64 (d, J = 9.0 Hz, 1H), 8.01-7.82 (m, 4H), 7.78 (dd, J = 8.9, 2.2 Hz, 1H). DMSO 387.0, 389.1 (M + 1) Method B (NH4HCO3) 97 Method C, G1 197 411.86 1H NMR (400 MHz, DMSO-d6): 10.50 (brs, 1H), 9.56 (s, 1H), 9.08-8.93 (m, 1H), 8.92-8.82 (m, 1H), 8.73 (d, J = 8.9 Hz, 1H), 8.21-8.11 (m, 2H), 8.02 (d, J = 1.9 Hz, 1H), 7.98-7.77 (m, 4H), 7.38 (s, 2H). DMSO 412.1, 414.1 (M + 1) Method B (NH4HCO3) 97 Method C, G1 198 385.22 1H NMR (400 MHz, DMSO-d6): 10.25 (s, 1H), 9.51 (d, J = 1.4 Hz, 1H), 8.77- 8.69 (m, 2H), 8.60 (d, J = 9.0 Hz, 1H), 8.27-8.20 (m, 1 H), 7.97 (d, J = 2.1 Hz, 1H), 7.90 (ddd, J = 9.0, 4.3, 2.6 Hz, 1H), 7.76 (dd, J = 8.9, 2.1 Hz, 1H), 7.64 (dd, J = 8.0, 4.9 Hz, 1H), 7.55 (t, J = 9.1 Hz, 1H). DMSO 385.0, 387.0 (M + 1) Method B (NH4HCO3) 100 Method C, G1 199 357.80 1H NMR (400 MHz, DMSO-d6): 10.36 (s, 1 H), 9.53-9.49 (m, 1H), 8.81-8.70 (m, 2H), 8.64 (d, J = 8.9 Hz, 1H), 8.45- 8.36 (m, 1H), 8.29-8.21 (m, 1H), 7.98 (d, J = 2.1 Hz, 1H), 7.77 (dd, J = 8.9, 2.1 Hz, 1H), 7.74-7.61 (m, 3H). DMSO 357.9, 359.9 (M + 1) Method B (NH4HCO3) 99 Method C, G1 200 0 435.23 1H-NMR (400 MHz, DMSO-d6): 10.44 (s, 1 H), 9.53 (s, 1H), 8.84-8.74 (m, 2H), 8.69-8.61 (m, 2H), 8.26 (dd, J = 8.8, 2.6 Hz, 1H), 7.99 (d, J = 2.1 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.78 (dd, J = 8.9, 2.1 Hz, 1H), 7.70 (dd, J = 7.7, 5.3 Hz, 1H). DMSO 435.0, 437.0 (M + 1) Method B (NH4HCO3) 99 Method C, G1 201 400.78 1H-NMR (400 MHz, DMSO-d6): 10.45 (s, 1H), 9.53 (d, J = 1.5 Hz, 1H), 8.85 (d, J = 8.1 Hz, 1H), 8.82 (dd, J = 5.0, 1.4 Hz, 1H), 8.69 (d, J = 9.0 Hz, 1H), 8.49 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 2.1 Hz, 1H), 7.83-7.67 (m, 3H), 7.56 (d, J = 7.8 Hz, 1H). DMSO 401.1, 403.0 (M + 1) Method B (NH4HCO3) 99 Method C, G1 202 375.79 1H-NMR (400 MHz, DMSO-d6): 10.47 (s, 1 H), 9.49 (s, 1H), 8.87-8.77 (m, 2H), 8.63 (d, J = 8.9 Hz, 1H), 8.42 (dd, J = 5.8, 2.7 Hz, 1H), 8.26 (ddd, J = 9.1, 4.9, 2.8 Hz, 1H), 7.98 (d, J = 2.1 Hz, 1H), 7.83-7.72 (m, 2H), 7.66 (t, J = 9.1 Hz, 1H). DMSO 375.9, 377.9 (M + 1) Method B (NH4HCO3) 99 Method C, G1 203 348.35 1H-NMR (400 MHz, DMSO-d6): 10.42 (s, 1H), 9.51 (s, 1H), 8.91 (d, J = 6.8 Hz, 1H), 8.86 (d, J = 4.4 Hz, 1H), 8.57 (d, J = 8.3 Hz, 1H), 8.11 (ddd, J = 13.0, 7.5, 2.5 Hz, 1H), 7.90-7.68 (m, 3H), 7.65-7.46 (m, 2H), 2.56 (s, 3H). DMSO 349.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 204 381.26 1H-NMR (400 MHz, DMSO-d6): 10.05 (s, 1 H), 9.54 (s, 1H), 8.75-8.65 (m, 2H), 8.46 (d, J = 8.5 Hz, 1 H), 8.42 (d, J = 2.4 Hz, 1H), 7.98 (dd, J = 8.8, 2.4 Hz, 1H), 7.72 (d, J = 9.1 Hz, 2H), 7.57 (dd, J = 7.9, 4.9 Hz, 1 H), 7.53 (d, J = 8.5 Hz, 1H), 2.55 (s, 3H). DMSO 381.0, 383.0 (M + 1) Method B (NH4HCO3) 100 Method C, G1 205 364.35 1H-NMR (400 MHz, DMSO-d6): 9.98 (s, 1H), 9.53 (s, 1H), 8.79-8.58 (m, 2H), 8.49 (d, J = 9.0 Hz, 1H), 8.13 (ddd, J = 9.2, 7.1, 1.7 Hz, 1H), 7.84-7.65 (m, 1H), 7.67-7.46 (m, 2H), 7.41-7.23 (m, 2H), 3.97 (s, 3H). DMSO 365.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 206 364.80 1H-NMR (400 MHz, DMSO-d6): 10.32 (s, 1H), 9.50 (d, J = 1.4 Hz, 1H), 8.92- 8.77 (m, 2H), 8.53 (d, J = 8.5 Hz, 1H), 8.24 (dd, J = 6.8, 2.5 Hz, 1H), 7.98- 7.87 (m, 1 H), 7.83-7.70 (m, 2H), 7.60- 7.50 (m, 2H), 2.56 (s, 3H). DMSO 365.1, 367.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 207 381.26 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1 H), 9.53 (s, 1 H), 8.87-8.73 (m, 2H), 8.50 (d, J = 8.5 Hz, 1 H), 8.17 (d, J = 1.7 Hz, 2H), 7.77 (s, 1H), 7.72 (dd, J = 7.8, 5.1 Hz, 1H), 7.57 (dd, J = 8.4, 0.9 Hz, 1H), 7.39 (t, J = 1.6 Hz, 1 H), 2.56 (s, 3H). DMSO 381.1, 383.0 (M + 1) Method B (NH4HCO3) 99 Method C, G1 208 337.38 1H-NMR (400 MHz, DMSO-d6): 10.12 (S, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.77- 8.63 (m, 2H), 8.53-8.42 (m, 2H), 8.28 (d, J = 8.3 Hz, 1H), 7.75 (s, 1H), 7.69 (t, J = 7.9 Hz, 1 H), 7.62 (d, J = 7.7 Hz, 1H), 7.60-7.51 (m, 2H), 2.55 (s, 3H). DMSO 338.2 (M + 1) Method B (NH4HCO3) 100 Method C, G1 209 355.39 1H-NMR (400 MHz, DMSO-d6): 13.09 (s, 1H), 9.60 (s, 1 H), 9.02 (d, J = 8.4 Hz, 1H), 8.96 (d, J = 8.4 Hz, 1H), 8.85 (d, J = 4.0 Hz, 1H), 8.49 (S, 1H), 8.13 (d, J = 8.4 Hz, 1 H), 7.97 (d, J = 7.8 Hz, 1H), 7.92 (s, 1H), 7.83 (dd, J = 8.0, 5.2 Hz, 1H), 7.80 (s, 1H), 7.73 (t, J = 7.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 2.56 (s, 3H). DMSO 356.1 (M + 1) Method B (NH4HCO3) 99 Method C, G1 210 0 375.81 1H-NMR (400 MHz, DMSO-d6): 13.13 (s, 1H), 9.59 (s, 1H), 9.03-8.89 (m, 3H), 8.50 (s, 1H), 8.21-8.19 (d, J = 8.6 Hz, 1H), 7.99-7.87 (m, 4H), 7.82-7.79 (dd, J = 8.8. 2.3 Hz, 1 H), 7.74-7.70 (m, 1 H), 7.28-7.24 (m, 1H). DMSO 376.1, 378.1 (M + 1) Method B (NH4HCO3) 98 Method C, G1 211 444.79 1H-NMR (400 MHz, DMSO-d6): 13.68 (bis, 1H), 11.98 (s, 1H), 9.49 (s, 1H), 8.83-8.64 (m, 2H), 8.11-7.90 (m, 3H), 7.81 (d, J = 2.0 Hz, 1H), 7.75-7.62 (m, 2H), 7.22 (t, J = 7.6 Hz, 1H). DMSO 444.9, 446.9 (M + 1) Method B (NH4HCO3) 100 Method C, G1 212 466.79 1H-NMR (400 MHz, DMSO-d6): 10.36 (s, 1H), 9.62 (s, 1H), 8.90 (dd, J = 8.2, 1.3 Hz, 1H), 8.69 (d, J = 9.0 Hz, 1H), 8.05 (d, J = 8.2 Hz, 1 H), 7.99 (d, J = 2.1 Hz, 1H), 7.92-7.86 (m, 1 H), 7.86-7.79 (m, 1H), 7.77 (dd, J = 8.9, 2.1 Hz, 1H), 7.53 (t, J = 8.2 Hz, 1H), 7.30 (t, J = 73.3 Hz, 1H), 7.04 (dd, J = 8.1, 2.1 Hz, 1H). DMSO 466.9, 468.9 (M + 1) Method B (NH4HCO3) 100 Method C, G1 213 469.67 1H-NMR (400 MHz, DMSO-d6): 10.31 (s, 1H), 9.57 (s, 1H), 8.85 (dd, J = 8.1, 1.3 Hz, 1H), 8.60 (d, J = 9.0 Hz, 1H), 8.35-8.23 (m, 1 H), 8.06 (d, J = 8.2 Hz, 1H), 8.00-7.90 (m, 2H), 7.80-7.65 (m, 2H). DMSO 468.9, 470.8 (M + 1) Method B (NH4HCO3) 100 Method C, G1 214 436.77 1H-NMR (400 MHz, DMSO-d6): 10.35 (S, 1H), 9.56 (s, 1 H), 8.84 (d, J = 8.3 Hz, 1H), 8.64 (d, J = 9.0 Hz, 1 H), 8.14-7.99 (m, 2H), 7.95 (d, J = 2.1 Hz, 1H), 7.81- 7.65 (m, 2H), 7.59-7.48 (m, 1H). DMSO 436.9, 438.9 (M + 1) Method B (NH4HCO3) 100 Method C, G1 215 440.37 1H-NMR (400 MHz, DMSO-d6): 13.81 (brs, 1H), 11.97 (s, 1H), 9.57 (s, 1H), 9.01-8.91 (m, 1 H), 8.84 (d, J = 8.3 Hz, 1H), 8.06 (dd, J = 7.9, 1.4 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.79-7.70 (m, 1H), 7.52 (dd, J = 9.1, 2.6 Hz, 1H), 7.49-7.44 (m, 1H), 7.20 (t, J = 7.6 Hz, 1H), 3.94 (s, 3H). DMSO 441.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 216 396.80 1H-NMR (400 MHz, DMSO-d6): 11.89 (s, 1H), 9.80 (s, 1H), 8.34 (dd, J = 9.6, 2.6 Hz, 1H), 8.22 (s, 1H), 8.11 (dd, J = 6.9, 2.6 Hz, 1 H), 7.88 (d, J = 2.7 Hz, 1H), 7.84-7.77 (m, 1 H), 7.74 (d, J = 9.1 Hz, 1H), 7.56-7.43 (m, 2H), 6.44 (d, J = 9.6 Hz, 1H), 3.95 (s, 3H). DMSO 397.1, 399.1 (M + 1) Method B (NH4HCO3) 100 Method D, G1 217 410.37 1H-NMR (400 MHz, DMSO-d6): 11.89 (s, 1H), 9.80 (s, 1H), 8.36 (dd, J = 9.6, 2.6 Hz, 1H), 8.25 (d, J = 2.2 Hz, 1H), 7.92 (d, J = 2.6 Hz, 1H), 7.80-7.67 (m, 3H), 7.53-7.46 (m, 2H), 7.27 (t, J = 74.0 Hz, 1H), 6.98 (dd, J = 8.2, 2.0 Hz, 1H), 6.43 (d, J = 9.6 Hz, 1 H), 3.96 (s, 3H). DMSO 411.1 (M + 1) Method B (NH4HCO3) 100 Method D, G1 218 387.39 1H-NMR (400 MHz, DMSO-d6): 12.98 (s, 1H), 12.58-12.05 (m, 1H), 8.55 (s, 2H), 8.41 (s, 1H), 8.33 (dd, J = 9.7, 2.5 Hz, 1H), 8.11-7.98 (m, 1H), 7.97-7.86 (m, 2H), 7.79-7.64 (m, 3H), 7.44-7.29 (m, 1 H), 6.52 (d, J = 9.7 Hz, 1H), 3.98 (s, 3H). DMSO 388.2 (M + 1) Method B (NH4HCO3) 100 Method D, G1 219 389.38 1H-NMR (400 MHz, DMSO-d6): 12.73 (s, 1H), 9.56 (s, 1H), 9.10 (dd, J = 8.9, 5.4 Hz, 1 H), 8.79-8.63 (m, 2H), 8.50 (s, 1H), 8.08 (s, 1H), 7.95-7.76 (m, 2H), 7.68-7.45 (m, 4H), 3.97 (s, 3H). DMSO 390.1 (M + 1) Method B (NH4HCO3) 98 Method C, G1 220 0 369.80 1H-NMR (400 MHz, DMSO-d6): 14.87 (brs, 1H), 10.08 (brs, 1H), 8.85-7.66 (m, 6H), 7.69-6.63 (m, 3H), 3.96 (s, 3H). DMSO 397.1, 399.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 221 387.39 1H-NMR (400 MHz, DMSO-d6): 14.80 (brs, 1H), 13.19 (s, 1H), 8.68 (d, J = 7.3 Hz, 1 H), 8.44 (s, 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 9.1 Hz, 1H), 8.10-8.03 (m, 1 H), 7.95 (d, J = 7.8 Hz, 1 H), 7.90 (s, 1H), 7.86 (s, 1H), 7.78-7.65 (m, 2H), 7.43 (t, J = 7.5 Hz, 1H), 6.78 (t, J = 6.8 Hz, 1H), 3.99 (s, 3H). DMSO 388.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 222 410.37 1H-NMR (400 MHz, DMSO-d6): 15.33 (brs, 1H), 13.47 (brs, 1H), 11.69 (s, 1H), 8.62 (dd, J = 7.5, 2.1 Hz, 1H), 8.45 (d, J = 2.3 Hz, 1H), 8.17 (d, J = 9.2 Hz, 1H), 8.07 (dd, J = 6.2, 2.1 Hz, 1H), 7.81- 7.68 (m, 3H), 7.61 (t, J = 8.1 Hz, 1H), 7.32 (t, J = 74.0 Hz, 1 H), 7.26-7.18 (m, 1H), 6.80-6.69 (m, 1 H), 4.03 (s, 3H). DMSO 411.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 223 401.22 1H-NMR (400 MHz, DMSO-d6): 11.22 (brs, 1H), 8.47 (d, J = 8.8 Hz, 1H), 8.30 (dd, J = 9.6, 2.3 Hz, 1H), 8.27-8.18 (m, 1H), 8.11 (dd, J = 6.8, 2.4 Hz, 1H), 7.90- 7.73 (m, 2H), 7.60 (dd, J = 8.8, 1.8 Hz, 1H), 7.47 (t, J = 9.1 Hz, 1 H), 6.44 (d, J = 9.6 Hz, 1H). DMSO 401.0, 403.0 (M + 1) Method B (NH4HCO3) 100 Method C, G1 224 414.79 1H-NMR (400 MHz, DMSO-d6): 12.00 (s, 1H), 10.07 (s, 1H), 8.54 (d, J = 8.9 Hz, 1H), 8.34 (dd, J = 9.6, 2.6 Hz, 1H), 8.30 (d, J = 2.3 Hz, 1 H), 7.87-7.69 (m, 3H), 7.62 (dd, J = 8.9, 2.1 Hz, 1H), 7.48 (t, J = 8.2 Hz, 1H), 7.26 (t, J = 74.0 Hz, 1H), 7.00 (dd, J = 8.1, 2.0 Hz, 1H), 6.44 (d, J = 9.6 Hz, 1H). DMSO 415.1, 417.1 (M + 1) Method B (NH4HCO3) 100 Method C, G1 225 432.78 1H-NMR (400 MHz, DMSO-d6): 12.06 (s, 1H), 10.15 (s, 1H), 8.55 (d, J = 9.0 Hz, 1H), 8.34 (dd, J = 9.6, 2.5 Hz, 1H), 8.29 (s, 1H), 7.97 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 2.1 Hz, 1H), 7.65 (dd, J = 8.8, 2.1 Hz, 1H), 7.57 (t, J = 8.2 Hz, 1 H), 7.17 (d, J = 7.8 Hz, 1 H), 6.44 (d, J = 9.6 Hz, 1H). DMSO 433.0, 435.0 (M + 1) Method B (NH4HCO3) 100 Method C, G1 226 428.36 1H-NMR (400 MHz, DMSO-d6): 12.28 (brs, 1H), 8.47-8.06 (m, 3H), 8.06- 7.76 (m, 3H), 7.67-7.59 (m, 2H), 7.28 (s, 1H), 6.47 (d, J = 9.7 Hz, 1H), 3.98 (s, 3H). DMSO 429.1 (M + 1) Method B (NH4HCO3) 94 Method D, G1 227 401.42 1H-NMR (400 MHz, DMSO-d6): 12.97 (s, 1H), 12.27 (s, 1H), 8.73-8.56 (m, 1H), 8.53 (s, 1H), 8.42 (s, 1H), 8.33 (dd, J = 9.7, 2.6 Hz, 1H), 8.04-7.86 (m, 3H), 7.74-7.59 (m, 3H), 7.34 (t, J = 8.7 Hz, 1H), 6.52 (d, J = 9.7 Hz, 1H), 4.23 (q, J = 6.9 Hz, 2H), 1.45 (t, J = 6.9 Hz, 3H). DMSO 402.2 (M + 1) Method B (NH4HCO3) 100 Method D, G1 228 465.91 1H-NMR (400 MHz, DMSO-d6): 8.43- 8.31 (m, 2H), 8.27 (s, 1H), 8.14 (dd, J = 6.7, 2.3 Hz, 1H), 7.89-7.70 (m, 3H), 7.47 (t, J = 9.1 Hz, 1H), 6.44 (d, J = 9.6 Hz, 1 H), 3.62 (d, J = 9.3 Hz, 6H), 2.42 (s, 4H). DMSO 466.1, 468.1 (M + 1) Method B (NH4HCO3) 97 Method D, G1 229 436.41 1H-NMR (400 MHz, DMSO-d6): 10.28 (brs, 1H), 9.47 (s, 1H), 8.91 (d, J = 7.2 Hz, 1H), 8.84 (d, J = 5.2 Hz, 1H), 8.08- 8.06 (m, 2H), 7.91 (d, J = 7.6 Hz, 1H), 7.85 (t, J = 8 Hz, 1H), 7.65-7.60 (m, 2H), 7.54-7.52 (m, 1H), 4.17 (t, J = 7.6 Hz, 2H), 1.86 (q, J = 6.8 Hz, 2H), 1.08- 1.03 (m, 3H). DMSO 423.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 230 0 403.41 1H-NMR (400 MHz, DMSO-d6): 13.42 (s, 1H), 9.53 (s, 1H), 9.10 (d, J = 12.8 Hz, 1H), 8.70-8.65 (m, 2H), 8.50 (s, 1H), 8.07-8.04 (m, 2H), 7.86 (d, J = 8.8 Hz, 1H), 7.60-7.55 (m, 2H), 7.48 (s, 1H), 7.06-7.01 (m, 1H), 4.21 (q, J = 6.8 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H). DMSO 403.9 (M + 1) Method A (TFA) 95 Method C, G1 231 440.42 1H-NMR (400 MHz, DMSO-d6): 10.57 (s, 1H), 9.48 (s, 1H), 9.01 (d, J = 7.6 Hz, 1H), 8.90 (d, J = 5.2 Hz, 1 H), 8.19 (s, 1 H), 8.04 (s, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.93 (t, J = 5.6 Hz, 1H), 7.64-7.60 (m, 2H), 7.22 (d, J = 8.4 Hz, 1 H), 4.19 (t, J = 6.4 Hz, 1H), 1.87-1.81 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H). DMSO 440.9 (M + 1) Method A (TFA) 95 Method C, G1 232 359.12 1H-NMR (400 MHz, DMSO-d6): 13.10 (s, 1H), 9.54 (s, 1 H), 8.96 (d, J = 8.4 Hz, 1H), 8.82-8.80 (m, 2H), 8.52 (s, 1H), 8.22-8.17 (m, 1H), 7.97-7.93 (m, 2H), 7.70-7.59 (m, 4H), 7.21 (t, J = 8.0 Hz, 1H). DMSO 360.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 233 381.26 1H-NMR (400 MHz, DMSO-d6): 9.48 (s, 1H), 9.08 (s, 1 H), 8.67-8.70 (m, 1 H), 8.64 (d, J = 8.0 Hz, 1H), 7.98 (s, 2H), 7.76-7.78 (m, 2H), 7.55-7.57 (m, 1H), 7.43-7.46 (m, 1H), 7.36 (s, 1H), 2.99 (s, 3H). DMSO 381.0, 383.0, 385.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 234 408.4 1H-NMR (400 MHz, DMSO-d6): 10.38 (S, 1H), 9.51 (s, 1H), 9.00 (d, J = 7.2 Hz, 1H), 8.88 (d, J = 4.8 Hz, 1H), 8.13 (s, 1H), 7.96 (d, J = 7.2 Hz, 1H), 7.88- 7.91 (m, 2H), 7.86 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 2.4 Hz, 1H), 7.62 (del, J = 9.2, 2.0 Hz, 1 H), 7.55 (t, J = 8.4 Hz, 1H), 7.31 (t, J = 74.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 4.28 (q, J = 6.8 Hz, 2H), 1.46 (t, J = 6.8 Hz, 3H). DMSO 409.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 235 412.36 1H-NMR (400 MHz, DMSO-d6): 10.81 (s, 1H), 9.49 (s, 1H), 9.02 (d, J = 8.4 Hz, 1H), 8.91 (dd, J = 5.2, 1.2 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H), 8.06 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.94-7.91 (m, 1H), 7.64-7.60 (m, 2H), 7.22 (d, J = 8.4 Hz, 1H), 4.02 (s, 3H). DMSO 412.9 (M + 1) Method A (TFA) 95 Method C, J1 236 395.46 1H-NMR (400 MHz, DMSO-d6): 9.64 (s, 1H), 8.90 (s, 1H), 8.77 (dd, J = 13.5, 6.2 Hz, 2H), 8.19 (d, J = 9.2 Hz, 1H), 7.81 (dd, J = 9.2, 2.4 Hz, 1H), 7.72- 7.56 (m, 3H), 7.33 (d, J = 2.0 Hz, 1H), 4.15 (q, J = 6.8 Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H), 1.38 (t, J = 6.8 Hz, 3H). DMSO 396.2 (M + 1) Method B (NH4HCO3) 98 Method C, G1 237 376.8 1H-NMR (400 MHz, DMSO-d6): 11.64 (brs, 1H), 11.31 (brs, 1H), 9.45 (s, 1H), 8.82-8.69 (m, 1H), 8.61 (s, 1H), 8.15 (d, J = 2.0 Hz, 1H), 8.04-7.91 (m, 1H), 7.81 (dd, J = 8.9, 2.1 Hz, 1H), 7.70- 7.55 (m, 1H), 7.47 (s, 1H), 7.06 (s, 1H), 6.98 (d, J = 8.2 Hz, 1H). DMSO 376.9, 378.9 (M + 1) Method B (NH4HCO3) 95 Method C, G8 238 412.23 1H-NMR (400 MHz, DMSO-d6): 10.70 (s, 1H), 9.62 (d, J = 2.4 Hz, 1H), 9.51 (d, J = 1.6 Hz, 1H), 8.76-8.79 (m, 2H), 8.57 (dd, J = 6.8. 2.0 Hz, 1H), 8.29 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.94 (dd, J = 6.8, 2.0 Hz, 1H), 7.71 (m, 2H). DMSO 412.0, 414.0, 416.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 239 381.26 1H-NMR (400 MHz, DMSO-d6): 10.04 (s, 1H), 9.59 (d, J = 1.2 Hz, 1H), 8.74-8.70 (m, 2H), 8.42-8.39 (m, 2H), 7.98 (dd, J = 2.4 Hz, 1H), 7.79 (d, J = 7.2 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.59-7.55 (m, 2H), 2.75 (s, 3H). DMSO 381, 383 (M + 1) Method B (NH4HCO3) 95 Method C, G1 240 0 348.35 1H-NMR (400 MHz, DMSO-d6): 10.00 (s, 1H), 9.57 (d, J = 1.2 Hz, 1H), 8.72-8.70 (m, 2H), 8.38 (d J = 8.4 Hz, 1H), 8.17- 8.12 (m, 1 H), 7.79-7.74 (m, 2H), 7.59- 7.50 (m, 3H), 2.74 (s, 3H). DMSO 349.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 241 355.39 1H-NMR (400 MHz, DMSO-d6): 11.10 (s, 1H), 9.60 (d, J = 1.6 Hz, 1H), 9.16 (d, J = 8.4 Hz, 1 H), 8.82-8.72 (m, 2H), 8.50 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.97- 7.92 (m, 2H), 7.77-7.72 (m, 2H), 7.63- 7.60 (m, 2H), 7.24-7.19 (m, 1H), 2.76 (s, 3H). DMSO 356.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 242 337.4 1H-NMR (400 MHz, DMSO-d6): 10.12 (s, 1 H), 9.57 (s, 1 H), 8.73-8.70 (m, 2H), 8.46 (s, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.72-7.56 (m, 4H), 2.76 (s, 3H). DMSO 338.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 243 396.37 1H-NMR (400 MHz, DMSO-d6): 10.07 (s, 1H), 9.59 (s, 1H), 8.75-8.69 (m, 2H), 8.44 (d, J = 8.0 Hz, IH), 8.20 (s, IH), 7.97-7.94 (m, 1 H), 7.89 (d, J = 7.2 Hz, 1H), 7.62-7.54 (m, 3H), 7.16 (d, J = 8.4 Hz, 1H), 2.76 (s, 3H). DMSO 397.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 244 378.37 1H-NMR (400 MHz, DMSO-d6): 9.98 (s, 1H), 9.60 (s, 1H), 8.75-8.69 (m, 2H), 8.44 (d, J = 8.0 Hz, 1H), 7.98 (s, 1H), 7.84 (d, J = 7.6 Hz, 1 H), 7.79 (d, J = 6.8 Hz, 1H), 7.58-7.00 (m, 4H), 6.98 (d, J = 2.0 Hz, 1H), 2.76 (s, 3H). DMSO 379.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 245 360.34 1 H-NMR (400 MHz, DMSO-d6): 11.95- 11.11 (m, 2H), 9.43 (d, J = 1.6 Hz, 1 H), 8.71 (dd, J = 4.7. 1.5 Hz, 1H), 8.56 (td, J = 8.0, 1.9 Hz, 1H), 8.15 (dd, J = 9.2. 5.3 Hz, 1H), 8.08 (dd, J = 9.4, 2.7 Hz, 1H), 8.02-7.88 (m, 2H), 7.54 (dd, J = 7.90, 4.81 Hz, 1H), 7.50-7.40 (m, 1H), 7.04 (t, J = 7.1 Hz, 1H), 6.96 (d, J = 8.1 Hz, 1H). DMSO 360.8 (M + 1) Method B (NH4HCO3) 95 Method C, G8 246 393.8 1 H-NMR (400 MHz, DMSO-d6): 13.29 (s, 1H), 9.54 (s, 1H), 9.29 (s, 1 H), 8.06 (d, J = 0.9 Hz, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.82 (dd, J = 26.4, 8.4 Hz, 2H), 7.58 (dd, J = 7.9, 4.8 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1 H), 8.72 (d, J = 3.6 Hz, 1 H), 8.67 (d, J = 7.8 Hz, 1 H), 8.64-8.53 (m, 1H). DMSO 394.0, 396.0 (M + 1) Method B (NH4HCO3) 95 Method C, J1 247 1H-NMR (400 MHz, DMSO-d6): 13.36 (brs, 1H), 9.54 (s, 1H), 9.36-9.08 (m, 1H), 8.12 (d, J = 8.8 Hz, 2H), 8.08-7.96 (m, 1H), 7.94-7.78 (m, 2H), 7.57 (dd, J = 7.8, 4.8 Hz, 1H), 7.29-7.16 (m, 1H), 8.94-8.49 (m, 3H). DMSO 444.1 (M + 1) Method B (NH4HCO3) 95 Method C, J1 248 376.8 1H-NMR (400 MHz, DMSO-d6): 9.57 (S, 1H), 8.71 (d, J = 5.6 Hz, 2H), 8.40 (d, J = 1.8 Hz, 1H), 8.01-7.97 (m, 2H), 7.89 (dd, J = 7.8, 1.5 Hz, 1H), 7.63- 7.51 (m, 1H), 7.29 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.76-6.74 (m, 1H). DMSO 377.0, 379.0 (M + 1) Method B (NH4HCO3) 95 Method C, G8 249 426.35 1H-NMR (400 MHz, DMSO-d6): 9.70 (d, J = 1.5 Hz, 1H), 8.74 (td, J = 8.0. 1.9 Hz, 1H), 8.71 (dd, J = 4.7, 1.7 Hz, 1H), 8.50 (d, J = 9.0 Hz, 1H), 7.88 (dd, J = 7.8, 1.9 Hz, 1H), 7.76 (d, J = 1.1 Hz, 1H), 7.20-7.11 (m, 1H), 7.64-7.56 (m, 2H)., 6.70-6.60 (m, 1H), 6.52 (dd, J = 10.8, 3.9 Hz, 1H). DMSO 427.1 (M + 1) Method B (NH4HCO3) 95 Method C, G8 250 0 360.34 1H-NMR (400 MHz, DMSO-d6): 9.69 (s, 1H), 8.83 (d, J = 7.4 Hz, 1H), 8.71 (d, J = 3.9 Hz, 1 H), 8.49 (t, J = 7.2 Hz, 1 H), 7.85 (d, J = 7.8 Hz, 1 H), 7.63-7.51 (m, 3H), 7.14 (t, J = 7.0 Hz, 1H), 6.61 (d, J = 8.0 Hz, 1 H), 6.46 (t, J = 7.2 Hz, 1H). DMSO 360.8 (M + 1) Method B (NH4HCO3) 95 Method C, G8 251 400.43 1H-NMR (400 MHz, DMSO-d6): 12.92 (s, 1H), 9.04 (d, J = 8.3 Hz, 1H), 8.66 (del, J = 7.7, 1.7 Hz, 1H), 8.48 (s, 1H), 8.10 (dd, J = 4.6, 1.7 Hz, 1H), 8.01- 7.94 (m, 2H), 7.89 (d, J = 8.9 Hz, 1H), 7.72 (t, J = 7.7 Hz, 1H), 7.55 (m, 2H), 7.20 (t, J = 7.5 Hz, 1H), 6.74 (dd, J = 7.7, 4.7 Hz, 1H), 4.24 (q, J = 6.9 Hz, 2H), 1.46 (t, J = 6.9 Hz, 3H). DMSO 401.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 252 483.44 1H-NMR (400 MHz, DMSO-d6): 13.28 (s, 1H), 9.54 (s, 1H), 9.28 (s, 1 H), 8.70- 8.66 (m, 2H), 8.59 (s, 1H), 8.11 (d, J = 8.8 Hz, 2H), 7.90 (d, J = 8.9 Hz, 1H), 7.64-7.49 (m, 3H), 7.18 (d, J = 8.2 Hz, 1H), 4.14 (t, J = 6.2 Hz, 2H), 1.86 (q, J = 6.8 Hz, 2H), 1.07 (t, J = 7.2 Hz, 3H). DMSO 484.0 (M + 1) Method B (NH4HCO3) 95 Method C, J1 253 1H-NMR (400 MHz, DMSO-d6): 13.24 (s, 1H), 9.56 (s, 1H), 9.39 (d, J = 2.1 Hz, 1H), 8.77-8.73 (m, 2H), 8.55 (s, 1H), 8.09 (s, 1H), 8.00 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.65 (dd, J = 7.9, 4.9 Hz, 1H), 7.59 (dd, J = 9.1, 2.5 Hz, 1H), 4.24 (q, J = 6.9 Hz, 2H), 1.46 (t, J = 6.9 Hz, 3H). DMSO 420.0, 422.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 254 469.42 1H-NMR (400 MHz, DMSO-d6): 13.34 (s, 1H), 9.60 (s, 1H), 9.35 (s, 1 H), 8.77 (d, J = 3.5 Hz, 1H), 8.72 (d, J = 7.9 Hz, 1H), 8.67 (s, 1H), 8.22 (s, 1 H), 8.17 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.69-7.58 (m, 2H), 7.55 (s, 1H), 7.24 (d, J = 8.5 Hz, 1 H), 4.29 (q, J = 7.0 Hz, 2H), 1.53 (t, J = 6.9 Hz, 3H). DMSO 470.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1 255 403.41 1H-NMR (400 MHz, DMSO-d6): 11.43 (s, 1H), 9.53 (s, 1H), 8.68-8.66 (m, 2H), 8.56 (d, J = 8.3 Hz, 1H), 8.23 (s, 1H), 8.12 (s, 1H), 7.88 (d, J = 9.1 Hz, 1H), 7.72-7.64 (m, 1H), 7.61-7.47 (m, 3H), 7.17-7.08 (m, 1H), 4.23 (q, J = 6.9 Hz, 2H), 1.46 (t, J = 6.9 Hz, 3H). DMSO 404.2 (M + 1) Method B (NH4HCO3) 95 Method C, G1

(189) TABLE-US-00002 Retention Molecular Time Purity Method of Number Product Salt Type Mass .sup.1H NMR .sup.1H NMR Solvent LCMS (min) LCMS Protocol percent Coupling 256 HCl 456.723 .sup.1H NMR (300 MHz, DMSO) 9.55 (s, 1H), 9.09 (d, J = 8.0 Hz, 1H), 9.01-8.76 (m, 2H), 8.50 (s, 1H), 8.37 (s, 1H), 8.13-7.91 7.91 (m, 4H), 7.85 (d, J = 8.9 Hz, 1H), 7.69 (t, J = 7.7 Hz, 1H), 7.25 (1, J = 7.6 Hz, 1H). DMSO 420 (M + 1) 1.89 Method D 100 Method G1 257 HCl 524.39 .sup.1H NMR (300 MHz, DMSO) 10.68 (s, 1H), 9.50 (s, 1H), 9.08 (d, J = 8.1 Hz, 1H), 8.92 (d, J = 5.2 Hz, 1H), 8.28 (s, 1H), 8.11 (s, 1H), 8.06-7.93 (m, 2H), 7.87 (d, J = 7.6 Hz, 1H), 7.70-7.51 (m, 2H), 7.19 (d, J = 7.6 Hz, 1H), 4.28 (t, J = 9.1 Hz, 2H), 4 DMSO 452 (M + 1) 1.34 Method D 100 Method G1 258 HCl 474.89 .sup.1H NMR (300 MHz, DMSO) 10.36 (s, 1H), 9.52 (s, 1H), 9.00 (d, J = 8.2 Hz, 1H), 8.89 (d, J = 4.4 Hz, 1H), 8.12 (s, 1H), 8.02- 7.78 (m, 4H), 7.64 (d, J = 9.2 Hz, 1H), 7.54 (t, J = 8.2 Hz, 1H), 7.07 (d, J = 7.7 Hz, 1H), 4.08-3.87 (m, 5H), 3.46 (s, 3H). DMSO 439 (M + 1) 2.21 Method C 98 Method G1 259 HCl 460.86 .sup.1H NMR (300 MHz, DMSO) 10.61 (s, 1H), 9.51 (s, 1H), 9.10 (d, J = 8.2 Hz, 1H), 8.94 (d, J = 4.9 Hz, 1H), 8.22 (s, 1H), 8.08- 7.94 (m, 2H), 7.93-7.78 (m, 2H), 7.65 (d, J = 9.1 Hz, 1H), 7.53 (t, J = 8.2 Hz, 1H), 7.08 (d, J = 7.3 Hz, 1H), 4.01 (s, 3H), 3 DMSO 425 (M + 1) 1.64 Method C 98 Method G1 260 00 HCl 429.67 No Data 428.9 (M + 1) 2.35 Method C 100 Method G1 261 01 HCl 443.24 .sup.1H NMR (300 MHz, DMSO) 10.35 (s, 1H), 9.52 (d, J = 1.5 Hz, 1H), 8.97 (dd, J = 6.6, 1.8 Hz, 2H), 8.91-8.83 (m, 1H), 8.07 (dd, J = 8.9, 2.0 Hz, 1H), 7.85 (dd, J = 14.6, 8.2 Hz, 4H), 7.54 (dd, J = 11.7, 4.6 Hz, 1H), 7.31 (s, 1H), 7.10-6.99 (m, 1H). DMSO 442.96 (M + 1) 2.36 Method C 100 Method G1 262 02 HCl 426.39 .sup.1H NMR (300 MHz, DMSO) 10.71 (s, 1H), 9.47 (s, 1H), 9.01 (d, J = 8.2 Hz, 1H), 8.90 (d, J = 4.0 Hz, 1H), 8.23 (s, 1H), 8.08- 7.86 (m, 4H), 7.61 (t, J = 8.2 Hz, 2H), 7.22 (d, J = 7.6 Hz, 1H), 4.28 (d, J = 7.0 Hz, 2H), 1.44 (t, J = 6.9 Hz, 3H). DMSO 427.1 (M + 1) 2.47 Method C 93 Method G1 263 03 HCl 446.13 1H NMR (300 MHz, DMSO) 10.35 (s, 1H), 9.47 (s, 1H), 8.90 (s, 3H), 8.27 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 9.0 Hz, 2H), 7.68 (d, J = 8.8 Hz, 1H). DMSO 494.0 (M + 1) 2.29 Method C 91 Method G1 264 04 395.46 1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 8.88 (s, 1H), 8.83- 8.71 (m, 2H), 8.18 (d, J = 9.2 Hz, 1H), 7.80 (dd, J = 9.2, 2.3 Hz, 1H), 7.69-7.57 (m, 3H), 7.32 (d, J = 2.1 Hz, 1H), 4.14 (q, J = 6.6 Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H), 1.37 (t, J = 6.9 Hz, 3 DMSO 396.10 (M + 1) 2.3 Method C 100 Method G12 265 05 HCl 469.53 1H NMR (300 MHz, DMSO) 12.13 (s, 1H), 9.54 (s, 1H), 8.99 (d, J = 7.4 Hz, 1H), 8.85 (s, 2H), 8.61 (d, J = 8.2 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.86 (d, J = 7.3 Hz, 2H), 7.68 (dd, J = 15.1, 7.8 Hz, 3H), 7.32 (d, J = 6.8 Hz, 1H), 4.00 (s, 3H), 3.71 (d, J DMSO 470.1 (M + 1) 2.15 Method C 100 Method G1 266 06 HCl 455.51 1H NMR (300 MHz, DMSO) 12.07 (s, 1H), 9.52 (s, 1H), 8.82- 8.65 (m, 4H), 7.88 (dd, J = 8.1, 5.0 Hz, 2H), 7.73-7.55 (m, 4H), 7.27 (t, J = 7.2 Hz, 1H), 3.98 (m, 1H), 3.82 (d, J = 10.4 Hz, 2H), 3.35 (t, J = 11.7 Hz, 2H), 1.68 (d, J = 10.3 Hz, 2H), 1.55- DMSO 456.1 (M + 1) 2.09 Method C 100 Method G1 267 07 HCl 408.36 1H NMR (300 MHz, DMSO) 10.57 (s, 1H), 9.45 (d, J = 1.5 Hz, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 3.9 Hz, 1H), 8.16 (d, J = 2.3 Hz, 1H), 8.05 (d, J = 2.0 Hz, 1H), 7.94 (t, J = 7.4 Hz, 2H), 7.63 (ddd, J = 9.3, 6.9, 2.3 Hz, 2H), 7.52 (d, J = 8.7 Hz, DMSO 409.1 (M + 1) 2.3 Method C 100 Method G1 268 08 HCl 367.4 1H NMR (300 MHz, DMSO) 11.12 (s, 1H), 9.81 (s, 1H), 9.43- 9.37 (m, 1H), 8.58 (ddd, J = 8.0, 4.8, 1.4 Hz, 2H), 8.09 (d, J = 2.5 Hz, 1H), 7.89 (d, J = 2.2 Hz, 1H), 7.80 (s, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.53-7.41 (m, 3H), 7.17 (1, J = 7.5 Hz, 1H), 7.0 DMSO 368.1 (M + 1) 1.98 Method C 100 Method G1 269 09 386.4 .sup.1H NMR (300 MHz, DMSO) 11.47 (s, 2H), 9.39 (s, 1H), 8.66 (d, J = 2.8 Hz, 1H), 8.56-8.47 (m, 1H), 8.01-7.90 (m, 2H), 7.69- 7.55 (m, 2H), 7.55-7.40 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 4.23 (q, J = 6.9 Hz, 2H), 1.44 (t, J = DMSO 387.0 (M + 1) 2.05 Method C 100 Method G8 270 0 407.45 .sup.1H NMR (300 MHz, DMSO) 10.52 (s, 1H), 9.44 (s, 1H), 8.92 (d, J = 7.4 Hz, 1H), 8.86 (d, J = 5.1 Hz, 1H), 8.46 (d, J = 6.4 Hz, 1H), 8.01 (d, J = 8.7 Hz, 2H), 7.92- 7.74 (m, 6H), 7.68 (dd, J = 9.2, 2.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 3.98 (s, 4H). DMSO 408.0 (M + 1) 1.92 Method C 100 Method G1, with two drops of conc. HCl 271 HCl 385.42 .sup.1H NMR (300 MHz, DMSO) 9.75 (s, 1H), 9.66 (s, 1H), 9.39 (s, 1H), 8.61 (d, J = 3.1 Hz, 1H), 8.54 (d, J = 8.2 Hz, 1H), 7.85 (s, 1H), 7.82 (s, 2H), 7.71 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.46 (dd, J = 7.5, 5.2 Hz, 1H), 7.35-7.23 (m, 2H), 3.9 DMSO 386.1 (M + 1) 1.79 Method C 96 Method G2 272 HCl 413.47 .sup.1HNMR (300 MHz, DMSO) 12.30 (s, 1H), 9.57 (d, J = 2.1 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.77- 8.67 (m, 2H), 8.63 (d, J = 7.7 Hz, 1H), 7.94-7.83 (m, 2H), 7.71 (t, J = 7.1 Hz, 1H), 7.66-7.52 (m, 3H), 7.25 (t, J = 7.4 Hz, 1H), 4.24- 4.06 (m, 1H), 3 DMSO 414.2 (M + 1) 2.36 Method C 100 Method G1 273 HCl 387.46 .sup.1H NMR (300 MHz, DMSO) 10.96 (s, 1H), 10.29 (s, 1H), 9.85 (s, 1H), 9.51 (d, J = 2.0 Hz, 1H), 8.71-8.62 (m, 2H), 8.47 (dd, J = 8.2, 0.9 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.67-7.62 (m, 2H), 7.60 (d, J = 2.5 Hz, 1H), 7.57 (d, J = 2.6 Hz, 1H), 7.55-7 DMSO 388.1 (M + 1) 2.01 Method C 95 Method G1 274 HCl 399.45 .sup.1H NMR (300 MHz, DMSO) 12.45 (s, 1H), 9.57 (d, J = 1.3 Hz, 1H), 8.96 (dd, J = 8.4, 0.9 Hz, 1H), 8.89 (t, J = 5.2 Hz, 1H), 8.75- 8.66 (m, 2H), 7.94-7.84 (m, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.65- 7.52 (m, 3H), 7.24 (1, J = 7.6 Hz, 1H), 4.00 (s, 3H), 3. DMSO 400.3 (M + 1) 2.21 Method C 100 Method G1 275 HCl 453.42 .sup.1H NMR (300 MHz, DMSO) 11.70 (s, 1H), 9.54 (d, J = 2.0 Hz, 1H), 9.40 (t, J = 6.1 Hz, 1H), 8.79 (d, J = 7.7 Hz, 1H), 8.73-8.63 (m, 2H), 7.89 (d, J = 9.8 Hz, 2H), 7.76 (t, J = 7.1 Hz, 1H), 7.64- 7.50 (m, 3H), 7.30 (t, J = 7.1 Hz, 1H), 4.16-4.01 (m, 2 DMSO 454.0 (M + 1) 2.28 Method C 100 Method G1 276 421.25 .sup.1H NMR (300 MHz, DMSO) 9.26 (d, J = 2.2 Hz, 1H), 8.71-8.62 (m, 2H), 8.46 (dt, J = 8.0, 1.9 Hz, 1H), 8.21 (dd, J = 8.9, 2.3 Hz, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.89 (s, 1H), 7.78 (dd, J = 7.6, 1.6 Hz, 1H), 7.72-7.62 (m, 1H), 7.56- 7.45 (m, 3H), 7.32 DMSO 423.0 (M + 1) 1.85 Method C 94 Method G1 277 HCl 447.49 .sup.1H NMR (300 MHz, DMSO) 11.25 (s, 1H), 10.46 (s, 1H), 9.45 (s, 1H), 8.93 (d, J = 7.9 Hz, 1H), 8.82 (d, J = 3.9 Hz, 1H), 8.22 (d, J = 8.1 Hz, 1H), 7.97-7.79 (m, 4H), 7.73 (t, J = 7.1 Hz, 1H), 7.62 (dd, J = 9.1, 2.5 Hz, 1H), 7.53- 7.39 (m, 3H), 7.19 (t, DMSO 448.1 (M + 1) 2.67 Method C 100 Method G1 278 HCl 399.45 .sup.1H NMR (300 MHz, DMSO) 12.59 (s, 1H), 9.57 (d, J = 1.4 Hz, 1H), 9.03 (dd, J = 8.4, 0.9 Hz, 1H), 8.91 (d, J = 4.6 Hz, 1H), 8.76- 8.64 (m, 2H), 7.88 (t, J = 7.8 Hz, 2H), 7.72 (t, J = 7.9 Hz, 1H), 7.63- 7.53 (m, 3H), 7.22 (td, J = 7.9, 1.1 Hz, 1H), 4.28 DMSO 400.1 (M + 1) 2.5 Method C 100 Method G1 279 HCl 399.45 .sup.1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.37 (d, J = 1.4 Hz, 1H), 8.61 (dd, J = 4.7, 1.7 Hz, 1H), 8.58-8.51 (m, 1H), 7.84 (dd, J = 9.0, 5.3 Hz, 3H), 7.65-7.42 (m, 4H), 7.38 (t, J = 7.5 Hz, 1H), 3.95 (s, 3H), 2.74 (s, 6H). DMSO 400.1 (M + 1) 2.2 Method C 100 Method G1 280 0 HCl 439.51 .sup.1H NMR (300 MHz, DMSO) 12.05 (s, 1H), 9.51 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 8.1 Hz, 1H), 8.88 (dd, J = 5.2, 1.3 Hz, 1H), 8.60 (d, J = 7.0 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.00-7.87 (m, 2H), 7.83 (dd, J = 7.8, 1.4 Hz, 1H), 7.77 (d, J = 1.9 Hz, 1H), DMSO 440.1 (M + 1) 2.52 Method C 100 Method G1 281 HCl 403.41 .sup.1H NMR (300 MHz, DMSO) 10.98 (s, 1H), 9.50 (s, 1H), 8.72- 8.55 (m, 3H), 8.38 (d, J = 8.2 Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.72- 7.45 (m, 4H), 7.19-7.07 (m, 1H), 3.96 (s, J = 5.2 Hz, 3H), 2.73 (d, J = 4.5 Hz, 3H). DMSO 404.1 (M + 1) 2.18 Method C 100 Method G1 282 HCl 417.44 .sup.1H NMR (300 MHz, DMSO) 10.96 (s, 1H), 9.50 (d, J = 1.9 Hz, 1H), 8.71-8.55 (m, 3H), 8.38 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.66 (dd, J = 14.8, 8.3 Hz, 1H), 7.60-7.47 (m, 3H), 7.21- 7.05 (m, 1H), 4.24 (q, J = 6.9 Hz, 2H), 2.73 (d, J = 4. DMSO 419.1 (M + 1) 2.38 Method C 100 Method G1 283 HCl 439.39 .sup.1H NMR (300 MHz, DMSO) 13.10 (s, 1H), 9.68 (d, J = 1.1 Hz, 1H), 9.52 (d, J = 1.4 Hz, 1H), 8.75- 8.58 (m, 3H), 8.26 (s, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.59-7.47 (m, 3H), 7.45 (d, J = 2.5 Hz, 1H), 3.95 (s, 3H). DMSO 440.1 (M + 1) 2.25 Method C 100 Method G1 284 HCl 453.42 .sup.1H NMR (300 MHz, DMSO) 13.08 (s, 1H), 9.70 (s, 1H), 9.55 (d, J = 1.3 Hz, 1H), 8.77-8.60 (m, 3H), 8.26 (s, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 9.1 Hz, 1H), 7.62-7.39 (m, 4H), 4.21 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 6.9 Hz, 3H). DMSO 454.1 (M + 1) 2.43 Method C 95 Method G1 285 HCl 410.43 .sup.1H NMR (300 MHz, DMSO) 12.87 (s, 1H), 9.50 (d, J = 1.5 Hz, 2H), 8.73-8.59 (m, 3H), 8.26 (s, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.64 (dd, J = 8.1, 1.5 Hz, 1H), 7.59-7.49 (m, 2H), 7.42 (d, J = 2.4 Hz, 1H), 4.19 (q, J = 6.9 Hz, 2H DMSO 411.1 (M + 1) 2.16 Method C 95 Method G1 286 HCl 397.43 .sup.1H NMR (300 MHz, DMSO) 13.63 (s, 1H), 9.55 (s, 1H), 9.13 (d, J = 8.3 Hz, 1H), 8.75-8.58 (m, 3H), 7.84 (d, J = 9.8 Hz, 1H), 7.69- 7.48 (m, 4H), 7.01 (d, J = 7.4 Hz, 1H), 3.94 (s, 3H), 3.46-3.36 (m, 2H), 2.96 (t, J = 5.7 Hz, 2H). DMSO 398.3 (M + 1) 2.12 Method C 100 Method G1 287 HCl 411.46 .sup.1H NMR (300 MHz, DMSO) 13.61 (s, 1H), 9.56 (s, 1H), 9.14 (d, J = 8.1 Hz, 1H), 8.75-8.60 (m, 3H), 7.84 (d, J = 9.8 Hz, 1H), 7.70- 7.46 (m, 4H), 7.02 (d, J = 7.2 Hz, 1H), 4.19 (q, J = 6.9 Hz, 3H), 3.48- 3.37 (m, 2H), 2.96 (t, J = 6.1 Hz, 2H), 1.44 (t, DMSO 412.4 (M + 1) 2.4 Method C 100 Method G1 288 HCl 383.4 .sup.1H NMR (300 MHz, DMSO) 11.62 (s, 1H), 9.60 (d, J = 1.5 Hz, 1H), 9.02 (s, 1H), 8.88 (d, J = 8.0 Hz, 1H), 8.80-8.65 (m, 2H), 7.90 (d, J = 9.0 Hz, 1H), 7.75 (t, J = 7.9 Hz, 1H), 7.66-7.51 (m, 3H), 7.27 (d, J = 7.6 Hz, 1H), 4.47 (s, 2H), 3.97 (s, 3H). DMSO 384.1 (M + 1) 2.01 Method C 95 Method G1 289 HCl 421.4 .sup.1H NMR (300 MHz, DMSO) 12.07 (s, 1H), 9.48 (d, J = 1.6 Hz, 1H), 8.76-8.55 (m, 3H), 8.34 (s, 1H), 8.14 (8, 1H), 7.87 (d, J = 9.1 Hz, 1H), 7.62-7.49 (m, 2H), 7.38 (d, J = 2.5 Hz, 1H), 7.14 (ddd, J = 11.5, 9.0, 2.6 Hz, 1H), 4.19 (q, J = 6.9 Hz, 2H), 1. DMSO 422.2 (M + 1) 2.35 Method C 100 Method G1 290 0 HCl 412.44 .sup.1H NMR (300 MHz, DMSO) 9.82 (s, 1H), 9.50 (d, J = 2.0 Hz, 1H), 8.68-8.58 (m, 2H), 7.98 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 1.8 Hz, 1H), 7.80 (d, J = 9.1 Hz, 1H), 7.55- 7.43 (m, 3H), 7.23 (d, J = 8.4 Hz, 1H), 3.96 (s, 3H), 3.37 (d, J = 4.2 Hz, 6H). DMSO 413.0 (M + 1) 1.79 Method C Method G1 291 HCl 426.47 .sup.1H NMR (300 MHz, DMSO) 9.78 (s, 1H), 9.50 (d, J = 2.0 Hz, 1H), 8.68-8.57 (m, 2H), 7.97 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 1.8 Hz, 1H), 7.79 (d, J = 9.1 Hz, 1H), 7.55- 7.43 (m, 3H), 7.22 (d, J = 8.4 Hz, 1H), 4.22 (q, J = 6.9 Hz, 2H), 3.37 (d, J = 4.3 H DMSO 427.1 (M + 1) 1.92 Method C Method G1 292 404.39 .sup.1H NMR (300 MHz, DMSO) 9.36 (d, J = 1.4 Hz, 1H), 8.66 (d, J = 2.7 Hz, 1H), 8.52 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 8.9 Hz, 2H), 7.64 (d, J = 13.5 Hz, 2H), 7.50 (dd, J = 7.7, 4.2 Hz, 1H), 6.86 (t, J = 6.8 Hz, 1H), 6.70 (dd, J = 11.8, 1.7 Hz, 1H), 4.22 (q, DMSO 405.1 (M + 1) 1.98 Method C 95 Method G8 293 406.82 .sup.1H NMR (300 MHz, DMSO) 9.23 (d, J = 1.4 Hz, 1H), 8.63 (d, J = 3.6 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.92 (s, 1H), 7.81-7.65 (m, 4H), 7.55 (dd, J = 8.4, 2.1 Hz, 1H), 7.48 (dd, J = 6.7, 3.8 Hz, 1H), 7.37 (s, 1H), 3.97 (s, 3H). DMSO 407.1 (M + 1) 1.88 Method C 100 Method G8 294 HCl 406.46 .sup.1H NMR (300 MHz, DMSO) 10.11 (s, 1H), 9.39 (d, J = 1.4 Hz, 1H), 8.63 (dd, J = 4.7, 1.7 Hz, 1H), 8.59-8.53 (m, 1H), 8.50 (dd, J = 8.2, 0.8 Hz, 1H), 8.03 (dd, J = 8.0, 1.4 Hz, 1H), 7.96-7.84 (m, 2H), 7.65-7.46 (m, 4H), 3.94 (s, 3H), 3.25 (s, 3H). DMSO 407.1 (M + 1) 2.13 Method C 95 Method G1

(190) TABLE-US-00003 Pu- .sup.1H rity Method Num- Starting Starting Salt NMR per- of ber Material 1 Material 2 Product Type .sup.1H NMR Solvent cent Coupling 295 .sup.1H NMR (400 MHz, DMSO) 13.12 (s, 1H), 9.90 (s, 1H), 9.47 (d, J = 1.4 Hz, 1H), 8.70-8.54 (m, 2H), 8.20- 8.15 (m, 1H), 8.14 (s, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.88-7.75 (m, 2H), 7.65 (d, J = 8.9 Hz, 1H), 7.59-7.44 (m, 2H), 3.98 (s, 3H). DMSO >98 G1 296 0 .sup.1H NMR (400 MHz, DMSO) 10.04 (s, 1H), 9.54-9.47 (m, 1 H), 9.36 (s, 1H), 8.72 (d, J = 2.0 Hz, 1H), 8.69- 8.59 (m, 2H), 8.19 (d, J = 8.8 Hz, 1H), 8.08-7.97 (m, 2H), 7.86 (d, J = 9.1 Hz, 1H), 7.61-7.47 (m, 2H), 3.99 (s, 3H). DMSO >98 G1 297 .sup.1H NMR (400 MHz, DMSO) 9.64 (s, 1H), 9.55-9.45 (m, 1H), 8.72-8.60 (m, 2H), 7.95 (d, J = 2.7 Hz, 1 H), 7.82 (d, J = 9.1 Hz, 1H), 7.58-7.48 (m, 3H), 7.34 (dd, J = 8.7, 2.5 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1 H), 4.39-4.23 (m, 4H), 3.97 (s, 3H). DMSO >98 G1 298 .sup.1H NMR (400 MHz, DMSO) 11.21 (s, 1H), 9.79 (s, 1H), 9.53 (d, J = 1.4 Hz, 1H), 8.75-8.58 (m, 2H), 8.07 (s, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.56-7.47 (m, 2H), 7.43 (dd, J = 8.5, 1.8 Hz, 1H), 7.39-7.34 (m, 1H), 6.50-6.41 (m, 1H), 3.99 (s, 3H). DMSO >98 G1 299 .sup.1H NMR (400 MHz, DMSO) 9.54 (s, 1H), 9.42-9.34 (m, 1H), 8.61 (dd, J = 4.7, 1.7 Hz, 1H), 8.57-8.47 (m, 1H), 7.93 (d, J = 2.7 Hz, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.56-7.44 (m, 2H), 7.19 (dd, J = 7.9, 1.5 Hz, 1 H), 7.00-6.91 (m, 1H), 6.86 (dd, J = 8.2, 1.6 Hz, 1H), 4.34-4.17 (m, 4H), 3.95 (s, 3H). DMSO >98 G1 300 0 .sup.1H NMR (400 MHz, DMSO) 10.76 (s, 1H), 10.01 (s, 1H), 9.17-9.06 (m, 1H), 8.53 (dd, J = 4.7, 1.7 Hz, 1H), 8.36-8.27 (m, 1H), 8.05 (d, J = 2.7 Hz, 1H), 7.84 (d, J = 9.1 Hz, 1H), 7.60- 7.48 (m, 2H), 7.36 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.32-7.28 (m, 1H), 7.25 (d, J = 6.8 Hz, 1 H), 7.16-7.04 (m, 1H), 6.54 (dd, J = 3.0, 1.9 Hz, 1H), 3.98 (s, 3H). DMSO >98 G1 301 .sup.1H NMR (400 MHz, DMSO) 10.02 (s, 1H), 9.48 (d, J = 1.5 Hz, 1H), 9.33 (d, J = 1.0 Hz, 1H), 8.69-8.59 (m, 2H), 8.37 (d, J = 1.7 Hz, 1H), 8.10 (dd, J = 9.0, 2.1 Hz, 1H), 8.00 (d, J = 2.7 Hz, 1H), 7.90 (d J = 9.0 Hz, 1H), 7.86 (d, J = 9.1 Hz, 1H), 7.57 (dd, J = 9.1, 2.7 Hz, 1H), 7.54-7.47 (m, 1H), 3.99 (s, 3H). DMSO >98 G1 302 .sup.1H NMR (400 MHz, DMSO) 10.52 (s, 1H), 9.18 (dd, J = 2.2, 0.8 Hz, 1H), 8.60 (dd, J = 4.7, 1.7 Hz, 1H), 8.45- 8.36 (m, 1H), 8.03 (d, J = 2.7 Hz, 1H), 7.97-7.90 (m, 2H), 7.88 (d, J = 7.0 Hz, 1H), 7.77 (dd, J = 9.0, 7.1 Hz, 1H), 7.61 (dd, J = 9.1, 2.7 Hz, 1H), 7.44 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 4.01 (s, 3H). DMSO >98 G1 303 0 .sup.1H NMR (400 MHz, DMSO) 9.86 (s, 1H), 9.60-9.56 (m, 1H), 8.72-8.67 (m, 1H), 8.65 (dd, J = 4.8, 1.7 Hz, 1H), 8.26-8.21 (m, 1H), 8.05 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1 H), 7.56-7.50 (m, 2H), 7.46 (dd, J = 8.5, 1.8 Hz, 1H), 7.35 (d, J = 3.1 Hz, 1H), 6.46 (dd, J = 3.1, 0.8 Hz, 1H), 3.99 (s, 3H), 3.86 (s, 3H). DMSO >98 G1 304 .sup.1H NMR (400 MHz, DMSO) 9.96 (s, 1H), 9.51-9.45 (m, 1H), 8.68-8.59 (m, 2H), 8.57-8.52 (m, 1H), 8.02- 7.88 (m, 3H), 7.87-7.80 (m, 1H), 7.58-7.46 (m, 2H), 3.98 (s, 3H), 2.83 (s, 3H). DMSO >98 G1 305 .sup.1H NMR (400 MHz, DMSO) 9.94 (s, 1H), 9.51-9.43 (m, 1H), 8.68-8.58 (m, 2H), 8.39 (d, J = 2.0 Hz, 1 H), 7.99 (d, J = 2.7 Hz, 1H), 7.87-7.80 (m, 2H), 7.78 (d, J = 8.6 Hz, 1H), 7.54 (dd, J = 9.1, 2.7 Hz, 1 H), 7.51 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 4.19 (s, 3H), 3.98 (s, 3H). DMSO >98 G1 306 0 .sup.1H NMR (400 MHz, DMSO) 9.72 (s, 1H), 9.52-9.47 (m, 1H), 8.67-8.60 (m, 2H), 7.98 (d, J = 2.7 Hz, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.78-7.74 (m, 1H), 7.68-7.62 (m, 1H), 7.55-7.48 (m, 2H), 7.32 (d, J = 8.1 Hz, 1H), 3.97 (s, 3H), 2.99-2.88 (m, 4H), 2.15- 2.04 (m, 2H). DMSO >98 G1 307 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.74 (s, 1H), 9.37-9.31 (m, 1H), 8.60 (dd, J = 4.7, 1.7 Hz, 1H), 8.53-8.46 (m, 1H), 7.95 (d, J = 2.7 Hz, 1 H), 7.82 (d, J = 9.1 Hz, 1H), 7.52 (dd, J = 9.1, 2.7 Hz, 1H), 7.47 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.34 (d, J = 7.0 Hz, 1H), 7.31- 7.24 (m, 1H), 7.22 (d, J = 7.1 Hz, 1H), 3.96 (s, 3H), 2.99 (t, J = 7.3 Hz, 2H), 2.82 (t, J = 7.4 Hz, 2H), 2.06-1.96 (m, 2H). DMSO >98 G1 308 HCl .sup.1H NMR (400 MHz, DMSO) 10.45 (s, 1H), 9.50-9.44 (m, 1H), 8.94- 8.87 (m, 1H), 8.83 (dd, J = 5.1, 1.5 Hz, 1H), 8.54 (d, J = 2.0 Hz, 1H), 8.13 (d, J = 2.4 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.97-7.89 (m, 2H), 7.83 (dd, J = 8.0, 5.2 Hz, 1H), 7.63 (dd, J = 9.1, 2.7 Hz, 1H), 4.01 (s, 3H), 2.83 (s, 3H). DMSO >98 G1 309 HCl .sup.1H NMR (400 MHz, DMSO) 10.64 (S, 1H), 9.47 (d, J = 1.5 Hz, 1H), 8.94 (d, J = 8.1 Hz, 1H), 8.86 (dd, J = 5.2, 1.5 Hz, 1H), 8.54-8.48 (m, 1H), 8.23- 8.16 (m, 1H), 8.04-7.94 (m, 2H), 7.92-7.83 (m, 2H), 7.78 (d, J = 5.4 Hz, 1H), 7.65 (dd, J = 9.1, 2.6 Hz, 1H), 7.51 (dd, J = 5.4, 0.7 Hz, 1H), 4.02 (s, 3H). DMSO >98 G1 310 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.86 (s, 1H), 9.43 (d, J = 1.6 Hz, 1H), 8.94 (d, J = 7.5 Hz, 1H), 8.89 (dd, J = 5.2, 1.5 Hz, 1H), 8.30-8.20 (m, 1H), 8.13- 7.99 (m, 3H), 7.94-7.84 (m, 1H), 7.74 (d, J = 1.3 Hz, 2H), 7.67 (66, J = 9.1, 2.5 Hz, 1H), 7.08 (d, J = 2.2 Hz, 1H), 4.02 (s, 3H). DMSO >98 G1 311 HCl .sup.1 H NMR (400 MHz, DMSO) 10.53 (S, 1H), 9.48 (d, J = 1.5 Hz, 1H), 8.93 (d, J = 7.7 Hz, 1H), 8.85 (dd, J = 5.2, 1.5 Hz, 1H), 8.44 (d, J = 1.9 Hz, 1H), 8.20-8.15(m, 1H), 8.13 (d, J = 8.7 Hz, 1H), 7.97 (d, J = 9.1 Hz, 1H), 7.92 (dd, J = 8.7, 2.0 Hz, 1H), 7.86 (dd, J = 7.8, 5.1 Hz, 1H), 7.64 (dd, J = 9.1, 2.6 Hz, 1H), 4.02 (s, 3H), 2.85 (s, 3H). DMSO >98 G1 312 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.85 (S, 1H), 9.54 (d, J = 1.5 Hz, 1H), 9.47 (s, 1H), 9.32 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 8.93-8.87 (m, 1H), 8.86- 8.78 (m, 2H), 8.44 (dd, J = 8.8, 1.9 Hz, 1H), 8.14 (d, J = 2.1 Hz, 1H), 8.10 (d, J = 8.7 Hz, 1H), 7.99-7.89 (m, 2H), 7.78-7.71 (m, 1H), 7.55 (d, J = 8.7 Hz, 1H). DMSO >98 G1 313 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 11.07 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.51 (d, J = 2.0 Hz, 1H), 9.46-9.39 (m, 1H), 9.10-9.01 (m, 1H), 8.97-8.88 (m, 2H), 8.86 (dd, J = 5.3, 1.3 Hz, 1H), 8.63-8.55 (m, 1H), 8.48 (dd, J = 8.8, 1.9 Hz, 1H), 8.15 (d, J = 8.7 Hz, 1H), 8.04-7.90 (m, 4H), 7.79 (d, J = 5.4 Hz, 1H), 7.52 (dd, J = 5.4, 0.7 Hz, 1H). DMSO >98 G1 314 HCl .sup.1H NMR (400 MHz, DMSO) 10.49 (s, 1H), 9.48 (d, J = 1.5 Hz, 1H), 8.93 (d, J = 7.9 Hz, 1H), 8.85 (dd, J = 5.2, 1.5 Hz, 1H), 8.24 (s, 1H), 8.16 (d, J = 2.5 Hz, 1H), 8.05 (d, J = 2.2 Hz, 1H), 7.96 (d, J = 9.1 Hz, 1H), 7.87 (dd, J = 8.1, 5.3 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.72(dd, J = 8.4, 1.8 Hz, 1H), 7.64 (dd, J = 9.1, 2.6 Hz, 1H), 7.03 (dd, J = 2.2, 1.0 Hz, 1H), 4.02 (s, 3H). DMSO >98 G1 315 HCl .sup.1H NMR (400 MHz, DMSO) 10.72 (s, 1H), 9.46 (d, J = 1.5 Hz, 1H), 8.96 (d, J = 8.2 Hz, 1H), 8.87 (dd, J = 5.2, 1.5 Hz, 1H), 8.50 (d, J = 1.8 Hz, 1 H), 8.21 (d, J = 2.4 Hz, 1H), 8.06-7.96 (m, 2H), 7.93-7.84 (m, 2H), 7.78 (d, J = 5.4 Hz, 1H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.51 (dd, J = 5.4, 0.7 Hz, 1H), 4.29 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H). DMSO >98 G1 316 00 .sup.1H NMR (400 MHz, DMSO) 10.04 (s, 1H), 9.60-9.52 (m, 1H), 8.75- 8.63 (m, 2H), 8.16 (d, J = 2.0 Hz, 1H): 8.04-7.95 (m, 2H), 7.93-7.83 (m, 2H), 7.63-7.53 (m, 2H), 6.32 (d, J = 1.2 Hz, 1H), 4.01 (s, 3H), 2.47 (s, 3H). DMSO >98 G1 (0.1N HCl added) 317 01 02 03 .sup.1H NMR (400 MHz, DMSO) 11.82 (s, 1H), 10.06 (s, 1H), 9.53-9.46 (m, 1H), 8.81-8.70 (m, 2H), 8.04 (d, J = 2.6 Hz, 1H), 7.88 (d, J = 9.1 Hz, 1 H), 7.81 (d, J = 2.1 Hz, 1H), 7.67 (dd, J = 7.9, 5.0 Hz, 1H), 7.57 (dd, J = 9.1, 2.7 Hz, 1H), 7.53 (dd, 8.7, 2.1 Hz, 1H), 7.39 (d, J = 8.6 Hz, 1H), 4.00 (s, 3H). DMSO >98 G1 (0.1N HCl added) 318 04 05 06 .sup.1H NMR (400 MHz, DMSO) 9.89 (s, 1H), 9.57-9.48 (m, 1H), 8.72-8.58 (m, 2H), 8.01 (d, J = 2.1 Hz, 1H), 7.99 (d, J = 2.7 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.59-7.49 (m, 3H), 7.43 (d, J = 8.6 Hz, 1 H), 3.98 (s, 3H), 3.41 (s, 3H). DMSO >98 G1 (0.1N HCl added) 319 07 08 09 .sup.1H NMR (400 MHz, DMSO) 9.88 (s, 1H), 9.52-9.44 (m, 1H), 8.71-8.59 (m, 2H), 8.02-7.91 (m, 2H), 7.83 (d, J = 9.1 Hz, 1H), 7.66 (dd, J = 8.4, 2.0 Hz, 1H), 7.58-7.48 (m, 2H), 7.36 (d, J = 8.4 Hz, 1 H), 3.98 (s, 3H), 3.40 (s, 3H). DMSO >98 G1 (0.1N HCl added) 320 0 .sup.1H NMR (400 MHz, DMSO) 10.01 (s, 1H), 9.58-9.51 (m, 1H), 9.45 (s, 1H), 8.75 (d, J = 1.9 Hz, 1H), 8.71- 8.63 (m, 2H), 8.25 (d, J = 8.7 Hz, 1H), 8.08-8.00 (m, 2H), 7.86 (d, J = 9.1 Hz, 1H), 7.61-7.50 (m, 2H), 4.00 (s, 3H). DMSO >98 G1 (0.1N HCl added) 321 .sup.1H NMR (400 MHz, DMSO) 10.43 (s, 1H), 9.72 (s, 1H), 9.51-9.45 (m, 1H), 8.67-8.57 (m, 2H), 7.96 (d, J = 2.7 Hz, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.73-7.68 (m, 1H), 7.64 (dd, J = 8.3, 2.1 Hz, 1H), 7.56-7.48 (m, 2H), 6.93 (d, J = 8.3 Hz, 1H), 3.97 (s, 3H), 3.58 (s, 2H). DMSO >98 G1 (0.1N HCl added) 322 .sup.1H NMR (400 MHz, DMSO) 9.95 (s, 1H), 9.54-9.45 (m, 1H), 8.67 (dd, J = 4.7, 1.7 Hz, 1H), 8.66-8.60 (m, 1H), 8.15 (d, J = 2.4 Hz, 1 H), 7.94 (d, J = 2.6 Hz, 1H), 7.89-7.83 (m, 2H), 7.63- 7.52 (m, 3H), 3.98 (s, 3H). DMSO >98 G1 (0.1N HCl added) 323 0 .sup.1H NMR (400 MHz, DMSO) 10.99 (s, 1H), 9.75 (s, 1H), 9.55-9.49 (m, 1H), 8.69-8.62 (m, 2H), 7.96 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.58-7.49 (m, 3H), 7.35 (dd, J = 8.7, 2.5 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 4.62 (s, 2H), 3.97 (s, 3H). DMSO >98 G1 (0.1N HCl added) 324 HCl .sup.1H NMR (400 MHz, DMSO) 10.24 (s, 1H), 9.58-9.51 (m, 1H), 8.92- 8.84 (m, 1H), 8.80 (dd, J = 5.0, 1.5 Hz, 1H), 8.16 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.6 Hz, 1H), 7.98 (dd, J = 8.8, 2.1 Hz, 1H), 7.91 (d, J = 9.1 Hz, 1H), 7.83-7.72 (m, 2H), 7.61 (dd, J = 9.1, 2.6 Hz, 1H), 6.37 (s, 1H), 4.75 (d, J = 1.2 Hz, 2H), 4.01 (s, 3H), 3.47 (s, 3H). DMSO >98 G1 (0.1N HCl added) 325 HCl .sup.1H NMR (400 MHz, DMSO) 12.01 (s, 1H), 10.15 (s, 1H), 9.58 (d, J = 1.5 Hz, 1H), 8.94-8.86 (m, 1H), 8.78 (dd, J = 5.0, 1.5 Hz, 1H), 8.07 (d, J = 2.6 Hz, 1H), 8.04-7.98 (m, 1H), 7.91 (dd, J = 9.3, 2.2 Hz, 2H), 7.78-7.69 (m, 2H), 7.66 (dd, J = 8.5, 2.0 Hz, 1H), 7.61 (dd, J = 9.1, 2.7Hz, 1H), 6.44 (d, J = 9.5 Hz, 1H), 4.01 (s, 3H). DMSO >98 G1 (0.1N HCl added) 326 0 HCl .sup.1H NMR (400 MHz, DMSO) 12.19 (s, 1H), 10.21 (s, 1H), 9.58-9.51 (m, 1H), 8.94-8.86 (m, 1H), 8.81 (dd, J = 5.1, 1.6 Hz, 1H), 8.10 (d, J = 2.6 Hz, 1H), 7.96-7.88 (m, 2H), 7.79 (dd, J = 7.9, 5.1 HZ, 1H), 7.68-7.56 (m, 3H), 4.00 (s, 3H). DMSO >98 G1 (0.1N HCl added) 327 HCl .sup.1H NMR (400 MHz, DMSO) 10.43 (s, 1H), 9.57-9.50 (m, 1H), 9.07- 8.98 (m, 1H), 8.88 (dd, J = 5.2, 1.4 Hz, 1H), 8.16 (d, J = 2.5 Hz, 1H), 8.06 (d, J = 1.9 Hz, 1 H), 8.00-7.89 (m, 2H), 7.75 (d, J = 8.5 Hz, 1H), 7.67 (dd, J = 8.5, 2.0 Hz, 1H), 7.63 (66, J = 9.1, 2.6 Hz, 1H), 4.02 (s, 3H), 3.47 (s, 3H). DMSO >98 G1 (0.1N HCl added) 328 HCl .sup.1H NMR (400 MHz, DMSO) 10.68 (s, 1H), 10.24 (s, 1H), 9.45 (d, J = 1.6 Hz, 1H), 9.05-8.95 (m, 1H), 8.92 (dd, J = 5.2, 1.5 Hz, 1H), 8.25-8.16 (m, 1H), 8.09-7.99 (m, 1H), 7.98- 7.89 (m, 1H), 7.71-7.60 (m, 3H), 6.98 (d, J = 8.3 Hz, 1H), 4.00 (s, 3H), 2.99 (t, J = 7.5 Hz, 2H), 2.57-2.52 (m, 2H). DMSO >98 G1 (0.1N HCl added) 329 2 HCl .sup.1H NMR (400 MHz, DMSO) 12.05 (s, 1H), 10.98 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 9.32 (s, 1 H), 9.03 (d, J = 8.2 Hz, 1H), 8.98 (d, J = 1.7 Hz, 1H), 8.92 (dd, J = 5.3, 1.4 Hz, 1H), 8.53 (d, J = 2.6 Hz, 1H), 8.46 (dd, J = 8.8, 1.8 Hz, 1H), 8.30 (s, 1 H), 8.13 (d, J = 2.1 Hz, 1H), 8.09 (d, J = 8.7 Hz, 1H), 7.95 (dd, J = 7.7, 5.3 Hz, 1H), 7.82 (dd, J = 8.6, 2.1 Hz, 1H), 7.26 (d, J = 8.6 Hz, DMSO >98 G1 (0.1N HCl added) 1H), 4.06 (s, 3H). 330 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.40 (s, 1H), 9.54 (d, J = 1.5 Hz, 1H), 9.05- 8.97 (m, 1H), 8.87 (dd, J = 5.2, 1.5 Hz, 1H), 8.15-8.06 (m, 3H), 8.00- 7.87 (m, 3H), 7.81 (d, J = 8.5 Hz, 1H), 7.64 (dd, J = 9.1, 2.7 Hz, 1H), 6.43 (d, J = 9.4 Hz, IH), 4.02 (S, 3H). DMSO >98 G1 (0.1N HCl added) 331 2 HCl .sup.1H NMR (400 MHz, DMSO) 12.05 (s, 1H), 10.77 (s, 1H), 9.51 (d, J = 1.5 Hz, 1H), 9.43-9.35 (m, 1H), 9.31- 9.21 (m, 1H), 9.04-8.93 (m, 1H), 8.88 (dd, J = 5.2, 1.5 Hz, 1H), 8.81 (dd, J = 5.1, 1.4 Hz, 1H), 8.73 (d, J = 8.4 Hz, 1H), 8.42 (dd, J = 8.8, 1.8 Hz, 1H), 8.13 (d, J = 2.1 Hz, 1H), 8.09 (d, J = 8.7 Hz, 1H), 7.94-7.83 (m, 2H), 7.80 (dd, J = 8.6, 2.2 Hz, 1H), 7.27 (d, J = 8.6 Hz, 1H). DMSO >98 G1 (0.1N HCl added) 332 HCl .sup.1H NMR (400 MHz, DMSO) 10.57 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 9.09- 9.01 (m, 1H), 8.90 (dd, J = 5.3, 1.5 Hz, 1H), 8.65-8.59 (m, 1H), 8.24- 8.16 (m, 2H), 8.14 (dd, J = 9.6, 0.8 Hz, 1H), 8.03-7.92 (m, 2H), 7.65 (dd, J = 9.1, 2.7 Hz, 1H), 4.03 (s, 3H). DMSO >98 G1 (0.1N HCl added) 333 0 HCl .sup.1H NMR (400 MHz, DMSO) 11.81 (s, 1H), 10.31 (s, 1H), 9.58 (d, J = 1.5 Hz, 1H), 9.08 (d, J = 7.9 Hz, 1H), 8.87 (dd, J = 5.2, 1.5 Hz, 1H), 8.13 (d, J = 2.6 Hz, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.98-7.88 (m, 2H), 7.81 (d, J = 8.8 Hz, 1H), 7.69 (dd, J = 8.8, 2.1 Hz, 1H), 7.63 (dd, J = 9.1, 2.7 Hz, 1H), 6.36 (s, 1H), 4.02 (s, 3H), 2.46 (d; J = 1.1 Hz, 3H). DMSO >98 G1 (0.1N HCl added) 334 HCl .sup.1H NMR (400 MHz, DMSO) 10.51 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 9.08- 9.02 (m, 1H), 8.90 (dd, J = 5.3, 1.5 Hz, 1H), 8.63-8.59 (m, 1H), 8.22- 8.10 (m, 3H), 8.00-7.92 (m, 2H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 4.30 (q. J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H). DMSO >98 G1 (0.1N HCl added) 335 HCl .sup.1H NMR (400 MHz, DMSO) 11.99 (s, 1H), 10.34 (s, 1H), 9.62-9.52 (m, 1H), 9.11 (d, J = 8.2 Hz, 1H), 8.90 (d, J = 4.4 Hz, 1H), 8.13 (d, J = 2.6 Hz, 1H), 8.06 (d, J = 1.8 Hz, 1H), 8.00- 7.88 (m, 3H), 7.75 (d, J = 8.6 Hz, 1H), 7.68-7.60 (m, 2H), 6.46 (d, J = 9.5 Hz, 1H), 4.29 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H). DMSO >98 G1 (0.1N HCl added) 336 0 HCl .sup.1H NMR (400 MHz, DMSO) 11.02 (s, 1H), 10.49 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 9.02 (d, J = 8.1 Hz, 1H), 8.90 (dd, J = 5.2, 1.5 Hz, 1H), 8.15 (d, J = 2.3 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1 H), 7.93 (dd, J = 7.8, 5.4 Hz, 1H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.54 (d, J = 2.4 Hz, 1H), 7.35 (dd, J = 8.7, 2.5 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 4.64 (s, 2H), 4.28 (q. J = 6.9 Hz, 2H), 1.45 (t, J = 7.0 Hz, 3H). DMSO >98 G1 (0.1N HCl added) 337 HCl .sup.1H NMR (400 MHz, DMSO) 10.36 (s, 1H), 10.25 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.98 (d, J = 8.1 Hz, 1H), 8.86 (dd, J = 5.2, 1.5 Hz, 1H), 8.10 (d, J = 2.4 Hz, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.87 (dd, J = 7.7, 5.2 Hz, 1H), 7.61 (dd, J = 9.1, 2.6 Hz, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.36 (dd, J = 8.1, 2.1 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 4.27 (q, J = 7.0 Hz, 2H), 2.93 (t, J = 7.5 Hz, 2H), 2.56-2.52 (m, 2H), 1.45 (t, J = DMSO >98 G1 (0.1N HCl added) 7.0 Hz, 3H). 338 .sup.1H NMR (400 MHz, DMSO) 10.25 (s, 1H), 9.50-9.39 (m, 1H), 9.03 (dd, J = 2.1, 0.7 Hz, 1H), 8.52 (dd, J = 4.7, 1.7 Hz, 1H), 8.48 (d, J = 6.0 Hz, 1H), 8.31-8.24 (m, 1H), 8.16 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 2.7 Hz, 1H), 8.04 (d, J = 7.3 Hz, 1H), 7.91-7.78 (m, 3H), 7.58 (dd, J = 9.1, 2.7 Hz, 1H), 7.35 (ddd, J = 8.0, 4.8, 0.7 Hz, 1H), 4.01 (s, 3H). DMSO >98 J2 339 .sup.1H NMR (400 MHz, DMSO) 10.23 (s, 1H), 9.37 (dd, J = 2.1, 0.7 Hz, 1H), 8.62 (dd, J = 4.7, 1.7 Hz, 1H), 8.57- 8.49 (m, 1H), 7.93 (d, J = 2.7 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.58 (dd, J = 9.1, 2.7 Hz, 1H), 7.47 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.40-7.30 (m, 3H), 3.98 (s, 3H). DMSO >98 J2 340 0 .sup.1H NMR (400 MHz, DMSO) 11.31 (s, 1H), 9.56 (s, 1H), 9.54 (dd, J = 2.1, 0.7 Hz, 1H), 8.80-8.66 (m, 2H), 8.14 (d, J = 9.2 Hz, 1H), 7.77 (dd, J = 9.2, 2.8 Hz, 1H), 7.58 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.03-6.94 (m, 1H), 6.68 (dd, J = 7.8, 0.8 Hz, 1H), 6.56 (dd, J = 8.2, 0.8 Hz, 1H), 3.86 (s, 3H). DMSO >98 J2 341 .sup.1H NMR (400 MHz, DMSO) 10.00 (s, 1H), 9.54-9.49 (m, 1H), 8.75 (s, 1H), 8.69-8.62 (m, 2H), 8.50 (d, J = 1.7 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1 H), 7.91-7.85 (m, 2H), 7.83 (dd, J = 8.6, 1.9 Hz, 1H), 7.60-7.51 (m, 2H), 4.00 (s, 3H). DMSO >98 J2 342 .sup.1H NMR (400 MHz, DMSO) 10.08 (s, 1H), 9.34-9.27 (m, 1H), 8.60 (dd J = 4.7, 1.7 Hz, 1H), 8.51-8.44 (m, 1H), 7.94 (d, J = 2.7 Hz, 1H), 7.88 (d, J = 9.1 Hz, 1H), 7.58 (dd, J = 9.1, 2.7 Hz, 1H), 7.56-7.51 (m, 1H), 7.51- 7.47 (m, 2H), 7.45 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 3.98 (s, 3H). DMSO >98 J2 343 0 .sup.1H NMR (400 MHz, DMSO) 10.99 (s, 1H), 9.93 (s, 1H), 9.26 (d, J = 1.4 Hz, 1H), 8.59 (dd, J = 4.8, 1.7 Hz, 1 H); 8.50-8.43 (m, 1H), 8.01 (d, J = 2.7 Hz, 1H), 7.98 (d, J = 9.5 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 9.1, 2.7 Hz, 1H), 7.49-7.42 (m, 1H), 7.36 (d, J = 8.3 Hz, 1H), 6.55 (dd, J = 9.5, 1.7 Hz, 1H), 3.98 (s, 3H), 2.33 (s, 3H). DMSO >98 J2 344 HCl .sup.1H NMR (400 MHz, DMSO) 9.34- 9.28 (m, 1H), 8.81-8.75 (m, 1H), 8.74-8.65 (m, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 2.7 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.80-7.72 (m, 2H); 7.69 (d, J = 2.8 Hz, 1H), 7.59 (dd, J = 8.8, 2.7 Hz, 1H), 4.00 (s, 3H). DMSO >98 G8 using DMF instead of THF 345 HCl .sup.1H NM R (400 MHz, DMSO) 9.35- 9.29 (m, 1H), 8.87-8.78 (m, 2H), 8.19 (d, J = 9.4 Hz, 1 H), 8.09 (d, J = 9.2 Hz, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.86 (dd, J = 8.0, 5.3 Hz, 1H), 7.77 (dd, J = 9.1, 2.9 Hz, 1H), 7.72 (d, J = 2.8 Hz, 1H), 7.67 (d, J = 2.3 Hz, 1H), 7.54 (dd, J = 8.5, 2.3 Hz, 1H), 6.56 (d, J = 9.6 Hz, 1H), 4.02 (s, 3H). DMSO >98 G12 at room temper- ature 346 0 HCl .sup.1H NMR (400 MHz, DMSO) 11.98 (s, 1H), 9.29 (d, J = 1.7 Hz, 1H), 8.88- 8.78 (m, 2H), 8.08 (d, J = 9.2 Hz, 1H), 7.97 (d, J = 9.6 Hz, 1H), 7.88 (dd, J = 8.1, 5.4 Hz, 1H), 7.81 (d, J = 2.6 Hz, 1H), 7.78-7.72 (m, 2H), 7.67 (dd, J = 8.9, 2.6 Hz, 1H), 7.48 (d, J = 8.9 Hz, 1H), 6.60 (d, J = 9.5 Hz, 1 H), 4.02 (s, 3H). DMSO >98 G12 at room temper- ature 347 HCl .sup.1H NMR (400 MHz, DMSO) 9.33- 9.28 (m, 1H), 8.87-8.67 (m, 2H), 8.06 (d, J = 9.1 Hz, 1 H), 7.91-7.79 (m, 1H), 7.75 (dd, J = 9.1, 2.9 Hz, 1H), 7.71 (d, J = 2.8 Hz, 1H), 7.67- 7.61 (m, 2H), 7.58-7.51 (m, 2H), 4.01 (s, 3H). DMSO >98 G12 at room temper- ature 348 HCl .sup.1H NMR (400 MHz, DMSO) 9.28 (d, J = 2.0 Hz, 1H), 8.85-8.67 (m, 2H), 8.06 (d, J = 9.0 Hz, 1 H), 7.88-7.77 (m, 1H), 7.77-7.69 (m, 2H), 7.62- 7.54 (m, 2H), 7.51-7.45 (m, 2H), 7.44-7.37 (m, 1H), 4.02 (d, J = 3.9 Hz, 3H). DMSO >98 G12 at room temper- ature 349 HCl .sup.1H NMR (400 MHz, DMSO) 9.23 (dd, J = 2.1, 0.7 Hz, 1 H); 8.80 (dd, J = 5.2, 1.6 Hz, 1H), 8.72-8.64 (m, 1H), 8.09 (d, J = 9.1 Hz, 1H), 7.84-7.71 (m, 4H), 7.66 (dd, J = 8.1, 1.6 Hz, 1H), 7.61-7.54 (m, 1H), 7.52-7.45 (m, 1H), 4.02 (s, 3H). DMSO >98 G12 at room temper- ature 350 00 01 02 HCl .sup.1H NMR (400 MHz, DMSO) 9.22 (d, J = 1.7 Hz, 1H), 8.87-8.79 (m, 1H), 8.77-8.67 (m, 1H), 8.06 (d, J = 92 Hz, 1H), 7.92-7.79 (m, 1H), 7.74 (dd, J = 9.1, 2.9 Hz, 1 H), 7.70 (d, J = 2.8 Hz, 1H), 7.45-7.37 (m, 2H), 7.33- 7.27 (m, 1H), 7.17-7.09 (m, 1H), 4.01 (s, 3H), 3.71 (s, 3H). DMSO >98 G12 at room temper- ature 351 03 04 05 2 HCl .sup.1H NMR (400 MHz, DMSO) 12.03 (s, 1H), 10.69 (S, 1H), 9.65 (d, J = 1.8 Hz, 1H), 9.26-9.21 (m, 1H), 9.20- 9.12 (m, 1H), 8.99-8.88 (m, 2H), 8.52 (d, J = 2.6 Hz, 1 H), 8.49-8.42 (m, 1H), 8.25-8.17 (m, 1H), 8.15- 8.08 (m, 2H), 8.02-7.96 (m, 1H), 7.93 (d, J = 9.4 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 1H), 7.72 (dd, J = 8.5, 1.9 Hz, 1H), 6.47 (d, J = 9.6 Hz, 1H), 4.04 (s, DMSO >98 G1 3H). 352 06 07 08 2 HCl .sup.1H NMR (400 MHz, DMSO) 12.04 (s, 1H), 10.92 (s, 1H), 9.65 (d, J = 1.7 Hz, 1H), 9.58-9.50 (m, 1H), 9.46- 9.39 (m, 1H), 9.27-9.18 (m, 1H), 9.01-8.92 (m, 2H), 8.88 (dd, J = 5.3, 1.2 Hz, 1H), 8.48 (dd, J = 8.8, 1.9 Hz, 1H), 8.20-8.10 (m, 2H), 8.09-8.01 (m, 2H), 7.93 (d, J = 9.5 Hz, 1 H), 7.81-7.72 (m, 2H), 6.47 (d, J = 9.5 Hz, 1H). DMSO >98 G1 353 09 0 HCl 1H NMR (300 MHz, DMSO) 10.90 (s, 1 H), 9.63 (s, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.76 (d, J = 4.0 Hz, 1H), 8.19 (d, J = 2.1 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1 H), 7.78-7.65 (m, 2H), 7.63-7.49 (m, 2H), 7.47-7.33 (m, 2H), 3.98 (s, 3H). DMSO >98 G1 354 HCl 1H NMR (300 MHz, DMSO) 11.44 (s, 1 H), 9.58 (d, J = 1.8 Hz, 1 H), 9.16 (d, J = 8.2 Hz, 1H), 8.96 (dd, J = 5.3, 1.3 Hz, 1H), 8.29 (d, J = 2.5 Hz, 1H), 8.13 (d, J = 9.2 Hz, 1 H), 7.99 (dd, J = 8.0, 5.4 Hz, 1H), 7.72-7.49 (m, 2H), 7.44-7.27 (m, 3H), 7.12 (s, 1H), 3.99 (s, 3H), 2.52 (s, 3H). DMSO >98 G1 355 HCl 1H NMR (300 MHz, DMSO) 11.38 (s, 1 H), 9.53 (s, 1H), 9.18 (d, J = 8.1 Hz, 1H), 8.97 (d, J = 5.3 Hz, 1 H), 8.21 (s, 1H), 8.14-8.02 (m, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.60 (d, J = 9.1 Hz, 1H), 6.90 (s, 1H), 3.99 (s, 3H). DMSO >98 G1 356 0 HCl 1H NMR (300 MHz, DMSO) 11.30 (s, 1H); 9.59 (d, J = 1.8 Hz, 1H), 9.19 (d, J = 8.2 Hz, 1H), 8.97 (dd, J = 5.3, 1.2 Hz, 1H), 8.24 (d, J = 2.5 Hz, 1H), 8.11-7.93 (m, 2H), 7.76-7.54 (m, 4H), 7.40 (t, J = 7.6 Hz, 1 H), 7.26 (s, 1H), 7.21 (d, J = 7.4 Hz, 1H), 3.98 (s, 3H), 2.41 (s, 3H). DMSO >98 G1 357 HCl 1H NMR (300 MHz, DMSO) 11.21 (s, 1 H), 9.59 (d, J = 1.7 Hz, 1 H), 9.22 (d, J = 8.1 Hz, 1H), 9.02-8.95 (m, 1H), 8.23 (d, J = 2.5 Hz, 1H), 8.13- 7.96 (m, 3H), 7.85 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.60 (dd, J = 9.1, 2.6 Hz, 1H), 7.31 (s, 1 H), 3.98 (s, 3H). DMSO >98 G1 358 HCl 1H NMR (300 MHz, DMSO) 10.87 (s, 1H), 9.65-9.55 (m, 1 H), 8.93 (dt J = 8.0, 1.8 Hz, 1H), 8.81 (dd, J = 5.0. 1.6 Hz, 1H), 8.18 (d, J = 2.6 Hz, 1H), 7.94-7.82 (m, 4H), 7.78 (dd, J = 8.0, 5.0 Hz, 1 H), 7.60-7.46 (m, 4H), 7.44- 7.35 (m, 1H), 7.32 (s, 1 H), 3.98 (s, 3H). DMSO >98 G1 359 HCl H NMR (300 MHz, DMSO) 11.29 (s, 1H), 9.59 (s, 1H), 9.20 (d, J = 8.1 Hz, 1H), 9.01-8.94 (m, 1H), 8.25 (s, 1H), 8.12-7.98 (m, 2H), 7.90-7.75 (m, 2H), 7.62(d, J = 9.1 Hz, 1H), 7.21 (s, 1H), 7.08 (d, J = 8.6 Hz, 2H), 3.99 (s, 3H), 3.84 (s, 3H). DMSO >98 G1 360 0 HCl 1H NMR (300 MHz, DMSO) 11.29 (s, 1H), 9.60 (s, 1H), 9.21 (d, J = 8.0 Hz, 1H), 8.99 (d, J = 5.3 Hz, 1H), 8.26 (d, J = 2.2 Hz, 1H), 8.11-7.99 (m, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.62 (dd, J = 9.1, 2.4 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.26 (s, 1H), 3.99 (s, 3H), 2.37 (s, 3H). DMSO >98 G1 361 HCl 1H NMR (300 MHz, DMSO) 11.00 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 8.96 (dt, J = 8.1, 1.7 Hz, 1H), 8.86 (dd, J = 5.1, 1.5 Hz, 1H), 8.19 (d, J = 2.6 Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.83 (dt, J = 9.5, 4.8 Hz, 1H), 7.55 (dd, J = 9.1, 2.6 Hz, 1H), 6.72 (s, 1H), 3.95 (d, J = 7.0 Hz, 3H), 2.35 (d, J = 3.5 Hz, 3H). DMSO >98 G1 362 HCl H NMR (300 MHz, DMSO) 11.21 (s 1H), 9.58 (d, J = 1.5 Hz, 1H), 9.21- 9.06 (m, 1H), 8.95 (d, J = 4.3 Hz, 1H) 8.22 (d, J = 2.3 Hz, 1H), 8.09-7.92 (m, 2H), 7.70-7.51 (m, 3H), 7.24- 7.17 (m, 1H), 7.13 (s, 1H), 3.99 (s, 3H). DMSO >98 G1 363 0 HCl 1H NMR (300 MHz, DMSO) 11.07 (s, 1H), 9.60 (s, 1H), 9.13 (d, J = 6.5 Hz, 1H), 8.93 (d, J = 5.1 Hz, 1H), 8.23 (s, 1H), 8.05-7.85 (m, 4H), 7.67- 7.54 (m, 1H), 7.43-7.23 (m, 3H), 3.99 (s, 3H). DMSO >98 G1 364 2 HCl 1H NMR (300 MHz, DMSO) 11.16 (s, 1H), 9.57 (d, J = 1.5 Hz, 1H), 9.14 (d, J = 8.1 Hz, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.18(d, J = 2.4 Hz, 1H), 8.03- 7.89 (m, 4H), 7.61-7.54 (m, 2H), 7.32 (s, 1H), 3.97 (s; 3H). DMSO >98 G1 365 2 HCl 1H NMR (300 MHz, DMSO) 11.29 (s, 1H), 9.58 (d, J = 1.6 Hz, 1H), 9.27 (d, J = 8.2 Hz, 1H), 9.06-8.99 (m, 1H), 8.18 (d, J = 2.5 Hz, 1H), 8.10 (dd, J = 8.1, 5.5 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.91 (dd, J = 10.7, 1.8 Hz, 1H), 7.80-7.65 (m, 2H), 7.57 (dd, J = 9.1, 2.G Hz, 1H), 7.29 (s, 1H), 3.96 (s, 3H). DMSO >98 G1 366 0 2 HCl 1H NMR (300 MHz, DMSO) 11.17 (s, 1H), 9.60 (s, 1H), 9.24 (d, J = 8.2 Hz, 1H), 8.98 (d, J = 5.1 Hz, 1H), 8.22 (d, J = 2.5 Hz, 1H), 8.11-8.04 (m, 1H), 8.02-7.91 (m, 2H), 7.82-7.68 (m, 2H), 7.62 (dd, J = 9.1, 2.5 Hz, 1H), 7.36 (s, 1H), 4.01 (d, J = 11.0 Hz, 3H). DMSO >98 G1 367 2 HCl 1H NMR (300 MHz, DMSO) 11.53 (s, 1H), 9.58 (d, J = 1.8 Hz, 1H), 9.20 (d, J = 8.2 Hz, 1H), 8.98 (dd, J = 5.3, 1.3 Hz, 1H), 8.25 (d, J = 2.5 Hz, 1H), 8.12 (d, J = 9.1 Hz, 1H), 8.04-7.95 (m, 1H), 7.80-7.68 (m, 2H), 7.63- 7.57 (m, 1H), 7.56-7.48 (m, 1H), 7.31 (s, 1H), 3.99 (d, J = 6.7 Hz, 3H). DMSO >98 G1 368 2 HCl 1H NMR (300 MHz, DMSO) 11.24 (s, 1H), 9.59 (d, J = 1.7 Hz, 1H), 9.26 (d, J = 8.3 Hz, 1H), 9.00 (d, J = 4.2 Hz, 1H), 8.23 (d, J = 2.6 Hz, 1H), 8.16 (d, J = 2.0 Hz, 1H), 8.09 (dd, J = 8.1, 5.4 Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.91 (dd, J = 8.4, 2.1 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.62 (dd, J = 9.1, 2.5 Hz, 1H), 7.37 (s, 1H), 3.98 (s, 3H). DMSO >98 G1 369 HCl 1H NMR (300 MHz, DMSO) 11.33 (s, 1H), 9.62 (s, 1H), 9.27 (d, J = 8.4 Hz, 1H), 9.01 (d, J = 5.2 Hz, 1 H); 8.29 -8.19 (m, 3H), 8.13-8.01 (m, 2H), 7.79-7.73 (m, 2H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.42 (s, 1H), 3.99 (s, 3H). DMSO >98 G1 370 0 HCl 1H NMR (300 MHz, DMSO) 11.31 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 9.07 (d, J = 7.9 Hz, 1H), 8.92 (d, J = 4.0 Hz, 1H), 8.26 (d, J = 2.5 Hz, 1H), 8.04 (d, J = 9.1 Hz, 1H), 7.98-7.68(m, 5H), 7.63 (dd, J = 9.2, 2.5 Hz, 1H), 7.13 (s, 1H), 4.00 (S.3H). DMSO >98 G1 371 2 HCl 1H NMR (300 MHz, CDCl3) 11.29 (s, 1H), 9.57 (d, J = 1.8 Hz, 1H), 9.07 (d, J = 8.1 Hz, 1H), 8.93 (dd, J = 5.2, 1.3 Hz, 1H), 8.25 (d, J = 2.5 Hz, 1H), 8.07-7.97 (m, 2H), 7.92 (dd, J = 8.0, 5.3 Hz, 1H), 7.67-7.51 (m, 4H), 7.28 (s, 1H), 3.99 (s, 3H). DMSO >98 G1 372 2 HCl 1H NMR (300 MHz, DMSO) 11.32 (s, 1 H), 9.60 (d, J = 1.7 Hz, 1H), 9.27 (d, J = 8.1 Hz, 1H), 9.03 (d, J = 5.4 Hz, 1H), 8.22 (d, J = 2.5 Hz, 1H), 8.12 (dd, J = 8.1, 5.7 Hz, 1H), 8.03 (d, J = 8.8 Hz, 3H), 7.59 (dd, J = 9.1, 2.5 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.32 (s, 1H), 3.98(d, J = 6.7 Hz, 3H). DMSO >98 G1 373 0 2 HCl 1H NMR (300 MHz, DMSO) 11.38 (s, 1 H), 9.61 (d, J = 1.6 Hz, 1H), 9.26 (d, J = 8.2 Hz, 1H), 9.02 (d, J = 5.3 Hz, 1H), 8.23 (d, J = 2.4 Hz, 1H), 8.12- 8.01 (m, 2H), 7.95 (d, J = 8.0 Hz, 1H), 7.89 (s, 1H), 7.71-7.56 (m, 2H), 7.45-7.33 (m, 2H), 4.10-3.90 (m, 3H). DMSO >98 G1 374 2 HCl 1H NMR (300 MHz, DMSO) 11.29 (s, 1 H), 9.56 (s, 1H), 9.12 (d, J = 7.7 Hz, 1H), 8.94 (d, J = 4.9 Hz, 1H), 8.26 (d, J = 2.3 Hz, 1H), 8.07-7.90 (m, 2H), 7.71-7.57 (m, 2H), 7.51 (s, 1H), 7.47-7.37 (m, 1H), 7.17 (s, 1H), 3.99 (s, 3H), 2.53 (s, 3H). DMSO >98 G1 375 2 HCl 1H NMR (300 MHz, DMSO) 13.13- 11.88 (m, 1H), 9.66 (d, J = 1.4 Hz, 1H), 9.36 (d J = 8.2 Hz, 1 H), 9.00 (d, J = 5.4 Hz, 1H), 8.38 (d, J = 2.2 Hz, 1H), 8.14(dd, J = 8.1, 5.6 Hz, 1H), 8.01 (d, J = 7.5 Hz, 2H), 7.89 (d, J = 9.1 Hz, 1H), 7.78 (s, 1 H), 7.64-7.35 (m, 9H), 5.23 (s, 2H). DMSO >98 J NaOtBu, Pd(OAc)2, Tri-t- butyl- phospho- nium tetra- fluoro- borate, Toluene 376 0 2 HCl 1H NMR (300 MHz, DMSO) 12.49 (s, 1 H), 9.63 (s, 1H), 9.27 (d, J = 8.1 Hz, 1H), 8.96 (d, J = 5.4 Hz, 1H), 8.34 (s, 1H), 8.07 (dd, J = 8.1, 5.6 Hz, 1H), 7.99 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 9.1 Hz, 1H), 7.80 (s, 1 H), 7.64-7.35 (m, 9H), 5.21 (s, 2H). DMSO >98 J NaOtBu, Pd(OAc)2, Tri-t- butyl- phospho- nium tetra- fluoro- borate, Toluene 377 2 HCl 1H NMR (300 MHz, DMSO) 9.56 (d, J = 1.8 Hz, 1H), 9.30-9.21 (m, 1H), 9.01 (dd, J = 5.5, 1.2 Hz, 1H), 8.18- 8.03 (m, 2H), 7.76-7.64 (m, 2H), 7.55-7.45 (m, 2H), 7.33 (dd, J = 8.6, 2.3 Hz, 1 H), 4.69 (t, J = 7.9 Hz, 2H), 3.92 (s, 3H), 3.26 (t, J = 7.8 Hz, 2H). DMSO >98 G8 378 2 HCl 1H NMR (300 MHz, DMSO) 9.54 (d, J = 1.9 Hz, 1H), 8.70-8.65 (m, 2H), 7.95 (d, J = 9.2 Hz, 1H), 7.66-7.50 (m, 2H), 7.45-7.36 (m, 2H), 7.27 (t, J = 8.0 Hz, 1H), 7.07 (d, J = 7.9 Hz, 1H), 4.61 (t, J = 8.1 Hz, 2H), 3.87 (s, 3H), 3.38-3.17 (m, 5H). DMSO >98 G8 at 50 C. 379 2 HCl 1H NMR (400 MHz, DMSO) 9.54 (d, J = 1.9 Hz, 1H), 9.28-9.18 (m, 1H), 8.99 (dd, J = 5.5, 1.3 Hz, 1H), 8.18- 8.02 (m, 2H), 7.69 (dd, J = 9.2, 2.7 Hz, 1H), 7.58-7.46 (m, 2H), 7.39 (dd, J = 8.2, 5.9 Hz, 1H), 6.96-6.85 (m, 1H), 4.71 (1, J = 8.0 Hz, 2H), 3.92 (s, 3H), 3.22 (t, J = 7.8 Hz, 2H). DMSO >98 G8 at 50 C. 380 0 2 HCl 1H NMR (300 MHz, DMSO) 9.55 (d, J = 1.8 Hz, 1H), 9.11 (d, J = 8.1 Hz, 1H), 8.93 (dd, J = 5.3, 1.4 Hz, 1H), 8.10-7.93 (m, 2H), 7.76 (dd, J = 8.7, 4.7 Hz, 1H), 7.67 (dd, J = 9.2, 2.6 Hz, 1H), 7.52 (d, J = 2.6 Hz, 1H), 7.28 (dd, J = 8.4, 2.6 Hz, 1 H), 7.12 (td, J = 9.0, 2.7 Hz, 1 H), 4.70 (t, J = 7.9 Hz, 2H), 3.92 (s, 3H), 3.26 (t, J = 7.5 Hz, 2H). DMSO >98 G8 at 50 C. 381 HCl 1H NMR (300 MHz, DMSO) 9.66 (d, J = 2.0 Hz, 1H), 9.15-9.06 (m, 1H), 8.91 (dd, J = 5.2, 1.5 Hz, 1H), 8.27- 8.17 (m, 2H), 8.01 (d, J = 8.9 Hz, 1H), 7.94 (dd, J = 8.2, 5.2 Hz, 1H), 7.88- 7.78 (m, 2H), 7.42 (d, J = 2.7 Hz, 1 H), 7.35 (dd, J = 8.8, 2.2 Hz, 1H), 6.96 (d, J = 3.5 Hz, 1H), 3.91 (s, 3H). DMSO >98 G8 at 50 C. 382 HCl 1H NMR (300 MHz, DMSO) 9.56 (d, J = 1.6 Hz, 1H), 9.26 (d, J = 8.2 Hz, 1H), 9.05-8.98 (m, 1H), 8.20-8.02 (m, 2H), 7.69 (dd, J = 9.2, 2.7 Hz, 1H), 7.53-7.40 (m, 2H), 7.32 (dd, J = 14.0, 8.0 Hz, 1H), 6.92 (1. J = 8.5 Hz, 1H), 4.71 (t, J = 7.9 Hz, 2H), 3.91 (s, 3H), 3.28 (t, J = 7.8 Hz, 2H). DMSO >98 G8 at 50 C. 383 00 01 2 HCl 1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.5 Hz, 1H), 9.23-9.09 (m, 1H), 8.93 (dd, J = 5.3, 1.5 Hz, 1H), 8.31- 8.16 (m, 2H), 8.08-7.93 (m, 2H), 7.82 (dd, J = 9.2, 2.8 Hz, 1H), 7.56 (dd, J = 9.4, 2.5 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.19 (Id, J = 9.2, 2.7 Hz, 1H), 7.02-6.89 (m, 1H), 3.91 (s, 3H). DMSO >98 G8 at 50 C. 384 02 03 04 2 HCl 1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.6 Hz, 1H), 9.23-9.09 (m, 1H), 8.94 (dd, J = 5.3, 1.5 Hz, 1H), 8.26- 8.14 (m, 2H), 8.00 (dd, J = 8.1, 5.3 Hz, 1H), 7.90-7.73 (m, 3H), 7.45 (d, J = 2.7 Hz, 1H), 7.25-7.10 (m, 1H), 6.98 (d, J = 3.5 Hz, 1H), 3.92 (s, 3H). DMSO >98 G8 at 50 C. 385 05 06 07 2 HCl 1H NMR (300 MHz, DMSO) 9.54 (d, J = 1.8 Hz, 1H), 9.21 (dt, J = 8.2, 1.6 Hz, 1H), 8.98 (dd, J = 5.5, 1.3 Hz, 1H), 8.20-8.00 (m, 2H), 7.68 (dd, J = 9.2, 2.7 Hz, 1H), 7.55-7.31 (m, 3H), 7.00-6.78 (m, 1H), 4.69 (t, J = 7.9 Hz, 2H), 4.19 (q, J = 7.0 Hz, 2H), 3.22 (t, J = 7.9 Hz, 2H), 1.41 (t, J = 6.9 Hz, 3H). DMSO >98 G8 at 50 C. 386 08 09 0 2 HCl 1H NMR (300 MHz, DMSO) 9.42 (d, J = 1.5 Hz, 1H), 9.06 (d, J = 8.1 Hz, 1H), 8.93 (d, J = 5.4 Hz, 1H), 8.09- 7.99 (m, 2H), 7.68 (dd, J = 9.1, 2.7 Hz, 1H), 7.53 (d, J = 2.6 Hz, 1H), 7.30- 7.16 (m, 3H), 4.66 (t, J = 7.9 Hz, 2H), 3.98 (s, 3H), 3.29 (t, J = 7.7 Hz, 2H). DMSO >98 G8 at 50 C. 387 2 HCl 1H NMR (300 MHz, DMSO) 9.37 (d, J = 1.4 Hz, 1H), 9.11 (d, J = 8.2 Hz, 1H), 8.99 (d, J = 4.9 Hz, 1H), 8.14 (dd, J = 8.2, 5.6 Hz, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.70 (dd, J = 9.2, 2.6 Hz, 1 H), 7.51 (d, J = 2.7 Hz, 1H), 7.45- 7.36 (m, 2H), 7.26-7.15 (m, 1H), 4.83 (d, J = 9.5 Hz, 1H), 4.49-4.38 (m, 2H), 4.00 (s, 3H), 3.48-3.28 (m, 1H), 3.27-3.05 (m, 1H). DMSO >98 G8 at 50 C. 388 2 HCl 1H NMR (400 MHz, DMSO) 9.56 (d, J = 1.9 Hz, 1H), 9.31-9.19 (m, 1H), 9.00 (dd, J = 5.5, 1.3 Hz, 1H), 8.21- 8.02 (m, 2H), 7.73-7.64 (m, 2H), 7.47 (dd, J = 5.4, 2.4 Hz, 2H), 7.32 (dd, J = 8.6, 2.3 Hz, 1H), 4.67 (t, J = 8.0 Hz, 2H), 4.18 (q, J = 7.0 Hz, 2H), 3.26 (t, J = 7.8 Hz, 2H), 1.41 (1, J = 6.9 Hz, 3H). DMSO >98 G8 at 50 C. 389 2 HCl 1H NMR (400 MHz, DMSO) 9.54 (d, J = 1.8 Hz, 1H), 9.25 (dt J = 8.2, 1.6 Hz, 1H), 9.04(dd, J = 5.5, 1.1 Hz, 1H), 8.26 (d, J = 2.1 Hz, 1H), 8.16 (dd, J = 8.0, 5.6 Hz, 1H), 8.11-7.96 (m, 2H), 7.91 (d, J = 8.6 Hz, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.34 (dd, J = 8.6, 2.3 Hz, 1H), 4.68 (t, J = 7.9 Hz, 2H), 3.25 (t, J = 7.8 Hz, 2H). DMSO >98 G8 at 50 C. 390 0 HCl .sup.1H NMR (400 MHz, DMSO) 9.37 (d, J = 1.4 Hz, 1H), 8.82 (dd, J = 5.1, 1.5 Hz, 1H), 8.76 (dd, J = 8.1 Hz, 1H), 8.62 (d; J = 1.9 Hz, 1H), 8.46 (dd, J = 8.8, 2.1 Hz, 1H), 8.20 (d, J = 8.7 Hz, 1H), 7.91 (dd, J = 6.3, 2.6 Hz, 1H), 7.80 (dd, J = 8.0, 5.1 Hz, 1H), 7.71- 7.59 (m, 2H), 7.52-7.38 (m, 3H), 7.10-7.01 (m, 1H), 3.89 (s, 3H). DMSO >98 G8 with DMF in- stead of THF 391 HCl 1H NMR (400 MHz, DMSO) 9.38 (d, J = 1.4 Hz, 1H), 8.82(d, J = 5.1 Hz, 1H), 8.76 (d, J = 7.9 Hz, 1H), 8.63 (d, J = 1.8 Hz, 1 H), 8.46 (dd, J = 8.8, 2.2 Hz, 1H), 8.20 (d, J = 8.7 Hz, 1H), 7.97 (d, J = 2.7 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.84-7.76 (m, 1H), 7.64 (dd, J = 8.8, 2.7 Hz, 1H), 7.52-7.39 (m, 3H), 7.10-7.02 (m, 1H), 3.88 (s, 3H). DMSO >98 G8 with DMF in- stead of THF 392 HCl .sup.1H NMR (400 MHz, DMSO) 9.39 (t, J = 3.2 Hz, 1H), 8.93-8.82 (m, 2H), 8.62 (d, J = 1.8 Hz, 1H), 8.47 (dd, J = 8.8, 2.2 Hz, 1H), 8.21 (d, J = 9.0 Hz, 1H), 7.91 (dd, J = 8.1, 5.3 Hz, 1H), 7.84-7.77 (m, 1 H); 7.73-7.63 (m, 1H), 7.53-7.40 (m, 4H), 7.09-7.03 (m, 1H), 3.87 (d, J = 6.5 Hz, 3H). DMSO >98 G8 with DMF in- stead of THF 393 0 HCl .sup.1H NMR (400 MHz, DMSO) 11.71 (s, 1H), 11.10 (s, 1H), 9.42 (d, J = 1.9 Hz, 1H), 8.90-8.69 (m, 2H), 8.62 (d, J = 1.7 Hz, 1H), 8.40 (dd, J = 8.8; 1.9 Hz, 1H), 8.14 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.84-7.69 (m, 1H), 7.57-7.40 (m, 3H), 7.11-7.02 (m, 2H), 6.96 (d, J = 8.3 Hz, 1H), 3.89 (s, 3H). DMSO >98 G8 with DMF in- stead of THF 394 HCl .sup.1H NMR (400 MHz, DMSO) 9.43- 9.29 (m, 1H), 8.75-8.64 (m, 2H), 8.60-8.48 (m, 1 H); 8.47-8.32 (m, 1H), 8.21-8.01 (m, 2H), 7.86-7.74 (m, 2H), 7.64 (d, J = 8.6 Hz, 1H), 7.59- 7.34 (m, 4H), 7.13-7.01 (m, 1H), 6.87 (d, J = 8.7 Hz, 1H), 3.90 (t, J = 5.3 Hz, 3H). DMSO >98 G8 with DMF in- stead of THF 395 HCl .sup.1H NMR (400 MHz, DMSO) 9.24 (dd, J = 2.2, 0.8 Hz, 1H), 8.76 (dd, J = 5.0, 1.7 Hz, 1H), 8.61-8.54 (m, 1H), 8.49 (dd, J = 1.8, 1.1 Hz, 1H), 8.21- 8.12 (m, 2H), 7.75 (dd, J = 8.0, 1.5 Hz, 1H), 7.70-7.62 (m, 2H), 7.62- 7.53 (m, 1H), 7.53-7.44 (m, 1H). DMSO >98 G8 with DMF in- stead of THF 396 0 HCl .sup.1H NMR (400 MHz, DMSO) 11.71 (s, 1H), 11.10 (s, 1H), 9.42 (d; J = 1.9 Hz, 1H), 8.90-8.69 (m, 2H), 8.62 (d, J = 1.7 Hz, 1H), 8.40 (dd, J = 8.8, 1.9 Hz, 1H), 8.14 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.84-7.69 (m, 1H), 7.57-7.40 (m, 3H), 7.11-7.02 (m, 2H), 6.96 (d, J = 8.3 Hz, 1H), 3.89 DMSO >98 G12 397 HCl .sup.1H NMR (400 MHz, DMSO) 10.40 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.99 (d, J = 8.2 Hz, 1H), 8.88 (dd, J = 5.3, 1.5 Hz, 1H), 8.30 (d, J = 2.5 Hz, 1H), 8.14-8.06 (m, 1H), 7.99-7.88 (m, 2H), 7.78-7.66 (m, 2H), 7.61-7.51 (m, 3H), 7.50-7.34 (m, 3H), 5.34 (s, 2H). DMSO >98 Method G1 398 .sup.1H NMR (400 MHz, DMSO) 9.96 (s, 1H), 9.52 (d, J = 1.4 Hz, 1H), 8.68 (dd, J = 9.9 Hz, 1 H), 8.65 (d, J = 9.9 Hz, 1H), 8.16 (dd, J = 2.5, 5.4 Hz, 2H), 7.68-7.41 (m, 2H), 7.78-7.66 (m, 8H), 7.39-7.19 (m, 1H), 5.30 (s, 2H). DMSO >98 Method G1 399 1H NMR (DMSO-d6) ppm 12.52 (s, 1 H); 9.78 (d, J = 1.56 Hz, 1 H), 8.91 8.88 (m, 1H), 8.74 (dd, J = 4.74, 1.69 Hz, 1H), 8.33 (brs, 1H), 8.96 (d, J = 8.56 Hz, 2H), 7.93 (d, J = 9.08 hz, 1H), 7.89 (s, 1H), 7.66-7.59 (m, 2H), 7.55 (d, J = 8.56 Hz, 2H), 4.01 (s, 3H). DMSO >98 G13 400 0 2 HCl 1H NMR (DMSO-d6) ppm 12.80- 12.40 (br, 1H), 977 (d, J = 1.84 Hz, 1H), 9.32 (d, J = 8.04 Hz, 1H), 8.97 (dd, J = 5.36, 1.40 Hz, 1H), 8.34 (d, J = 2.68 Hz, 1 H), 8.09-8.06 (m, 3H), 7.97 (d, J = 9.12 Hz, 1H), 7.91 (s, 1H), 7.64 (dd, J = 9.12, 2.68 Hz, 1H), 7.55 (d, J = 8.60 Hz, 2H), 4.01 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 401 2 HCl 1H NMR (DMSO-d6) ppm 11.14 (brs, 1H), 9.58 (s, 1H), 9.13 (dd, J = 7.96 Hz, 1H), 8.93 (d, J = 5.24 Hz, 1H), 8.54 (d, J = 4.72 Hz, 1H), 8.48 (d, J = 8.32 Hz, 1H), 8.28 (brs, 1H), 8.09 (bit, J = 7.16 Hz, 1H), 8.02-7.96 (m, 2H), 7.65 (dd, J = 8.80, 2.48 Hz, 1H), 7.34 (brt, J = 6.52 Hz, 1H), 4.01 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 J2 402 2 HCl 1H NMR (DMSO-d6) ppm 10.89 (s, 1H), 9.57 (d, J = 1.60 Hz, 1H), 9.04 (d, J = 8.04 Hz, 1H), 8.88 (dd, J = 5.16, 1.40 Hz, 1H), 8.55 (dd, J = 2.64, 0.52 Hz, 1H), 8.50 (d, J = 8.92 Hz, 1H), 8.22 (d, J = 2.68 Hz, 1H), 8.08 (d, J = 8.92, 2.68 Hz, 1H), 7.94-7.90 (m, 2H), 7.61 (dd, J = 9.08, 2.68 Hz, 1H), 3.99 (s, 3H). The 1H of 2HCl was not observed. DMSO DMSO J2 403 0 2 HCl 1H NMR (DMSO-d6) ppm 10.53 (s, 1H), 9.38 (s, 1H), 8.99 (d, J = 8.08 Hz, 1H), 8.88 (d, J = 4.60 Hz, 1H), 8.11 (brs, 1H), 8.01-7.95 (m, 2H), 7.90 (d, J = 8.60 Hz, 2H), 7.66 (dd, J = 9.12, 2.68 Hz, 1H), 7.50 (d, J = 8.60 Hz, 2H), 6.93 (s, 1H), 4.00 (s, 3H), 3.80 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 J2 404 HCl 1H NMR (DMS0-d6) ppm 11.81 (brs, 1H), 9.64 (s, 1H), 9.00 (d, J = 7.48 Hz, 1H), 8.85 (brs, 1H), 8.14 (d J = 2.56 Hz, 1H), 8.00 (d, J = 8.60 Hz, 2H), 7.96 (d, J = 9.08 Hz, 1H), 7.86 (br, 1H), 7.66-7.63 (m, 3H), 7.25 (s, 1H), 4.00 (s, 3H). The 1H of HCl was not observed. DMSO >98 J2 405 HCl 1H NMR (DMSO-d6) ppm 11.80 (brs, 1H), 9.65 (brs, 1H), 9.04 (d, J = 7.92 Hz, 1H), 8.88 (brs, 1H), 8.14 (d, J = 2.60 Hz, 1H), 8.05-8.02 (m, 2H), 7.96 (d, J = 9.12 Hz, 1H), 7.89 (m, 1H), 7.64 (dd, J = 9.12, 2.60 Hz, 1H), 7.42 (t, J = 8.84 Hz, 2H), 7.23 (s, 1H), 3.99 (s, 3H). The 1H of HCl was not observed. DMSO >98 J2 406 0 HCl 1H NMR (DMSO-d6) ppm 10.31 (s, 1H), 9.37 (s, 1 H), 8.88 (m, 2H), 8.04 (d J = 2.60 Hz, 1 H), 7.94 (d, J = 9.12 Hz, 1H), 7.91 (m, 1H), 7.64 (dd, J = 9.12, 2.68 Hz, 1H), 7.56 (d, J = 1.88 Hz, 1H), 6.40 (d, J = 1.88Hz, 1H), 3.98 (s, 3H), 3.74 (s, 3H). The 1H of HCl was not observed. DMSO >98 J2 407 2 HCl 1H NMR (DMSO-d6) ppm 12.89 (brs, 1H), 9.56 (s, 1H), 8.92 (d, J = 4.92 Hz, 2H), 8.04 (d, J = 8.84 Hz, 1H), 7.98 (d, J = 2.88 Hz, 1H), 7.84 (br. 1H), 7.71-7.66 (m, 3H), 7.45-7.39 (m, 2H), 4.00 (s, 3H), 3.94 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 J2 408 HCl 1H NMR (DMSO-d6) ppm 10.39 (s, 1H), 9.38 (s, 1H), 8.90 (d, J = 8.00 Hz, 1H), 8.84 (d, J = 4.76 hz, 1H), 8.06 (d, J = 2.68 Hz, 1H), 7.95 (d, J = 9.16 Hz, 1H), 7.90-7.88 (m, 3H), 7.65 (dd, J = 9.16, 2.68 Hz, 1H), 7.44 (bit J = 7.40 Hz, 2H), 7.35-7.31 (m, 1H), 6.88 (s, 1H), 3.99 (s, 3H), 3.80 (s, 3H). The 1H of HCl was not observed. DMSO >98 J2 Tempera- ture at 100 C. 409 HCl 1H NMR (DMSO-d6) ppm 10.44 (brs, 1H), 9.01 (s, 1H), 8.68 (brs, 1H), 8.39 (brs, 1H), 8.23 (s, 1H), 8.07 (brs, 1H), 7.84 (d, J = 9.04 Hz, 1H), 7.70-7.54 (m, 2H), 7.44 (brd, J = 7.32 Hz, 2H), 7.15 (bit J = 7.56 Hz, 2H), 7.00 (brt, 7.40 Hz, 1H), 3.97 (s, 3H), 3.93 (s, 3H). The 1H of HCl was not observed. DMSO >98 J2 Tempera- ture at 100 C. 410 0 HCl 1H NMR (DMSO-d6) ppm 11.13 (s, 1H), 9.59 (d, J = 1.64 Hz, 1H), 9.03 (brs, 1H), 8.88 (brs, 1 H), 8.63 (d, J = 2.52 Hz, 1H), 8.23 (d, J = 2.32 Hz, 1H), 7.93-7.82 (brm, 4H), 7.61-7.53 (m, 3H), 7.35-7.31 (brm, 2H), 4.00 (s, 3H). The 1H of HCl was not obseived. DMSO >98 J2 Tempera- ture at 100 C. 411 1H NMR (DMSO-d6) ppm 9.54 (s, 1H), 8.79 (s, 1H), 8.69 (d, J = 7.60 Hz, 1H), 7.89 (brd, J = 8.96 Hz, 2H), 7.68-7.58 (m, 4H), 7.38-7.30 (m, 2H), 3.98 (s, 3H). The 1H of NH was not observed. DMSO >98 J2 Tempera- ture at 100 C. 412 HCl 1H NMR (DMSO-d6) ppm 9.70 (s, 1H), 9.05 (d, J = 7.88 Hz, 1H), 8.85 (brd, J = 4.44 Hz, 1H), 8.24 (brs, 1H), 8.04 (d, J = 8.44 Hz, 2H), 7.94 (d, J = 9.00 Hz, 1H), 7.84 (m, 1 H), 7.66 (d, J = 8.44 Hz, 2H), 7.62 (dd, J = 9.00, 2.64 Hz, 1H), 3.99 (s, 3H). The 1H of HCl and NH were not observed. DMSO >98 G12 Tempera- ture at 100 C. 413 0 1H NMR (CDCl3) ppm 15.18 (brs, 1H), 9.57 (d, J = 2.32 Hz, 1H), 8.86 (dd, J = 4.80, 1.56 Hz, 1H), 8.59-8.56 (m, 1 H), 7.78-7.73 (m, 4H), 7.55-7.52 (m, 1H), 7.43 (d, J = 8.56 Hz, 2H), 7.38 (dd, J = 8.88, 2.96 Hz, 1H), 7.34 (s, 1H), 3.97 (s, 3H), 3.30 (s, 3H), 3.11 (s, 3H). CDCl3 >98 J2 Tempera- ture at 100 C.

(191) TABLE-US-00004 .sup.1H Pu- Meth- NMR rity od of Reten- Num- Starting Starting Salt Sol- per- Cou- tion LCMS ber Material 1 Material 2 Product type .sup.1H NMR vent cent pling LCMS Time Method 414 2 HCl 1H NMR (DMSO- d6) ppm 9.72 (s, 1H), 9.16 (brs, 1H), 8.93 (d, J = 4.36 Hz, 1H), 8.14 (br, 1H), 7.96 (brm, 2H), 7.63 (dd, J = 9.08, 2.56 Hz, 1H), 7.00 (s, 1H), 3.98 (s, 3H), 2.37 (s, 3H). The 1H of 2HCL and NH were not observed. DMSO >98 G12 Tem- pera- ture at 100 C. 415 2 HCl 1H NMR (DMSO- d6) ppm 12.60 (brs, 1H), 9.78 (s, 1H), 9.12 (d, J = 8.00 Hz, 1H), 8.86 (brs, 1H), 8.35 (brd, J = 2.60 Hz, 1H), 8.01 (d, J = 8.56 Hz, 2H), 7.96 (d, J = 9.08 Hz, 1H), 7.92 (s, 1H), 7.86 (m, 1H), 7.69 (d, J = 8-56 Hz, 2H), 7.63 (dd, J = 9.08, 2.60 Hz, 1H), 4.02 (s, 3H). The 1H of HCl was not observed. DMSO >98 G12 Tem- pera- ture at 100 C. 416 00 HCl 1H NMR (DMSO- d6) ppm 12.80- 12.40 (br, 1H), 9.79 (d, J = 1.64 Hz, 1H), 9.16 (d, J = 7.88 Hz, 1H), 8.88 (d, J = 3.88 Hz, 1H), 8.36 (brd, J = 2.64 Hz, 1H), 8.06-8.04 (m, 2H), 7.96 (d, J = 9.08 Hz, 1H), 7.90 (m, 1H), 7.85 (s, 1H), 7.63 (dd, J = 9.08, 2.64 Hz, 1H), 7.49 (m, 2H), 7.38 (m, 1H), 4.02 (s, DMSO >98 G12 Tem- pera- ture at 100 C. 3H). The 1H of HCl was not observed. 417 01 02 03 HCl 1H NMR (DMSO- d6) ppm 12.80 (s, 1H), 9.74 (d, J = 1.60 Hz, 1H), 9.01 (brs, 1H), 8.83 (brs, 1H), 8.31 (d, J = 2.64 Hz, 1H), 8.15 (d, J = 1.00 Hz, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.78 (br, 1H), 7.64 (dd, J = 9.12, 2.64 Hz, 1H), 3.99 (s, 3H). The 1H of HCl was not observed. DMSO >98 G12 Tem- pera- ture at 100 C. 418 04 05 06 HCl 1H NMR (DMSO- d6) ppm 12.60 (br, 1H), 9.79 (d, J = 1.72 Hz, 1H), 9.19 (d, J = 8.00 Hz, 1H), 8.93 (dd, J = 5.16 , 1.44 Hz, 1H), 8.23 (brs, 1H), 8.10 (s, 1H), 7.99 (m, 1H), 7.95 (d, J = 9.08 Hz, 1H), DMSO >98 G12 Tem- pera- ture at 100 C. 7.77-7.75 (br, 2H), 7.62 (dd, J = 9.08, 2.72 Hz, 1H), 7.50 (m, 2H), 7.37 (m, 1H), 3.99 (s,3H). The 1H of HCl was not observed. 419 07 08 09 HCl 1H NMR (DMSO- d6) ppm 12.56 (s, 1H), 9.78 (s, 1H), 9.09 (d, J = 8.20 Hz, 1H), 8.84 (d, J = 3.96 Hz, 1H), 8.35 (d, J = 2.60 Hz, 1H), 8.10- 8.07 (m, 2H), 7.95 (d, J = 9.12 Hz, 1H), 7.83 (bit, J = 6.60 Hz, 2H), 7.63 (dd, J = 9.12, 2.60 Hz, 1H), 7.32 (m, 2H), 4.02 (s, 3H). The 1H of HCl was not observed. DMSO >98 G12 Tem- pera- ture at 100 C. 420 0 HCl 1H NMR (DMSO- d6) ppm 9.74 (s, 1H), 9.04 (d, J = 6.68 Hz, 1H), 8.86 (brs, 1H), 8.29 (brs, 1H), 8.05 (brs, J = 7.44 Hz, 2H), 7.97 (d, J = 9.08 Hz, 1H), 7.89 (br, 1H), 7.67- 7.58 (m, 4H), 4.00 (s, 3H).The 1H of HCl and NH were not observed. DMSO >98 G12 Tem- pera- ture at 100 C. 421 1H NMR (DMSO- d6) ppm 9.88 (s, 1H), 9.51 (dd, J = 2.16, 0.8 Hz, 1H), 8.68-8.64 (m, 2H), 7.98 (d, J = 2.40 Hz, 1H), 7.91 (d, J = 8.84 Hz, 2H), 7.86 (d, J = 9.12 Hz, 1H), 7.68 (d, J = 8.84 Hz, 2H), 7.58-7.53 (m, 2H), 3.98 (s, 3H). DMSO >98 G1 422 HCl 1H NMR (DMSO- d6) ppm 10.24 (br, 1H), 9.54 (s, 1H), 8.92 (d, J = 7.52 Hz, 1H), 8.82 (d, J = 3.96 Hz, 1H), 8.10 (d, J = 2.44 Hz, 1H), 8.03 (d, J = 8.68 Hz, 2H), 7.92 (d, J = 9.08 Hz, 1H), 7.84 (d, J = 8.68 Hz, 2H), 7.81 (m, 1H), 7.77- DMSO >98 J3 using Na.sub.2CO.sub.3 instead of K.sub.2CO.sub.3 7.75 (m, 2H), 7.62 (dd, J = 9.08, 2.44 Hz, 1H), 7.50 (m, 2H), 7.38 (m, 1H), 4.01 (s, 3H) The 1H of HCl was not observed. 423 0 HCl 1H NMR (DMSO- d6) ppm 9.72 (s, 1H), 9.09 (d, J = 8.00 Hz, 1H), 8.89 (d, J = 4.24 Hz, 1H), 8.26 (brs, 1H), 8.12-8.09 (m, 2H), 7.96 (d, J = 9.12 Hz, 1H), 7.91 (m, 1H), 7.64 (dd, J = 9.12, 2.64 Hz, 1H), 7.45 (t, J = 8.80 Hz, 2H), 3.99 (s, 3H). The 1H of HCl and NH were not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 424 HCl 1H NMR (DMSO- d6) ppm 10.30- 10.15 (br, 1H), 9.54 (s, 1H), 8.91 (brs, 1H), 8.82 (brs, 1H), 8.10 (brs, 1H), 8.04 (d, J = 8.56 Hz, 2H), 7.92 (d, J = 9.6 Hz, 1H), 7.85 (d, J = 8.56 Hz, 2H), 7.80 (m, 1H), 7.79 (d, J = 8.56 Hz, 2H), 7.65-7.59 DMSO >98 J3 (brm, 1H), 7.55 (d, J = 8.56 Hz, 2H), 4.01 (s, 3H).The 1H of HCl was not ob- served. 425 HCl 1H NMR (DMSO- d6) ppm 9.91 (s, 1H), 9.53 (d, J = 1.84 Hz, 1H), 8.69 (d, J = 5.56 Hz, 2H), 8.31 (t, J = 1.88 Hz, 1H), 7.99 (d, J = 2.68 Hz, 1H), 7.98- 7.94 (m, 1H), 7.87 (d, J = 9.08 Hz, 1H), 7.60-7.54 (m, 2H), 7.46 (t, J = 8.04 Hz, 1H), 7.39-7.35 (m, 1H), 3.99 (s, 3H). The 1H of HCl was not observed. DMSO >98 G1 426 0 HCl 1H NMR (DMSO- d6) ppm 10.25 (br, 1H), 9.52 (s, 1H), 8.89 (brs, 1H), 8.88 (brs, 1H), 8.22 (brs, 1H), 8.11 (brs, 1H), 7.98- 7.92 (brm, 2H), 7.80-7.70 (brm, 3H), 7.63- 7,.69 (brm, 2H), 7.55- 7.50 (brm, 3H), 7.41 (m, 1H), 4.00 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 120 C. 427 HCl 1H NMR (DMSO- d6) ppm 10.31 (br, 1H), 9.51 (brs, 1H), 8.92 (brd, J = 7.44 Hz, 1H), 8.84 (brs, 1H), 8.22 (brs, 1H), 8.12 (brd, J = 2.28 Hz, 1H), 8.00-7.93 (brm, 2H), 7.83- 7.77 (brm, 3H), 7.64-7.54 (brm, 5H), 4.01 (s, 3H) . The 1H of HCl was not observed. DMSO >98 J3 using Na.sub.2CO.sub.3 instead of K.sub.2CO.sub.3 428 4 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.72 Hz, 1H), 9.06 (d, J = 8.08 Hz, 1H), 8.88 (d, J = 3.72 Hz, 1H), 8.28 (brs, 1H), 8.01- 7.96 (m, 3H), 7.88 (m, 1H), 7.81 (d, J = 8.60 Hz, 2H), 7.65 (dd, J = 9.08, 2.64 Hz, 1H), 4.00 (s, 3H). The 1H of 4HCl and NH were not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 429 HCl 1H NMR (DMSO- d6) ppm 12.60 (br, 1H), 9.78 (d, J = 1.76 Hz, 1H), 9.28 (d, J = 8.04 Hz, 1H), 8.95 (dd, J = 5.20 , 1.20 Hz, 1H), 8.36 (d, J = 2.28 Hz, 1H), 8.04-7.93 (m, 4H), 7.77 (s, 1H), 7.64 (dd, J = 9.12, 2.68 Hz, 1H), 7.30 (d, J = 8.04 Hz, 2H), 4.02 (s, 3H), 2.36 (s, 3H). The 1H of HCl was not ob- served. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 430 0 2 HCl 1H NMR (DMSO- d6) ppm 12.70- 12.40 (br, 1H), 9.71 (s, 1H), 9.27 (d, J = 8.20 Hz, 1H), 8.94 (d, J = 4.24 Hz, 1H), 8.34 (d, J = 2.64 Hz, 1H), 8.13 (t, J = 1.80 Hz, 1H), 8.04-7.95 (m, 4H), 7.63 (dd, J = 9.08, 2.68 Hz, 1H), 7.52 (t, J = 7.88 Hz, 1H), 7.44-7.42 (m, 1H), 4.02 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 431 HCl 1H NMR (DMSO- d6) ppm 12.57 (br, 1H), 9.80 (brs, 1H), 9.04 (d, J = 7.36 Hz, 1H), 8.82 (brs, 1H), 8.34 (brs, 1H), 7.99 (brd, J = 7.28 Hz, 1H), 7.95 (d, J = 9.08 Hz, 1H), 7.82 (brs, 1H), 7.76 (brm, 1H), 7.62 (m, 2H), 7.50-7.41 (m, 2H), 4.00 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 432 HCl 1H NMR (DMSO- d6) ppm 10.40 (br, 1H), 9.23 (s, 1H), 8.80 (d, J = 4.68 Hz, 1H), 8.66 (brd, J = 8.20 Hz, 1H), 7.92 (brs, 1H), 7.87 (brd, J = 9.28 Hz, 1H), 7.78 (brm, 1H), 7.63-7.52 (m, 5H), 7.47-7.44 (m, 2H), 7.21-7.12 (m, 3H), 3.91 (s, 3H). . The 1H of HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 433 0 HCl 1H NMR (DMSO- d6) ppm 12.34 (br, 1H), 9.75 (s, 1H), 9.01 (d, J = 7.52 Hz, 1H), 8.81 (brs, 1H), 8.40-8.20 (br, 1H), 7.92 (d, J = 9.08 Hz, 1H), 7.77 (m, 1H), 7.60 (dd, J = 9.08, 2.72 Hz, H), 6.95 (br, 1H), 3.98 (s, 3H), 2.67 (m, 1H), 2.05 (m, 2H), 1.83- 1.70 (m, 3H), 1.54- 1.23 (m, 5H) . The 1H of HClwas not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 434 2 HCl 1H NMR (DMSO- d6) ppm 12.58 (br, 1H), 9.79 (s, 1H), 9.19 (d, J = 7.32 Hz, 1H), 8.90 (d, J = 5.6 Hz, 1H), 8.36 (s,lH), 7.96 (d, J = 9.08 Hz, 1H), 7.94 (m, 1H), 7.88 (s, 1H), 7.65-7.62 (m, 3H), 7.40 (t, J = 8.16 Hz, 1H), 6.96-6.93 (m, 1H), 4.02 (s, 3H), 3.84 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 435 2 HCl 1H NMR (DMSO- d6) ppm 12.80- 12.40 (br, 1H), 9.79 (d, J = 1.44 Hz, 1H), 9.26 (d, J = 8.24 Hz, 1H), 8.93 (d, J = 4.08 Hz, 1H), 8.36 (d, J = 2.28 Hz, 1H), 8.02-7.96 (m, 4H), 7.68 (s, 1H), 7.64 (dd, J = 9.12, 2.68 Hz, 1H), 7.05 (d, J = 8.92 Hz, 2H), 4.02 (s, 3H), 3.82 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 436 0 HCl 1H NMR (DMSO- d6) ppm 12.52 (br, 1H), 9.79 (s, 1H), 9.23 (d, J = 8.00 Hz, 1H), 8.91 (d, J = 4.12 Hz, 1H), 8.35 (brs, 1H), 8.25 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 9.08 Hz, 1H), 7.93 (m, 1H), 7.85 (s, 1H), 7.64 (dd, J = 9.08, 2.68 Hz, 1H), 7.39-7.35 (m, 1H), 7.18 (d, J = 7.72 Hz, 1H), 7.11- 7.07 (m, 1H), 4.02 (s, 3H), 3.96 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 437 1H NMR (DMSO- d6) ppm 9.94 (s, 1H), 9.27 (d, J = 1.92 Hz, 1H), 8.59 (dd, J = 4.72, 1.68 Hz, 1H), 8.45 (dt, J = 8.04, 1.8 Hz, 1H), 7.96 (d, J = 2.72 Hz, 1H), 7.84 (d, J = 8.28 Hz, 2H), 7.67 (d, J = 8.00 Hz, 1H), 7.55 (m, 2H), 7.46- 7.43 (m, 1H), 7.33 DMSO >98 G13 using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 (m, 1H), 3.96 (s, 3H). 438 HCl 1H NMR (DMSO- d6) ppm 10.48 (br, 1H), 9.23 (s,lH), 8.83 (brd, J = 3.68 Hz, 1H), 8.70 (brd, J = 7.36 Hz, 1H), 7.95 (brs, 1H), 7.91 (d, J = 9.12 Hz, 1H), 7.82 (m, 1H), 7.63- 7.51 (m, 5H), 7.48 (d, J = 8.52 Hz, 2H), 7.26 (d, J = 8.52 Hz, 2H), 3.93 (s, 3H). The 1H of HCl was not observed. DMSO >98 J3 using Na.sub.2CO.sub.3 instead of K.sub.2CO.sub.3 439 HCl 1H NMR (DMSO- d6) ppm 12.60 (br, 1H), 9.78 (s, 1H), 9.17 (d, J = 7.96 Hz, 1H), 8.88 (d, J = 4.20 Hz, 1H), 8.35 (d, J = 2.60 Hz, 1H), 8.24-8.21 (m, 1H), 7.96 (d, J = 9.08 Hz, 1H), 7.91- 7.88 (brm, 1H), 7.74 (d, J = 2.48 Hz, 1H), 7.63 (dd, J = 9.08, 2.60 Hz, 1H), 7.47- 7.41 (m, 1H), 7.36 8m, 2H), 4.02 (s, 3H). The 1H DMSO >98 G13 at 100 C. of HCl was not observed. 440 0 HCl 1H NMR (DMSO- d6) ppm 12.60- 12.45 (br, 1H), 9.79 (d, J = 1.52 Hz, 1H), 9.15 (d, J = 8.36 Hz, 1H), 8.88 (d, J = 5.04 Hz, 1H), 8.35(d, J = 2.44 Hz, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.89 (bit, J = 7.08 Hz, 2H), 7.82 (brm, 1H), 7.81 (s, 1H), 7.63 (dd, J = 9.12, 2.44 Hz, 1H), 7.37 (t, J = 7.64 Hz, 1H), 7.19 (d, DMSO >98 G13 at 100 C. J = 7.48 Hz, 1H), 4.02 (s, 3H), 2.40 (s, 3H). The 1H of HCl was not observed. 441 HCl 1H NMR (DMSO- d6) ppm 12.60 (br, 1H), 9.77 (s, 1H), 9.25 (d, J = 8.08 Hz, 1H), 8.93 (d, J = 4.28 Hz, 1H), 8.34 (d, J = 2.60 Hz, 1H), 8.01-7.84 (m, 5H), 7.63 (dd, J = 9.12, 2.60 Hz, 1H), 7.56-7.51 (m, 1H), 7.21 (m, 1H). The 1H of HCl was not observed. DMSO >98 G13 at 100 C. 442 2 HCl 1H NMR (DMSO- d6) ppm 12.66 (brs, 1H), 9.78 (d, J = 1.68 Hz, 1H), 9.27 (d, J = 8.08 Hz, 1H), 8.94 (dd, J = 5.20 , 1.40 Hz, 1H), 8.36 (d, J = 2.56 Hz, 1H), 8.17 (d, J = 8.84 Hz, 2H), 8.01 (m, 1H), 7.97 (d, J = 9.08 Hz, 1H), 7.93 (s, 1H), 7.64 (dd, J = 9.08, 2.56 Hz, 1H), 7.49 (brd, J = 8.84 Hz, 2H), 4.02 (s, 3H). The 1H of 2HCl was DMSO >98 G13 at 100 C. not observed. 443 0 2 HCl 1H NMR (DMSO- d6) ppm 12.64 (br, 1H), 9.79 (s, 1H), 9.13 (d, J = 7.56 Hz, 1H), 8.87 (d, J = 5.08 Hz, 1H), 8.36 (d, J = 2.60Hz, 1H), 8.27 (d, J = 8.00 Hz, 2H), 8.08 (s, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.87 (m, 1H), 7.86 (d, J = 8.00 Hz, 2H), 7.64 (dd, J = 9.12, 2.60 Hz, 1H), 4.02 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 at 100 C. 444 2 HCl 1H NMR (MeOD- d4) ppm 9.79 (s, 1H), 9.37 (br, 1H), 8.49 (dd, J = 5.28, 1.32 Hz, 1H), 8.12 (m, 1H), 8.09 (d, J = 2.72 Hz, 1H), 7.98 (d, J = 9.16 Hz, 1H), 7.68 (dd, J = 9.16, 2.72 Hz, 1H), 7.58 (d, J = 7.12 Hz, 1H), 7.42-7.30 (m, 3H), 7.30 (s, 1H), 4.05 (s, 3H), 2.50 (s, 3H). The 1H of 2HCl was not MeOD >98 G13 observed. 445 2 HCl 1H NMR (DMSO- d6) ppm 12.59 (br, 1H), 9.78 (d, J = 1.48 Hz, 1H), 9,19 (d, J = 8.00 Hz, 1H), 8.90 (dd, J = 5.16, 1.48 Hz, 1H), 8.34 (d, J = 2.60 Hz, 1H), 8.10-8.04 (m, 1H), 7.97-7.88 (m, 4H), 7.64 (dd, J = 2.60 Hz, 1H), 7.59-7.52 (m, 1H), 4.02 (s, 3H) . The 1H of 2HCl was not observed. DMSO >98 G13 446 0 HCl 1H NMR (DMSO- d6) ppm 12.61 (br, 1H), 9.78 (d, J = 1.72 Hz, 1H), 9.20 (d, J = 7.92 Hz, 1H), 8.90 (d, J = 4.00 Hz, 1H), 8.35 (d, J = 2.60 Hz, 1H), 8.27-8.21 (m, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.93 (m, 1H), 7.71 (d, J = 2.56 Hz, 1H), 7.64 (dd, J = 9.12, 2.60 Hz, 1H), 7.43 (m, 1H), 7.27 (m, 1H), 4.02 (s, 1H). The 1H of HCl was not observed. DMSO >98 G13 447 2 HCl 1H NMR (DMSO- d6) ppm 12.57 (br, 1H), 9.77 (d, J = 1.76 Hz, 1H), 9.25 (d, J = 8.08 Hz, 1H), 8.93 (dd, J = 5.16, 1.2 Hz, 1H), 8.34 (d, J = 2.60 Hz, 1H), 8.29 (t, J = 1.76 Hz, 1H), 8.05 (dd, J = 7.84, 1.12 Hz, 1H), 8.02-7.98 (m, 1H), 7.99 (s, 1H), 7.96 (d, J = 9.08 Hz, 1H), 7.64 (dd, DMSO >98 G13 J = 9.08, 2.60 Hz, 1H), 7.58-7.56 (m, 1H), 7.45 (t, J = 7.84 Hz, 1H), 4.02 (s, 3H). The 1H of 2HCl was not observed. 448 HCl 1H NMR (DMSO- d6) ppm 12.62 (br, 1H), 9.77 (d, J = 1.52 Hz, 1H), 9.10 (d, J = 8.16 Hz, 1H), 8.85 (dd, J = 5.00, 1.56 Hz, 1h), 8.34 (d, J = 2.60 Hz, 1H), 8.24 (d, J = 8.60 Hz, 2H), 8.13 (s, 1H), 7.96 (d, J = 8.60 Hz, 2H), 7.96 (d, J = 9.08 Hz, 1H), 7.86-7.83 (brm, 1H), 7.63 (dd, J = 9.08, 2.60 Hz, 1H), 4.02 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 449 2 HCl 1H NMR (DMSO- d6) ppm 12.56 (brs, 1H), 9.79 (brs, 1H), 9.11 (d, J = 8.04 Hz, 1H), 8.87 (brs, 1H), 8.43 (brs, 1H), 8.34 (brs, 2H), 8.09 (s, 1H), 7.96 (d, J = 9.08 Hz, 1H), 7.87 (brs, 1H), 7.74 (brd, J = 5.00 Hz, 2H), 7.64 (dd, J = 9.08, 2.48 Hz, 1H), 4.03 (s, 3H). The 1H of 2HCl was not DMSO >98 G13 at 100 C. observed. 450 00 01 02 2 HCl 1H NMR (DMSO- d6) ppm 12.63 (br, 1H), 9.80 (d, J = 1.72 Hz, 1H), 9.27 (d, J = 8.16 Hz, 1H), 8.93 (dd, J = 5.20 , 1.36 Hz, 1H), 8.33 (d, J = 2.24 Hz, 1H), 7.99 (m, 1H), 7.98 (d, J = 9.08 Hz, 1H), 7.88 (brd, J = 7.72 Hz, 1H), 7.71-7.75 (m, 2H), 7.70- 7.63 (m, 2H), DMSO >98 G13 at 100 C. 7.45 (s, 1H), 3.98 (s, 3H). The 1H of 2HCl was not observed. 451 03 04 05 HCl 1H NMR (DMSO- d6) ppm 12.70 (br, 1H), 9.79 (d, J = 1.60 Hz, 1H), 9.30 (d, J = 7.56 Hz, 1H), 8.95 (d, J = 4.96 Hz, 1H), 8.34 (d, J = 2.20 Hz, 1H), 8.02 (m, 1H), 7.98 (d, J = 9.12 Hz, 1H), 7.85- 7.77 (m, 2H), 7.73 (s, 1H), 7.64 (dd, J = 9.12, 2.68 Hz, 1H), 7.52 (m, 1H), 7.36 (m, 1H), 4.00 (s, 3H). The 1H DMSO >98 G13 of HCl was not observed. 452 06 07 08 HCl 1H NMR (DMSO- d6) ppm 12.64 (br, 1H), 9.78 (d, J = 1.72 Hz, 1H), 9.19 (d, J = 7.92 Hz, 1H), 8.90 (d, J = 3.88 Hz, 1H), 8.36 (d, J = 2.64 Hz, 1H), 8.02-7.91 (m, 3H), 7.83 (d, J = 2.40 hz, 1H), 7.64 (dd, J = 9.08, 2.64 Hz, 1H), 7.46 (m, 1H), 7.36 (m, 1H), 4.02 (s, 3H). The 1H of HCl was not DMSO >98 G13 observed. 453 09 0 2 HCl 1H NMR (DMSO- d6) ppm 12.62 (br, 1H), 9.77 (d, J = 1.84 Hz, 1H), 9.30 (d, J = 8.00 Hz, 1H), 8.46 (dd, J = 5.36, 1.48 Hz, 1H), 8.48 (br, 1H), 8.39-8.33 (m, 2H), 8.08 (s, 1H), 8.05 (m, 1H), 7.97 (d, J = 9.12 Hz, 1H), 7.85-7.83 (m, DMSO >98 G13 1H), 7.71 (t, J = 7.84 Hz, 1H), 7.64 (dd, J = 9.12, 2.60 Hz, 1H), 4.02 (s, 3H). The 1H of 2HCl was not observed. 454 2 HCl 1H NMR (DMSO- d6) ppm 12.65 (br, 1H), 9.79 (d, J = 1.72 Hz, 1H), 9.25 (d, J = 8.04 Hz, 1H), 8.92 (d, J = 5.36 Hz, 1H), 8.36 (d, J = 2.60 Hz, 1H), 8.24-8.22 (,m, 1H), 7.97 (d, J = 9.08 Hz, 1H), 7.96 (m, 1H), 7.69 (s, 1H), 7.65 (dd, J = 9.08, 2.60 DMSO >98 G13 Hz, 1H), 7.55 (m, 3H), 4.02 (s, 3H). The 1H of 2HCl was not observed. 455 HCl 1H NMR (DMSO- d6) ppm 12.52 (br, 1H), 9.78 (d, J = 1.48 Hz, 1H), 9.03 (d, J = 6.6 Hz, 1H), 8.81 (d, J = 4.72 Hz, 1H), 8.34 (d, J = 2.56 Hz, 1H), 8.09 (d, J = 7.88 Hz, 1H), 8.03 (brs, 2H), 7.96 (d, J = 9.12 Hz, 1H), 7.78 (br, 1H),7.65 (m, 2H), 7.38 (m, 1H), 4.02 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 456 0 2 HCl 1H NMR (DMSO- d6) ppm 12.45 (br, 1H), 9.78 (d, J = 1.64 Hz, 1H), 9.15 (br, 1H), 8.89 (d, J = 4.52 Hz, 1H), 8.30 (brs, 1H), 7.94 (d, J = 9.08 Hz, 1H), 7.90 (brm, 1H), 7.76 (m, 2H), 7.62 (dd, J = 9.08, 2.64 Hz, 1H), 7.51 (m, 2H), 7.40 (m, 1H), 3.99 (s, 3H), 2.61 (s, 3H). The 1H of 2HCl was not observed. DMSO >98 G13 457 HCl 1H NMR (DMSO- d6) ppm 12.55 (br, 1H), 9.78 (d, J = 1.48 Hz, 1H), 9.08 (d, J = 8.48 Hz, 1H), 8.84 (dd, J = 5.04, 1.56 Hz, 1H), 8.34 (d, J = 2.72 Hz, 1H), 8.09 (s, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.84 (m, 1H), 7.77 (m, 2H), 7.64 (dd, J = 9.12, 2.72 Hz, 1H), 7.25 (m, 1H), 4.02 (s, 3H). The 1H of HCl was not observed. DMSO >98 G13 458 HCl 1H NMR (DMSO- d6) ppm 12.55 (br, 1H), 9.77 (d, J = 1.56 Hz, 1H), 9.14 (d, J = 8.00 Hz, 1H), 8.87 (dd, J = 5.08, 1.48 Hz, 1H), 8.34 (d, J = 2.60 Hz, 1H), 7.98 (m, 1H), 7.96 (d, J = 9.08 Hz, 1H), 7.89-7.86 (brm, 1H), 7.83 (d, J = 2.44 Hz, 1H), 7.64 (dd, J = 9.08, 2.60 Hz, 1H), 7.47-7.41 (m, 1H), 7.29 (m, 1H), 4.02 (s, 3H). DMSO >98 G13 The 1H of HCl was not observed. 459 HCl 1H NMR (DMSO- d6) ppm 12.66 (br, 1H), 9.79 (d, J = 1.60 Hz, 1H), 9.25 (d, J = 7.16 Hz, 1H), 8.92 (d, J = 5.20 Hz, 1H), 8.35 (d, J = 2.56 Hz, 1H), 7.98 (d, J = 9.12 Hz, 1H), 7.97 (m, 1H), 7.68 (s, 1H), 7.64 (dd, J = 9.12, 2.56 Hz, 1H), 7.55 (m, 1H), 7.27 (m, 2H), 3.99 (s, 3H).The 1H of HCl was not observed. DMSO >98 G13 460 0 2 HCl 1H NMR (DMSO- d6) ppm 9.73 (s, 1H), 9.17 (brs, 1H), 8.92 (dd, J = 5.16, 1.4 Hz, 1H), 8.30- 8.10 (br, 1H), 7.97 (d, J = 9.04 Hz, 1H), 7.96 (m, 1H), 7.63 (dd, J = 9.04, 2.72 Hz, 1H), 7.02 (s, 1H), 3.98 (s, 3H), 2.57 (d, J = 7.16 Hz, 2H), 2.08 (m, 1H), 0.94 (d, J = 6.60 Hz, 6H) .The 1H of HCl and NH were not observed. DMSO >98 G13 461 2 HCl 1H NMR (DMSO- d6) ppm 12.80- 12.20 (br, 1H), 9.78 (d, J = 1.76 Hz, 1H), 9.28 (d, J = 8.04 Hz, 1H), 8.96 (dd, J =5.28, 1.32 Hz, 1H), 8.29 (brs, 1H), 8.07-8.03 (brm, 1H), 7.95 (d, J = 9.12 Hz, 1H), 7.79 (d, J = 8.60 Hz, 2H), 7.62 (dd, J = 9.12, 2.64 Hz, 1H), 7.57 (d, J = 8.60 Hz, 2H), 3.99 (s, 3H), 2.61 (brs, 3H). The 1H of 2HCl DMSO >98 G13 was not observed. 462 2 HCl 1H NMR (DMSO- d6) ppm 12.80- 12.20 (br, 1H),. 9.74 (s, 1H), 9.19 (d, J = 4.96 Hz, 1H), 8.91 (dd, J = 5.2, 1.4 Hz, 1H), 8.22 (brs, 1H), 7.96 (br, 1H), 7.95 (d, J = 9.08 Hz, 1H), 7.61 (dd, J = 9.08, 2.68 Hz, 1H), 7.35-7.31 (m, 4H), 7.23 (m, 1H), 7.09 (brs, 1H), 4.07 DMSO >98 G13 (brs, 2H), 3.96 (brs, 3H). The 1H of 2HCl was not observed. 463 0 2 HCl 1H NMR (DMSO- d6) ppm 12.50 (br, 1H), 9.78 (d, J = 1.76 Hz, 1H), 9.25 (brs, 1H), 8.96 (brd, J = 4.68 Hz, 1H), 8.29 (brs, 1H), 8.04 (brs, 1H), 7.96 (d, J = 9.20 Hz, 1H), 7.70 (brm, 2H), 7.63 (dd, J = 9.20, 2.68 Hz, 1H), 7.51 (brm, 2H), 7.41 (brm, 1H), 3.99 (s, 3H), 3.02 (q, J = 7.40 DMSO >98 G13 Hz, 2H), 1.49 (t, J = 7.40 Hz, 3H). The 1H of 2HCl was not observed. 464 2 HCl 1H NMR (DMSO- d6) ppm 12.53 (br, 1H), 9.78 (d, J = 1.76 Hz, 1H), 9.20 (d, J = 8.36 Hz, 1H), 8.94 (dd, J = 5.2, 1.4 Hz., 1H), 8.29 (brs, 1H), 8.00 (brm, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.66- 7.61 (m, 3H), 7.52 (brm, 2H), 7.43 (t, J 7.40 Hz, 1H), 3.98 (s, 3H), 1.43 (d, J = 6.8 Hz, 6H). The 1H of 2HCl DMSO >98 G13 was not observed. The CH proton of iPr group was not observed because of overlapping the H2O peak. 465 2 HCl 1H NMR (DMSO- d6) ppm 12.59 (brs, 1H), 9.77 (d, J = 1.72 Hz, 1H), 9.25 (d, J = 7.76 Hz, 1H), 8.96 (d, J = 4.04 Hz, 1H), 8.29 (br, 1H), 8.04 (m, 1H), 7.96 (d, J = 9.12 Hz, 1H), 7.69 (brd, J = 7.12 Hz, 2H), 7.63 (dd, J = 9.12, 2.68 Hz, H), 7.51 (t, J = 7.36 Hz, 2H), DMSO >98 G13 7.42 (t, J = 7.36 Hz, 1H), 3.99 (s, 3H), 2.96 (t, J = 7.52 Hz, 2H), 1.78 (m, 2H), 1.01 (t, J = 7.24 Hz, 3H). The 1H of 2HCl was not observed. 466 0 2 HCl 1H NMR (DMSO- d6) ppm 12.96 (brs, 1H), 9.74 (d, J = 2.04 Hz, 1H), 9.11 (d, J = 7.96 Hz, 1H), 8.90 (d, J = 4.96 Hz, 1H), 8.31 (brd, J = 2.64 Hz, 1H), 7.97 (d, J = 9.12 Hz, 1H), 7.87 (brm, 1H), 7.83- 7.80 (m, 2H), 7.64 (dd, J = 9.12, 2.62 Hz, DMSO >98 G13 1H), 7.48 (m, 3H), 4.25 (q, J = 7.04 Ha, 2H), 3.98 (s, 3H), 1.29 (t, J = 7.04 Hz, 3H). The 1H of 2HCl was not observed. 467 HCl 1H NMR (DMSO- d6) ppm 12.63 (br, 1H), 9.76 (d, J = 1.76 Hz, 1H), 9.29 (d, J =8.16 Hz, 1H), 8.95 (dd, J = 5.28, 1.36 Hz, 1H), 8.32 (brd, J =2.60 Hz, 1H), 8.07 (d, J = 8.52 Hz, 2H), 8.08-8.00 (m, 1H), 7.95 (d, J = 9.12 Hz, 1H), 7.90 (s, 1H), 7.61 (dd, J = 9.12, 2.60 Hz, 1H), 7.55 (d, J = 8.52 Hz, 2H), 4.24 (q, DMSO >98 G13 J =6.88 Hz,2H), 1.47 (t, J = 6.88 Hz, 3H). The 1H of HCl was not observed. 468 2 HCl 1H NMR (DMSO- d6) ppm 12.58 (brs, 1H), 9.76 (d, J = 1.80 Hz, 1H), 9.27 (d, J = 8.16 Hz, 1H), 8.94 (dd, J = 5.20, 1.32 Hz, 1H), 8.32 (d, J = 2.48 Hz, 1H), 8.09- 8.01 (m, 2H), 7.96-7.89 (m, 3H), 7.62-7.52 (m, 2H), 4.29 (q, J = 6.88 Hz, 2H), 1.47 (t, J = 6.88 Hz, 3H). The 1H of DMSO >98 G13 2HCl was not observed. 469 2 HCl 1H NMR (DMSO- d6) ppm 9.72 (s, 1H), 9.13 (brd, J = 5.52 Hz, 1H), 8.92 (d, J = 3.52 Hz, 1H), 8.16 (brs, 1H), 7.95 (brd, J = 9.08 Hz, 2H), 7.62 (dd, J = 2.4 Hz, 1H), 7.39 (brs, 1H), 3.97 (s, 3H), 2.47 (s, 3H). The 1H of 2HCl DMSO >98 G13 and NH were not observed. 470 0 HCl 1H NMR (DMSO- d6) ppm 12.58 (brs, 1H), 9.76 (d, J = 1.68 Hz, 1H), 9.17 (d, J = 8.12 Hz, 1H), 8.89 (dd, J = 5.12, 1.48 Hz, 1H), 8.32 (d, J = 2.56 Hz, 1H), 8.01- 8.00 (m, 1H), 7.94 (d, J = 9.08 Hz, 1H), 7.930-7.90 (m, 1H), 7.81 DMSO >98 G13 (d, J = 2.4 Hz, 1H), 7.60 (dd, J = 9.08, 2.40 Hz, 1H), 7.50-7.43 (m, 1H), 7.38-7.33 (m, 1H), 4.28 (q, J = 7.00 Hz, 2H), 1.47 (t, J = 7.00 Hz, 3H). The 1H of HCl was not observed. 471 2 HCl 1H NMR (DMSO- d6) ppm 12.53 (brs, 1H), 9.73 (d, J = 1.76 Hz, 1H), 9.29 (d, J = 8.16 Hz, 1H), 8.95 (dd, J = 5.32, 1.36 Hz, 1H), 8.29 (d, J = 2.56 Hz, 1H), 8.05- 8.02 (brm, 1H), 7.97-7.92 (m, 1H), 7.93 (d, J = 9.08 Hz, 1H), 7.78 (d, J = 2.36 Hz, 1H), DMSO >98 G13 7.60 (dd, J = 9.08, 2.6 Hz, 1H), 7.46- 7.40 (m, 1H), 7.31-7.25 (m, 1H), 4.27 (q, J = 6.92 Hz, 2H), 1.47 (t, J = 6.92 Hz, 3H). The 1H of 2HCl was not observed. 472 3 HCl 1H NMR (DMSO- d6) ppm 12.61 (brs, 1H), 9.76 (d, J = 1.8 Hz, 1H), 9.29 (d, J = 8.16 Hz, 1H), 8.95 (dd, J = 5.24, 1.2 Hz, 1H), 8.32 (d, J = 2.52 Hz, 1H), 8.24- 8.20 (m, 1H), 8.05- 8.01 (brm, 1H),7.95 (d, J = 9.08 Hz, 1H), 7.68 (d, J =2.52 HZ, 1H), 7.61 (dd, J = 9.08, 2.52 Hz, 1H), 7.46-7.40 (m, 1H), 7.28-7.24 (m, 1H), 4.28 (q, DMSO >98 G13 J = 6.92 Hz, 2H), 1.47 (t, J = 6.92 Hz, 3H). The 1H of 3HCl was not observed. 473 0 2 HCl 1H NMR (DMSO- d6) ppm 12.63 (brs, 1H), 9.78 (d, J = 1.68 Hz, 1H), 9.32 (d, J = 8.12 Hz, 1H), 8.97 (d, J = 5.24 Hz, 1H), 8.35 (d, J = 2.16 Hz, 1H), 8.08-8.04 (m, 3H), 7.96 (d, J = 9.08 Hz, 1H), 7.85 (s, 1H), 7.62 (dd, J = 9.08, 2.52 Hz, 1H), 7.49 (t, J = 7.44 Hz, 2H), 7.38 (t, DMSO >98 G13 J = 7.28 Hz, 1H), 4.30 (q, J = 6.96 Hz, 2H), 1.47 (t, J = J = 6.96 Hz, 3H). The 1H of 2HCl was not observed. 474 1H NMR (DMSO- d6) ppm 12.68 (s, 1H), 9.73 (d, J = 1.64 Hz, 1H), 8.87-8.84 (m, 1H), 8.75-8.73 (m, 1H), 8.33 (brs, 1H), 8.24 (brs, 1H), 7.93 (d, J = 9.16 Hz, 1H), 7.64-7.59 (m, 2H), 4.34 (q, J = 7.08 Hz, 2H), 3.98 (s, 3H), 1.34 (t, J = 7.08 Hz, 3H). DMSO >98 G13 475 HCl .sup.1H NMR (300 MHz, DMSO) 10.35 (s, 1H), 9.42 (s, 1H), 8.99-8.76 (m, 2H), 8.11 (d, J = 6.7 Hz, 1H), 7.99-7.75 (m, 3H), 7.67-7.43 (m, 2H), 7.23 (d, J = 8.2 Hz, 1H), 4.14 (s, 3H). DMSO 98 G1 381 (M + 1) 2.07 Method A (Formic acid) 476 HCl 1H NMR (300 MHz, DMSO) 13.78 (s, 1H), 9.62 (d, J = 1.7 Hz, 1H), 9.21 (d, J = 8.1 Hz, 1H), 8.98 (d, J = 4.2 Hz, 1H), 8.07 (dd, J = 7.9, 5.3 Hz, 1H), 7.83 (d, J = 9.1 Hz, 2H), 7.63-7.50 (m, 4H), 7.41 (d, J = 6.5 Hz, 2H), 7.14 (d, J = 2.5 Hz, 1H), 5.30 (s, 1H), 3.91 (s, 3H), 2.15 (s, 3H). DMSO 95 Method G1 468.1 (M + 1) Method C 477 0 HCl 1H NMR (300 MHz, DMSO) 13.78 (s, 1H), 9.64 (d, J = 1.5 Hz, 1H), 9.11 (d, J = 8.2 Hz, 1H), 8.90 (d, J = 3.8 Hz, 1H), 7.95 (dd, J = 10.6, 2.6 Hz, 1H), 7.84 (d, J = 9.1 Hz, 2H), 7.60-7.48 (m, 4H), 7.38 (d, J = 6.5 Hz, 2H), 7.17 (d, J = 2.4 Hz, 1H), 5.28 (s, 1H), 4.14 (q, J = 6.9 Hz, 2H), 2.15 DMSO 95 Method G1 482.1 (M + 1) Method C (s, 3H), 1.42 (t, J = 6.9 Hz, 3H). 478 HCl 1H NMR (300 MHz, DMSO) 12.59 (s, 1H), 9.56 (s, 1H), 8.70 (d, J = 5.8 Hz, 2H), 8.58 (d, J = 5.2 Hz, 1H), 7.95 (d, J = 5.2 Hz, 2H), 7.87 (d, J = 9.1 Hz, 2H), 7.64-7.49 (m, 2H), 7.40 (d, J = 2.4 Hz, 1H), 4.21 (q, J = 6.8 Hz, 2H), 1.44 (t, J = 6.9 Hz, 3H). DMSO 99 Method G1 392.1 (M + 1) Method C 479 HCl 1H NMR (300 MHz, DMSO) 13.75 (s, 1H), 9.60 (s, 1H), 8.98 (s, 1H), 8.82 (d, J = 3.6 Hz, 1H), 7.82 (d, J = 9.0 Hz, 3H), 7.52 (d, J = 9.3 Hz, 1H), 7.15 (s, 1H), 6.94-6.62 (s, 1H), 4.13 (d, J = 6.9 Hz, 2H), 2.90 (d, J = 21.9 Hz, 4H), 2.41 (s, 2H), 1.43 (t, J = 6.9 Hz, 3H). DMSO 95 Method G1 432.1 (M + 1) Method C 480 HCl 1H NMR (300 MHz, DMSO) 12.50 (s, 1H), 9.56 (s, 1H), 8.89 (s, 1H), 8.68 (d, J = 5.3 Hz, 2H), 8.00-7.79 (m, 3H), 7.73 (d, J = 7.2 Hz, 4H), 7.62- 7.38 (m, 9H), 7.34 (d, J = 2.2 Hz, 2H), 4.18 (dd, J = 13.5, 6.5 Hz, 2H), 1.43 (t, J = 6.9 Hz, 3H). DMSO 99 Method G1 468.1 (M + 1) Method C 481 HCl 1H NMR (300 MHz, DMSO) 12.51 (s, 1H), 9.54 (s, 1H), 8.86 (s, 1H), 8.74-8.61 (m, 2H), 7.90 (s, J = 15.7 Hz, 2H), 7.83 (d, J = 9.1 Hz, 1H), 7.72 (d, J = 7.1 Hz, 2H), 7.63- 7.40 (m, 6H), 7.33 (d, J = 2.3 Hz, 1H), 3.92 (s, 3H). DMSO 99 Method G1 454.1 (M + 1) Method C 482 0 HCl 1H NMR (300 MHz, DMSO) 13.70 (s, 1H), 9.70 (d, J = 2.1 Hz, 1H), 8.81 (d, J = 8.0 Hz, 1H), 8.70 (dd, J = 4.8, 1.7 Hz, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.66- 7.53 (m, 2H), 7.29 (d, J = 2.2 Hz, 1H), 3.95 (s, 3H), 2.78 (d, J = 12.9 Hz, 4H), 1.78 (s, 4H). DMSO 99 Method G1 432.1 (M + 1) Method C 483 HCl 1H NMR (300 MHz, DMSO) 13.64 (s, 1H), 9.68 (s, 1H), 8.79 (d, J = 7.9 Hz, 1H), 8.69 (d, J = 4.7 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.63- 7.50 (m, 2H), 7.24 (s, 1H), 4.18 (q, J = 6.7 Hz, 2H), 2.76 (d, J = 10.4 Hz, 4H), 1.78 (s, 4H), 1.43 (t, J = 6.9 Hz, 3H). DMSO 99 Method G1 446.1 (M + 1) Method C 484 HCl 1H NMR (300 MHz, DMSO) 12.82 (s, 1H), 9.67 (d, J = 2.1 Hz, 1H), 8.77 (dt, J = 8.1, 2.0 Hz, 1H), 8.71 (dd, J = 4.8, 1.7 Hz, 1H), 7.87 (d, J = 9.1 Hz, 1H), 7.83 (s, 1H), 7.60- 7.53 (m, 3H), 7.48 (s, 1H), 7.20 (d, J = 2.6 Hz, 1H), 4.20 (q, J = DMSO 95 Method G1 422.1 (M + 1) Method C 6.9 Hz, 2H), 2.90 (d, J = 4.7 Hz, 3H), 1.44 (t, J = 6.9 Hz, 3H). 485 HCl 1H NMR (300 MHz, DMSO) 9.66 (s, 1H), 9.44 (d, J = 1.4 Hz, 1H), 8.64-8.55 (m, 2H), 7.90 (s, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.76 (d, J = 2.5 Hz, 1H), 7.69 (s, 2H), 7.54- 7.45 (m, 2H), 4.19 (q, J = 7.0 Hz, 2H), 4.04 (s, 3H), 1.42 (t, J = 6.9 Hz, 3H). DMSO 99 Method G1 390.1 (M + 1) Method C 486 2 HCl 1H NMR (300 MHz, DMSO) 9.57 (d, J = 1.5 Hz, 1H), 9.07 (d, J = 4.6 Hz, 1H), 8.94 (dd, J = 5.2, 1.4 Hz, 1H), 8.04 (d, J = 9.1 Hz, 1H), 7.97 (dd, J = 6.7, 6.0 Hz, 1H), 7.67 (dd, J = 9.1, 2.8 Hz, 1H), 7.55 (d, J = 2.7 Hz, 1H), 7.36 (dd, J = 6.4, 2.3 Hz, 2H), 7.14- DMSO 99 Method G1 382.5 (M + 1) Method C 7.03 (m, 2H), 3.74 (s, 3H), 3.69 (s, 3H). 487 000 001 2 HCl 1H NMR (300 MHz, DMSO) 12.59 (s, 1H), 9.58 (d, J = 2.0 Hz, 1H), 8.94 (d( J = 8.2 Hz, 1H), 8.84 (d, J = 5.2 Hz, 1H), 8.73 (s, 1H), 8.09 (s, 1H), 7.95 (s, 3H), 7.82 (dd, J = 8.4, 5.4 Hz, 2H), 7.75 (d, J = 7.4 Hz, 2H), 7.59- 7.42 (m, 3H). DMSO 99 Method G1 458.4 (M + 1) Method C 488 002 003 2 HCl 1H NMR (300 MHz, DMSO) 13.79 (s, 1H), 9.49 (d, J = 1.5 Hz, 1H), 8.96 (d, J = 8.0 Hz, 1H), 8.86 (d, J = 3.7 Hz, 1H)( 7.95- 7.71 (m, 4H), 7.65 (d, J = 1.6 Hz, 1H), 6.76 (s, 1H), 2.85 (d, J = 22.5 Hz, 4H), 2.44-2.29 (m, 2H). DMSO 93 Method G1 422.4 (M + 1) Method C 489 004 005 2 HCl 1H NMR (300 MHz, DMSO) 9.53 (d, J = 1.8 Hz, 1H), 9.04 (d, J = 7.9 Hz, 1H), 8.93 (d, J = 3.9 Hz, 1H), 7.95 (dd, J = 8.0, 5.2 Hz, 1H), 7.90-7.78 (m, 2H), 7.70 (d, J = 1.7 Hz, 1H), 2.29 (s, 3H), 2.24 (s, 3H). DMSO 94 Method G1 410.3 (M + 1) Method C 490 006 007 1H NMR (300 MHz, DMSO) 13.07 (s, 1H), 9.93 (d, J = 1.8 Hz, 1H), 9.64 (d, J = 1.6 Hz, 1H), 8.90- 8.78 (m, 1H), 8.76-8.62 (m, 2H), 8.29 (s, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.71 (dd, J = 8.3, 1.9 Hz, 1H), 7.65 (s, DMSO 99 Method G1 464.2 (M + 1) Method C 1H), 7.57 (dd, J = 9.1, 2.5 Hz, 1H), 7.53-7.44 (m, 2H), 7.01 (s, 1H), 4.21 (q, J = 6.9 Hz, 2H), 3.34 (s, 3H), 1.44 (t, J = 6.9 Hz, 3H). 491 008 009 1H NMR (300 MHz, DMSO) 9.78 (s, 1H), 9.50 (d, J = 2.0 Hz, 1H), 8.68-8.57 (m, 2H), 7.97 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 1.8 Hz, 1H), 7.79 (d, J = 9.1 Hz, 1H), 7.55-7.43 (m, 3H), 7.22 (d, J = 8.4 DMSO 99 Method G1 427.5 (M + 1) Method C Hz, 1H), 4.22 (q, J = 6.9 Hz, 2H), 3.37 (d, J = 4.3 Hz, 6H), 1.43 (t, J = 6.9 Hz, 3H). 492 010 1H NMR (300 MHz, DMSO) 11.48 (s, 1H), 10.97 (s, 1H), 9.28 (d, J = 1.5 Hz, 1H),8.64 (dd, J = 4.6, 1.7 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 7.94-7.80 (m, 3H), 7.53-7.35 (m, 2H), 7.02 (t, J = 7.5 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 4.04 (s, H). DMSO 99 Method F5, G13 391.1 (M + 1) Method C 493 011 2 HCl 1H NMR (300 MHz, DMSO) 11.28 (s, 1H), 9.62 (d, J = 1.7 Hz, 1H), 9.17 (d, J = 7.8 Hz, 1H), 8.93 (dd, J = 5.2, 1.3 Hz, 1H), 8.60 (s, 1H), 8.05 (s, 1H), 8.03- 7.94 (m, 2H), 7.77 (s, 1H), 7.64 (dd, J = 9.2, 2.5 Hz 1H), 7.40 (d, J = 2.6 Hz, 1H), 3.97 (s, 3H). DMSO 99 Method G14 362.4 (M + 1) Method C 494 012 .sup.1H-NMR (400 MHz, DMSO-d6): 10.14 (s, 1H), 9.54 (s, 1H), 8.70- 8.67 (m, 2H), 8.48 (s, 1H), 8.16 (s, 1H), 7.96- 7.89 (m, 3H), 7.60 ft, J = 8.0 Hz, 1H), 7.55-7.52 (m, 1H), 7.17 (d, J = 8.8 Hz, 1H), 3.71 (s, 2H), 2.72- 2.65 (m, 8H). DMSO 95 Method G1 498.1 (M + 1) t = 2.128 min Method B (NH.sub.4HCO.sub.3) 495 013 .sup.1H-NMR (400 MHz, DMSO-d6): 10.71 (s, 1H), 9.37 (s, 1H), 8.93 (s, 1H), 8.67 (d, J = 3.2 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 7.93 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.65 (m, 2H), 7.04 (d, J = 8.0 Hz, 1H), 2.95 (t, J = 8.0 Hz, 2H), 2.64 (t, J = 8.0 Hz, 2H). DMSO 95 Method G1 402.2 (M + 1) t = 1.746 min Method B (NH.sub.4HCO.sub.3) 496 014 .sup.1H-NMR (400 MHz, DMSO-d6): 11.38 (s, 1H), 9.51 (s, 1H), 8.67- 8.60 (m, 3H), 8.24- 8.10 (m, 2H), 7.88-7.83 (m, 2H), 7.58-7.55 (m, 3H), 7.33 (dd, J = 7.2, 4.8 Hz, 1H), 3.97 (s, 3H). DMSO 95 Method J1 373.0 (M + 1) t = 1.523 min Method B (NH.sub.4HCO.sub.3) 497 015 2 HCl .sup.1H-NMR (400 MHz, DMSO-d6): 9.92 (s, 1H), 9.30 (s, 1H), 8.60 (d, J = 3.4 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.40 (d, J = 4.4 Hz, 1H), 7.87 (d, J = 2.2 Hz, 1H), 7.84 (d, J = 9.1 Hz, 1H), 7.59-7.40 (m, 5H), 4.24 (q, J = 6.9 Hz, 2H), 2.55 (d, J = 4.5 Hz, 3H), DMSO 95 Method G1 418.2 (M + 1) 1.782 min Method B (NH.sub.4HCO.sub.3) 1.45 (t, J = 6.9 Hz, 3H). 498 016 .sup.1H-NMR (400 MHz, DMSO-d6): 10.14 (s, 1H), 9.54 (d, J = 2.0 Hz, 1H), 8.70-8.67 (m, 2H), 8.50 (s, 1H), 8.15 (s, 1H), 7.94- 7.92 (m, 3H), 7.61 (t, J = 8.0 Hz, 1H), 7.55 (dd, J = 8.0, 4.8 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 3.90 (s, 2H), 3.17 (s, 4H), 2.98 DMSO 95 Method G1 530.0 (M + 1) 1.856 min Method B (NH.sub.4HCO.sub.3) (s, 4H). 499 017 2 HCl .sup.1H-NMR (400 MHz, DMSO-d6): 13.19 (s, 1H), 9.65 (s, 1H), 9.17 (d, J = 8.2 Hz, 1H), 8.97 (d, J = 4.5 Hz, 1H), 8.93 (s, 1H), 8.81 (d, J = 8.2 Hz, 1H), 8.45 (s, 1H), 8.40 (dd, J = 8.7, 1.7 Hz, 1H), 8.16 (d, J = 8.7 Hz, 1H), 7.99 (dd, J = 16.0, 10.4 Hz, 3H), 7.74 (t, J = 7.4 Hz, 1H), DMSO 95 Method G1 420.1 (M + 1) t = 1.478 min Method B (NH.sub.4HCO.sub.3) 7.32 (t, J = 7.6 Hz, 1H), 3.38 (s, 3H). 501 018 HCl .sup.1H-NMR (400 MHz, DMSO-d6): 13.46 (s, 1H), 9.46 (s, 1H), 8.97 (d, J = 7.9 Hz, 1H), 8.93 (d, J = 4.4 Hz, 1H), 8.77 (d, J = 12.1 Hz, 1H), 8.55 (s, 1H), 8.16- 7.91 (m, 4H), 7.83 (t, J = 7.5 Hz, 1H), 7.73 (d, J = 9.3 Hz, 1H), 7.05 (t, J = 6.9 Hz, 1H). DMSO 95 Method G1 378.1 (M + 1) t = 1.873 min Method B (NH.sub.4HCO.sub.3) 502 019 .sup.1H-NMR (400 MHz, DMSO-d6): 13.00 (s, 1H), 9.83 (s, 1H), 9.17 (d, J = 8.0 Hz, 1H), 9.00 (d, J = 8.0 Hz, 1H), 8.73-8.72 (m, 1H), 8.49 (s, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H), 7.76 (t, J = 7.2 Hz, 1H), 7.63- 7.53 (m, 3H), 7.28 (d, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H). DMSO 95 Method G1 358.0 (M + 1) t = 1.644 min Method B (NH.sub.4HCO.sub.3) 503 020 .sup.1H-NMR (400 MHz, DMSO-d6): 11.34 (s, 1H), 9.50 (s, 1H), 8.69 (d, J = 3.6 Hz, 1H), 8.65 (d, J = 7.6 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.15 (s, 1H), 8.10 (s, 1H), 8.00-7.97 (m, 1H), 7.91- 7.84 (m, 2H), 7.69- 7.66 (m, 1H), 7.55- 7.52 (m, 1H)( 7.16 (t, J = 9.2 Hz, 1H). DMSO 95 Method G1 378.0 (M + 1) t = 1.780 min Method B (NH.sub.4HCO.sub.3) 504 021 HCl 1H-NMR (300 MHz, DMSO): 10.48 (s, 1H), 9.57 (s, 1H), 9.13 (d, J = 7.6 Hz, 1H)( 8.97-8.80 (m, 2H), 8.31 (s, 1H), 8.19 (s, 1H), 8.10 (d, J = 6.5 Hz, 1H), 7.97 (d, J = 9.1 Hz, 2H), 7.83 (d, J = 7.7 Hz, 1H), 7.66 (t, J = 7.9 DMSO 95 Method G1 396.1 (M + 1) Method C Hz, 2H), 7.47 (d, J = 5.4 Hz, 1H), 4.02(s, 3H). 505 022 023 024 .sup.1H NMR (400 MHz, DMSO) 15.71 (s, 1H), 10.01 (s, 1H), 9.59-9.51 (m, 1H), 8.73- 8.62 (m, 2H), 8.60- 8.54 (m, 1H), 8.13- 7.96 (m, 2H), 7.93- 7.82 (m, 2H), 7.62- 7.49 (m, 2H), 4.01 (s, 3H). DMSO >98 G1 506 025 026 027 .sup.1H NMR (400 MHz, DMSO) 10.77 (s, 1H), 9.75 (s, 1H), 9.55-9.46 (m, 1H), 8.73- 8.60 (m, 2H), 7.96 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.63 (d, J = 2.1 Hz, 1H), 7.58- 7.47 (m, 3H), 6.99 (d, J = 8.5 Hz, 1H), DMSO >98 G1 (0.1N HCl added) 4.64 (s, 2H), 3.97 (s, 3H). 507 028 029 030 .sup.1H NMR (400 MHz, DMSO) 12.54 (s, 1H), 9.85 (s, 1H), 9.51 (s, 1H), 8.70-8.60 (m, 2H), 8.27-8.16 (m, 2H), 8.03 (d, J = 2.5 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.72- 7.59 (m, 2H), 7.56- 7.47 (m, 2H), 3.99 (s, 3H). DMSO >98 G1 508 031 032 033 .sup.1H NMR (400 MHz, DMSO) 9.87 (s, 1H), 9.50-9.47 (m, 1H), 8.66- 8.61 (m, 2H), 8.21 (s, 1H), 8.16 (4, J = 1.6 Hz, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 9.1 Hz, 1H), 7.74 (dd, J = 8.7, 1.9 Hz, 1H), 7.67 (d, J = 8.6 Hz, 1H), 7.56- 7.47 (m, 2H), 3.99 DMSO >98 G1 (s, 3H), 3.90 (s, 3H). 509 034 035 036 .sup.1H NMR (400 MHz, DMSO) 9.90 (s, 1H), 9.47 (dd, J = 2.1, 0.8 Hz, 1H), 8.67-8.60 (m, 2H), 8.15 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 2.7 Hz, 1H), 7.88-7.81 (m, 2H), 7.57- 7.49 (m, 2H), 7.44 (d, J = 8.7 DMSO >98 G1 (0.1N HCl added) Hz, 1H), 3.98 (s, 3H), 3.47 (s, 3H). 510 037 038 039 .sup.1H NMR (400 MHz, DMSO) 10.76 (s, 1H), 10.62 (s, 1H), 9.71 (s, 1H), 9.53-9.48 (m, 1H), 8.68-8.62 (m, 2H), 7.98 (d, J = 2.6 Hz, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.63 (d, J = 1.8 Hz, 1H), 7.55-7.49 (m, 2H), 7.37 (dd, J = 8.4, DMSO >98 G1 (0.1N HCl added) 2.0 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 3.97 (s, 3H). 511 040 041 042 .sup.1H NMR (400 MHz, DMSO) 9.96 (s, 1H), 9.49 (dd, J = 2.1, 0.8 Hz, 1H), 8.79 (s, 1H), 8.67-8.61 (m, 2H), 8.39-8.36 (m, 1H), 8.02 (d, J = 2.7 Hz, 1H), 7.90- 7.84 (m, 3H), 7.56 (dd, J = 9.1, 2.7 Hz, 1H), 7.54-7.50 (m, 1H), 3.99 (s, 3H). DMSO >98 J2 512 043 044 045 .sup.1H NMR (400 MHz, DMSO) 9.87 (s, 1H), 9.48 (dd, J = 2.1, 0.8 Hz, 1H), 8.67-8.61 (m, 2H), 8.10- 8.08 (m, 1H), 8.00 (d, J = 2.7 Hz, 1H), 7.84 (d, J = 9.1 Hz, 1H), 7.65- 7.63 (m, 2H), 7.57- DMSO >98 G1 7.49 (m, 2H), 4.22 (s, 3H), 3.99 (s, 3H). 513 046 047 048 .sup.1H NMR (100 MHz, DMSO) 9.92 (s, 1H), 9.49 (dd, J = 2.1, 0.8 Hz, 1H)( 8.67-8.60 (m, 2H), 8.22 (d, J = 1.8 Hz, 1H), 8.00 (d, J = 2.7 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.70-7.64 (m, 1H), DMSO >98 J2 7.60 (d, J = 8.5 Hz, 1H), 7.57-7.49 (m, 2H), 4.21 (s, 3H), 3.98 (s, 3H). 514 049 050 051 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.97 (s, 1H), 9.43 (d, J = 1.6 Hz, 1H), 8.98-8.91 (m, 1H), 8.89 (dd, J = 5.2, 1.3 Hz, 1H), 8.43 (s, 1H), 8.27 (s, 1H), 8.13-8.04 (m, 2H), 7.92-7.85 (m, 1H), 7.73 (d, J = DMSO >98 G1 9.2 Hz, 1H), 7.70- 7.63 (m, 2H), 4.21 (s, 3H), 4.02 (s, 3H). 515 052 053 054 HCl .sup.1H NMR (400 MHz, DMSO) 11.90 (s, 1H), 10.45 (s, 1H), 9.46 (d, J = 1.7Hz, 1H), 8.97- 8.89 (m, 1H), 8.85 (dd, J = 5.2, 1.5 Hz, 1H), 8.16- 8.10 (m( 2H), 8.03-7.97 (m, 2H), 7.94 (d, J = 9.1 Hz, 1H), 7.90- DMSO >98 G1 (0.1N HCl added) 7.82 (m, 1H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 6.58 (d, J = 9.4 Hz, 1H), 4.00 (s, 3H). 516 055 056 057 .sup.1H NMR (400 MHz, DMSO) 9.90 (s, 1H), 9.53-9.50 (m, 1H), 8.68-8.63 (m, 2H), 8.27 (d, J = 2.0 Hz, 1H) (8.01 (d, J = 2.7 Hz, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.81 DMSO >98 G1 (dd, J = 8.7, 2.1 Hz, 1H), 7.58- 7.50 (m, 2H), 4.20 (s, 3H), 3.99 (s, 3H). 517 058 059 060 HCl .sup.1H NMR (300 MHz, DMSO) 11.35 (s, 1H), 9.58 (d, J = 1.6 Hz, 1H), 9.24 (d, J = 8.2 Hz, 1H), 9.05- 8.97 (m, 1H), 9.05-8.95 (m, 1H), 8.21 (d, J = 2.4 Hz, 1H), 8.11-8.02 (m, 3H), 7.90 (d, DMSO >98 G1 J = 7.8 Hz, 1H), 7.58 (dd, J =8.8, 2.0 Hz, 2H), 7.52- 7.46 (m, 1H), 7.28 (s, 1H), 3.98 (d, J = 9.2 Hz, 3H). 518 061 062 063 2 HCl .sup.1H NMR (300 MHz, DMSO) 11.32 (s, 1H), 9.60 (s, 1H),9.23 (d, J = 8.0 Hz, 1H), 8.98 (d, J = 5.4 Hz, 1H), 8.26 (s, 1H), 8.06 (dd, J = 13.2, 7.3 Hz, 2H), 7.63 (d, J = 9.1 Hz, 1H), 7.50- DMSO >98 G1 7.36 (m, 4H), 7.32 (s, 1H), 7.06- 6.90 (m, 1H), 3.99 (s, 3H), 3.86 (s, 3H). 519 064 065 066 2 HCl 1H NMR (400 MHz, DMSO) 11.90 (s, 1H), 10.45 (s, 1H), 9.46 (d( J = 1.7 Hz, 1H), 8.97- 8.89 (m, 1H), 8.85 (66, J = 5.2, 1.5 Hz, 1H), 8.16- 8.10 (m( 2H), 8.03-7.97 (m, 2H), 7.94 (d, J = 9.1 Hz, 1H), 7.90-7.82 (m, 1H), 7.63 (dd, J = DMSO >98 G1 9.1, 2.6 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 6.58 (d, J = 9.4 Hz, 1H), 4.00 (s, 3H). 520 067 068 069 HCl .sup.1H NMR (400 MHz, DMSO) 9.90 (s, 1H), 9.53-9.50 (m, 1H), 8.68- 8.63 (m, 2H), 8.27 (d, J = 2.0 Hz, 1H), 8.01 (d, J = 2.7 Hz, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.81 DMSO >98 G1 (dd, J = 8.7, 2.1 Hz, 1H), 7.58- 7.50 (m, 2H), 4.20 (s, 3H), 3.99 (s, 3H). 521 070 071 072 HCl .sup.1H NMR (300 MHz, DMSO) 11.35 (s( 1H)( 9.58 (d, J = 1.6 Hz, 1H), 9.24 (d, J = 8.2 Hz, 1H), 9.05-8.97 (m, 1H), 9.05-8.95 (m, 1H), 8.21 (d, J = 2.4 Hz, 1H), 8.11- 8.02 (m, 3H), 7.90 (d, J = 7.8 Hz, 1H), 7.58 (dd, J = 8.8, 2.0 Hz, 2H), DMSO >98 G1 7.52-7.46 (m, 1H), 7.28 (s, 1H), 3.98 (d, J = 9.2 Hz, 3H). 1758 073 074 075 3 HCl 1H NMR (300 MHz, DMSO) 11.32 (s, 1H), 9.60 (s, 1H), 9.23 (d, J = 8.0 Hz, 1H), 8.98 (d, J = 5.4 Hz, 1H), 8.26 (s, 1H), 8.06 (dd, J = 13.2, 7.3 Hz, 2H), 7.63 (d, J = 9.1 Hz, 1H), 7.50-7.36 (m, 4H), 7.32 (s, 1H), 7.06- 6.90 (m, 1H), 3.99 (s, 3H), 3.86 (s, 3H). DMSO >98 G13 1759 076 077 078 3 HCl 1H NMR (DMSO- d6) ppm 10.35 (br, 1H), 9.37 (d, J = 1.6 Hz, 1H), 8.96 (d, J = 7.28 Hz, 1H), 8.90 (d, J = 4.2 Hz, 1H), 8.04 (s, 1H), 7.98 (m, 1H), 7.95 (d, J = 9.16 Hz, 1H), 7.64 (dd, J = 9.16, 2.56 Hz, 1H), 6.18 (s, 1H), 3.98 (s, 3H), 3.66 (s, 3H), 2.24 (s, 3H). The DMSO >98 J2 1H of 3HCl was not observed.

(192) ##STR01079## ##STR01080##

(193) ##STR01081## ##STR01082##

(194) Method K: 2-Amino-5-methoxybenzoic acid (viii-a) 5-Methoxy-2-nitrobenzoic acid (30.0 g, 152.2 mmol) was hydrogenated over Pd/C (10%, 300 mg) in THF (250 mL) at room temperature under H.sub.2 balloon. The mixture was stirred for 18 h. After the reaction was completed, the catalyst was removed by filtration over Celite and the filtrate was concentrated to afford 25.0 g of 2-amino-5-methoxybenzoic acid as a brown solid (98%). LCMS m/z=168.1 (M+1), 150.1 (M-17) (Method B) (retention time=0.53 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 7.31 (d, J=2.8 Hz, 1H), 6.61 (dd, J=8.8, 3.2 Hz, 1H), 6.44 (d, J=8.8 Hz, 1H), 3.60 (s, 3H).

(195) Method H: 6-Methoxyquinazoline-2,4(1H, 3H)-dione (ix-a) 2-Amino-5-methoxybenzoic acid (13.0 g, 77.8 mmol, 1.0 eq.) was suspended in water (200 mL) and glacial acetic acid (5.2 mL) at 35 C. A freshly prepared solution of potassium cyanate (8.21 g, 101.4 mmol, 1.3 eq.) in water (86 mL) was added dropwise to the stirred mixture. After 4 h, NaOH (104.0 g, 2600 mL, 33.4 eq.) was added in portions, keeping the reaction temperature below 40 C. A clear solution was obtained momentarily before a precipitate formed. After cooling, the precipitate was filtered off and dissolved in hot water which was acidified to pH 5. The precipitate was collected and washed with water, dried by lyophilization to afford 9.63 g of 6-methoxyquinazoline-2, 4(1H, 3H)-dione as a white solid (65%). LCMS m/z=193.1 (M+1) (Method B) (retention time=1.22 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.26 (s, 1H), 11.01 (s, 1H), 7.31-7.25 (m, 2H), 7.10 (d, 1H, J=8.8 Hz), 3.77 (s, 3H).

(196) Method F1: 2,4-Dichloro-6-methoxyquinazoline (x-a) To a mixture of 6-methoxyquinazoline-2,4(1H, 3H)-dione (9.63 g, 50.2 mmol) in POCl.sub.3 (150 mL) was added N,N-dimethylaniline (0.5 mL). The resulting mixture was stirred at 120 C. for 2 h. After the reaction was completed, POCl.sub.3 was removed in vacuo, and the residue was added to ice-water slowly. The pH was adjusted to 7 by slowly adding NaHCO.sub.3 (sat.) at 0 C., then a precipitate formed. The solid was collected and dried in vacuo to give 11.2 g of 2,4-dichloro-6-methoxyquinazoline in a 98% yield as a brown solid. LCMS m/z=229.1, 231.0 (M+1) (Method B) (retention time=1.87 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 7.89 (d, J=9.2 Hz, 1H), 7.71 (dd, J=8.8, 2.4 Hz, 1H), 7.38 (d, J=1.6 Hz, 1H), 3.91 (s, 3H).

(197) Method M: 2-Chloro-6-methoxyquinazolin-4-ol (xi-a) A mixture of 2,4-dichloro-6-methoxyquinazoline (4.20 g, 18.5 mmol, 1.0 eq.) in THF (60 mL) and H.sub.2O (60 mL) was treated with NaOH (4.00 g, 100 mmol, 5.4 eq.). The resulting mixture was stirred at 40 C. for 2 h. The reaction color turned to dark green and then a precipitate formed. After the reaction was completed, the mixture was cooled to room temperature. The precipitate was filtered off and the filtrate was concentrated down to 60 mL. The pH was then adjusted to 6 by adding 2N HCl in water. The precipitate which formed was collected and dried in vacuo to give 4.00 g of 2-chloro-6-methoxyquinazolin-4-ol as a grey solid (98%). LCMS m/z=211.1, 213.0 (M+1) (Method B) (retention time=1.11 min)

(198) Method N: 6-Methoxy-2-(pyridin-3-yl) quinazolin-4-ol (xii-a) To a mixture of 2-chloro-6-methoxyquinazolin-4-ol (1.20 g, 5.7 mmol, 1.0 eq.), pyridin-3-ylboronic acid (1.27 g, 8.6 mmol, 1.5 eq.), K.sub.2CO.sub.3 (2.37 g, 17.1 mmol, 3.0 eq.) in dioxane (100 mL) and H.sub.2O (10 mL) was added Pd(PPh.sub.3).sub.2Cl.sub.2 (230 mg, 0.29 mmol, 0.05 eq.) under N.sub.2 atmosphere. The resulting mixture was stirred at 105 C. under N.sub.2 atmosphere overnight. After reaction was completed, the mixture was cooled to room temperature, and the resultant precipitate was removed by filtration. The filtrate was concentrated in vacuo and the residue was partitioned between H.sub.2O (30 mL) and ethyl acetate (100 mL3). The combined organic layers were washed with brine, dried over MgSO.sub.4. After filtration and evaporation, the crude product was obtained, which was combined with the filter cake and dried in vacuo to give 1.35 g of 6-methoxy-2-(pyridin-3-yl) quinazolin-4-ol as a gray solid. LCMS m/z=254.1 (M+1) (Method B) (retention time=1.39 min) The crude product was used for the next step without further purification.

(199) Method F1: 4-Chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (xiii-a) To a mixture of 6-methoxy-2-(pyridin-3-yl) quinazolin-4-ol (600 mg, 2.37 mmol) in POCl.sub.3 (5 mL) was added N,N-dimethylaniline (1 drop). The resulting mixture was stirred at 120 C. for 30 min After the reaction was completed, POCl.sub.3 was removed in vacuo, and the residue was added to ice-water slowly. The pH was adjusted to 7 by slowly adding NaHCO.sub.3 (sat.) at 0 C. and then a precipitate formed. The solid was collected and was purified by chromatography on silica gel eluted with petroleum ether/ethyl acetate (v/v=4:1 to 1:1) to give 260 mg of 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline as a pale yellow solid (40.4%). LCMS m/z=272.1, 274.0 (M+1) (Method B) (retention time=1.90 min)

(200) Method G1: N-(2-Fluorophenyl)-6-methoxy-2-(pyridin-3-yl)quinazolin-4-amine (xiv-a) A mixture of 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (80 mg, 0.293 mmol, 1.0 eq.) and 2-fluoroaniline (65 mg, 0.58 mmol, 2 eq.) in i-PrOH (5 mL) was stirred at 85 C. for 18 h. After the reaction was completed, the mixture was filtered, and the filter cake was washed with H.sub.2O (10 mL) and diethyl ether (10 mL). After drying, the crude product was purified by PREP-HPLC (Condition C: Gradient: B=5%-50%, Target Peak: at 7.2 min) to give 16.5 mg of N-(2-fluorophenyl)-6-methoxy-2-(pyridin-3-yl)quinazolin-4-amine as a yellow solid, yield 16.4%. LCMS m/z=347.0 (M+1) (Method A) (retention time=1.31 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.08 (s, 1H), 9.33 (s, 1H), 8.72 (d, J=4.4 Hz, 1H), 8.66 (d, J=8.0 Hz, 1H), 8.80 (d, J=1.2 Hz, 1H), 7.88 (d, J=9.2 Hz, 1H), 7.70-7.65 (m, 2H), 7.58 (dd, J=8.8, 1.2 Hz, 1H), 7.44-7.35 (m, 3H), 3.97 (s, 3H).

(201) The compounds in the following table were prepared in a manner analogous to that described in Scheme 6 substituting with appropriate nitro benzoic acid, boronic acid and aniline

(202) TABLE-US-00005 TABLE 2 Mole- .sup.1H Purity Method Num- Salt cular NMR LCMS per- for ber Product type Mass .sup.1H-NMR Solvent LCMS Protocol cent Coupling 522 083 455.34 1H-NMR (400 MHz, DMSO- d6): 9.76 (s, 1H), 9.52-9.51 (m, 1H), 8.63- 8.66 (m, 2H), 8.32 (d, J = 2.4 Hz, 1H), 7.94- 7.91 (m, 2H), 7.72 (d, J = 8.8 Hz, 1H), 7.54 (q, J = 3.2 Hz, 1H), 7.32 (s, 1H), 4.87-4.90 (m, 1H), 3.96 (s, 3H), 1.38 (d, J = 6.0 Hz, 6H). DMSO 454.9, 457.0 (M + 1), 228.8 (M/2 + 1) Method A (TFA) 95 Method N, G1 523 084 438.88 1H-NMR (400 MHz, DMSO- d6): 9.68 (s, 1H), 9.49 (d, J = 2.0 Hz, 1H), 8.60-8.66 (m, 2H), 8.18 (dd, J = 6.4, 2.4 Hz, 1H), 7.84- 7.88 (m, 2H), 7.50-7.54 (m, 2H), 7.31 (s, 1H), 4.85-4.88 (m, 1H), 3.96 (s, 3H), 1.38 (d, J = 6.4 Hz, 6H). DMSO 439.1, 441.1 (M + 1), 220.1, 220.8 (M/2 + 1) Method A (TFA) 95 Method N,G1 524 085 422.43 1H-NMR (400 MHz, DMSO- d6): 9.76 (s, 1H), 9.48 (s, 1H), 8.60-8.65 (m, 2H), 8.04- 8.10 (m, 1H), 7.92 (s, 1H), 7.49-7.66 (m, 3H), 7.30 (s, 1H), 4.86-4.92 (m, 1H), 3.96 (s, 3H), 1.37 (d, J = 6.0 Hz, 6H) DMSO 423.2 (M + 1), 212.2 (M/2 + 1) Method A (TFA) 95 Method N, G1 525 086 HCl 429.47 1H-NMR (400 MHz, DMSO- d6): 12.96 (s, 1H), 9.60 (d, J = 8.0 Hz, 1H), 8.68-8.74 (m, 2H), 8.46 (s, 1H), 7.95-7.96 (m, 2H), 7.74- 7.70 (m, 1H), 7.59-7.54 (m, 2H), 7.36 (s, 1H), 7.19-7.15 (m, 1H), 4.76- 4.82 (m, 1H), 3.99 (s, 3H), 1.44 (d, J = 6.0 Hz, 6H). DMSO 430.2 (M + 1) 215.7 (M/2 + 1) Method A (TFA) 95 Method N, G1 526 087 452.45 1H-NMR (400 MHz, DMSO- d6): 9.70 (s, 1H), 9.52-9.53 (m, 1H), 8.64- 8.67 (m, 2H), 7.89-7.94 (m, 2H), 7.73-7.74 (m, 1H), 7.48- 7.53 (m, 3H), 7.32 (t, J = 83.6 Hz, 1H), 6.96- 6.99 (m, 1H), 4.89-4.92 (m, 1H), 3.98 (s, 3H), 1.38 (d, J = 6.0 Hz, 6H). DMSO 453.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 527 088 455.34 1H-NMR (400 MHz, DMSO- d6): 9.53 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 8.64-8.68 (m, 2H), 8.12-8.13 (m, 2H), 7.90 (s, 1H), 7.54- 7.58 (m, 1H), 7.34-7.36 (m, 2H), 4.86-4.92 (m, 1H), 3.98 (s, 3H), 1.40 (d, J = 6.0 Hz, 6H). DMSO 455.0, 457.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 528 089 455.34 1H-NMR (400 MHz, DMSO- d6): 9.76 (s, 1H), 9.52 (d, J = 1.2 Hz, 1H), 8.64-8.67 (m, 2H), 8.32 (d, J = 2.8 Hz, 1H), 7.94 (dd, J = 8.8, 2.4 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.53- 7.56 (m, 1H), 7.32 (s, 1H), 4.14 (t, J = 6.4 Hz, 2H), 3.99 (s, 3H), 1.85- 1.92 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H). DMSO 455.1, 457.1 (M + 1) 229.1 (M/2 + 1) Method A (TFA) 95 Method N, G1 529 090 438.88 1H-NMR (400 MHz, DMSO- d6): 9.72 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.62-8.66 (m, 2H), 8.20 (dd, J = 6.4, 2.4 Hz, 1H), 7.85-7.89 (m, 2H), 7.50-7.55 (m, 2H), 7.31 (s, 1H), 4.13 (t, J = 6.4 Hz, 2H), 3.98 (s, 3H), 1.82-1.90 (m, 2H), 1.06 (t, J = 7.6 Hz, 3H). DMSO 439.1, 441.1 (M + 1) 220.1, 220.8 (M/2 + 1) Method A (TFA) 95 Method N, G1 530 091 422.43 1H-NMR (400 MHz, DMSO- d6): 9.74-9.76 (m, 1H), 9.52 (d, J = 1.6 Hz, 1H), 8.64-8.69 (m, 2H), 8.08- 8.14 (m, 1H), 7.90 (s, 1H), 7.68-7.70 (m, 1H), 7.52-7.60 (m, 2H), 7.34 (s, 1H), 4.16 (t, J = 6.4 Hz, 2H), 4.01 (s, 3H), 1.85-1.94 (m, 2H), 1.09 (t, J = 7.2 Hz, 3H). DMSO 423.0 (M + 1) 445.0 (M + 23) 212.1 (M/2 + 1) Method A (TFA) 95 Method N, G1 531 092 HCl 429.47 1H-NMR (400 MHz, DMSO- d6): 12.86 (s, 1H), 9.59 (d, J = 1.6 Hz, 1H), 9.05 (d, J = 8.4 Hz, 1H), 8.85 (d, J = 8.0 Hz, 1H), 8.76-8.78 (m, 1H), 8.44 (s, 1H), 7.96 (dd, J = 8.0, 1.6 Hz, 2H), 7.70-7.73 (m, 2H), 7.53 (s, 1H), 7.37 (s, 1H), 6.96-7.22 (m, 1H), 4.16 (t, J = 6.4 Hz, 2H), 4.01 (s, 3H), 1.86-1.90 (m, 2H), 1.07 (t, J = 7.2 Hz, 3H). DMSO 430.1 (M + 1) Method B (NH4CO3) 95 Method N, G1 532 093 452.45 1H-NMR (400 MHz, DMSO- d6): 9.67 (s, 1H), 9.50 (d, J = 4.0 Hz, 1H), 8.62-8.65 (m, 2H), 7.89-7.92 (m, 3H), 7.44- 7.54 (m, 1H), 7.29-7.31 (m, 3H), 7.26 (t, J = 74.0 Hz, 1H), 4.14 (t, J = 6.8 Hz, 2H), 3.98 (s, 3H), 1.84- 1.90 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H). DMSO 453.1 (M + 1) 227.2 (M/2 + 1) Method A (TFA) 95 Method N, G1 533 094 HCl 454.88 1H-NMR (400 MHz, DMSO- d6): 9.73 (s, 1H), 9.50 (d, J = 2.4 Hz, 1H), 8.62-8.67 (m, 2H), 8.20 (dd, J = 7.2 Hz, 2.8 Hz, 1H), 7.85- 7.89 (m, 2H), 7.51-7.57 (m, 2H), 7.33 (s, 1H), 4.31 (t, J = 4.0 Hz, 2H), 3.99 (s, 3H) 3.80 (t, J = 4.8 Hz, 2H), 3.37 (s, 3H). DMSO 455.1, 457.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 534 095 445.47 1H-NMR (400 MHz, CD3OD): 9.34 (s, 1H), 8.92 (d, J = 6.0 Hz, 1H), 8.73 (m, 2H), 7.84 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.15 (s, 2H), 4.21 (s, 2H), 3.92 (s, 3H), 3.78 (t, J = 4.4 Hz, 2H), 3.40 (s, 3H). CD3OD 446.2, 447.2 (M + 1) Method B (NH4HCO3) 95 Method N, G1 535 096 HCl 468.45 1H-NMR (400 MHz, DMSO- d6): 9.72 (s, 1H), 9.53 (s, 1H), 8.66 (d, J = 5.6 Hz, 2H), 7.91 (d, J = 6.4 Hz, 2H), 7.75 (d, J = 7.2 Hz, 1H), 7.51 (dd, J = 7.6 Hz, 2H), 7.34 (s, 1H), 7.30 (t, J = 74.0 Hz, 1H), 6.97 (dd, J = 8.0, 2.0 Hz, 1H), 4.32 (t, J = 4.4 Hz, 2H), 3.99 (s, 3H), 3.80 (t, J = 4.4 Hz, 2H), 3.37 (s, 3H). DMSO 469.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 536 097 468.91 1H-NMR (400 MHz, DMSO- d6): 10.42 (s, 1H), 9.47 (s, 1H), 8.96 (d, J = 6.4 Hz, 1H), 8.90 (d, J = 5.2 Hz, 1H), 8.11 (dd, J = 6.8 Hz, 2.4 Hz, 1H), 8.05 (s, 2H), 7.85- 7.94 (m, 2H), 7.55 (t, J = 9.2 Hz, 1H), 7.47 (s, 1H), 4.26 (t, J = 6.4 Hz, 2H), 4.01 (s, 3H), 3.55 (t, J = 6.0 Hz, 2H), 3.29 (s, 3H), 2.06-2.13 (m, 2H). DMSO 469.0, 471.0 (M + 1) 234.9, 235.6 (M/2 + 1) Method A (TFA) 95 Method N, G1 537 098 397.26 1H-NMR (400 MHz, DMSO- d6): 10.08 (s, 1H), 9.54 (s, 1H), 8.76 (s, 2H), 8.49 (d, J = 7.0 Hz, 1H), 8.36 (s, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.66- 7.23 (m, 2H), 7.33 (s, 2H), 3.98 (s, 3H). DMSO 397.1, 399.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 538 099 397.26 1H-NMR (400 MHz, DMSO- d6): 10.00 (s, 1H), 8.54 (d, J = 1.3 Hz, 1H), 8.71-8.56 (m, 2H), 8.47 (d, J = 9.2 Hz, 1H), 8.17 (s, 1H), 8.16 (s, 1H), 7.59-7.56 (m, 1H), 7.35-7.30 (m, 3H), 3.98 (s, 3H). DMSO 397.0, 399.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 539 00 364.35 1H-NMR (400 MHz, DMSO- d6): 9.94 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.70-8.65 (m, 2H), 8.47 (d, J = 8.4 Hz, 1H), 8.12 (ddd, J = 13.2, 7.6, 2.8 Hz, 1H), 7.72-7.70 (m, 1H), 7.58-7.49 (m, 2H), 7.32- 7.27 (m, 2H), 3.97 (s, 3H). DMSO 365.2 (M + 1) Method B (NH4HCO3) 95 Method N, G1 540 01 353.38 1H-NMR (400 MHz, DMSO- d6): 10.06 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.71-8.66 (m, 2H), 8.50-8.43 (m, 2H), 8.26- 8.24 (m, 1H), 7.70-7.54 (m, 3H), 7.34-7.30 (m, 2H), 3.98 (s, 3H). . DMSO 354.2 (M + 1) Method B (NH4HCO3) 95 Method N, G1 541 02 394.37 1H-NMR (400 MHz, DMSO- d6): 9.93 (s, 1H), 9.54 (s, 1H), 8.68 (d, J = 5.2 Hz, 2H), 8.51 (d, J = 9.2 Hz, 1H), 7.96 (s, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.55-7.10 (m, 5H), 6.96 (dd, J = 8.0, 2.0 Hz, 1H), 3.96 (s, 3H). DMSO 395.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 542 03 371.39 1H-NMR (400 MHz, DMSO- d6): 12.97 (s, 1H), 9.60 (s, 1H), 9.10 (d, J = 8.4 Hz, 1H), 8.75-8.71 (m, 2H), 8.48 (s, 1H), 8.07 (d, J = 9.6 Hz, 1H), 7.95-7.90 (m, 2H), 7.74- 7.70 (m, 1H), 7.58 (dd, J = 8.0, 4.8 Hz, 1H), 7.35-7.33 (m, 2H), 7.19 (t, J = 7.2 Hz, 1H), 3.97 (s, 3H). DMSO 372.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 543 04 431.7 1H-NMR (400 MHz, DMSO- d6): 10.03 (s, 1H), 9.49-9.48 (m, 1H), 8.69- 8.67 (m, 1H), 8.63-8.59 9m, 1H), 8.31 (d, J = 2.4 Hz, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.93-7.90 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.56-7.53 (m, 1H), 4.07 (s, 3H). DMSO 430.9, 432.9, 434.9 (M + 1) Method B (NH4HCO3) 95 Method N, G1 544 05 431.7 1H-NMR (400 MHz, DMSO- d6): 9.94 (s, 1H), 9.46 (d, J = 3.2 Hz, 1H), 8.68 (dd, J = 4.8, 2.0 Hz, 1H), 8.60-8.57 (m, 1H), 8.09 (s, 1H), 8.08 (s, 1H), 7.97 (s, 2H), 7.54 (dd, J = 8.8, 4.8 Hz, 1H), 7.38 (t, J = 2.0 Hz, 1H), 4.05 (s, 3H). DMSO 430.9, 432.9, 434.9 (M + 1) Method B (NH4HCO3) 95 Method N, G1 545 06 415.25 1H-NMR (400 MHz, DMSO- d6): 10.02 (s, 1H), 9.47 (s, 1H), 8.70-8.62 (m, 2H), 8.19- 8.17 (m, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.84-7.88 (m, 1H), 7.59-7.53 (m, 2H), 4.07 (s, 3H). DMSO 415.1, 417.0, 419.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 546 07 398.79 1H-NMR (400 MHz, DMSO- d6): 10.01 (s, 1H), 9.47 (d, J = 1.6 Hz, 1H), 8.69-8.67 (m, 1H), 8.62-8.59 (m, 1H), 8.08- 8.04 (m, 2H), 8.00 (s, 1H), 7.65-7.53 (m, 3H), 4.07 (s, 3H). DMSO 399.1, 401.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 547 08 428.82 1H-NMR (400 MHz, DMSO- d6): 10.32 (s, 1H), 9.45 (d, J = 1.2 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.83 (d, J = 4.0 Hz, 1H), 8.21 (s, 1H), 8.00 (s, 1H), 7.85-7.78 (m, 3H), 7.55- 7.51 (m, 1H), 7.31 (t, J = 72.8 Hz, 1H), 7.05- 7.03 (m, 1H), 4.07 (s, 3H). DMSO 429.1, 431.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 548 09 387.82 1H-NMR (400 MHz, DMSO- d6): 10.62 (s, 1H), 9.38 (s, 1H), 8.97-8.90 (m, 2H), 8.32- 8.26 (m, 3H), 7.97-7.94 (m, 2H), 7.69-7.65 (m, 2H), 4.08 (s, 3H). DMSO 387.9, 390.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 549 0 405.84 1H-NMR (400 MHz, DMSO- d6): 12.98 (s, 1H), 9.36 (s, 1H), 8.94-8.77 (m, 3H), 8.48 (s, 1H), 7.98-7.83 (m, 4H), 7.59- 7.14 (m, 2H), 7.17 (s, 1H), 3.96 (s, 3H). DMSO 405.9, 408.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 550 436.12 1H-NMR (400 MHz, DMSO- d6): 10.24 (s, 1H), 9.39 (s, 1H), 8.87 (s, 1H), 8.81 (d, J = 4.4 Hz, 1H), 8.73 (d, J = 8.0 Hz, 1H), 8.24 (s, 1H), 8.01 (s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.76-7.73 (m, 1H), 7.66 (d, J = 8.8 Hz, 1H). DMSO 434.9, 436.9, 438.8 (M + 1) Method B (NH4HCO3) 95 Method N, G1 551 410.26 1H-NMR (400 MHz, DMSO- d6): 13.15 (s, 1H), 9.46 (s, 1H), 8.87 (d, J = 8.4 Hz, 1H), 8.74 (d, J = 3.6 Hz, 1H), 8.68 (d, J = 7.2 Hz, 1H), 8.49 (s, 1H), 8.23 (s, 1H), 8.02 (s, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.69- 7.61 (m, 2H), 7.23-7.20 (m, 1H). DMSO 410.0, 412.0, 413.9 (M + 1) 432.0 (M + 22) Method A (TFA) 95 Method N, G1 552 433.24 1H-NMR (400 MHz, DMSO- d6): 10.30 (s, 1H), 9.53 (s, 1H), 9.02 (s, 1H), 8.83-8.80 (m, 2H), 8.20 (s, 1H), 7.91 (s, 1H), 7.81- 7.79 (m, 1H), 7.74-7.71 (m, 1H), 7.56-7.52 (m, 1H), 7.30 (t, J = 73.6 Hz, 1H), 7.05 (d, J = 8.8 Hz, 1H). DMSO 432.9, 434.9 (M + 1) Method B (NH4HCO3) 95 Method N, G1 553 419.67 1H-NMR (400 MHz, DMSO- d6): 10.43 (s, 1H), 9.40 (s, 1H), 8.97 (s, 1H), 8.89-8.85 (m, 2H), 8.15- 8.14 (m, 1H), 8.05 (s, 1H), 7.89-7.87 (m, 2H), 7.51-7.47 (m, 1H). DMSO 419.0, 421.0, 423.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 554 403.21 1H-NMR (400 MHz, DMSO- d6): 10.39 (s, 1H), 9.40 (s, 1H), 8.96 (s, 1H), 8.84-8.89 (m, 2H), 8.04- 8.00 (m, 2H), 7.88 (s, 1H), 7.69-7.67 (m, 1H), 7.54-7.47 (m, 1H). DMSO 402.9, 404.9 (M + 1) Method B (NH4HCO3) 95 Method N, G1 555 436.12 1H-NMR (400 MHz, DMSO- d6): 10.26 (s, 1H), 8.28 (s, 1H), 8.88 (d, J = 4.8 Hz, 1H), 8.85 (s, 1H), 8.76 (d, J = 8.0 Hz, 1H), 7.97 (s, 1H), 7.96 (s, 1H), 7.90-7.86 (m, 2H), 7.29 (s, 1H). DMSO 434.9, 436.9, 438.9 (M + 1) Method A (TFA) 95 Method N, G1 556 441.31 1H-NMR (400 MHz, DMSO- d6): 9.74 (s, 1H), 9.50 (s, 1H), 8.66-8.64 (m, 2H), 8.31 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.84 (s, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.52 (dd, J = 7.4, 5.0 Hz, 1H), 7.29 (s, 1H), 4.22 (q, J = 6.8 Hz, 2H), 3.97 (s, 3H), 1.45 (t, J = 6.8 Hz, 3H). DMSO 441.0, 443.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 557 424.86 1H-NMR (400 MHz, DMSO- d6): 9.93 (s, 1H), 9.48 (s, 1H), 8.74-8.73 (m, 2H), 8.18- 8.16 (m, 1H), 7.90-7.85 (m, 2H), 7.67-7.65 (m, 1H), 7.53 (t, J = 9 Hz, 1H), 7.33 (s, 1H), 4.24 (q, J = 7.2 Hz, 2H), 3.98 (s, 3H), 7.2 Hz, 2H), 3.98 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H). DMSO 425.0, 427.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 558 408.4 1H-NMR (400 MHz, DMSO- d6): 9.68 (s, 1H), 9.49 (s, 1H), 8.66-8.61 (m, 2H), 8.10- 8.04 (m, 1H), 7.84 (s, 1H), 7.66-7.64 (m, 1H), 7.56-7.49 (m, 2H), 7.30 (s, 1H), 4.23 (q, J = 6.8 Hz, 2H), 3.98 (s, 3H), 1.46 (t, J = 6.8 Hz, 3H). DMSO 409.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 559 0 397.43 1H-NMR (400 MHz, DMSO- d6): 10.67 (s, 1H), 9.43 (s, 1H), 8.82-8.78 (m, 2H), 8.32 (s, 1H), 8.23 (d, J = 7.6 Hz, 1H), 7.98 (s, 1H), 7.77-7.73 (m, 1H), 7.68-7.60 (m, 2H), 7.35 (s, 1H), 4.23 (q, J = 6.8 Hz, 2H), 3.96 (s, 3H), 1.44 (t, J = 6.8 Hz, 3H). DMSO 398.1 (M + 1) Method B (NH4HCO3) 95 Method N, G1 560 410.83 1H-NMR (400 MHz, DMSO- d6): 9.89 (s, 1H), 9.48 (s, 1H), 8.74 (d, J = 6.0 Hz, 2H), 8.16 (dd, J = 6.8, 2.4 Hz, 1H), 7.85- 7.88 (m, 2H), 7.67 (t, J = 6.4 Hz, 1H), 7.53 (t, J = 8.7 Hz, 1H), 7.32 (s, 1H), 3.98 (s, 6H). DMSO 411.1, 413.1 (M + 1) Method A (TFA) 95 Method N, G1 561 394.37 1H-NMR (400 MHz, DMSO- d6): 9.92 (s, 1H), 9.49 (s, 1H), 8.77 (d, J = 6.4 Hz, 2H), 8.02- 8.08 (m, 1H), 7.90 (s, 1H), 7.70-7.74 (m, 1H), 7.64-7.66 (m, 1H), 7.52- 7.59 (m, 1H), 7.33 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H). DMSO 395.0 (M + 1), 198.1 (M/2 + 1) Method A (TFA) 95 Method N, G1 562 383.4 1H-NMR (400 MHz, DMSO- d6): 9.87 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.63-8.68 (m, 2H), 8.38 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.89 (s, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.52- 7.56 (m, 1H), 7.33 (s, 1H), 4.00 (s, 3H), 3.98 (s, 3H). DMSO 384.2 (M + 1) Method B (NH4HCO3) 95 Method N, G1 563 427.28 1H-NMR (400 MHz, DMSO- d6): 9.70 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.66 (d, J = 4.8 Hz, 1H), 8.62 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 1.2 Hz, 2H), 7.79 (s, 1H), 7.53 (dd, J = 7.6, 4.8 Hz, 1H), 7.31 (s, 1H), 7.28 (s, 1H), 3.97 (s, 6H). DMSO 427.1, 429.1, 431.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 564 2HCl 389.3824 1H-NMR (400 MHz, DMSO- d6): 13.08 (s, 1H), 9.40 (s, 1H), 8.86 (d, J = 8.1 Hz, 1H), 8.78 (s, 1H), 8.53 (d, J = 10.0 Hz, 1H), 8.46 (s, 1H), 8.03 (d, J = 8.7 Hz, 1H), 8.00- 7.88 (m, 2H), 7.73 (t, J = 7.8 Hz, 1H), 7.66 (d, J = 10.3 Hz, 2H), 7.28 (t, J = 7.6 Hz, 1H), 3.99 (s, 3H). DMSO 390.0 (M + 1) Method B (NH4HCO3) 95 Method N, G1 565 2HCl 401.4180 1H-NMR (400 MHz, CD3OD): 9.20 (s, 1H), 8.85 (s, 1H), 8.78 (s, 1H), 8.72 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.77- 7.67 (m, 3H), 7.39 (t, J = 7.6 Hz, 1H), 4.18 (s, 3H), 4.08 (s, 3H). MeOD 402.1 (M + 1) Method B (NH4CO3) 95 Method N, G1

(203) ##STR01127## ##STR01128##

(204) ##STR01129## ##STR01130##
Method O1: CuI/Pd(PPh.sub.3).sub.2Cl.sub.2/Et.sub.3N/DMF/rt O2: Propargyl bromide/CuI/Pd(PPh.sub.3).sub.2Cl.sub.2/Nucleophile/DMF/rt O3: Pd(OAc).sub.2/PPh.sub.3/TBAB/piperdine/THFH.sub.2O/rt

(205) Method O1: 6-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (xv-a) A suspension of N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-iodo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (1.00 g, 2.10 mmol), tert-butyldimethyl(2-propynyloxy)silane (0.85 ml, 4.20 mmol), copper(I) iodide (4.0 mg, 0.021 mmol), dichlorobis(triphenylphosphine) palladium (II) (Pd(PPh.sub.3).sub.2Cl.sub.2) (29 mg, 0.042 mmol), and triethylamine (1.17 ml, 8.39 mmol) in DMF (15 mL) was stirred overnight at room temperature under argon atmosphere. Water (30 mL) and ethyl acetate (30 mL) were added to the mixture. The resultant precipitate was removed by filtration. The filtrate was extracted with EtOAc (250 mL). The combined organic layer was washed with water (1100 mL) and brine (1100 mL) and was dried over Na.sub.2SO.sub.4. After filtration and evaporation, the crude product was obtained, which was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 1:3) to give 0.73 g of 6-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine as light brown solid (67%). LCMS m/z=519 (M+1) (Method D) (retention time=3.22 min). .sup.1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.35 (s, 1H), 8.62-8.44 (m, 3H), 8.11 (dd, J=6.8, 2.6 Hz, 1H), 7.76-7.66 (m, 3H), 7.45-7.30 (m, 2H), 4.48 (s, 2H), 0.75 (s, 9H), 0.16 (s, 6H).

(206) Method P: 6-(3-(tert-butyldimethylsilyloxy)propyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (xvi-a) A suspension of 6-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (0.20 g, 0.39 mmol) and 5% PdSC(40 mg) in EtOAc (5 mL) and MeOH (5 mL) was stirred overnight at room temperature under hydrogen atmosphere. The reaction mixture was filtered through Celite. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 2:3) to give 0.15 g of 6-(3-(tert-butyldimethylsilyloxy)propyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine as yellow solid (74%). LCMS m/z=523 (M+1) (Method D) (retention time=3.35 min). .sup.1H NMR (300 MHz, CDCl.sub.3) 9.69 (dd, J=2.2, 0.8 Hz, 1H), 8.79-8.65 (m, 2H), 8.07 (dd, J=6.5, 2.7 Hz, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.76-7.61 (m, 3H), 7.47-7.37 (m, 2H), 7.31-7.18 (m, 1H), 3.68 (t, J=6.1 Hz, 2H), 3.01-2.83 (m, 2H), 2.03-1.86 (m, 2H), 0.94 (s, 9H), 0.08 (s, 6H).

(207) Method Q: 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propan-1-ol (xvii-a) To a suspension of 6-(3-(tert-butyldimethylsilyloxy)propyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (0.35 g, 0.67 mmol) in MeOH (10 mL) was added 1-chloroethyl chloroformate (7.2 l, 0.067 mmol). The mixture was stirred overnight at room temperature. Methanol was removed in vacuo. Sat. NaHCO.sub.3 aqueous (10 mL) and CH.sub.2Cl.sub.2 (10 mL) were added to the residue and stirred for a while. The resultant solid was collected by filtration and dried to give 0.25 g of 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propan-1-ol as light yellow solid (91%). MS m/z=409 (M+1) (Method D) (retention time=1.71 min). .sup.1H NMR (300 MHz, DMSO) 10.01 (s, 1H), 9.51 (s, 1H), 8.66 (m, 2H), 8.37 (s, 1H), 8.29-8.20 (m, 1H), 7.94-7.67 (m, 3H), 7.63-7.43 (m, 2H), 4.60 (t, J=5.0 Hz, 1H), 3.56-3.35 (m, 2H), 2.94-2.69 (m, 2H), 2.15-1.56 (m, 2H).

(208) Method R: 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate (xviii-a) To a suspension of 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propan-1-ol (0.25 g, 0.61 mmol) and triethylamine (0.17 ml, 1.22 mmol) in CH.sub.2Cl.sub.2 (10 mL) was added methanesulfonyl chloride (0.057 ml, 0.73 mmol). The mixture was stirred at room temperature for 1 h. Water (10 mL) was added to the mixture and stirred for a while. The resultant precipitate was collected by filtration and washed with CH.sub.2Cl.sub.2 and dried to give 0.27 g of 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate as pale yellow solid (91%), which was used without further purification.

(209) Method G4: N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (xviv-a) This method is representative of method G4 and G5. These two methods can be implemented in a similar way except for substitution of the appropriate solvent and temperature) A solution of 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate (40 mg, 82 mmol) and 40% Me.sub.2NH aqueous (1 mL) in methanol (2 mL) was placed in a microwave reaction vial. The mixture was heated under microwave irradiation conditions at 150 C. for 30 minutes after which the solvent was removed in vacuo. The crude product was obtained, which was purified by column chromatography on basic silica gel (eluted with ethyl acetate/methanol 1:0.fwdarw.5:1). The HCl salt generated by 4 M HCl in dioxane was crystallized from 2-propanol to give 10 mg of N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as pale brown powder (24%). LCMS m/z=436 (M+1) (Method C) (retention time=1.68 min). .sup.1H NMR (300 MHz, DMSO) 10.59 (s, 1H), 10.18 (s, 1H), 9.51 (s, 1H), 8.98-8.76 (m, 2H), 8.65 (s, 1H), 8.26 (dd, J=6.8, 2.6 Hz, 1H), 8.05-7.74 (m, 4H), 7.54 (t, J=9.1 Hz, 1H), 3.19-3.03 (m, 2H), 2.97-2.83 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 2.16 (s, 2H).

(210) ##STR01131##

(211) N-(3-chloro-4-fluorophenyl)-6-(3-morpholinoprop-1-ynyl)-2-(pyridin-3-yl) quinazolin-4-amine (xx-a) To a solution of N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-iodo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (2.19 g, 4.6 mmol, 1 eq.), Pd(PPh.sub.3).sub.2Cl.sub.2 (161 mg, 0.23 mmol, 0.05 eq.), CuI (87 mg, 0.46 mmol, 0.1 eq.) in morpholine (15 mL) was added 3-bromoprop-1-yne (814 mg, 6.9 mmol, 1.5 eq.) at 0 C. under Ar atmosphere, following a procedure from Tetrahedron, 2007, 63, 10671-10683. The mixture was stirred at 40 C. overnight. After cooling, the mixture was filtered and methanol (60 mL) was added to the filtrate to form a precipitate. The precipitate was collected and re-crystallized from ethyl acetate twice to afford 1.60 g of xx-a as yellow solid (yield 74%). LCMS m/z=474.1 (M+1), 476.1 (M+3) (Method C) (retention time=1.97 min)

(212) The compounds in the following table were prepared in a manner analogous to that described in Scheme 8 substituting with appropriate nucleophile.

(213) TABLE-US-00006 TABLE 3 Re- ten- Pu- Method Mole- .sup.1H- tion rity for Num- Salt cular NMR Time LCMS per- Coup- ber Product type Mass .sup.1H-NMR Solvent LCMS (Min) Protocol cent ling 566 519.085 1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.35 (s, 1H), 8.62-8.44 (m, 3H), 8.11 (dd, J = 6.8, 2.6 Hz, 1H), 7.76-7.66 (m, 3H), 7.45- 7.30 (m, 2H), 4.48 (s, 2H), 0.75 (s, 9H), 0.00 (s, 6H). DMSO 519 (M + 1) 3.22 Method D 96 Method O1 567 523.117 1H NMR (300 MHz, CDCl3) 9.69 (dd, J = 2.2, 0.8 Hz, 1H), 8.79-8.65 (m, 2H), 8.07 (dd, J = 6.5, 2.7 Hz, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.76-7.61 (m, 3H), 7.47-7.37 (m, 2H), 7.31- 7.18 (m, 1H), 3.68 (t, J = 6.1 Hz, 2H), 3.01- 2.83 (m, 2H), 2.03-1. CDCl3 523 (M + 1) 3.35 Method D 100 Methods O1, P 568 408.856 1H NMR (300 MHz, DMSO) 10.01 (s, 1H), 9.51 (s, 1H), 8.66 (m, 2H), 8.37 (s, 1H), 8.29-8.20 (m, 1H), 7.94-7.67 (m, 3H), 7.63- 7.43 (m, 2H), 4.60 (t, J = 5.0 Hz, 1H), 3.56- 3.35 (m, 2H), 2.94-2.69 (m, 2H), 2.15-1.56 (m, 2H). DMSO 409 (M + 1) 1.71 Method D 100 Methods O1, P, Q 569 2 HCl 508.846 1H NMR (300 MHz, DMSO) 10.59 (s, 1H), 10.18 (s, 1H), 9.51 (s, 1H), 8.98-8.76 (m, 2H), 8.65 (s, 1H), 8.26 (dd, J = 6.8, 2.6 Hz, 1H), 8.05-7.74 (m, 4H), 7.54 (t, J = 9.1 Hz, 1H), 3.19-3.03 (m, 2H), 2.97- 2.83 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 2. DMSO 436 (M + 1) 1.68 Method C 100 Method G4 570 409.841 1H NMR (300 MHz, CDCl3) 9.49 (d, J = 1.4 Hz, 1H), 8.73-8.51 (m, 2H), 8.14 (s, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.81 (dd, J = 8.6, 1.9 Hz, 1H), 7.51-7.13 (m, 4H), 3.77 (dd, J = 11.5, 6.2 Hz, 2H), 3.11-2.86 (m, 2H), 2.16- 1.93 (m, 2H), 1.44 (t, J = 5 CDCl3 410 (M + 1) 1.95 Method D 100 Methods O1, P, Q 571 2 HCl 550.882 1H NMR (300 MHz, DMSO) 10.83-10.37 (m, 2H), 9.51 (s, 1H), 8.97- 8.74 (m, 2H), 8.62 (s, 1H), 8.27 (d, J = 4.2 Hz, 1H), 8.05-7.72 (m, 4H), 7.54 (t, J = 9.0 Hz, 1H), 3.96 (d, J = 12.7 Hz, 2H), 3.76 (t, J = 12.1 Hz, 2H), 3.47 (d, J = 12.0 Hz, 2H), 3.24 DMSO 478 (M + 1) 2.01 Method C 100 Method G4 572 422.882 1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.51 (s, 1H), 8.75-8.60 (m, 2H), 8.37 (s, 1H), 8.26 (dd, J = 6.9, 2.6 Hz, 1H), 7.99-7.88 (m, 1H), 7.88- 7.73 (m, 2H), 7.60-7.46 (m, 2H), 3.39 (dd, J = 8.4, 4.1 Hz, 2H), 3.27 (s, 3H), 2.92-2.78 (m, 2H), 2.05 DMSO 423 (M + 1) 2.09 Method D 100 Method G4 573 HCl 548.909 1H NMR (300 MHz, DMSO) 10.69 (s, 1H), 10.12 (s, 1H), 9.51 (s, 1H), 9.02-8.80 (m, 2H), 8.69 (s, 1H), 8.27 (dd, J = 6.9, 2.7 Hz, 1H), 8.08-7.78 (m, 4H), 7.54 (t, J = 9.1 Hz, 1H), 3.46 (d, J = 10.2 Hz, 2H), 3.17-3.00 (m, 2H), 2.99- 2.75 (m, 4H), 2.3 DMSO 476 (M + 1) 1.79 Method C 100 Method G4 574 0 HCl 500.395 1H NMR (300 MHz, DMSO) 10.68 (s, 1H), 9.49 (s, 1H), 9.12-8.99 (m, 1H), 8.94 (d, J = 3.9 Hz, 1H), 8.58 (d, J = 11.5 Hz, 1H), 8.17 (dd, J = 6.7, 2.6 Hz, 1H), 8.07-7.82 (m, 5H), 7.55 (t, J = 9.1 Hz, 1H), 3.43-3.29 (m, 2H), 3.08- 2.65 (m, 5H), 2.09- DMSO 464 (M + 1) 1.78 Method D 95 Method G4 follow- ed by acyla- tion with acetyl chlo- ride/ TEA/ DCM, rt 575 HCl 600.39 1H NMR (300 MHz, DMSO) 11.79 (s, 1H), 10.81 (s, 1H), 9.50 (s, 1H), 8.98 (d, J = 8.2 Hz, 1H), 8.89 (d, J = 5.0 Hz, 1H), 8.75 (s, 1H), 8.27 (d, J = 4.8 Hz, 1H), 8.10-7.79 (m, 4H), 7.53 (t, J = 9.1 Hz, 1H), 5.18-3.09 (m, 10H), 3.01- 2.69 (m, 5H), 2.37 DMSO 491 (M + 1) 1.76 Method C 100 Method G4 576 473.93 1H NMR (300 MHz, DMSO) 10.17 (s, 1H), 9.52 (s, 1H), 8.70 (s, 1H), 8.66 (d, J = 8.1 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 7.93 (s, 2H), 7.70 (d, J = 8.4 Hz, 1H), 7.61-7.51 (m, 2H), 3.67-3.61 (m, 6H), 2.61- 2.55 (m, 4H). DMSO 473.9 (M + 1) 2.2 Method C 100 Method O1 577 435.92 1H NMR (300 MHz, DMSO) 10.06 (s, 1H), 9.54 (s, 1H), 8.77-8.63 (m, 2H), 8.52 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 6.8 Hz, 1H), 7.93 (s, 1H), 7.79 (s, 1H), 7.64-7.51 (m, 3H), 3.00 (t, J = 8.2 Hz, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.72 (s, 6H), 2.14-1.99 ( DMSO 436.0 (M + 1) 1.68 Method C 100 Methods O1, P 578 519.09 1H NMR (300 MHz, DMSO) 10.17 (s, 1H), 9.67-9.43 (m, 1H), 8.68 (s, 2H), 8.55 (d, J = 8.4 Hz, 1H), 8.28 (s, 1H), 7.89 (s, 2H), 7.68 (s, 1H), 7.56 (d, J = 9.1 Hz, 2H), 4.64 (s, 2H), 0.92 (s, 9H), 0.18 (s, 6H). DMSO 518.8 (M + 1) 3.18 Method C 100 Method O1 579 404.82 1H NMR (300 MHz, DMSO) 10.19 (s, 1H), 9.51 (s, 1H), 8.65 (d, J = 8.1 Hz, 2H), 8.54 (d, J = 8.4 Hz, 1H), 8.26 (s, 1H), 7.85 (s, 2H), 7.67-7.60 (m, 1H), 7.52 (d, J = 7.0 Hz, 2H), 5.48 (s, 1H), 4.39 (d, J = 5.8 Hz, 2H). DMSO 404.9 (M + 1) 2.05 Method C 100 Methods O1, Q 580 477.96 1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.51 (s, 1H), 8.73-8.61 (m, 2H), 8.45 (d, J = 8.6 Hz, 1H), 8.28 (dd, J = 6.8, 2.5 Hz, 1H), 7.97-7.86 (m, 1H), 7.71 (s, 1H), 7.60- 7.47 (m, 3H), 3.63-3.51 (m, 4H), 2.82 (t, J = 7.5 Hz, 2H), 2.42-2.25 (m, 6H), DMSO 477.9 (M + 1) 1.99 Method C 100 Methods O1, P 581 523.12 1H NMR (300 MHz, CDCl3) 9.67 (d, J = 1.3 Hz, 1H), 8.76-8.66 (m, 2H), 8.03 (dd, J = 6.5, 2.7 Hz, 1H), 7.82- 7.74 (m, 2H), 7.64 (ddd, J = 8.9, 4.0, 2.7 Hz, 1H), 7.46 (s, 1H), 7.44- 7.37 (m, 2H), 7.20 (t, J = 8.7 Hz, 1H), 3.67 (t, J = 6.1 Hz, 2H), 2.95 CDCl3 523.1 (M + 1) 3.35 Method C 100 Methods O1, P 582 408.86 1H NMR (300 MHz, CD3OD) 9.50 (d, J = 1.3 Hz, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.62 (dd, J = 4.9, 1.6 Hz, 1H), 8.26 (d, J = 8.5 Hz, 1H), 8.18 (dd, J = 6.7, 2.6 Hz, 1H), 7.83-7.71 (m, 2H), 7.61- 7.47 (m, 2H), 7.30 (t, J = 9.0 Hz, 1H), 3.65 (t, J = 6.4 Hz CD3OD 409.0 (M + 1) 1.99 Method C 100 Methods O1, P, Q 583 494.03 1H NMR (300 MHz, CD3OD) 9.50-9.46 (m, 1H), 8.77-8.70 (m, 1H), 8.61 (dd, J = 4.9, 1.6 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 8.17 (dd, J = 6.8, 2.6 Hz, 1H), 7.75 (ddd, J = 9.0, 4.2, 2.7 Hz, 1H), 7.70 (s, 1H), 7.54 (ddd, J = 8.0, 4.9, 0.8 Hz, 1H), 7.46 (d CD3OD 494.0 (M + 1) 2.29 Method C 91 Method G4 584 0 522 1H NMR (300 MHz, DMSO) 10.15 (s, 1H), 8.74-8.61 (m, 2H), 8.25 (d, J = 3.5 Hz, 1H), 7.96-7.80 (m, 4H), 7.59-7.46 (m, 2H), 3.79 (s, 2H), 3.18 (s, 4H), 3.06 (s, 4H). DMSO 522.0 (M + 1) 2.18 Method C 100 Method O2 585 526.06 1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.52 (d, J = 2.0 Hz, 1H), 8.72- 8.62 (m, 2H), 8.37 (s, 1H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 7.96-7.88 (m, 1H), 7.83 (d, J = 2.6 Hz, 2H), 7.61-7.50 (m, 2H), 3.10 (s, J = 17.4 Hz, 6H), 2.95-2.80 (m, 8H), 2.58- DMSO 526.1 (M + 1) 2.11 Method C 91 Methods O2, P 586 HCl 494.82 1H NMR (300 MHz, DMSO) 10.49 (s, 1H), 9.50 (s, 1H), 8.96-8.53 (m, 5H), 8.25 (dd, J = 6.9, 2.5 Hz, 1H), 8.05-7.73 (m, 4H), 7.54 (t, J = 9.1 Hz, 1H), 3.02-2.78 (m, 4H), 2.64- 2.37 (m, 3H), 2.15-1.99 (m, 2H). DMSO 422 (M + 1) 1.64 Method B (Ammon- ium formate) 100 Method O2 587 HCl 480.79 1H NMR (300 MHz, DMSO) 10.61 (s, 1H), 9.50 (s, 1H), 9.00-8.78 (m, 2H), 8.66 (s, 1H), 8.25 (dd, J = 6.8, 2.6 Hz, 1H), 8.13-7.75 (m, 7H), 7.54 (t, J = 9.1 Hz, 1H), 3.02-2.73 (m, 4H), 2.14- 1.94 (m, 2H). DMSO 408 (M + 1) 1.60 Method B (Ammon- ium formate) 100 Method O2 588 431.89 1H NMR (300 MHz, DMSO) 10.18 (s, 1H), 8.65 (d, J = 6.6 Hz, 1H), 8.56 (d, J = 8.7 Hz, 1H), 8.23 (dd, J = 6.9, 2.4 Hz, 1H), 8.01 (s, 1H), 7.91 (dd, J = 7.0, 3.5 Hz, 1H), 7.73 (d, J = 8.5 Hz, 1H), 7.68-7.39 (m, 3H), 4.07 (s, 2H), 2.67 (s, 6H). DMSO 431.9 (M + 1) Method C 99 Method O1 589 435.92 1H NMR (300 MHz, DMSO) 10.06 (s, 1H), 9.53 (s, 1H), 8.76-8.62 (m, 2H), 8.51 (d, J = 8.4 Hz, 1H), 8.28 (dd, J = 6.9, 2.5 Hz, 1H), 7.92 (dd, J = 4.5, 1.8 Hz, 1H), 7.79 (s, 1H), 7.65-7.49 (m, 3H), 3.08- 2.95 (m, 2H), 2.86 (t, J = 7.6 Hz, 2H), 2.71 (s, J = 7.2 Hz, 6H), 2.05 (dt, J = 13.8, 7.1 Hz, 2H). DMSO 436.0 (M + 1) Method C 99 Method O1, P 590 409.44 1H NMR (300 MHz, DMSO): 13.19 (s, 1H), 9.11 (s, 1H), 8.88 (s, 1H), 8.53 (s, 1H), 8.29 (s, 1H), 8.06 (s, 1H), 7.94 (d, J = 10.6 Hz, 4H), 7.78 (s, 1H), 7.25 (s, 1H), 4.44 (s, 2H), 3.37 (s, 3H). DMSO 410.5 (M + 1) Method C 95 Method O1 591 413.47 DMSO 415.5 (M + 1) Method C 95 Method O1, P

(214) ##STR01158## Method N1: Pd(APhos).sub.2Cl.sub.2/K.sub.3PO.sub.4 or Cs.sub.2CO.sub.3/Boronic acid or ester/DioxaneH.sub.2O, heat Method N2: Pd(PPh.sub.3).sub.2Cl.sub.2/K.sub.2CO.sub.3/Boronic acid or ester/DME-EtOHH.sub.2O/microwave, 120 C. Method N3: Pd(OAc).sub.2/Xphos/Cs.sub.2CO.sub.3/THFH.sub.2O, 80 C. Method N4: Pd(OAc).sub.2/Sphos/K.sub.2CO.sub.3/MeCNH.sub.2O, microwave, 120 C. Method N5: Pd(PPh.sub.3).sub.4/K.sub.3PO.sub.4/DioxaneH.sub.2O, heat Method N6: Pd(dppf)Cl.sub.2CH.sub.2Cl.sub.2/K.sub.3PO.sub.4/DioxaneH.sub.2O, heat

(215) ##STR01159##

(216) N-(3-chloro-4-fluorophenyl)-6-(6-methoxypyridin-3-yl)-2-(pyridin-3-yl)quinazolin-4-amine (xxi-a) A 2.0 dram reaction vial was charged with 6-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol, 1.0 equiv), 6-methoxypyridin-3-ylboronic acid (44.5 mg, 0.291 mmol, 1.25 equiv), Pd(APhos).sub.2Cl.sub.2 (6.6 mg, 0.0093 mmol, 4 mol %) and potassium phosphate monohydrate (69 mg, 0.70 mmol, 3.0 equiv). The mixture was suspended in dioxane/water (9:1, 4 mL), and the reaction was heated at 90 C. for 14 h. The reaction mixture was cooled to room temperature, diluted with water (15 mL) and the resultant precipitate was collected by filtration. The crude product was purified by stirring in methanol for 30 min at 60 C. to give the desired product as a pale yellow solid (58 mg, 54%) LCMS m/z=458.1 (M+1) (Method C) (retention time=2.56 min). .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.53 (s, 1H), 8.82 (s, 1H), 8.70 (dd, J=16.9, 5.4 Hz, 3H), 8.25 (d, J=8.6 Hz, 3H), 8.01-7.87 (m, 2H), 7.57 (dd, J=11.2, 6.0 Hz, 2H), 7.03 (d, J=8.6 Hz, 1H), 3.94 (s, 3H).

(217) ##STR01160##

(218) N-(3-chloro-4-fluorophenyl)-7-(6-methoxypyridin-3-yl)-2-(pyridin-3-yl)quinazolin-4-amine (xxi-b) A microwave vial was charged with 7-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 4-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol), 6-methoxypyridin-3-ylboronic acid (44.5 mg, 0.291 mmol, 1.25 equiv), Pd(PPh.sub.3).sub.2Cl.sub.2 (8.1 mg, 5 mol %) and potassium carbonate (160.1 mg, 1.16 mmol, 5.0 equiv). The mixture was suspended in DME/water/ethanol (7:3:2, 4 mL), and the reaction was heated under microwave irradiation conditions at 120 C. for 10 minutes. The crude reaction mixture was diluted with water (10 mL) and then filtered. The solid residue was dissolved in methanol/THF (1:1, 5 mL) with heating and then filtered through Celite to remove the catalyst. The resulting filtrate was concentrated to afford the desired product as a tan solid (7.0 mg, 6.5%). LCMS m/z=458.1 (M+1) (Method C) (retention time=2.51 min). .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.55 (s, 1H), 8.76 (d, J=2.5 Hz, 1H), 8.72-8.65 (m, 2H), 8.62 (d, J=8.6 Hz, 1H), 8.34-8.26 (m, 2H), 8.15 (d, J=1.6 Hz, 1H), 8.02 (d, J=8.7 Hz, 1H), 7.97-7.88 (m, 1H), 7.61-7.49 (m, 2H), 6.99 (d, J=8.7 Hz, 1H), 3.94 (s, 3H).

(219) ##STR01161##

(220) N-(3-chloro-4-fluorophenyl)-7-(piperidin-1-ylmethyl)-2-(pyridin-3-yl)quinazolin-4-amine (xxi-c) A dry 15 mL sealed tube was charged with 7-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 4-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol), potassium 1-trifluoroboratomethylpiperidine (52.5 mg, 0.256 mmol), cesium carbonate (227.5 mg, 0.698 mmol), Pd(OAc).sub.2 (1.6 mg, 3 mol %) and XPhos (6.7 mmol, 6 mol %) in THF/water (10:1, 3.3 mL). The reaction mixture was stirred at 80 C. for 16 hours. The reaction mixture was filtered through a pad of Celite and solvent was removed in vacuo. The crude product was purified by ISCO (silica, 12 g column, 97% dichloromethane3% methanol0.1% NH.sub.4OH) to yield the desired compound as a yellow solid (23.3 mg, 22%). LCMS m/z=448.0 (M+1) (Method C) (retention time=1.95 min). .sup.1H NMR (300 MHz, CD.sub.3OD) 9.40 (d, J=1.4 Hz, 1H), 8.70-8.62 (m, 1H), 8.56 (dd, J=4.9, 1.6 Hz, 1H), 8.18-8.09 (m, 2H), 7.69 (ddd, J=6.8, 4.1, 2.1 Hz, 2H), 7.54-7.45 (m, 2H), 7.23 (t, J=9.0 Hz, 1H), 3.61 (s, 2H), 2.47 (s, 4H), 1.64 (dd, J=13.9, 8.9 Hz, 5H), 1.49 (d, J=4.1 Hz, 2H).

(221) ##STR01162##

(222) N-(3-chloro-4-fluorophenyl)-6-(3-chlorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (xxi-d) A mixture of N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (1.0 g, 2.10 mmol), 3-chlorophenylboronic acid (0.49 g, 3.13 mmol), Pd(PPh.sub.3).sub.4 (0.24 g, 0.210 mmol), K.sub.3PO.sub.4 (1.34 g, 6.31 mmol) in dioxane (20 mL) and water (2.0 mL) was stirred under reflux for 2 h. Ethyl acetate (20 mL) was added to the cooled mixture and filtered. The filtered solid was recrystallized from DMF and water to give the title compound (0.50 g, 51.6%). .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.54 (s, 1H), 8.87 (s, 1H), 8.74-8.65 (m, 2H), 8.31-8.23 (m, 2H), 8.04-7.85 (m, 4H), 7.64-7.49 (m, 4H).

(223) ##STR01163##

(224) 2-(7-(3-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide dihydrochloride (xxi-e) A mixture of 2-(7-bromo-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (0.40 g, 0.952 mmol), 3-fluorophenylboronic acid (0.20 g 1.43 mmol), Pd(dppf).sub.2Cl.sub.2(77 mg, 0.094 mmol), K.sub.3PO.sub.4 (606 mg, 2.85 mmol) in dioxane (8 mL) and water (2 mL) was refluxed under argon atmosphere for 4 h and cooled. Ethyl acetate (10 mL) was added to the mixture and a precipitate formed and was filtered. The filtered solid was recrystallized from DMF and water to give the title compound as free form. The solid as free form was suspended in ethyl acetate (10 mL) and 4N HCl in ethyl acetate (0.71 mL) was added to the suspension. A precipitate formed and was subjected to sonication for 20 min, filtered and dried to give the title compound (0.24 g, 49.6%). .sup.1H NMR (400 MHz, DMSO) 13.19 (s, 1H), 9.64 (s, 1H), 9.21-9.08 (m, 1H), 9.07-8.89 (m, 2H), 8.51 (s, 1H), 8.38-8.26 (m, 2H), 8.16 (d, J=8.5 Hz, 1H), 8.07-7.87 (m, 3H), 7.83-7.70 (m, 3H), 7.62 (dd, J=14.2, 7.7 Hz, 1H), 7.40-7.22 (m, 2H).

(225) The compounds in the following table were prepared in a manner analogous to that described in Scheme 11 substituting with appropriate boronic acid/ester or boronate salt, catalyst and solvent

(226) TABLE-US-00007 TABLE 4 Salt Molecular .sup.1H-NMR Retention LCMS Purity Method for Number PRODUCT type Mass .sup.1H-NMR Solvent LCMS Time (min) Protocol percent Coupling 592 2 HCl 536.401 .sup.1H NMR (300 MHz, DMSO) 11.34 (s, 1H), 10.53 (s. 1H), 9.56 (s, 1H), 9.17- 8.95 (m, 2H), 8.89 (d, J = 4.5 Hz, 1H), 8.19 (d, J = 8.8 Hz, 1H). 8.08-7.81 (m, 4H), 7.62-6.98 (m, 3H), 4.53 (s, 2H), 4.05-3.74 (m, 4H), 3.48-3.07 (m, 4H). DMSO 464 (M + 1) 2.01 Method C 100 Method N3 593 HCl 515.406 .sup.1H NMR (300 MHz, DMSO) 10.40 (s, 1H), 9.51 (s, 1H), 9.00-8.78 (m, 2H), 8.55 (s, 1 H), 8.20 (d, J = 4.4 Hz, 1H), 8.03- 7.75 (m, 4H), 7.54 (t, J = 9.1 Hz, 1H), 4.68 (s, 2H), 3.83 (d, J = 11.2 Hz, 2H), 3.44-3.18 (m, 4H), 1.98-1.78 (m, 1H), 1.62 (d, J DMSO 479 (M + 1) 2.08 Method D 97 Method N3 594 448.920 .sup.1H NMR (300 MHz, DMSO) 10.10 (s, 1H, 9.51 (s, 1 H), 8.75-8.60 (m, 2H), 8.47 (s, 1H), 8.32-8.19 (m, 1H), 7.97- 7.77 (m, 3H), 7.63-7.44 (m, 2H), 4.62 (s, 2H), 4.16-3.97 (m, 1H), 1.88-1.42 (m, 8H). DMSO 449 (M + 1) 2.62 Method D 92 Method N3 595 457.89 .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.53 (s, 1H), 8.82 (s, 1H), 8.70 (dd, J = 16.9, 5.4 Hz, 3H), 8.25 (d, J = 8.6 Hz, 3H), 8.01-7.87 (m, 2H), 7.57 (dd, J = 11.2, 6.0 Hz, 2H), 7.03 (d, J = 8.6 Hz, 1H), 3.94 (s, 3H). DMSO 458.2 (M + 1) 2.56 Method C 100 Method N1 596 449.91 .sup.1H NMR (300 MHz, DMSO) 10.13 (s, 1H), 9.52 (s, 1H), 8.67 (d, J = 9.8 Hz, 2H), 8.47 (s, 1H), 8.34-8.20 (m, 1H), 8.02- 7.84 (m, 3H), 7.54 (t, J = 9.2 Hz, 2H), 3.64 (d, J = 17.6 Hz, 6H), 2.43 (s, 4H). DMSO 449.9 (M + 1) 2.13 Method C 100 Method N3 597 456.9 DMSO 456.0 (M + 1) 2.64 Method C 100 Method N1 598 0 445.88 .sup.1H NMR (300 MHz, DMSO) 10.04 (s, 1H), 9.52 (s, 1H), 8.68 (t, J = 6.5 Hz, 2H), 8.51 (s, 1 H), 8.22 (dd, J = 6.7, 2.4 Hz, 1H), 8.03-7.83 (m, 3H), 7.54 (dd, J = 11.9, 6.6 Hz, 2H), 2.50 (s, 3H), 2.33 (s, 3H). DMSO 446 (M + 1) 2.35 Method C 100 Method N1 599 427.86 .sup.1H NMR (300 MHz, DMSO) 10.10 (s, 1H), 9.51 (s, 1H), 9.13 (s, 1H), 8.86 (s, 1H), 8.66 (s, 3H), 8.24 (s, 3H), 7.94 (d, J = 8.7 Hz, 2H), 7.55 (dd, J = 16.7, 9.9 Hz, 3H). DMSO 427.95 (M + 1) 2.25 Method C 100 Method N1 600 430.86 .sup.1H NMR (300 MHz, DMSO) 9.98 (s, 1H), 9.51 (d, J = 1.6 Hz, 1H), 8.66 (dd, J = 11.7, 2.2 Hz, 3H), 8.38-8.20 (m, 2H), 8.20-8.02 (m, 2H), 8.02-7.80 (m, 2H), 7.71-7.42 (m, 2H), 3.93 (s, 3H). DMSO 430.9 (M + 1) 2.17 Method C 100 Method N1 601 449.91 .sup.1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.52 (d, J = 1.3 Hz, 1H), 8.77- 8.55 (m, 2H), 8.41 (s, 1H), 8.28 (dd, J = 6.9, 2.6 Hz, 1H), 8.03-7.77 (m, 3H), 7.65-7.44 (m, 2H), 3.34 (s, 8H), 3.15-2.90 (m, 5H), 2.90-2.64 (m, 5H). DMSO 449.9 (M + 1) 2.04 Method C 100 Method N1 602 445.85 .sup.1H NMR (300 MHz, DMSO) 10.09 (s, 1H), 9.50 (s, 1 H). 8.88-8.74 (m, 2H), 8.66 (dd, J = 14.1, 5.5 Hz, 2H), 8.56- 8.42 (m, 1H), 8.23 (dd, J = 10.0, 5.7 Hz, 2H), 7.98-7.85 (m, 2H), 7.62-7.46 (m, 2H), 7.45-7.36 (m, 1H). DMSO 445.9 (M + 1) 2.43 Method C 99 Method N1 603 512.97 .sup.1H NMR (300 MHz, DMSO) 10.05 (s, 1H), 9.51 (s, 1H), 8.70 (dd, J = 24.1, 7.0 Hz, 4H), 8.22 (dd, J = 14.3, 7.3 Hz, 2H), 8.10 (d, J = 7.9 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 7.4 Hz, 2H), 7.00 (d, J = 8.8 Hz, 1H), 3.74 (s, 4H), 3.55 (d, J = 4.7 DMSO 512.9 (M + 1) 2.5 Method C 100 Method N1 604 456.9 .sup.1H NMR (300 MHz, DMSO) 10.16 (s, 1H), 9.53 (s, 1H), 8.81 (s, 1H), 8.73-8.60 (m, 2H), 8.30-8.20 (m, 2H), 7.99-7.89 (m, 2H), 7.55 (dd, J = 8.2, 4.7 Hz, 2H), 7.46 (t, J = 7.6 Hz, 3H), 7.10-6.96 (m, 1H), 3.88 (s, 3H). DMSO 458.9 (M + 2) 2.65 Method C 100 Method N1 605 486.92 .sup.1H NMR (300 MHz, DMSO) 10.16 (s, 1H), 9.54 (s, 1H), 8.79 (d, J = 9.7 Hz, 1 H), 8.71 (s, 2H), 8.26 (d, J = 8.7 Hz, 1H), 7.95 (dd, J = 8.7, 3.7 Hz, 2H), 7.56 (dd, J = 11.7, 6.4 Hz, 1H), 7.43 (d, J = 15.2 Hz, 2H), 7.22-7.06 (m, 2H), 3.92 (s, 3H), 3.84 (s, DMSO 486.9 (M + 1) 2.48 Method C 100 Method N1 606 486.92 DMSO 487.1 (M + 1) 2.58 Method C 100 Method N1 607 390.84 DMSO 390.9 (M + 1) 2.48 Method C 100 Method N1 608 0 539.99 .sup.1H NMR (300 MHz, DMSO) 10.15 (s, 1H), 9.51 (s. 1H), 8.84 (s, 1H), 8.66 (dd, J = 9.7, 6.5 Hz, 2H), 8.29-8.19 (m, 2H), 7.92 (ddd, J = 8.9, 7.5, 4.6 Hz, 4H), 7.65 - 7.48 (m, 4H), 3.64 (s, 6H), 3.35 (s, 2H). DMSO 539.9 (M + 1) 2.23 Method C 100 Method N1 609 526 526.16 (M + 1) 2.55 Method C 94 Method N1 610 471.91 .sup.1H NMR (300 MHz, DMSO) 10.03 (s, 1H), 9.56 (d, J = 2.1 Hz, 1H), 8.77-8.66 (m, 3H), 8.64 (s, 1H), 8.24 (ddd, J = 8.7, 6.6, 2.6 Hz, 2H), 8.13 (s, 1 H), 7.96-7.90 (m, 1H), 7.62-7.52 (m, 2H), 7.01 (d, J = 8.7 Hz, 1H), 3.94 (s, 3H), 2.78 (s, 3H). CDCl.sub.3 471.9 (M + 1) 2.93 Method C 100 Method N1 611 474.34 .sup.1H NMR (300 MHz, DMSO) 10.09 (s, 1H), 9.53 (s, 1H), 8.77 (s, 1H), 8.67 (dd, J = 12.3, 4.1 Hz, 3H), 8.35 (d, J = 2.3 Hz, 1H), 8.27-8.13 (m, 2H), 8.02-7.88 (m, 2H), 7.72 (d, J = 8.8 Hz, 1H), 7.55 (dd, J = 7.7, 4.6 Hz, 1H), 7.00 (d, J = 8.6 Hz, 1H), 3. DMSO 474.02 (M + 1) 2.72 Method C 100 Method N1 612 442.88 DMSO 443.1 (M + 1) 2.37 Method C 100 Method N1 613 465.91 .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.54 (s, 1H), 8.75-8.63 (m, 3H), 8.20 (dd, J = 8.2, 5.6 Hz, 2H), 8.09 (d, J = 8.5 Hz, 2H), 8.01 (d, J = 8.5 Hz, 2H), 7.88 (s, 1H), 7.55 (d, J = 9.1 Hz, 2H), 2.76 (s, 3H). DMSO 466.1 (M + 1) 2.78 Method C 100 Method N1 614 457.89 .sup.1H NMR (300 MHz, DMSO) D 10.18 (s, 1H), 9.51 (s, 1H), 8.92 (s, 1H), 8.67 (dd, J = 12.7, 5.8 Hz, 2H), 8.39-8.16 (m, 3H), 7.91 (dd, J = 14.8, 5.7 Hz, 2H), 7.65-7.45 (m, 3H), 7.35 (s, 1H), 3.94 (s, 3H). DMSO 458.1 (M + 1) 2.62 Method C 100 Method N1 615 514.93 .sup.1H NMR (300 MHz, DMSO) d 10.19 (s, 1H), 9.52(s, 1H), 8.86 (s, 1H), 8.67 (dd, J = 7.7, 2.1 Hz, 2H), 8.06-7.75 (m, 2H), 7.54 (dd, J = 9.0, 4.1 Hz, 4H), 3.99 (s, 3H), 3.82 (s, 3H) DMSO 515.1 (M + 1) 2.54 Method C 100 Method N1 616 451.88 1H NMR (300 MHz, DMSO) d 10.16 (s, 1H), 9.50 (s, 1H), 8.86 (s, 1H), 8.66 (dd, J = 15.2, 6.9 Hz, 2H), 8.35-8.16 (m, 2H), 8.15-7.82 (m, 6H), 7.55 (dd, 11.1, 6.0 Hz, 2H). DMSO 452.0 (M + 1) 2.61 Method C 96 Method N1 617 436.47 437.2 (M + 1) 2.08 Method C 95 Method N1 618 0 421.45 422.2 (M + 1) 1.8 Method C 100 Method N1 619 449.91 .sup.1H NMR (300 MHz, DMSO) 10.06 (s, 1H). 9.52 (d, J = 1.3 Hz, 1H), 8.73-8.64 (m, 2H), 8.51 (d, J = 8.5 Hz, 1H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 7.96-7.86 (m, 1H), 7.82 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.57 (t, J = 3.9 Hz, 1H), 7.52 (t, J = 9.1 Hz, 1H), 3.69 (s, 2H), 3.62 (s, 4H), 2.44 (s, 4H). DMSO 449.9 (M + 1) 2.13 Method C 100 Method N3 620 457.89 .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.55 (s, 1H), 8.76 (d, J = 2.5 Hz, 1H), 8.72-8.65 (m, 2H), 8.62 (d, J = 8.6 Hz, 1H), 8.34-8.26 (m, 2H), 8.15 (d, J = 1.6 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.97- 7.88 (m, 1H), 7.61-7.49 (m, 2H), 6.99 (d, J = 8.7 Hz, 1H), 3.94 (s, 3H). DMSO 458.1 (M + 1) 2.51 Method C 100 Method N2 621 462.95 .sup.1H NMR (300 MHz, CD.sub.3OD) 9.40 (s, 1H), 8.66 (d, J = 8.0 Hz, 1 H), 8.56 (s, 1H), 8.19-8.09 (m, 2H), 7.74 (s, 1H), 7.72- 7.65 (m, 1H), 7.54-7.45 (m, 2H), 7.24 (t, J = 9.0 Hz, 1H), 3.68 (d, J = 8.0 Hz, 2H), 2.75-2.41 (m, 8H), 2.30 (s, 3H). CD.sub.3OD 463.0 (M + 1) 1.71 Method C 100 Method N3 622 433.91 434.0 (M + 1) 1.73 Method C 100 Method N3 623 435.92 436.0 (M + 1) 1.84 Method C 100 Method N3 624 430.865 .sup.1H NMR (300 MHz, DMSO) 10.01 (s, 1H), 9.52 (d, J = 1.3 Hz, 1H), 8.72-8.60 (m, 2H), 8.49 (d, J = 8.6 Hz, 1H), 8.44 (s, 1H), 8.28 (dd, J = 6.9, 2.6 Hz, 1H), 8.15 (s, 1H), 8.03 (d, J = 1.5 Hz, 1H), 7.95- 7.83 (m, 2H), 7.60-7.45 (m, 2H), 3.91 (s, 3H). DMSO 431.0 (M + 1) 2.12 Method C 100 Method N2 625 465.97 .sup.1H NMR (300 MHz, CD.sub.3OD) 9.56-9.50 (m, 1H), 8.79 (dt, J = 8.1, 1.6 Hz, 1H), 8.63 (dd, J = 4.9, 1.7 Hz, 1H), 8.30 (s, 1H), 8.19 (dd, J = 6.7, 2.6 Hz, 1H), 7.91 (d, J = 1.1 Hz, 2H), 7.80 (ddd, J = 9.0, 4.2, 2.7 Hz, 1H), 7.58 (dd, J = 8.0, 4.9 Hz, 1H), 7.33 (t, J = 9.0 Hz, 1H), 3.75 (s, 2H), 2.84- 2.66 (m, 8H). CD.sub.3OD 466.0 (M + 1) 2.46 Method C 94 Method N3 626 491.94 .sup.1H NMR (300 MHz, DMSO) 10.00 (s, 1H), 9.52 (s, 1H), 8.73-8.63 (m, 2H), 8.42 (s, 1H), 8.28 (dd, J = 6.8, 2.6 Hz, 1H), 7.92 (ddd, J = 6.8, 4.2, 2.0 Hz, 1H), 7.85 (s, 2H), 7.60-7.50 (m, 2H), 3.56- 3.43 (m, 9H), 3.07 (t, J = 7.6 Hz, 2H), 2.79 (t, J = 7.7 Hz, 2H). DMSO 491.9 (M + 1) 2 Method C 93 Method N1 627 463.93 .sup.1H NMR (300 MHz, DMSO) 9.99 (s, 1H), 9.54 (s, 1 H), 8.67 (d, J = 5.3 Hz, 2H), 8.30- 8.22 (m, 2H), 7.96-7.87 (m, 1H), 7.73 (s, 1H), 7.60-7.46 (m, 2H), 3.60 (s, 6H), 2.71 (s, 3H), 2.41 (s, 4H). DMSO 464.0 (M + 1) 2.52 Method C 100 Method N3 628 00 419.43 .sup.1H NMR (300 MHz, DMSO) 9.41 (d, J = 1.4 Hz, 1H), 9.15 (d, J = 1.7 Hz, 1H), 8.74- 8.64 (m, 3H), 8.55 (dt, J = 7.9, 1.8 Hz, 1H), 8.42 (dd, J = 8.7, 2.0 Hz, 1H), 8.36- 8.29 (m, 1H), 8.15 (d, J = 8.7 Hz, 1H), 7.90 (dd, J = 7.8, 1.7 Hz, 1 H), 7.61 (dd, J = 8.0, 4.8 Hz, 1H), 7.53 (dd, J = 7.9, 4.8 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 7.7 Hz, 1 H). DMSO 420.1 (M + 1) 2.12 Method C 99 Method N4

(227) TABLE-US-00008 .sup.1H Purity Method Num- Starting Starting Salt NMR Per- of ber Material 1 Material 2 Product type .sup.1H NMR Solvent cent Coupling 629 01 02 03 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.54 (s, 1H), 8.87 (s, 1H), 8.74- 8.65 (m, 2H), 8.31- 8.23 (m, 2H), 8.04-7.85 (m, 4H), 7.64-7.49 (m, 4H). DMSO >98 N5 630 04 05 06 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.54 (d, J = 1.4 Hz, 1H), 8.86 (s, 1H), 8.76-8.64 (m, 2H), 8.26 (dd, J = 6.8, 2.3 Hz, 2H), 8.03-7.89 (m, 4H), 7.70-7.52 (m, 4H). DMSO >98 N5 631 07 08 09 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.54 (d, J = 1.4 Hz, 1H), 8.86 (s, 1H), 8.76-8.64 (m, 2H), 8.26 (dd, J = 6.8, 2.3 Hz, 2H), 8.03-7.89 (m, 4H), 7.70-7.52 (m, 4H). DMSO >98 N5 632 0 .sup.1H NMR (400 MHz, DMSO) 10.22- 10.11 (m, 1H), 9.54 (s, 1H), 8.86- 8.77 (m, 1H), 8.74- 8.65 (m, 2H), 8.30-8.17 (m, 2H), 8.01-7.90 (m, 2H), 7.74-7.66 (m, 2H), 7.60-7.51 (m, 2H), 7.51-7.42 (m, 1H), 7.28 (d, J = 7.5 Hz, 1H), 2.45 (s, 3H). DMSO >98 N5 633 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.61-9.53 (m, 1H), 8.92 (s, 1H), 8.78-8.67 (m, 2H), 8.43-8.24 (m, 3H), 8.14-7.89 (m, 3H), 7.84-7.76 (m, 1H), 7.66-7.53 (m, 2H) DMSO >98 N5 634 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H), 8.89 (s, 1H), 8.75-8.67 (m, 2H), 8.35-8.22 (m, 2H), 8.00 (d, J = 8.7 Hz, 1H), 7.96- 7.90 (m, 1H), 7.84- 7.75 (m, 2H), 7.66-7.52 (m, 3H), 7.34-7.27 (m, 1H). DMSO >98 N5 635 0 .sup.1H NMR (400 MHz, DMSO) 10.27 (s, 1H), 9.54 (d, J = 1.2 Hz, 1H), 8.94 (s, 1H), 8.77-8.66 (m, 3H), 8.40-8.21 (m, 4H), 7.99 (d, J = 8.9 Hz, 1H), 7.88 (t, J = 8.0 Hz, 2H), 7.61-7.50 (m, 2H). DMSO >98 N5 636 .sup.1H NMR (400 MHz, DMSO) 10.13 (s, 1H), 9.56 (s, 1H), 8.77- 8.68 (m, 2H), 8.65 (s, 1H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 8.04-7.97 (m, 2H), 7.96-7.88 (m, 1H), 7.70-7.43 (m, 6H). DMSO >98 N5 637 .sup.1H NMR (400 MHz, DMSO) 10.10 (s, 1H), 9.56 (s, 1H), 8.76-8.68 (m, 2H), 8.63 (s, 1H), 8.28 (dd, J = 6.7, 2.7 Hz, 1H), 8.05 (dd, J = 8.7, 1.8 Hz, 1H), 8.00-7.90 (m, 2H), 7.70-7.43 (m, 4H), 7.21 (d, J = 8.1 Hz, 1H), 7.14 (t, J = 7.4 Hz, 1H), 3.82 (s, 3H). DMSO >98 N5 638 0 .sup.1H NMR (400 MHz, DMSO) 10.16 (s, 1H), 9.54 (s, 1H), 8.81 (s, 1H), 8.74- 8.64 (m, 2H), 8.30- 8.17 (m, 2H), 8.01-7.87 (m, 4H), 7.61-7.51 (m, 2H), 7.42 (t, J = 8.8 Hz, 2H). DMSO >98 N5 639 1H NMR (400 MHz, DMSO) 10.21 (s, 1H), 9.57 (s, 1H), 8.80 (d, J = 1.8 Hz, 1H), 8.76-8.69 (m, 2H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 8.14 (dd, J = 8.6, 1.8 Hz, 1H), 8.10-8.02 (m, 2H), 7.97- 7.88 (m, 2H), 7.83 (d, J = 6.8 Hz, 1H), 7.70 (td, J = 7.6, 1.2 Hz, 1H), 7.63- DMSO >98 N5 7.52 (m, 2H). 640 .sup.1H NMR (400 MHz, DMSO) 10.12 (s, 1H), 9.55 (s, 1H), 8.77-8.66 (m, 2H), 8.62 (s, 1H), 8.25 (dd, J = 6.8, 2.3 Hz, 1H), 8.16 (d, J = 8.3 Hz, 1H), 7.99- 7.80 (m, 4H), 7.80- 7.71 (m, 2H), 7.61-7.49 (m, 2H). DMSO >98 N5 641 .sup.1H NMR (400 MHz, DMSO) 9.57 (s, 1H), 8.85-8.55 (m, 3H), 8.20-7.95 (m, 3H), 7.85-7.20 (m, 7H) DMSO >98 N5 642 0 .sup.1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H), 8.83 (s, 1H), 8.74-8.66 (m, 2H), 8.32-8.23 (m, 2H), 8.02-7.89 (m, 2H), 7.61- 7.53 (m, 2H), 7.05 (d, J = 2.2 Hz, 2H), 6.62 (t, J = 2.1 Hz, 1H), 3.88 (s, 6H). DMSO >98 N5 643 .sup.1H NMR (400 MHz, DMSO) 10.18 (s, 1H), 9.55 (d, J = 2.0 Hz, 1H), 8.81 (d, J = 1.7 Hz, 1H), 8.74-8.65 (m, 2H), 8.31-8.20 (m, 2H), 8.04-7.88 (m, 2H), 7.65-7.53 (m, 2H), 7.42-7.34 (m, 1H), 7.23-7.09 (m, 2H), 6.83 (dd, J = 8.3, 1.9 Hz, 1H), 3.02 (s, 6H). DMSO >98 N5 644 1H NMR (400 MHz, DMSO) 10.14 (s, 1H), 9.55 (s, 1H), 8.77-8.68 (m, 2H), 8.65 (d, J = 1.5 Hz, 1H), 8.28 (dd, J = 6.9, 2.6 Hz, 1H), 8.05 (dd, J = 8.6, 1.7 Hz, 1H), 8.01-7.90 (m, 2H), 7.60- 7.51 (m, 2H), 7.29- 7.21 (m, 1H), 7.18 (dd, J = 8.3, 1.6 Hz, 1H), 7.12 DMSO >98 N5 (dd, J = 7.6, 1.6 Hz, 1H), 3.89 (s, 3H), 3.58 (s, 3H). 645 0 1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.56 (s, 1H), 8.74-8.67 (m, 2H), 8.64 (s, 1H), 8.28 (dd, J = 6.9, 2.6 Hz, 1H), 8.06 (dd, J = 8.6, 1.7 Hz, 1H), 7.98-7.89 (m, 2H), 7.62-7.51 (m, 2H), 7.14 (d, J = 9.0 Hz, 1H), 7.09 (d, J = 3.1 Hz, 1H), 7.02 (dd, J = 8.9, 3.1 DMSO >98 N5 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H). 646 .sup.1H NMR (400 MHz, DMSO) 9.99 (s, 1H), 9.56 (d, J = 0.9 Hz, 1H), 8.71 (dd, J = 7.1, 1.6 Hz, 2H), 8.46 (d, J = 1.5 Hz, 1H), 8.29 (dd, J = 6.9, 2.6 Hz, 1H), 8.00-7.87 (m, 2H), 7.73 (dd, J = 8.5, 1.7 Hz, 1H), 7.63- 7.47 (m, 2H), 7.41 (t, J = 8.4 Hz, 1H), 6.84 (d, J = 8.5 Hz, DMSO >98 N5 2H), 3.77-3.66 (m, 6H). 647 .sup.1H NMR (400 MHz, DMSO) 10.06- 9.96 (m, 1H), 9.52 (s, 1H), 8.75-8.62 (m, 3H), 8.40-8.33 (m, 1H), 8.28- 8.22 (m, 1H), 8.22- 8.14 (m, 1H), 7.97-7.85 (m, 3H), 7.64-7.49 (m, 2H), 7.16 (s, 1H). DMSO >98 N5 648 0 .sup.1H NMR (400 MHz, DMSO) 10.10 (s, 1H), 9.54 (s, 1H), 8.85 (s, 1H), 8.77- 8.65 (m, 2H), 8.32 (d, J = 8.7 Hz, 1H), 8.26 (dd, J = 6.8, 2.6 Hz, 1H), 8.12 (s, 1H), 7.94 (d, J = 8.7 Hz, 2H), 7.86- 7.76 (m, 2H), 7.64- 7.54 (m, 2H). DMSO >98 N5 649 1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.53 (s, 1H), 8.78 (s, 1H), 8.71- 8.64 (m, 2H), 8.26- 8.19 (m, 2H), 7.95-7.90 (m, 2H), 7.77-7.69 (m, 2H), 7.60-7.53 (m, 2H), 7.26 (t, J = 3.7 Hz, 1H). DMSO >98 N5 650 .sup.1H NMR (400 MHz, DMSO) 10.12 (s, 1H), 9.55 (d, J = 2.2 Hz, 1H), 8.75- 8.67 (m, 3H), 8.33- 8.23 (m, 2H), 8.13 (dd, J = 8.7, 1.8 Hz, 1H), 8.00- 7.90 (m, 3H), 7.63- 7.51 (m, 2H), 7.22 (dd, J = 7.3, 5.0 Hz, 1H), 3.95 (s, 3H). DMSO >98 N5 651 .sup.1H NMR (400 MHz, DMSO) 10.22 (s, 1H), 9.53 (s, 1H), 8.97 (s, 1H), 8.75 (d, J = 5.5 Hz, 2H), 8.73-8.64 (m, 2H), 8.38-8.30 (m, 1H), 8.24 (d, J = 6.8 Hz, 1H), 8.05- 7.97 (m, 1H), 7.97- 7.88 (m, 3H), 7.63- 7.51 (m, 2H). DMSO >98 N5 652 0 1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.50 (s, 1H), 9.33 (s, 2H), 9.26 (s, 1H), 8.90 (s, 1H), 8.69 (d, J = 3.6 Hz, 1H), 8.64 (d, J = 8.0 Hz, 1H), 8.33 (d, J = 8.6 Hz, 1H), 8.22 (dd, J = 6.7, 2.0 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.93- 7.86 (m, 1H), 7.61-7.48 (m, 2H). DMSO >98 N5 653 .sup.1H NMR (400 MHz, DMSO) 10.10 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H), 8.77- 8.67 (m, 2H), 8.61 (s, 1H), 8.26 (dd, J = 6.9, 2.6 Hz, 1H), 8.12 (dd, J = 8.7, 1.8 Hz, 1H), 8.01- 7.89 (m, 3H), 7.62- 7.51 (m, 2H), 4.02 (s, 3H), 4.00 (s, 3H). DMSO >98 N5 654 .sup.1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.56 (s, 1H), 8.77-8.68 (m, 2H), 8.65 (d, J = 1.6 Hz, 1H), 8.30 (dd, J = 6.9, 2.6 Hz, 1H), 8.17 (dd, J = 8.7, 1.7 Hz, 1H), 7.99-7.88 (m, 2H), 7.61- 7.50 (m, 2H), 7.42- 7.33 (m, 2H), 7.21-7.08 (m, 2H), 2.53 (s, 6H). DMSO >98 N5 655 0 .sup.1H NMR (400 MHz, DMSO) 10.08 (s, 1H), 9.55 (s, 1H), 8.74-8.66 (m, 2H), 8.63 (s, 1H), 8.26 (dd, J = 6.8, 2.5 Hz, 1H), 8.12 (d, J = 8.7 Hz, 1H), 7.97- 7.88 (m, 3H), 7.62- 7.51 (m, 2H), 6.61 (d, J = 8.1 Hz, 1H), 3.97 (s, 3H), 3.96 (s, 3H). DMSO >98 N5 656 .sup.1H NMR (400 MHz, DMSO) 10.21 (s, 1H), 9.54 (d, J = 2.0 Hz, 1H), 8.91 (s, 1H), 8.76-8.65 (m, 2H), 8.31 (d, J = 8.8 Hz, 1H), 8.26 (dd, J = 6.8, 2.6 Hz, 1H), 8.15-7.89 (m, 7H), 7.61-7.52 (m, 2H), 7.46 (s, 1H). DMSO >98 N5 657 .sup.1H NMR (400 MHz, DMSO) 10.21 (s, 1H), 9.54 (d, J = 2.0 Hz, 1H), 8.91 (s, 1H), 8.76-8.65 (m, 2H), 8.31 (d, J = 8.8 Hz, 1H), 8.26 (dd, J = 6.8, 2.6 Hz, 1H), 8.15-7.89 (m, 7H), 7.61-7.52 (m, 2H), 7.46 (s, 1H). DMSO >98 N5 658 0 .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.54 (s, 1H), 8.88 (s, 1H), 8.79- 8.61 (m, 2H), 8.34- 8.22 (m, 2H), 8.05-7.84 (m, 4H), 7.72 (t, J = 8.0 Hz, 1H), 7.65-7.53 (m, 2H), 7.47 (d, J = 8.4 Hz, 1H). DMSO >98 N5 659 1H NMR (400 MHz, DMSO) 10.06 (s, 1H), 9.53 (s, 1H), 8.75 (s, 1H), 8.75- 8.66 (m, 3H), 8.28- 8.21 (m, 1H), 8.20 (dd, J = 7.7, 1.8 Hz, 1H), 8.06 (dd, J = 8.9, 2.5 Hz, 1H), 7.96-7.90 (m, 2H), 7.58-7.54 (m, 2H), 6.81 (d, J = 8.9 Hz, 1H), 3.11 (s, 6H). DMSO >98 N5 660 .sup.1H NMR (400 MHz, DMSO) 10.15 (s, 1H), 9.54 (s, 1H), 8.91 (s, 1H), 8.76 (s, 1H), 8.74-8.66 (m, 2H), 8.39 (d, J = 2.7 Hz, 1H), 8.37- 8.30 (m, 1H), 8.26 (dd, J = 6.8, 2.6 Hz, 1H), 8.03-7.97 (m, 1H), 7.97-7.90 (m, 1H), 7.85 (d, J = 1.9 Hz, 1H), 7.62-7.52 (m, 2H), 3.98 (s, 3H). DMSO >98 N5 661 .sup.1H NMR (400 MHz, DMSO) 10.06 (s, 1H), 9.52 (d, J = 1.3 Hz, 1H), 8.76 (d, J = 19.6 Hz, 1H), 8.73-8.61 (m, 3H), 8.29-8.16 (m, 3H), 7.99-7.87 (m, 2H), 7.61-7.51 (m, 2H), 6.98 (d, J = 8.6 Hz, 1H), 4.39 (q, J = 7.0 Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H). DMSO >98 N5 662 00 01 02 .sup.1H NMR (400 MHz, DMSO) 10.11 (s, 1H), 9.53 (dd, J = 2.1, 0.7 Hz, 1H), 8.75 (d, J = 1.9 Hz, 1H), 8.73-8.64 (m, 2H), 8.25 (dd, J = 6.9, 2.6 Hz, 1H), 8.19 (dd, J = 8.7, 1.9 Hz, 1H), 7.97-7.89 (m, 2H), 7.61-7.50 (m, 3H), 7.41 (dd, J = 8.1, 1.9 Hz, 1H), DMSO >98 N5 7.11 (d, J = 8.1 Hz, 1H), 6.13 (s, 2H). 663 03 04 05 .sup.1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.54 (s, 1H), 8.85 (s, 1H), 8.76- 8.66 (m, 2H), 8.33- 8.22 (m, 2H), 8.00-7.89 (m, 2H), 7.62-7.52 (m, 3H), 7.43 (s, 1H), 7.14 (s, 1H), 3.91 (s, 3H). DMSO >98 N5 664 06 07 08 .sup.1H NMR (400 MHz, DMSO) 10.16 (s, 1H), 9.52 (d, J = 1.3 Hz, 1H), 8.89- 8.81 (m, 1H), 8.73- 8.64 (m, 2H), 8.37-8.28 (m, 1H), 8.28-8.21 (m, 1H), 8.01-7.86 (m, 2H), 7.81-7.69 (m, 2H), 7.60- 7.51 (m, 2H), 7.33 (s, 1H), 3.97 (s, 3H). DMSO >98 N5 665 09 0 1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.53 (d, J = 1.9 Hz, 1H), 8.89 (s, 1H), 8.73-8.61 (m, 2H), 8.57 (d, J = 4.5 Hz, 1H), 8.34- 8.18 (m, 2H), 8.09- 7.86 (m, 5H), 7.62- 7.49 (m, 2H), 2.88-2.80 (m, 4H). DMSO >98 N5 666 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.57 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 9.21 (s, 2H), 9.08-9.02 (m, 1H), 9.02-8.96 (m, 1H), 8.89 (dd, J = 5.2, 1.5 Hz, 1H), 8.39-8.30 (m, 1H), 8.25-8.18 (m, 1H), 8.07-7.87 (m, 3H), 7.56 (t, J = 9.1 Hz, 1H). DMSO >98 N5 667 HCl .sup.1H NMR (400 MHz, DMSO) 10.78 (s, 1H), 9.53 (s, 1H), 9.16-9.02 (m, 2H), 8.99-8.88 (m, 1H), 8.66-8.55 (m, 1H), 8.38 (d, J = 8.2 Hz, 1H), 8.20 (d, J = 5.0 Hz, 1H), 8.04 (dt, J = 27.3, 13.6 Hz, 7H), 7.57 (t, J = 8.8 Hz, 1H), 2.84 (d, J = 3.8 Hz, 3H). DMSO >98 N5 668 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.49 (s, 1H), 9.53 (d, J = 1.5 Hz, 1H), 8.99- 8.83 (m, 3H), 8.34- 8.25 (m, 1H), 8.21 (dd, J = 6.8, 2.6 Hz, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.98-7.91 (m, 1H), 7.86 (dd, J = 7.8, 5.2 Hz, 1H), 7.78- 7.70 (m, 2H), 7.57 (t, J = 9.1 Hz, 1H), DMSO >98 N5 7.47 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.5 Hz, 1H), 2.45 (s, 6H). 669 HCl .sup.1H NMR (400 MHz, DMSO) 10.22 (s, 1H), 9.55 (d, J = 1.4 Hz, 1H), 8.81- 8.70 (m, 3H), 8.25 (dd, J = 6.8, 2.6 Hz, 1H), 8.13-8.05 (m, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.97-7.89 (m, 1H), 7.64 (dd, J = 7.9, 4.9 Hz, 1H), 7.61- 7.49 (m, 2H), 7.37- 7.26 (m, 2H), DMSO >98 N5 2.41 (s, 3H). 670 HCl .sup.1H NMR (400 MHz, DMSO) 10.77 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 9.09- 8.95 (m, 2H), 8.90 (dd, J = 5.2, 1.5 Hz, 1H), 8.41-8.29 (m, 1H), 8.23 (dd, J = 6.8, 2.6 Hz, 1H), 8.05 (d, J = 8.7 Hz, 1H), 8.01-7.88 (m, 2H), 7.56 (t, J = 9.1 Hz, 1H), 7.50-7.38 (m, 2H), DMSO >98 N5 7.32 (d, J = 8.2 Hz, 1H), 3.97 (s, 3H), 2.23 (s, 3H). 671 HCl .sup.1H NMR (400 MHz, DMSO) 10.77 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 9.09- 8.95 (m, 2H), 8.90 (dd, J = 5.2, 1.5 Hz, 1H), 8.41-8.29 (m, 1H), 8.23 (dd, J = 6.8, 2.6 Hz, 1H), 8.05 (d, J = 8.7 Hz, 1H), 8.01-7.88 (m, 2H), 7.56 (t, J = 9.1 Hz, 1H), 7.50-7.38 (m, 2H), DMSO >98 N5 7.32 (d, J = 8.2 Hz, 1H), 3.97 (s, 3H), 2.23 (s, 3H). 672 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.67 (s, 1H), 9.47 (d, J = 1.6 Hz, 1H), 9.04- 8.94 (m, 2H), 8.89 (dd, J = 5.3, 1.5 Hz, 1H), 8.26 (dd, J = 8.8, 1.9 Hz, 1H), 8.18 (dd, J = 6.8, 2.6 Hz, 1H), 8.09- 8.00 (m, 1H), 8.00- 7.87 (m, 3H), 7.86-7.77 (m, 1H), 7.68-7..57 (m, DMSO >98 N5 1H), 7.53 (t, J = 9.1 Hz, 1H). 673 HCl .sup.1H NMR (400 MHz, DMSO) 10.82 (s, 1H), 9.53 (s, 1H), 9.17-9.04 (m, 1H), 9.04-8.93 (m, 2H), 8.34 (dd, J = 8.7, 1.7 Hz, 1H), 8.18 (dd, J = 6.8, 2.6 Hz, 1H), 8.08 (d, J = 8.6 Hz, 1H), 8.05- 7.89 (m, 2H), 7.57 (t, J = 9.0 Hz, 1H), 7.53-7.44 (m, 3H), 7.09-6.98 (m, 1H), 4.82 (dt, J = DMSO >98 N5 11.7, 5.9 Hz, 1H), 1.33 (d, J = 6.0 Hz, 6H). 674 HCl .sup.1H NMR (400 MHz, DMSO) 10.60 (s, 1H), 9.50 (d, J = 1.7 Hz, 1H), 9.11- 9.02 (m, 1H), 8.99- 8.91 (m, 1H), 8.76 (d, J = 8.8 Hz, 1H), 8.25 (d, J = 1.4 Hz, 1H), 8.19 (dd, J = 6.8, 2.6 Hz, 1H), 8.10-7.92 (m, 4H), 7.82-7.72 (m, 1H), 7.65-7.56 (m, 1H), 7.52 (t, DMSO >98 N5 J = 9.1 Hz, 1H). 675 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.51 (s, 1H), 9.51 (d, J = 1.7 Hz, 1H), 9.07- 9.00 (m, 1H), 8.93 (dd, J = 5.3, 1.4 Hz, 1H), 8.75 (d, J = 8.8 Hz, 1H), 8.28 (d, J = 1.7 Hz, 1H), 8.21 (dd, J = 6.8, 2.6 Hz, 1H), 8.10 (dd, J = 8.7, 1.9 Hz, 1H), 8.02-7.93 (m, 2H), 7.74-7.65 (m, 2H), 7.52 (t, J = 9.1 Hz, 1H), 7.40- DMSO >98 N5 7.31 (m, 1H). 676 HCl .sup.1H NMR (400 MHz, DMSO) 10.63 (s, 1H), 9.54 (d, J = 1.7 Hz, 1H), 9.10 (d, J = 8.1 Hz, 1H), 8.95 (dd, J = 5.3, 1.4 Hz, 1H), 8.81 (d, J = 8.7 Hz, 1H), 8.26- 8.14 (m, 2H), 8.08- 7.91 (m, 3H), 7.75-7.64 (m, 1H), 7.51 (ddd, J = 14.7, 14.2, 6.9 Hz, 2H), 7.44-7.34 DMSO >98 N5 677 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.52 (s, 1H), 9.60-9.49 (m, 1H), 9.37-9.31 (m, 1H), 8.99 (d, J = 8.3 Hz, 1H), 8.95- 8.81 (m, 3H), 8.75 (d, J = 8.3 Hz, 1H), 8.40 (d, J = 1.7 Hz, 1H), 8.30- 8.18 (m, 2H), 8.04- 7.87 (m, 3H), 7.56 (t, J = 9.1 Hz, 1H). DMSO >98 N5 678 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.42 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 9.38 (s, 2H), 9.30 (s, 1H), 9.00-8.92 (m, 1H), 8.92-8.86 (m, 1H), 8.76 (d, J = 8.7 Hz, 1H), 8.34 (d, J = 1.7 Hz, 1H), 8.23 (dd, J = 6.8, 2.6 Hz, 1H), 8.15 (dd, J = 8.6, 1.8 Hz, 1H), 7.99-7.85 (m, 2H), DMSO >98 N5 7.52 (t, J = 9.1 Hz, 1H). 679 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.47 (s, 1H), 9.58-9.49 (m, 1H), 9.21 (s, 2H), 9.09-8.98 (m, 1H), 8.92 (d, J = 3.8 Hz, 1H), 8.77 (d, J = 8.8 Hz, 1H), 8.32 (d, J = 1.8 Hz, 1H), 8.27-8.20 (m, 1H), 8.15 (dd, J = 8.7, 1.8 Hz, 1H), 8.03-7.89 (m, 2H), 7.55 (t, J = 9.1 DMSO >98 N5 Hz, 1H), 4.02 (s, 3H). 680 .sup.1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.56 (d, J = 1.3 Hz, 1H), 8.75- 8.67 (m, 2H), 8.60 (d, J = 8.7 Hz, 1H), 8.32 (dd, J = 6.9, 2.6 Hz, 1H), 8.10 (d, J = 1.6 Hz, 1H), 8.03-7.87 (m, 4H), 7.60-7.50 (m, 2H), 7.12 (d, J = 8.8 Hz, 2H), 3.85 (s, DMSO >98 N5 681 .sup.1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.55-9.46 (m, 1H), 8.69-8.60 (m, 2H), 8.56 (d, J = 8.7 Hz, 1H), 8.25 (dd, J = 6.9, 2.6 Hz, 1H), 8.10 (d, J = 1.8 Hz, 1H), 7.96 (dd, J = 8.7, 1.9 Hz, 1H), 7.91-7.85 (m, 1H), 7.55-7.35 (m, 5H), 7.03-6.95 (m, 1H), 3.83 (s, DMSO >98 N5 3H). 682 0 .sup.1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.55 (d, J = 1.9 Hz, 1H), 8.74- 8.67 (m, 2H), 8.57 (d, J = 8.7 Hz, 1H), 8.32 (dd, J = 6.9, 2.6 Hz, 1H), 8.00- 7.91 (m, 2H), 7.80 (dd, J = 8.6, 1.7 Hz, 1H), 7.60-7.41 (m, 4H), 7.21 (d, J = 7.8 Hz, 1H), 7.12 (td, J = 7.4, 0.9 Hz, 1H), 3.84 (s, 3H). DMSO >98 N5 683 .sup.1H NMR (400 MHz, DMSO) 10.10 (s, 1H), 9.55 (s, 1H), 8.74-8.65 (m, 2H), 8.56 (d, J = 8.6 Hz, 1H), 8.35-8.26 (m, 1H), 7.99-7.89 (m, 2H), 7.81 (s, 1H), 7.70 (dd, J = 8.6, 1.6 Hz, 1H), 7.63-7.47 (m, 6H), 7.40 (s, 1H). DMSO >98 N5 684 .sup.1H NMR (400 MHz, DMSO) 10.16 (s, 1H), 9.61-9.53 (m, 1H), 8.76-8.62 (m, 3H), 8.35-8.28 (m, 1H), 8.24 (d, J = 1.8 Hz, 1H), 8.16-7.99 (m, 6H), 7.99-7.92 (m, 1H), 7.63-7.51 (m, 2H), 7.45 (s, 1H). DMSO >98 N5 685 0 .sup.1H NMR (400 MHz, DMSO) 10.21 (s, 1H), 9.55 (d, J = 1.5 Hz, 1H), 8.78- 8.62 (m, 3H), 8.31 (dd, J = 6.9, 2.6 Hz, 1H), 8.15-8.00 (m, 2H), 8.00- 7.80 (m, 5H), 7.74- 7.65 (m, 1H), 7.64-7.51 (m, 2H). DMSO >98 N5 686 .sup.1H NMR (400 MHz, DMSO) 10.18 (s, 1H), 9.60-9.55 (m, 1H), 8.77-8.65 (m, 2H), 8.46 (s, 1H), 8.37-8.28 (m, 2H), 8.17-8.10 (m, 1H), 7.99-7.93 (m, 2H), 7.81-7.72 (m, 2H), 7.62- 7.50 (m, 3H). DMSO >98 N5 687 .sup.1H NMR (400 MHz, DMSO) 10.18 (s, 1H), 9.56 (d, J = 2.2 Hz, 1H), 8.75- 8.61 (m, 3H), 8.32 (dd, J = 6.8, 2.6 Hz, 1H), 8.07 (s, 1H), 7.99-7.91 (m, 1H), 7.91-7.85 (m, 1H), 7.82-7.75 (m, 1H), 7.61-7.50 (m, 3H), 7.47- 7.36 (m, 2H). DMSO >98 N5 688 0 .sup.1H NMR (400 MHz, DMSO) 10.14 (s, 1H), 9.60-9.53 (m, 1H), 8.74-8.61 (m, 3H), 8.31 (dd, J = 6.9, 2.6 Hz, 1H), 8.20 (d, J = 1.8 Hz, 1H), 8.06 (dd, J = 8.7, 1.9 Hz, 1H), 7.99-7.90 (m, 1H), 7.86-7.77 (m, 2H), 7.65-7.48 (m, 3H), 7.37- 7.26 (m, 1H). DMSO >98 N5 689 .sup.1H NMR (400 MHz, DMSO) 10.13 (s, 1H), 9.56 (d, J = 1.5 Hz, 1H), 8.75- 8.60 (m, 3H), 8.31 (dd, J = 6.9, 2.6 Hz, 1H), 8.15 (d, J = 1.7 Hz, 1H), 8.07- 7.88 (m, 4H), 7.65- 7.49 (m, 2H), 7.39 (t, J = 8.8 Hz, 2H). DMSO >98 N5 690 .sup.1H NMR (400 MHz, DMSO) 10.14 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 8.76- 8.60 (m, 3H), 8.34- 8.25 (m, 1H), 8.21 (d, J = 1.7 Hz, 1H), 8.13 (d, J = 8.4 Hz, 2H), 8.10- 7.97 (m, 3H), 7.97- 7.87 (m, 1H), 7.62- 7.45 (m, 2H). DMSO >98 N5 691 HCl .sup.1H NMR (400 MHz, DMSO) 10.45 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 8.99- 8.91 (m, 1H), 8.91- 8.83 (m, 1H), 8.75 (d, J = 8.8 Hz, 1H), 8.42 (s, 1H), 8.31 (t, J = 3.2 Hz, 1H), 8.29-8.22 (m, 2H), 8.13 (dd, J = 8.7, 1.8 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 8.03- DMSO >98 N5 7.92 (m, 2H), 7.86 (dd, J = 8.0, 5.2 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.59- 7.46 (m, 2H). 692 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.38 (s, 1H), 9.56 (d, J = 1.5 Hz, 1H), 8.93 (d, J = 8.2 Hz, 1H), 8.85 (dd, J = 5.1, 1.5 Hz, 1H), 8.71 (d, J = 8.8 Hz, 1H), 8.27 (dd, J = 6.8, 2.6 Hz, 1H), 8.21 (d, J = 1.7 Hz, 1H), 8.10 (dd, J = 8.7, 1.8 Hz, 1H), 8.01-7.90 (m, 3H), 7.83 (dd, J = DMSO >98 N5 7.8, 5.0 Hz, 1H), 7.64-7.46 (m, 4H). 693 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.91 (s, 1H), 9.52 (d, J = 1.5 Hz, 1H), 9.14 (d, J = 8.1 Hz, 1H), 9.00 (dd, J = 5.4, 1.2 Hz, 1H), 8.91 (d, J = 8.8 Hz, 1H), 8.34 (d, J = 5.1 Hz, 1H), 8.20 (dd, J = 6.8, 2.6 Hz, 1H), 8.14- 8.04 (m, 2H), 8.04- 7.89 (m, 2H), 7.75- 7.48 (m, 4H), DMSO >98 N5 3.18 (s, 6H). 694 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.99 (s, 1H), 9.52 (d, J = 1.7 Hz, 1H), 9.08 (d, J = 8.0 Hz, 1H), 8.97 (dd, J = 5.3, 1.4 Hz, 1H), 8.80 (d, J = 8.8 Hz, 1H), 8.33 (d, J = 2.3 Hz, 1H), 8.18 (dd, J = 6.8, 2.6 Hz, 1H), 8.10 (dd, J = 8.8, 1.8 Hz, 1H), 8.04-7.91 (m, 2H), 7.85 (d, J = 8.7 Hz, 2H), 7.56 (t, J = 9.1 Hz, 1H), DMSO >98 N5 7.09 (s, 2H), 3.05 (s, 6H). 695 00 01 HCl .sup.1H NMR (400 MHz, DMSO) 10.67 (s, 1H), 9.53 (d, J = 1.7 Hz, 1H), 9.07 (d, J = 8.2 Hz, 1H), 8.95 (dd, J = 5.3, 1.4 Hz, 1H), 8.78 (d, J = 8.7 Hz, 1H), 8.26 (s, 1H), 8.21 (dd, J = 6.8, 2.6 Hz, 1H), 8.09 (dd, J = 8.7, 1.8 Hz, 1H), 8.04- 7.92 (m, 2H), 7.79- 7.67 (m, 2H), DMSO >98 N5 7.55 (t, J = 9.1 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H), 2.45 (s, 3H). 696 02 03 04 HCl .sup.1H NMR (400 MHz, DMSO) 10.48 (s, 1H), 9.54 (d, J = 1.5 Hz, 1H), 8.97 (d, J = 8.1 Hz, 1H), 8.93-8.84 (m, 1H), 8.71 (d, J = 8.8 Hz, 1H), 8.30-8.16 (m, 2H), 8.08 (dd, J = 8.7, 1.8 Hz, 1H), 8.01-7.78 (m, 4H), 7.55 (t, J = 9.1 Hz, 1H), 7.39 (d, J = 7.9 Hz, 2H), DMSO >98 N5 2.40 (s, 3H). 697 05 06 07 HCl .sup.1H NMR (400 MHz, DMSO) 10.68 (s, 1H), 9.52 (s, 1H), 9.08 (d, J = 8.1 Hz, 1H), 8.95 (d, J = 4.7 Hz, 1H), 8.82 (d, J = 8.7 Hz, 1H), 8.25-8.12 (m, 2H), 8.06-7.88 (m, 3H), 7.63-7.48 (m, 3H), 7.47-7.35 (m, 1H). DMSO >98 N5 698 08 09 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.47 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 9.01- 8.92 (m, 1H), 8.87 (dd, J = 5.1, 1.4 Hz, 1H), 8.73 (d, J = 8.7 Hz, 1H), 8.24 (dd, J = 6.8, 2.6 Hz, 1H), 8.09 (s, 1H), 7.99-7.78 (m, 4H), 7.59-7.42 (m, 2H), 7.37-7.25 (m, 1H). DMSO >98 N5 699 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.12 (s, 1H), 9.59 (s, 1H), 9.10 (d, J = 8.1 Hz, 1H), 9.00-8.86 (m, 2H), 8.50 (s, 1H), 8.22-8.07 (m, 2H), 8.03-7.86 (m, 4H), 7.72 (t, J = 7.9 Hz, 1H), 7.28 (t, J = 7.1 Hz, 1H). DMSO >98 Scheme 4 synthesis using method N6 coupling 700 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.19 (s, 1H), 9.64 (s, 1H), 9.21-9.08 (m, 1H), 0.07-8.89 (m, 2H), 8.51 (s, 1H), 8.38- 8.26 (m, 2H), 8.16 (d, J = 8.5 Hz, 1H), 8.07-7.87 (m, 3H), 7.83-7.70 (m, 3H), 7.62 (dd, J = 14.2, 7.7 Hz, 1H), 7.40-7.22 (m, 2H). DMSO >98 N6 701 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.17 (s, 1H), 9.65 (s, 1H), 9.13-8.99 (m, 2H), 8.89 (d, J = 5.1 Hz, 1H), 8.50 (s, 1H), 8.31 (d, J = 8.7 Hz, 1H), 8.21 (d, J = 1.8 Hz, 1H), 8.11 (dd, J = 8.6, 1.9 Hz, 1H), 8.05-7.84 (m, 5H), 7.81-7.67 (m, 1H), 7.46-7.34 (m, 2H), 7.27 (dd, J = 11.8, 4.5 Hz, 1H). DMSO >98 N6 702 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.19 (s, 1H), 9.66 (d, J = 1.8 Hz, 1H), 9.20 (d, J = 7.5 Hz, 1H), 9.04-8.89 (m, 2H), 8.50 (s, 1H), 8.35 (d, J = 8.7 Hz, 1H), 8.17 (s, 1H), 8.11- 7.86 (m, 4H), 7.86- 7.68 (m, 2H), 7.65- 7.52 (m, 1H), 7.52-7.39 (m, 2H), 7.39-7.23 (m, 1H). DMSO >98 N6 703 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.17 (s, 1H), 9.62 (d, J = 1.6 Hz, 1H), 9.18 (d, J = 8.2 Hz, 1H), 9.03-8.91 (m, 2H), 8.51 (s, 1H), 8.34- 8.20 (m, 2H), 8.16- 7.86 (m, 5H), 7.84- 7.68 (m, 2H), 7.68-7.54 (m, 1H), 7.35-7.19 (m, 1H). DMSO >98 N6 704 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.19 (s, 1H), 9.61 (d, J = 1.8 Hz, 1H), 9.32- 9.22 (m, 1H), 9.02 (dd, J = 5.5, 1.2 Hz, 1H), 8.88 (d, J = 7.8 Hz, 1H), 8.75 (s, 1H), 8.53 (s, 1H), 8.28 (d, J = 8.7 Hz, 1H), 8.16- 8.07 (m, 2H), 8.01- 7.88 (m, 3H), 7.85-7.76 (m, 1H), 7.76-7.65 (m, 1H), 7.54-7.42 (m, DMSO >98 N6 1H), 7.37-7.19 (m, 2H). 705 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.20 (s, 1H), 9.63 (s, 1H), 9.26 (d, J = 8.1 Hz, 1H), 9.01 (d, J = 5.0 Hz, 1H), 8.91 (d, J = 8.3 Hz, 1H), 8.52 (s, 1H), 8.33 (d, J = 8.7 Hz, 1H), 8.21- 8.06 (m, 2H), 8.06-7.87 (m, 3H), 7.72 (t, J = 7.7 Hz, 1H), 7.66-7.52 (m, 2H), 7.49- 7.35 (m, 1H), 7.29 (t, J = 7.5 Hz, 1H). DMSO >98 N6 706 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.64 (d, J = 1.7 Hz, 1H), 9.25 (d, J = 8.2 Hz, 1H), 9.05-8.89 (m, 2H), 8.67-8.45 (m, 1H), 8.34 (d, J = 8.7 Hz, 1H), 8.19 (s, 1H), 8.09 (dd, J = 8.0, 5.5 Hz, 1H), 8.04-7.88 (m, 3H), 7.79-7.62 (m, 2H), 7.56-7.35 (m, 2H), 7.35-7.23 (m, 1H). DMSO >98 N6 707 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.18 (s, 1H), 9.62 (d, J = 1.6 Hz, 1H), 9.16 (d, J = 8.1 Hz, 1H), 9.08-8.88 (m, 2H), 8.51 (s, 1H), 8.37- 8.23 (m, 2H), 8.19- 8.09 (m, 1H), 8.09- 7.88 (m, 3H), 7.83-7.63 (m, 3H), 7.43-7.32 (m, 1H), 7.32-7.21 (m, 1H). DMSO >98 N6 708 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.52 (s, 1H), 9.56 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 7.8 Hz, 1H), 8.92 (d, J = 4.8 Hz, 1H), 8.78 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 1.7 Hz, 1H), 8.13-8.08 (m, 2H), 8.08-7.98 (m, 3H), 7.98-7.88 (m, DMSO >98 N6/F5 followed by G1 1H), 7.63 (t, J = 8.2 Hz, 1H), 7.42 (t, J = 8.8 Hz, 2H), 7.28-7.15 (m, 1H). 709 HCl .sup.1H NMR (400 MHz, DMSO) 10.60 (s, 1H), 9.56 (s, 1H), 9.07 (d, J = 7.9 Hz, 1H), 8.93 (d, J = 4.3 Hz, 1H), 8.77 (d, J = 8.7 Hz, 1H), 8.41 (s, 1H), 8.37- 8.27 (m, 1H), 8.24 (d, J = 1.7 Hz, 1H), 8.11 (dd, J = 8.7, 1.8 Hz, 1H), 8.08- 7.94 (m, 3H), 7.79- 7.65 (m, 2H), DMSO >98 N6/F5 followed by G1 7.41 (t, J = 8.8 Hz, 2H). 710 1H NMR (DMSO-d6) ppm 3.81(s, 3H), 3.88 (s, 3H), 7.11- 7.71 (m, 9H), 7.91 (d, 1H, J = 8.7 Hz), 8.23 (d, 1H, J = 8.7 Hz), 8.53-8.64 (m, 2H), 8.87 (d, 1H, J = 1.5 Hz), 9.37 (d, 1H, J = 1.5 Hz), 9.83 (s, 1H) DMSO >98 N6/F5 followed by G1 711 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.04 (d, 1H, J = 4.1 Hz), 7.48-7.57 (m, 5H), 7.98 (dd, 1H, J = 7.1, 1.7 Hz), 8.26-8.29 (m, 3H), 8.27 (dd, 1H, J = 7.1, 8.7 Hz), 8.78- 9.53 (m, 3H), 9.54 (s, 1H), 10.37 (s, 1H) DMSO >98 N6/F5 followed by G1 712 0 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.05 (d, 1H, J = 4.1 Hz), 7.48-7.57 (m, 4H), 7.88 (dd, 1H, J = 7.1, 1.7 Hz), 8.25-8.29 (m, 3H), 8.37 (dd, 1H, J = 7.1, 8.7 Hz), 8.78- 9.53 (m, 3H), 9.54 (s, 1H), 10.37 (s, 1H) DMSO >98 N6/F5 followed by G1 713 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.05-7.51 (m, 9H), 7.95 (d, 1H, J = 8.7 Hz), 8.26 (d, 1H, J = 8.7 Hz), 8.54- 8.88 (m, 3H), 9.38 (s, 1H), 10.19 (s, 1H) DMSO >98 N6/F5 followed by G1 714 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.04-7.06 (m, 2H), 7.46-7.76 (m, 8H), 7.95 (d, 2H, J = 8.6 Hz), 8.24 (d, 1H, J = 1.7 Hz), 8.69- 8.87 (m, 3H), 9.56 (s, 1H), 10.18 (s, 1H) DMSO >98 N6/F5 followed by G1 715 0 1H NMR (DMSO-d6) ppm 3.84 (s, 3H), 3.89 (s, 3H), 6.81- 7.56 (m, 2H), 7.40- 7.70 (m, 7H), 7.95 (d, 1H, J = 8.5 Hz), 8.23 (d, 1H, J = 1.5 Hz), 8.69-8.89 (m, 3H), 9.58 (s, 1H), 10.06 (s, 1H) DMSO >98 N6/F5 followed by G1 716 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.03-7.06 (m, 1H), 7.50-8.39 (m, 10H), 8.86-8.98 (m, 3H), 9.58 (s, 1H), 10.06 (s, 1H) DMSO >98 N6/F5 followed by G1 717 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.02-7.07 (m, 2H), 7.31 (s, 1H), 7.47- 7.56 (m, 5H), 7.81- 8.26 (m, 4H), 8.26- 8.90 (m, 3H), 9.57 (s, 1H), 10.27 (s, 1H) DMSO >98 N6/F5 followed by G1 718 0 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), 7.03-7.50 (m, 8H), 7.98 (d, 1H, J = 8.7 Hz), 8.30 (d, 1H, J = 8.7 Hz), 8.48- 8.91 (m, 3H), 9.30 (s, 1H), 10.19 (s, 1H) DMSO >98 N6/F5 followed by G1 719 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.03-7.54 (m, 8H), 7.97 (d, 1H, J = 8.7 Hz), 8.28 (d, 1H, J = 8.7 Hz), 8.56- 8.86 (m, 3H), 9.40 (s, 1H), 10.23 (s, 1H) DMSO >98 N6/F5 followed by G1 720 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.03-7.52 (m, 8H), 7.95 (d, 1H, J = 8.7 Hz), 8.26 (d, 1H, J = 8.7 Hz), 8.52- 8.85 (m, 3H), 9.38 (s, 1H), 10.17 (s, 1H) DMSO >98 N6/F5 followed by G1 721 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), 7.05-7.54 (m, 8H), 8.00 (d, 1H, J = 8.7 Hz), 8.27 (d, 1H, J = 8.7 Hz), 8.55- 8.87 (m, 3H), 9.38 (s, 1H), 10.34 (s, 1H) DMSO >98 N6/F5 followed by G1 722 0 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.05-7.53 (m, 7H), 7.93 (s, 1H), 7.96 (d, 1H, J = 8.7 Hz), 8.16 (s, 1H), 8.26 (d, 1H, J = 8.7 Hz), 8.74-8.89 (m, 3H), 9.55 (s, 1H), 10.27 (s, 1H) DMSO >98 N6/F5 followed by G1 723 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.03-7.54 (m, 7H), 7.92 (s, 1H), 7.97 (d, 1H, J = 8.7 Hz), 8.28 (d, 1H, J = 8.7 Hz), 8.56-8.85 (m, 3H), 9.40 (s, 1H), 10.25 (s, 1H) DMSO >98 N6/F5 followed by G1 724 1H NMR (DMSO-d6) ppm 3.88 (s, 3H), 7.03-7.74 (m, 8H), 7.98 (d, 1H, J = 8.7 Hz), 8.27 (d, 1H, J = 8.7 Hz), 8.52- 8.87 (m, 3H), 9.32 (s, 1H), 10.22 (s, 1H) DMSO >98 N6/F5 followed by G1 725 0 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.05-7.71 (m, 8H), 7.99 (d, 1H, J = 8.6 Hz), 8.30 (d, 1H, J = 8.7 Hz), 8.67- 8.92 (m, 3H), 9.37 (s, 1H), 10.52 (s, 1H) DMSO >98 N6/F5 followed by G1 726 1H NMR (DMSO-d6) ppm 3.89 (s, 3H), 7.03-7.71 (m, 9H), 7.99 (d, 1H, J = 8.7 Hz), 8.29 (d, 1H, J = 8.7 Hz), 8.67- 8.92 (m, 3H), 9.37 (s, 1H), 10.52 (s, 1H) DMSO >98 N6/F5 followed by G1 727 1H NMR (DMSO-d6 at 70 C.) ppm 3.89 (s, 3H), 7.02-7.52 (m, 8H), 7.90 (d, 1H, J = 8.5 Hz), 7.93 (s, 1H), 7.99 (d, 1H, J = 8.6 Hz), 8.22 (s, 1H), 8.74- 8.91 (m, 3H), 9.52 (s, 1H), 10.23 (s, 1H) DMSO >98 N6/F5 followed by G1 728 00 1H NMR (DMSO-d.sub.6) ppm 2.50 (s, 3H), 3.89 (s, 3H), 7.06 (s, 1H), 7.49-7.85 (m, 9H), 8.01-8.96 (m, 4H), 9.58 (s, 1H), 10.50 (s, 1H) DMSO >98 N6/F5 followed by G1 729 01 02 03 .sup.1H NMR (DMSO-d.sub.6) ppm 3.89 (s, 3H), 7.04 (br s, 1H), 7.22 (s, 1H), 7.49-8.30 (m, 9H), 8.77-8.91 (m, 3H), 9.55 (s, 1H), 10.37 (s, 1H) DMSO >98 N6/F5 followed by G1 730 04 05 06 .sup.1H NMR (DMSO-d.sub.6) ppm 3.89 (s, 3H), 7.04 (s, 1H), 7.49- 8.32 (m, 9H), 8.91- 9.04 (m, 3H), 9.54 (s, 1H), 10.63 (s, 1H) DMSO >98 N6/F5 followed by G1 731 07 08 09 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), 7.03 (s, 1H), 7.44- 8.25 (m, 9H), 8.71- 8.84 (m, 3H), 9.52 (s, 1H), 10.23 (s, 1H) DMSO >98 N6/F5 followed by G1 732 0 .sup.1H NMR (400 MHz, DMSO) 12.02 (s, 1H), 10.53 (s, 1H), 9.49 (s, 1H), 9.02- 8.72 (m, 3H), 8.30 (dd, J = 8.7, 1.6 Hz, 1H), 8.05 (dd, J = 32.2, 5.3 Hz, 2H), 7.81-7.72 (m, 2H), 7.49 (dd, J = 8.0, 5.4 Hz, 3H), 7.25 (t, J = 9.2 Hz, 1H), 7.11-6.98 (m, 1H), 3.89 (s, 3H). DMSO >98 N6/F5 followed by G1 733 .sup.1H NMR (400 MHz, DMSO) 10.54 (s, 1H), 9.43 (s, 1H), 8.86 (d, J = 1.8 Hz, 1H), 8.64 (dd, J = 21.1, 5.9 Hz, 2H), 8.31 (dd, J = 8.7, 1.9 Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.59-7.45 (m, 4H), 7.42-7.30 (m, 3H), 7.09-6.98 (m, 1H), 3.89 (s, 3H). DMSO >98 N6/F5 followed by G1 734 .sup.1H NMR (400 MHz, DMSO) 13.18 (s, 1H), 10.57 (s, 1H), 9.48 (s, 1H), 8.98 (d, J = 1.3 Hz, 1H), 8.78 (t, J = 7.1 Hz, 2H), 8.30 (dd, J = 8.7, 1.7 Hz, 1H), 8.18 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.7 Hz, 1H), 7.83 (dd, J = 8.9, 1.8 Hz, 1H), 7.74-7.62 (m, 2H), 7.56-7.43 (m, DMSO >98 N6/F5 followed by G1 2H), 7.09-7.01 (m, 1H), 3.90 (s, 3H). 735 0 .sup.1H NMR (400 MHz, DMSO) 11.16 (s, 1H), 10.11 (s, 1H), 9.51 (d, J = 1.2 Hz, 1H), 8.91 (d, J = 1.7 Hz, 1H), 8.71- 8.58 (m, 2H), 8.23 (dd, J = 8.7, 1.9 Hz, 1H), 7.95 (dd, J = 23.9, 5.2 Hz, 2H), 7.60-7.34 (m, 5H), 7.06-6.98 (m, 1H), 6.06 (s, 2H), 3.89 (s, 3H). DMSO >98 N6/F5 followed by G1 736 .sup.1H NMR (400 MHz, DMSO) 10.78 (s, 1H), 10.65 (s, 1H), 10.08 (s, 1H), 9.55 (d, J = 2.0 Hz, 1H), 8.88 (d, J = 1.8 Hz, 1H), 8.76-8.66 (m, 2H), 8.24 (dd, J = 8.7, 1.9 Hz, 1H), 7.94 (d, J8.7 Hz, 1H), 7.65 (d, J = 1.9 Hz, 1H), 7.58 (dd, J = 7.7, 5.1 Hz, 1H), 7.49 (dt, J = 4.7, DMSO >98 N6/F5 followed by G1 3.1 Hz, 3H), 7.41 (dd, J = 8.4, 2.0 Hz, 1H), 7.08-6.99 (m, 3H), 3.88 (s, 3H). 737 HCl .sup.1H NMR (400 MHz, DMSO) 9.93 (s, 1H), 9.40 (s, 1H), 8.86 (d, J = 1.7 Hz, 1H), 8.64 (dd, J = 28.9, 5.8 Hz, 2H), 8.27 (dd, J = 8.7, 1.9 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 2.6 Hz, 1H), 7.61-7.45 (m, 5H), 7.38 (dd, J = 8.8, 2.6 Hz, 1H), 7.24 (d, J = 8.9 Hz, DMSO >98 N6/F5 followed by G1 1H), 7.09-6.98 (m, 1H), 3.89 (d, J = 2.9 Hz, 1H), 3.83 (s, 3H). 738 0 .sup.1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.56 (s, 1H), 8.88 (d, J = 1.7 Hz, 1H), 8.75 (t, J = 7.2 Hz, 2H), 8.27 (dd, J = 8.6, 1.4 Hz, 1H), 8.14 (d, J = 1.6 Hz, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.84 (dd, J = 8.2, 2.0 Hz, 1H), 7.63 (dd, J = 7.7, 4.9 Hz, 1H), 7.48 (dd, J = 11.4, 4.0 Hz, 4H), 7.10- DMSO >98 N6/F5 followed by G1 6.98 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H). 739 .sup.1H NMR (400 MHz, DMSO) 10.07 (s, 1H), 9.55 (s, 1H), 8.85 (s, 1H), 8.70 (d, J = 5.5 Hz, 2H), 8.24 (dd, J = 8.7, 1.5 Hz, 1H), 8.10 (d, J = 2.4 Hz, 1H), 7.99-7.83 (m, 2H), 7.60-7.40 (m, 4H), 7.30 (d, J = 9.0 Hz, 1H), 7.04 (dd, J = 7.1, 4.4 Hz, 1H), 3.90 (s, 3H), DMSO >98 N6/F5 followed by G1 2.29 (s, 3H). 740 .sup.1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.60 (s, 1H), 8.89 (d, J = 1.8 Hz, 1H), 8.71 (dd, J = 12.8, 6.3 Hz, 2H), 8.24 (dd, J = 8.7, 1.9 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.68 (d, J = 1.7 Hz, 1H), 7.61-7.45 (m, 5H), 7.44-7.37 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 3.89 (s, 3H), 3.65 (s, 3H). DMSO >98 N6/F5 followed by G1 741 .sup.1H NMR (400 MHz, DMSO) 10.04 (s, 1H), 9.60 (s, 1H), 8.89 (d, J = 1.7 Hz, 1H), 8.71 (dd, J = 12.7, 6.3 Hz, 2H), 8.24 (dd, J = 8.7, 1.9 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.68 (d, J = 1.7 Hz, 1H), 7.59-7.45 (m, 4H), 7.44-7.37 (m, 1H), 7.25 (t, J = 6.7 Hz, 1H), 7.07- 6.98 (m, 1H), 3.89 (s, 6H), 2.19 (s, 3H). DMSO >98 N6/F5 followed by G1 742 0 .sup.1H NMR (400 MHz, DMSO) 9.73 (s, 1H), 9.37 (s, 1H), 8.86 (d, J = 1.6 Hz, 1H), 8.63 (d, J = 3.4 Hz, 1H), 8.54 (d, J = 8.0 Hz, 1H), 8.23 (dd, J = 8.7, 1.8 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.55- 7.42 (m, 5H), 7.05- 6.98 (m, 1H), 6.77 (d, J = 2.6 Hz, 1H), 6.68 (dd, J = 8.6, 2.6 Hz, 1H), 3.89 (s, 3H), 3.85 (s, DMSO >98 N6/F5 followed by G1 3H), 3.79 (s, 3H). 743 .sup.1H NMR (400 MHz, DMSO) 10.25 (s, 1H), 9.56 (s, 1H), 8.84 (d, J = 1.7 Hz, 1H), 8.71 (d, J = 9.1 Hz, 1H), 8.27 (dd, J = 8.7, 1.8 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.86- 7.77 (m, 2H), 7.65- 7.56 (m, 1H), 7.52- 7.44 (m, 4H), 7.09-6.99 (m, 2H), 3.89 (s, 3H). DMSO >98 N6/F5 followed by G1 744 .sup.1H NMR (400 MHz, DMSO) 10.42 (s, 1H), 9.55 (s, 1H), 8.87 (d, J = 26.7 Hz, 3H), 8.31 (dd, J = 8.7, 1.7 Hz, 2H), 8.17 (d, J = 1.7 Hz, 2H), 8.02 (d, J = 8.7 Hz, 1H), 7.81 (s, 1H), 7.54-7.39 (m, 3H), 7.11-6.98 (m, 1H), 3.89 (s, 3H). DMSO >98 N6/F5 followed by G1 745 0 .sup.1H NMR (400 MHz, DMSO) 14.27 (s, 1H), 9.79 (s, 1H), 9.32 (d, J = 8.4 Hz, 1H), 8.98 (d, J = 5.2 Hz, 1H), 8.34 (dd, J = 8.7, 1.8 Hz, 1H), 8.29-8.19 (m, 2H), 8.07 (dd, J = 14.6, 8.3 Hz, 2H), 7.93 (s, 1H), 7.64 (d, J = 5.9 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.39 (dd, J = 8.9, 4.9 Hz, 2H), 7.23 (d, J = 5.8 Hz, DMSO >98 N6/F5 followed by G1 1H), 7.08 (dd, J = 8.2, 1.8 Hz, 1H), 3.86 (s, 3H). 746 2 HCl .sup.1H NMR (400 MHz, DMSO) 11.10 (s, 1H), 9.36 (s, 1H), 9.11 (s, 1H), 9.00 (dd, J = 23.2, 6.7 Hz, 2H), 8.41 (d, J = 9.1 Hz, 1H), 8.16 (d, J = 8.7 Hz, 1H), 8.05 (dd, J = 7.9, 5.5 Hz, 1H), 7.80- 7.65 (m, 2H), 7.59-7.44 (m, 3H), 7.41-7.32 (m, 1H), 7.06 (d, J = 8.0 Hz, 1H), 3.90 (s, 3H). DMSO N6/F5 followed by G1 747 .sup.1H NMR (400 MHz, DMSO) 12.92 (d, J = 17.9 Hz, 1H), 9.64 (s, 1H), 9.09 (d, J = 7.9 Hz, 1H), 8.92 (d, J = 4.9 Hz, 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.38 (s, 1H), 8.30 (dd, J = 8.7, 1.7 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.98-7.84 (m, 3H), 7.50 (t, J = 7.9 Hz, 1H), 7.39 (dd, J = 8.1, 5.0 Hz, 2H), 7.06 (dd, J = DMSO >98 N6/F5 followed by G1 8.2, 1.8 Hz, 2H), 3.89 (s, 3H).

(228) TABLE-US-00009 Pu- Method .sup.1H rity of Num- Starting Starting Salt NMR per- Cou- LCMS ber Material 1 Material 2 Product type .sup.1H NMR Solvent cent pling LCMS Method 748 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.71 (s, 1H), 9.56 (s, 1H), 9.45 (s, 2H), 9.29 (s, 1H), 9.22 (s, 1H), 9.13 (d, J = 7.8 Hz, 1H), 8.96 (d, J = 4.3 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H), 8.16- 8.08 (m, 2H), 8.07- 7.99 (m, 1H), 7.75 (s, 1H), 7.59 (dd, J = 19.3, 9.0 DMSO >98 Method N6 Hz, 1H). 749 .sup.1H NMR (400 MHz, DMSO) 10.12 (s, 1H), 9.55 (d, J = 1.4 Hz, 1H), 8.74-8.66 (m, 3H), 8.28 (d, J = 4.9 Hz, 1H), 8.17-8.08 (m, 2H), 7.98- 7.91 (m, 2H), 7.73 (d, J = 9.1 Hz, 1H), 7.61-7.51 (m, 2H), 7.22 (dd, J = 7.3, 5.0 Hz, 1H), 3.95 (s, 3H). DMSO >98 Method N6 750 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.92 (s, 1H), 9.55 (d, J = 1.5 Hz, 1H), 9.33 (s, 1 H), 9.10- 8.99 (m, 2H), 8.93 (d, J = 5.2 Hz, 1H), 8.54 (d, J = 2.5 Hz, 1H), 8.46 (dd, J = 8.8, 1.8 Hz, 1H), 8.33 (s, 1H), 8.18 (ddd, J = 13.0, 7.4, 2.4 Hz, 1H), 8.08 (d, J = DMSO >98 Method N6 8.7 Hz, 1H), 8.01- 7.93 (m, 1H), 7.84 (d, J = 9.0 Hz, 1H), 7.57 (dd, J = 19.7, 9.1 Hz, 1H), 4.03 (s, 3H). 751 HCl .sup.1H NMR (400 MHz, DMSO) 10.57 (s, 1H), 9.53 (d, J = 1.7 Hz, 1H), 9.00 (dd, J = 14.9, 4.8 Hz, 2H), 8.90 (dd, J = 5.1, 1.4 Hz, 1H), 8.78 (d, J = 2.1 Hz, 1H), 8.31 (dt, J = 8.7, 2.2 Hz, 2H), 8.11 (ddd, J = 12.9, 7.5, 2.5 Hz, 1H), 8.03 (d, J = 8.7 Hz, DMSO >98 Method N6 1H), 7.93 (dd, J = 8.0, 5.1 Hz, 1H), 7.75 (dd, J = 6.0, 2.9 Hz, 1H), 7.63- 7.51 (m, 1H), 7.03 (d, J = 8.6 Hz, 1H), 3.94 (d, J = 8.4 Hz, 3H). 752 0 .sup.1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.52 (s, 1H), 9.14 (d, J = 5.6 Hz, 2H), 8.84 (s, 1H), 8.68 (dd, J = 14.0, 6.4 Hz, 2H), 8.28 (dd, J = 8.7, 1.7 Hz, 1H), 8.17-8.06 (m, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.70 (d, J = 9.0 Hz, 1H), 7.62-7.50 (m, DMSO >98 Method N6 2H), 4.02 (s, 3H). 753 .sup.1H NMR (400 MHz, DMSO) 10.17 (s, 1H), 9.54 (d, J = 1.5 Hz, 1H), 9.16 (d, J = 1.9 Hz, 1H), 8.93 (d, J = 1.7 Hz, 1H), 8.74- 8.60 (m, 3H), 8.35-8.26 (m, 2H), 8.19-8.07 (m, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.77- 7.69 (m, 1H), 7.64- 7.51 (m, 3H). DMSO >98 Method N6 754 .sup.1H NMR (400 MHz, DMSO) 10.12 (s, 1H), 9.53 (d, J = 1.4 Hz, 1H), 8.79-8.62 (m, 3H), 8.24-8.06 (m, 2H), 7.94 (t, J = 7.7 Hz, 1H), 7.73 (dd, J = 6.2, 2.9 Hz, 1H), 7.56 (ddd, J = 15.3, 10.1, 4.8 Hz, 3H), 7.41 (dd, J = 8.1, 1.8 Hz, 1H), 7.11 (d, J = DMSO >98 Method N6 8.1 Hz, 1H), 6.13 (s, 2H). 755 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 11.36 (s, 1H), 9.73 (d, J = 1.7 Hz, 1H), 9.52 (d, J = 1.8 Hz, 1H), 9.13-9.02 (m, 3H), 8.96 (dd, J = 5.4, 1.4 Hz, 1H), 8.79 (d, J = 6.9 Hz, 2H), 8.56 (dd, J = 8.9, 1.9 Hz, 1 H), 8.19 (ddd, J = 13.0, 7.5, 2.5 Hz, 1H), 8.09 (d, DMSO >98 Method N6 J = 8.8 Hz, 1 H), 8.02 (dd, J= 8.0, 5.4 Hz, 1H), 7.90 (dt, J = 9.0, 2.8 Hz, 1H), 7.62-7.50 (m, 1H). 756 .sup.1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.55 (d, J = 1.4 Hz, 1H), 8.86 (d, J = 1.7 Hz, 1H), 8.69 (dd, J = 8.8, 2.9 Hz, 2H), 8.25 (dd, J = 8.7, 1.8 Hz, 1H), 8.18-8.07 (m, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 7.2 Hz, 2H), 7.78- 7.68 (m, 1H), DMSO >98 Method N6 7.62-7.53 (m, 4H), 7.47 (t, J = 7.4 Hz, 1H). 757 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.84 (s, 1H), 9.55 (s, 1H), 9.19-9.05 (m, 2H), 8.95 (d, J = 4.1 Hz, 1H), 8.53 (s, 1H), 8.41 (dd, J = 8.7, 1.7 Hz, 1H), 8.28 (s, 1H), 8.16-8.07 (m, 3H), 8.05-7.92 (m, 2H), 7.79 (d, J = 9.1 Hz, 1H), 7.70-7.46 (m, 3H). DMSO >98 Method N6 758 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.78 (s, 1H), 9.55 (d, J = 1.8 Hz, 1H), 9.12 (d, J = 8.6 Hz, 2H), 8.96 (dd, J = 5.4, 1.4 Hz, 1H), 8.40 (dd, J = 8.8, 1.8 Hz, 1H), 8.16- 7.96 (m, 8H), 7.79-7.71 (m, 1H), 7.64-7.53 (m, 1H), 7.47 (s, 1H). DMSO >98 Method N6 759 HCl .sup.1H NMR (400 MHz, DMSO) 10.41 (s, 1H), 9.56 (s, 1H), 8.98-8.77 (m, 3H), 8.23-8.02 (m, 4H), 7.99- 7.65 (m, 5H), 7.56 (dd, J = 19.1, 9.4 Hz, 1H). DMSO >98 Method N6 760 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.51 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 8.1 Hz, 1 H), 8.95-8.84 (m, 2H), 8.21-8.02 (m, 3H), 7.93 (dt, J = 10.6, 5.3 Hz, 1H), 7.77- 7.68 (m, 1H). 7.63- 7.51 (m, 3H), 7.49-7.38 (m, 1H). DMSO >98 Method N6 761 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.51 (s, 1H), 9.55 (d, J = 1.5 Hz, 1H), 9.03 (d, J = 8.2 Hz, 1H), 8.91 (dd, J = 5.3, 1.5 Hz, 1H), 8.82 (s, 1H), 8.16-8.00 (m, 3H), 7.94 (dd, J = 8.0, 5.2 Hz, 1H), 7.87-7.78 (m, 1H), 7.75-7.66 (m, 1H), 7.61- DMSO >98 Method N6 7.44 (m, 2H), 7.39- 7.28 (m, 1H). 762 00 01 02 HCl .sup.1H NMR (400 MHz, DMSO) 10.75 (s, 1H), 9.53 (d, J = 1.7 Hz, 1H), 9.07 (dd, J = 23.2, 4.9 Hz, 2H), 8.95 (dd, J = 5.3, 1.4 Hz, 1H), 8.36 (dd, J = 8.8, 1.9 Hz, 1H), 8.15-7.96 (m, 3H), 7.76 (dd, J = 9.0, 4.1 Hz, 1H), 7.64-7.50 (m, 1H), 7.41 (dt, J = DMSO >98 Method N6 12.9, 1.6 Hz, 2H), 6.99-6.90 (m, 1H), 3.90 (s, 3H). 763 03 04 05 HCl .sup.1H NMR (400 MHz, DMSO) 10.54 (s, 1H), 9.55 (s, 1H), 9.05 (d, J = 8.2 Hz, 1H), 8.92 (d, J = 4.6 Hz, 1H), 8.84 (s, 1H), 8.17-8.02 (m, 3H), 7.96 (dd, J = 7.9, 5.4 Hz, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.56 (dd, J = 19.6, 9.1 Hz, 1H), 7.39-7.21 (m, DMSO >98 Method N6 3H), 3.89 (s, 3H). 764 06 07 08 HCl .sup.1H NMR (400 MHz, DMSO) 10.68 (s, 1H), 9.51 (d, J = 1.3 Hz, 1H), 9.04 (d, J = 8.1 Hz, 1H), 8.97-8.87 (m, 2H), 8.51 (s, 1H), 8.32-8.22 (m, 2H), 8.16-8.05 (m, 2H), 8.00- 7.90 (m, 2H), 7.80- 7.73 (m, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.60-7.47 DMSO >98 Method N6 (m, 2H). 765 09 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.43 (s, 1H), 9.46 (d, J = 1.3 Hz, 1H), 9.01 (d, J = 8.1 Hz, 1H), 8.91 (d, 1H), 8.63 (s, 1H), 8.13-7.91 (m, 3H), 7.73-7.66 (m, 1H), 7.59- 7.49 (m, 2H), 7.44 (dd, J = 8.2, 1.8 Hz, 1H), 7.07 (d, DMSO >98 Method N6 J = 8.1 Hz, 1H), 6.12 (s, 2H). 766 .sup.1H NMR (400 MHz, DMSO) 10.33 (s, 1H), 9.52 (s, 1H), 8.83 (s, 1H), 8.70 (d, J = 6.3 Hz, 2H), 8.32 (d, J = 8.6 Hz, 2H), 8.13- 8.03 (m, 1H), 7.70 (d, J = 7.3 Hz, 1H), 7.58 (dd, J = 7.3, 5.7 Hz, 3H), 7.42 (s. 1 H), 3.95 (s, 3H). DMSO >98 Method N6 767 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.71 (s, 1H), 9.52-9.41 (m, 3H), 9.26 (s, 1H), 9.11-9.02 (m, 2H), 8.96 (d, J = 5.4 Hz, 1H), 8.37 (d, J = 11.6 Hz, 1H), 8.14-7.99 (m, 2H), 7.80- 7.71 (m, 1H), 7.55 (d, J = 9.1 Hz, 1H). DMSO >98 Method N6 768 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.53 (s, 1H), 9.51 (d, J = 1.6 Hz, 1H), 9.07-9.00 (m, 1H), 8.91 (dd, J = 5.3, 1.5 Hz, 1H), 8.79 (s, 1H), 8.20 (dd, J = 11.9, 1.6 Hz, 1H), 8.13- 8.03 (m, 1H), 8.00- 7.91 (m, 3H), 7.76-7.68 (m, 1H), 7.62-7.44 (m, 4H). DMSO >98 Method N6 769 3 HCl .sup.1H NMR (400 MHz, DMSO) 11.13 (s, 1H), 9.64 (d, J = 1.7 Hz, 1H), 9.47 (d, J = 1.5 Hz, 1H), 9.38 (s, 1H), 9.09 (t, J = 7.3 Hz, 2H), 9.01- 8.94 (m, 1H), 8.91- 8.83 (m, 1H), 8.39 (dd, J = 11.6, 1.3 Hz, 1H), 8.22- 8.13 (m, 1H), 8.11- 7.98 (m, 2H), DMSO >98 Method N6 7.93-7.84 (m, 1H), 7.53 (dd, J = 19.7, 9.2 Hz, 1H). 770 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.69 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.97 (dd, J = 5.4, 1.4 Hz, 1H), 8.81 (d, J = 8.7 Hz, 1H), 8.30 (d, J = 1.3 Hz, 1H), 8.15-7.99 (m, 3H), 7.96-7.88 (m, 2H), 7.81-7.72 (m, 1H), 7.63- DMSO >98 Method N6 7.47 (m, 4H). 771 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.89 (s, 1H), 9.54-9.45 (m, 2H), 9.17 (t, J = 8.6 Hz, 1H), 9.10-8.93 (m, 4H), 8.48 (d, J = 1.5 Hz, 1H), 8.25- 8.06 (m, 4H), 7.89- 7.79 (m, 1H), 7.53 (dd, J = 19.6, 9.2 Hz, 1H). DMSO >98 Method N6 772 0 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.67 (s, 1H), 9.54 (d, J = 1.7 Hz, 1H), 9.40 (s, 2H), 9.31 (s, 1H), 9.20 (d, J = 8.2 Hz, 1H), 9.02 (d, J = 4.3 Hz, 1H), 8.89 (d, J = 8.7 Hz, 1H), 8.43 (s, 1H), 8.22 (dd, J = 8.7, 1.9 Hz, 1H), 8.17-8.06 (m, 2H), 7.82- DMSO >98 Method N6 7.74 (m, 1H), 7.56 (dd, J = 19.7, 9.2 Hz, 1H). 773 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.81 (s, 1H), 9.56 (s, 1H), 9.11 (d, J = 8.2 Hz, 1H), 8.94 (dd, J = 17.5, 6.7 Hz, 2H), 8.42 (d, J = 11.9 Hz, 2H), 8.28 (s, 1H), 8.22- 7.94 (m, 5H), 7.81 (d, J = 8.8 Hz, 1H), 7.71-7.46 (m, 3H). DMSO >98 Method N6 774 HCl .sup.1H NMR (400 MHz, DMSO) 10.32 (s, 1H), 9.54 (s, 1H), 8.95-8.78 (m, 2H), 8.65 (d, J = 8.8 Hz, 1H), 8.19-8.09 (m, 2H), 8.02 (d, J = 8.7, 1H), 7.85-7.69 (m, 2H), 7.62- 7.37 (m, 3H), 7.09 (d, J = 7.0 Hz, 1H), 6.13 (s, 2H). DMSO >98 Method N6 775 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.59 (s, 1H), 9.56 (d, J = 1.7 Hz, 1H), 9.11 (d, J = 8.1 Hz, 1H), 9.01-8.88 (m, 1H), 8.79 (d, J = 8.7 Hz, 1H), 8.18-8.06 (m, 2H), 8.05-7.91 (m, 2H), 7.82-7.72 (m, 2H), 7.61- 7.52 (m, 2H), 7.48- 7.37 (m, 2H). DMSO >98 Method N6 776 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.46 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 9.04 (dt, J = 8.1, 1.6 Hz, 1H), 8.91 (dd, J = 5.2, 1.4 Hz, 1H), 8.73 (d, J = 8.7 Hz, 1H), 8.24 (d, J = 1.8 Hz, 1H), 8.15-8.04 (m, 2H), 7.96 (dd, J = 8.0, 5.3 Hz, 1H), 7.84-7.70 (m, DMSO >98 Method N6 2H), 7.65-7.48 (m, 2H), 7.39- 7.25 (m, 1H). 777 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.62 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 9.12 (d, J = 8.1 Hz, 1H), 8.96 (dd, J = 5.3, 1.3 Hz, 1H), 8.78 (d, J = 8.7 Hz, 1H), 8.25 (d, J = 1.7 Hz, 1H), 8.16-7.91 (m, 6H), 7.81-7.69 (m, 1H), 7.56 (dd, J = 19.7, 9.1 Hz, 1H), DMSO >98 Method N6 7.41 (t, J = 8.8 Hz, 1H). 778 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.65 (s, 1H), 9.55 (d, J = 1.7 Hz, 1H), 9.14 (d, J = 8.1 Hz, 1H), 8.97 (dd, J = 5.4, 1.3 Hz, 1H), 8.81 (d, J = 8.7 Hz, 1H), 8.20-8.00 (m, 3H), 7.96- 7.71 (m, 3H), 7.63- 7.42 (m, 2H), 7.38-7.25 (m, 1H). DMSO >98 Method N6 779 HCl .sup.1H NMR (400 MHz, DMSO) 10.40 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.00 (d, J = 8.1 Hz, 1H), 8.90 (dd, J = 5.2, 1.4 Hz, 1H), 8.71 (d, J = 8.7 Hz, 1H), 8.23 (d, J = 1.8 Hz, 1H), 8.17-8.01 (m, 3H), 7.93 (dd, J = 8.0, 5.2 Hz, 1H), 7.84-7.71 (m, DMSO >98 Method N6 2H), 7.69-7.49 (m, 2H). 780 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.78 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.19 (d, J = 8.1 Hz, 1H), 9.06-8.96 (m, 1H), 8.87 (d, J = 8.7 Hz, 1H), 8.22-8.04 (m, 3H), 7.93 (t, J = 10.1 Hz, 1H), 7.78 (dd, J = 6.1, 2.9 Hz, 1H), 7.64-7.49 (m, 3H), 7.47- DMSO >98 Method N6 7.35 (m, 1H). 781 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.47 (s, 1H), 9.53 (d, J = 1.7 Hz, 1H), 9.08 (d, J = 8.1 Hz, 1H), 8.94 (dd, J = 5.3, 1.3 Hz, 1H), 8.74 (d, J = 8.8 Hz, 1H), 8.29 (d, J = 1.8 Hz, 1H), 8.17-7.95 (m, 3H), 7.80-7.65 (m, 3H), 7.61-7.48 (m, 1H), 7.42- 7.30 (m, 1H). DMSO >98 Method N6 782 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.20 (s, 1H), 9.63 (s, 1H), 9.20 (d, J = 8.1 Hz, 1H), 8.97 (dd, J = 5.3, 1.3 Hz, 1H), 8.89 (d, J = 8.3 Hz, 1H), 8.56 (d, J = 1.6 Hz, 1H), 8.46 (s, 1H), 8.31 (dd, J = 8.7, 1.8 Hz, 1H), 8.13-7.92 (m, 4H), 7.90-7.83 (m, 2H), 7.77-7.70 (m, 1H), 7.59 (dd, DMSO >98 Method N6 J = 10.4, 4.8 Hz, 2H), 7.53-7.46 (m, 2H), 7.34-7.25 (m, 1H). 783 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.22 (s, 1H), 9.65 (s, 1H), 9.19 (d, J = 8.1 Hz, 1H), 9.00- 8.91 (m, 2H), 8.44 (d, J = 12.8 Hz, 2H), 8.18- 7.89 (m, 5H), 7.84- 7.70 (m, 2H), 7.56-7.45 (m, 1H), 7.38-7.23 (m, 2H). DMSO >98 Method N6 784 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.15 (s, 1H), 9.65 (s, 1H), 9.38-9.27 (m, 3H), 9.17 (d, J = 9.2 Hz, 1H), 8.92 (dd, J = 25.3, 6.7 Hz, 2H), 8.68 (s, 1H), 8.45 (d, J = 8.9 Hz, 2H), 8.12 (d, J = 9.8 Hz, 1H), 8.04-7.92 (m, 3H), 7.74 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 8.1 Hz, 1H). DMSO >98 Method N6 785 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 13.10 (s, 1H), 9.63 (s, 1H), 9.18 (d, J = 8.0 Hz, 1H), 8.96 (dd, J = 5.3, 1.3 Hz, 1H), 8.87 (d, J = 8.1 Hz, 1H), 8.46 (d, J = 21.1 Hz, 2H), 8.27 (dd, J = 8.7, 1.8 Hz, 1H), 8.09-7.89 (m, 4H), 7.74 (t, J = 7.1 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.38 (dd, J = DMSO >98 Method N6 8.1, 1.9 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.12 (d, J = 8.1 Hz, 1H), 6.12 (s, 2H). 786 2 HCl 1H NMR (DMSO- d6) ppm 9.79 (d, J = 1.56 Hz, 1H), 9.26 (brd, J = 7.2 Hz, 1H), 9.00-8.90 (brm, 2H), 8.18 (d, J = 8.64 Hz, 1H), 8.11 (d, J = 8.64 Hz, 1 H), 8.01 (brt, J = 6.28 Hz, 1H), 7.86-7.80 (brm, 1H), 7.72 (d, J = 3.96 Hz, 1H), DMSO >98 N6 using Na.sub.2CO.sub.3 instead of K.sub.3PO.sub.4 7.53-7.46 (m, 2H), 7.37-7.32 (brm, 1H). The 1H of 2HCl and NH- were not observed. 787 1H NMR (DMSO- d6) ppm 12.63 (brs, 1H), 9.80 (d, J = 1.64 Hz, 1H), 9.05- 8.91 (brm, 2H), 8.76 (brd, J = 4.6 Hz, 1H), 8.10 (brd, J = 8.64 Hz, 1H), 8.02 (d, J = 8.64 Hz, 1H), 7.86- 7.80 (brm, 1H), 7.66-7.62 (brm, 1H), 7.51-7.45 (brm, 1H), 7.34-7.30 (brm, 1H), 6.94 DMSO >98 N6 using Na.sub.2CO.sub.3 instead of K.sub.3PO.sub.4 (brs, 1H), 2.35 (brs, 3H). 788 1H NMR (300 MHz, CD3OD) 9.40 (s, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.56 (d, J = 3.2 Hz, 1H), 8.18-8.08 (m, 2H), 7.76-7.65 (m, 2H), 7.54- 7.44 (m, 2H), 7.23 (t, J = 9.0 Hz, 1H), 3.66 (s, J = 8.0 Hz, 2H), 2.55 (s, J = 20.6 Hz, 8H), 2.30 (s, 3H). CD3OD 99 Method N3 463.0 (M + 1) Method C 789 99 Method N3 434.0 (M + 1) Method C 790 0 99 Method N3 436.0 (M + 1) Method C 791 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.20 (s, 1H), 9.64 (s, 1H), 9.58 (s, 1H), 8.73 (d, J = 5.5 Hz, 2H), 8.60 (s, 1H), 8.53 (dd, J = 7.2, 1.5 Hz, 1H), 8.28-8.25 (m, 1H), 7.99 (d, DMSO 95 Method N1 422.2 (M + 1) Method B (NH4HCO3) J = 8.7 Hz, 1H), 7.61-7.58 (m, 1H), 7.50 (t, J = 4.5 Hz, 3H), 7.30 (d, J = 5.8 Hz, 1H), 7.06 (dd, J = 7.4, 4.1 Hz, 1H), 6.49 (t, J = 6.9 Hz, 1H), 3.91 (s, 3H). 792 HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.42 (s, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.64 (td, J = 7.6, 2.0 Hz, 1H), 8.51 (s, 1H), 8.44 (d, J = 4.4 Hz, 1H), 8.01-7.95 (m, 3H), 7.68- 7.58 (m, 4H), 7.24 (t, J = 7.8 Hz, 1H), 4.26 (q, J = 2.8 Hz, 2H), 1.47 (t, J = 2.8 Hz, 3H). DMSO 95 Method N1 404.0 (M + 1) Method B (NH4HCO3) 793 HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.31 (s, 1H), 9.13 (d, J = 2.0 Hz, 1H), 8.83 (td, J = 8.4, 2.4 Hz, 1H), 8.09 (d, J = 1.2 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.66- 7.60 (m, 2H), 7.36 (dd, J = 8.8, DMSO 95 Method N1 445.0 (M + 1) Method B (NH4HCO3) 2.4 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1 H), 4.28 (q, J = 6.8 Hz, 2H), 1.47 (t, J = 6.8 Hz, 3H). 794 2HCl DMSO 95 Method N1 382.5 (M + 1) Method C 795 3HCl 1H-NMR (300 MHz, DMSO): 13.10 (s, 1H), 9.61 (s, 1H), 9.12 (d, J = 9.8 Hz, 1H), 8.93 (s, 1H), 8.83 (d, J = 15.2 Hz, 2H), 8.66 (s, 1H), 8.58-8.36 (m, 3H), 8.08 (d, J = 11.6 Hz, 2H), 7.96 (d, J = 9.2 Hz, 3H), 7.73 (s, 1H), 7.29 (t, J = 8.7 Hz, 1H), 4.02 (s, 3H). DMSO 95 Method N1 449.4 (M + 1) Method C 796 3HCl 1H-NMR (300 MHz, DMSO): 12.79 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.18 (d, J = 8.2 Hz, 1H), 9.08 (d, J = 6.7 Hz, 2H), 9.05-8.96 (m, 2H), 8.63-8.46 (m, 4H), 8.39 (s, 1H), 8.08 (dd, J = 11.6, 8.5 Hz, 2H), 7.92 (d, J = 6.7 Hz, 1H), 7.77 (s, 1 H), 7.68 (t, J = 7.1 Hz, 1H), 7.32 (t, DMSO 95 Method N1 419.1 (M + 1) Method C J = 7.2 Hz, 1H). 797 3HCl 1H-NMR (300 MHz, DMSO): 12.81 (s, 1H), 9.54 (s, 1H), 9.45 (s, 1H), 9.23 (d, J = 8.2 Hz, 1H), 9.08- 8.93 (m, 3H), 8.83 (s, 1H), 8.52 (d, J = 8.2 Hz, 1H), 8.47-8.34 (m, 2H), 8.14 (ddd, J = 12.9, 8.1, 4.9 Hz, 3H), 7.92 (d, J = 6.6 Hz, 1H), 7.79 (s, 1H), 7.68 (t, J = 7.2 Hz, DMSO 95 Method N1 419.1 (M + 1) Method C 1H), 7.32 (t, J = 7.2 Hz, 1H). 798 2HCl 1H-NMR (300 MHz, DMSO): 13.20 (s, 1H), 9.62 (s, 1H), 9.13 (d, J = 8.1 Hz, 1H), 8.94 (d, J = 3.5 Hz, 2H), 8.55 (s, 1H), 8.48 (s, 1H), 8.31 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.96 (s, 3H), 7.74 (s, 1H), 7.55-7.40 (m, 3H), 7.29 (s, 1H), 7.06 (d, J = 7.4 Hz, 1H), 3.90 (s, DMSO 95 Method N1 448.1 (M + 1) Method C 3H). 799 1H-NMR (300 MHz, DMSO): 13.13 (s, 1H), 9.60 (d, J = 1.4 Hz, 1H), 9.12 (d, J = 7.8 Hz, 1H), 8.73 (dd, J = 9.7, 6.4 Hz, 2H), 8.52 (s, 1H), 8.35 (s, 1H), 8.28 (s, 1H), 8.14 (d, J = 8.7 Hz, 1H), 8.08-7.88 (m, 4H), 7.76 (d, J = 7.2 Hz, 1H), 7.59 (dd, J = 7.4, 4.8 Hz, 1H), 7.23 (t, J = DMSO 95 Method N1 422.2 (M + 1) Method C 7.1 Hz, 1H), 3.94 (s, 3H). 800 0 .sup.1H NMR (400 MHz, DMSO) 10.08 (s, 1H), 9.59-9.49 (m, 1H), 8.79- 8.63 (m, 3H), 8.55 (d, J = 2.1 Hz, 1H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 8.18 (dd, J = 8.7, 1.9 Hz, 1H), 8.02- 7.90 (m, 3H), 7.63- 7.51 (m, 2H), 6.62 (d, J = 8.6 Hz, 1H), 6.24 (s, DMSO >98 N5 2H). 801 MsOH 1H NMR (DMSO- d6) ppm 9.78 (brs, 1H), 9.20- 8.80 (br, 3H), 8.14 (brd, J = 8.64 Hz, 1H), 8.04 (d, J = 8.64 Hz, 1H), 7.83 brm, 2H), 7.52- 7.47 (m,1H), 7.35- 7.31 (m, 1H), 7.00 (brs, 1H), 2.36 (brs, 3H), 2.30 (brs, 3H). The 1H of MsOH and NH were not observed. DMSO >98 N6 using Na.sub.2CO.sub.3 instead of K.sub.3PO.sub.4

(229) TABLE-US-00010 Number PRODUCT Salt type Molecular Mass .sup.1H-NMR .sup.1H-NMR Solvent LCMS LCMS Protocol Purity percent Method for Coupling 802 494.87 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.18 (s. 1H), 9.21 (d, J = 1.8 Hz, 1H), 8.65-8.60 (m, 2H), 8.34-8.24 (m, 2H), 7.96-7.90 (m, 2H), 7.85-7.68 (m, 4H), 7.56 (t, J = 9.0 Hz, 1H), 7.51-7.44 (m, 2H). DMSO 495.0, 497.0 (M + 1) Method B (NH4HCO3) 95 Method N1 803 458.89 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.14 (s, 1H), 9.44 (s, 1H), 8.73-8.63 (m, 1H), 8.55 (t, J = 6.6 Hz, 2H), 8.27 (d, J = 4.6 Hz, 1H), 7.96 (d, J = 6.8 Hz, 2H), 7.76-7.64 (m, 3H), 7.58-7.52 (m, 2H), 7.31 (t, J = 9.2 Hz, 1H), 2.37 (s, 3H). DMSO 459.0, 461.0 (M + 1) Method B (NH4HCO4) 95 Method N1 804 427.86 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.19 (s, 1H), 9.42 (d, J = 1.5 Hz, 1H), 8.74 (d, J = 5.6 Hz, 2H), 8.69-8.63 (m, 2H), 8.52 (d, J = 8.0 Hz, 1H), 8.28 (dd, J = 6.8, 2.6 Hz, 1H), 8.05 (d, J = 7.2 Hz, 1H), 7.96-7.91 (m, 1H), 7.80 (dd, J = 14.6, 6.8 Hz, 3H), 7.59-7.52 (m, 2H). DMSO 428.0, 430.0 (M + 1) 214.6 (M/2 + 1) Method A (TFA) 95 Method N1 805 426.87 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.13 (s, 1H), 9.43 (d, J = 1.6 Hz, 1H), 8.66 (dd, J = 4.7, 1.6 Hz, 1H), 8.59-8.56 (m, 1H), 8.52 (td, J = 7.9, 1.8 Hz, 1H), 8.30 (dd, J = 6.84, 2.60 Hz, 1H), 7.99-7.92 (m, 2H), 7.82-7.73 (m, 3H), 7.58-7.51 (m, 4H), 7.46 (t, J = 7.4 Hz, 1H). DMSO 427.1, 429.1 (M + 1) Method A (TFA) 95 Method N1 806 00 456.9 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.13 (s, 1H), 9.45 (s, 1H), 8.67 (dd, J = 4.7, 1.7 Hz, 1H), 8.62-8.49 (m, 2H), 8.29 (dd, J = 6.8, 2.6 Hz, 1H), 8.03-7.88 (m, 2H), 7.81-7.68 (m, 1H), 7.62-7.49 (m, 2H), 7.48-7.30 (m, 3H), 7.04 (dd, J = 7.8, 2.1 Hz, 1H), 3.87-3.81 (m, 3H). DMSO 457.1, 459.1 (M + 1) Method A (TFA) 95 Method N1 807 01 456.9 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.10 (s, 1H), 9.31 (d, J = 1.6 Hz, 1H), 8.63 (dd, J = 4.8, 1.7 Hz, 1H), 8.61-8.52 (m, 1H), 8.41 (td, J = 8.0, 1.9 Hz, 1H), 8.30 (dd, J = 6.9, 2.6 Hz, 1H), 7.97-7.92 (m, 1H), 7.83 (dd, J = 7.2, 1.2 Hz, 1H), 7.78- 7.66 (m, 1H), 7.62-7.40 (m, 3H), 7.36 (dd, J = 7.4, 1.7 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.4 Hz, 1H), 3.66 (s, 3H). DMSO 457.1, 459.1 (M + 2) Method B (NH4HCO3) 95 Method N1

(230) ##STR01702##

(231) ##STR01703##

(232) Method S: N.sup.4-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)-N.sup.6-(3-(pyrrolidin-1-yl)propyl)quinazoline-4,6-diamine (xxii-a) A 2.0 dram reaction vial was charged with 6-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol, 1.0 equiv), 3-(pyrrolidin-1-yl)propan-1-amine (40 mg, 0.345 mmol, 1.5 equiv), copper(I) iodide (4.4 mg, 0.023 mmol, 0.1 equiv), L-proline (5.3 mg, 0.046 mmol, 0.2 equiv), and potassium carbonate (96 mg, 0.69 mmol, 3.0 equiv) in DMF (3 mL). The reaction mixture was heated at 100 C. overnight. After cooling, water was added to the reaction mixture, and the resultant precipitate was collected by filtration. The crude product was purified via prep-TLC (silica, 2000 micron plate, 95% dichloromethane 5% methanol0.1% NH.sub.4OH) to yield the desired compound as a brown solid (17.2 mg, 15%). LCMS m/z=477.4 (M+1) (Method C) (retention time=1.68 min). .sup.1H NMR (300 MHz, DMSO) 9.68 (s, 1H), 9.46 (s, 1H), 8.59 (d, J=9.4 Hz, 2H), 8.25 (dd, J=6.8, 2.6 Hz, 1H), 7.93 (dd, J=8.3, 3.5 Hz, 1H), 7.69-7.59 (m, 1H), 7.52 (dd, J=11.0, 7.1 Hz, 2H), 7.36-7.19 (m, 2H), 6.41 (s, 1H), 3.34 (m, 2H), 2.69 (m, 6H), 2.02-1.82 (m, 2H), 1.75 (bs, 4H).

(233) ##STR01704##

(234) Method T: N-(3-chloro-4-fluorophenyl)-6-(2-morpholinoethoxy)-2-(pyridin-3-yl)quinazolin-4-amine (xxii-b) A 2.5 dram reaction vial was charged with N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (0.250 g, 0.524 mmol), 2-morpholinoethanol (1 ml, 8.17 mmol) as solvent, copper(I) iodide (0.020 g, 0.105 mmol), racemic-2,2-diamino-1,1-binaphthyl (0.030 g, 0.105 mmol), and cesium carbonate (0.513 g, 1.573 mmol). The reaction mixture was heated at 110 C. overnight. After cooling, water was added to the reaction mixture, and the resultant precipitate was collected by filtration. The solid residue was purified via ISCO (silica, 12 g column, 95% dichloromethane5% methanol0.1% NH.sub.4OH) to yield the desired compound as a brown solid. The solid was further washed with a mixture of water and saturated NaHCO.sub.3 solution and dried. The product off the column was further purified by prep TLC (silica gel, 1000 micron, 95% dichloromethane5% methanol0.1% NH.sub.4OH) to afford the desired product as a light brown solid (21.2 mg, 8%). LCMS m/z=480.0 (M+1) (Method C) (retention time=2.09 min). .sup.1H NMR (300 MHz, DMSO) 9.81 (s, 1H), 9.47 (d, J=1.8 Hz, 1H), 8.66-8.57 (m, 2H), 8.21 (dd, J=6.8, 2.6 Hz, 1H), 7.92 (d, J=2.5 Hz, 1H), 7.87 (ddd, J=8.9, 4.3, 2.7 Hz, 1H), 7.81 (d, J=9.1 Hz, 1H), 7.57-7.47 (m, 3H), 4.25 (t, J=5.8 Hz, 2H), 3.64-3.55 (m, 4H), 2.78 (t, J=5.7 Hz, 2H), 2.55-2.49 (m, 4H).

(235) The compounds in the following table were prepared in a manner analogous to that described in Scheme 20 substituting with appropriate amine or alcohol

(236) TABLE-US-00011 TABLE 5 Salt Molecular .sup.1H-NMR Retention LCMS Purity Method for Number Product type Mass .sup.1H-NMR Solvent LCMS Time (min.) Protocol Percent Coupling 808 05 476.98 1H NMR (300 MHz, DMSO) 9.68 (s, 1H), 9.46 (s, 1H), 8.59 (d, J = 9.4 Hz, 2H), 8.25 (dd, J = 6.8, 2.6 Hz, 1H), 7.93 (dd, J = 8.3, 3.5 Hz, 1H), 7.69-7.59 (m, 1H), 7.52 (dd, J = 11.0, 7.1 Hz, 2H), 7.36-7.19 (m, 2H), 6.41 (s, 1H), 3.34 (m, 2H), 2.69 (m, DMSO 477.4 (M + 1) 1.68 Method C 95 Method S 809 06 492.98 1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 9.46 (s, 1H), 8.60 (td, J = 4.2, 2.4 Hz, 2H), 8.23 (dd, J = 6.8, 2.6 Hz, 1H), 7.90 (ddd, J = 8.9, 4.2, 2.6 Hz, 1H), 7.65 (d, J = 9.0 Hz, 1H), 7.57-7.45 (m, 2H), 7.32 (dd, J = 9.1, 2.2 Hz, 1H), 7.20 (s, 1H), 6.38 (s DMSO 493 (M + 1) 1.97 Method C 100 Method S 810 07 423.87 1H NMR (300 MHz, DMSO) 9.60 (s, 1H), 9.46 (s, 1H), 8.60 (dd, J = 9.1, 3.1 Hz, 2H), 8.22 (dd, J = 6.9, 2.5 Hz, 1H), 7.89 (ddd, J = 9.0, 4.3, 2.7 Hz, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.58-7.46 (m, 2H), 7.37 (dd, J = 9.1, 2.2 Hz, 1H), 7.25 (s, 1H), 6.40 (t DMSO 423.9 (M + 1) 2.16 Method C 100 Method S 811 08 463.93 1H NMR (300 MHz, DMSO) 9.62 (s, 1H), 9.49 (d, J = 1.7 Hz, 1H), 8.70- 8.59 (m, 2H), 8.27 (dd, J = 6.9, 2.5 Hz, 1H), 8.19 (dd, J = 9.0, 5.0 Hz, 1H), 7.91- 7.82 (m, 1H), 7.57-7.43 (m, 2H), 7.01 (dd, J = 9.0, 2.1 Hz, 1H), 6.77 (t, J = 5.3 Hz, 1H), 6.72 DMSO 464.0 (M + 1) 2.19 Method C 100 Method S 812 09 449.91 1H NMR (300 MHz, DMSO) 9.65 (s, 1H), 9.49 (d, J = 2.1 Hz, 1H), 8.69- 8.59 (m, 2H), 8.27 (dd, J = 6.9, 2.6 Hz, 1H), 8.20 (d, J = 9.0 Hz, 1H), 7.87 (ddd, J = 9.0, 4.3, 2.7 Hz, 1H), 7.56- 7.43 (m, 2H), 7.00 (dd, J = 9.1, 2.2 Hz, 1H), 6.79 (d, J = 2.1 Hz, DMSO 449.9 (M + 1) 2.12 Method C 100 Method S 813 0 409.84 1H NMR (300 MHz, DMSO) 9.71 (s, 1H), 9.46 (s, 1H), 8.66-8.55 (m, 2H), 8.24 (d, J = 4.3 Hz, 1H), 7.96-7.87 (m, 1H), 7.64 (d, J = 9.1 Hz, 1H), 7.58- 7.46 (m, 3H), 7.36 (d, J = 9.0 Hz, 1H), 7.28 (s, 1H), 6.38 (s, 1H), 4.96 (s, 1H), 3.69 (s, 2H), 3.42 DMSO 409.9 (M + 1) 1.86 Method C 100 Method S 814 463.93 1H NMR (300 MHz, DMSO) 9.59 (s, 1H), 9.45 (d, J = 1.2 Hz, 1H), 8.60 (dd, J = 7.4, 5.7 Hz, 2H), 8.23 (dd, J = 6.8, 2.5 Hz, 1H), 7.90 (dd, J = 9.0, 2.7 Hz, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.57- 7.46 (m, 2H), 7.36 (d, J = 9.1 Hz, 1H), 7.19 (s, 1H), 6.38 (s DMSO 464.0 (M + 1) 2.19 Method C 95 Method S 815 479.93 1H NMR (300 MHz, DMSO) 9.81 (s, 1H), 9.47 (d, J = 1.8 Hz, 1H), 8.66- 8.57 (m, 2H), 8.21 (dd, J = 6.8, 2.6 Hz, 1H), 7.92 (d, J = 2.5 Hz, 1H), 7.87 (ddd, J = 8.9, 4.3, 2.7 Hz, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.57-7.47 (m, 3H), 4.25 (t, J = 5.8 Hz, 2H). DMSO 480.0 (M + 1) 2.09 Method C 91 Method T 816 423.87 1H NMR (300 MHz, DMSO) 9.60 (s, 1H), 9.47 (s, 1H), 8.67-8.55 (m, 2H), 8.23 (dd, J = 6.9, 2.5 Hz, 1H), 7.90 (ddd, J = 9.0, 4.3, 2.7 Hz, 1H), 7.65 (d, J = 9.0 Hz, 1H), 7.58-7.47 (m, 2H), 7.37 (dd, J = 9.1, 2.2 Hz, 1H), 7.25 (d, J = 1.3 Hz, 1H), 6.41 (t, J = 5.6 Hz, 1H), 3.63 (t, J = 5.7 Hz, 2H), 3.48- 3.35 (m, 5H). DMSO 423.9 (M + 1) Method C 99 Method S 817 437.9 1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 9.47 (s, 1H), 8.66-8.55 (m, 2H), 8.23 (dd, J = 6.9, 2.5 Hz, 1H), 7.90 (ddd, J = 8.8, 4.3, 2.5 Hz, 1H), 7.65 (d, J = 9.0 Hz, 1H), 7.58-7.45 (m, 2H), 7.32 (dd, J = 9.0, 1.8 Hz, 1H), 7.21 (s, 1H), 6.34 (t, J = 5.0 Hz, 1H), 3.50 (t, J = 6.1 Hz, 2H), 3.31-3.20 (m, 5H), 1.92 (p, J = 6.5 Hz, 2H). DMSO 438.1 (M + 1) Method C 99 Method S 818 449.91 1H NMR (300 MHz, DMSO) 9.61 (s, 1H), 9.46 (d, J = 2.1 Hz, 1H), 8.65- 8.56 (m, 2H), 8.23 (dd, J = 6.9, 2.6 Hz, 1H), 7.90 (ddd, J = 8.9, 4.2, 2.6 Hz, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.58- 7.47 (m, 2H), 7.40 (dd, J = 8.9, 2.2 Hz, 1H), 7.26 (d, J = 1.7 Hz, 1H), 6.39 (t, J = 5.7 Hz, 1H), 4.12 (t, J = 6.2 Hz, 1H), 3.85 (dd, J = 14.2, 7.7 Hz, 1H), 3.34-3.25 (m, 5H), 2.15-1.99 (m ,1H), 1.97- 1.80 (m, 3H), 1.74-1.58 (m, 2H). DMSO 449.9 (M + 1) Method C 94 Method S 819 1H-NMR (300 MHz, DMSO): 10.04 (s, 1H), 9.48 (s, 1H), 8.67 (s, 2H), 8.43- 8.31 (m, 1H), 8.14-8.01 (m, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.65 (s, 1H), 7.54 (dd, J = 9.7 Hz, 2H), 7.35 (d, J = 9.0 Hz, 1H), 6.77 (s, 1H), 3.67 (broad doublet, 4H), 3.41 (bs, 2H), 3.08 (d, J = 4.7 Hz, 2H), 2.03 (bs, 2H), 1.91 (bs, 2H). DMSO 463.9 (M + 1) Method C 95 Method S

(237) ##STR01717##

(238) ##STR01718##

(239) Method U: 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (xxiii-a) To a suspension of 2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (synthesized as described in Scheme 1 and 4, substituting 5-methoxy-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid) (371 mg, 1.0 mmol) in CH.sub.2Cl.sub.2 (4.5 mL) was slowly added boron tribromide, 1M solution in dichloromethane (4.5 ml, 4.5 mmol) at 0 C. The reaction mixture was stirred overnight at room temperature after which it was carefully poured into a vigorously stirring mixture of ice and saturated solution of aqueous NaHCO.sub.3. The resultant solid was collected by filtration, dried and then stirred in a saturated solution of aqueous NH.sub.4Cl for 1 h after which the suspension was filtered to give the desired product as a yellowish tan solid (262 mg, 73%). LCMS m/z=357.9 (M+1) (Method C) (retention time=1.68 min). .sup.1H NMR (300 MHz, DMSO) 12.80 (s, 1H), 10.50 (s, 1H), 9.57 (s, 1H), 9.15 (d, J=8.5 Hz, 1H), 8.70 (t, J=7.3 Hz, 2H), 8.50 (s, 1H), 8.08-7.79 (m, 3H), 7.73 (t, J=7.5 Hz, 1H), 7.57 (dd, J=7.6, 4.8 Hz, 1H), 7.46 (d, J=8.5 Hz, 2H), 7.19 (t, J=7.6 Hz, 1H).

(240) Method V: 2-(6-(2-chloroethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (xxiv-a) The suspension of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (50 mg, 0.14 mmol), 1-bromo-2-chloroethane (0.015 ml, 0.15 mmol), and potassium carbonate (23 mg, 0.17 mmol) in DMF (5 mL) was stirred for 3 days at room temperature. Water (10 mL) was added to the mixture and extracted with ethyl acetate (210 mL). The combined organic layer was washed with water (120 mL) and brine (120 mL) and was dried over MgSO.sub.4. After filtration and evaporation, the crude product was obtained, which was washed with hexane and dried to give 48 mg of 2-(6-(2-chloroethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide as light brown solid (79%).

(241) Method G4: 2-(6-(2-morpholinoethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (xxv-a) 2-(6-(2-morpholinoethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide was prepared from 2-(6-(3-chloroethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide and morpholine in a manner analogous to that described for N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride in Scheme 9 using Method G4 to give 50 mg of 2-(6-(2-morpholinoethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide as light yellow solid. LCMS m/z=485 (M+1) (Method C) (retention time=1.71 min) .sup.1H NMR (300 MHz, DMSO) 9.57 (s, 1H), 9.12 (d, J=8.5 Hz, 1H), 8.78-8.63 (m, 2H), 8.48 (s, 1H), 8.02-7.93 (m, 2H), 7.88 (d, J=9.0 Hz, 1H), 7.73 (t, J=8.0 Hz, 1H), 7.63-7.49 (m, 3H), 7.20 (t, J=7.6 Hz, 1H), 4.29-4.16 (m, 2H), 3.65-3.51 (m, 4H), 3.44-3.21 (m, 2H), 2.45-2.31 (m, 4H), 2.06-1.91 (m, 2H).

(242) ##STR01719##

(243) Method W: 2-(6-(2-(methylamino)-2-oxoethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide The suspension of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (synthesized as described in Scheme 24) (0.20 g, 0.56 mmol), 2-chloro-N-methylacetamide (90 mg, 0.80 mmol), cesium carbonate (0.37 g, 1.12 mmol) and potassium iodide (0.19 g. 1.12 mmol) in DMF (10 mL) was stirred for 4 days at room temperature. Water (20 mL) was added to the mixture. The resultant solid was collected by filtration. The obtained solid was washed with CH.sub.2Cl.sub.2-THF (1:1) solution and dried to give 0.11 g of 2-(6-(2-(methylamino)-2-oxoethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide as pale brown solid (46%). LCMS m/z=429 (M+1) (Method C) (retention time=1.65 min). .sup.1H NMR (300 MHz, DMSO) 9.58 (s, 1H), 9.12 (d, J=8.4 Hz, 1H), 8.82-8.64 (m, 2H), 8.48 (s, 1H), 8.32-8.17 (m, 1H), 8.10-7.87 (m, 3H), 7.81-7.49 (m, 4H), 7.21 (t, J=7.5 Hz, 1H), 4.66 (s, 2H), 2.71 (d, J=4.5 Hz, 3H).

(244) ##STR01720##

(245) Method X: 2-(6-(2-(dimethylamino)ethoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide A suspension of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (synthesized as described in Scheme 24) (25 mg, 0.07 mmol), 2-chloro-N,N-dimethylethylamine hydrochloride (20 mg, 0.14 mmol) and cesium carbonate (68.4 mg, 0.21 mmol) in DMF (1 mL) was stirred at 60 C. overnight. The reaction mixture was cooled to room temperature, diluted with water (5 mL) and extracted with dichloromethane (35 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude product was purified by prep-TLC (silica, 2000 micron plate, 95% dichloromethane5% methanol0.1% NH.sub.4OH) to yield the desired compound as a brown solid (12.6 mg, 40%). LCMS m/z=428.9 (M+1) (Method C) (retention time=1.41 min). .sup.1H NMR (300 MHz, DMSO) 12.99 (s, 1H), 9.59 (d, J=1.3 Hz, 1H), 9.12 (d, J=8.4 Hz, 1H), 8.81-8.66 (m, 2H), 8.52 (s, 1H), 8.06-7.88 (m, 3H), 7.80-7.53 (m, 4H), 7.22 (t, J=7.6 Hz, 1H), 4.46 (s, 2H), 3.35 (s, 2H), 2.69 (s, 6H).

(246) The compounds in the following table were prepared in a manner analogous to that described in Scheme 23 substituting with appropriate nucleophile.

(247) TABLE-US-00012 TABLE 6 .sup.1H- Reten- Puri- Meth- Molecu- NMR tion LCMS ty od for Num- Salt lar Sol- Time Proto- Per- Coupl- ber Product type Mass .sup.1H-NMR vent LCMS (min.) col cent ing 820 484.550 1H NMR (300 MHz, DMSO) 9.57 (s, 1H), 9.12 (d, J = 8.5 Hz, 1H), 8.78-8.63 (m, 2H), 8.48 (s, 1H), 8.02-7.93 (m, 2H), 7.88 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.63-7.49 (m, 3H), 7.20 (t, J = 7.6 Hz, 1H), 4.29- 4.16 (m, 2H), 3.65-3.51 (m DMSO 485 (M + 1) 1.71 Method C 100 Methods V, G4 821 470.523 1H NMR (300 MHz, DMSO) 9.58 (s, 1H), 9.24-9.08 (m, 1H), 8.82-8.61 (m, 2H), 8.49 (s, 1H), 8.09-7.84 (m, 3H), 7.73 (t, J = 7.8 Hz, 1H), 7.67-7.47 (m, 3H), 7.19 (t, J = 7.5 Hz, 1H), 4.29- 4.09 (m, 2H), 3.63-3.42 (m, 2H), 3.07-2.77 (m, 3H), 2.2 DMSO 471 (M + 1) 1.75 Method C 100 Methods V, G4 followed by acylation with acetyl chloride/ TEA in DCM at rt. 822 442.470 1H NMR (300 MHz, DMSO) 9.58 (s, 1H), 9.16 (d, J = 8.4 Hz, 1H), 8.82-8.60 (m, 2H), 8.49 (s, 1H), 8.05-7.80 (m, 3H), 7.79- 7.68 (m, 1H), 7.67-7.51 (m, 2H), 7.43 (s, 1H), 7.29-7.12 (m, 1H), 5.03 (s, 2H), 3.10 (s, 3H), 2.89 (s, 3H). DMSO 443 (M + 1) 1.63 Method C 100 Method W 823 HCl 561.94 1H NMR (300 MHz, DMSO) 10.51 (s, 1H), 9.49 (s, 1H), 8.95 (d, J = 6.6 Hz, 1H), 8.85 (d, J = 5.0 Hz, 1H), 8.26 (s, 1H), 8.10 (s, 1H), 8.03-7.80 (m, 3H), 7.73- 7.51 (m, 2H), 7.19 (d, J = 7.4 Hz, 1H), 5.12 (s, 2H), 3.75-3.36 (m, 8H). DMSO 526 (M + 1) 2.02 Method C 100 Method W 824 HCl 598.44 1H NMR (300 MHz, DMSO) 10.98 (s, 1H), 10.59 (s, 1H), 9.50 (s, 1H), 8.96 (d, J = 8.1 Hz, 1H), 8.86 (d, J = 5.1 Hz, 1H), 8.31 (s, 1H), 8.10 (s, 1H), 8.07-7.93 (m, 2H), 7.92-7.80 (m, 1H), 7.71- 7.54 (m, 2H), 7.21 (d, J = 8.0 Hz, 1H), 4.47-4.23 (m, 2 DMSO 526 (M + 1) 2.25 Method C 100 Methods V, G4 825 469.42 1H NMR (300 MHz, DMSO) 9.95 (s, 1H), 9.51 (s, 1H), 8.76- 8.56 (m, 2H), 8.26-8.08 (m, 2H), 8.01 (s, 1H), 7.95-7.81 (m, 2H), 7.70-7.56 (m, 2H), 7.52 (dd, J = 7.9, 4.9 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 4.69 (s, 2H), 2.71 (d, J = 4.5 Hz, 3H). DMSO 470 (M + 1) 2.04 Method C 100 Method W 826 483.44 1H NMR (300 MHz, DMSO) 9.92 (s, 1H), 9.51 (s, 1H), 8.74- 8.57 (m, 2H), 8.17 (s, 1H), 8.01 (d, J = 2.5 Hz, 1H), 7.96-7.83 (m, 2H), 7.70-7.46 (m, 3H), 7.16 (d, J = 7.0 Hz, 1H), 5.03 (s, 2H), 3.06 (s, 3H), 2.88 (s, 3H). DMSO 484 (M + 1) 1.71 Method D 1.00 Method W 827 HCl 564.91 1H NMR (300 MHz, DMSO) 10.59 (s, 1H), 9.99 (s, 1H), 9.49 (s, 1H), 8.97 (d, J = 7.7 Hz, 1H), 8.87 (d, J = 5.3 Hz, 1H), 8.33- 8.18 (m, 2H), 8.04-7.83 (m, 3H), 7.68-7.47 (m, 2H), 4.41- 4.27 (m, 2H), 3.55-3.43 (m, 2H), 3.34-3.20 (m, 2H), 3.03- 2. DMSO 492 (M + 1) 1.81 Method C 1.00 Methods V, G4 828 437.85 1H NMR (300 MHz, DMSO) 9.87 (s, 1H), 9.49 (s, 1H), 8.76- 8.53 (m, 2H), 8.32-8.08 (m, 2H), 8.01-7.77 (m, 3H), 7.69- 7.43 (m, 3H), 4.67 (s, 2H), 2.71 (d, J = 4.6 Hz, 3H). DMSO 438 (M + 1) 1.65 Method D 1.00 Method W 829 0 493.92 1H NMR (300 MHz, DMSO) 9.86 (s, 1H), 9.50 (s, 1H), 8.76- 8.57 (m, 2H), 8.27 (d, J = 7.0 Hz, 1H), 8.05-7.80 (m, 3H), 7.69- 7.45 (m, 3H), 5.04 (s, 2H), 3.78- 3.41 (m, 8H). DMSO 494 (M + 1) 1.98 Method C 98 Method W 830 479.93 1H NMR (300 MHz, DMSO) 9.85 (s, 1H), 9.50 (s, 1H), 8.76- 8.53 (m, 2H), 8.26 (dd, J = 6.9, 2.5 Hz, 1H), 8.08-7.76 (m, 3H), 7.71-7.41 (m, 3H), 4.98 (s, 2H), 3.52-3.09 (m, 4H), 1.37-0.88 (m, 6H). DMSO 480 (M + 1) 2.20 Method C 100 Method W 831 HCl 580.91 1H NMR (300 MHz, DMSO) 10.71 (s, 2H), 9.48 (s, 1H), 9.10- 8.95 (m, 1H), 8.94-8.79 (m, 1H), 8.36-8.27 (m, 1H), 8.26- 8.16 (m, 1H), 8.07-7.83 (m, 3H), 7.68-7.46 (m, 2H), 4.39- 4.18 (m, 2H), 4.05-3.89 (m, 2H), 3.79 (t, J = 11.9 Hz, 2H), 3.53- DMSO 508 (M + 1) 2.14 Method C 100 Methods V, G4 832 451.88 1H NMR (300 MHz, DMSO) 9.85 (s, 1H), 9.50 (s, 1H), 8.71- 8.58 (m, 2H), 8.25 (dd, J = 6.8, 2.5 Hz, 1H), 8.01-7.80 (m, 3H), 7.66-7.45 (m, 3H), 5.02 (s, 2H), 3.06 (s, 3H), 2.88 (s, 3H). DMSO 452 (M + 1) 1.99 Method C 100 Method W 833 HCl 566.88 1H NMR (300 MHz, DMSO) 11.18 (s, 1H), 10.93 (s, 1H), 9.48 (s, 1H), 9.08 (d, J = 8.4 Hz, 1H), 8.94 (d, J = 5.0 Hz, 1H), 8.42 (s, 1H), 8.23 (dd, J = 6.8, 2.5 Hz, 1H), 8.12-7.89 (m, 3H), 7.63 (d, J = 9.1 Hz, 1H), 7.54 (t, J = 9.1 Hz, 1H), 4.45-4.26 (m, DMSO 494 (M + 1) 2.10 Method C 100 Methods V, G4 834 366.78 1H NMR (300 MHz, DMSO) 9.98-9.59 (m, 1H), 9.53-9.41 (m, 1H), 8.71-8.48 (m, 2H), 8.31 (dd, J = 6.9, 2.5 Hz, 1H), 8.01-7.85 (m, 1H), 7.83-7.66 (m, 2H), 7.59-7.35 (m, 3H). DMSO 367 (M + 1) 1.69 Method D 100 Method U 835 428.44 1H NMR (300 MHz, DMSO) 9.58 (s, 1H), 9.12 (d, J = 8.4 Hz, 1H), 8.82-8.64 (m, 2H), 8.48 (s, 1H), 8.32-8.17 (m, 1H), 8.10- 7.87 (m, 3H), 7.81-7.49 (m, 4H), 7.21 (t, J = 7.5 Hz, 1H), 4.66 (s, 2H), 2.71 (d, J = 4.5 Hz, 3H). DMSO 429 (M + 1) 1.65 Method C 100 Method W 836 484.51 1H NMR (300 MHz, DMSO) 9.58 (s, 1H), 9.13 (d, J = 8.3 Hz, 1H), 8.78-8.64 (m, 2H), 8.50 (s, 1H), 8.02-7.80 (m ,3H), 7.73 (t, J = 7.9 Hz, 1H), 7.68-7.53 (m, 2H), 7.49 (s, 1H), 7.20 (t, J = 7.5 Hz, 1H), 5.07 (s, 1H), 3.79-3.40 (m, 8H). DMSO 485 (M + 1) 1.72 Method C 91 Method W 837 442.47 1H NMR (300 MHz, DMSO) 9.59 (s, 1H), 9.12 (d, J = 8.4 Hz, 1H), 8.78-8.63 (m, 1H), 8.49 (s, 1H), 8.29 (s, 1H), 8.11-7.88 (m, 2H), 7.79-7.47 (m, 4H), 7.26- 7.14 (m, 1H), 4.58 (s, 2H), 3.27- 3.08 (m ,2H), 1.18-0.93 (m, 3H). DMSO 443 (M + 1) 1.69 Method C 100 Method W 838 357.37 1H NMR (300 MHz, DMSO) 12.80 (s, 1H), 10.50 (s, 1H), 9.57 (s, 1H), 9.15 (d, J = 8.5 Hz, 1H), 8.70 (t, J = 7.3 Hz, 2H), 8.50 (s, 1H), 8.08-7.79 (m, 3H), 7.73 (t, J = 7.5 Hz, 1H), 7.57 (dd, J = 7.6, 4.8 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H). DMSO 357.9 (M + 1) 1.68 Method C 100 Method U 839 0 2HCl 443.86 1H NMR (300 MHz, DMSO) 10.57 (s, 1H), 9.49 (s, 1H), 8.97 (d, J = 8.2 Hz, 1H), 8.89 (s, 1H), 8.81 (s, 1H), 8.16 (ddd, J = 12.2, 10.9, 5.2 Hz, 3H), 8.05 (d, J = 2.3 Hz, 1H), 8.00-7.86 (m, 3H), 7.55 (t, J = 9.1 Hz, 1H), 6.55 (d, J = 9.5 Hz, 1H). DMSO 443.9 (M + 1) 1.87 Method C 100 Method U 840 2HCl 457.89 1H NMR (300 MHz, DMSO) 10.27 (s, 1H), 9.47 (s, 1H), 9.09 (d, J = 8.1 Hz, 1H), 8.91 (d, J = 4.4 Hz, 1H), 8.56 (s, 1H), 8.18- 8.08 (m, 2H), 8.01 (d, J = 6.3 Hz, 3H), 7.96-7.89 (m, 1H), 7.49 (t, J = 9.1 Hz, 1H), 6.52 (d, J = 9.6 Hz, 1H), 2.71 (s, 3H). DMSO 458.0 (M + 1) 2.12 Method D 100 Method U 841 448.48 1H NMR (300 MHz, DMSO) 13.08 (s, 1H), 9.59 (s, 1H), 9.16 (d, J = 8.4 Hz, 1H), 8.88-8.44 (m, 5H), 8.12-7.85 (m, 4H), 7.73 (q, J = 8.7 Hz, 3H), 7.58 (dd, J = 7.9, 4.8 Hz, 1H), 7.49 (dd, J = 7.8, 4.8 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 5.36 (s, 2H). DMSO 449.2 (M + 1) 1.93 Method C 96 Method X 842 448.48 1H NMR (300 MHz, DMSO) 13.00 (s, 1H), 9.57 (s, 1H), 9.12 (d, J = 8.4 Hz, 1H), 8.76-8.60 (m, 4H), 8.50 (s, 1H), 8.03-7.89 (m, 3H), 7.68 (dd, J = 15.6, 5.2 Hz, 3H), 7.57 (t, J = 4.6 Hz, 3H), 7.19 (t, J = 7.6 Hz, 1H), 5.37 (s, 2H). DMSO 449.1 (M + 1) 1.89 Method C 100 Method X 843 425.48 1H NMR (300 MHz, DMSO) 12.95 (s, 1H), 9.56 (s, 1H), 9.10 (d, J = 8.4 Hz, 1H), 8.75-8.64 (m, 2H), 8.46 (s, 1H), 7.98-7.91 (m, 2H), 7.85 (dd, J = 9.0, 0.8 Hz, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.61-7.48 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 4.12 (d, J = 6.6 Hz, 2H), 2.84 (dd, J = 14.3, 7.4 Hz, 1H), 2.18-2.05 (m, 2H), 1.97- 1.84 (m, 5H). DMSO 426.2 2.46 Method C 100 Method X 844 457.89 1H-NMR (400 MHz, DMSO-d6): 9.95 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 8.82 (d, J = 1.7 Hz, 1H), 8.78- 8.59 (m, 3H), 8.29 (dd, J = 6.8, 2.6 Hz, 1H), 8.16 (d, J = 2.5 Hz, 1H), 8.06-7.86 (m, 3H), 7.69 (dd, J = 9.1, 2.5 Hz, 1H), 7.64- 7.47 (m, 3H), 5.37 (s, 2H). DMSO 458.1, 460.1 (M + 1) 229.6, 230.3 (m/2 + 1) Method A 95 Method X 845 487.91 1H-NMR (400 MHz, DMSO-d6): 9.74 (s, 1H), 9.34 (s, 1H), 8.57- 8.41 (m, 2H), 8.22 (d, J = 2.2 Hz, 1H), 8.10 (dd, J = 6.8, 2.6 Hz, 1H), 7.95 (d, J = 2.5 Hz, 1H), 7.80-7.63 (m, 3H), 7.53-7.30 (m, 3H), 6.82-6.68 (m, 1H), 5.07 (s, 2H), 3.71 (s, 3H). DMSO 488.1, 490.1 (M + 1) 244.6, 245.4 (M/2 + 1) Method A 95 Method X Starting Starting Number Material R.sup.1 Material R.sup.3 Product 846 847 0 848 849 850 0 851 852 853 0 854 855 856 857 0 858 859 860 0 861 862 863 00 864 01 02 03 865 04 05 06 866 07 08 09 867 0 868 869 870 871 872 873 874 875 0 876 1757 Salt .sup.1H NMR Purity Method Number Type .sup.1H NMR Solvent percent of Coupling 846 HCl 1H NMR (400 MHz, DMSO) 9.31 (d, J = 1.7 Hz, DMSO >98 Method X using K.sub.2CO.sub.3 instead of 1H), 8.83-8.76 (m, 1H), 8.76-8.67 (m, 1H), Cs.sub.2CO.sub.3 8.07 (d, J = 9.2 Hz, 1H), 7.86 (dd, J = 6.3, 2.8 Hz, 1H), 7.83-7.73 (m, 2H), 7.70 (d, J = 2.8 Hz, 1H), 7.68-7.61 (m, 1H), 7.60-7.52 (m, 1H), 5.12 (s, 2H), 3.05 (s, 3H), 2.88 (s, 3H). 847 1H NMR (400 MHz, DMSO) 9.28 (dd, J = 2.2, 0.8 DMSO >98 Method X using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 Hz, 1H), 8.66 (dd, J = 4.8, 1.7 Hz, 1H), 8.50- 8.44 (m, 1H), 8.04 (d, J = 9.2 Hz, 1H), 7.92 (d, J = 2.7 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.75 (dd, J = 9.2, 2.9 Hz, 1H), 7.67 (d, J = 2.8 Hz, 1H), 7.56 (dd, J = 8.8, 2.7 Hz, 1H), 7.52 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 5.10 (s, 2H), 3.05 (s, 3H), 2.88 (s, 3H). 848 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.45 (dd, J = 2.1, 0.8 CDCl3 >98 Method X using K.sub.2CO.sub.3 instead of Cs.sub.2CO.sub.3 Hz, 1H), 8.61 (dd, J = 4.8, 1.7 Hz, 1H), 8.59- 8.53 (m, 1H), 8.01 (dd, J = 8.7, 0.8 Hz, 1H), 7.72- 7.62 (m, 2H), 7.56-7.47 (m, 2H), 7.39-7.29 (m, 4H), 4.90 (s, 2H), 3.15 (s, 3H), 3.04 (s, 3H). 849 2 HCl 1H NMR (300 MHz, DMSO) 13.01-11.72 (m, DMSO >98 W 1H), 9.70 (s, 1H), 9.40-9.30 (m ,1H), 8.99 (d, J = 4.5 Hz, 1H), 8.23 (d, J = 2.6 Hz, 1H), 8.12 (dd, J = 8.1, 5.5 Hz, 1H), 8.06-7.98 (m, 2H), 7.92 (d, J = 9.1 Hz, 1H), 7.84 (d, J = 4.9 Hz, 1H), 7.63 (dd, J = 9.1, 2.6 Hz, 1H), 7.56-7.49 (m, 2H), 5.05 (s, 3H), 3.11 (s, 3H), 2.92 (s, 3H). 850 2 HCl 1H NMR (300 MHz, DMSO) 9.74 (d, J = 1.8 Hz, DMSO >98 W 1H), 9.47-9.36 (m, 1H), 9.01 (dd, J = 5.5, 1.2 Hz, 1H), 8.28 (d, J = 2.6 Hz, 1H), 8.16 (dd, J = 8.2, 5.5 Hz, 1H), 8.06-7.93 (m, 3H), 7.81 (s, 1H), 7.66 (dd, J = 9.1, 2.6 Hz, 1H), 7.54-7.44 (m, 2H), 7.42-7.33 (m, 1H), 5.07 (s, 2H), 3.11 (s, 3H), 2.91 (s, 3H). 851 2 HCl 1H NMR (300 MHz, DMSO) 12.67 (s, 1H), 9.31- DMSO >98 W 9.25 (m, 1H), 8.73 (dd, J = 4.8, 1.6 Hz, 1H), 8.52- 8.42 (m, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.66 (d, J = 2.9 Hz, 1H), 7.61-7.47 (m, 4H), 7.45-7.31 (m, 3H), 5.27 (s, 2H), 3.30 (s, 3H). 852 3 HCl 1H NMR (300 MHz, DMSO) 9.56 (d, J = 1.8 Hz, DMSO >98 W 1H), 9.25 (d, J = 8.2 Hz, 1H), 9.08-8.98 (m, 1H), 8.81 (d, J = 4.5 Hz, 1H), 8.31 (td, J = 7.8, 1.6 Hz, 1H), 8.20-8.08 (m, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.88-7.63 (m, 4H), 7.47 (d, J = 2.1 Hz, 1H), 7.30 (dd, J = 8.6, 2.2 Hz, 1H), 5.60 (s, 2H), 4.63 (t, J = 7.8 Hz, 2H), 3.25 (t, J = 7.7 Hz, 2H). 853 3 HCl 1H NMR (300 MHz, DMSO) 9.56 (d, J = 1.8 Hz, DMSO >98 W 1H), 9.22 (d, J = 8.3 Hz, 1H), 9.00 (dd, J = 5.5, 1.3 Hz, 1H), 8.80 (d, J = 4.4 Hz, 1H), 8.29 (td, J = 7.8, 1.6 Hz, 1H), 8.21-8.05 (m, 2H), 8.00-7.66 (m, 5H), 7.29 (dd, J = 8.4, 2.6 Hz, 1H), 7.12 (td, J = 9.0, 2.8 Hz, 1H), 5.59 (s, 2H), 4.66 (t, J = 7.8 Hz, 2H), 3.25 (t, J = 7.6 Hz, 2H). 854 2 HCl 1H NMR (300 MHz, DMSO) 9.55 (d, J = 1.8 Hz, DMSO >98 W 1H), 9.30-99.18 (m, 1H), 9.00 (dd, J = 5.5, 1.3 Hz, 1H), 8.18-8.02 (m, 2H), 7.87 (dd, J = 8.8, 4.8 Hz, 1H), 7.71 (dd, J = 9.2, 2.7 Hz, 1H), 7.49 (d, J = 2.7 Hz, 1H), 7.29 (dd, J = 8.4, 2.6 Hz, 1H), 7.13 (td, J = 9.1, 2.8 Hz, 1H), 5.05 (s, 2H), 4.63 (d, J = 7.7 Hz, 2H), 3.25 (t, J = 7.5 Hz, 2H), 3.02 (s, 3H), 2.86 (s, 3H). 855 2 HCl 1H NMR (300 MHz, DMSO) 9.55 (d, J = 1.7 Hz, DMSO >98 W 1H), 9.15 (d, J = 8.2 Hz, 1H), 8.99-8.90 (m, 1H), 8.10-7.98 (m, 2H), 7.77 (dd, J = 8.9, 4.7 Hz, 1H), 7.67 (dd, J = 9.1, 2.7 Hz, 1H), 7.51 (d, J = 2.6 Hz, 1H), 7.28 (dd, J = 8.4, 2.7 Hz, 1H), 7.12 (dd, J = 10.3, 7.7 Hz, 1H), 4.70 (t, J = 7.8 Hz, 2H), 4.23-4.14 (m, 2H), 3.26 (t, J = 7.9 Hz, 2H), 1.41 (t, J = 6.9 Hz, 3H). 856 2 HCl 1H NMR (300 MHz, DMSO) 9.54 (d, J = 1.7 Hz, DMSO >98 W 1H), 9.19 (d, J = 8.1 Hz, 1H), 8.98 (d, J = 4.3 Hz, 1H), 8.15-8.02 (m, 2H), 7.90-7.72 (m, 2H), 7.60 (d, J = 2.6 Hz, 1H), 7.53-7.41 (m, 1H), 7.40- 7.05 (m, 5H), 5.34 (s, 2H), 4.59 (t, J = 7.8 Hz, 2H), 3.22 (t, J = 7.5 Hz, 2H). 857 HCl .sup.1H NMR (400 MHz, DMSO) 10.56 (s, 1H), 9.49 DMSO >98 Method W (d, J = 1.8 Hz, 1H), 9.11 (d, J = 8.0 Hz, 1H), 8.95 (dd, J = 5.4, 1.3 Hz, 1H), 8.26 (dd, J = 24.6, 3.5 Hz, 2H), 8.12-7.95 (m, 3H), 7.71 (dt, J = 9.1, 4.5 Hz, 2H), 7.56 (dd, J = 19.7, 9.1 Hz, 1H), 4.75 (s, 2H), 2.72 (d, J = 5.0 Hz, 3H). 858 .sup.1H NMR (400 MHz, DMSO) 9.77 (br s, J = 81.7 DMSO >98 Method W Hz, 1H), 9.50 (d, J = 1.5 Hz, 1H), 8.71-8.57 (m, 2H), 8.22-8.07 (m, 1H), 7.97 (t, J = 5.1 Hz, 1H), 7.87 (d, J = 9.1 Hz, 1H), 7.81-7.39 (m, 4H), 5.01 (s, 2H), 3.07 (s, 3H), 2.90 (s, 3H). 859 HCl .sup.1H NMR (400 MHz, DMSO) 10.62 (s, 1H), 9.50 DMSO >98 Method W (d, J = 1.7 Hz, 1H), 9.01 (d, J = 8.1 Hz, 1H), 8.90 (dd, J = 5.3, 1.5 Hz, 1H), 8.32 (d, J = 2.3 Hz, 1H), 8.20-8.09 (m, 1H), 7.95 (dd, J = 8.5, 4.7 Hz, 2H), 7.83-7.74 (m, 1H), 7.67 (dd, J = 9.1, 2.6 Hz, 1H), 7.55 (dd, J = 19.7, 9.1 Hz, 1H), 5.15 (s, 2H), 4.29-3.00 (m, 8H). 860 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.39 (s, 1H), 9.51 DMSO >98 Method W (d, J = 1.6 Hz, 1H), 8.81 (dd, J = 19.3, 6.0 Hz, 2H), 8.29 (s, 1H), 8.16 (dd, J = 10.6, 7.5 Hz, 1H), 7.94 (d, J = 9.0 Hz, 1H), 7.77 (s, 2H), 7.69-7.51 (m, 2H), 4.67 (s, 2H), 3.99 (s, 2H), 3.81 (br s, 4H), 3.70 (br s, 4H). 861 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.82 (s, 1H), 9.50 DMSO >98 Method W (d, J = 1.3 Hz, 1H), 9.02 (d, J = 8.0 Hz, 1H), 8.90 (d, J = 4.4 Hz, 1H), 8.46 (s, 1H), 8.21-8.10 (m, 1H), 8.03-7.90 (m, 2H), 7.84 (d, J = 8.7 Hz, 2H), 7.68 (dd, J = 9.1, 2.3 Hz, 1H), 7.55 (dd, J = 19.5, 9.3 Hz, 1H), 4.67 (s, 2H), 3.23-3.05 (m, 6H), 2.10-1.78 (m, 4H). 862 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.77 (s, 1H), 9.49 DMSO >98 Method W (d, J = 1.6 Hz, 1H), 9.12 (d, J = 8.1 Hz, 1H), 8.99- 8.91 (m, 1H), 8.23 (d, J = 2.1 Hz, 1H), 8.12- 7.99 (m, 3H), 7.78-7.71 (m, 1H), 7.66-7.54 (m, 2H), 4.02 (d, J = 6.5 Hz, 2H), 2.24-2.00 (m, 1H), 1.07 (d, J = 6.7 Hz, 6H). 863 2 HCl .sup.1H NMR (400 MHz, CDCl.sub.3) 10.71 (s, 1H), 9.80 (s, DMSO >98 Method W 1H), 9.40 (d, J = 8.2 Hz, 1H), 8.95 (d, J = 5.2 Hz, 1H), 8.54 (d, J = 2.4 Hz, 1H), 8.24 (d, J = 9.2 Hz, 1H), 8.08 (dd, J = 8.0, 5.6 Hz, 1H), 7.86-7.76 (m, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.56 (d, J = 8.8, 2.2 Hz, 1H), 7.31 (s, 1H), 5.08 (s, 2H), 3.69 (t, J = 6.8 Hz, 2H), 3.55 (t, J = 6.9 Hz, 2H), 2.13-2.01 (m, 2H), 1.98-1.85 (m, 2H). 864 2 HCl 1H NMR (400 MHz, DMSO) 10.62 (s, 1H), 9.50 DMSO >98 Method W (d, J = 1.9 Hz, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.96 (dd, J = 5.5, 1.4 Hz, 1H), 8.27 (d, J = 2.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.15-7.97 (m, 3H), 7.75 (ddd, J = 11.9, 7.4, 3.3 Hz, 2H), 7.56 (dt, J = 10.6, 9.1 Hz, 1H), 4.74 (s, 2H), 4.07-3.93 (m, 1H), 1.13 (d, J = 6.6 Hz, 6H). 865 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.83 (s, 1H), 9.51 DMSO >98 Method W (d, J = 1.8 Hz, 1H), 9.15 (d, J = 8.2 Hz, 1H), 8.97 (dd, J = 5.4, 1.3 Hz, 1H), 8.82-8.74 (m, 1H), 8.55 (d, J = 2.6 Hz, 1H), 8.28-8.19 (m, 1H), 8.16- 8.01 (m, 3H), 7.94 (d, J = 7.9 Hz, 1H), 7.85- 7.75 (m, 2H), 7.70 (dd, J = 7.0, 5.8 Hz, 1H), 7.61- 7.49 (m, 1H), 5.63 (s, 2H). 866 4 HCl .sup.1H NMR (400 MHz, DMSO) 10.62 (s, 1H), 9.50 DMSO >98 Method W (d, J = 1.8 Hz, 1H), 9.11 (d, J = 8.1 Hz, 1H), 8.95 (d, J = 5.4 Hz, 1H), 8.76 (d, J = 5.0 Hz, 1H), 8.42 (s, 1H), 8.18 (t, J = 7.8 Hz, 1H), 8.08-7.96 (m, 4H), 7.89 (d, J = 7.8 Hz, 1H), 7.80 (dd, J = 9.1, 2.6 Hz, 1H), 7.64 (t, J = 8.2 Hz, 2H), 7.24 (d, J = 8.3 Hz, 1H), 5.57 (s, 2H). 867 HCl 1H NMR (300 MHz, DMSO) d 9.58 (s, 1H), 9.05 (d, DMSO 94 Method X (K2CO3, J = 8.2 Hz, 1H), 8.98 (d, J = 8.1 Hz, 1H), 8.88 (d, DMF-THF (1:1), rt) J = 5.1 Hz, 1H), 8.47 (s, 1H), 8.05-7.85 (m, 4H), 7.71 (m, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.24 (dd, J = 7.6 Hz, 1H). 868 2 HCl 1H NMR (300 MHz, DMSO) 13.07 (s, 1H), 9.59 DMSO 99 Method W (d, J = 1.4 Hz, 1H), 9.13 (d, J = 8.1 Hz, 1H), 8.97 (d, J = 7.8 Hz, 1H), 8.92 (d, J = 4.1 Hz, 1H), 8.49 (s, 1H), 8.08-7.92 (m, 4H), 7.80-7.64 (m, 3H), 7.26 (td, J = 7.8, 1.1 Hz, 1H), 7.14 (d, J = 1.5 Hz, 1H), 7.09 (dd, J = 7.9, 1.6 Hz, 1H), 6.95 (d, J = 7.9 Hz, 1H), 6.03 (s, 2H), 5.19 (s, 2H). 869 3HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.67 (s, 1H), 9.40 DMSO 98 Method X (d, J = 7.6 Hz, 1H), 9.01 (d, J = 8.4 Hz, 2H), 8.93 (d, J = 8.4 Hz, 1H), 8.31 (d, J = 7.6 Hz, 1H), 8.22 (t, J = 7.2 Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.97- 7.92 (m, 2H), 7.79-7.71 (m, 3H), 7.33 (t, J = 8.0 Hz, 1H), 5.54 (s, 2H). 870 2HCl .sup.1H-NMR (400 MHz, CD3OD): 9.62 (d, J = 6.9 Hz, MeOD 95 Method W 1H), 9.40 (d, J = 8.2 Hz, 1H), 8.99 (d, J = 5.3 Hz, 1H), 8.82 (t, J = 8.2 Hz, 1H), 8.22 (dd, J = 8.1, 5.7 Hz, 1H), 8.02-7.88 (m, 2H), 7.76-7.60 (m, 3H), 7.31 (t, J = 7.6 Hz, 1H), 4.81 (q, J = 8.1 Hz, 2H). 871 4HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.96 (s, 1H), DMSO- 95 Method X 9.59 (s, 1H), 9.24 (d, J = 8.1 Hz, 1H), 9.00 (s, d.sub.6 1H), 8.80 (d, J = 5.7 Hz, 2H), 8.50 (s, 1H), 8.22 (t, J = 7.2 Hz, 1H), 8.09 (d, J = 9.2 Hz, 2H), 7.99- 7.79 (m, 5H), 7.74-7.54 (m, 6H), 7.30 (t, J = 7.5 Hz, 1H), 5.55 (s, 2H). 872 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.82 (s, 1H), DMSO 95 Method X 9.58 (s, 1H), 9.13 (d, J = 6.9 Hz, 1H), 8.93 (s, 1H), 8.82 (d, J = 8.0 Hz, 1H), 8.43 (s, 1H), 8.04- 7.88 (m, 4H), 7.74-7.69 (m, 3H), 7.28 (t, J = 7.6 Hz, 1H), 7.01-6.91 (m, 2H), 6.87-6.85 (m, 2H), 4.74-4.70 (m, 1H), 4.55-4.53 (m, 1H), 4.50- 4.47 (m, 1H), 4.29-4.24 (m, 1H). 873 3HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.07 (s, 1H), DMSO 95 Method X 9.61 (s, 1H), 9.05-9.00 (m, 2H), 8.88 (d, J = 4 Hz, 1H), 8.51 (s, 1H), 8.25 (s, 1H), 8.11-8.08 (m, 2H), 7.99-7.97 (m, 3H), 7.91-7.88 (m, 2H), 7.76-7.72 (m, 2H), 7.47 (dd, J = 2.0, 8.8 Hz, 1H), 7.27 (t, J = 8.8 Hz, 1H), 5.61 (s, 2H). 874 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.89 (s, 1h), DMSO 95 Method X 10.72 (s, 1H), 9.83 (s, 1H), 9.38 (d, J = 8.2 Hz, 1H), 9.22 (d, J = 5.6 Hz, 1H), 9.03 (d, J= 8.3 Hz, 1H), 8.51 (s, 1H), 8.37-8.27 (m, 1H), 8.02-7.86 (m, 3H), 7.71 (t, J = 7.6 Hz, 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.51 (s, 1H), 7.25 (t, J = 7.5 Hz, 1H), 4.71 (d, J = 7.3 Hz, 2H), 1.56 (s, 1H), 0.81-0.64 (m, 4H). 875 3HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.88 (s, 1H), DMSO 95 Method X 9.57 (s, 1H), 9.24 (d, J = 8.1 Hz, 1H), 9.01 (d, J = 5.3 Hz, 1H), 8.73 (d, J = 8.2 Hz, 1H), 8.49 (s, 1H), 8.37 (t, J = 7.8 Hz, 1H), 8.10 (dd, J = 11.3, 7.0 Hz, 2H), 7.97 (d, J = 7.8 Hz, 2H), 7.86 (s, 2H), 7.80 (d, J = 7.1 Hz, 2H), 7.71 (t, J = 7.8 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 5.65 (s, 2H), 2.78 (s, 3H). 876 CF3COOH .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.93 (s, 1H), DMSO 95 Method W 10.74 (s, 1H), 9.75 (s, 1H), 9.40 (s, 1H), 9.05 (d, J = 8.0 Hz, 2H), 8.99 (d, J = 6.0 Hz, 1H), 7.99 (s, 1H), 7.98-7.96 (m, 1H), 7.89-7.86 (m, 2H), 7.72-7.51 (m, 2H), 7.24 (t, J = 6.0 Hz, 1H), 5.84 (s, 2H), 3.60-3.56 (m, 2H), 3.43-3.39 (m, 2H), 2.06-2.01 (m, 2H), 1.99-1.84 (m, 2H). 1757 .sup.1H NMR (400 MHz, DMSO) 9.32-9.27 (m, 1H), DMSO >98 Method W using K.sub.2CO.sub.3 8.66 (dd, J = 4.8, 1.7 Hz, 1H), 8.64-8.60 (m, instead of Cs.sub.2CO.sub.3 1H), 8.50-8.43 (m, 1H), 8.30-8.03 (m, 1H), 7.93-7.80 (m, 4H), 7.68-7.60 (m, 2H), 7.59- 7.49 (m, 2H), 7.39 (ddd, J = 7.5, 4.8, 1.1 Hz, 1H), 5.43 (s, 2H).

(248) ##STR01825##

(249) ##STR01826##

(250) Method Y: 2-Amino-N-cyclohexyl-benzamide (ii-b) To a dry reaction vial was added cyclohexylamine (40 mol, 1.0 eq) and PS-carbodiimide resin (72 mol, 1.8 eq). The solution of 2-amino-benzoic acid (44 mol, 1.1 eq), diisopropyl ethyl amine (10 Ll) and HOBt (44 mol, 1.1 eq) in THF (500 L) was added to the above vial. The reaction mixture was heated at 40 C. for 6 h on a shaker. The resin was removed by filtration and washed with 10% MeOH/CH.sub.2Cl.sub.2. The solvent was removed in vacuo and the residue was applied to solid phase extraction cartridge (basic silica, 200 mg) and eluted with 50% EtOAc/CH.sub.2Cl.sub.2. After removal of the solvents, the crude 2-amino-N-cyclohexyl-benzamide was obtained and used for the following reaction.

(251) Method Z: N-Cyclohexyl-2-(6-methoxy-2-pyridin-3-yl-quinazolin-4-ylamino)-benzamide (xiv-f) To the crude amide was added the solution of 4-chloro-6-methoxy-2-pyridin-3-yl-quinazoline (20 mol) in 2-propanol (200 L). The mixture was refluxed for 8 h. After evaporation, the residue was dissolved in 5% TFA/MeOH-DMF(1:1) and purified by PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound whose structure was finally confirmed by LCMS using LCMS Method E.

(252) The compounds in the following table were prepared in a manner analogous to that described in Scheme 27, replacing cyclohexylamine with the appropriate amine.

(253) TABLE-US-00013 TABLE 7 Method Exact LCMS of Number Product Mass (M + 1) Coupling 877 489 490 Methods Y, Z 878 453 454 Methods Y, Z 879 495 496 Methods Y, Z 880 0 495 496 Methods Y, Z 881 491 492 Methods Y, Z 882 491 492 Methods Y, Z 883 493 494 Methods Y, Z 884 467 468 Methods Y, Z 885 441 442 Methods Y, Z 886 529 530 Methods Y, Z 887 543 544 Methods Y, Z 888 543 544 Methods Y, Z 889 543 544 Methods Y, Z 890 0 487 488 Methods Y, Z 891 493 494 Methods Y, Z 892 467 468 Methods Y, Z 893 441 442 Methods Y, Z 894 529 530 Methods Y, Z 895 543 544 Methods Y, Z 896 543 544 Methods Y, Z 897 543 544 Methods Y, Z 898 487 488 Methods Y, Z 899 467 468 Methods Y, Z 900 0 501 502 Methods Y, Z 901 465 466 Methods Y, Z 902 435 436 Methods Y, Z 903 519 520 Methods Y, Z 904 487 488 Methods Y, Z 905 487 488 Methods Y, Z 906 467 468 Methods Y, Z 907 501 502 Methods Y, Z 908 465 466 Methods Y, Z 909 435 436 Methods Y, Z 910 0 519 520 Methods Y, Z

(254) ##STR01861##

(255) ##STR01862##

(256) Method Z: Synthesis of N-(4-chlorophenyl)-6-methoxy-2-(pyridin-3-yl)quinazolin-4-amine (vi-k) To 4-chloroaniline (24 mol) was added the solution of 4-chloro-6-methoxy-2-pyridin-3-yl-quinazoline (20 mol) in 2-propanol (200 L). The mixture was refluxed for 8 h. After evaporation, the residue was dissolved in 5% TFA/MeOH-DMF(1:1) and purified by PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound as the TFA salt whose structure was finally confirmed by LCMS using LCMS Method E.

(257) The compounds in the following table were prepared in a manner analogous to that described in Scheme 29, replacing 4-chloroaniline with the appropriate aniline

(258) TABLE-US-00014 TABLE 8 Exact LCMS Method of Number Product Mass (M + 1) Coupling 911 362 363 Method Z 912 358 359 Method Z 913 396 397 Method Z 914 392 393 Method Z 915 388 389 Method Z 916 372 373 Method Z 917 388 389 Method Z 918 0 342 343 Method Z 919 353 354 Method Z 920 416 417 Method Z 921 396 397 Method Z 922 396 397 Method Z 923 356 357 Method Z 924 364 365 Method Z 925 372 373 Method Z 926 392 393 Method Z 927 376 377 Method Z 928 0 426 427 Method Z 929 407 408 Method Z 930 430 431 Method Z 931 440 441 Method Z 932 392 393 Method Z 933 380 381 Method Z 934 380 381 Method Z 935 380 381 Method Z 936 434 435 Method Z 937 421 422 Method Z 938 0 378 379 Method Z 939 376 377 Method Z 940 387 388 Method Z 941 414 415 Method Z 942 392 393 Method Z 943 380 381 Method Z 944 390 391 Method Z 945 428 429 Method Z 946 428 429 Method Z 947 391 392 Method Z 948 00 356 357 Method Z 949 01 377 378 Method Z 950 02 392 393 Method Z 951 03 368 369 Method Z 952 04 397 398 Method Z 953 05 441 442 Method Z 954 06 379 380 Method Z 955 07 401 402 Method Z 956 08 383 384 Method Z 957 09 382 383 Method Z 958 0 379 380 Method Z 959 393 394 Method Z 960 411 412 Method Z 961 379 380 Method Z 962 370 371 Method Z 963 385 386 Method Z 964 427 428 Method Z 965 395 396 Method Z 966 379 380 Method Z 967 402 403 Method Z 968 0 384 385 Method Z

(259) ##STR01921##

(260) ##STR01922##

(261) Method Z: Synthesis of 6-chloro-N-(4-chlorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (vi-c) To 4-chloroaniline (24 mol) was added the solution of 4,6-dichloro-2-(pyridin-3-yl)quinazoline (20 mol) in 2-propanol (200 L). The mixture was refluxed for 8 h. After evaporation, the residue was dissolved in 5% TFA/MeOH-DMF(1:1) and purified by PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound as the TFA salt whose structure was finally confirmed by LCMS using LCMS Method E.

(262) The compounds in the following table were prepared in a manner analogous to that described in Scheme 31, replacing 4-chloroaniline with the appropriate aniline

(263) TABLE-US-00015 TABLE 9 Exact LCMS Method Number Product Mass (M + 1) Coupling 969 366 367 Method Z 970 362 363 Method Z 971 366 367 Method Z 972 346 347 Method Z 973 392 393 Method Z 974 392 393 Method Z 975 419 420 Method Z 976 0 392 393 Method Z 977 346 347 Method Z 978 350 351 Method Z 979 350 351 Method Z 980 350 351 Method Z 981 376 377 Method Z 982 420 421 Method Z 983 360 361 Method Z 984 360 361 Method Z 985 360 361 Method Z 986 0 360 361 Method Z 987 368 369 Method Z 988 368 369 Method Z 989 380 381 Method Z 990 376 377 Method Z 991 396 397 Method Z 992 380 381 Method Z 993 430 431 Method Z 994 392 393 Method Z 995 396 397 Method Z 996 0 380 381 Method Z 997 382 383 Method Z 998 384 385 Method Z 999 465 466 Method Z 1000 357 358 Method Z 1001 396 397 Method Z 1002 425 426 Method Z 1003 380 381 Method Z 1004 434 435 Method Z 1005 396 397 Method Z 1006 0 384 385 Method Z 1007 446 447 Method Z 1008 415 416 Method Z 1009 381 382 Method Z 1010 381 382 Method Z 1011 396 397 Method Z

(264) ##STR01966##

(265) N-(3-Carbamoylthiophen-2-yl)nicotinamide (iii-b) To a solution of 2-aminothiophene-3-carboxamide (800 mg, 5.63 mmol, 1.0 eq.) in THF (15 mL) and Et.sub.3N (626 mg, 6.19 mmol, 1.1 eq.) was added nicotinoyl chloride (795 mg, 5.63 mmol, 1.0 eq.) in anhydrous THF (15 mL) dropwise. The resulted mixture was stirred at room temperature overnight. After the reaction was completed, the volatiles were evaporated. The residue was washed with CH.sub.2Cl.sub.2 (20 mL). The resulting solid was collected and dried in vacuo to give 1.50 g of N-(3-carbamoylthiophen-2-yl)nicotinamide as a brown solid (quantitative yield). LCMS m/z=248.1(M+1) (Method B) (retention time=1.34 min).

(266) 2-(Pyridin-3-yl) thieno[2,3-d]pyrimidin-4(3H)-one (iv-b) A mixture of N-(3-carbamoylthiophen-2-yl)nicotinamide (1.50 g salt, 6.07 mmol, 1.0 eq.) in EtOH (300 mL) was added NaOH (1.50 g, 37.5 mmol, 6.18 eq.). The resulting mixture was stirred at 80 C. for 7 days. After the reaction was completed, the volatiles were removed in vacuo. Water (20 mL) was added to the residue and the pH was adjusted to around 2 by adding dilute HCl (2N in water). The solution was concentrated in vacuo to give 11.0 g of the HCl salt as a beige solid. LCMS m/z=230.0 (M+1) (Method B) (retention time=1.21 min). The crude product containing salts were used for the next step without further purification.

(267) 4-Chloro-2-(pyridin-3-yl) thieno[2,3-d]pyrimidine (v-c) The suspension of 2-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4(3H)-one (6.0 g, containing salts) in POCl.sub.3 (30 mL) was stirred at 120 C. for 10 h. After the reaction was completed, the mixture was added to ice-water slowly. The pH was adjusted to 7 by slowly adding NH.sub.3.H.sub.2O at 0 C., then a precipitate formed. The solid was collected and 540 mg of 4-chloro-2-(pyridin-3-yl) thieno[2,3-d]pyrimidine was obtained as a brown solid. LCMS m/z=247.9, 250.0 (M+1) (Method B) (retention time=1.85 min)

(268) N-(3-Chloro-4-fluorophenyl)-2-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-amine (vi-l) A mixture of 4-chloro-2-(pyridin-3-yl)thieno[2,3-d]pyrimidine (80 mg, 0.32 mmol, 1.0 eq.) and 3-chloro-4-fluorobenzenamine (93 mg, 0.64 mmol, 2.0 eq.) in i-AmOH (8 mL) was stirred at 130 C. overnight. A yellow precipitate formed and was collected and washed with MeOH (10 mL). The solid was suspended in H.sub.2O (10 mL) and NH.sub.3H.sub.2O (1 mL) was added. After filtration and drying in vacuo, 23.0 mg of the product was obtained as a yellow solid (20.0%). LCMS m/z=357.0, 359.0 (M+1) (Method B) (retention time=1.96 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.99 (s, 1H), 9.48 (d, J=1.6 Hz, 1H), 8.70-8.67 (m, 1H), 8.63 (d, J=8.0 Hz, 1H), 8.27 (dd, J=6.8, 2.6 Hz, 1H), 7.76-7.93 (m, 3H), 7.54-7.57 (m, 2H).

(269) The compounds in the following table were prepared in a manner analogous to that described in Scheme 33, replacing 4-fluoro-3-chloroaniline with the appropriate aniline

(270) TABLE-US-00016 TABLE 10 Salt Molecular Number PRODUCT type Mass .sup.1H-NMR 1012 347.39 1H-NMR (400 MHz, DMSO-d6): 12.69 (s, 1H), 9.55 (d, J = 1.3 Hz, 1H), 9.00 (d, J = 8.0 Hz, 1H), 8.44 (s, 1H), 8.60-8.78 (m, 2H), 7.82- 8.00 (m, 3H), 7.42-7.79 (m, 3H), 7.20 (t, J = 7.2 Hz, 1H). 1013 370.38 1H-NMR (400 MHz, DMSO-d6): 9.96 (s, 1H), 9.51 (d, J = 1.2 Hz, 1H), 8.60-8.77 (m, 2H), 7.98- 7.94 (m, 2H), 7.71-7.86 (m, 2H), 7.56-7.50 (m, 1H), 7.30 (t, J = 74.0 Hz, 1H), 6.96 (dd, J = 8.8, 2.0 Hz, 1H). 1014 388.37 1H-NMR (400 MHz, DMSO-d6): 10.04 (s, 1H), 9.50 (d, J = 1.6 Hz, 1H), 8.58-8.75 (m, 2H), 8.18 (s, 1H), 7.77-8.00 (m, 3H), 7.50- 7.65 (m, 2H), 7.08-7.18 (m, 1H) 1015 0 356.8 1H-NMR (400 MHz, DMSO-d6): 9.99 (s, 1H), 9.48 (d, J = 1.6 Hz, 1H), 8.70-8.67 (m, 1H), 8.63 (d, J = 8.0 Hz, 1H), 827 (dd, J = 6.8, 2.6 Hz, 1H), 7.76-7.93 (m, 3H), 7.54-7.57 (m, 2H). Number .sup.1H-NMR Solvent LCMS LCMS Protocol Purity percent Method for Coupling 1012 DMSO 348.1 Method B 95 Method C, G3 (M + 1) (NH4HCO3) 1013 DMSO 371.0 Method B 95 Method C, G3 (M + 1) (NH4HCO3) 1014 DMSO 389.0 Method B 95 Method C, G3 (M + 1) (NH4HCO3) 1015 DMSO 357.0, 359.0 Method B 95 Method C, G3 (M + 1) (NH4HCO3)

(271) ##STR01971##

(272) ##STR01972##

(273) Method AA: 2-Amino-N-(cyclopropylmethyl)benzamide (ii-c) A 100 mL round bottom flask was charged with anthranilic acid (500 mg, 3.65 mmol), added DMF (15 mL) under nitrogen atmosphere and stirring. Then, added N-methylmorpholine (1 mL, 9.12 mmol), aminomethylcyclopropane (311 mg, 4.38 mmol), N-ethyl-N-dimethylaminopropylcarbodiimide (EDCI) (840 mg, 4.38 mmol) and HOBt (670 mg, 4.38 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with diethyl ether (50 mL x 2). The organic extracts were combined, washed with brine, dried over MgSO.sub.4, filtered and concentrated to afford amorphous colorless 2-amino-N-(cyclopropylmethyl)benzamide (500 mg, 72% yield), which was checked by NMR and used for next step without further purification. .sup.1H-NMR (Bruker 300 MHz, DMSO-d6) 0.20-1.01 (m, 4H), 1.01-1.04 (m, 1H), 3.06-3.11 (m, 2H), 6.37-8.21 (m, 7H).

(274) Method Z: 2-(6-chloro-2-(pyridin-3-yl)quinazolin-4-ylamino)-N-(cyclopropylmethyl) benzamide (xiv-g) A 100 mL round bottom flask was charged with 4,6-dichloro-2-(pyridin-3-yl)quinazoline (synthesized as described in Scheme 1 and 4, substituting 5-chloro-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid) (150 mg, 0.54 mmol) and 2-amino-N-(cyclopropylmethyl)benzamide) (310 mg, 1.63 mmol) and anhydrous i-PrOH (20 mL) was added and refluxed for 3 h. The reaction mixture was cooled to room temperature and Et.sub.3N (3eq) was added. The solvent was removed in vacuo. To the crude product was added a water-methanol mixture (5:1, 50 mL), and then sonicated for 5 min. The solidified compound was collected by filtration, and the solid was recrystallized from hot methanol and washed with water. The product was dried at 50 C. to give 2-(6-chloro-2-(pyridin-3-yl)quinazolin-4-ylamino)-N-(cyclopropylmethyl)benzamide as a colorless cotton (220 mg, 94%). The structure was confirmed by NMR and elemental analysis. .sup.1H NMR (Bruker 300 MHz, DMSO-d.sub.6) ppm 0.20-0.98 (m, 5H), 3.07-3.21 (m, 2H), 7.24-8.26 (m, 7H), 8.68-9.55 (m, 5H), 12.22 (s, 1H). CHN Calcd. C, 67.05; H, 4.69; N, 16.29 Found C, 67.15; H, 4.89; N, 16.25.

(275) The compounds in the following table were prepared in a manner analogous to that described in Scheme 34, replacing aminomethylcyclopropane with the appropriate amine.

(276) TABLE-US-00017 TABLE 11 .sup.1H NMR Purity Method of Number Product .sup.1H NMR Solvent percent Coupling 1016 .sup.1H NMR (DMSO-d.sub.6) ppm 1.46 (d, 3H, J = 6.7 Hz), 3.90 (s, 3H), 5.17-5.22 (m, 1H), 7.19-7.98 (m, 12H), 8.67-8.71 (m, 2H), 8.90 (d, 1H, J = 8.2 Hz), 9.22 (d, 1H, J = 8.3 Hz), 9.55 (s, 1H), 12.18 (s, 1H). DMSO >98 Method Z 1017 .sup.1H NMR (DMSO-d.sub.6) ppm 1.49- 1.62 (m, 8H), 3.99 (s, 3H), 4.24- 4.26 (m, 1H), 7.24-7.71 (m, 7H), 8.65-9.55 (m, 5H), 12.19 (s, 1H). DMSO >98 Method Z 1018 .sup.1H NMR (DMSO-d.sub.6) ppm 0.88- 1.99 (m, 7H), 3.14-3.16 (m, 2H), 3.02 (s, 3H), 7.57-7.91 (m, 7H), 8.68-9.55 (m, 5H), 12.19 (s, 1H). DMSO >98 Method Z 1019 .sup.1H NMR (DMSO-d.sub.6) ppm 1.07- 1.12 (m, 3H), 3.44-3.52 (m, 2H), 4.01 (s, 3H), 7.24-786 (m, 8H), 8.68-9.55 (m, 5H), 12.19 (s, 1H). DMSO >98 Method Z 1020 1H NMR (DMSO-d.sub.6) ppm 0.87- 0.92 (m, 3H), 1.53-1.62 (m, 2H,), 3.30-3.32 (m, 2H), 3.98 (s, 3H), 7.21-7.89 (m, 7H), 8.67-9.55 (m, 5H), 12.38 (s, 1H). DMSO >98 Method Z 1021 1H NMR (DMSO-d.sub.6) ppm 0.83- 1.51 (m, 7H), 3.30-3.32 (m, 2H), 3.99 (s, 3H), 7.24-7.90 (m, 7H), 8.67-9.55 (m, 5H), 12.38 (s, 1H). DMSO >98 Method Z 1022 1H NMR (DMSO-d.sub.6) ppm 0.79- 1.52 (m, 9H), 3.25-3.30 (m, 2H), 3.98 (s, 3H), 7.21-7.88 (m, 7H), 8.68-9.55 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1023 0 1H NMR (DMSO-d.sub.6) ppm 0.80- 1.49 (m, 11H), 3.26-3.30 (m, 2H), 3.99 (s, 3H), 7.24-7.90 (m, 7H), 8.67-9.56 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1024 1H NMR (DMSO-d.sub.6) ppm 3.99- 4.10 (m, 5H), 5.07-5.33 (m, 2H), 5.89-5.91 (m, 1H), 7.24-7.90 (m, 7H), 8.68-9.55 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1025 1H NMR (DMSO-d.sub.6) ppm 3.13 (s, 1H), 3.99-4.12 (m, 5H), 7.21-7.89 (m, 7H), 8.67-9.54 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1026 1H NMR (DMSO-d.sub.6) ppm 1.68- 2.22 (m, 6H), 3.99 (s, 3H), 4.24- 4.26 (m, 1H), 7.22-7.92 (m, 7H), 8.66-9.55 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1027 1H NMR (DMSO-d.sub.6) ppm 1.41- 1.86 (m, 12H), 3.90 (br s, 4H), 7.23-7.89 (m, 7H), 8.63-9.55 (m, 5H), 12.30 (s, 1H). DMSO >98 Method Z 1028 1H NMR (DMSO-d.sub.6) ppm 0.85- 1.60 (m, 9H), 3.27-3.33 (m, 2H), 3.99 (s, 3H), 7.21-7.91 (m, 7H), 8.68-9.55 (m, 5H), 12.19 (s, 1H). DMSO >98 Method Z 1029 1H NMR (DMSO-d.sub.6) ppm 1.03- 1.34 (m, 6H), 3.17-3.31 (m, 4H), 7.40-7.88 (m, 7H), 8.55-10.03 (m, 5H), 12.32 (s, 1H). DMSO >98 Method Z 1030 1H NMR (DMSO-d.sub.6) ppm 0.83- 1.52 (m, 5H), 3.20-3.29 (m, 2H), 7.27-8.21 (m, 7H), 8.67-9.53 (m, 5H), 12.33 (s, 1H). DMSO >98 Method Z 1031 1H NMR (DMSO-d.sub.6) ppm 1.02- 1.07 (m, 3H), 3.24-3.32 (m, 2H), 7.27-8.22 (m, 7H), 8.67-9.53 (m, 5H), 12.34 (s, 1H). DMSO >98 Method Z 1032 1H NMR (DMSO-d.sub.6) ppm 0.75- 1.37 (m, 7H), 3.18-3.20 (m, 2H), 7.21-8.19 (m, 7H), 8.64-9.48 (m, 5H), 12.15 (s, 1H). DMSO >98 Method Z 1033 0 1H NMR (DMSO-d.sub.6) ppm 3.90- 3.92 (m, 2H), 5.02-5.17 (m, 2H), 5.81-5.86 (m, 1H), 7.27-8.23 (m, 7H), 8.68-9.55 (m, 5H), 12.25 (s, 1H). DMSO >98 Method Z 1034 1H NMR (DMSO-d.sub.6) ppm 0.78- 1.42 (m, 11H), 3.20-3.29 (m, 2H), 7.25-7.91 (m, 7H), 8.23-9.53 (m, 5H), 12.17 (s, 1H). DMSO >98 Method Z 1035 .sup.1H NMR (DMSO-d.sub.6) ppm 3.06 (s, 1H), 4.05-4.08 (m, 2H), 7.28-8.22 (m, 7H), 8.65-9.51 (m, 5H), 12.12 (s, 1H). DMSO >98 Method Z 1036 1H NMR (DMSO-d.sub.6) ppm 0.88- 1.92 (m, 7H), 3.05-3.16 (m, 2H), 7.23-7.94 (m, 7H), 8.22-9.54 (m, 5H), 12.21 (s, 1H). DMSO >98 Method Z 1037 1H NMR (DMSO-d.sub.6) ppm 1.37- 1.79 (m, 12H), 3.90-3.96 (m, 1H), 7.25-8.24 (m, 7H), 8.55-9.52 (m, 5H), 12.07 (s, 1H). DMSO >98 Method Z 1038 1H NMR (DMSO-d.sub.6) ppm 1.49- 1.85 (m, 8H), 4.24-4.26 (m, 1H), 7.23-7.69 (m, 6H), 7.85-9.53 (m, 6H), 12.06 (s, 1H). DMSO >98 Method Z 1039 1H NMR (DMSO-d.sub.6) ppm 1.12- 1.14 (m, 6H), 4.11-4.18 (m, 1H), 7.23-7.94 (m, 8H), 8.33-9.53 (m, 4H), 12.30 (s, 1H). DMSO >98 Method Z 1040 1H NMR (DMSO-d.sub.6) ppm 0.84- 1.16 (m, 9H), 3.28-3.34 (m, 2H), 7.23-7.91 (m, 6H), 8.25-9.53 (m, 6H), 12.16 (s, 1H). DMSO >98 Method Z 1041 1H NMR (DMSO-d.sub.6) ppm 0.79- 1.52 (m, 9H), 3.25-3.32 (m, 2H), 7.24-7.91 (m, 6H), 8.23-9.53 (m, 6H), 12.18 (s, 1H). DMSO >98 Method Z 1042 1H NMR (DMSO-d.sub.6) ppm 1.04- 1.81 (m, 10H), 3.77-3.82 (m, 1H), 7.21-8.05 (m, 8H), 8.65-9.52 (m, 4H), 11.96 (s, 1H). DMSO >98 Method Z 1043 000 1H NMR (DMSO-d.sub.6) ppm 0.47- 0.67 (m, 4H), 2.85-2.88 (m, 1H), 7.26-8.26 (m, 7H), 8.66-9.52 (m, 5H), 12.26 (s, 1H). DMSO >98 Method Z 1044 001 1H NMR (DMSO-d.sub.6) ppm 1.14 (s, 9H), 7.30-7.93 (m, 7H), 8.21- 9.50 (m, 5H), 12.22 (s, 1H). DMSO >98 Method Z 1045 002 1H NMR (DMSO-d.sub.6) ppm 3.98 (s, 3H), 4.36 (s, 2H), 6.47 (s, 1H), 7.21-7.91 (m, 9H), 8.68-9.56 (m, 5H), 12.22 (s, 1H). DMSO >98 Method Z 1046 003 1H NMR (DMSO-d.sub.6) ppm 4.30 (s, 2H), 6.42 (s, 1H), 7.28-8.24 (m, 9H), 8.70-9.53 (m, 5H), 12.22 (s, 1H). DMSO >98 Method Z 1047 004 1H NMR (DMSO-d.sub.6) ppm 1.69- 2.55 (m, 6H), 4.41-4.44 (m, 1H), 7.23-8.24 (m, 7H), 8.65-9.54 (m, 5H), 12.06 (s, 1H). DMSO >98 Method Z 1048 005 1H NMR (DMSO-d.sub.6) ppm 4.55 (s, 2H), 7.17-8.21 (m, 12H), 8.65- 9.54 (m, 5H), 12.06 (s, 1H). DMSO >98 Method Z 1049 006 1H NMR (DMSO-d.sub.6) ppm 7.02- 8.67 (m, 15H), 9.47 (s, 1H), 10.04 (s, 1H), 12.06 (s, 1H). DMSO >98 Method Z 1050 007 1H NMR (DMSO-d.sub.6) ppm 2.75- 2.80 (m, 2H), 3.48-3.54 (m, 2H), 7.08-8.20 (m, 12H), 8.69-9.56 (m, 5H), 12.16 (s, 1H). DMSO >98 Method Z 1051 008 1H NMR (DMSO-d.sub.6) ppm 4.01- 4.10 (m, 2H), 7.28-8.27 (m, 7H), 8.59-9.51 (m, 5H), 11.45 (s, 1H). DMSO >98 Method Z 1052 009 1H NMR (DMSO-d.sub.6) ppm 4.38- 4.57 (m, 4H), 7.27-8.24 (m, 7H), 8.69-9.56 (m, 5H), 12.10 (s, 1H). DMSO >98 Method Z 1053 010 1H NMR (DMSO-d.sub.6) ppm 2.85- 2.92 (br s, 3H), 7.20-8.22 (m, 7H), 8.67-9.56 (m, 5H), 12.61 (s, 1H). DMSO >98 Method Z 1054 011 1H NMR (DMSO-d.sub.6) ppm 1.04- 1.81 (m, 10H), 3.77-3.82 (m, 1H), 7.24-8.05 (m, 8H), 8.65-9.52 (m, 4H), 12.27 (s, 1H). DMSO >98 Method Z 1055 012 1H NMR (DMSO-d.sub.6) ppm 2.49- 2.51 (m, 2H), 3.57-3.59 (m, 2H), 7.21-8.16 (m, 12H), 8.69-9.56 (m, 5H), 12.16 (s, 1H). DMSO >98 Method Z 1056 013 1H NMR (DMSO-d.sub.6) ppm 0.79- 1.44 (m, 11H), 3.26-3.30 (m, 2H), 7.24-7.92 (m, 7H), 8.67-9.52 (m, 5H), 12.45 (s, 1H). DMSO >98 Method Z 1057 014 1H NMR (DMSO-d.sub.6) ppm 1.04- 1.16 (m, 3H), 3.33-3.38 (m, 2H), 7.20-8.22 (m, 7H), 8.60-9.53 (m, 5H), 12.34 (s, 1H). DMSO >98 Method Z 1058 015 1H NMR (DMSO-d.sub.6) ppm 7.09- 8.68 (m, 15H), 9.51 (s, 1H), 10.34 (s, 1H), 12.06 (s, 1H). DMSO >98 Method Z 1059 016 1H NMR (DMSO-d.sub.6) ppm 3.78 (s, 3H), 4.43 (s, 2H), 6.77-8.23 (m, 11H), 8.68-9.54 (m, 5H), 12.06 (s, 1H). DMSO >98 Method Z 1060 017 1H NMR (DMSO-d.sub.6) ppm 3.69 (s, 3H), 4.48 (s, 2H), 6.89-8.15 (m, 11H), 8.68-9.54 (m, 5H), 12.44 (s, 1H). DMSO >98 Method Z 1061 018 1H NMR (DMSO-d.sub.6) ppm 2.24 (s, 3H), 4.46 (s, 2H), 7.03-8.13 (m, 11H), 8.67-9.54 (m, 5H), 12.21 (s, 1H). DMSO >98 Method Z 1062 019 1H NMR (DMSO-d.sub.6) ppm 4.51 (s, 2H), 7.11-8.14 (m, 11H), 8.67- 9.54 (m, 5H), 12.34 (s, 1H). DMSO >98 Method Z 1063 020 1H NMR (DMSO-d.sub.6) ppm 4.47 (s, 2H), 7.05-8.14 (m, 11H), 8.67- 9.54 (m, 5H), 12.37 (s, 1H). DMSO >98 Method Z 1064 021 1H NMR (DMSO-d.sub.6) ppm 3.95 (s, 3H), 4.47 (s, 2H), 7.05-8.14 (m, 11H), 8.67-9.54 (m, 5H), 12.32 (s, 1H). DMSO >98 Method Z Starting Starting Number Material R.sup.1 Material R.sup.3 Product 1065 022 023 024 1066 025 026 027 1067 028 029 030 1068 031 032 033 1069 034 035 036 1070 037 038 039 1071 040 041 042 1072 043 .sup.1H NMR Number Salt Type .sup.1H NMR Solvent Purity percent Method of Coupling 1065 .sup.1H NMR (DMSO-d.sub.6) ppm 4.52 (d, 2H, J = 5.8 Hz), DMSO >98 Method Y, Z 7.21-7.30 (m, 5H), 7.50 (t, J = 7.9 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.89-7.92 (m, 3H), 8.21 (d, J = 1.8 Hz, 1H), 8.65-8.70 (m, 3H), 8.99 (s, 1H), 9.52 (s, 1H), 11.88 (s, 1H) 1066 .sup.1H NMR (DMSO-d.sub.6) ppm 4.49 (d, 2H, J = 5.6 Hz), DMSO >98 Method Y, Z 7.24-7.35 (m, 5H), 7.50 (t, J = 7.2 Hz, 1H), 7.70 (t, J = 7.8 Hz, 1H), 7.91-7.95 (m, 3H), 8.22 (d, J = 1.5 Hz, 1H), 8.67-8.73 (m, 3H), 9.19 (s, 1H), 9.53 (s, 1H), 11.98 (s, 1H) 1067 .sup.1H NMR (DMSO-d.sub.6) ppm 4.58 (d, 2H, J = 5.7 Hz), DMSO >98 Method Y, Z 7.16-7.36 (m, 5H), 7.50 (t, J = 7.5 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.88-7.96 (m, 3H), 8.22 (d, J = 1.5 Hz, 1H), 8.65-8.69 (m, 3H), 8.98 (s, 1H), 9.52 (s, 1H), 11.87 (s, 1H) 1068 .sup.1H NMR (DMSO-d.sub.6) ppm 4.47 (d, 2H, J = 5.6 Hz), DMSO >98 Method Y, Z 7.30 (br s, 5H), 7.54 (t, J = 7.7 Hz, 1 H), 7.70 (t, J = 7.8 Hz, 1H), 7.88-7.96 (m, 3H), 8.15 (d, J = 1.5 Hz, 1H), 8.68-8.81 (m, 3H), 8.98 (s, 1H), 9.52 (s, 1H), 12.29 (s, 1H) 1069 .sup.1H NMR (DMSO-d.sub.6) ppm 4.57 (d, 2H, J = 5.6 Hz), DMSO >98 Method Y, Z 7.23-7.29 (m, 5H), 7.39 (t, J = 7.9 Hz, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.94-7.99 (m, 3H), 8.15 (d, J = 1.4 Hz, 1H), 8.68-8.84 (m, 3H), 9.24 (s, 1H), 9.55 (s, 1H), 12.23 (s, 1H) 1070 .sup.1H NMR (DMSO-d.sub.6) ppm 4.50 (d, 2H, J = 5.5 Hz), DMSO >98 Method Y, Z 7.25-7.53 (m, 5H), 7.69 (t, J = 7.1 Hz, 1H), 7.73 (t, J = 7.0 Hz, 1H), 7.94-8.15 (m, 3H), 8.18 (d, J = 1.4 Hz, 1H), 8.68-8.82 (m, 3H), 9.24 (s, 1H), 9.54 (s, 1H), 12.21 (s, 1H) 1071 .sup.1H NMR (DMSO-d.sub.6) ppm 3.90 (s, 3H), 4.56 (d, DMSO >98 Method Y, Z 2H, J = 5.6 Hz), 7.22-7.44 (m, 7H), 7.44 (t, J = 7.9 Hz, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.94-7.99 (m, 2H), 8.68-8.81 (m, 3H), 9.24 (s, 1H), 9.55 (s, 1H), 12.19 (s, 1H) 1072 HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.17 (s, 1H), DMSO 95 Method Y, Z 9.52 (s, 1H), 9.08 (s, 1H), 8.95 (d, J = 7.6 Hz, 1H), 8.85 (s, 1H), 8.66 (d, J = 7.8 Hz, 1H), 7.91 (t, J = 9.4 Hz, 2H), 7.84 (s, 1H), 7.75-7.67 (m, 1H), 7.65 (s, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H), 4.47 (d, J = 47.3 Hz, 2H), 4.26 (d, J = 6.8 Hz, 2H), 3.58-3.50 (m, 2H), 1.47 (t, J = 6.7 Hz, 3H).

(277) ##STR02044##

(278) ##STR02045## ##STR02046##

(279) Method AB: Methyl 3-(4-hydroxy-2-(pyridin-3-yl)quinazolin-6-yl)acrylate (xxvi-a) To a solution of 6-iodo-2-(pyridin-3-yl) quinazolin-4-ol (synthesized as described in Scheme 1 and 4, substituting 5-iodo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid) (3.00 g, 8.6 mmol, 1.0 eq.), Pd(OAc).sub.2 (48 mg, 0.21 mmol, 0.025 eq.) and PPh.sub.3 (113 mg, 0.43 mmol, 0.05 eq.) in DMF (8 mL) was added methyl acrylate (3.22 g, 25.8 mmol, 3.0 eq.) and DIPEA (1.22 g, 9.46 mmol, 1.1 eq.) under Ar atmosphere. The mixture was stirred at 110 C. overnight. After cooling, the mixture was filtered and the solid was washed with ethyl acetate three times to afford 1.30 g of xxxvi-a as green solid (yield 49%). LCMS m/z=308.0 (M+1) (Method B) (retention time=1.41 min).

(280) Methyl 3-(4-hydroxy-2-(pyridin-3-yl) quinazolin-6-yl)propanoate (xxvii-a)

(281) Methyl 3-(4-hydroxy-2-(pyridin-3-yl) quinazolin-6-yl) propanoate was prepared in a manner analogous to that described for 2-amino-5-methoxybenzoic acid in Method K, replacing 5-methoxy-2-nitrobenzoic acid with methyl 3-(4-hydroxy-2-(pyridin-3-yl)quinazolin-6-yl)acrylate to afford 1.40 g of xxvii-a in quantitative yield as a yellow solid. LCMS m/z=310.0 (M+1) (Method B) (retention time=1.42 min).

(282) 3-(4-Chloro-2-pyridin-3-yl-quinazolin-6-yl)-propionic acid methyl ester (xxviii-a)

(283) 3-(4-Chloro-2-pyridin-3-yl-quinazolin-6-yl)-propionic acid methyl ester (prepared in a manner analogous to that described for 4-chloro-6-propoxy-2-pyridin-3-yl-quinazoline using Method F, replacing 6-propoxy-2-pyridin-3-yl-1H-quinazolin-4-one with methyl 3-(4-hydroxy-2-(pyridin-3-yl)quinazolin-6-yl)propanoate) was obtained in quantitative yield to give 1.50 g of xxvii-a as a red solid. LCMS m/z=328.1, 330.0 (M+1) (Method B) (retention time=1.86 min).

(284) 3-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-propionic acid methyl ester (xxviv-a) 3-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-propionic acid methyl ester (prepared in a manner analogous to that described for 2-(6-propoxy-2-pyridin-3-yl-quinazolin-4-ylamino)-benzamide in Method G1, replacing 4,7-dichloro-2-(4-chlorophenyl)quinazoline and 2-aminobenzamide with 3-(4-chloro-2-pyridin-3-yl-quinazolin-6-yl)-propionic acid methyl ester and 3-chloro-4-fluoro-phenylamine) was obtained in a 43% yield to give 1.04 g of xxviv-a as a yellow solid. LCMS m/z=437.1, 439.1 (M+1) (Method B) (retention time=1.62 min).

(285) Method AC: 3-(4-(3-Chloro-4-fluorophenylamino)-2-(pyridin-3-yl) quinazolin-6-yl)propanoic acid (xxx-a) To a solution of 3-[4-(3-chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-propionic acid methyl ester (1.04 g, 2.39 mmol, 1.0 eq.) in DMF (20 mL) was added a solution of NaOH (0.57 g, 14.3 mmol, 6.0 eq.) in H.sub.2O (8 mL). The mixture was stirred at room temperature for 2 h. 50 mL of water was added to the mixture. After filtration, the resulting filter cake was washed with water and dried in vacuo to give 933 mg of xxx-a as a yellow solid (yield 93%). LCMS m/z=423.1, 425.1 (M+1) (Method A) (retention time=1.51 min).

(286) 3-(4-(3-Chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)-N,N-dimethyl propanamide (xxxi-a) 3-(4-(3-Chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)-N,N-dimethyl propanamide (prepared in a manner analogous to that described for 2-benzamido-5-methoxy-3-methylbenzamide in Method D, replacing nicotinic acid and 2-amino-5-methoxy-3-methylbenzamide with 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propanoic acid and dimethylamine hydrochloride) was obtained in 90% yield to give 891 mg of xxxi-a as a yellow solid. LCMS m/z=450.0, 452.0 (M+1) (Method B) (retention time=1.834 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.95 (s, 1H), 9.51 (d, J=1.6 Hz, 1H), 8.69-8.63 (m, 2H), 8.38 (s, 1H), 8.28 (dd, J=6.8, 2.4 Hz, 1H), 7.94-7.90 (m, 1H), 7.81 (s, 2H), 7.55-7.51 (m, 2H), 3.04 (t, J=7.6 Hz, 2H), 2.99 (s, 3H), 2.85 (s, 3H), 2.77 (t, J=8.0 Hz, 2H).

(287) The compounds in the following table were prepared in a manner analogous to that described in Scheme 36, replacing dimethylamine with the appropriate amine and 4-fluoro, 3-chloro aniline with the appropriate aniline.

(288) TABLE-US-00018 TABLE 12 Salt Molecular .sup.1H-NMR LCMS Purity Method for Number PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1073 047 421.85 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.01 (s, 1H), 9.52 (s, 1H), 8.65-8.69 (m, 2H), 8.39 (s, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.92-7.93 (m, 1H), 7.82 (q, J = 8.0 Hz, 2H), 7.52-7.57 (m, 2H), 7.35 (s, 1H), 6.84 (s, 1H), 3.05 (t, J = 7.2 Hz, 2H), 2.51-2.54 (m, 2H). DMSO 422.1 (M + 1) Method B (NH4HCO3) 95 Method C 1074 048 435.43 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.01 (s, 1H), 9.55 (d, J = 2.4 Hz, 1H), 8.68-8.70 (m, 2H), 8.47 (s, 1H), 7.97-7.99 (m, 1H), 7.79-7.86 (m, 3H), 7.50- 7.55 (m, 2H), 7.36 (s, 1H), 7.30 (t, J = 73.6 Hz, 1H), 6.99 (dd, J = 8.4, 2.4 Hz, 1H), 6.82 (s, 1H), 3.05 (t, J = 8.0 Hz, 2H), 2.52 (t, J = 8.4 Hz, 2H). DMSO 436.2 (M + 1) Method B (NH4HCO3) 95 Method C 1075 049 435.88 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.00 (s, 1H), 9.52 (s, 1H), 8.65-8.69 (m, 2H), 8.39 (s, 1H), 8.27- 8.29 (m, 1H), 7.79 (dd, J = 9.2, 2.4 Hz, 1H), 7.76- 7.85 (m, 3H), 7.52-7.57 (m, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.57 (d, J = 4.4 Hz, 3H), 2.52-2.54 (m, 2H). DMSO 436.1 (M + 1) Method B (NH4HCO3) 95 Method D 1076 050 449.91 .sup.1H-NMR (400 MHz, DMSO-d6): 9.95 (s, 1H), 9.51 (d, J = 1.6 Hz, 1H), 8.63-8.69 (m, 2H), 8.38 (s, 1H), 8.28 (dd, J = 6.8, 2.4 Hz, 1H), 7.90-7.94 (m, 1H), 7.81 (s, 2H), 7.51-7.55 (m, 2H), 3.04 (t, J = 7.6 Hz, 2H), 2.99 (s, 3H), 2.85 (s, 3H), 2.77 (t, J = 8.0 Hz, 2H). DMSO 450.0 (M + 1) Method B (NH4HCO3) 95 Method D 1077 051 540.01 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.01 (s, 1H), 9.52 (d, J = 1.6 Hz, 1H), 8.61-8.74 (m, 2H), 8.41 (s, 1H), 8.28 (dd, J = 6.8, 2.6 Hz, 1H), 7.80-7.99 (m, 3H), 7.46-7.63 (m, 2H), 3.89 (s, 4H), 3.20 (s, 2H), 3.08 (t, J = 7.4 Hz, 4H), 2.90 (t, J = 7.6 Hz, 2H). DMSO 540.2, 542.2 (M + 1) Method B (NH4HCO3) 95 Method D

(289) ##STR02052##

(290) ##STR02053##

(291) (E)-4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-but-3-enenitrile (xxxii-a) (E)-4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-but-3-enenitrile (prepared in a manner analogous to that described for (E)-methyl 3-(4-hydroxy-2-(pyridin-3-yl)quinazolin-6-yl)acrylate using Method AB, replacing 6-iodo-2-(pyridin-3-yl)quinazolin-4-ol and methyl acrylate with N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine and but-3-enenitrile) was obtained in a 48% yield to give 400 mg of xxxii-a as grey solid. LCMS m/z=416.0 (M+1) (Method B) (retention time=1.99 min).

(292) 4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-butyronitrile (xxxiii-a) 4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-butyronitrile (prepared in a manner analogous to that described for 2-amino-5-methoxybenzoic acid in Method K, replacing 5-methoxy-2-nitrobenzoic acid with (E)-4-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)but-3-enenitrile) was obtained in a 95% yield to give 190 mg of xxxiii-a as a brown solid. LCMS m/z=418.1(M+1) (Method B) (retention time=1.95 min).

(293) Method AD: 4-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)butanoic acid (xxxiv-a) 4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-butyronitrile (190 mg, 046 mmol, 1.0 eq.) was treated with concentrated HCl (8 mL). The mixture was stirred at 100 C. for 2 days. The volatiles were removed in vacuo, and the residue was washed with water to afford 70 mg of xxxiv-a in a 35% yield as a yellow solid. LCMS m/z=437.1, 439.1 (M+1) (Method B) (retention time=1.46 min).

(294) 4-(4-(3-Chloro-4-fluorophenylamino)-2-(pyridin-3-yl) quinazolin-6-yl)-1-morpholino butan-1-one (xxxv-a) 4-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl) quinazolin-6-yl)-1-morpholinobutan-1-one was prepared in a manner analogous to that described for 2-benzamido-5-methoxy-3-methylbenzamide in Method D, replacing nicotinic acid and 2-amino-5-methoxy-3-methylbenzamide with 4-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl) butanoic acid and morpholine to give 32 mg of xxxv-a in a 40% yield as a beige solid. LCMS m/z=506.2, 508.1 (M+1) (Method B) (retention time=1.85 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 10.04 (s, 1H), 9.52 (d, J=1.6 Hz, 1H), 8.69-8.65 (m, 2H), 8.39-8.38 (m, 1H), 8.27 (dd, J=6.8, 2.8 Hz, 1H), 7.94-7.90 (m, 1H), 7.86-7.84 (m, 1H), 7.80-7.77 (m, 1H), 7.57-7.52 (m, 2H), 3.56-3.53 (m, 4H), 3.46-3.41 (m, 4H), 2.85 (t, J=8.0 Hz, 2H), 2.40 (t, J=7.6 Hz, 2H), 1.97 (t, J=7.6 Hz, 2H).

(295) ##STR02054##

(296) The compounds in the following table were prepared in a manner analogous to that described in Scheme 38 in the synthesis of 4-(4-(3-Chloro-4-fluorophenyl amino)-2-(pyridin-3-yl) quinazolin-6-yl)-1-morpholino butan-1-one, replacing (E)-4-[4-(3-Chloro-4-fluoro-phenylamino)-2-pyridin-3-yl-quinazolin-6-yl]-but-3-enenitrile with 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazoline-6-carbonitrile.

(297) TABLE-US-00019 TABLE 13 Salt Molecular .sup.1H-NMR LCMS Purity Method for Number PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1078 055 411.46 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.64 (d, J = 1.6 Hz, 1H), 8.78 (td, J = 7.9, 1.8 Hz, 1H), 8.71 (dd, J = 4.7, 1.6 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.59 (brs, 1H), 7.58 (dd, J = 7.6, 4.8 Hz, 1H), 7.52 (dd, J = 9.2, 2.8 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 6.4 Hz, 1H), 6.84 (dd, J = 8.0, 1.1 Hz, 1H), 6.69 (s, 1H), 4.36 (t, J = 6.5 Hz, 2H), 4.09 (t, J = 6.4 Hz, 2H), 3.46 (s, 3H), 2.30 (s, 3H). DMSO 412.2 (M + 1) Method B (NH4HCO3) 95 Method C, G 1079 056 506.96 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 10.42 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.08 (d, J = 1.2 Hz, 1H), 8.73- 8.65 (m, 3H), 8.28 (dd, J = 6.8, 2.4 Hz, 1H), 7.97- 7.93 (m, 2H), 7.60-7.53 (m, 2H), 3.60-3.58 (m, 4H), 3.51-3.46 (m, 2H), 2.55-2.53 (m, 2H), 2.41- 2.48 (m, 4H). DMSO 508.1 (M + 1) 254.1 254.9 (M/2 + 1) Method B (NH4HCO3) 95 Method C, G, C 1080 057 461.92 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 10.21 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 8.72-8.67 (m, 2H), 8.64 (d, J = 1.2 Hz, 1H), 8.28 (dd, J = 7.0, 2.6 Hz, 1H), 7.95- 7.86 (m, 3H), 7.60-7.53 (m, 2H), 3.68 (d, J = 2.4 Hz, 2H), 3.37-3.34 (m, 2H), 1.65-1.51 (m, 6H). DMSO 462.0 464.0 (M + 1) 232.3 (M/2 + 1) Method A (TFA) 95 Method C, G, C 1081 058 479.96 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 10.20 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.72-8.67 (m, 2H), 8.64 (d, J = 1.2 Hz, 1H), 8.28 (dd, J = 6.8, 2.8 Hz, 1H), 7.97- 7.90 (m, 3H), 7.60-7.54 (m, 2H), 3.97-3.94 (m, 2H), 3.66-3.60 (m, 2H), 2.77-2.67 (m, 4H). DMSO 480.0 482.0 (M + 1) 240.6 (M/2 + 1) Method A (TFA) 95 Method C, G, C 1082 059 421.85 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.20 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 8.79-8.64 (m, 3H), 8.29 (dd, J = 6.8, 2.6 Hz, 1H), 8.01-7.87 (m, 3H), 7.53-7.60 (m, 2H), 3.15-3.05 (m, 3H), 3.02 (s, 3H). DMSO 422.1, 424.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G, D 1083 060 463.89 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.22 (s, 1H), 9.55 (d, J = 1.4 Hz, 1H), 8.77-8.65 (m, 3H), 8.02-7.87 (m, 3H), 7.60-7.54 (m, 2H), 3.56-3.39 (m, 2H), 3.82-3.55 (m, 6H). DMSO 464.1, 466.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G, D 1084 061 407.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.41 (s, 1H), 9.54 (d, J = 1.5 Hz, 1H), 9.08 (d, J = 1.3 Hz, 1H), 8.76- 8.63 (m, 3H), 8.32-8.20 (m, 2H), 7.96-7.93 (m, 2H), 7.63-7.50 (m, 2H), 2.88 (d, J = 4.5 Hz, 3H). DMSO 408.0, 410.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G, D 1085 062 447.89 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 9.55 (d, J = 1.5 Hz, 1H), 8.68-8.77 (m, 3H), 8.28 (dd, J = 6.9, 2.6 Hz, 1H), 8.02 (dd, J = 8.6, 1.6 Hz, 1H), 7.99-7.90 (m, 2H), 7.53-7.58 (m, 2H), 3.57 (t, J = 6.8 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 1.85-1.95 (m, 4H). DMSO 448.1, 420.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G, D 1086 063 476.93 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.22 (s, 1H), 9.54 (d, J = 1.5 Hz, 1H), 8.75-8.63 (m, 3H), 8.29 (dd, J = 6.8, 2.6 Hz, 1H), 8.01-7.84 (m, 3H), 7.60-7.53 (m, 2H), 3.72 (d, J = 2.2 Hz, 2H), 3.51-3.39 (m, 2H), 2.48-2.40 (m, 2H), 2.33 (d, J = 1.3 Hz, 2H), 2.24 (s, 3H). DMSO 477.1, 479.1 (M + 1) 239.1, 239.9 (M/2 + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G, D 1087 064 511.96 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.19 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.59-8.82 (m, 3H), 8.26 (dd; J = 6.8, 2.6 Hz, 1H), 7.81-8.14 (m, 3H), 7.57 (m, 2H), 3.83-4.10 (m, 4H), 3.33-3.35 (m, 4H). DMSO 512.1, 514.1 (M + 1) Method B (NH4HCO3) 95 Method C, G, C 1088 065 481.91 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.47 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 9.23 (d, J = 1.2 Hz, 1H), 8.72- 8.74 (m, 3H), 8.22-8.42 (m, 2H), 7.85-8.12 (m, 2H), 7.55-7.59 (m, 2H), 4.61 (t, J = 5.4 Hz, 1H), 3.47 (t, J = 5.2 Hz, 2H), 3.37 (s, 6H). DMSO 482.1, 484.2 (M + 1) Method B (NH4HCO3) 95 Method C, G, D 1089 066 421.85 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 9.59 (d, J = 1.2 Hz, 1H), 8.72-8.77 (m, 2H), 8.68 (d, J = 8.4 Hz, 1H), 8.34 (dd, J = 7.2, 2.0 Hz, 1H), 7.96- 8.00 (m, 1H), 7.92 (m, 1H), 7.72-7.74 (m, 1H), 7.58-7.65 (m, 2H), 3.13 (s, 3H), 3.03 (s, 3H). DMSO 422.0 (M + 1) Method A (TFA) 95 Method C, G, D 1090 067 394.79 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.25 (s, 1H), 9.54 (s, 1H), 8.68-8.70 (m, 2H), 8.60 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.32 (dd, J = 7.2, 2.8 Hz, 1H), 8.11 (d, J = 7.2 Hz, 1H), 7.93-7.97 (m, 1H), 7.51- 7.58 (m, 2H). DMSO 395.0 (M + 1) Method A (TFA) 95 Method C, G, D 1091 068 476.93 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.19 (s, 1H), 9.53 (s, 1H), 8.62-8.72 (m, 3H), 8.29 (dd, J = 6.8, 2.4 Hz, 1H), 7.91-7.94 (m, 1H), 7.83 (s, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.53-7.59 (m, 2H), 3.69-3.71 (s, 2H), 3.36-3.38 (s, 2H), 2.42-2.44 (s, 2H), 2.30- 2.32 (s, 2H), 2.23 (s, 3H). DMSO 477.2 (M + 1) 239.1 (1/2M + 1) Method B (NH4HCO3) 95 Method C, G, D 1092 069 463.89 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.18 (s, 1H), 9.52 (S, 1H), 8.62-8.71 (m, 3H), 8.28 (d, J = 4.8 Hz, 1H), 7.87-7.96 (m, 2H), 7.68 (d, J = 8.0 Hz, 1H), 7.52-7.58 (m, 2H), 3.61-3.71 (m, 6H), 3.40 (m, 2H). DMSO 464.1 (M + 1) Method B (NH4HCO3) 95 Method G, D 1093 070 393.8 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.20 (s, 1H), 9.54 (d, J = 1.6 Hz, 1H), 8.62-8.72 (m, 3H), 8.42 (d, J = 1.2 Hz, 1H), 8.37 (s, 1H), 8.30 (dd, J = 7.2, 2.8 Hz, 1H), 8.08 (dd, J = 8.4, 1.2 Hz, 1H), 7.91-7.95 (m, 1H), 7.71 (s, 1H), 7.53-7.60 (m, 2H). DMSO 394.1 (M + 1) Method B (NH4HCO3) 95 Method G, D 1094 071 407.83 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.19 (s, 1H), 9.53 (s, 1H), 8.84 (d, J = 4.0 Hz, 1H), 8.60-8.72 (m, 3H), 8.35 (s, 1H), 8.29 (dd, J = 6.8, 2.8 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.90-7.93 (m, 1H), 7.52- 7.59 (m, 2H), 2.87 (d, J = 4.8 Hz, 3H). DMSO 408.1 (M + 1) Method B (NH4HCO3) 95 Method G, D 1095 072 506.96 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.20 (s, 1H), 9.53 (d, J = 1.6 Hz, 1H), 8.85 (t, J = 5.6 Hz, 1H), 8.61- 8.72 (m, 3H), 8.36 (d, J = 1.2 Hz, 1H), 7.98 (dd, J = 6.4, 2.4 Hz, 1H), 8.03 (dd, J = 8.8, 1.6 Hz, 1H), 7.91- 7.95 (m, 1H), 7.52-7.59 (m, 2H), 3.60 (t, J = 4.4 Hz, 4H), 3.46-3.48 (q, J = 6.4 Hz, 2H), 2.51-2.54 (m, 2H), 2.42-2.48 (m, 4H). DMSO 507.1 (M + 1) 254.1 (M/2 + 1) Method B (NH4HCO3) 95 Method G, C 1096 073 511.96 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.22 (s, 1H), 9.56 (d, J = 1.8 Hz, 1H), 8.61-8.79 (m, 3H), 8.31 (dd, J = 6.8, 2.6 Hz, 1H), 7.88-8.11 (m, 2H), 7.78 (dd, J = 8.4, 1.4 Hz, 1H), 7.51-7.66 (m, 2H), 4.12 (brs, 2H), 3.76 (brs, 2H), 3.30-3.33 (m, 4H). DMSO 512.1, 514.1 (M + 1) Method B (NH4HCO3) 95 Method G, D 1097 074 474 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.64 (brs, 1H), 9.53 (s, 1H), 9.44 (t, J = 6.4 Hz, 1H), 9.35 (s, 1H), 8.90 (d, J = 8.0 Hz, 1H), 8.85 (d, J = 4.8 Hz, 1H), 8.35 (dd, J = 8.4, 1.2 Hz, 1H), 8.27 (dd, J = 6.8, 2.4 Hz, 1H), 8.00-7.97 (m, 2H), 7.82 (dt, J = 13.2, 5.2 Hz, 1H), 7.55 (t, J = 8.8 Hz, 1H), 4.22-4.18 (m, 2H). DMSO 475.7, 476.6 (M + 1) Method B (NH4HCO3) 95 Method C, G, D

(298) ##STR02075##

(299) ##STR02076##

(300) Method AE: 2-(7-(Methylamino)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (xxxvi-a): A mixture of 2-(7-amino-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (160 mg, 0.449 mmol, 1.0 eq.) and HCHO (40%, 37 mg, 0.494 mmol, 1.1 eq.), acetic acid (2 drops) were stirred at room temperature for 0.5 h. NaBH.sub.3CN (34 mg, 0.449 mmol, 1.0 eq.) was added and the mixture was stirred at room temperature overnight. After filtration, the filtrate was concentrated to give the crude product, which was purified by reverse phase chromatography (MeOH/H.sub.2O=3:7) to afford 28 mg of xxxvi-a as a white solid (17%). LCMS m/z=371.1 (M+1), 372.1 (M+2) (Method B) (retention time=1.60 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.71 (s, 1H), 9.58 (d, J=1.6 Hz, 1H), 9.14-9.12 (m, 1H), 8.74-8.69 (m, 2H), 8.45 (s, 1H), 7.93-7.91 (m, 1H), 7.85 (d, J=9.2 Hz, 2H), 7.67-7.71 (m, 1H), 7.59-7.55 (m, 1H), 7.12-7.16 (m, 1H), 7.06-7.03 (m, 1H), 6.82-6.81 (m, 1H), 6.70 (d, J=2.4 Hz, 1H), 2.84 (d, J=4.8 Hz, 3H).

(301) The compounds in the following table were prepared in a manner analogous to that described in Scheme 41, replacing formaldehyde with the appropriate aldehyde and 2-aminobenzamide with the appropriate aniline.

(302) TABLE-US-00020 TABLE 14 Molec- .sup.1H- Method Num- Salt ular NMR LCMS Purity for ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1098 077 370.41 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.87 (s, 1H), 9.57 (d, J = 1.2 Hz, 1H), 9.25 (d, J = 8.8 Hz, 1H), 8.65- 8.71 (m, 2H), 8.47 (s, 1 H), 7.95- 7.99 (m, 2H), 7.69-7.74 (m, 2H), 7.56 (dd, J = 7.7, 5.0 Hz, 1H), 7.33 (dd, J = 9.1, 1.9 Hz, 1H), 7.16 (t, J = 7.2 Hz, 1H), 6.90 (d, J = 1.2 Hz, 1H), 6.62 (d, J = 4.8 Hz, 1H), 2.88 (d, J = 4.8 Hz, 3H). DMSO 371.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method AE 1099 078 370.41 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.71 (s, 1H), 9.58 (d, J = 1.4 Hz, 1H), 9.13 (d, J = 7.7 Hz, 1H), 8.80- 8.64 (m, 2H), 8.45 (s, 1H), 7.92 (dd, J = 7.9, 1.4 Hz, 1H), 7.85 (d, J = 9.2 Hz, 2H), 7.76-7.62 (m, 1H), 7.57 (dd, J = 7.9, 4.8 Hz, 1H), 7.15 (dd, J = 11.2, 4.0 Hz, 1H), 7.04 (dd, J = 9.0, 2.3 Hz, 1H), 6.81 (q, J = 4.8 Hz, 1H), 6.70 (d, J = 2.2 Hz, 1H), 2.85 (d, J = 4.9 Hz, 3H). DMSO 371.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method AE

(303) ##STR02079##

(304) ##STR02080##

(305) Method AG: 1-(Benzyloxy)-3-chloro-7-methoxyisoquinoline (xxxvii-a) 1,3-dichloro-7-methoxyisoquinoline (2.00 g, 8.8 mmol, 1.0 eq.) was dissolved in 30 mL anhydrous toluene and sodium benzyloxide (2.30 g, 17.6 mmol, 2.0 eq.) was added. The mixture was heated to 80 C. for 18 h. TLC indicated the reaction was complete. The mixture was concentrated to give the crude product, which was purified by chromatography on silica gel (eluted with petroleum ether) to give 2.20 g of xxxvii-a as a white solid (84.6%). LCMS m/z=300.1, 302.0 (M+1) (Method B) (retention time=2.23 min).

(306) 1-(Benzyloxy)-7-methoxy-3-(pyridin-3-yl)isoquinoline (xxxviii-a) 1-(Benzyloxy)-7-methoxy-3-(pyridin-3-yl)isoquinoline was prepared using Method N2. 1-(Benzyloxy)-3-chloro-7-methoxyisoquinoline (93 mg, 0.5 mmol, 1.0 eq.), potassium carbonate (357 mg, 2.5 mmol, 5.0 eq.), and Pd(PPh.sub.3).sub.2Cl.sub.2 (18 mg, 0.026 mmol, 0.05 eq.) was dissolved in the mixed solvent of 1,4-dioxane (3 mL) and water (1 mL). The resulting mixture was stirred at 120 C. for 30 min under the microwave condition. The solid was filtrated off and the filtrate was concentrated. The residue was partitioned between ethyl acetate and water. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. After filtration and evaporation, the residue was purified by silica gel chromatography (petroleum ether/ethyl acetate=1:10) to afford 100 mg of xxxviii-a as a yellow solid (84.7%).

(307) 7-Methoxy-3-(pyridin-3-yl)isoquinolin-1-ol (xxxviv-a): 7-Methoxy-3-(pyridin-3-yl)isoquinolin-1-ol (prepared in a manner analogous to that described for 2-amino-5-methoxybenzoic acid in Method K, replacing 5-methoxy-2-nitrobenzoic acid with 1-(benzyloxy)-7-methoxy-3-(pyridin-3-yl) isoquinoline) was obtained in a 63.6% yield to give 280 mg of xxxviv-a as a yellow solid. This was carried on without further purification.

(308) 1-Chloro-7-methoxy-3-(pyridin-3-yl)isoquinoline (xl-a) 1-Chloro-7-methoxy-3-(pyridin-3-yl)isoquinoline (prepared in a manner analogous to that described for 4-chloro-6-propoxy-2-pyridin-3-yl-quinazoline in Method F1, replacing 6-propoxy-2-pyridin-3-yl-1H-quinazolin-4-one with 3-(pyridin-3-yl)isoquinolin-1-ol) was obtained in a 73.0% yield to give 60 mg of xl-a as a brown solid. MS m/z=241.1 (M+1) (Method A) (retention time=1.34 min)

(309) N-(3-Chloro-4-fluorophenyl)-7-methoxy-3-(pyridin-3-yl)isoquinolin-1-amine (xli-a) N(N-(3-chloro-4-fluorophenyl)-7-methoxy-3-(pyridin-3-yl)isoquinolin-1-amine was prepared using Method J. A mixture of 1-chloro-7-methoxy-3-(pyridin-3-yl)isoquinoline (40 mg, 0.17 mmol, 1.0 eq.), 3-chloro-4-fluoro aniline (30 mg, 0.21 mmol, 1.2 eq.), Pd.sub.2(dba).sub.3 (10 mg, 0.011 mmol, 0.06 eq.), Xantphos (15 mg, 0.026 mmol, 0.15 eq.), cesium carbonate (167 mg, 0.52 mmol, 3.0 eq.) was suspended in the mixed solvent of 1,4-dioxane (4 mL) and water (1 mL). The resulting mixture was stirred at 120 C. for 30 min under the microwave conditions. After cooling, the resulting mixture was partitioned between water and ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate. After filtration and evaporation, the residue was purified by prep-HPLC to afford 3 mg of xli-a as a yellow solid (yield 5.2%). LCMS m/z=380.1 (M+1) (Method B). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.35 (s, 1H), 9.30 (d, J=2.0 Hz, 1H), 8.57 (dd, J=4.7, 1.5 Hz, 1H), 8.41 (td, J=8.0, 1.8 Hz, 1H), 8.30 (dd, J=6.9, 2.6 Hz, 1H), 7.94-7.87 (m, 4H), 7.43-7.49 (m, 3H), 3.99 (s, 3H).

(310) The compounds in the following table were prepared in a manner analogous to that described in Scheme 43, replacing with the appropriate isoquinoline and aniline.

(311) TABLE-US-00021 TABLE 15 Pu- Method Molec- .sup.1H- rity for Num- Salt ular NMR LCMS per- Cou- ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol cent pling 1100 081 379.81 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.35 (s, 1H), 9.30 (d, J = 2.0 Hz, 1H), 8.57 (dd, J = 4.7, 1.5 Hz, 1H), 8.41 (td, J = 8.0, 1.8 Hz, 1H), 8.30 (dd, J = 6.9, 2.6 Hz, 1H), 7.94-7.87 (m, 4H), 7.43- 7.49 (m, 3H), 3.99 (s, 3H). DMSO 380.1, 382.0 (M + 1) Method B (NH4HCO3) 95 Method J 1101 082 411.38 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.46 (s, 1H), 9.31 (d, J = 1.75 Hz, 1H), 8.57 (dd, J = 4.6, 1.3 Hz, 1H), 8.45-8.41 (m, 1 H), 8.19 (s, 1H), 7.99-7.94 (m, 2H), 7.91-7.86 (m, 2H), 7.54-7.44 (m, 3H), 7.01 (d, J = 8.1 Hz, 1H), 4.00 (s, 3H). DMSO 412.1 (M + 1) Method B (NH4HCO3) 95 Method J 1102 083 388.39 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.35 (s, 1H), 9.34 (d, J = 1.9 Hz, 1H), 8.80 (d, J = 8.4 Hz, 1H), 8.59 (dd, J = 4.7, 1.48 Hz, 1H), 8.49-8.45 (m, 1H), 8.26 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.97- 7.92 (m, 1H), 7.61 (td, J = 14.9, 7.5 Hz, 1H), 7.56-7.48 (m, 3H), 6.95 (dd, J = 10.3, 8.3 Hz, 1H), 3.98 (s, 3H). DMSO 389.1 (M + 1) Method B (NH4HCO3) 95 Method J 1103 084 370.4 .sup.1H-NMR (400 MHz, CDCl3): 11.89 (s, 1H), 9.39 (s, 1H), 9.29 (s, 1H), 8.63-8.59 (m, 1H), 8.42- 8.37 (m, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.60-7.62 (m, 4H), 7.44-7.33 (m, 3H), 7.05-7.00 (m, 1H), 4.06 (s, 3H). CDCl3 371.1 (M + 1) Method B (NH4HCO3) 95 Method J 1104 085 407.37 .sup.1H-NMR (400 MHz, CDCl3): 9.28 (s, 1H), 8.60 (d, J = 4.6 Hz, 1H), 8.34 (d, J = 7.8 Hz, 1H), 7.85 (s, 1H), 7.79 (d, J = 8.9 Hz, 1H), 7.63 (s, 1H), 7.43-7.35 (m, 2H), 7.22 (d, J = 8.6 Hz, 1H), 7.17 (s, 1H), 7.09-7.03 (m, 2H), 4.00 (s, 3H). CDCl3 408.1 (M + 1) Method B (NH4HCO3) 95 Method J 1105 086 454.4 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.00 (s, 1H), 9.43 (d, J = 1.2 Hz, 1H), 9.35 (s, 1H), 8.63 (d, J = 3.7 Hz, 1H), 8.53 (s, 1H), 8.48-8.44 (m, 1H), 8.03-8.09 (m, 3H), 7.97 (d, J = 8.9 Hz, 1H), 7.65 (d, J = 1.8 Hz, 1H), 7.56-7.50 (m, 2H), 7.05 (dd, J = 8.6, 1.93 Hz, 1H), 4.01 (s, 3H). DMSO 455.1 (M + 1) Method B (NH4HCO3) 95 Method J 1106 087 455.91 1H-NMR (400 MHz, DMSO-d.sub.6): 9.65 (s, 1H), 9.37 (d, J = 1.7 Hz, 1H), 8.83 (s, 1H), 8.63 (dd, J = 4.7, 1.3 Hz, 1H), 8.54-8.43 (m, 1H), 8.35 (dd, J = 6.9, 2.6 Hz, 1H), 8.15 (dd, J = 8.5, 1.4 Hz, 1 H), 8.03 (t, J = 4.3 Hz, 2H), 7.91-7.95 (m, 1H), 7.46- 7.55 (m, 5H), 7.11-7.01 (m, 1H), 3.91 (s, 3H). DMSO 456.1, 458.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method J 1107 088 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (s, 1H), 9.36 (d, J = 1.9 Hz, 1H), 9.19 (d, J = 1.9 Hz, 1H), 8.91 (s, 1H), 8.67 (dd, J = 4.8, 1.5 Hz, 1H), 8.62 (dd, J = 4.7, 1.5 Hz, 1H), 8.53-8.44 (m, 1H), 8.35-8.32 (m, 2H), 8.19 (dd, J = 8.5, 1.5 Hz, 1H), 8.13-8.01 (m, 2H), 7.92 (ddd, J = 9.1, 4.3, 2.7 Hz, 1H), 7.61 (dd, J = 7.9, 4.8 Hz, 1H), 7.55 (dd, J = 8.0, 4.8 Hz, 1H), 7.50 (t, J = 9.1 Hz, 1H). DMSO 426.7 428.7 (M + 1) Method B (NH4HCO3) 95 Method J

(312) ##STR02089##

(313) ##STR02090##

(314) Method AI: Ethyl 2-cyano-4,4-diethoxybutanoate (xlii-a) 2-Bromo-1,1-diethoxyethane (4 g, 20 mmol, 1.0 eq.) was added to a mixture of ethyl 2-cyanoacetate (11.4 g, 101 mmol, 5.0 eq.), K.sub.2CO.sub.3 (2.8 g, 20 mmol, 1.0 eq.) and NaI (200 mg, 1.3 mmol, 0.06 eq.), as described in J. Chem. Soc., 1960, 131-138. The reaction mixture was refluxed for 4 h at 145 C. After cooling, the reaction mixture was purified by chromatography on silica gel (eluted with petroleum ether/ethyl acetate (80:1.fwdarw.40:1.fwdarw.40:1) to give 3.57 g of xlii-a as a colorless oil (78%). .sup.1H NMR (400 MHz, CDCl.sub.3): 4.70 (t, J=5.6 Hz, 1H), 4.26 (q, J=7.2 Hz, 2H), 3.78-3.64 (m, 3H), 3.62-3.45 (m, 2H), 2.35-2.14 (m, 2H), 1.34 (q, J=7.2 Hz, 3H), 1.25-1.16 (m, 6H).

(315) Method AJ: 2-(Pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (xliii) To a solution of nicotinimidamide (5.03 g, 41.6 mmol, 1.2 eq.) in EtOH (100 mL), was added NaOMe (4.8 g, 88.8 mmol, 2.5 eq.). The mixture was stirred at room temperature for 4 h. The reaction mixture was added to ethyl 2-cyano-4,4-diethoxybutanoate (8.00 g, 34.9 mmol, 1 eq.). This mixture was stirred at 105 C. overnight. After cooling, the reaction mixture was acidified with conc. HCl and stirred at room temperature for 2 h. A precipitate formed and was collected and washed with H.sub.2O (20 mL2). After lyophilization, 3.10 g of product was obtained as a gray yellow solid (yield 41.8%). LCMS m/z=213.1 (M+1) (Method B) (retention time=1.07 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 12.26 (s, 1H), 12.04 (s, 1H), 9.23 (d, J=1.6 Hz, 1H), 8.70 (dd, J=4.8, 1.2 Hz, 1H), 8.43-8.40 (m, 1H), 7.55 (dd, J=8.0, 4.8 Hz, 1H), 7.12 (d, J=1.6 Hz, 1H), 6.51 (d, J=2.8 Hz, 1H).

(316) 4-Chloro-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (xlv-a) 4-Chloro-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (prepared in a manner analogous to that described for 4-chloro-6-propoxy-2-pyridin-3-yl-quinazoline in Method F1, replacing 6-propoxy-2-pyridin-3-yl-1H-quinazolin-4-one with 2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol) to give 450 mg of xliv-a in a 69.0% yield as a brown solid. LCMS m/z=231.0, 233.0 (M+1) (Method B) (retention time=1.60 min)

(317) N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (xlv-a) N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (prepared in a manner analogous to that described for N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine using Method G6, replacing 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate with 4-chloro-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine) to give a 11.3% yield, 10 mg of xlv-a as brown solid. LCMS m/z=340.1, 342.0 (M+1) (Method B) (retention time=1.814 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.48 (d, J=1.6 Hz, 1H), 8.62 (dd, J=4.8, 1.6 Hz, 1H), 8.60-8.56 (m, 1H), 8.27 (dd, J=6.4, 2.4 Hz, 1H), 8.06 (ddd, J=8.8, 4.0, 2.8 Hz, 1H), 7.71 (d, J=3.6 Hz, 1H), 7.66 (t, J=9.2 Hz, 1H), 7.50 (dd, J=8.0, 4.8 Hz, 1H), 7.41 (br s, 2H), 6.85 (d, J=3.6 Hz, 1H).

(318) The compounds in the following table were prepared in a manner analogous to that described in Scheme 45, replacing with the appropriate aniline.

(319) TABLE-US-00022 TABLE 16 Molec- .sup.1H- Method Num- Salt ular NMR LCMS Purity for ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1108 091 330.34 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (s, 1H), 12.09 (s, 1H), 9.54 (d, J = 1.2 Hz, 1H), 9.11 (d, J = 8.4 Hz, 1H), 8.65-8.68 (m, 1H), 8.35 (s, 1H), 7.89 (dd, J = 8.0, 1.2 Hz, 1H), 7.79 (s, 1H), 7.67 (td, J = 8.8, 1.2 Hz, 1H), 7.55 (dd, J = 7.2, 4.8 Hz, 1H), 7.43-7.41 (m, 1H), 7.10 (td, J = 8.0, 1.2 Hz, 1H), 6.49 (d, J = 3.6 Hz, 1H). DMSO 331.1 (M + 1) Method B (NH4HCO3) 95 Method AJ, F, G6 1109 092 371.32 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.02 (d, J = 1.3 Hz, 1H), 9.75 (s, 1H), 9.50 (d, J = 1.5 Hz, 1H), 8.68-8.53 (m, 2H), 8.29 (s, 1H), 7.94-7.75 (m, 1H), 7.61-7.44 (m, 2H), 7.41-7.29 (m, 1H), 7.04 (s, 1H), 6.88 (dd, J = 3.4, 1.9 Hz, 1H). DMSO 372.0 (M + 1) Method A (TFA) 95 Method AJ, F, G6 1110 093 366.32 1H-NMR (400 MHz, DMSO-d6): 11.98 (s, 1H), 9.69 (s, 1H), 9.48 (d, J = 1.8 Hz, 1H), 8.64-8.59 (m, 2H), 8.19 (d, J = 2.0 Hz, 1H), 7.63 (dd, J = 8.8, 2.0 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.34 (d, J = 3.0 Hz, 1H), 6. DMSO 368.1 (M + 1) Method A (TFA) 95 Method AJ, F, G6 1111 094 339.75 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.51 (s, 1H), 8.78 (d, J = 8.0 Hz, 2H), 8.17 (d, J = 9.2 Hz, 1H), 7.80 (dd, J = 9.2, 2.8 Hz, 1H), 7.70-7.64 (m, 1H), 7.46 (d, J = 2.8 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 4.0 Hz, 2H), 7.16-7.08 (m, 1H). DMSO 340.1, 342.0 (M + 1) Method B (NH4HCO3) 95 Method AJ, F, G6

(320) ##STR02095##

(321) ##STR02096##

(322) Method AK: 4-Chloro-7-methyl-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (xliv-a) To a solution of 4-chloro-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (80 mg, 0.34 mmol, 1.0 eq.) in dry DMF (20 mL) was added Cs.sub.2CO.sub.3 (221 mg, 0.68 mmol, 2.0 eq.) and iodomethane (54.3 mg, 0.38 mmol, 1.1 eq.) at 0 C. The reaction mixture was warmed to room temperature and stirred for 2.5 h. The reaction mixture was poured into ice water and extracted with EtOAc (20 mL x 3). The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4. After filtration and concentration, the residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 8:1) to give 65 mg of xlvi-a as brown solid (56.7%).

(323) N-(3-chloro-4-fluorophenyl)-7-methyl-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (xlvii-a) N-(3-chloro-4-fluorophenyl)-7-methyl-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (prepared in a manner analogous to that described for N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine using Method G6, replacing 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate with 4-chloro-7-methyl-2-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine) to give a 70.0% yield, 30 mg of xlvii-a as a brown solid. LCMS m/z=354.1, 356.1 (M+1) (Method B) (retention time=1.94 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.97 (s, 1H), 9.53 (s, 1H), 9.15 (d, J=8.0 Hz, 1H), 8.91 (d, J=5.2 Hz, 1H), 8.25 (dd, J=6.8, 2.4 Hz, 1H), 8.04 (dd, J=7.6, 5.6 Hz, 1H), 7.94-7.90 (m, 1H), 7.48-7.43 (m, 2H), 6.95 (d, J=3.2 Hz, 1H), 3.88 (s, 3H).

(324) The compounds in the following table were prepared in a manner analogous to that described in Scheme 46, replacing with the appropriate aniline.

(325) TABLE-US-00023 TABLE 17 Molec- .sup.1H- Method Num- Salt ular NMR LCMS Purity for ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1112 097 HCl 353.78 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.97 (s, 1H), 9.53 (s, 1H), 9.15 (d, J = 8.0 Hz, 1H), 8.91 (d, J = 5.2 Hz, 1H), 8.25 (dd, J = 6.8, 2.4 Hz, 1H), 8.04 (dd, J = 7.6, 5.6 Hz, 1H), 7.94-7.90 (m, 1H), 7.48-7.43 (m, 2H), 6.95 (d, J = 3.2 Hz, 1H), 3.88 (s, 3H). DMSO 354.1, 356.1 (M + 1) Method B (NH4HCO3) 95 Method AK, G6 1113 098 385.34 .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.81 (s, 1H), 9.56 (d, J = 1.6 Hz, 1H), 8.69-8.64 (m, 2H), 8.29 (s, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.55-7.51 (m, 2H), 7.41 (d, J = 3.6 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 3.87 (s, 3H). DMSO 386.1 (M + 1) Method B (NH4HCO3) 95 Method AK, G6 1114 099 1H-NMR (400 MHz, DMSO-d6): 12.32 (s, 1H), 9.61 (s, 1H), 9.11 (d, J = 7.6 Hz, 1H), 9.11 (d, J = 7.6 Hz, 1H), 8.74 (dt, J = 8.0, 1.9 Hz, 1H), 8.67 (d, J = 3.6 Hz, 1H), 8.38 (s, 1H), 8.38 (s, 1H), 7.90 (dd, J = 7.9, 1.4 Hz, 1H), 7.82 (s, 1H), 7.68 (dd DMSO 344.9 (M + 1) Method B (NH4HCO3) 95 Method AK, G6

(326) ##STR02100##

(327) ##STR02101##

(328) Method AL: 4-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)-2-(pyridin-3-yl)quinazoline-6-carboxamide (xlviii-a) To a suspension of 4-oxo-2-(pyridin-3-yl)-1,4-dihydroquinazoline-6-carboxamide (prepared as described in scheme 4) (100 mg, 0.376 mmol, 1.0 eq.) in dry DMF (20 mL) was added benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (216 mg, 0.488 mmol, 1.3 eq.) and diaza(1,3)bicyclo[5.4.0]undecene (114.5 mg, 0.752 mmol, 2.0 eq.) following a procedure outlined in J. Org. Chem., 2007, 72, 10194-10210. To the clear solution was then added 5,6-dimethyl-1H-benzo[d]imidazole (165.2 mg, 1.13 mmol, 3.0 eq.) and the mixture was stirred overnight at room temperature. The resultant precipitate was then collected by filtration and washed with dichloromethane, water, and ether. The product was dried in vacuo to give 26.3 mg of the desired product (xlviii-a) as an off-white solid (6.7%). LCMS m/z=395.1 (M+1) (Method C) (retention time=1.68 min). .sup.1H NMR (300 MHz, DMSO) 9.69 (s, 1H), 8.90 (s, 1H), 8.82 (d, J=15.2 Hz, 2H), 8.66 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 8.42 (s, 1H), 8.30 (d, J=8.5 Hz, 1H), 7.79 (s, 1H), 7.68 (s, 3H), 2.39 (s, 3H), 2.36 (s, 3H).

(329) ##STR02102##

(330) ##STR02103##

(331) Method AM: Synthesis of 2-(6-(2-(piperidin-1-yl)ethoxy)-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (xlviv-a) To 1-(2-chloroethyl)piperidine (45 mol) was added the solution of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (30 mol) in NMP (200 L). PS-BEMP (90 mol) was added to the vials by resin dispenser. After the reaction mixture was heated at 90 C. for 12 h, the residue was diluted with methanol and purified by mass triggered PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound whose structure was finally confirmed by LCMS using LCMS Method E.

(332) The compounds in the following table were prepared in a manner analogous to that described in Scheme 51, replacing 1-(2-chloroethyl)piperidine with the appropriate alkyl halide.

(333) TABLE-US-00024 TABLE 18 Mass Num- Starting Starting Salt Exact Found Purity ber Material 1 Material 2 Product Type Mass (M + 1) (%) 1116 04 05 06 468 469 98 1117 07 08 09 454 455 98 1118 0 456 457 98 1119 468 469 98 1120 482 483 98 1121 0 TFA 496 497 98 1122 465 466 98 1123 505 506 98

(334) ##STR02128##

(335) To a suspension of ethyl 2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-4-phenylthiazole-5-carboxylate (1.3956 g, 2.89 mmol) in dioxane (40 mL) was added 1N NaOH (20 ml, 20.00 mmol) at room temperature to give a clear solution. The reaction mixture was stirred at room temperature for 1 h and then warmed to 50 C. overnight, however starting material remained. An additional 20 mL of 1N NaOH was added and heating was continued at 50 C. for 1 h and at 70 C. for 5 h 30 min. The reaction mixture was cooled to room temperature and diluted with water and ethyl acetate. The water phase was removed and adjusted to an acidic pH with 1N HCl (40 mL). A precipitate formed and was collected and washed with water. The product was dried in vacuo to give 1.20 g of a brown solid in a 91% yield. .sup.1H NMR (DMSO-d.sub.6) ppm 12.88 (br, 2H), 9.77 (dd, J=2.12, 0.6 Hz, 1H), 8.92-8.89 (m, 1H), 8.78 (dd, J=4.8, 1.68 Hz, 1H), 8.32 (br, 1H), 7.96 (d, J=9.12 Hz, 1H), 7.82-7.80 (m, 2H), 7.70-7.67 (m, 1H), 7.63 (dd, J=9.12, 2.68 Hz, 1H), 7.50-7.44 (m, 3H), 3.98 (s, 3H).

(336) Method AN: 2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-N-methyl-4-phenylthiazole-5-carboxamide To a suspension of 2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-4-phenylthiazole-5-carboxylic acid (291.8 mg, 0.641 mmol) in DMF(20 mL) under nitrogen atmosphere was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (189 mg, 0.986 mmol) and 1-hydroxybenzotriazole hydrate (147 mg, 0.961 mmol) at room temperature. The reaction mixture was stirred at room temperature for 10 min to give a clear solution and methylamine in a methanol solution (4 mL) was added at room temperature. The reaction mixture was stirred at room temperature for 2 h 15 min. Additional methyl amine in a methanol solution (4 mL) was added at room temperature and then heated to 50 C. for 1 h followed by room temperature for 2 days. The reaction mixture was partitioned between water and ethyl acetate. The water phase was collected and a solid precipitated from the water phase. The solid was filtered and dried in an oven at 60 C. to give 107.9 mg (0.23 mmol) as the parent compound. The parent compound was suspended in methanol and 4N HCl in ethyl acetate (ca. 2 mL) was added to give a clear solution which precipitated over time. The solid was collected by filtration and dried in oven at 60 C. for 2 days to give 82.4 mg of the HCl salt as a yellow solid in 24% yield. .sup.1H NMR (DMSO-d.sub.6) 12.77 (brs, 1H), 9.76 (d, J=1.72 Hz, 1H), 9.18 (d, J=7.88 Hz, 1H), 8.92 (d J=5.04 Hz, 1H), 8.35 (brs, 1H), 8.27 (brd, J=4.56 Hz, 1H), 7.99-7.965 (m, 2H), 7.79 (brd, J=7.16 Hz, 2H), 7.65 (dd, J=9.12, 2.56 Hz, 1H), 7.50-7.41 (m, 3H), 4.00 (s, 3H), 2.76 (d, J=4.56 Hz, 3H). The 1H of 2HCl was not observed.

(337) The compounds in the following table were prepared in a manner analogous to that described in Scheme 53, replacing N-methyl amine with the appropriate alkyl amine.

(338) TABLE-US-00025 TABLE 19 Number Starting Material 1 Starting Material 2 Product 1124 0 1125 NH.sub.3 1126 Method Salt .sup.1H NMR Purity of Number Type .sup.1H NMR Solvent percent Coupling 1124 2 HCl 1H NMR (DMSO-d6) ppm 12.77 (brs, DMSO >98 Method AN 1H), 9.76 (d, J = 1.72 Hz, 1H), 9.18 (d, J = 7.88 Hz, 1H), 8.92 (d, J = 5.04 Hz, 1H), 8.35 (brs, 1H), 8.27 (brd, J = 4.56 Hz, 1H), 7.99-7.965 (m, 2H), 7.79 (brd, J = 7.16 Hz, 2H), 7.65 (dd, J = 9.12, 2.56 Hz, 1H), 7.50-7.41 (m, 3H), 4.00 (s, 3H), 2.76 (d, J = 4.56 Hz, 3H). The 1H of 2HCl was not observed. 1125 2 HCl 1H NMR (DMSO-d6) ppm 12.75 (brs, DMSO >98 Method AN 1H), 9.77 (d, J = 1.52 Hz, 1H), 9.13 (brs, 1H), 8.88 (brd, J = 5.08 Hz, 1H), 8.34 (d, J = 2.04 Hz, 1H), 7.98 (d, J = 9.12 HZ, 1H), 7.90 (brm, 1H), 7.83-7.80 (m, 2H), 7.66-7.53 (brm, 3H), 7.52-7.42 (m, 3H), 4.00 (s, 3H). The 1H of 2HCl was not observed. 1126 1H NMR (DMSO-d6) ppm 12.66 (s, DMSO >98 Method AN 1H), 9.76 (s, 1H), 8.88 (d, J = 7.76 HZ, 1H), 8.75 (d, J = 3.68 Hz, 1H), 8.40-8.20 (br, 2H), 7.94 (br, 1H), 7.80 (d, J = 7.16 Hz, 2H), 7.63 (m, 2H), 7.49-7.41 (m, 3H), 3.99 (s, 3H), 3.24 (q, J = 7.24 Hz, 2H), 1.07 (t, J = 7.24 Hz, 3H)

(339) ##STR02137##

(340) ##STR02138##

(341) Method AO: N-tert-butyl-2-(4-(3,4-difluorophenyl-amino)-2-(pyridin-3-yl)quinazolin-6-yloxy)acetamide To a solution of carboxylic acid derivative (500 mg, 1.2 mmol) in DMF was added 2-aminoisobutane (134 mg, 1.8 mmol), NMM (0.4 mL, 3.6 mmol), WSCDI (282 mg, 1.4 mmol) and HOBT (225 mg, 1.4 mmol). The reaction mixture was stirred at room temperature overnight. The resulting solution was poured into ice-water and the precipitate formed and was filtered off. The solid was washed with water and dried to give 350 mg (62% yield) of desired product. .sup.1H NMR (400 MHz, DMSO) 9.86 (s, 1H), 9.49 (d, J=1.5 Hz, 1H), 8.71-8.57 (m, 2H), 8.11 (ddd, J=13.3, 7.5, 2.5 Hz, 1H), 8.00-7.93 (m, 1H), 7.87 (d, J=9.1 Hz, 1H), 7.67 (ddd, J=11.7, 7.1, 2.1 Hz, 2H), 7.59-7.47 (m, 3H), 4.61 (s, 2H), 1.35 (s, 9H).

(342) The compounds in the following table were prepared in a manner analogous to that described in Scheme 54, replacing 2-aminoisobutane with the appropriate alkyl amine

(343) TABLE-US-00026 TABLE 20 Num- Starting Starting ber Material R.sup.1 Material R.sup.3 Product 1127 0 1128 1129 Method Salt .sup.1H NMR Purity of Number Type .sup.1H NMR Solvent percent Coupling 1127 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.60 DMSO >98 Method AO (s, 1H), 9.48 (d, J = 1.9 Hz, 1H), 9.14 (dt, J = 8.2, 1.6 Hz, 1H), 8.96 (dd, J = 5.5, 1.3 Hz, 1H), 8.37 (t, J = 6.0 Hz, 1H), 8.24 (d, J = 2.6 Hz, 1H), 8.11-7.97 (m, 3H), 7.74 (ddd, J = 11.8, 7.4, 3.3 Hz, 2H), 7.55 (dt, J = 10.5, 9.1 Hz, 1H), 4.79 (s, 2H), 3.01 (t, J = 6.5 Hz, 2H), 1.86-1.59 (m, 1H), 0.85 (d, J = 6.7 Hz, 6H). 1128 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.81 DMSO >98 Method AO (s, 1H), 9.50 (d, J = 1.9 Hz, 1H), 9.16 (d, J = 8.2 Hz, 1H), 8.98 (dd, J = 5.5, 1.3 Hz, 1H), 8.40 (d, J = 2.5 Hz, 1H), 8.29 (t, J = 6.4 Hz, 1H), 8.18-7.95 (m, 3H), 7.83-7.67 (m, 2H), 7.55 (dt, J = 10.5, 9.1 Hz, 1H), 4.88 (s, 2H), 2.98 (d, J = 6.4 Hz, 1H), 0.84 (s, 9H). 1129 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.87 DMSO >98 Method AO (s, 1H), 9.50 (d, J = 1.9 Hz, 1H), 9.16 (d, J = 8.2 Hz, 1H), 8.98 (dd, J = 5.5, 1.3 Hz, 1H), 8.41 (d, J = 2.5 Hz, 1H), 8.23-7.96 (m, 4H), 7.85- 7.66 (m, 2H), 7.55 (dt, J = 10.5, 9.1 Hz, 1H), 4.85 (s, 2H), 3.80-3.43 (m, 1H), 1.65-1.21 (m, 4H), 0.81 (t, J = 7.4 Hz, 6H).

(344) ##STR02148##

(345) 2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-N,N-dimethyl-1H-benzo[d]imidazole-1-carboxamide (334.1 mg, 0.760 mmol) was dissolved in concentrated HCl (0.063 ml, 0.760 mmol). The solution was stirred at room temperature overnight and then at 50 C. for 3 h 30 min followed by 100 C. for 3 h. The solid was collected and dried in vacuo to give 116.2 mg of a yellow solid in a yield 35%. .sup.1H NMR (DMSO-d.sub.6) 13.22 (br, 1H), 9.55 (s, 1H), 8.92 (dd, J=4.96, 1.36 Hz, 1H), 8.88 (br, 1H), 8.01 (d, J=9.12 Hz, 1H), 7.92 (br, 1H), 7.83 (br, 1H), 7.67 (dd, J=9.12, 2.80 Hz, 1H), 7.61 (m, 2H), 7.38 (m, 2H), 3.97 (s, 3H). The 1H of 2HCl and NHwere not observed.

(346) ##STR02149##

(347) 4-(4-chlorophenyl)-2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-N,N-dimethyl-1H-imidazole-1-carboxamide and concentrated HCl.sub.(aq) (10 mL) were added to a round bottom flask, a precipitate appeared upon refluxing the mixture for 3 h. The solid was collected (373.4 mg) and trituated with CH.sub.2Cl.sub.2/methanol overnight. The product was filtered and dried to give 261.7 mg of a solid. A suspension of the product in methanol was added to a 1N solution of NaOH.sub.(aq.) (5 mL) followed by CH.sub.2Cl.sub.2 and H.sub.2O. The solid was collected and washed with methanol to give 255.7 mg (0.596 mmol) of the parent product. The free parent was suspended in CH.sub.2Cl.sub.2/methanol and converted to the HCl salt by addition of a 0.3 ml solution of 4N HCl in ethyl acetate. The HCl salt was collected and dried in vacuo to give 248.4 mg as brown solid in a 26% yield. .sup.1H NMR (DMSO-d.sub.6) 13.61 (br, 1H), 12.81 (br, 1H), 9.46 (s, 1H), 8.87 (d, J=5.24 Hz, 1H), 8.70 (br, 1H), 7.91-7.87 (m, 5H), 7.75 (m, 1H), 7.62-7.56 (m, 3H), 3.95 (s, 3H). The 1H of 2HCl was not observed.

(348) ##STR02150##

(349) To a mixture of N-(6-(benzyloxy)-2-(pyridin-3-yl)quinazolin-4-yl)-4-(4-chlorophenyl)thiazol-2-amine and catechol, dimethyl ether (0.16 g, 1.15 mmol) was added methanesulfonic acid (4.0 mL). The mixture was stirred for 1 hr and was then poured into water. The slurry was added to a stirring sat. NaHCO.sub.3(aq). l , solution slowly and allowed to stir for 30 min. The precipitate was filtered to give a brown solid which was washed with methanol to give 4-(4-(4-chlorophenyl)thiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol (0.23 g, 91.0%).

(350) Scheme 59: Synthesis of 4-(4-phenylthiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol (Compound 1133) Synthesis of 4-(4-phenylthiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol was performed in a similar manner to that described for 4-(4-(4-chlorophenyl)thiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol substituting for 4-(4-phenylthiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol for the N-(6-(benzyloxy)-2-(pyridin-3-yl)quinazolin-4-yl)-4-(4-chlorophenyl)thiazol-2-amine giving 4-(4-phenylthiazol-2-ylamino)-2-(pyridin-3-yl)quinazolin-6-ol. .sup.1H NMR (300 MHz, DMSO) 10.06-9.22 (m, 2H), 8.95 (dt, J=7.9, 1.6 Hz, 1H), 8.62 (dd, J=4.7, 1.4 Hz, 1H), 7.99 (d, J=7.5 Hz, 2H), 7.87 (d, J=2.8 Hz, 1H), 7.59-7.47 (m, 2H), 7.45-7.32 (m, 3H), 7.30-7.09 (m, 2H).

(351) ##STR02151##

(352) To a mixture of 4-chloro-6-methoxy-2-(pyridin-3-yl)quinazoline (0.50 g, 1.84 mmol) and 5-fluorospiro[[1,3]dioxolane-2,3-indolin]-2-one (0.42 g, 2.02 mmol) in dry DMSO (4 mL) was added KOH powder (0.11 g, 2.02 mmol). The reaction mixture was stirred for 15 h at room temperature and then the reaction mixture was poured into water. The aqueous layer was washed with ethyl acetate (220 mL) and the resulting aqueous layer was acidified with 5N HCl to give a precipitate. The solid was filtered to give 2-(5-fluoro-2-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)phenyl)-1,3-dioxolane-2-carboxylic acid as a light yellow powder (0.27 g, 0.58 mmol, 32%). LCMS m/z=432 (M+1) (Method C).sup.1H NMR (300 MHz, DMSO) 9.50-9.38 (m, 2H), 8.69-8.59 (m, 2H), 8.42 (dd, J=9.7, 5.3 Hz, 1H), 7.86 (d, J=9.1 Hz, 1H), 7.64 (d, J=2.6 Hz, 1H), 7.61-7.41 (m, 4H), 4.25-4.11 (m, 4H), 3.98 (s, 3H).

(353) ##STR02152##

(354) In a 50 mL round-bottomed flask was added 2,4-dichloro-6-iodoquinazoline (0.52 g, 1.6 mmol), 3-chloro-4-fluoroaniline (0.30 g, 2.1 mmol), and sodium acetate (0.20 g, 2.4 mmol) in THF (6 mL) and water (2 mL) to give a brown suspension. After being stirred at room temperature for 6 days, the reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (210 mL). The organic layers were combined and washed with brine (120 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting product was washed with CH.sub.2Cl.sub.2 and dried to give 0.51 g of 2-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amine as a light brown solid in a 73% yield. .sup.1H NMR (300 MHz, DMSO) 10.29 (s, 1H), 8.95 (s, 1H), 8.14 (dd, J=1.5, 9.0 Hz, 1H), 8.06 (dd, J=2.7, 6.6 Hz, 1H), 7.81-7.76 (m, 1H), 7.52-7.46 (m, 2H).

(355) In a 50 mL round-bottomed flask was added 2-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amine (200 mg, 0.46 mmol), N,N-dimethylpropargylamine (99 mL, 0.92 mmol), NEt.sub.3 (0.26 mL, 1.84 mmol), CuI (0.88 mg, 4.6 mmol) and PdCl.sub.2(PPh.sub.3).sub.2 (6.5 mg, 9.2 mmol) in DMF (3 mL) to give a light yellow suspension. The mixture was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was diluted with water (10 mL) and ethyl acetate (10 mL) and then a precipitate formed. The resulting precipitate was removed by filtration through Celite. The filtrate was extracted with ethyl acetate (210 mL). The combined organic layer was washed with water (115 mL) and brine (115 mL) and was dried over Na.sub.2SO.sub.4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with CH.sub.2Cl.sub.2/MeOH 1:0 to 9:1). The desired product was washed with CH.sub.2Cl.sub.2 to give 61 mg of 2-chloro-N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)prop-1-ynyl)quinazolin-4-amine as pale yellow solid in a 34% yield. LCMS m/z=389 (M+1) (Method C) (retention time=2.24 min). .sup.1H NMR (300 MHz, DMSO) 10.30 (s, 1H), 8.68 (s, 1H), 8.07 (dd, J=2.7, 6.9 Hz, 1H), 7.86 (dd, J=1.8, 8.7 Hz, 1H), 7.81-7.70 (m, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.49 (t, J=9.2 Hz, 1H), 3.52 (s, 2H), 2.28 (s, 6H).

(356) In a 50 mL round-bottomed flask was added 2-chloro-N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)prop-1-ynyl)quinazolin-4-amine (61 mg, 0.16 mmol), 3-pyridineboronic acid (25 mg, 0.20 mmol), K.sub.2CO.sub.3 (0.11 mg, 0.78 mmol) and PdCl.sub.2(PPh.sub.3).sub.2 (5.5 mg, 7.8 mM) in dioxane (2 mL) to give a yellow suspension. The mixture was heated at reflux for 3 h under argon. After cooling to room temperature, water (10 mL) and ethyl acetate (10 mL) were added to the mixture to form a precipitate. The resulting precipitate was filtered through Celite. The filtrate was extracted with ethyl acetate (210 mL) and the combined organic layers were washed with water (115 mL) and brine (115 mL) and then dried over Na.sub.2SO.sub.4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with AcOEt/MeOH 1:0 to 9:1). The desired product was washed with CH.sub.2Cl.sub.2 to give 25 mg of N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)prop-1-ynyl)-2-(pyridin-3-yl)quinazolin-4-amine as a light brown solid in 37% yield. LCMS m/z=432 (M+1) (Method C) (retention time=1.86 min). .sup.1H NMR (300 MHz, DMSO) 10.13 (s, 1H), 9.51 (s, 1H), 8.77-8.56 (m, 3H), 8.26 (dd, J=6.9, 2.5 Hz, 1H), 8.02-7.78 (m, 3H), 7.64-7.47 (m, 2H), 3.54 (s, 2H), 2.30 (s, 6H).

(357) ##STR02153##

(358) A mixture of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (200 mg, 0.283 mmol), (isocyanatomethyl)benzene (5 mL) and Et.sub.3N (57 mg, 0.283 mmol) in tetrahydrofuran (THF) (10 mL) was stirred at room temperature overnight. Water (10 mL) was added to the above mixture and the mixture was concentrated in vacuo. The precipitate was collected by filtration and washed with water (6 mL2) to afford 72 mg of the desired product as a white solid in a yield 26.0%. LCMS: rt=1.829 min, [MH].sup.+=491.1 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.05 (s, 1H), 9.63 (s, 1H), 9.07 (d, J=8.5 Hz, 1H), 8.87 (d, J=8.0 Hz, 1H), 8.79 (d, J=3.7 Hz, 1H), 8.59 (t, J=6.1 Hz, 1H), 8.49 (s, 1H), 8.02-7.89 (m, 4H), 7.82-7.68 (m, 3H), 7.46-7.22 (m, 6H), 4.35 (d, J=6.1 Hz, 2H).

(359) ##STR02154##

(360) 4-(2-carbamoylphenylamino)-2-(pyridin-3-yl)quinazolin-6-yl ethylcarbamate was synthesized in a similar manner to that described for 4-(2-carbamoylphenylamino)-2-(pyridin-3-yl)quinazolin-6-yl benzylcarbamate substituting isocyanatoethane for (isocyanatomethyl)benzene. The resulting product was analyzed by LCMS: rt=1.11 min, [M+1].sup.+=429.0. .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 13.06 (s, 1H), 9.66 (s, 1H), 9.10 (d, J=8.3 Hz, 1H), 8.87-8.80 (m, 2H), 8.51 (s, 1H), 8.06-7.94 (m, 4H), 7.88 (s, 1H), 7.79-7.63 (m, 3H), 7.24 (t, J=7.6 Hz, 1H), 3.22-3.11 (m, 2H), 1.14 (t, J=7.2 Hz, 3H).

(361) ##STR02155##

(362) A mixture of 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazoline-6-carbonitrile (1.5 g, 4.0 mmol) in HCl (conc, 25 mL) was heated to 100 C. and stirred overnight. After cooling and filtration, the solid was washed with water (10 mL) twice to give 1.4 g of the desired product 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazoline-6-carboxylic acid as a yellow solid in a 89.0% yield. LCMS: r.t=1.271 min, NM.sup.+=394.9

(363) A mixture of 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazoline-6-carboxylic acid (900 mg, 2.4 mmol), DIPEA (620 mg, 4.8 mmol) and HATU (1.4 g, 3.6 mmol) in DMF (10 mL) was pre-stirred for 20 min, and 2,2,2-trifluoro-N-methylethanamine (360 mg, 2.4 mmol) was added in one portion. The resulting mixture was stirred at room temperature overnight. Water (80 mL) was added and a precipitate formed which was collected and purified by prep-HPLC to afford 490 mg of the desired product 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide as a white solid in 42.0% yield. LCMS: r.t=1.970 min, [MH].sup.+=490.0 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.79 (brs, 1H), 9.59 (s, 1H), 9.19 (d, J=7.6 Hz, 1H), 9.04 (d, J=4.8 Hz, 1H), 8.90 (s, 1H), 8.22-8.00 (m, 5H), 7.62 (t, J=9.2 Hz, 1H), 4.55-4.52 (m, 2H), 3.22 (s, 3H).

(364) To a mixture of 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide (60 mg, 0.12 mmol) in THF (1 mL) was added BH.sub.3-THF (2 mol/L, lmL). The mixture was stirred at room temperature overnight. Methanol (0.2 mL) was added to quench the reaction mixture. The mixture was purified by prep-HPLC to give the desired product N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amine (GL001H-3309) as a white solid 15 mg in a yield of 26.0%. LCMS: r.t=2.154 min, [MH].sup.+=476.1. .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.09 (s, 1H), 9.53 (s, 1H), 8.70-8.66 (m, 2H), 8.44 (s, 1H), 8.27-8.25 (m, 1H), 7.93-7.91 (m, 3H), 7.57-7.55 (m, 2H), 3.93 (s, 2H), 3.39-3.32 (m, 2H), 2.40 (s, 3H).

(365) Synthesis of 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide (compound 1139) 4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide was synthesized in a similar manner to that described for 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide substituting 2,2,2-trifluoroethylamine for 2,2,2-trifluoro-N-methylethylamine. The resulting product was analyzed. LCMS: r.t=1.934 min, [M+1].sup.+=476.0. .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.43 (s, 1H), 9.54 (s, 1H), 9.32 (t, J=6.1 Hz, 1H), 9.14 (s, 1H), 8.72 (d, J=4.6 Hz, 1H), 8.68 (d, J=8.0 Hz, 1H), 8.32 (d, J=8.7 Hz, 1H), 8.27 (dd, J=6.7, 2.2 Hz, 1H), 7.98 (d, J=8.7 Hz, 1H), 7.96-7.90 (m, 1H), 7.62-7.51 (m, 2H), 4.27-4.14 (m, 2H).

(366) ##STR02156##
Method E for Cyclization E1: Sodium methoxide/Toluene E2: NaOH/EtOH
Method G for Coupling Conditions G1: i-PrOH/85-100 C. G2: THF/reflux G3: i-AmOH/100-130 C. G4: MeOH/microwave/150 C. G5: i-AmOH/microwave/150 C. G6: THF/Et.sub.3N/reflux

(367) ##STR02157##

(368) Method D: N-(2-carbamoylphenyl)pyridazine-4-carboxamide (iii-c) A mixture of pyridazine-4-carboxylic acid (500 mg, 4.0 mmol, 1.0 eq.), 2-aminobenzamide (603 mg, 4.4 mmol, 1.1 eq.) and HBTU (3.0 g, 8.0 mmol, 2.0 eq.) was suspended in 15 mL of DMF. DIPEA (2.0 mL, 1.56 g, 12.0 mmol, 3.0 eq.) was added dropwise at room temperature and was stirred over night. After quenching with water, the resulting precipitate was collected and washed with a small amount of DCM. A white solid (388 mg) was obtained, LCMS m/z=243.1 (M+1) (Method B) (retention time=0.99 min), was used in the next step without further purification.

(369) Method E1: 2-(pyridazin-4-yl) quinazolin-4(3H)-one (iv-f) A 100 mL round-bottom flask equipped with a Dean-Stark trap was charged with a mixture of N-(2-carbamoylphenyl)pyridazine-4-carboxamide (300 mg, 1.0 eq.), sodium methoxide (401 mg, 7.4 mmol, 6.0 eq.) and 10 mL of anhydrous toluene. The reaction mixture was heated to 110 C. and refluxed overnight. After cooling, the volatiles were removed in vacuo and the residue was quenched with a saturated aqueous solution of NH.sub.4Cl (10 mL). The pH of the mixture was adjusted to 3 with 10% HCl in water. The solution was extracted with DCM (50 ml3). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4. After filtration and evaporation, 88 mg of a yellow solid was obtained, LCMS m/z=225.1 (M+1) (Method A) (retention time=1.10 min) which was used in the next step without further purification.

(370) Method F5: 4-chloro-2-(pyridazin-4-yl)quinazoline (v-f) A 100-mL round-bottom flask was charged with 2-(pyridazin-4-yl) quinazolin-4(3H)-one (30 mg) which was suspended in 3 mL of POCl.sub.3. The reaction mixture was heated to reflux for 1 h. The reaction mixture turned to a clear brown solution. After cooling, 50 mL of ice/water was carefully added. An aqueous ammonia solution (25% by weight in water) was added dropwise to the mixture with stirring until the pH of the mixture was adjusted to 7-8. An internal temperature of 0 C. was maintained by the addition of ice. The mixture was warmed to room temperature and extracted with DCM (50 ml x 3). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4. After filtration and evaporation, 32 mg was obtained as a light brown solid. LCMS m/z=242.9 (M+1) (Method B) (retention time=1.65 min) The solid was used directly in the next step without further purification.

(371) Method G1: N-(3,4-difluorophenyl)-2-(pyridazin-4-yl)quinazolin-4-amine (vi-r) (This method is representative of method G1, G2, and G3. These three methods can be implemented in a similar way except for substitution of the appropriate solvent and temperature) The mixture of 4-chloro-2-(pyridazin-4-yl)quinazoline (10 mg, 0.041 mmol, 1 eq.) and 3,4-difluorobenzenamine (11 mg, 0.082 mmol, 2eq.) was suspended in i-PrOH. The mixture was heated at 85 C. overnight. After cooling, the resulting precipitate was filtered and purified on HPLC (Condition C). 7.3 mg of N-(3,4-difluorophenyl)-2-(pyridazin-4-yl)quinazolin-4-amine was obtained (yield 53%). LCMS m/z=336.0 (M+1) (Method B) (retention time=1.731 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.23 (s, 1H), 10.00 (dd, J=2.2, 1.3 Hz, 1H), 9.44 (dd, J=5.4, 1.2 Hz, 1H), 8.59 (d, J=8.1 Hz, 1H), 8.39 (dd, J=5.4, 2.4 Hz, 1H), 8.05-8.13 (m, 1H), 7.99 (s, 1H), 7.97 (d, J=3.6 Hz, 1H), 7.72-7.79 (m, 2H), 7.51-7.61 (m, 1H).

(372) The compounds in the following table were prepared in a manner analogous to that described in Scheme 1 and 64 (prepared according to method procedure A-G as designated).

(373) TABLE-US-00027 TABLE 21 Pu- Molec- rity Method Num- Salt ular .sup.1H-NMR LCMS per- for ber Product type Mass .sup.1H-NMR Solvent LCMS Protocol cent Coupling 1140 402.66 1H-NMR (400 MHz, CD3OD): 9.40 (s, 1H), 9.84-9.86 (m, 2H), 8.52 (d, J = 8.4 Hz, 1H), 8.15 (s, 1H), 8.02 (s, 1H), 7.84 (dd. J = 9.2, 2.4 Hz, 1H), 7.66-7.67 (m, 2H). CD3OD 402.0, 404.0, 405.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1141 386.21 1H-NMR (400 MHz, DMSO-d6): 10.78 (s, 1H), 9.49 (s, 1H), 8.89 (d, J = 10.8 Hz, 2H), 8.75 (d, J = 8.8 Hz, 1H), 8.44 (dd, J = 6.8, 2.4 Hz, 1H), 8.12 (d, J = 2.0 Hz, 1H), 7.94- 7.99 (m, 1H), 7.87 (dd, DMSO 386.0, 388.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 J = 8.8, 2.0 Hz, 1H), 7.56 (t, J = 9.2 Hz, 1H). 1142 0 369.76 1H-NMR (400 MHz, CD3OD): 9.40 (s, 1H), 8.76 (d, J = 10.8 Hz, 2H), 8.40 (d, J = 8.8 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.80-7.86 (m, 1H), 7.68 (dd, J = 8.8, 1.6 Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), CD3OD 370.0, 372.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 7.33 (q, J = 9.2 Hz, 1H). 1143 376.8 1H-NMR (400 MHz, CD3OD): 9.55 (s, 1H), 8.80 (d, J = 7.2 Hz, 3H), 8.26 (d, J = 8.8 Hz, 1H), 8.04 (s, 1H), 7.85 (d, J = 6.8 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.66 (t, J = 7.2 Hz, 1H), 7.28 (t, J = CD3OD 377.1, 379.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 7.6 Hz, 1H). 1144 358.78 1H-NMR (400 MHz, CD3OD): 9.39 (d, J = 1.6 Hz, 1H), 8.79 (d, J = 6.8 Hz, 2H), 8.47 (d, J = 9.2 Hz, 1H), 8.20 (s, 1H), 8.05-8.10 (m, 2H), 7.77 (dd, J = 8.8, 2.0 Hz, 1H), 7.63-7.65 (m 2H). CD3OD 359.0, 361.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1145 399.78 1H-NMR (400 MHz, DMSO-d6): 10.63 (s, 1H), 9.52 (d, J = 1.2 Hz, 1H), 8.86 (t, J = 6.0 Hz, 2H), 8.77 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 15.6 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.53 (t, J = 8.0 Hz, 1H), 7.32 (t, J = 74.0 Hz, 1H), 7.04 (dd, DMSO 400.0, 402.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 J = 8.0, 1.6 Hz, 1H). 1146 402.66 1H-NMR (400 MHz, CD3OD): 9.40 (s, 1H), 8.85-8.88 (m, 2H), 8.53 (d, J = 9.2 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H), 7.80- 7.88 (m, 3H), 7.46 (s, 1H). CD3OD 401.9, 403.9, 405.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1147 377.78 1H-NMR (400 MHz, DMSO-d6): 12.28 (s, 1H), 9.58 (s, 1H), 9.14 (d, J = 8.4 Hz, 1H), 8.87 (s, 1H), 8.80 (d, J = 2.0 Hz, 1H), 8.28 (d, J = 9.2 Hz, 1H), 8.07- 8.12 (m, 2H), 7.86 (dd, J = 8.8, 2.0 Hz, DMSO 378.1, 380.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1H), 7.77 (t, J = 8.8 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H). 1148 381.79 1H-NMR (400 MHz, DMSO-d6): 11.69- 11.49 (m, 1H), 9.40 (d, J = 1.2 Hz, 1H), 9.00-8.86 (m, 3H), 8.24 (dd, J = 6.6, 2.1 Hz, 1H), 7.91 (ddd, J = 8.9, 4.2, 2.6 Hz, 1H), 7.71 (d, J = 1.4 Hz, 1H), DMSO 382.1, 384.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 7.61 (t, J = 9.0 Hz, 1H), 7.49 (dd, J = 9.2, 2.3 Hz, 1H) 4.00 (s, 3H). 1149 395.36 1H-NMR (400 MHz, DMSO-d6): 9.96 (s, 1H), 9.57 (d, J = 1.4 Hz, 1H), 8.83- 8.74 (m, 2H), 8.57 (d, J = 9.1 Hz, 1H), 8.28 (t, J = 2.0 Hz, 1H), 7.86 (dd, J = 8.2, 1.2 Hz, 1H), 7.50- 7.32 (m, 3H), 7.31 (t, J = 74.0 Hz, 1H), 6.94 (dd, J = DMSO 396.1, (M + 1), 397.2 (M + 2) Method B (NH4HCO3) 95 Method C, G1 8.0, 2.2 Hz, 1H), 3.98 (s, 3H). 1150 383.33 1H-NMR (400 MHz, DMSO-d6): 10.27 (s, 1H), 9.57 (s, 1H), 8.80 (dd, J = 19.8, 1.7 Hz, 2H), 8.72-8.66 (m, 1H), 8.50 (s, 1H), 8.07- 7.94 (m, 3H), 7.75 (t, J = 7.2 Hz, DMSO 384.1, (M + 1) Method B (NH4HCO3) 95 Method C, G1 1H), 7.57 (t, J = 8.2 Hz, 1H), 7.14 (d, J = 8.8 Hz, 1H). 1151 385.42 1H-NMR (400 MHz, DMSO-d6): 13.01 (s, 1H), 10.04 (s, 1H), 9.40 (d, J = 5.4 Hz, 1H), 9.20 (d, J = 8.4 Hz, 1H), 8.48 (s, 1H), 8.42 (dd, J = 5.3, 1.9 Hz, 1H), 8.04-7.94 (m, 2H), 7.84 (d, J = 9.2 DMSO 386.0 (M + 1) Method A (TFA) 95 Method D, G1 Hz, 1H), 7.75 (t, J = 7.9 Hz, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H), 7.13 (s, 1H), 3.15 (s, 6H). 1152 0 HCl 394.83 1H-NMR (400 MHz, DMSO-d6): 10.96 (s, 1H), 9.97 (d, J = 1.1 Hz, 1H), 9.55 (d, J = 5.5 Hz, 1H), 8.61 (dd, J = 5.5, 2.2 Hz, 1H), 8.15 (dd, J = 6.8, 2.6 Hz, 1H), 8.08 (d, J = DMSO 395.1, 397.1 (M + 1) Method A (TFA) 95 Method D, G1 9.3 Hz, 1H), 7.94 (ddd, J = 8.9, 4.3, 2.6 Hz, 1H), 7.74 (s, 1H), 7.62 (dd, J = 9.4, 2.5 Hz, 1H), 7.56 (t, J = 9.1 Hz, 1H), 3.16 (s, 6H). 1153 HCl 408.4 1H-NMR (400 MHz, DMSO-d6): 10.71 (brs, 1H), 10.01- 9.99 (m, 1H), 9.52 (dd, J = 5.5, 1.0 Hz, 1H), 8.60 (dd, J = 5.5, 2.3 Hz, 1H), 8.07 ((d, J = DMSO 409.1 (M + 1) Method A (TFA) 95 Method D, G1 9.2 Hz 1H), 7.85-7.78 (m, 2H), 7.71 (s, 1H), 7.65 (dd, J = 9.3, 2.5 Hz, 1H), 7.56 (t, J = 8.2 Hz, 1H), 7.33 (t, J = 74.0 Hz, 1H), 7.09 (dd, J = 8.1, 2.1 Hz, 1H), 3.17 (s, 6H). 1154 372.38 1H-NMR (400 MHz, DMSO-d6): 13.13 (s, 1H), 9.63 (d, J = 1.2 Hz, 1H), 9.34 (d, J = 7.6 Hz, 1H), 8.91- 8.84 (m, 1H), 8.79 (d, J = 2.4 Hz, 1H), 8.49 (s, 1H), 8.12 (d, J = 9.6 Hz, 1H), 8.03-7.85 DMSO 373.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 (m, 2H), 7.75- 7.61 (m, 1H), 7.48- 7.30 (m, 2H), 7.28-7.06 (m, 1H), 3.99 (s, 3H). 1155 381.79 1H-NMR (400 MHz, DMSO-d6): 10.16 (s, 1H), 9.99- 9.95 (m, 1H), 9.42 (dd, J = 5.2, 1.2 Hz, 1H), 8.58- 8.51 (m, 1H), 8.35 (dd, J = 5.2, 2.4 Hz, 1H), 8.21 (dd, J = 6.8, 2.4 Hz, 1H), 7.93 (ddd, J = DMSO 382.0, 384.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 8.8, 4.2, 2.7 Hz, 1H), 7.53 (dd, J = 11.7, 6.4 Hz, 1H), 7.32 (dd, J = 6.6, 2.6 Hz, 2H), 3.97 (s, 3H). 1156 395.36 1H-NMR (400 MHz, DMSO-d6) 10.07 (s, 1H), 10.01 (d, J = 1.3 Hz, 1H), 9.43 (dd, J = 5.2, 1.2 Hz, 1H), 8.55 (d, J = 10.0 Hz, 1H), 8.40 (dd, J = 5.2, 2.0 Hz, 1H), 7.91 (d, J = 2.0 Hz, 1H), 7.86-7.77 (m, 1H), 7.55- 7.35 (m, 3H), 7.32 (t, DMSO 396.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 J = 74.0 Hz, 1H), 7.01 (dd, J = 8.0, 2.0 Hz, 1H), 3.99 (s, 3H). 1157 376.80 1H-NMR (400 MHz, DMSO-d6): 13.34 (s, 1H), 9.61 (s, 1H), 9.28 (d, J = 8.4 Hz, 1H), 8.87 (s, 1H), 8.80 (s, 1H), 8.53 (s, 1H), 8.25 (s, 1H), 7.94- 8.06 (m, 4H), 7.70 (t, J = 8.0 Hz, 1H), 7.23 (t, J = DMSO 377.0, 379.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 7.6 Hz, 1H). 1158 358.78 1H-NMR (400 MHz, DMSO-d6): 10.35 (s, 1H), 9.54 (s, 1H), 8.77- 8.84 (m, 4H), 8.32 (d, J = 8.0 Hz, 1H), 8.00-8.03 (m, 2H), 7.62- 7.70 (m, 2H). DMSO 359.0, 361.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1159 386.21 1H-NMR (400 MHz, DMSO-d6): 10.55 (s, 1H), 9.50 (s, 1H), 8.83 8.87 (m, 3H), 8.47-8.49 (m, 1H), 7.96- 8.06 (m, 3H), 7.54 (t, J = 9.2 Hz, 1H). DMSO 386.0, 388.0, 390.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1160 402.66 1H-NMR (400 MHz, DMSO-d6): 10.54 (s, 1H), 9.53 (s, 1H), 8.84- 8.88 (m, 3H), 8.62 (d, J = 2.0 Hz, 1H), 8.01-8.07 (m, 3H), 7.73 (d, J = 8.8 Hz, 1H). DMSO 401.9, 403.9, 406.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1161 402.66 1H-NMR (400 MHz, DMSO-d6): 10.42 (s, 1H), 9.55 (d, J = 1.6 Hz, 1H), 8.87- 8.88 (m, 1H), 8.82 (d, J = 2.4 Hz, 1H), 8.36 (d, J = 2.0 Hz, 2H), 8.00-8.07 (m, 2H), 7.40 (t, J = 1.6 Hz, 1H). DMSO 401.9, 403.8, 405.8 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1162 0 468.2 1H-NMR (400 MHz, DMSO-d6): 13.36 (s, 1H), 9.59 (d, J = 1.2 Hz, 1H), 9.15- 9.12 (m, 1H) 8.90-8.85 (m, 2H), 8.68 (d, J = 1.2 Hz, 1H), 8.52 (s, 1H), 8.28- 8.25 (m, 1H), 8.07 (s, 1H), 7.99- DMSO 469.0 (M + 1) Method B (NH4HCO3) 90 Method C, G1 7.96 (m, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.74-7.70 (m, 1H), 7.28 (t, J = 7.6 Hz, 1H). 1163 491.23 1H-NMR (400 MHz, DMSO-d6): 10.83 (s, 1H), 9.32 (s, 1H), 9.07 (s, 1H), 8.74 (s, 2H), 8.16 (dd, J = 8.0, 1.6 Hz, 1H), 7.87 (s, 1H), 7.74-7.64 DMSO 492.0 (M + 1) Method B (NH4HCO3) 90 Method C, G1 (m, 2H), 7.39 (t, J = 8.0 Hz, 1H), 7.16 (t, J = 74.0 Hz, 1H), 6.95- 6.92 (m, 1H). 1164 477.66 1H-NMR (400 MHz, DMSO-d6): 11.48 (s, 1H), 9.42 (s, 1H), 9.34 (s, 1H), 8.95- 8.93 (m, 2H), 8.35-8.30 (m, 2H), 7.97- 7.90 (m, 2H), 7.60 (t, J = 9.0 Hz, 1H). DMSO 478.0, 480.0 (M + 1) Method B (NH4HCO3) 90 Method C, G1 1165 413.81 1H-NMR (400 MHz, DMSO-d6): 10.07 (s, 1H), 9.99 (s, 1H), 9.40 (d, J = 5.6 Hz, 1H), 8.56 (d, J = 1.6 Hz, 1H), 8.36 (dd, J = 5.2, 2.0 Hz, 1H), 7.87 DMSO 414.1, 416.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 (m, 1H), 7.81 (m, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.30 (t, J = 74.0 Hz, 1H), 8.36 (dd, J = 8.4, 2.0 Hz, 1H), 2.70 (s, 3H). 1166 400.24 1H-NMR (400 MHz, DMSO-d6): 10.16 (s, 1H), 10.01 (s, 1H), 9.46 (d, J = 5.2 Hz, 1H), 8.56 (d, J = 1.6 Hz, 1H), 8.39 (dd, J = 5.4, 2.2 Hz, 1H), 8.20 (dd, J = 7.2, 2.6 Hz, DMSO 400.0, 402.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1H), 7.95- 7.91 (m, 1H), 7.89 (s, 1H), 7.57 (t, J = 9.0 Hz, 1H), 2.75 (s, 3H). 1167 409.39 1H-NMR (400 MHz, DMSO-d6): 10.05- 10.3 (m, 2H), 9.45 (dd, J = 5.2, 1.2 Hz, 1H), 8.42 (dd, J = 5.2, 1.2 Hz, 1H), DMSO 410.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 8.06 (d, J = 2.8 Hz, 1H), 7.97-7.94 (m, 2H), 7.86 (dd, J = 8.0, 1.2 Hz, 1H), 7.66-7.60 (m, 2H), 7.38 (t, J = 74.0 Hz, 1H), 7.10- 7.08 (m, 1H), 4.32 (q, J = 6.8 Hz, 2H), 1.51 (t, J = 7.0 Hz, 3H). 1168 379.36 1H-NMR (400 MHz, DMSO-d6): 10.13 (s, 1H), 10.07 (d, J = 2.0 Hz, 1H), 9.44 (dd, J = 5.2, 2.4 Hz, 1H), 8.48-8.44 (m, 2H), 7.93 (t, J = 2.0 Hz, 1H), 7.86- 7.84 (m, 2H), 7.66-7.62 (m, 1H), 7.54 (t, J = 8.4 Hz, 1H), 7.32 (t, J = 74.0 DMSO 380.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 Hz, 1H), 7.02 (dd, J = 8.0, 2.4 Hz, 1H), 2.77 (s, 3H). 1169 444.23 1H-NMR (400 MHz, DMSO-d6): 10.17 (s, 1H), 9.55 (s, 1H), 8.98 (s, 1H), 8.79 (d, J = 12.8 Hz, 2H), 8.26 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.92- DMSO 444.0, 446.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 7.88 (m, 2H), 7.52-7.50 (m, 1H), 7.32 (t, J = 71.6 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H). 1170 430.66 1H-NMR (400 MHz, DMSO-d6): 10.11 (s, 1H), 9.52 (s, 1H), 8.89 (d, J = 1.2 Hz, 1H), 8.83 (s, 1H), 8.77 (d, J = 2.4 Hz, 1H), 8.56 (dd, J = 6.8, 2.4 Hz, 1H), 8.05 (dd, J = DMSO 430.0, 432.0, 434.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 9.2, 2.0 Hz, 1H), 8.02- 7.96 (m, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.49 (t, J = 9.2 Hz, 1H). 1171 386.41 1H-NMR (400 MHz, DMSO-d6): 13.07 (s, 1H), 9.63 (s, 2H), 9.33 (s, 1H), 8.95 (d, J = 8.0 Hz, 1H), 8.50 (s, 1H), 7.99- 7.94 (m, 3H), 7.76-7.71 (m, 1H), 7.62-7.59 (m, DMSO 387.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 2H), 7.24 (t, J = 7.4 Hz, 1H), 4.23 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H). 1172 0 372.38 1H-NMR (400 MHz, DMSO-d6): 13.11 (s, 1H), 9.61 (s, 2H), 9.34 (s, 1H), 8.91 (d, J = 8.0 Hz, 1H), 8.49 (s, 1H), 7.98- 7.95 (m, 3H), 7.72 (t, J = 8.0 Hz, 1H), 7.62-7.60 (m, 2H), 7.24 (t, J = 7.6 DMSO 373.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 Hz, 1H), 3.97 (s, 3H). 1173 HCl 379.32 1H-NMR (400 MHz, DMSO-d6): 10.55 (brs, 1H), 9.59 (s, 2H), 9.35 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.09- 8.07 (m, 1H), 8.00-7.96 (m, 2H), 7.76- 7.72 (m, 1H), 7.67 (dd, DMSO 380.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 J = 8.8, 2.0 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H). 1174 HCl 464.47 1H-NMR (400 MHz, DMSO-d6): 10.14 (s, 1H), 9.59 (s, 1H), 8.80 (m, 2H), 8.62 (d, J = 7.6 Hz, 1H), 8.30 (s, 1H), 7.90 (s, 2H), 7.70 (d, J = 7.6 Hz, 1H), 7.53- 7.45 (m, 1H), 7.39-6.86 DMSO 465.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 (m, 1H), 7.30 (t, J = 74.1 Hz, 1H), 3.73 (s, 2H), 3.63- 3.58 (m, 4H), 2.48-2.43 (m, 4H). 1175 357.37 1H-NMR (400 MHz, DMSO-d6): 9.70 (s, 1H), 9.43 (d, J = 8.4 Hz, 1H), 8.90 (s, 1H), 8.78 (d, J = 2.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 2.8 Hz, 1H), 7.60-7.65 DMSO 358.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 (m, 2H), 7.09- 7.13 (m, 3H), 2.76 (s, 3H). 1176 365.79 1H-NMR (400 MHz, DMSO-d6): 10.02 (s, 1H), 9.62 (s, 1H), 8.85 (s, 1H), 8.76 (d, J = 2.4 Hz, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.03- 8.07 (m, 1H), 7.81 (d, J = 6.8 Hz, 1H), 7.61 (t, J = 7.6 Hz, DMSO 366.0, 368.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1H), 7.49 (t, J = 9.2 Hz, 1H), 2.75 (s, 3H). 1177 379.36 1H-NMR (400 MHz, DMSO-d6): 10.02 (s, 1H), 9.64 (s, 1H), 8.83 (s, 1H), 8.76 (d, J = 2.0 Hz, 1H), 8.50 (d, J = 8.0 Hz, 1H), 8.38 (s, 1H), 7.92 (d, DMSO 380.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 J =8.4 Hz, 1H), 7.81 (d, J = 6.8 Hz, 1H), 7.61 (t, J =7.8 Hz, 1H), 7.49 (t, J = 8.4 Hz, 1H), 7.32 (t, J = 74.0 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H), 2.75 (s, 3H). 1178 382.25 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1H), 9.62 (s, 1H), 8.86 (t, J = 2.4 Hz, 1H), 8.78 (t, J = 3.2 Hz, 2H), 8.52 (d, J = 8.4 Hz, 1H), 8.10-8.13 (m, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.68 (d, J = 9.2 DMSO 381.9, 383.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 2.75 (s. 3H). 1179 349.34 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1H), 9.60 (s, 1H), 8.87 (s, 1H), 8.78 (d, J = 2.4 Hz 1H), 8.50- 8.60 (m, 2H), 7.80-7.85 (m, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.46- 7.54 (m, 1H), 2.74 (s, DMSO 350.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 3H). 1180 382.25 1H-NMR (400 MHz, DMSO-d6): 10.20 (s, 1H), 9.62 (s, 1H), 8.85 (s, 1H), 8.77 (d, J = 2.8 Hz, 1H), 8.47- 8.52 (m, 3H), 7.81 (d, J = 3.2 Hz 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 1.6 Hz, 1H), DMSO 381.9, 383.9 (M + 1) Method B (NH4HCO3) 95 Method C, G1 2.51 (s, 3H). 1181 338.37 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1H) 9.64 (s, 1H), 8.86 (d, J = 9.2 Hz, 2H), 8.78 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 7.84 (d, DMSO 339.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 J = 7.2 Hz, 1H), 7.61- 7.65 (m, 3H), 2.76 (s, 3H). 1182 00 383.33 1H-NMR (400 MHz, DMSO-d6): 10.24 (s, 1H), 9.99 (s, 1H), 9.41 (d, J = 5.2 Hz, 1H), 8.62 (d, J = 8.4 Hz, 1H), 8.36-8.38 (m, 1H), 8.10 (s, 1H), 7.95-7.98 (m, 3H), 7.73- DMSO 384.2 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.74 (m, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H). 1183 01 365.34 1H-NMR (400 MHz, DMSO-d6): 10.19 (s, 1H), 10.01 (s, 1H), 9.41- 9.43 (m, 1H), 8.63 (d, J = 8.0 Hz, 1H), 8.39-8.41 (m, 1H), 7.93- 7.97 (m, 3H), 7.84 (d, DMSO 366.2 (M + 1) Method B (NH4HCO3) 95 Method D, G1 J = 8.4 Hz, 1H), 7.74 (m, 1H), 7.54- 7.56 (m, 1H), 7.32 (t, J = 74.0 Hz, 1H), 7.02-7.04 (m, 1H). 1184 02 398.25 1H-NMR (400 MHz, DMSO-d6): 10.27 (s, 1H), 9.96 (s, 1H), 9.44 (d, J = 4.8 Hz, 1H), 8.40- 8.41 (m, 1H), 8.29 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.4 Hz, 1H), 7.99-8.02 (m, 1H), 7.89 (d, J = 8.8 DMSO 398.0, 400.0, 402.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.56- 7.58 (m, 1H), 3.99 (s, 3H). 1185 03 381.79 1H-NMR (400 MHz, DMSO-d6): 9.92 (s, 1H), 9.36- 9.38 (m, 1H), 8.27-8.29 (m, 1H), 8.14- 8.16 (m, 1H), 7.51 (s, 1H), 7.83- 7.91 (m, 3H), 7.51-7.56 (m, 2H), 3.97 (s, 3H). DMSO 382.1, 384.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1186 04 365.34 1H-NMR (400 MHz, DMSO-d6): 9.95- 10.00 (m, 2H), 9.40 (d, J = 5.6 Hz, 1H), 8.32-8.33 (m, 1H), 8.06 (m, 1H), 7.96 (s, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.69 (m, 1H), 7.54-7.59 (m, 2H), 3.98 DMSO 366.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 (s, 3H). 1187 05 354.36 1H-NMR (400 MHz, DMSO-d6): 10.00 (s, 1H), 9.90 (m, 1H), 9.35- 9.36 (m, 1H), 8.23-8.30 (m, 3H), 7.84-7.90 (m, 2H), 7.62-7.71 (m, 2H), 7.54-7.57 (m, 1H), 3.96 (s, 3H). DMSO 355.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1188 06 413.35 1H-NMR (400 MHz, DMSO-d6): 9.96-10.0 (m, 2H), 8.39-8.40 (m, 1H), 8.31- 8.33 (m, 1H), 8.07 (s, 1H), 7.88-7.96 (m, 3H), 7.57-7.67 (m, 2H), 7.22 (d, J = 8.0 Hz, 1H), 4.01 (s, 3H). DMSO 414.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1189 07 373.36 1H-NMR (400 MHz, DMSO-d6): 12.15 (s, 1H), 10.02 (s, 1H), 9.41 (d, J = 5.2 Hz, 1H), 8.94 (d, J = 7.6 Hz, 1H), 8.41 (m, 1H), 8.09 (d, J = 7.6 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.80 (t, J = 8.4 DMSO 374.1, 376.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 Hz, 1H), 7.60-7.62 (m, 2H), 7.25 (t, J = 7.6 Hz, 1H), 4.01 (s, 3H). 1190 08 398.25 1H-NMR (400 MHz, DMSO-d6): 9.95 (s, 1H), 9.54 (s, 1H), 8.81- 8.82 (m, 1H), 8.74 (d, J = 2.0 Hz, 1H), 8.66 (d, J = 2.4 Hz, 1H), 8.06 (dd, J = 8.8, 2.4 Hz, 1H), 8.00 (d, J = 2.4 Hz, 1H), 7.92 (d, DMSO 397.9, 400.0, 401.9 (M + 1) Method B (NH4HCO3) 95 Method D, G6 J = 8.8 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 3.40 (s, 3H). 1191 09 381.79 1H-NMR (400 MHz, DMSO-d6): 9.90 (s,1H), 9.52 (s, 1H), 8.81 (m, 1H), 8.73 (d, J = 2.4 Hz, 1H), 8.53 (dd, J = 6.8, 2.4 Hz, 1H), 7.98- 8.03 (m, 2H), 7.91 (d, J = 9.2 Hz, 1H), 7.59 (dd, J = 5.2, 2.4 Hz, DMSO 382.0, 384.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 7.51 (t, J = 8.8 Hz, 1H), 3.40 (s, 3H). 1192 0 365.34 1H-NMR (400 MHz, DMSO-d6): 9.89 (s, 1H), 9.52- 9.53 (m, 1H), 8.81-8.82 (m, 1H), 8.73 (d, J = 2.4 Hz, 1H), 8.45- 8.51 (m, 1H), 7.98 (m, 1H), 7.90 (d, J = 9.2 Hz, 1H), 7.75- 7.78 (m, 1H), DMSO 366.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 7.47-7.59 (m, 2H), 3.40 (s, 3H). 1193 354.36 1H-NMR (400 MHz. DMSO-d6): 10.06 (s, 1H), 9.54 (s, 1H), 8.74- 8.81 (m, 3H), 8.35 (d, J = 8.4 Hz, 1H), 8.04 (m, 1H), 7.92-7.95 (m, 1H), 7.59- 7.69 (m, 3H), 3.40 (s, 3H). DMSO 355.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1194 398.25 1H-NMR (400 MHz, DMSO-d6): 9.91 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H), 8.81 (t, J = 2.0 Hz, 1H), 8.74 (d, J = 2.4 Hz, 1H), 8.39 (d, J = 1.6 Hz, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, DMSO 398.0, 399.9, 402.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 7.59 (dd, J = 8.8, 2.4 Hz, 1H), 7.32 (t, J = 1.6 Hz. 1H), 3.40 (s, 3H). 1195 395.36 1H-NMR (400 MHz, DMSO-d6): 9.91 (s, 1H), 9.55 (m, 1H), 874- 8.79 (m, 2H), 8.25 (s, 1H), 8.03 (d, J = 2.4 Hz. 1H), 7.92 (d, J = 9.2 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.60 (dd, J = 9.2, 2.4 Hz, 1H), 7.48-7.52 (m, 1H), 7.34 (t, DMSO 396.1 (M + 1) Method B (NH4HCO3) 95 Method D, G6 J = 74.0 Hz, 1H), 6.96- 6.98 (m, 1H), 3.40 (s, 3H). 1196 377.78 1H-NMR (400 MHz, DMSO-d6): 12.26 (s, 1H), 9.94 (s, 1H), 9.41- 9.42 (m, 1H), 8.75 (d, J = 8.0 Hz, 1H,), 8.33-8.34 (m, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.93 (m, 1H), DMSO 378.0, 380.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 7.75-7.77 (m, 2H), 7.05- 7.30 (m, 2H). 1197 343.34 1H-NMR (400 MHz, DMSO-d6): 13.86 (s, 1H), 12.39 (s, 1H), 9.62 (d, J = 0.8 Hz, 1H), 9.29 (d, J = 8.0 Hz, 1H), 8.87 (s, 1H), 8.80 (d, J = 2.4 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.12 (dd, J = 8.0, DMSO 344.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1.6 Hz, 1H), 7.97-8.05 (m, 3H), 7.75-7.79 (m, 2H), 7.24 (t, J = 7.6 Hz, 1H). 1198 372.38 1H-NMR (400 MHz, DMSO-d6): 13.05 (s, 1H), 9.99 (s, 1H), 9.39 (d, J = 5.2 Hz, 1H), 9.05 (d, J = 8.4 Hz, 1H), 8.47 (s, 1H), 8.36- 8.38 (m, 1H), 7.85-7.98 (m, 3H), 7.71 (t, J = 7.6 Hz, 1H), 7.46- DMSO 373.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.60 (m, 2H), 7.20 (t, J = 7.6 Hz, 1H), 3.95 (s, 3H). 1199 376.8 1H-NMR (400 MHz, DMSO-d6): 13.15 (s, 1H), 10.00 (s, 1H), 9.44 (d, J = 4.2 Hz, 1H), 8.95 (d, J = 8.4 Hz, 1H), 8.49 (s, 1H), 8.40- 8.42 (m, 1H), 8.15 (d, J = 9.2 Hz, 1H), 7.91- 7.97 (m, 3H), DMSO 377.0, 379.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.80 (t, J = 7.6 Hz, 1H), 7.73 (t, J = 7.6 Hz, 1H), 7.25 (t, J = 7.2 Hz, 1H). 1200 399.78 1H-NMR (400 MHz, DMSO-d6): 12.29 (s, 1H), 9.98 (s, 1H), 9.42 (d, J = 5.2 Hz, 1H), 8.66 (d, J = 9.2 Hz, 1H), 8.36-8.38 (m, 1H), 8.00 (d, J = 1.5 Hz, 1H), 7.89 (s, 1H), 7.79-7.81 (m, 2H), 7.49- 7.57 (m, 1H), 7.31 (t, J = 74.0 Hz, 1H), DMSO 400.0, 401.9 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.04 (dd, J = 8.0, 1.2 Hz, 1H). 1201 386.21 1H-NMR (400 MHz, DMSO-d6): 9.94 (s, 1H), 9.43 (d, J = 5.2 Hz, 1H), 8.72 (d, J = 8.8 Hz, 1H), 8.33 (dd, J = 5.6, 2.4 Hz, 1H), 8.21 (dd, J = 6.4, 1.6 Hz, 1H), 7.93-7.98 DMSO 386.0, 387.8 (M + 1) Method A (TFA) 95 Method D, G1 (m, 2H), 7.78 (dd, J = 8.8, 2.0 Hz, 1H), 7.54 (t, J = 9.2 Hz, 2H). 1202 0 369.76 1H-NMR (400 MHz, DMSO-d6): 10.28 (s, 1H), 9.95 (m, 1H), 9.44- 9.45 (m, 1H), 8.60 (d, J = 8.8 Hz, 1H), 8.32-8.34 (m, 1H), 8.02- 8.08 (m, 1H), 7.98 (d, J = 6.4 Hz, DMSO 369.9, 371.0 (M + 1) Method A (TFA) 95 Method D, G1 1H), 7.79 (dd, J = 9.2, 2.4 Hz, 1H), 7.70- 7.72 (m, 1H), 7.56 (q, J = 9.2 Hz, 1H). 1203 358.78 1H-NMR (400 MHz, DMSO-d6): 10.36 (s, 1H), 9.92 (s, 1H), 9.42 (d, J = 4.8 Hz, 1H), 8.59 (d, J = 8.4 Hz, 1H), 8.23-8.33 (m, 3H), 7.96 (d, J = 1.6 Hz, 1H), 7.65- 7.79 (m, DMSO 359.0, 361.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 3H). 1204 402.66 1H-NMR (400 MHz, DMSO-d6): 10.32 (s, 1H), 9.96 (s, 1H), 9.44 (d, J = 5.2 Hz, 1H), 8.60 (d, J = 8.4 Hz, 1H), 8.28-8.35 (m, 2H), 7.94- 7.99 (m, 2H), 7.79 (d, J = 8.8 Hz, DMSO 401.9, 403.9, 405.9 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1H), 7.73 (d, J = 8.8 Hz, 1H). 1205 402.66 1H-NMR (400 MHz, DMSO-d6): 9.90 (s, 1H), 9.42 (d, J = 4.8 Hz, 1H), 8.58 (d, J = 8.8 Hz, 1H), 8.27 (s, 1H), 8.07 (s, 2H), 7.92 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.36 (s, 1H). DMSO 401.9, 403.9, 405.9 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1206 351.76 1H-NMR (400 MHz, DMSO-d6): 10.59 (s, 1H), 9.43 (m, 1H), 9.07 (d, J = 5.2 Hz, 1H), 8.71 (d, J = 8.4 Hz, 1H), 8.50 (dd, J = 6.4, 2.0 Hz, 1H), 8.31 (dd, J = 5.2, 0.8 Hz, 1H), 8.00- 8.09 (m, 3H), DMSO 352.0, 354.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.80 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 9.2 Hz, 1H). 1207 342.35 1H-NMR (400 MHz, DMSO-d6): 13.31 (s, 1H), 9.38- 9.43 (m, 2H), 9.05 (d, J = 5.2 Hz, 1H), 8.52 (s, 1H), 8.47 (d, J = 5.2 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.95-8.04 (m, 4H), 7.82 (t, J = 7.2 DMSO 343.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H). 1208 365.34 1H-NMR (400 MHz, DMSO-d6): 10.13 (s, 1H), 9.37 (d, J = 1.2 Hz, 1H), 9.01 (d, J = 5.2 Hz, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.40 (dd, J = 5.2, 1.2 Hz, 1H), 8.28 (t, J = 1.2 Hz, 1H), 7.92-8.00 (m, 3H), 7.77- 7.79 (m, 1H), 7.47-7.52 (m, DMSO 366.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1H), 7.34 (t, J = 74.0 Hz, 1H), 6.97 (dd, J = 8.4, 2.4 Hz, 1H). 1209 HCl (batch 02) 351.6 1H-NMR (400 MHz, DMSO-d6): 10.82 (s, 1H), 9.59 (s, 2H), 9.36 (s, 1H), 8.74 (d, J = 8.4 Hz, 1H), 8.22 (dd, J = 6.8, 2.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 8.00 (t, J = 7.6 Hz, 1H), 7.90- 7.94 (m, DMSO 352.0, 354.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1H), 7.75 (t, J = 7.2 Hz, 1H), 7.56 (t, J = 9.2 Hz, 1H). 1210 342.35 1H-NMR (400 MHz, DMSO-d6): 13.17 (s, 1H), 9.65 (s, 2H), 9.36 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 8.51 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.92- 8.02 (m, 4H), 7.72-7.79 (m, 2H), 7.26 (t, J = 7.6 DMSO 343.1 (M + 1) Method B (NH4HCO3) 95 Method D, G4 Hz, 1H). 1211 365.34 1H-NMR (400 MHz, DMSO-d6): 10.15 (s, 1H), 9.62 (s, 2H), 9.32 (s, 1H), 8.63 (d, J = 8.0 Hz, 1H), 7.94- 7.97 (m, 3H), 7.81 (dd, J = 8.4, 1.2 Hz, 1H), 7.69- 7.74 (m, 1H), 7.50-7.55 (m, 1H), 7.31 (t, J = 74.0 Hz, 1H), 7.01 (dd, J = 8.4, DMSO 366.1 (M + 1) Method B (NH4HCO3) 95 Method D, G6 2.4 Hz, 1H). 1212 0 399.78 1H-NMR (400 MHz, DMSO-d6): 10.27 (s, 1H), 10.01- 10.02 (m, 1H), 9.44- 9.46 (m, 1H), 8.62 (d, J = 8.4 Hz, 1H), 8.40 (dd, J = 5.2, 2.0 Hz, 1H), 8.04 (t, J = 1.6 Hz, DMSO 400.0, 402.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 8.00 (d, J = 3.2 Hz, 2H), 7.94 (m, 1H), 7.76- 7.80 (m, 1H), 7.38 (t, J = 73.6 Hz, 1H), 7.16 (t, J = 2.0 Hz, 1H),. 1213 398.79 1H-NMR (400 MHz, DMSO-d6): 10.16 (s, 1H), 9.56 (m, 1H), 8.69- 8.72 (m, 2H), 8.59 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 1.6 Hz, 1H), 7.94-7.97 (m, 2H), 7.69- 7.73 (m, DMSO 399.0, 401.1 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 7.55- 7.58 (m, 1H), 7.36 (t, J = 73.6 Hz, 1H), 7.13 (t, J = 2.0 Hz, 1H). 1214 365.34 1H-NMR (400 MHz, DMSO-d6): 11.17 (s, 1H), 9.49 (s, 1H), 8.88- 8.92 (m, 3H), 8.16 (d, J = 8.0 Hz, 1H), 8.07 (t, J = 7.6 Hz, 2H), 7.84 (t, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.36 (t, J = 74.0 Hz, 1H), 7.10-7.12 (m, 1H). DMSO 366.1 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1215 368.22 1H-NMR (400 MHz, DMSO-d6): 10.23 (s, 1H), 10.00 (s, 1H), 9.44 (d, J = 5.2 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.38 (dd, J = 2.4, 5.2 Hz, 1H), 8.32 (d, J = 2.0 Hz, 1H), DMSO 367.8, 369.8, 371.8 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.96-8.00 (m, 3H), 7.73- 7.77 (m, 2H). 1216 351.76 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1H), 9.99 (s, 1H), 9.43 (d, J = 5.2 Hz, 1H), 8.58 (d, J = 8.4 Hz, 1H), 8.38 (dd, J = 5.2, 2.0 Hz, 1H), 8.22 (dd, J = 7.0, 2.6 Hz, 1H), DMSO 351.9, 353.8 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.89-7.93 (m, 3H), 7.68- 7.72 (m, 1H), 7.55 (t, J = 8.6 Hz, 1H). 1217 324.34 1H-NMR (400 MHz, DMSO-d6): 10.32 (s, 1H), 9.99 (dd, J = 2.0, 1.2 Hz, 1H), 9.44 (dd, J = 5.2, 0.8 Hz, 1H), 8.61 (d, J = 8.4 Hz, 1H), 8.38-8.40 (m, 2H), 8.28-8.31 (m, DMSO 325.0 (M + 1) Method B (NH4HCO3) 95 Method D, G1 1H), 7.99 (s, 1H), 7.97 (d, J = 3.6 Hz, 1H), 7.66- 7.80 (m, 3H). 1218 368.22 1H-NMR (400 MHz, DMSO-d6): 11.94 (s, 1H), 9.44 (d, J = 0.8 Hz, 1H), 9.06 (d, J = 8.0 Hz, 1H), 9.00 (d, J = 2.4 Hz, 1H), 8.97 (t, J = 1.8 Hz, 1H), 8.38 (d, J = 2.4 Hz, DMSO 367.9, 369.9, 371.8 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 8.38 (d, J = 2.4 Hz, 1H), 8.12 (t, J = 7.4 Hz, 1H), 8.00 (dd, J = 8.6, 2.2 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.82 (d, J = 8.8 Hz, 1H). 1219 351.76 1H-NMR (400 MHz, DMSO-d6): 11.62 (s, 1H), 9.40 (d, J = 0.8 Hz, 1H), 8.60- 8.83 (m, 3H), 8.32 (dd, J = 6.6, 2.2 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 8.09 (t, J = 7.4 Hz, DMSO 352.0, 354.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 1H), 7.95- 8.00 (m, 1H), 7.85 (t, J = 7.8 Hz, 1H), 7.61 (t, J = 9.2 Hz, 1H). 1220 335.31 1H-NMR (400 MHz, DMSO-d6): 11.05 (s, 1H), 9.48 (d, J = 0.8 Hz, 1H), 8.91- 8.93 (m, 2H), 8.81 (d, J = 8.4 Hz, 1H), 8.28-8.33 (m, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.06 DMSO 336.1 (M + 1) Method B (NH4HCO3) 95 Method D, G6 (t, J = 7.6 Hz, 1H), 7.77- 7.85 (m, 2H), 7.56-7.63 (m, 1H) 1221 324.34 1H-NMR (400 MHz, DMSO-d6): 12.09 (s, 1H), 9.40 (d, J = 1.6 Hz, 1H), 9.10 (d, J = 8.4 Hz, 1H), 9.00 (d, J = 2.0 Hz, 1H), 8.97 (t, J = 2.0 Hz, 1H), 8.49 (s, 1H), 8.26- DMSO 324.9 (M + 1) Method B (NH4HCO3) 95 Method D, G6 8.30 (m, 2H), 8.12-8.06 (m, 1H), 7.87- 7.91 (m, 1H), 7.76- 7.84 (m, 2H) 1222 0 368.22 1H-NMR (400 MHz, DMSO-d6): 10.21 (s, 1H), 9.59 (d, J = 1.2 Hz, 1H), 8.85 (t, J = 1.8 Hz, 1H), 3.78 (d, J = 2.0 Hz, 1H), 8.64 (d, J = 8.4 Hz, 1H), 3.42 (d, J = 1.6 Hz, 2H), 7.96- 8.02 (m, 2H), DMSO 368.0, 370.0, 372.0 (M + 1) Method B (NH4HCO3) 95 Method D, G6 7.74-7.78 (m, 1H), 7.35 (d, J = 1.6 Hz, 1H). 1223 368.22 1H-NMR (400 MHz, DMSO-d6): 10.26 (s, 1H), 10.00 (s, 1H), 9.45 (d, J = 5.2 Hz, 1H), 8.56 (d, J = 8.4 Hz, 1H), 8.38 (dd, J = 5.0, 1.8 Hz, 1H), 8.09 (s, 2H), 7.94 (s, 1H), 7.92 (d, J = 9.2 Hz, 1H), DMSO 368.1, 370.1 (M + 1) Method B (NH4HCO3) 95 Method D, G1 7.70-7.74 (m, 1H), 7.35 (s,1H). 1224 413.81 1H-NMR (400 MHz, DMSO-d6): 10.05 (s, 1H), 9.63 (s, 1H), 8.82 (s, 1H), 8.78 (s, 1H), 8.66 (s, 1H), 8.31 (s, 1H), 7.89- 7.91 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 73.6 Hz, 1H), 6.96 (d, J = 7.6 Hz, 1H), 2.74 (s, 3H). DMSO 414.0 416.0 (M + 1) Method B (NH4HCO3) 95 Method C, G3 1225 400.24 1H-NMR (400 MHz, DMSO-d6): 9.90 (s, 1H), 9.54 (s, 1H), 8.77- 8.80 (m, 2H), 8.60 (s, 1H), 8.50 (s, 1H), 7.99 (s, 1H), 7.76 (s, 1H), 7.44 (s, 1H), 2.67 (s, 3H). DMSO 400.0 401.9 (M + 1) Method B (NH4HCO3) 95 Method C, G3 1226 390.83 1H-NMR (400 MHz, DMSO-d6): 13.33 (s, 1H), 9.67 (s, 1H), 9.38 (d, J = 8.0 Hz, 1H), 8.88 (s, 1H), 8.79 (s, 1H), 8.52 (s, 1H), 8.08 (s, 1H), 8.04 (s, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.69 (d, DMSO 391.0 392.0 (M + 1) Method A (TFA) 95 Method C, G3 J = 7.2 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 2.75 (s, 3H). 1227 391.81 1H-NMR (400 MHz, DMSO-d6): 16.00 (s, 1H), 9.69 (s, 1H), 9.39 (d, J = 8.4 Hz, 1H), 8.90 (s, 1H), 8.79 (s, 1H), 8.29 (s, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.82 (s, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.06 (t, DMSO 392.0 393.1 (M + 1) Method A (TFA) 95 Method C, G3 J = 7.2 Hz, 1H), 2.73 (s, 3H). 1228 372.81 1H-NMR (400 MHz, DMSO-d6): 10.07 (s, 1H), 9.57 (s, 1H), 8.82 (s, 2H), 8.76 (s, 1H), 8.57 (s, 1H), 8.32 (d, J = 7.6 Hz, 1H), 7.81 (s, 1H), 7.57- 7.63 (m, 2H), 2.70 (s, 3H). DMSO 373.0 374.0 (M + 1) Method B (NH4HCO3) 95 Method C, G3 1229 416.69 1H-NMR (400 MHz, DMSO-d6): 10.09 (s, 1H), 9.63 (d, J = 1.2 Hz, 1H), 8.85 (dd, J = 2.4, 1.6 Hz, 1H), 8.78 (d, J = 2.4 Hz, 2H), 8.63 (d, J = 1.6 Hz, 1H), 8.45 (s, 2H), 7.34 (t, J = 2.0 Hz, 1H), DMSO 416.9 417.9 (M + 1) Method B (NH4HCO3) 95 Method C, G3 2.74 (s, 3H). 1230 HCl 351.76 1H-NMR (400 MHz, DMSO-d6): 10.42 (s, 1H), 9.60 (s, 2H), 9.34 (s, 1H), 8.64 (d, J = 8.4 Hz, 1H), 8.24 (dd, J = 8.4, 2.4 Hz, 1H), 7.98- 7.92 (m, 3H), 7.76- 7.71 (m, 1H), 7.56 (t, J = 8.8 Hz, 1H). DMSO 352.0, 354.0 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1231 HCl 383.33 1H-NMR (400 MHz, DMSO-d6): 10.58 (s, 1H), 9.61 (s, 2H), 9.34 (s, 1H), 8.71 (d, J = 8.4 Hz, 1H), 8.13 (s, 1H), 8.04- 7.93 (m, 3H), 7.78-7.73 (m, 1H), 7.62 (t, J = 8.4 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H). DMSO 384.1 (M + 1) Method B (NH4HCO3) 95 Method C, G1 1232 0 421.25 1H-NMR (400 MHz, DMSO-d6): 10.34 (s, 1H), 9.58 (s, 1H), 9.27-9.25 (m, 1H), 8.84- 8.77 (m, 2H), 9.52 (s, 1H), 8.35 (s, 1H), 8.07- 7.67 (m, 5H), 7.20 (t, J = 7.5 Hz, 1H). DMSO 421.0, 423.0 (M + 1) Method B (NH4HCO3) 95 Method C, G6 1233 1H-NMR (400 MHz, DMSO-d6): 13.15 (s, 1H), 10.00 (s, 1H), 9.44 (d, J = 5.2 Hz, 1H), 8.95 (d, J = 8.4 Hz, 1H), 8.48 (s, 1H), 8.42- 8.40 (m, 1H), 8.16 (d, J = 9.2 Hz, 1H), 7.97- 7.91 (m, 3H), 7.81-7.73 DMSO 377.0 (M + 1) Method B (NH4HCO3) 95 Method G (m, 2H), 7.25 (t, J = 2.4 Hz, 1H). 1234 1H-NMR (400 MHz, DMSO-d6): 9.95 (s, 1H), 9.54 (s, 1H), 8.82 (s, 1H), 8.74 (d, J = 2.0 Hz, 1H), 8.66 (d, J = 2.4 Hz, 1H), 8.07 (dd, J = 8.8, 2.4 Hz, 1H), 8.00 (d, J = 2.4 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.70 DMSO 397.9, 400.0 (M + 1) Method B (NH4HCO3) 95 Method G (d, J = 8.8 Hz, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 4.00 (s, 3H).

(374) ##STR02253## ##STR02254##

(375) Method C: 5-Nitro-2-(pyrazine-2-carboxamido)benzoic acid (li-a) To a solution of pyrazine-2-carboxylic acid (1.36 g, 10.9 mmol, 1 eq.) in SOCl.sub.2 (20 mL) was added DMF (2 drops). The mixture was stirred at 60 C. for 20 min. The volatiles were removed in vacuo to give crude pyrazine-2-carbonyl chloride, which was used in the next step directly. To a suspension of 2-amino-5-nitrobenzoic acid (2.00 g, 10.9 mmol, 1.0 eq.) in THF (50 mL) was added Et.sub.3N (1.09 g) and pyrazine-2-carbonyl chloride in anhydrous THF (50 mL) dropwise. The resulting mixture was stirred at room temperature for 18 h. After the reaction was completed, the volatiles were removed. The residue was suspended in H.sub.2O (10 mL) and the pH was adjusted to 5 by slow addition of 2N HCl in water. The resulting solid was collected and dried in vacuo to give 3.12 g of 5-nitro-2-(pyrazine-2-carboxamido)benzoic acid as a brown solid (99%). LCMS m/z=289.0 (M+1) (Method B) (retention time=1.24 min)

(376) Method A: N-(2-carbamoyl-4-nitrophenyl)pyrazine-2-carboxamide (iii-d) A mixture of 5-nitro-2-(pyrazine-2-carboxamido)benzoic acid (3.12 g, 10.8 mmol) in SOCl.sub.2 (20 mL) was stirred at 80 C. for 2 h. After cooling, the volatiles were removed and the residue was suspended in DCM (150 mL), and a solution of NH.sub.3.H.sub.2O (25% by weight in water, 40 mL) was added and stirred for 4 h. The resulting precipitate was collected and dried in vacuo to give 2.42 g of N-(2-carbamoyl-4-nitrophenyl)pyrazine-2-carboxamide as a dark red solid (74.6%). LCMS m/z=288.0 (M+1) (Method B) (retention time=1.11 min)

(377) Method E2: 6-nitro-2-(pyrazin-2-yl)quinazolin-4(1H)-one (iv-g) To a mixture of N-(2-carbamoyl-4-nitrophenyl)pyrazine-2-carboxamide (2.42 g, 8.43 mmol, 1.0 eq.) in EtOH (60 mL) was added NaOH (1.98 g, 49.5 mmol, 5.0 eq.). The resulting mixture was stirred at room temperature for 18 h. After the reaction was completed, the volatiles were removed in vacuo. The residue was partitioned between H.sub.2O (50 mL) and ethyl acetate (50 mL). The aqueous layer was neutralized to pH 5 by slow addition of aqueous citric acid. The resulting precipitate was collected and dried to give 2.00 g of 6-nitro-2-(pyrazin-2-yl)quinazolin-4(3H)-one as a yellow solid (88%). LCMS m/z=270.1 (M+1) (Method A) (retention time=1.36 min)

(378) Method F2: 4-Chloro-6-nitro-2-(pyrazin-2-yl)quinazoline (v-g) To a mixture of 6-nitro-2-(pyrazin-2-yl)quinazolin-4(3H)-one (1.00 g, 3.7 mmol) in POCl.sub.3 (10 mL) was added N,N-dimethylbenzenamine (0.1 mL). The resulting mixture was stirred at 120 C. for 2 h. After the reaction was completed, POCl.sub.3 was removed in vacuo, and the residue was co-evaporated with toluene twice to give a dark crude product, which was used for the next step without further purification.

(379) Method G6: N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl)quinazolin-4-amine (vi-s) A mixture of 4-chloro-6-nitro-2-(pyrazin-2-yl)quinazoline (1.00 g, crude, 3.7 mmol, 1.0 eq.), 3-(difluoromethoxy)benzenamine (600 mg, 3.7 mmol, 1.0 eq.) and Et.sub.3N (1.00 g, 10 mmol, 3.0 eq) in THF (80 mL) was stirred at 75 C. for 18 h. After cooling, the volatiles were removed in vacuo and the residue was washed with H.sub.2O (100 mL2). The solid was dried in vacuo to afford 1.40 g of N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl)quinazolin-4-amine as a black solid (90.2% of two steps). LCMS m/z=411.0 (M+1) (Method A) (retention time=1.61 min)

(380) Method B: N.sup.4-(3-(difluoromethoxy)phenyl)-2-(pyrazin-2-yl)quinazoline-4,6-diamine (lii-a) To a mixture of N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl) quinazolin-4-amine (1.40 g, 3.4 mmol, 1.0 eq.) in MeOHH.sub.2O (v/v, 3:1, 110 mL) was added NH.sub.4Cl (1.80 g, 34 mmol, 10.0 eq.) and Fe (1.91 g, 34 mmol, 10.0 eq.). The resulting mixture was stirred at 60 C. for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and the iron was filtered off. The filtrate was concentrated to 15 mL and a precipitate formed and was collected and dried in vacuo to give 1.13 g of N.sup.4-(3-(difluoromethoxy)phenyl)-2-(pyrazin-2-yl)quinazoline-4,6-diamine as a pale yellow solid (87.5%). LCMS m/z=381.1 (M+1) (Method B) (retention time=1.60 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.69 (s, 1H), 9.52 (d, J=1.2 Hz, 1H), 8.75 (d, J=2.4 Hz, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.30 (s, 1H), 7.87 (dd, J=8.4, 0.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.33-7.32 (m, 1H), 7.31 (t, J=74 Hz, 1H), 5.85 (s, 2H).

(381) Method C: N-(4-(3-(difluoromethoxy)phenylamino)-2-(pyrazin-2-yl)quinazolin-6-yl)-6-methoxynicotinamide (liii-a) To a solution of 6-methoxynicotinic acid (100 mg, 0.65 mmol) in SOCl.sub.2 (2 mL) was added DMF (1 drop). The mixture was stirred at 60 C. for 20 min. The volatiles were removed in vacuo to give 6-methoxynicotinoyl chloride, which was used for the next step directly. To a suspension of N.sup.4-(3-(difluoromethoxy)phenyl)-2-(pyrazin-2-yl)quinazoline-4,6-diamine (130 mg, 0.34 mmol, 0.5 eq.) in THF (5 mL) and Et.sub.3N (101 mg, 1 mmol, 3.0 eq) was added 6-methoxynicotinoyl chloride in anhydrous THF (5 mL) dropwise. The resulting mixture was stirred at room temperature for 18 h. The volatiles were removed in vacuo. The residue was washed with MeOH and re-crystallized from THF/MeOH twice, and purified by reverse phase chromatography PREP-HPLC (A=NH.sub.4HCO.sub.3H.sub.2O, 10 mmol/L, B=MeOH) to afford 33 mg of N-(4-(3-(difluoromethoxy)phenylamino)-2-(pyrazin-2-yl)quinazolin-6-yl)-6-methoxynicotinamide as a pale yellow solid (18.8%). LCMS m/z=516.1 (M+1), 258.6 (M/2+1) (Method A) (retention time=1.57 min). .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.71 (s, 1H), 10.18 (s, 1H), 9.57 (d, J=1.6 Hz, 1H), 9.01 (d, J=1.6 Hz, 1H), 8.91 (d, J=2.4 Hz, 1H), 8.81 (t, J=2.0 Hz, 1H), 8.76 (d, J=2.4 Hz, 1H), 8.34 (dd, J=8.8, 2.8 Hz, 1H), 8.23 (s, 1H), 8.08 (dd, J=8.8, 2.0 Hz, 1H), 8.00 (d, J=9.2 Hz, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.46-7.50 (m, 1H), 7.32 (t, J=74.4 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 6.95 (dd, J=8.0, 2.0 Hz, 1H), 3.97 (s, 3H).

(382) The compounds in the following table were prepared in a manner analogous to that described in Scheme 67 (prepared according to method procedure A-G as designated).

(383) TABLE-US-00028 TABLE 22 Pu- Method Molec- .sup.1H- rity for Num- Salt ular NMR LCMS per- Cou- ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol cent pling 1242 422.39 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.10- 10.45 (m, 2H), 9.68 (s, 1H), 8.45-9.10 (m, 2H), 7.68-8.37 (m, 4H), 7.36-7.52 (m, 2H), 7.02-7.08 (m, 1H), 2.21 (s, 3H). DMSO 423.0 (M + 1) Method A (TFA) 95 Method C, G4, C 1243 515.47 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.71 (s, 1H), 10.18 (s, 1H), 9.57 (d, J = 1.6 Hz, 1H), 9.01 (d, J = 1.6 Hz, 1H), 8.91 (d, J = 2.4 Hz, 1H), 8.81 (t, J = 2.0 Hz, 1H), 8.76 (d, J = 2.4 Hz, 1H), 8.34 (dd, J = 8.8, 2.8 Hz, 1H), 8.23 (s, 1H), 8.08 (dd, J = 8.8, 2.0 Hz, 1H), 8.00 (d, J = 9.2 Hz, 1H), 7.90 (d, J = 9.2 Hz, DMSO 516.2 (M + 1) Method B (NH4HCO3) 95 Method C, G4, C 1 H), 7.46-7.50 (m, 1H), 7.32 (t, J = 74.4 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 6.95 (dd, J = 8.0, 2.0 Hz, 1H), 3.97 (s, 3H). 1244 514.48 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.56 (s, 1H), 10.16 (s, 1H), 9.57 (s, 1H), 9.00 (d, J = 1.6 Hz, 1H), 8.81 (d, J = 2.4 Hz, 1H), 8.76 (d, J = 2.8 Hz, 1H), 8.23 (s, 1H), 8.07-8.12 (m, 3H), 7.99 (d, J = 9.2 Hz, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.46-7.50 (m, 1H), 7.32 (t, J = 72.8 Hz, 1H), 7.11- 7.13 (m, 2H), 6.95 DMSO 515.2 (M + 1) Method B (NH4HCO3) 95 Method C, G4, C (dd, J = 8.4, 2.4 Hz, 1H), 3.87 (s, 3H). 1245 520.53 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.30 (s, 1H), 10.16 (s, 1H), 9.54 (s, 1H), 8.89 (s, 1H), 8.79 (t, J = 2.4 Hz, 1H), 8.74 (d, J = 2.8 Hz, 1H), 8.20 (s, 1H), 7.93 (s, 2H), 7.87 (d, J = 8.4 Hz, 1H), 7.48 (dd, J = 10.0, 2.0 Hz, 1H), 7.31 (t, J = 74.0 Hz, 1H), 6.94 (dd, J = 8.4, 2.0 Hz, 1H), 3.26 (s, 3H), 3.18-3.22 (m, DMSO 521.2 (M + 1) Method B (NH4HCO3) 95 Method C, G4, C 1H), 1.91-1.96 (m, 2H), 1.66-1.78 (m, 2H), 1.53-1.63 (m, 2H), 1.38-1.49 (m, 2H). 1246 492.48 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.35 (s, 1H), 10.15 (s, 1H), 9.54 (s, 1H), 8.90 (d, J = 2.0 Hz, 1H), 8.80 (dd, J = 2.4, 1.2 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H), 8.19 (s, 1H), 7.95 (d, J = 8.8 Hz, 1H), 7.86-7.91 (m, 2H), 7.48 (dd, J = 10.8, 2.8 Hz, 1H), 7.31 (t, J = 74.4 Hz, 1H), 6.94 (dd, J = 7.6, 2.0 Hz, 1H), DMSO 493.2 (M + 1) Method B (NH4HCO3) 95 Method C, G4, C 3.94-3.97 (m, 2H), 3.40-3.43 (m, 2H), 2.70-2.73 (m, 1H), 1.65-1.78 (m, 4H).

(384) ##STR02260##

(385) Method BF: 6-(3-methoxyphenyl)-N-methyl-2-(pyrimidin-5-yl)quinazolin-4-amine (compound 1247) In a 10 mL microwave vial was added 2-chloro-6-(3-methoxyphenyl)-N-methylquinazolin-4-amine (0.080 g, 0.267 mmol), pyrimidine-5-boronic acid (0.099 g, 0.801 mmol), dichlorobis(triphenylphosphine)palladium (II) (Pd(PPh.sub.3).sub.2Cl.sub.2) (9.37 mg, 0.013 mmol), and potassium carbonate (0.111 g, 0.801 mmol) in DME (3 mL), EtOH (1.286 mL), and water (0.857 mL) to give a yellow suspension. The vial was irradiated at 120 C. for 15 min under argon. Water (10 mL) was added to the mixture and extracted with ethyl acetate (210 mL). The organic layers were combined and washed with brine (120 mL) and then dried over MgSO.sub.4, filtered and concentrated. The residue was washed with MeOHCH.sub.2Cl.sub.2 and dried to give 35 mg of 6-(3-methoxyphenyl)-N-methyl-2-(pyrimidin-5-yl)quinazolin-4-amine as a white solid (38%). LCMS m/z=344 (M+1) (Method D) (retention time=1.78 min). .sup.1H NMR (300 MHz, DMSO) 9.79-9.59 (m, 2H), 9.30 (s, 1H), 8.72 (d, J=4.6 Hz, 1H), 8.59 (s, 1H), 8.16 (d, J=8.6 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.53-7.28 (m, 3H), 7.00 (d, J=6.8 Hz, 1H), 3.86 (s, 3H), 3.18 (d, J=3.9 Hz, 3H).

(386) ##STR02261##

(387) In a 100 mL round-bottomed flask was added 6-iodo-2-(pyrazin-2-yl)quinazolin-4(3H)-one (0.500 g, 1.428 mmol), BOP (0.821 g, 1.857 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.426 ml, 2.86 mmol) in DMF (10 mL) to give a colorless solution. Methylamine, 2M in THF (2.142 ml, 4.28 mmol) was added and stirred at room temperature overnight. The reaction mixture was diluted with water (50 mL) and then a precipitate formed. The resulting solid was collected by filtration and dried to give 0.515 g of 6-iodo-N-methyl-2-(pyrazin-2-yl)quinazolin-4-amine as a pale brown solid in a 99% yield. LCMS m/z=364 (M+1) (Method D) (retention time=1.25 min). .sup.1H NMR (300 MHz, DMSO) 9.60 (s, 1H), 8.89-8.65 (m, 3H), 8.65-8.48 (m, 1H), 8.06 (d, J=8.7 Hz, 1H), 7.59 (d, J=8.7 Hz, 1H), 3.11 (d, J=4.2 Hz, 3H).

(388) In a 50 mL round-bottomed flask was added 6-iodo-N-methyl-2-(pyrazin-2-yl)quinazolin-4-amine (0.100 g, 0.275 mmol), 3-methoxyphenylboronic acid (0.063 g, 0.413 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine) dichloropalladium(II) (0.016 g, 0.022 mmol), and potassium phosphate tribasic monohydrate (0.190 g, 0.826 mmol) in dioxane (5 mL) and water (0.5 mL) to give a brown suspension. The reaction mixture was heated at 80 C. overnight under argon. After cooling to room temperature, the reaction mixture was diluted with water (10 mL) and then a precipitate formed. The resulting solid was collected by filtration and washed with ethyl acetate and dried to give 25 mg of 6-(3-methoxyphenyl)-N-methyl-2-(pyrazin-2-yl)quinazolin-4-amine as a pale yellow solid in a 26% yield. LCMS m/z=344 (M+1) (Method D) (retention time=1.43 min). .sup.1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.85-8.78 (m, 1H), 8.77-8.71 (m, 1H), 8.70-8.63 (m, 1H), 8.63-8.55 (m, 1H), 8.18 (d, J=8.8 Hz, 1H), 7.89 (d, J=8.9 Hz, 1H), 7.53-7.31 (m, 3H), 7.09-6.92 (m, 1H), 3.86 (s, 3H), 3.17 (d, J=3.6 Hz, 3H).

(389) The compounds in the following table were prepared in a manner analogous to that described in Scheme 69 (prepared according to method described for 6-(3-methoxyphenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine).

(390) TABLE-US-00029 TABLE 23 Molecular .sup.1H-NMR Number PRODUCT Salt type Mass .sup.1H-NMR Solvent LCMS LCMS Protocol Purity percent Method for Coupling 1235 343.38 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.85-8.78 (m, 1 H), 8.77-8.71 (m, 1H), 8.70-8.63 (m, 1 H), 8.63- 8.55 (m, 1H), 8.18 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 8.9 Hz, 1H), 7.53-7.31 (m, 3H), 7.09-6.92 (m, 1H), 3.86 (s, 3H), 3.17 (d, J = 3.6 Hz, 3H). DMSO 344 (M + 1) Method D 100 Method AP/AQ 1236 338.37 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.87-8.61 (m, 4H), 8.24 (d, J = 8.8 Hz, 1H), 8.15-7.98 (m, 4H), 7.92 (d, J = 8.7 Hz, 1H), 3.17 (d, J = 4.0 Hz, 3H). DMSO 339 (M + 1) Method D 100 Method C, G1 1237 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.17 (s, 1H), 9.54 (6, J = 5.2 Hz, 1H), 9.36 (s, 1H), 8.63 (s, 2H), 8.13- 8.06 (m, 2H), 7.58-7.51 (m, 2H), 7.43-7.38 (m, 1H), 3.23 (d, J = 4.0 Hz, 3H). DMSO 350.1, 351.1, (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 1238 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.14 (s, 1H), 9.50 (d, J = 5.2 Hz, 1H), 9.24 (s, 1H), 8.60 (dd, J = 5.4, 1.8 Hz, 1H), 8.55 (s, 1H), 8.04 (q, J = 8.8 Hz, 2H), 7.76 (dd, J = 15.4, 9.0 Hz, 1 H), 7.51-7.45 (m, 1H), 7.32 (dt, J = 8.4, 2.0 Hz, 1H), 3.23 (d, J = 4.4 Hz, 3H). DMSO 350.0, 351.0, (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 1239 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.73(s, 1H), 9.32 (s, 1H), 8.74 (d, J = 4.4Hz, 1H), 8.51 (s, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.54-7.49 (m, 2H), 7.42-7.37 (m, 1H), 4.12 (q, J = 5.2 Hz, 1H), 3.17 (t, J = 4.5 Hz, 3H). DMSO 350.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 1240 2HCl .sup.1H-NMR (400 MHz, CD3OD): 9.77 (s, 1H), 8.85 (d, J = 11.4 Hz, 2H), 8.42 (s, 1H), 8.19-8.03 (m, 2H), 7.60 (dd, J = 15.6, 7.8 Hz, 1H), 7.10 (t, J = 8.4 Hz, 2H), 3.38 (s, 3H). CD3OD 350.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1 1241 2HCl .sup.1H-NMR (400 MHz, DMSO): 10.84 (d, J = 1.8 Hz, 1 H), 9.87 (s, 1H), 9.06 (d, J = 13.6 Hz, 2H), 8.90 (s, 1H), 8.32 (t, J = 9.8 Hz, 2H), 7.67-7.35 (m, 3H), 3.39 (s, 3H). DMSO 349.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 95 Method C, G1

(391) ##STR02269##

(392) ##STR02270##

(393) Method B2: 2-Amino-3-methylbenzoic acid (lv-a) Pd/C catalyst (150 mg) was suspended in a solution of 3-methyl-2-nitrobenzoic acid (1.50 g, 8.28 mmol 1.0 eq) in THF (60 mL), the mixture was stirred under H.sub.2 atmosphere at room temperature overnight. The Pd/C was removed by filtration over Celite and the THF was removed in vacuo to give 1.23 g of lv-a as a white solid (yield 98%). LCMS m/z=152.1 (M+1) (Method B) (retention time=0.73 min). The product was used further without purification.

(394) Method AZ: 2-Amino-5-bromo-3-methylbenzoic acid (lvi-a) To a solution of 2-amino-3-methylbenzoic acid (1.23 g, 8.14 mmol, 1.0 eq) in 15 mL of DMSO was added 40% HBr (6.00 mL, 44.7 mmol, 5 eq). The resulting mixture was stirred at room temperature overnight. A white precipitate formed during the course of the reaction. The reaction mixture was quenched with saturated aqueous NaHCO.sub.3 resulting in a white solid that was filtered and dried in vacuo to yield 950 mg in 51% yield of lvi-a as white solid. LCMS m/z=229.9 (M+1) (Method B) (retention time=1.20 min).

(395) Method C: 2-Amino-5-bromo-3-methylbenzamide (ii-c) A mixture of 2-amino-5-bromo-3-methylbenzoic acid (950 mg, 4.15 mmol) and SOCl.sub.2 (20 mL) was stirred at 80 C. for 2 h. After the reaction was completed, the mixture was cooled to room temperature. The SOCl.sub.2 was removed in vacuo and the residue was dissolved in anhydrous THF (10 mL). The THF solution was then added dropwise to a 28% by weight solution of NH.sub.3H.sub.2O (10 mL). After 1 h, the resulting precipitate was collected and dried in vacuo to give 820 mg of ii-c as a yellow solid (87%). LCMS m/z=288.9, 230.9 (M+1) (Method B) (retention time=1.49 min).

(396) ##STR02271##
Method G for Coupling Conditions G1: i-PrOH/85-100 C. G2: THF/heat G3: i-AmOH/100-130 C. G4: MeOH/microwave/150 C. G5: i-AmOH/microwave/150 C. G6: THF/Et.sub.3N/reflux G7: THFH.sub.2O/NaOAc/rt-60 C. G8: NaH/THF G9: n-BuLi/THF G10: LHMDS/THF G11: LDA/THF G12: K.sub.2CO.sub.3/DMF/60 C. G13: Cs.sub.2CO.sub.3/DMA/80 C. G14: NaOtBu/DMF/Microwave/100 C.
Method AQ for Coupling Conditions AQ1: Pd(PPh.sub.3).sub.2Cl.sub.2/K.sub.2CO.sub.3/Dioxane-H.sub.2O AQ2: Pd.sub.2(APhos).sub.2Cl.sub.2/K.sub.3PO.sub.4/Dioxane-H.sub.2O AQ3: Pd(PPh.sub.3).sub.4/K.sub.3PO.sub.4/Dioxane-H.sub.2O AQ4: Pd(dppf)Cl.sub.2CH.sub.2Cl.sub.2/K.sub.3PO.sub.4/Dioxane-H.sub.2O AQ5: Pd(OAc).sub.2Cl.sub.2/S-Phos/K.sub.3PO.sub.4/Dioxane-H.sub.2O AQ6: Pd(dppf)Cl.sub.2CH.sub.2Cl.sub.2/Na.sub.2CO.sub.3/Dioxane-H.sub.2O

(397) ##STR02272##

(398) Method C: N-(4-bromo-2-carbamoyl-6-methylphenyl)nicotinamide (iii-e) To a solution of 2-amino-5-bromo-3-methylbenzamide (820 mg, 3.55 mmol, 1.0 eq.) in THF (15 mL) and Et.sub.3N (0.7 mL) was added nicotinoyl chloride (551 mg, 3.91 mmol, 1.1 eq.) in anhydrous THF (15 mL) dropwise. The resulting mixture was stirred at room temperature overnight. After the reaction was completed, the resultant precipitate was filtered and dried in vacuo to give 1.74 g of crude iii-e as a yellow solid. LCMS m/z=333.8, 335.8 (M+1) (Method B) (retention time=1.42 min)

(399) Method E: 6-Bromo-8-methyl-2-(pyridin-3-yl)quinazolin-4-ol (iv-h) A mixture of N-(4-bromo-2-carbamoyl-6-methylphenyl)nicotinamide (1.74 g salt, 5.22 mmol, 1.0 eq) in EtOH (50 mL) was treated with NaOH (1.04 g, 26.1 mmol, 5.0 eq). The resulting mixture was stirred at room temperature overnight. After the reaction was completed, the volatiles were removed in vacuo. Water (30 mL) was added to the residue and the mixture was adjusted to pH 1 or 2 by slow addition of aqueous HCl. The resultant precipitate was collected and dried to give 870 mg of iv-h as a yellow solid (77% yield after two steps). LCMS m/z=315.7, 317.7 (M+1) (Method B) (retention time=1.74 min).

(400) Method F5: 6-Bromo-4-chloro-8-methyl-2-(pyridin-3-yl)quinazoline (v-h) 6-Bromo-8-methyl-2-(pyridin-3-yl)quinazolin-4-ol (870 mg, 2.76 mmol) was added to POCl.sub.3 (10 mL). The resulting mixture was stirred at 120 C. overnight. After the reaction was completed, the mixture was carefully poured into ice-water. The pH was adjusted to 7 by slow addition of NH.sub.4OH at 0 C. The resultant solid was collected to give 1.00 g of v-h as a beige solid (quantitative yield). LCMS m/z=333.9, 335.9 (M+1) (Method B) (retention time=2.23 min)

(401) Method G6: 6-Bromo-N, 8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (vi-t) A mixture of 6-bromo-4-chloro-8-methyl-2-(pyridin-3-yl)quinazoline (200 mg, 0.60 mmol, 1.0 eq.), methylamine (81 mg, 1.20 mmol, 2.0 eq.) and Et.sub.3N (0.2 mL) in i-PrOH (10 mL) was stirred at 85 C. overnight. The resultant yellow precipitate was collected to afford 125 mg of vi-t as a beige solid (63.4%). LCMS m/z=328.8, 330.8 (M+1) (Method B) (retention time=1.95 min)

(402) Method G2: 7-bromo-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (vi-u) To a suspension of 7-bromo-4-chloro-2-(pyridin-3-yl)quinazoline (5.0 g, 0.0156 mol) in THF (100 mL) was added dropwise a methylamine solution (40 wt. % in H.sub.2O) (24 ml, 0.272 mmol) with cooling. The suspension was stirred at 60 C. for 3 h, cooled, filtered, and dried to give the title compound. (3.62 g, 73.5%)

(403) Method AQ1: 6-(3-Methoxyphenyl)-N, 8-dimethyl-2-(pyridin-3-yl) quinazolin-4-amine (lviii-a) (This method is representative of method AQ2 and can be implemented in a similar way except for substitution of the appropriate catalyst and base) To a mixture of 6-bromo-N, 8-dimethyl-2-(pyridin-3-yl) quinazolin-4-amine (130 mg, 0.396 mmol, 1.0 eq), 3-methoxyphenylboronic acid (60 mg, 0.396 mmol, 1.0 eq), K.sub.2CO.sub.3 (295 mg, 2.14 mmol, 5.4 eq.) in dioxane (8 mL) and H.sub.2O (4 mL) was added Pd(PPh.sub.3).sub.2Cl.sub.2 (15 mg, 0.021 mmol, 0.054 eq) under N.sub.2 atmosphere. The resulting mixture was stirred at 120 C. under N.sub.2 atmosphere overnight. After the reaction was completed, the mixture was filtered, and the filtrate was concentrated in vacuo. The residue was purified by reverse phase HPLC column to afford 11 mg of lviii-a as a white solid (yield 7.8%). LCMS m/z=357.2, (M+1) (Method B (retention time=2.11 min) 1H NMR (400 MHz, DMSO-d.sub.6): 9.68 (d, J=1.2 Hz, 1H), 8.75 (d, J=8.0 Hz, 1H), 8.62 (d, J=4.6 Hz, 1H), 8.49 (d, J=4.4 Hz, 1H), 8.35 (s, 1H), 7.97 (s, 1H), 7.49 (dd, J=7.8, 4.8 Hz, 1H), 7.44-7.29 (m, 3H), 6.93 (dd, J=6.8, 2.4 Hz, 1H), 3.81 (s, 3H), 3.12 (d, J=4.4 Hz, 3H), 2.68 (s, 3H).

(404) Method AQ3: 6-(4-Fluorophenyl)-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (lviii-b) 6-Bromo-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (340 mg, 1.03 mmol), 3-fluorobenzeneboronic acid (217 mg, 1.55 mmol), K.sub.3PO.sub.4 (658 mg, 3.10 mmol) and Pd(PPh.sub.3).sub.4 (59.7 mg, 0.052 mmol) were dissolved in the mixed solvent of 1,4-dioxane (10 mL) and water (1 mL). The resulting mixture was stirred at 90 C. for 6 hours under a nitrogen atmosphere. After the reaction was completed, water was added to the mixture and stirred for 30 minutes. The resulting precipitate was collected by filtration and purified by column chromatography on NH-silica gel (eluted with THF) to give a yellow powder. The solid was suspended in ethanol and 5N HCl (1 mL) was added to the mixture. The mixture was sonicated for 10 min and the resulting precipitate was collected by filtration and dried to give 304 mg of 6-(3-fluorophenyl)-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as a yellow powder in 71% yield.

(405) Method AQ4: 6-(2,4-Difluorophenyl)-N,5-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine(lviii-c) 6-Bromo-N,5-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (350 mg, 1.06 mmo 1), 2,4-difluorophenylboronic acid (252 mg, 1.595 mmol), K.sub.3PO.sub.4 (677 mg, 3.19 mmol) and Pd(dppf)Cl.sub.2-CH.sub.2Cl.sub.2 (87 mg, 0.106 mmol) were dissolved in the mixed solvent of 1,4-dioxane (10 mL) and water (1 mL). The resulting mixture was stirred at 90 C. for 2.5 hours under N.sub.2. After the reaction was completed, water was added to the mixture and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over Na.sub.2SO.sub.4. After filtration and evaporation, the crude product was purified by column chromatography on NH-silica gel (eluted with isocratic 33% ethyl acetate/67% hexane) to give a white powder. The solid was suspended in ethanol and 5N HCl (1.0 mL) was added to the mixture. The mixture was sonicated for 10 min and the resultant precipitate was collected by filtration and dried to give 139 mg of 6-(2,4-difluorophenyl)-N,5-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as a pale yellow powder in a 30% yield.

(406) Method AQ5: 7-(3-fluorophenyl)-N,6-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (lviii-d) A mixture of 7-chloro-N,6-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (400 mg, 1.40 mmol), 3-fluorophenylboronic acid (294 g, 2.10 mmol), Pd(OAc).sub.2 (15.8 mg, 0.070 mmol), 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl (86.7 mg, 0.211 mmol), K.sub.3PO.sub.4 (900 mg, 4.23 mmol) in dioxane (10 mL) and water (2 mL) was stirred under reflux for 2.5 h. Ethyl acetate (20 mL) was added to the cooled mixture and a precipiate formed and was filtered. The solid was recrystallized from DMF and water to give the title compound as free form. The solid was suspended in ethyl acetate (10 mL) and 4N HCl in ethyl acetate (1.0 mL) was added. The resulting solid was subjected to sonication for 20 min, filtered and dried to give the title compound as the bis-HCl salt (0.10 g, 18.7%).

(407) Method AQ6:7-(3,4-difluorophenyl)-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (lviii-e) To a suspension of 3,4-difluorophenylboronic acid (389 mg, 2.46 mmol) and 7-bromo-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (395.4 mg, 1.201 mmol) in dioxane/H.sub.2O (2/1) (30 mL) under a nitrogen atmosphere was added Na.sub.2CO.sub.3 (633.2 mg, 5.97 mmol) and (1,1-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (98 mg, 0.120 mmol) at room temperature. The mixture was stirred at 100 C. for 1.5 h. Water was added to the reaction mixture and then a precipitate formed. The solid was filtered and washed with water and dried. The dried solid was then heated in a methanol/dioxane mixture to give a clear solution and filtered through Celite. The filtrate was concentrated to give the crude product. The crude product was sonicated in methanol/CH.sub.2Cl.sub.2 for ca.15 min and filtered to give 305.2 mg of a pale brown solid as the parent compound. To a suspension of parent compound in methanol was added 4N HCl in ethyl acetate (ca. 4 mL) to give a clear solution. The solution was concentrated and recystallized from ethanol to give the HCl salt. The salt was collected and dried in an oven at 60 C. to give 231.3 mg in a 44% yield as pale yellow solid. .sup.1H NMR (DMSO-d.sub.6) 9.73 (s, 1H), 9.37 (brd, J=8.08 Hz, 1H), 8.97 (brd, J=5.24 Hz, 1H), 8.77 (brs, 1H), 8.20 (d, J=8.48 Hz, 1H), 8.10-8.07 (brm, 1H), 7.63-7.55 (brm, 2H), 7.47 (d, J=8.48 Hz, 1H), 7.32 (brm, 1H), 3.20 (d, J=4.20 Hz, 3H), 2.65 (s, 3H). The 1H of 2HCl was not observed.

(408) ##STR02273##

(409) ##STR02274##

(410) Method AP: 6-bromo-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine (vi-u) To a solution of 6-bromo-2-(pyridin-3-yl)quinazolin-4(3H)-one (5.00 g, 16.6 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (9.52 g, 21.5 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (4.94 ml, 33.1 mmol) in DMF (50 mL) was added methylamine, 2M in THF (16.6 mL, 33.1 mmol). The mixture was stirred overnight at room temperature. Water (100 mL) was added to the mixture and stirred. The resultant precipitate was collected by filtration and dried to give 5.15 g of 6-bromo-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine as pale yellow solid (99%). LCMS m/z=315 (M+1) (Method D) (retention time=1.34 min). .sup.1H NMR (300 MHz, DMSO) 9.60 (dd, J=2.1, 0.8 Hz, 1H), 8.79-8.70 (m, 1H), 8.67 (dd, J=4.8, 1.7 Hz, 1H), 8.57 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 7.90 (dd, J=8.9, 2.1 Hz, 1H), 7.71 (d, J=8.9 Hz, 1H), 7.52 (ddd, J=7.9, 4.8, 0.9 Hz, 1H), 3.13 (d, J=4.5 Hz, 3H).

(411) Method AQ2: 6-(6-methoxypyridin-3-yl)-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine (lviii-f) To a 1 dram reaction vial was added 6-bromo-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine (35 mg, 0.111 mmol), 6-methoxypyridin-3-ylboronic acid (20.4 mg, 0.133 mmol), Pd(APhos).sub.2Cl.sub.2 (3.2 mg, 0.004 mmol) and potassium phosphate monohydrate (77 mg, 0.33 mmol) in a mixture of dioxane-water (9:1, 2 mL). The reaction mixture was heated to 90 C. for 14 h after which it was cooled to room temperature and diluted with water (5 mL). The resultant precipitate was collected by filtration and recrystallized from methanol to give 6-(6-methoxypyridin-3-yl)-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine as a pale yellow solid (19.1 mg, 51%). LCMS m/z=344 (M+1) (Method C) (retention time=2.01 min). .sup.1H NMR (300 MHz, DMSO) 9.64 (d, J=1.3 Hz, 1H), 8.84-8.74 (m, 1H), 8.68 (dd, J=6.2, 1.7 Hz, 2H), 8.57 (d, J=1.6 Hz, 2H), 8.16 (ddd, J=14.4, 8.7, 2.2 Hz, 2H), 7.85 (d, J=8.7 Hz, 1H), 7.54 (dd, J=7.9, 4.8 Hz, 1H), 7.00 (d, J=8.7 Hz, 1H), 3.93 (s, 3H), 3.18 (d, J=4.3 Hz, 3H).

(412) The compounds in the following table were prepared in a manner analogous to that described in Scheme 72 or 74, replacing methylamine with the appropriate amine and 6-methoxypyridin-3-ylboronic acid with the appropriate boronic acid.

(413) TABLE-US-00030 TABLE 24 Reten- Method Num- Molecular .sup.1H-NMR tion LCMS Purity for ber Product Salt Mass .sup.1H-NMR Solvent LCMS Time Protocol percent Coupling 1248 HCl 342.4 .sup.1H-NMR (400 MHz, DMSO-d6): 9.66 (s, 1H), 8.50-8.89 (m, 3H), 8.16 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.30-7.61 (m, 4H), 7.01 (d, J = 6.4 Hz, 1 H), 3.88 (s, 3H), 3.32 (brs, 1H), 3.19 (s, 3H). DMSO 343.1 (M + H) Method B (NH4HCO3) 95 Method AQ1 1249 372.4 1H-NMR (400 MHz, DMSO-d6): 9.63 (s, 1H), 8.77 (d, J = 7.9 Hz, 1H), 8.67 (d, J = 3.7 Hz, 1H), 8.50 (s, 1H), 8.11 (s, 1H), 7.56-7.53 (m, 2H), 7.48-7.40 (m, 3H), 7.01 (d, J = 3.9 Hz, 1H), 4.07 (s, 3H), 3.88 (s, 3H), 3.17 (d, J = 4.0 Hz, 3H). DMSO 372.9 (M + H) Method B (NH4HCO3) 95 Method AQ1 1250 356.4 1H-NMR (400 MHz, DMSO-d6): 9.63 (s, 1H), 8.79-8.74 (m, 1H), 8.69 (d, J = 4.0 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.57-7.51 (m, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.37-7.30 (m, 1H), 7.02-6.92 (m, 3H), 3.82 (s, 3H), 3.18 (d, J = 4.0 Hz, 3H), 2.69 (s, 3H). DMSO 357.1 (M + H) Method B (NH4HCO3) 95 Method AQ1 1251 356.4 1H-NMR (400 MHz, DMSO-d6): 9.68 (d, J = 1.2 Hz, 1H), 8.75 (d, J = 8.0 Hz, 1 H), 8.62 (d, J = 4.6 Hz, 1H), 8.49 (d, J = 4.4 Hz, 1H), 8.35 (s, 1H), 7.97 (s, 1H), 7.49 (dd, J = 7.8, 4.8 Hz, 1H), 7.44-7.29 (m, 3H), 6.93 (dd, J = 6.8, 2.4 Hz, 1H), 3.81 (s, 3H), 3.12 (d, J = 4.4 Hz, 3H), 2.68 (s, 3H). DMSO 357.2 (M + H) Method B (NH4HCO3) 95 Method AQ1 1252 329.3 1H NMR (300 MHz, DMSO) 9.31 (s, 1H), 8.76 (d, J = 4.7 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.37 (d, J = 2.0 Hz, 1H), 8.18 (dd, J = 8.5, 2.2 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 7.9, 4.8 Hz, 1H), 7.49-7.23 (m, 3H), 6.99 (d, J = 6.7 Hz, 1H), 3.85 (s, 3H). DMSO 330 (M + H) 1.76 Method D 100 1253 0 HCl 342.4 1H NMR (300 MHz, DMSO) 10.11 (s, 1H), 9.63 (s, 1H), 9.07-8.86 (m, 2H), 8.58 (s, 1H), 8.16 (s, 2H), 7.92-7.77 (m, 1H), 7.54- 7.36 (m, 2H), 7.20 (d, J = 8.6 Hz, 1H), 7.16- 7.07 (m, 1H), 3.81 (s, 3H), 3.29 (d, J = 3.9 Hz, 3H). DMSO 343 (M + H) 1.47 Method D 100 Method AQ2 1254 330.3 1H NMR (300 MHz, DMSO) 9.59 (s, 1H), 8.73 (d, J = 8.3 Hz, 1H), 8.65 (d, J = 4.7 Hz, 1H), 8.37-8.22 (m, 1H), 8.18-8.05 (m, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.71 (s, 1H), 7.56- 7.43 (m, 2H), 4.58 (s, 2H), 3.14 (d, J = 4.4 Hz, 3H), 2.69 (d, J = 4.6 Hz, 3H). DMSO 331 (M + H) 1.52 Method D 100 Method AQ2 1255 312.4 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.88-8.47 (m, 4H), 8.25-8.05 (m, 1H), 7.97-7.72 (m, 3H), 7.67-7.35 (m, 4H), 3.18 (d, J = 4.4 Hz, 3H). DMSO 313 (M + H) 1.48 Method D 100 Method AQ2 1256 HCl 337.4 1H NMR (300 MHz, DMSO) 9.93 (s, 1H), 9.63 (s, 1H), 9.00 (d, J = 8.3 Hz, 1H), 8.95- 8.82 (m, 2H), 8.46-8.32 (m, 2H), 8.25 (d, J = 7.0 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.88-7.70 (m, 2H), 3.29 (d, J = 4.2 Hz, 3H). DMSO 338 (M + H) 1.50 Method D 100 Method AQ2 1257 337.4 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.77 (d, J = 7.9 Hz, 1H), 8.73-8.59 (m, 3H), 8.21 (d, J = 8.8 Hz, 1H), 8.11-7.94 (m, 4H), 7.87 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 3.18 (d, J = 4.0 Hz, 3H). DMSO 338 (M + H) 1.50 Method D 100 Method AQ2 1258 346.8 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.77 (d, J = 7.9 Hz, 1H), 8.72-8.52 (m, 3H), 8.14 (d, J = 8.7 Hz, 1H), 7.97-7.74 (m, 3H), 7.68-7.45 (m, 3H), 3.18 (d, J = 4.0 Hz, 3H). DMSO 347 (M + H) 1.60 Method D 100 Method AQ2 1259 346.8 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.78 (d, J = 8.0 Hz, 1H), 8.72-8.54 (m, 3H), 8.17 (d, J = 8.7 Hz, 1H), 7.94 (s, 1H), 7.90- 7.78 (m, 2H), 7.61-7.42 (m, 3H), 3.19 (d, J = 4.4 Hz, 3H). DMSO 347 (M + H) 1.66 Method D 100 Method AQ2 1260 372.4 1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 8.77 (dd, J = 7.9, 1.8 Hz, 1H), 8.67 (d, J = 4.7 Hz, 1H), 8.46 (d, J = 4.4 Hz, 1H), 8.26 (s, 1H), 7.95-7.84 (m, 1H), 7.75 (d, J = 8.6 Hz, 1H), 7.53 (dd, J = 7.9, 4.8 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 6.77-6.60 (m, 2H), 3.80 (ss, 6H), 3.14 (d, J = 4.3 Hz, 3H). DMSO 373 (M + H) 1.49 Method D 100 Method AQ2 1261 348.3 1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 8.77 (dd, J = 8.0, 1.9 Hz, 1H), 8.68 (d, J = 4.6 Hz, 1H), 8.59 (s, 2H), 8.21-8.09 (m, 1H), 8.02-7.88 (m, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.71 (s, 1H), 7.67-7.58 (m, 1H), 7.53 (dd, J = 7.6, 5.1 Hz, 1H), 3.18 (d, J = 4.4 Hz, 3H). DMSO 349 (M + H) 1.61 Method D 100 Method AQ2 1262 313.4 1H NMR (300 MHz, DMSO) 9.65 (s, 1H), 9.09 (s, 1H), 8.78 (d, J = 8.0 Hz, 1H), 8.73- 8.55 (m, 4H), 8.30-8.14 (m, 2H), 7.89 (d, J = 8.6 Hz, 1H), 7.63-7.47 (m, 2H), 3.19 (d, J = 4.3 Hz, 3H). DMSO 314 (M + H) 1.70 Method C 96 Method AQ2 1263 0 343.4 1H NMR (300 MHz, DMSO) 9.64 (d, J = 1.3 Hz, 1H), 8.84-8.74 (m, 1H), 8.68 (dd, J = 6.2, 1.7 Hz, 2H), 8.57 (d, J = 1.6 Hz, 2H), 8.16 (ddd, J = 14.4, 8.7, 2.2 Hz, 2H), 7.85 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.00 (d, J = 8.7 Hz, 1H), 3.93 (s, 3H), 3.18 (d, J = 4.3 Hz, 3H). DMSO 344.1 (M + H) 1.94 Method C 95 Method AQ2 1264 356.4 1H NMR (300 MHz, DMSO) 10.76 (s, 1H), 9.75 (d, J = 1.6 Hz, 1H), 9.23 (d, J = 8.2 Hz, 1H), 9.05-8.86 (m, 2H), 8.41-8.24 (m, 2H), 8.24-8.05 (m, 2H), 7.96 (dd, J = 8.1, 5.2 Hz, 1H), 6.56 (d, J = 9.5 Hz, 1H), 4.81 (s, 2H), 3.34 (s, 3H), 3.29 (d, J = 4.3 Hz, 3H). DMSO 357.1 (M + H) 2.13 Method C 100 Method AQ2 1265 342.4 1H NMR (300 MHz, DMSO) d 9.64 (s, 1H), 8.78 (dd, J = 8.0, 1.9 Hz, 1H), 8.67 (dd, J = 6.3, 4.7 Hz, 2H), 8.58 (s, 1H), 8.17-8.06 (m, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.79 (s, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.60-7.44 (m, 2H), 7.37 (d, J = 7.5 Hz, 1H), 5.31 (t, J = 5.4 Hz, 1H), 4.62 (d, J = 4.9 Hz, 2H), 3.18 (d, J = 4.4 Hz, 3H). DMSO 343.1 (M + H) 1.78 Method C 99 Method AQ2 1266 344.4 1H NMR (300 MHz, DMSO) 9.65 (d, J = 2.1 Hz, 1H), 8.92-8.59 (m, 3H), 8.59-8.47 (m, 1H), 8.40-8.11 (m, 2H), 8.04 (d, J = 8.5 Hz, 1H), 7.58 (dd, J = 7.9, 4.8 Hz, 1H), 6.95 (d, J = 8.6 Hz, 1H), 4.29 (s, 3H), 3.93 (s, 3H). DMSO 345.1 (M + H) 2.32 Method C 100 Method AQ2 1267 329.4 1H NMR (300 MHz, DMSO) 12.77 (s, 1H), 9.33 (d, J = 1.7 Hz, 1H), 8.77 (dd, J = 4.7, 1.5 Hz, 1H), 8.60-8.46 (m, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.04 (d, J = 1.5 Hz, 1H), 7.87 (dd, J = 8.3, 1.8 Hz, 1H), 7.67-7.53 (m, 1H), 7.52- 7.29 (m, 3H), 7.04 (ddd, J = 7.7, 2.4, 1.5 Hz, 1H), 3.57 (s, 3H). DMSO 330 (M + H) 1.78 Method C 100 Method AQ2 1268 342.4 1H NMR (300 MHz, DMSO) 9.65 (dd, J = 2.1, 0.8 Hz, 1H), 8.84-8.74 (m, 1H), 8.68 (dd, J = 4.7, 1.7 Hz, 1H), 8.52 (d, J = 4.4 Hz, 1H), 8.30 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 1.7 Hz, 1 H), 7.85 (dd, J = 8.5, 1.8 Hz, 1H), 7.54 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.47-7.34 (m, 3H), 7.08-6.96 (m, 1H), 3.34 (s, 3H), 3.17 (d, J = 4.4 Hz, 3H). DMSO 343.3 (M + H) 2.09 Method C Method AQ2 1269 342.4 1H NMR (300 MHz, DMSO) 9.53 (d, J = 2.0 Hz, 1 H), 8.65 (dd, J = 5.9, 3.5 Hz, 2H), 8.51 (d, J = 4.2 Hz, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.65-7.25 (m, 5H), 7.00 (dd, J = 8.1, 2.6 Hz, 1H), 3.33 (s, 3H), 3.17 (d, J = 4.2 Hz, 3H). DMSO 343.3 (M + H) 2.16 Method C 100 Method AQ2 1270 2HCl 374.5 1H NMR (300 MHz, DMSO) 10.67 (s, 1H), 9.69 (s, 1H). 9.12 (d, J = 11.6 Hz. 2H), 8.97 (d, J = 5.0 Hz, 1H), 8.43 (d, J = 7.4 Hz, 1H), 8.31 (d, J = 8.6 Hz, 1H), 8.20 (s, 1H), 8.07 (s, 1H), 7.98-7.86 (m, 1H), 7.77 (s, 2H), 3.31 (d, J = 3.9 Hz, 3H), 2.90 (s, 3H). DMSO 375.1 (M + H) 1.67 Method C 95 Method AQ2 1271 374.5 1H NMR (300 MHz, DMSO) 9.70-9.57 (m, 1H), 8.84-8.72 (m, 1H), 8.73-8.62 (m, 3H), 8.19 (dd, J = 8.7, 1.9 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.86 (dd, J = 10.6, 8.5 Hz, 3H), 7.60- 7.49 (m, 1H), 3.19 (d, J = 4.4 Hz, 2H), 2.81 (s, 3H). DMSO 375.1 (M + H) 1.64 Method C 95 Method AQ2 1272 2HCl 425.5 1H NMR (300 MHz, DMSO) 10.54 (s, 1H), 9.70 (d, J = 1.7 Hz, 1H), 9.12 (d, J = 8.1 Hz, 1H), 8.98 (dd, J = 5.5, 4.0 Hz, 2H), 8.37 (dd, J = 26.8, 7.9 Hz, 2H), 8.09-7.84 (m, 3H), 7.63 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 3.67 (bs, 8H), 3.31 (d, J = 4.3 Hz, 3H). DMSO 426.2 (M + H) 1.72 Method C 95 Method AQ2 1273 00 HCl 342.4 1H NMR (300 MHz, DMSO) 9.64 (s, 1 H), 8.77 (d, J = 7.9 Hz, 1H), 8.71-8.65 (m, 1H), 8.60 (s, 1H), 8.53 (s, 1H), 8.10 (d, J = 8.7 Hz, 1H), 7.87-7.77 (m, 3H), 7.59-7.49 (m, 1H), 7.10 (d, J = 8.7 Hz, 2H), 3.83 (d, J = 0.9 Hz, 3H), 3.19 (s, 3H). DMSO 343.1 (M + H) 2.06 Method C 100 Method AQ2 1274 01 329.4 1H NMR (300 MHz, DMSO) 9.34 (d, J = 1.5 Hz, 1 H), 8.74 (dd, J = 4.8, 1.6 Hz, 1H), 8.53 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 2.1 Hz, 1H), 8.10 (dd, J = 8.5, 2.3 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.76 (s, 1H), 7.73 (s, 1H), 7.58 (dd, J = 8.0, 4.8 Hz, 1H), 7.07 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H). DMSO 330.0 (M + H) 1.75 Method C 100 Method AQ2 1275 02 343.4 1H NMR (300 MHz, DMSO) 9.65 (d, J = 1.5 Hz, 1H), 8.84-8.65 (m, 4H), 8.31 (d, J = 5.4 Hz, 1H), 8.24 (dd, J = 8.7, 1.9 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.59-7.46 (m, 2H), 7.33 (d, J = 0.9 Hz, 1H), 3.93 (s, 3H), 3.20 (d, J = 4.4 Hz, 3H). DMSO 344.1 (M + H) 1.95 Method C 95 Method AQ2 1276 03 331.3 1H NMR (300 MHz, DMSO) 9.63 (d, J = 1.4 Hz, 1H), 8.81-8.74 (m, 1H), 8.73 (d, J = 2.3 Hz, 1H), 8.68 (dd, J = 4.7, 1.7 Hz, 1H), 8.66- 8.56 (m, 2H), 8.44 (td, J = 8.2, 2.6 Hz, 1H), 8.18 (dd, J = 8.7, 2.0 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.38 (dd, J = 8.5, 2.9 Hz, 1H), 3.18 (d, J = 4.4 Hz, 3H). DMSO 332.1 (M + H) 1.89 Method C 100 Method AQ2 1277 04 425.5 1H NMR (300 MHz, DMSO) 9.63 (d, J = 1.4 Hz, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.70-8.59 (m, 3H), 8.15 (dd, J = 8.7, 1.6 Hz, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.7 Hz, 1H), 7.62-7.48 (m, 3H), 3.62 (s, J = 54.7 Hz, 8H), 3.17 (d, J = 4.2 Hz, 3H). DMSO 426.2 (M + H) 1.69 Method C 100 Method AQ2 1278 05 343.4 1H NMR (300 MHz, DMSO) 9.67 (d, J = 1.5 Hz, 1H), 8.86-8.77 (m, 1H), 8.74 (dd, J = 4.7, 1.6 Hz, 1H), 8.37-8.25 (m, 2H), 8.06 (d, J = 8.7 Hz, 1H), 7.60 (dd, J = 7.9, 4.1 Hz, 1H), 7.50-7.30 (m, 3H), 7.02 (dd, J = 7.9, 1.4 Hz, 1H), 4.31 (s, 3H), 3.87 (s, 3H). DMSO 344.2 (M + H) 2.47 Method C 100 Method AQ2

(414) TABLE-US-00031 .sup.1H Pu- Method NMR rity of Num- Starting Starting Salt Sol- Per- Cou- LCMS ber Material 1 Material 2 Product type .sup.1H NMR vent cent pling LCMS Method 1279 06 07 08 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.69 (d, J = 1.8 Hz, 1H), 9.40- 9.33 (m, 1H), 9.03-8.93 (m, 2H), 8.64-8.59 (m, 1H), 8.18-8.14 (m, 1H), 8.13- 8.05 (m, 3H), 8.04-7.97 (m, DMSO >98 AQ3 2H), 3.21 (d, J = 4.4 Hz, 3H), 2.77 (s, 3H). 1280 09 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.71-9.65 (m, 1H), 9.44-9.36 (m, 1H), 9.06-8.94 (m, 2H), 8.59- 8.54 (m, 1H), 8.19-8.10 (m, 2H), 7.79-7.71 (m, 2H), 7.61- 7.54 (m, 1H), 7.29- 7.22 (m, 1H), 3.21 (d, J = 3.9 Hz, 3H), DMSO >98 AQ3 2.76 (s, 3H). 1281 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.72-9.65 (m, 1H), 9.43-9.36 (m, 1H), 9.04-8.91 (m, 2H), 8.63- 8.55 (m, 1H), 8.36-8.31 (m, 1H), 8.26-8.20 (m, 1H), 8.20- 8.11 (m, 2H), DMSO >98 AQ3 7.91-7.85 (m, 1H), 7.78-7.70 (m, 1H), 3.22 (d, J = 4.2 Hz, 3H), 2.76 (s, 3H). 1282 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.70-9.65 (m, 1H), 9.37 (d, J = 8.2 Hz, 1H), 9.03- 8.90 (m, 2H), 8.49-8.42 (m, 1H), 8.12 (dd, J = 8.1, 5.6 Hz, 1H), 8.08-8.03 (m, 1H), 7.88-7.78 DMSO >98 AQ3 (m, 2H), 7.15- 7.04 (m, 2H), 3.84 (s, 3H), 3.21 (d, J = 3.9 Hz, 3H), 2.76 (s, 3H). 1283 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.73-9.67 (m, 1H), 9.36 (d, J = 7.4 Hz, 1H), 9.02-8.96 (m, 1H), 8.82 (s, 1H), 8.26-8.19 (m, 1H), 8.15-8.07 (m, 1H), 7.89-7.83 (m, 1H), 7.47- 7.38 (m, 2H), DMSO >98 AQ3 7.21-7.15 (m, 1H), 7.14-7.06 (m, 1H), 3.81 (s, 3H), 3.19 (d, J = 4.5 Hz, 3H), 2.77 ( s, 3H). 1284 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.72 (d, J = 1.8 Hz, 1H), 9.34- 9.28 (m, 1H), 8.95 (dd, J = 5.4, 1.4 Hz, 1H), 8.88-8.78 (m, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.07- 8.00 (m, 2H), DMSO >98 AQ3 7.95-7.90 (m, 1H), 7.90-7.83 (m, 1H), 7.76 (dd, J = 7.8, 0.7 Hz, 1H), 7.68- 7.63 (m, 1H), 3.19 (d, J = 4.5 Hz, 3H), 2.77 (s, 3H). 1285 .sup.1H NMR (400 MHz, DMSO) 9.63 (dd, J = 2.1, 0.8 Hz, 1H), 8.80-8.75 (m, 1H), 8.69 (dd, J = 3.7, 1.8 Hz, 1H), 7.72 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.58-7.49 (m, DMSO >98 AQ4 2H), 7.46-7.40 (m, 1H), 7.39- 7.32 (m, 1H), 7.28-7.18 (m, 1H), 3.18 (d, J = 4.4 Hz, 3H), 2.64 (s, 3H). 1286 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.67-9.60 (m, 1H), 9.06-8.88 (m, 3H), 8.12 (d, J = 8.8 Hz, 1H), 7.91- 7.79 (m, 2H) 7.53-7.40 (m, 2H), 7.34- 7.24 (m, 1H), 3.34 (d, J = 4.6 DMSO >98 AQ4 Hz, 3H), 2.66 (s, 3H). 1287 0 HCl .sup.1H NMR (400 MHz, DMSO) 9.62-9.57 (m, 1H), 8.94-8.86 (m, 2H), 8.62 (s, 1H), 7.95 (d, J = 8.5 Hz, 1H), 7.86- 7.75 (m, 2H), 7.52-7.36 (m, 2H), 7.35-7.28 (m, 1H), 3.31 (d, J = 4.5 Hz, 3H), 2.67 (s, 3H). DMSO >98 AQ4 1288 HCl .sup.1H NMR (400 MHz, DMSO) 9.63-9.58 (m, 1H), 8.95-8.86 (m, 2H), 8.73 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.87-7.75 (m, 2H), 7.61-7.50 (m, 1H), 7.45-7.33 (m, 3H), 3.32 (d, DMSO >98 AQ4 J = 4.5 Hz, 3H), 2.66 (s, 3H). 1289 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.64-9.60 (m, 1H), 9.00-8.86 (m, 3H), 8.06 (d, J = 8.5 Hz, 1H), 7.91-7.79 (m, 2H), 7.65-7.55 (m, 1H), 7.37- 7.29 (m, 1H), 7.29-7.22 (m, 2H), 3.35 (d, J = 4.6 Hz, 3H), DMSO >98 AQ4 2.72 (s, 3H). 1290 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.69-9.64 (m, 1H), 9.14-8.99 (m, 2H), 8.96 (dd, J = 5.0, 1.5 Hz, 1H), 8.15 (d, J = 8.6 Hz, 1H), 7.90-7.81 (m, 2H), 7.50-7.34 (m, 4H), 3.35 (d, DMSO >98 AQ4 J = 4.6 Hz, 3H), 2.72 (s, 3H). 1291 HCl .sup.1H NMR (300 MHz, CDCl.sub.3) 9.63 (s, 2H), 8.96 (d, J = 8.2 Hz, 1H), 8.90 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 8.16- 7.99 (m, 2H), 7.82 (dd, J = 8.0, 4.9 Hz, 1H), 7.71-7.62 (m, 1H), 7.61-7.47 DMSO >98 G2/AQ3 (m, 3H), 3.26 (d, J = 4.5 Hz, 3H). 1292 2 HCl .sup.1H NMR (300 MHz, CDCl.sub.3) 10.27 (s, 1H), 9.69 (s, 1H), 9.09 (d, J = 8.1 Hz, 1H), 8.97 (d, J = 5.0 Hz, 1H), 8.56 (s, 1H), 8.32 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.89 (dd, J = DMSO >98 G2/AQ3 8.0, 5.1 Hz, 1H), 7.45-7.26 (m, 4H), 3.29 (d, J = 4.2 Hz, 3H), 2.32 (s, 3H). 1293 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.40 (s, 1H), 9.73 (s, 1H), 9.15 (d, J = 7.9 Hz, 1H), 8.98 (d, J = 5.1 Hz, 1H), 8.67 (s, 1H), 8.33 (d, J = 8.6 Hz, 1H), 8.18 (d, J = 8.7 Hz, 1H), 7.91 (dd, J = 7.9, 5.2 Hz, DMSO >98 G2/AQ3 1H), 7.45 (m, 2H), 7.20 (d, J = 8.2 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 3.82 (s, 3H), 3.29 (d, J = 4.1 Hz, 3H). 1294 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.66 (s, 1H), 8.80 (d, J = 7.9 Hz, 1H), 8.74-8.67 (m, 1H), 8.60 (m, 1H), 8.49 (s, 1H), 8.00 (dd, J = 18.5, 10.4 Hz, 2H), 7.96-7.81 (m, 2H), 7.76 (d, DMSO >98 G2/AQ3 J = 7.6 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.56 (dd, J = 7.6, 5.0 Hz, 1H), 3.18 (d, J = 4.2 Hz, 3H). 1295 2 HCl .sup.1H NMR (300 MHz, CDCl.sub.3) 9.88 (s, 1H), 9.66 (s, 1H), 9.01 (d, J = 8.3 Hz, 1H), 8.90 (d, J = 4.2 Hz, 1H), 8.70 (s, 1H), 8.27- 8.08 (m, 2H), 7.81 (dd, J = 8.0, 5.1 Hz,1H), 7.72 DMSO >98 G2/AQ3 (t, J = 7.6 Hz, 1H), 7.60-7.48 (m, 1H), 7.48- 7.27 (m, 2H), 3.27 (d, J = 4.3 Hz, 3H). 1296 2 HCl .sup.1H NMR (300 MHz, CDCl.sub.3) 9.63 (m, 2H), 8.93 (d, J = 7.7 Hz, 1H), 8.88 (d, J = 4.1 Hz, 1H), 8.76 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 7.94 (dd, J = 8.6, 5.5 DMSO >98 G2/AQ3 Hz, 2H), 7.82- 7.73 (m, 1H), 7.41 (t, J = 8.7 Hz, 2H), 3.28 (d, J = 4.3 Hz, 3H). 1297 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.82 (s, 1H), 9.64 (d, J = 1.7 Hz, 1H), 9.00 (d, J = 8.0 Hz, 1H), 8.95- 8.86 (m, 2H), 8.69 (t, J = 1.9 Hz, 1H), 8.51-8.34 (m, 2H), 8.30 (dd, J = 7.9, 1.8 DMSO >98 G2/AQ3 Hz, 1H), 8.13 (d, J = 8.7 Hz, 1H), 7.93-7.76 (m, 2H), 3.30 (d, J = 4.5 Hz, 3H). 1298 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.30 (s, 1H), 9.70 (d, J = 2.1 Hz, 1H), 9.11 (d, J = 8.2 Hz, 1H), 9.04-8.83 (m, 1H), 8.56 (s, 1H), 8.26 (d, J = 8.6 Hz, 1H), 8.01- 7.80 (m, 3H), DMSO >98 G2/AQ3 7.78-7.64 (m, 1H), 7.60 (t, J = 7.2 Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 3.29 (d, J = 4.4 Hz, 3H), 2.44 (s, 3H). 1299 .sup.1H NMR (300 MHz, DMSO) 10.50 (s, 1H), 9.66 (s, 1H), 9.09 (d, J = 8.2 Hz, 1H), 9.01 (s, 1H), 8.94 (d, J = 5.0 Hz, 1H), 8.40 (d, J = 8.7 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.13- DMSO >98 G2/AQ3 8.00 (m, 4H), 7.88 (dd, J = 8.0, 5.2 Hz, 1H), 3.30 (d, J = 4.1 Hz, 3H), 2.62 (s, 3H). 1300 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.49 (s, 1H), 9.66 (s, 1H), 9.09 (d, J = 7.9 Hz, 1H), 9.01 (s, 1H), 8.95 (d, J = 5.0 Hz, 1H), 8.40 (d, J = 8.6 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 8.15- 7.94 (m, 4H), 7.88 (dd, J = DMSO >98 G2/AQ3 7.9, 5.2 Hz, 1H), 3.31 (d, J = 4.1 Hz, 3H), 2.63 (s, 3H). 1301 3 HCl .sup.1H NMR (300 MHz, DMSO) 10.97 (s, 1H), 9.71 (d, J = 2.0 Hz, 1H), 9.29 (s, 1H), 9.15 (d, J = 8.0 Hz, 1H), 8.98 (dd, J = 5.0, 1.3 Hz, 1H), 8.49-8.38 (m, 1H), 8.34 (d, DMSO >98 G2/AQ3 J = 8.8 Hz, 1H), 8.21 (s, 1H), 7.92 (dd, J = 8.1, 5.1 Hz, 1H), 7.84 (s, 1H), 7.69-7.52 (m, 2H), 3.31 (d, J = 4.3 Hz, 3H), 3.23 (s, 6H). 1302 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.33 (s, 1H), 9.73 (d, J = 1.7 Hz, 1H), 9.20 (d, J = 8.0 Hz, 1H), 9.00 (d, J = 4.2 Hz, 1H), 8.68 (s, 1H), 8.32 (d, J = 8.6 Hz, 1H), 8.16 (d, J = 7.9 DMSO >98 G2/AQ3 Hz, 1H), 8.01- 7.93 (m, 2H), 7.90 (t, J = 7.2 Hz, 1H), 7.74 (dd, J = 15.4, 7.7 Hz, 2H), 3.24 (t, J = 18.2 Hz, 3H). 1303 0 HCl .sup.1H NMR (300 MHz, DMSO) 10.46 (s, 1H), 9.76 (d, J = 2.1 Hz, 1H), 9.21 (d, J = 8.2 Hz, 1H), 9.00 (dd, J = 5.1, 1.2 Hz, 1H), 8.58 (d, J = 1.3 Hz, 1H), 8.41 (d, J = 8.6 Hz, 1H), DMSO >98 G2/AQ3 8.08-7.86 (m, 2H), 7.36-7.09 (m, 3H), 3.29 (d, J = 4.3 Hz, 3H), 2.33 (s, 3H), 2.17 (s, 3H). 1304 .sup.1H NMR (300 MHz, DMSO) 9.65 (d, J = 2.1 Hz, 1H), 8.79 (dt, J = 8.0, 1.9 Hz, 1H), 8.69 (dd, J = 4.7, 1.6 Hz, 1H), 8.46 (d, J = 4.5 Hz, 1H), 8.20 (d, J = 1.7 Hz, 1H), 7.83 (d, J = 8.5 DMSO >98 G2/AQ3 Hz, 1H), 7.75 (dd, J = 8.5, 1.6 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.28- 7.02 (m, 3H), 3.33 (s, 6H), 3.15 (d, J = 4.4 Hz, 3H), 2.51 (dt, J = 3.6, 1.7 Hz, 1H), 2.35 (s, 3H), 2.27 (s, 3H). 1305 HCl .sup.1H NMR (300 MHz, DMSO) 10.48 (s, 1H), 9.70 (s, 1H), 9.11 (d, J = 7.8 Hz, 1H), 8.97 (d, J = 4.7 Hz, 1H), 8.90 (s, 1H), 8.36 (d, J = 8.6 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 7.98- DMSO >98 G2/AQ3 7.80 (m, 1H), 7.74 (s, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 3.32 (d, J = 4.0 Hz, 3H), 2.33 (d, J = 10.0 Hz, 3H), 2.29 (s, 3H). 1306 HCl .sup.1H NMR (300 MHz, DMSO) 10.45-10.35 (m, 1H), 9.69 (s, 1H), 9.09 (s, 1H), 8.99 (s, 1H), 8.88 (s, 1H), 8.37 (d, J = 8.6 Hz, 1H), 8.28 (d, J = 8.7 Hz, 1H), 7.94 (s, 1H), 7.54 (s, 1H), 7.11 (s, 1H), 3.34 (d, J = DMSO >98 G2/AQ3 4.3 Hz, 3H), 2.40 (s, 3H). 1307 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.28 (s, 1H), 9.84-9.66 (m, 1H), 9.17 (d, J = 8.1 Hz, 1H), 8.99 (d, J = 5.0 Hz, 1H), 8.46 (s, 1H), 8.36 (d, J = 8.6 Hz, 1H), 7.98-7.80 (m, DMSO >98 G2/AQ3 2H), 7.41 (t, J = 8.4 Hz, 1H), 6.83 (d, J = 8.4 Hz, 2H), 3.71 (s, 6H), 3.29 (d, J = 4.2 Hz, 3H). 1308 HCl .sup.1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.96- 8.91 (m, 1H), 8.89-8.83 (m, 2H), 8.41 (d, J = 9.1 Hz, 2H), 8.38- 8.32 (m, 1H), 8.16 (d, J = 9.0 Hz, 2H), 8.02 (d, J = 9.1 Hz, 1H), 7.81-7.73 (m, 1H), 3.27 (d, J = DMSO >98 G2/AQ3 4.3 Hz, 3H). 1309 .sup.1H NMR (300 MHz, DMSO) 9.64 (d, J = 2.0 Hz, 1H), 8.78 (ddd, J = 14.6, 8.2, 6.5 Hz, 1H), 8.70 (dd, J = 4.7, 1.4 Hz, 1H), 8.56 (d, J = 4.3 Hz, 1H), 8.33 (d, J = 1.5 Hz, 1H), 8.06 DMSO >98 G2/AQ3 (dd, J = 8.6, 1.4 Hz, 1H), 7.81 (d, J = 8.6 Hz, 1H), 7.56 (dd, J = 7.9, 4.8 Hz, 1H), 7.34 (t, J = 7.5 Hz, 2H), 7.20- 7.00 (m, 2H), 3.16 (d, J = 4.4 Hz, 3H). 1310 00 01 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.63 (s, 1H), 9.69 (s, 1H), 9.16 (s, 1H), 9.10 (d, J = 7.9 Hz, 1H), 8.97 (d, J = 5.0 Hz, 1H), 8.52 (s, 1H), 8.45 (d, J = 8.7 Hz, 1H), 8.29 (d, J = 8.7 Hz, 2H), 8.07 (d, J = 7.8 Hz, 1H), 8.01-7.84 (m, DMSO >98 G2/AQ3 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.54 (s, 1H), 3.31 (d, J = 4.3 Hz, 3H). 1311 02 03 04 HCl .sup.1H NMR (300 MHz, DMSO) 10.20 (s, 1H), 9.65 (s, 1H), 9.02 (s, 1H), 8.95 (s, 2H), 8.43 (d, J = 8.7 Hz, 1H), 8.26- 8.14 (m, 1H), 8.04 (dd, J = 18.8, 8.1 Hz, 4H), 7.88 (s, 1H), 7.47 (s, 1H), 3.32 (s, DMSO >98 G2/AQ3 3H), 3.17 (d, J = 1.8 Hz, 9H). 1312 05 06 07 HCl .sup.1H NMR (300 MHz, DMSO) 9.79 (s, 1H), 9.66 (d, J = 1.7 Hz, 1H), 9.02 (d, J = 8.1 Hz, 1H), 8.96-8.86 (m, 1H), 8.57 (s, 1H), 8.18 (d, J = 8.7 Hz, 1H), 8.05 (dd, J = 8.7, 1.4 Hz, DMSO >98 G2/AQ3 1H), 7.82 (dd, J = 8.1, 5.0 Hz, 1H), 7.79-7.72 (m, 1H), 7.64-7.45 (m, 2H), 3.25 (d, J = 4.4 Hz, 3H). 1313 08 09 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.01 (s, 1H), 9.65 (s, 1H), 9.06 (d, J = 7.8 Hz, 1H), 8.95 (d, J = 4.8 Hz, 1H), 8.59 (s, 1H), 8.21 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 9.1 Hz, 1H), 7.95- DMSO >98 G2/AQ3 7.77 (m, 2H), 7.66-7.52 (m, 2H), 3.27 (d, J = 4.3 Hz, 3H), 3.17 (d, J = 0.7 Hz, 1H). 1314 HCl .sup.1H NMR (300 MHz, DMSO) 10.10 (s, 1H), 9.69 (s, 1H), 9.13 (d, J = 8.0 Hz, 1H), 8.98 (d, J = 5.1 Hz, 1H), 8.62 (s, 1H), 8.27 (d, J = 8.6 Hz, 1H), 8.13 (d, J = 8.3 Hz, 1H), 8.02- 7.83 (m, 1H), 7.77-7.65 (m, DMSO >98 G2/AQ3 2H), 7.60 (d, J = 8.5 Hz, 1H), 3.29 (d, J = 3.9 Hz, 3H). 1315 HCl .sup.1H NMR (300 MHz, DMSO) 9.62 (s, 1H), 9.02- 8.93 (m, 1H), 8.89 (d, J = 4.5 Hz, 1H), 8.80 (s, 1H), 8.35 (d, J = 8.7 Hz, 1H), 8.18 (s, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.96-7.75 (m, DMSO >98 G2/AQ3 2H), 3.29 (d, J = 4.2 Hz, 3H). 1316 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.36 (s, 1H), 9.67 (s, 1H), 9.13 (d, J = 8.2 Hz, 1H), 9.01-8.82 (m, 2H), 8.40 (d, J = 9.1 Hz, 1H), 8.26 (d, J = 8.7 Hz, 1H), 7.97 (s, 2H), 7.90 (dd, J = 8.0, 5.2 Hz, 1H), 7.65 (s, 1H), DMSO >98 G2/AQ3 3.31 (d, J = 4.3 Hz, 3H). 1317 0 .sup.1H NMR (300 MHz, DMSO) 9.65 (d, J = 1.9 Hz, 1H), 8.89- 8.75 (m, 1H), 8.74-8.67 (m, 1H), 8.67-8.56 (m, 1H), 8.48 (s, 1H), 8.06-7.94 (m, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.68- 7.51 (m, 2H), 7.46 (td, J = 9.6, DMSO >98 G2/AQ3 4.7 Hz, 1H), 7.39-7.21 (m, 1H), 3.18 (d, J = 4.4 Hz, 3H). 1318 HCl .sup.1H NMR (300 MHz, DMSO) 10.57 (s, 1H), 9.69 (d, J = 2.0 Hz, 1H), 9.15 (d, J = 8.0 Hz, 1H), 9.02 (s, 1H), 8.97 (d, J = 4.4 Hz, 1H), 8.40 (d, J = 8.8 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 7.91 (dd, J = 8.0, 5.2 DMSO >98 G2/AQ3 Hz, 1H), 7.77- 7.63 (m, 2H), 7.37-7.18 (m, 1H), 3.29 (d, J = 4.3 Hz, 3H). 1319 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.58 (d, J = 2.0 Hz, 1H), 8.78-8.60 (m, 2H), 8.35 (d, J = 1.7 Hz, 1H), 8.11-7.84 (m, 3H), 7.78 (d, J = 8.6 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.48- DMSO >98 G2/AQ3 7.34 (m, 2H), 7.17 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.4 Hz, 1H), 3.81 (s, 3H).

(415) TABLE-US-00032 1320 0 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.62 (d, J = 2.1 Hz, 1H), 8.82- 8.72 (m, 1H), 8.72-8.66 (m, 1H), 8.30 (s, 1H), 7.93 (dd, J = 8.7, 1.2 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.54 (dd, J = DMSO >98 G2/AQ3 7.9, 4.8 Hz, 1H), 7.50-7.33 (m, 2H), 7.18 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 3.82 (s, 3H), 3.46 (s, 6H). 1321 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.59 (d, J = 2.1 Hz, 1H), 8.76- 8.66 (m, 2H), 8.50 (s, 2H), 8.06 (brs, 1H), 7.99 (dt, J = 8.6, 1.7 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.75-7.63 (m, DMSO >98 G2/AQ3 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.52-7.44 (m, 1H), 7.44-7.32 (m, 2H). 1322 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.59 (d, J = 2.1 Hz, 1H), 8.79- 8.62 (m, 3H), 8.21 (dd, J = 8.8, 1.9 Hz, 1H), 8.10 (brs, 2H), 7.86 (d, J = 8.7 Hz, 1H), 7.80-7.69 (m, 2H), 7.68-7.49 (m, DMSO >98 G2/AQ3 2H), 7.32- 7.20 (m, 1H). 1323 0 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.58 (d, J = 2.0 Hz, 1H), 8.80-8.64 (m, 2H), 8.62 (d, J = 1.8 Hz, 1H), 8.14 (dd, J = 8.7, 1.9 Hz, 1H), 8.07 (brs, 2H), 7.98-7.87 (m, 2H), 7.85 (d, J = DMSO >98 G2/AQ3 8.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.38 (t, J = 8.8 Hz, 2H). 1324 .sup.1H NMR (300 MHz, CDCl.sub.3) 9.65-9.57 (m, 1H), 8.82-8.70 (m, 1H), 8.70-8.63 (m, 1H), 8.36 (d, J = 1.8 Hz, 1H), 8.11 (dd, J = 8.7, 1.7 Hz, 1H), 7.89 (d, J = 8.7 Hz, 1H), 7.72- DMSO >98 G2/AQ3 7.60 (m, 2H), 7.60-7.47 (m, 2H), 7.32-7.18 (m, 1H), 3.49 (s, 6H). 1325 .sup.1H NMR (400 MHz, DMSO) 9.64 (d, J = 1.4 Hz, 1H), 8.78 (dt, J = 8.3, 1.8 Hz, 1H), 8.69 (dd, J = 4.7, 1.8 Hz, 1H) 8.61-8.46 (m, 2H), 8.40 (d, J = 1.6 Hz, 1H), 7.99 (dd, J = DMSO >98 G2/AQ3 9.0, 1.8 Hz, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.54 (dd, J = 8.4, 4.5 Hz, 1H), 3.99 (d, J = 8.9 Hz, 6H), 3.17 (d, J = 4.6 Hz, 3H). 1326 .sup.1H NMR (300 MHz, DMSO) 9.64-9.55 (m, 1H), 8.81-8.62 (m, 3H), 8.40 (s, 1H), 8.23 (dd, J = 8.8, 1.4 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 7.7 Hz, 2H), DMSO >98 G2/AQ3 7.89 (d, J = 8.7 Hz, 1H), 7.69 (t, J = 7.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 2.71 (s, 3H). 1327 0 .sup.1H NMR (300 MHz, DMSO) 9.58 (d, J = 2.1 Hz, 1H), 8.76- 8.65 (m, 3H), 8.24 (dd, J = 8.7, 1.8 Hz, 1H), 8.19- 7.93 (m, 6H), 7.88 (d, J = 8.8 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 2.65 (s, 3H). DMSO >98 G2/AQ3 1328 .sup.1H NMR (300 MHz, DMSO) 9.60 (d, J = 1.8 Hz, 1H), 8.73 (dt, J = 8.0, 1.8 Hz, 1H), 8.69 (dd, J = 4.8, 1.6 Hz, 1H), 8.37 (s, 1H), 7.99 (brs, 2H), 7.92-7.81 (m, 2H), 7.67-7.60 DMSO >98 G2/AQ3 (m, 1H), 7.60- 7.52 (m, 2H), 7.52-7.43 (m, 2H). 1329 .sup.1H NMR (300 MHz, DMSO) 9.60 (d, J = 2.0 Hz, 1H), 8.77-8.65 (m, 3H), 8.19 (dd, J = 8.7, 1.8 Hz, 1H), 8.09 (brs, 2H), 7.99- 7.94 (m, 1H), 7.90-7.79 (m, 2H), 7.63-7.51 DMSO >98 G2/AQ3 (m, 2H), 7.48 (d, J = 8.1 Hz, 1H). 1330 0 .sup.1H NMR (300 MHz, DMSO) 9.65 (s, 1H), 8.87- 8.75 (m, 1H), 8.70 (s, 1H), 8.55 (s, 1H), 8.41 (s, 1H), 8.25 (s, 1H), 8.09-7.76 (m, 3H), 7.62-7.44 (m, 1H), 7.18 (s, 1H), 3.93 (s, 3H), DMSO >98 G2/AQ3 3.17 (s, 3H). 1331 .sup.1H NMR (300 MHz, DMSO) 9.61 (s, 1H), 8.75 (d, J = 7.6 Hz, 1H), 8.68 (s, 1H), 8.45 (s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 8.07 (d, J = 8.2 Hz, 2H), 8.01-7.87 (m, 3H), 7.55 (s, 1H), 3.51 (s, 6H), 2.63 (s, 3H). DMSO >98 G2/AQ3 1332 .sup.1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 8.83- 8.72 (m, 1H), 8.70 (d, J = 3.8 Hz, 1H), 8.21 (s, 1H), 7.89 (q, J = 8.6 Hz, 2H), 7.74- 7.41 (m, 5H), 3.47 (s, 6H). DMSO >98 G2/AQ3 1333 0 .sup.1H NMR (300 MHz, DMSO) 9.62 (d, J = 2.0 Hz, 1H), 8.76 (dt, J = 7.9, 1.8 Hz, 1H), 8.70 (dd, J = 4.8, 1.6 Hz, 1H), 8.38 (d, J = 1.9 Hz, 1H), 8.13 (dd, J = 8.7, 1.9 Hz, 1H), 7.98-7.84 DMSO >98 G2/AQ3 (m, 2H), 7.78 (d, J = 7.6 Hz, 1H), 7.66-7.41 (m, 3H), 3.51 (s, 6H). 1334 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.81-9.63 (m, 1H), 9.18 (d, J = 8.4 Hz, 1H), 9.07- 8.89 (m, 1H), 8.39 (d, J = 8.7 Hz, 1H), 8.31 (d, J = 1.7 Hz, 1H), 8.22-8.07 (m, 1H), 8.02 (dd, DMSO >98 G2/AQ3 J = 8.7, 1.7 Hz, 1H), 7.98-7.91 (m, 1H), 7.91- 7.83 (m, 1H), 7.80-7.68 (m, 2H), 3.65 (s, 6H). 1335 .sup.1H NMR (300 MHz, DMSO) 9.65- 9.62 (m, 1H), 8.82-8.75 (m, 1H), 8.73-8.68 (m, 1H), 8.61- 8.56 (m, 1H), 8.50 (d, J = 2.0 Hz, 1H), 8.34-8.20 (m, 3H), 7.97 (d, J = 8.7 Hz, 1H), DMSO >98 G2/AQ3 7.82 (t, J = 8.0 Hz, 1H), 7.57 (dd, J = 8.3, 5.2 Hz, 1H), 3.54 (s, 6H). 1336 .sup.1H NMR (300 MHz, DMSO) 9.61 (d, J = 1.8 Hz, 1H), 8.80-8.72 (m, 1H), 8.72- 8.67 (m, 1H), 8.47 (d, J = 1.6 Hz, 1H), 8.39- 8.29 (m, 2H), 8.19 (dd, J = 8.7, 1.8 Hz, 1H), 8.14-8.07 (m, 2H), 7.94 (d, J = 8.7 DMSO >98 G2/AQ3 Hz, 1H), 7.55 (dd, J = 7.9, 4.8 Hz, 1H), 3.52 (s, 6H). 1337 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.67- 9.61 (m, 1H), 8.82-8.73 (m, 1H), 8.73-8.65 (m, 1H), 8.39 (s, 1H), 8.03-7.96 (m, 3H), 7.90- 7.72 (m, 2H), 7.72-7.60 (m, 1H), 7.56 (dd, DMSO >98 G2/AQ3 J = 7.6, 5.1 Hz, 1H), 3.53 (s, 6H). 1338 .sup.1H NMR (300 MHz, DMSO) 9.65 (d, J = 2.1 Hz, 1H), 8.78 (dt, J = 8.1, 1.8 Hz, 1H), 8.71-8.59 (m, 3H), 8.19 (dd, J = 8.6, 1.7 Hz, 1H), 8.07-7.95 (m, 2H), 7.93- 7.81 (m, 2H), 7.54 (dd, J = 7.9, DMSO >98 G2/AQ3 4.7 Hz, 1H), 7.47-7.34 (m, 2H), 3.23-3.20 (m, 3H). 1339 .sup.1H NMR (300 MHz, DMSO) 9.68-9.64 (m, 1H), 8.83-8.75 (m, 1H), 8.69 (d, J = 4.7 Hz, 1H), 8.56-8.45 (m, 2H), 8.17-8.05 (m, 1H), 8.05- 7.87 (m, 4H), 7.58-7.40 (m, 3H), 3.18 (d, J = 4.1 Hz, 3H). DMSO >98 G2/AQ3 1340 0 .sup.1H NMR (300 MHz, DMSO) 9.67 (d, J = 1.5 Hz, 1H), 8.80 (dt, J = 7.9, 1.9 Hz, 1H), 8.69 (dd, J = 4.8, 1.7 Hz, 1H), 8.57-8.41 (m, 2H), 8.08 (dd, J = 6.1, 2.6 Hz, 1H), 7.99 (dd, J = 8.6, 1.8 Hz, DMSO >98 G2/AQ3 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.84 (d, J = 5.6 Hz, 1H), 7.62- 7.44 (m, 4H), 3.17 (d, J = 4.5 Hz, 3H). 1341 .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.5 Hz, 1H), 8.79 (dt, J = 7.9, 1.9 Hz, 1H), 8.68 (dd, J = 4.8, 1.7 Hz, 1H), 8.65 (d, J = 1.9 Hz, 1H), 8.61- 8.53 (m, 1H), 8.35 (d, J = 1.6 DMSO >98 G2/AQ3 Hz, 1H), 8.21 (dd, J = 8.7, 2.0 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.92-7.80 (m, 3H), 7.59-7.48 (m, 2H), 3.21 (d, J = 4.5 Hz, 3H). 1342 .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.6 Hz, 1H), 8.79 (dt, 7 = 8.0, 1.9 Hz, 1H), 8.73-8.61 (m, 3H), 8.50 (s, 1H), 8.24 (dd, J = 8.7, 1.9 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.96- 7.82 (m, 3H), 7.60-7.50 (m, DMSO >98 G2/AQ3 2H), 3.21 (d, J = 4.4 Hz, 3H). 1343 00 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.41 (brs, 1H), 9.75 (d, J = 1.7 Hz, 1H), 9.24- 9.19 (m, 1H), 9.01 (dd, J = 5.2, 1.5 Hz, 1H), 8.90 (d, J = 1.5 Hz, 1H), 8.46 (d, J = 8.7 Hz, 1H), 8.39 (dd, J = 8.7, 1.7 Hz, 1H), DMSO >98 G2/AQ3 8.06-7.91 (m, 2H), 7.86 (d, J = 5.5 Hz, 1H), 7.66-7.52 (m, 3H), 3.29 (d, J = 4.5 Hz, 3H). 1344 01 02 03 HCl .sup.1H NMR (300 MHz, DMSO) 10.33 (brs, 1H), 9.78 (d, J = 2.0 Hz, 1H), 9.23 (d, J = 8.1 Hz, 1H), 9.01 (d, J = 5.0 Hz, 1H), 8.73 (s, 1H), 8.48 (d, J = 8.6 Hz, 1H), 8.14 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 8.0 Hz, 2H), 7.95 (dd, J = DMSO >98 G2/AQ3 8.1, 5.2 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.72- 7.50 (m, 4H), 3.27 (d, J = 4.3 Hz, 3H). 1345 04 05 06 .sup.1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.4 Hz, 1H), 8.85- 8.77 (m, 1H), 8.77-8.62 (m, 3H), 8.40 (s, 1H), 8.30 (dd, J = 8.7, 1.6 Hz, 1H), 8.14- 7.95 (m, 4H), 7.91 (d, J = 8.7 Hz, 1H), 7.63- 7.50 (m, 3H), 3.22 (d, J = 4.3 Hz, 3H). DMSO >98 G2/AQ3 1346 07 08 09 .sup.1H NMR (300 MHz, DMSO) 9.67 (d, J = 2.0 Hz, 1H), 8.80 (dt, J = 8.0, 1.9 Hz, 1H), 8.69 (dd, J = 4.7, 1.7 Hz, 1H), 8.67-8.55 (m, 2H), 8.25 (dd, J = 8.7, 1.8 Hz 1H), 8.13-8.09 (m, 1H), 7.92- 7.77 (m, 4H), 7.71 DMSO >98 G2/AQ3 (d, J = 7.8 Hz, 1H), 7.67-7.47 (m, 4H), 7.47- 7.37 (m, 1H), 3.20 (d, J = 4.4 Hz, 3H). 1347 0 .sup.1H NMR (300 MHz, DMSO) 9.68-9.65 (m, 1H), 8.79 (dt, J = 8.0, 1.9 Hz, 1H), 8.69 (dd, J = 4.8, 1.7 Hz, 1H), 8.68- 8.60 (m, 2H), 8.20 (dd, J = 8.7, 1.9 Hz, 1H), 7.99-7.95 (m, 2H), 7.92-7.81 DMSO >98 G2/AQ3 (m, 3H), 7.80- 7.73 (m, 2H), 7.61-7.46 (m, 3H), 7.46-7.36 (m, 1H), 3.20 (d, J = 4.4 Hz, 3H). 1348 .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.5 Hz, 1H), 8.80 (dt, J = 7.9, 1.9 Hz, 1H), 8.70 (dd, J = 4.7, 1.7 Hz, 1H), 8.55 (d, J = 4.6 Hz, 1H), 8.32 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 1.8 DMSO >98 G2/AQ3 Hz, 1H), 7.92- 7.84 (m, 3H), 7.60-7.50 (m, 3H), 7.50-7.42 (m, 1H), 3.18 (d, J = 4.5 Hz, 3H). 1349 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.23 (brs, 1H), 9.67 (d, J = 2.1 Hz, 1H), 9.04 (d, J = 7.7 Hz, 1H), 8.98-8.91 (m, 1H), 8.57 (d, J = 8.7 Hz, 1H), 8.48 (s, 1H), 8.08 (d, J = 8.3 Hz, 1H), DMSO >98 G2/AQ3 7.91-7.76 (m, 3H), 7.22-7.10 (m, 2H), 3.85 (s, 3H), 3.31 (d, J = 4.4 Hz, 3H). 1350 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.48 (brs, 1H), 9.74 (d, J = 1.9 Hz, 1H), 9.19 (d, J = 8.3 Hz, 1H), 9.07-8.97 (m, 1H), 8.71 (d, J = 8.8 Hz, 1H), 8.64 (s, 1H), 8.36 (s, 1H), 8.19 (d, J = DMSO >98 G2/AQ3 7.6 Hz, 1H), 8.16-8.06 (m, 2H), 7.95 (dd, J = 8.1, 5.0 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 3.31 (d, J = 4.4 Hz, 3H), 2.71 (s, 3H). 1351 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.47 (brs, 1H), 9.73 (d, J = 1.3 Hz, 1H), 9.19 (d, J = 8.3 Hz, 1H), 9.03-8.94 (m, 1H), 8.69-8.62 (m, 2H), 8.15- 8.07 (m, 3H), 8.02-7.77 (m, 3H), 3.29 (d, J = 4.3 Hz, 3H), 2.65 DMSO >98 G2/AQ3 (s, 3H). 1352 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.44 (brs, 1H), 9.74 (s, 1H), 9.19 (d, J = 7.3 Hz, 1H), 8.99 (d, J = 5.2 Hz, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.03-7.90 (m, 1H), 7.83 (d, J = DMSO >98 G2/AQ3 8.2 Hz, 1H), 7.72-7.62 (m, 1H), 7.53 (d, J = 9.6 Hz, 3H), 3.32 (d, J = 4.0 Hz, 3H). 1353 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.48 (brs, 1H), 9.77 (s, 1H), 9.29- 9.23 (m, 1H), 9.05-8.97 (m, 1H), 8.74-8.59 (m, 2H), 8.20- 8.08 (m, 1H), 8.02-7.95 (m, 1H), 7.90 (s, DMSO >98 G2/AQ3 1H), 7.84-7.79 (m, 1H), 7.68-7.57 (m, 2H), 3.35- 3.29 (m, 3H). 1354 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.35 (brs, 1H), 9.72 (d, J = 2.0 Hz, 1H), 9.21- 9.11 (m, 1H), 8.98 (dd, J = 5.1, 1.4 Hz, 1H), 8.65 (d, J = 8.7 Hz, 1H), 8.59 (s, 1H), 8.09 (dd, DMSO >98 G2/AQ3 J = 8.8, 1.7 Hz, 1H), 7.95-7.82 (m, 3H), 7.70- 7.60 (m, 2H), 3.30 (d, J = 4.4 Hz, 3H). 1355 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.51 (brs, 1H), 9.77 (d, J = 1.9 Hz, 1H), 9.22 (d, J = 8.2 Hz, 1H), 9.01 (dd, J = 5.1, 1.4 Hz, 1H), 8.69 (s, 1H), 8.40 (d, J = 8.7 Hz, 1H), 8.17 (dd, DMSO >98 G2/AQ3 J = 8.7, 1.6 Hz, 1H), 7.96 (dd, J = 8.1, 5.2 Hz, 1H), 7.30-7.15 (m, 2H), 7.10 (dd, J = 7.3, 1.9 Hz, 1H), 3.89 (s, 3H), 3.59 (s, 3H), 3.30 (d, J = 4.5 Hz, 3H). 1356 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.42 (s, 1H), 9.71 (d, J = 1.8 Hz, 1H), 9.12 (d, J = 8.1 Hz, 1H), 8.97 (dd, J = 5.1, 1.5 Hz, 1H), 8.71 (s, 1H), 8.30 (d, J = 8.7 Hz, 1H), 8.19 (dd, J = 8.7, 1.6 Hz, 1H), 7.90 (dd, J = 7.9, 5.1 Hz, DMSO >98 G2/AQ3 1H), 7.18-7.06 (m, 2H), 7.01 (dd, J = 8.9, 3.1 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 3.30 (d, J = 4.4 Hz, 3H). 1357 0 HCl .sup.1H NMR (300 MHz, DMSO) 10.21 (brs, 1H), 9.63 (s, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.93 (d, J = 3.7 Hz, 1H), 8.87 (s, 1H), 8.37 (d, J = 8.9 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.91- 7.78 (m, 1H), 7.05 (d, J = 2.1 DMSO >98 G2/AQ3 Hz, 2H), 6.66- 6.58 (m, 1H), 3.87 (s, 6H), 3.31 (d, J = 4.2 Hz, 3H). 1358 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.43 (brs, 1H), 9.73 (d, J = 1.8 Hz, 1H), 9.17 (d, J = 8.2 Hz, 1H), 8.99 (dd, J = 5.0, 1.3 Hz, 1H), 8.69 (d, J = 8.6 Hz, 1H), 8.49 (s, 1H), 8.05-7.88 DMSO >98 G2/AQ3 (m, 2H), 7.71 (t, J = 7.9 Hz, 1H), 7.64-7.50 (m, 1H), 7.50-7.33 (m, 2H), 3.32 (d, J = 4.3 Hz, 3H). 1359 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.29 (s, 1H), 9.70 (d, J = 1.7 Hz, 1H), 9.14 (d, J = 8.3 Hz, 1H), 8.97 (dd, J = 5.1, 1.3 Hz, 1H), 8.63 (d, J = 8.7 Hz, 1H), 8.58 (s, 1H), 8.15-8.04 DMSO >98 G2/AQ3 (m, 1H), 7.90 (dd, J = 8.0, 5.1 Hz, 1H), 7.75- 7.57 (m, 3H), 7.43-7.30 (m, 1H), 3.30 (d, J = 4.3 Hz, 3H). 1360 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.41 (brs, 1H), 9.73 (d, J = 1.9 Hz, 1H), 9.16 (d, J = 8.3 Hz, 1H), 8.98 (dd, J = 5.1, 1.4 Hz, 1H), 8.65 (d, J = 8.8 Hz, 1H), 8.60 (s, 1H), 8.12-8.02 DMSO >98 G2/AQ3 (m, 1H), 8.00- 7.84 (m, 3H), 7.49-7.33 (m, 2H), 3.30 (d, J = 4.4 Hz, 3H).

(416) TABLE-US-00033 1361 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.39 (s, 1H), 9.71 (d, J = 1.8 Hz, 1H), 9.17-9.08 (m, 1H), 8.97 (dd, J = 5.1, 1.5 Hz, 1H), 8.64 (d, J = 8.7 Hz, 1H), 8.58 (s, 1H), 8.07 (dd, J = 8.6, DMSO >98 G2/AQ3 1.7 Hz, 1H), 7.88 (dd, J = 8.1, 5.2 Hz, 1H), 7.70-7.58 (m, 2H), 7.46 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 7.4 Hz, 1H), 3.30 (d, J = 4.4 Hz, 3H), 2.43 (s, 3H). 1362 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.37 (brs, 1H), 9.70 (d, J = 1.7 Hz, 1H), 9.10 (d, J = 8.1 Hz, 1H), 8.96 (dd, J = 5.0, 1.4 Hz, 1H), 8.62 (d, J = 8.7 Hz, 1H), 8.58 (s, 1H), 8.08 (dd, DMSO >98 G2/AQ3 J = 8.6, 1.6 Hz, 1H), 7.87 (dd, J = 7.9, 5.0 Hz, 1H), 7.74 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 3.30 (d, J = 4.4 Hz, 3H), 2.40 (s, 3H). 1363 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.82 (brs, 1H), 9.65 (s, 1H), 9.14- 9.02 (m, 1H), 9.02-8.90 (m, 1H), 8.64-8.51 (m, 1H), 8.20 (s, 1H), 8.07 (d, J = 7.8 Hz, 1H), 8.00-7.85 (m, DMSO >98 G2/AQ3 3H), 7.85-7.66 (m, 2H), 3.30 (s, 3H). 1364 HCl .sup.1H NMR (300 MHz, DMSO) 9.83 (brs, 1H), 9.68-9.63 (m, 1H), 9.12-9.02 (m, 1H), 9.01-8.91 (m, 1H), 8.56 (d, J = 9.2 Hz, 1H), 8.42 (s, 1H), 8.35 (s, 1H), 8.19 (d, J = 8.7 Hz, DMSO >98 G2/AQ3 1H), 8.13 (d, J = 9.3 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.93-7.84 (m, 1H), 7.79 (t, J = 8.2 Hz, 1H), 3.28 (d, J = 4.5 Hz, 3H). 1365 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.27 (brs, 1H), 9.72 (s, 1H), 9.23- 9.10 (m, 1H), 8.98 (s, 1H), 8.77- 8.55 (m, 2H), 8.18-7.86 (m, 6H), 3.34-3.27 (m, 3H). DMSO >98 G2/AQ3 1366 .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J = 2.0 Hz, 1H), 8.79 (dt, J = 7.9, 1.9 Hz, 1H), 8.69 (dd, J = 4.7, 1.6 Hz, 1H), 8.65-8.53 (m, 2H), 8.22-8.12 (m, 3H), 7.92 (dd, J = 8.8, 1.5 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), DMSO >98 G2/AQ3 7.80 (d, J = 8.8 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 4.11 (s, 3H), 3.20 (d, J = 4.4 Hz, 3H). 1367 0 .sup.1H NMR (300 MHz, DMSO) 11.10 (s, 1H), 9.63 (d, J = 2.0 Hz, 1H), 8.85 (d, J = 1.7 Hz, 1H), 8.81-8.70 (m, 2H), 8.39 (dd, J = 8.9, 1.9 Hz, 1H), 8.15-8.02 (m, 5H), 7.60 (dd, J = 8.0, 4.8 Hz, 1H), 2.65 (s, 3H), DMSO >98 G2/AQ3 2.61 (s, 3H). 1368 HCl .sup.1H NMR (300 MHz, DMSO) 9.72 (d, J = 1.8 Hz, 1H), 9.27-9.21 (m, 1H), 8.97 (dd, J = 5.3, 1.4 Hz, 1H), 8.50 (dd, J = 8.8, 2.1 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.15- 8.09 (m, 2H), DMSO >98 G2/AQ3 8.09-7.98 (m, 3H), 3.55 (s, 3H), 2.65 (s, 3H), 2.22 (s, 3H). 1369 HCl .sup.1H NMR (300 MHz, DMSO) 11.16 (s, 1H), 9.67 (s, 1H), 9.20 (d, J = 8.2 Hz, 1H), 8.97 (d, J = 4.3 Hz, 1H), 8.75 (s, 1H), 8.23 (d, J = 8.7 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 8.02 (dd, J = 8.0, 5.5 Hz, 1H), 7.66-7.47 DMSO >98 G2/AQ3 (m, 2H), 7.47- 7.34 (m, 1H), 2.56 (s, 3H). 1370 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.17 (brs, 1H), 9.68 (d, J = 2.0 Hz, 1H), 9.06 (d, J = 8.0 Hz, 1H), 8.95 (dd, J = 5.0, 1.4 Hz, 1H), 8.77 (s, 1H), 8.31 (s, 2H), 8.16 (d, J = 2.1 Hz, 1H), 7.87 (dd, J = 7.8, 5.2 Hz, 1H), DMSO >98 G2/AQ3 7.72 (d, J = 7.8 Hz, 1H), 7.61- 7.47 (m, 2H), 7.19 (d, J = 1.4 Hz, 1H), 3.31 (d, J = 4.4 Hz, 3H). 1371 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.28 (brs, 1H), 9.71 (s, 1H), 9.16 (d, J = 7.9 Hz, 1H), 8.98 (d, J = 4.2 Hz, 1H), 8.67 (d, J = 8.9 Hz, 1H), 8.45 (s, 1H), 8.01-7.83 (m, 2H), 7.68-7.50 DMSO >98 G2/AQ3 (m, 2H), 7.50- 7.35 (m, 1H), 3.31 (d, J = 4.1 Hz, 3H). 1372 HCl .sup.1H NMR (300 MHz, DMSO) 9.72-9.45 (m, 2H), 8.95 (d, J = 7.6 Hz, 1H), 8.88 (d, J = 3.8 Hz, 1H), 8.49 (d, J = 8.5 Hz, 1H), 8.13 (s, 1H), 7.91-7.75 (m, 3H), 7.53- 7.43 (m, 1H), DMSO >98 G2/AQ3 7.36-7.25 (m, 1H), 3.27 (d, J = 4.3 Hz, 3H). 1373 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.04 (brs, 1H), 9.70 (s, 1H), 9.22-9.07 (m, 1H), 8.93 (s, 1H), 8.62 (d, J = 7.6 Hz, 1H), 8.55 (s, 1H), 8.06 (d, J = 8.9 Hz, 1H), 7.99-7.79 (m, DMSO >98 G2/AQ3 2H), 7.79-7.55 (m, 2H), 3.33-3.27 (m, 3H). 1374 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 9.34 (brs, 1H), 9.06- 8.92 (m, 1H), 8.86 (s, 1H), 8.50- 8.37 (m, 1H), 8.25 (s, 1H), 8.11- 7.95 (m, 1H), 7.85-7.74 (m, 1H), 7.74-7.57 (m, 2H), 7.43- 7.29 (m, 1H), 3.28- DMSO >98 G2/AQ3 3.21 (m, 3H). 1375 HCl .sup.1H NMR (300 MHz, DMSO) 9.63 (d, J = 1.6 Hz, 1H), 9.38 (brs, 1H), 9.01-8.91 (m, 1H), 8.84 (dd, J = 5.0, 1.6 Hz, 1H), 8.60 (s, 1H), 8.08 (s, 2H), 7.76 (dd, J = 7.9, 5.1 Hz, 1H), 7.64-7.38 (m, 2H), 3.26 (d, J = DMSO >98 G2/AQ3 3.7 Hz, 3H). 1376 HCl .sup.1H NMR (300 MHz, DMSO) 9.88 (brs, 1H), 9.65 (s, 1H), 9.18- 8.99 (m, 1H), 8.90 (s, 1H), 8.70 (s, 1H), 8.31-8.03 (m, 2H), 7.94- 7.77 (m, 2H), 7.77-7.57 (m, 1H), 3.28 (s, 3H). DMSO >98 G2/AQ3 1377 00 01 02 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.33 (s, 1H), 9.67 (s, 1H), 9.10 (d, J = 7.8 Hz, 1H), 9.02 (s, 1H), 8.92 (d, J = 5.0 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.25 (d, J = 8.8 Hz, 1H), 8.03- 7.76 (m, 3H), 3.31 (s, 3H). DMSO >98 G2/AQ3 1378 03 04 05 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J = 1.7 Hz, 1H), 9.56-9.34 (m, 1H), 9.26- 9.10 (m, 1H), 9.05 (d, J = 4.7 Hz, 1H), 8.44 (s, 1H), 8.19 (dd, J = 8.1, 5.7 Hz, 1H), 7.95 (d, J = DMSO >98 G2/AQ3 11.5 Hz, 1H), 7.63-7.45 (m, 2H), 7.45-7.26 (m, 1H), 3.19 (d, J = 4.4 Hz, 3H). 1379 06 07 08 HCl .sup.1H NMR (300 MHz, DMSO) 9.67-9.59 (m, 1H), 9.38 (d, J = 8.3 Hz, 1H), 9.22- 9.10 (m, 1H), 9.03 (d, J = 4.9 Hz, 1H), 8.37 (s, 1H), 8.16 (dd, J = 8.1, 5.6 Hz, 1H), 7.89 (d, J = DMSO >98 G2/AQ3 11.6 Hz, 1H), 7.78 (td, J = 8.9, 6.6 Hz, 1H), 7.54-7.36 (m, 1H), 7.30 (td, J = 8.3, 2.0 Hz, 1H), 3.18 (d, J = 4.4 Hz, 3H). 1380 09 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.72 (d, J = 1.6 Hz, 1H), 9.25- 9.14 (m, 1H), 8.99 (dd, J = 5.2, Hz, 1H), 8.51 (s, 1H), 8.44 (d, J = 8.7 Hz, 1H), 8.26-8.11 (m, 1H), 7.94 (dd, DMSO >98 G2/AQ3 J = 8.0, 5.2 Hz, 1H), 7.65-7.49 (m, 2H), 7.49- 7.29 (m, 1H), 3.69 (s, 6H). 1381 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.71 (s, 1H), 9.18 (d, J = 8.0 Hz, 1H), 8.98 (d, J = 5.1 Hz, 1H), 8.49-8.36 (m, 2H), 8.16 (d, J = 8.8 Hz, 1H), 7.99- 7.86 (m, 1H), 7.86-7.72 (m, DMSO >98 G2/AQ3 1H), 7.46 (t, J = 10.2 Hz, 1H), 7.29 (t, J = 8.5 Hz, 1H), 3.69 (s, 6H). 1382 HCl .sup.1H NMR (300 MHz, DMSO) 10.25 (brs, 1H), 9.66 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 8.2 Hz, 1H), 8.94 (dd, J = 5.0, 1.6 Hz, 1H), 8.70 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 8.16 (dd, J = 8.7, 1.5 Hz, 1H), 7.84 (dd, DMSO >98 G2/AQ3 J = 8.0, 5.1 Hz, 1H), 7.71 (dd, J = 8.0, 1.4 Hz, 1H), 7.65-7.55 (m, 2H), 3.90 (s, 3H), 3.29 (d, J = 4.5 Hz, 3H), 2.64 (s, 3H). 1383 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.18 (brs, 1H), 9.68 (d, J = 1.8 Hz, 1H), 9.17 (d, J = 8.0 Hz, 1H), 8.99 (dd, J = 5.2, 1.4 Hz, 1H), 8.86 (s, 1H), 8.31 (d, J = 8.7 Hz, 1H), 8.22 (d, J = DMSO >98 G2/AQ3 8.8 Hz, 1H), 7.97 (dd, J = 8.0, 5.3 Hz, 1H), 7.64-7.49 (m, 2H), 7.49-7.34 (m, 1H), 4.06- 3.92 (m, 2H), 3.73 (t, J = 5.5 Hz, 2H), 3.33 (s, 3H). 1384 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.18 (brs, 1H), 9.67 (d, J = 1.6 Hz, 1H), 9.14 (d, J = 8.1 Hz, 1H), 8.99 (dd, J = 5.2, 1.5 Hz, 1H), 8.80 (s, 1H), 8.29 (d, J = 8.7 Hz, 1H), 8.18 (d, J = DMSO >98 G2/AQ3 8.7 Hz, 1H), 7.95 (dd, J = 8.2, 5.2 Hz, 1H), 7.79 (td, J = 8.9, 6.6 Hz, 1H), 7.50 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.33 (td, J = 8.3, 2.3 Hz, 1H), 4.08-3.94 (m, 3H), 3.73 (t, J = 5.5 Hz, 3H), 3.32 (s, 3H). 1385 2 HCl .sup.1H NMR (300 MHz, DMSO) 10.33 (brs, 1H), 9.70 (d, J = 1.7 Hz, 1H), 9.15 (d, J = 8.2 Hz, 1H), 8.99 (dd, J = 5.2, 1.5 Hz, 1H), 8.81 (s, 1H), 8.33 (d, J = 8.7 Hz, 1H), 8.18 (d, J = DMSO >98 G2/AQ3 8.7 Hz, 1H), 7.95 (dd, J = 8.1, 5.2 Hz, 1H), 7.81 (td, J = 8.9, 6.6 Hz, 1H), 7.49 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.32 (td, J = 8.5, 2.2 Hz, 1H), 3.96-3.78 (m, 2H), 3.48 (t, J = 6.1 Hz, 2H), 3.27 (s, 3H), 2.14-1.93 (m, 2H). 1386 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.73 (s, 1H), 9.17 (d, J = 8.4 Hz, 1H), 8.99 (s, 1H), 8.52 (s, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.21 (d, J = 9.0 Hz, 1H), 8.02-7.90 (m, 1H), 7.87-7.78 (m, 1H), 7.57-7.38 (m, 1H), 7.38-7.24 DMSO >98 G2/AQ3 (m, 1H), 4.31-4.18 (m, 4H), 2.08 (s, 4H). 1387 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.7 Hz, 1H), 9.17 (d, J = 8.3 Hz, 1H), 8.99 (dd, J = 5.2, 1.5 Hz, 1H), 8.34 (d, J = 8.6 Hz, 1H), 8.24-8.12 (m, 2H), 7.97 (dd, J = 8.0, 5.2 Hz, 1H), 7.81 (td, J = 8.9, 6.6 Hz, 1H), 7.49 (ddd, J = DMSO >98 G2/AQ3 11.6, 9.3, 2.5 Hz, 1H), 7.30 (td, J = 8.4, 2.1 Hz, 1H), 4.16 (brs, 4H), 1.80 (brs, 6H). 1388 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.7 Hz, 1H), 9.26 (d, J = 8.3 Hz, 1H), 9.01 (dd, J = 5.3, 1.4 Hz, 1H), 8.37- 8.19 (m, 2H), 8.15 (d, J = 8.7 Hz, 1H), 8.02 (dd, J = 8.1, 5.3 Hz, 1H), 7.81 (td, J = 8.9, 6.5 Hz, 1H), 7.48 DMSO >98 G2/AQ3 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.30 (td, J = 8.4, 2.3 Hz, 1H), 4.23-4.12 (m, 4H), 3.90-3.80 (m, 4H). 1389 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.7 Hz, 1H), 9.17 (d, J = 8.2 Hz, 1H), 8.99 (dd, J = 5.2, 1.5 Hz, 1H), 8.34 (d, J = 8.7 Hz, 1H), 8.27-8.13 (m, 2H), 7.97 (dd, J = 8.1, 5.4 Hz, 1H), 7.67-7.48 (m, 2H), 7.41 (ddd, J = 14.7, 9.9, 4.9 DMSO >98 G2/AQ3 Hz, 1H), 4.16 (brs, 4H), 1.80 (brs, 6H). 1390 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.8 Hz, 1H), 9.26 (d, J = 8.3 Hz, 1H), 9.01 (dd, J = 5.3, 1.4 Hz, 1H), 8.36- 8.23 (m, 2H), 8.18 (d, J = 8.7 Hz, 1H), 8.03 (dd, J = 8.0, 5.4 Hz, 1H), 7.64- 7.46 (m, 2H), 7.46-7.29 (m, DMSO >98 G2/AQ3 1H), 4.23-4.16 (m, 4H), 3.85 (d, J = 4.7 Hz, 4H). 1391 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.7 Hz, 1H), 9.18 (d, J = 8.2 Hz, 1H), 9.00 (dd, J = 5.2, 1.2 Hz, 1H), 8.62 (s, 1H), 8.39 (d, J = 8.7 Hz, 1H), 8.21 (d, J = 8.8 Hz, 1H), 7.98 (dd, DMSO >98 G2/AQ3 J = 8.0, 5.2 Hz, 1H), 7.64-7.47 (m, 2H), 7.46- 7.27 (m, 1H), 4.26 (t, J = 5.2 Hz, 2H), 3.85 (t, J = 5.3 Hz, 2H), 3.72 (s, 3H), 3.33 (s, 3H). 1392 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.67 (d, J = 1.7 Hz, 1H), 9.15 (d, J = 8.1 Hz, 1H), 8.99 (d, J = 4.1 Hz, 1H), 8.56 (s, 1H), 8.36 (d, J = 8.7 Hz, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.96 (dd, J = 8.1, DMSO >98 G2/AQ3 5.2 Hz, 1H), 7.86- 7.70 (m, 1H), 7.55- 7.40 (m, 1H), 7.30 (td, J = 8.5, 2.2 Hz, 1H), 4.36-4.18 (m, 2H), 3.88- 3.77 (m, 2H), 3.72 (s, 3H), 3.33 (s, 3H). 1393 0 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.7 Hz, 1H), 9.24-9.06 (m, 1H), 8.99 (dd, J = 5.1, 1.5 Hz, 1H), 8.52 (s, 1H), 8.40 (d, J = 8.7 Hz, 1H), 8.30-8.14 (m, 1H), 7.93 (dd, J = 8.0, DMSO >98 G2/AQ3 5.2 Hz, 1H), 7.63-7.46 (m, 2H), 7.46-7.25 (m, 1H), 4.22- 4.11 (m, 2H), 3.73 (s, 3H), 3.59 (t, J = 5.9 Hz, 2H), 2.10-1.92 (m, 2H). 1394 2 HCl .sup.1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.7 Hz, 1H), 9.11 (d, J = 8.3 Hz, 1H), 8.97 (dd, J = 5.1, 1.5 Hz, 1H), 8.46 (s, 1H), 8.36 (d, J = 8.7 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.90 DMSO >98 G2/AQ3 (dd, J = 8.1, 5.2 Hz, 1H), 7.80 (td, J = 8.9, 6.6 Hz, 1H), 7.47 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.29 (td, J = 8.4, 2.1 Hz, 1H), 4.22-4.08 (m, 2H), 3.72 (s, 3H), 3.59 (t, J = 5.9 Hz, 2H), 2.10- 1.94 (m, 2H). 1395 HCl .sup.1H NMR (300 MHz, DMSO) 9.97- 9.66 (m, 2H), 9.66-9.58 (m, 1H), 9.17-9.05 (m, 1H), 8.99 (dd, J = 5.2, 1.5 Hz, 1H), 8.66 (d, J = 8.6 Hz, 1H), 8.50 (s, 1H), DMSO >98 G2/AQ3 8.01-7.88 (m, 2H), 7.62 (ddd, J = 9.1, 6.1, 3.1 Hz, 1H), 7.58- 7.36 (m, 2H). 1396 HCl .sup.1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.8 Hz, 1H), 9.16 (d, J = 8.3 Hz, 1H), 8.98 (d, J = 3.9 Hz, 1H), 8.58-8.42 (m, 2H), 8.00- 7.82 (m, 2H), 7.69-7.38 (m, 3H), 3.69 (s, 6H). DMSO >98 G2/AQ3

(417) TABLE-US-00034 1397 0 HCl .sup.1H NMR (400 MHz, DMSO) 10.47 (s, 1H), 9.68 (d, J = 1.8 Hz, 1H), 9.11 (d, J = 8.0 Hz, 1H), 9.04 (s, 1H), 8.96 (dd, J = 5.1, 1.4 Hz, 1H), 8.41 (dd, J = 8.8, 1.6 Hz, 1H), 8.30 (d, J = 8.7 Hz, 1H), DMSO >98 AQ4 8.14 (d, J = 8.2 Hz, 2H), 7.90 (d, J = 8.4 Hz, 3H), 3.34 (t, J = 17.1 Hz, 3H). 1398 HCl .sup.1H NMR (400 MHz, DMSO) 10.15 (s, 1H), 9.65 (d, J = 1.7 Hz, 1H), 9.06 (d, J = 7.9 Hz, 1H), 8.99-8.90 (m, 2H), 8.44 (d, J = 7.2 Hz, 1H), 8.28- 8.17 (m, 3H), 7.94-7.76 (m, 3H), 3.32 (d, J = 4.5 Hz, 3H). DMSO >98 AQ4 1399 HCl .sup.1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.65 (d, J = 2.1 Hz, 1H), 9.10-9.00 (m, 1H), 8.96 (dd, J = 5.1, 1.5 Hz, 1H), 8.65 (s, 1H), 8.26-8.17 (m, 1H), 8.16- 8.07 (m, 1H), 7.90 (dd, J = 7.8, 5.3 Hz, 1H), DMSO >98 AQ4 7.77-7.69 (m, 1H), 7.68-7.55 (m, 3H), 3.29 (d, J = 4.6 Hz, 3H). 1400 0 HCl .sup.1H NMR (400 MHz, DMSO) 9.77 (s, 1H), 9.63 (d, J = 1.7 Hz, 1H), 9.04-8.85 (m, 2H), 8.63 (s, 1H), 8.12 (q, J = 8.7 Hz, 2H), 7.83 (dd, J = 7.8, 4.9 Hz, 1H), 7.38- 7.25 (m, 2H), DMSO >98 AQ4 7.25-7.17 (m, 1H), 3.92 (s, 3H). 1401 HCl .sup.1H NMR (400 MHz, DMSO) 10.05 (s, 1H), 9.64 (d, J = 1.7 Hz, 1H), 9.04 (d, J = 7.6 Hz, 1H), 8.99-8.92 (m, 1H), 8.89 (s, 1H), 8.41 (d, J = 8.8 Hz, 1H), 8.33- 8.20 (m, 2H), 8.16 DMSO >98 AQ4 (d, J = 8.6 Hz, 1H), 7.94-7.84 (m, 1H), 7.81- 7.68 (m, 1H), 3.32 (d, J = 4.5 Hz, 3H). 1402 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.30 (s, 1H), 9.68 (d, J = 1.8 Hz, 1H), 9.15-9.05 (m, 1H), 8.97 (dd, J = 5.1, 1.4 Hz, 1H), 8.52 (s, 1H), 8.10 (s, 1H), 7.96-7.82 (m, 1H), 7.67-7.55 DMSO >98 AQ5 (m, 1H), 7.42- 7.26 (m, 3H), 3.31 (d, J = 4.5 Hz, 3H), 2.40 (s, 3H). 1403 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.87 (s, 1H), 9.59 (d, J = 1.5 Hz, 1H), 9.00-8.89 (m, 2H), 8.42 (s, 1H), 7.93-7.80 (m, 2H), 7.62- 7.54 (m, 1H), 7.49-7.36 (m, 3H), 3.30 (d, J = 4.6 DMSO >98 AQ5 Hz, 3H), 2.32 (s, 3H). 1404 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.19 (s, 1H), 9.68-9.61 (m, 1H), 9.05-8.98 (m, 1H), 8.94 (dd, J = 5.0, 1.6 Hz, 1H), 8.48 (d, J = 5.7 Hz, 1H), 8.02 (s, 1H), 7.91-7.82 (m, DMSO >98 AQ5 1H), 7.59-7.50 (m, 2H), 7.43- 7.36 (m, 2H), 3.31 (d, J = 4.6 Hz, 3H), 2.40 (s, 3H). 1405 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.11 (s, 1H), 9.69-9.61 (m, 1H), 9.11-9.02 (m, 1H), 8.95 (dd, J = 5.1, 1.5 Hz, 1H), 8.52 (s, 1H), 8.05 (s, 1H), 7.89 (dd, J = 8.1, 5.1 Hz, 1H), DMSO >98 AQ5 7.68-7.56 (m, 1H), 7.48-7.38 (m, 1H), 7.33- 7.25 (m, 1H), 3.31 (d, J = 4.6 Hz, 3H), 2.33 (s, 3H). 1406 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.03 (s, 1H), 9.63 (dd, J = 2.2, 0.7 Hz, 1H), 9.09-9.00 (m, 1H), 8.95 (dd, J = 5.1, 1.6 Hz, 1H), 8.48 (s, 1H), 8.00 (s, 1H), 7.89 (dd, J = 7.9, 5.2 Hz, 1H), 7.54- 7.35 (m, 3H), DMSO >98 AQ5 3.30 (d, J = 4.6 Hz, 3H), 2.33 (s, 3H). 1407 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.08-8.98 (m, 1H), 8.95 (dd, J = 5.1, 1.5 Hz, 1H), 8.46 (s, 1H), 7.98 (s, 1H), 7.87 (dd, J = 8.1, 5.1 Hz, 1H), DMSO >98 AQ5 7.64 (ddt, J = 16.8, 14.3, 5.3 Hz, 2H), 7.40- 7.30 (m, 1H), 3.30 (d, J = 4.6 Hz, 3H), 2.41 (s, 3H). 1408 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.92 (s, 1H), 9.61 (d, J = 1.6 Hz, 1H), 9.03-8.97 (m, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.42 (s, 1H), 7.93 (s, 1H), 7.87 (dd, J = 8.1, 5.0 Hz, 1H), 7.44- 7.36 (m, 1H), 7.33-7.23 (m, DMSO >98 AQ5 2H), 3.29 (d, J = 4.6 Hz, 3H), 2.41 (s, 3H). 1409 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.11 (s, 1H), 9.64 (d, J = 2.2 Hz, 1H), 9.10-9.03 (m, 1H), 8.96 (dd, J = 5.1, 1.5 Hz, 1H), 8.49 (s, 1H), 8.05-7.94 (m, 3H), 7.94- 7.88 (m, 1H), DMSO >98 AQ5 7.88-7.82 (m, 1H), 7.77 (t, J = 7.7 Hz, 1H), 3.31 (d, J = 4.5 Hz, 3H), 2.40 (s, 3H). 1410 00 01 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.22 (s, 1H), 9.67 (d, J = 1.6 Hz, 1H), 9.14-9.07 (m, 1H), 8.97 (dd, J = 5.1, 1.5 Hz, 1H), 8.52 (s, 1H), 8.10-8.00 (m, 3H), 7.91 (dd, J = 7.9, 5.3 DMSO >98 AQ5 Hz, 1H), 7.75- 7.67 (m, 2H), 3.31 (d, J = 4.5 Hz, 3H), 2.39 (s, 3H). 1411 02 03 04 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.20-9.85 (m, 1H), 9.58 (s, 1H), 8.94-8.85 (m, 2H), 8.38 (s, 1H), 7.88-7.76 (m, 2H), 7.54- 7.44 (m, 1H), 7.24-7.16 (m, 2H), 7.12 (td, DMSO >98 AQ5 J = 7.4, 0.9 Hz, 1H), 3.76 (s, 3H), 3.31 (d, J = 4.5 Hz, 3H), 2.24 (s, 3H). 1412 05 06 07 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.69-9.61 (m, 1H), 9.01 (d, J = 7.8 Hz, 1H), 8.93 (dd, J = 5.0, 1.6 Hz, 1H), 8.49 (s, 1H), 8.06 (s, 1H), 7.83 DMSO >98 AQ5 (dd, J = 8.0, 5.1 Hz, 1H), 7.51- 7.41 (m, 1H), 7.13-7.05 (m, 1H), 7.05-6.95 (m, 2H), 3.81 (d, J = 10.8 Hz, 3H), 3.31 (d, J = 4.6 Hz, 3H), 2.41 (s, 3H). 1413 08 09 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.09 (s, 1H), 9.60 (s, 1H), 9.00- 8.88 (m, 2H), 8.42 (s, 1H), 7.94 (s, 1H), 7.86-7.78 (m, 1H), 7.48- 7.39 (m, 2H), 7.16-7.06 (m, 2H), 3.85 (s, 3H), DMSO >98 AQ5 3.31 (d, J = 4.6 Hz, 3H), 2.43 (s, 3H). 1414 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.02 (s, 1H), 9.63 (s, 1H), 9.05- 8.91 (m, 2H), 8.36 (s, 1H), 8.10- 7.99 (m, 1H), 7.91-7.80 (m, 1H), 7.59-7.50 (m, 2H), 7.44- 7.32 (m, 2H), 3.27 DMSO >98 AQ5 (d, J = 4.5 Hz, 3H), 2.45 (s, 3H). 1415 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.01 (s, 1H), 9.65 (s, 1H), 9.10- 8.99 (m, 1H), 8.97 (d, J = 5.0 Hz, 1H), 8.41 (s, 1H), 8.09 (s, 1H), 7.97-7.83 (m, 1H), 7.61-7.41 (m, 2H), 7.31 (td, DMSO >98 AQ5 J = 8.4, 2.2 Hz, 1H), 3.26 (d, J = 4.5 Hz, 3H), 2.35 (s, 3H). 1416 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.01-9.69 (m, 1H), 9.61 (s, 1H), 8.94 (m, J = 5.0 Hz, 2H), 8.36 (s, 1H), 7.99 (s, 1H), 7.92- 7.81 (m, 1H), 7.71-7.57 (m, 2H), 7.41-7.31 (m, 1H), 3.26 (d, J = 4.5 Hz, 3H), DMSO >98 AQ5 2.47 (s, 3H). 1417 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.90 (s, 1H), 9.63 (d, J = 1.8 Hz, 1H), 9.08-8.89 (m, 2H), 8.40 (s, 1H), 8.02 (s, 1H), 7.92-7.81 (m, 1H), 7.44-7.25 (m, 3H), 3.27 (d, J = 4.5 Hz, 3H), 2.49 (s, 3H). DMSO >98 AQ5 1418 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.99 (s, 1H), 9.62 (s, 1H), 8.95 (d, J = 5.0 Hz, 2H), 8.27 (s, 1H), 8.11- 7.99 (m, 1H), 7.89-7.80 (m, 1H), 7.53-7.45 (m, 1H), 7.24 (dd, J = 7.4, 1.7 DMSO >98 AQ5 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.12 (td, J = 7.4, 0.9 Hz, 1H), 3.74 (d, J = 8.9 Hz, 3H), 3.26 (d, J = 4.6 Hz, 3H), 2.28 (s, 3H). 1419 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.30 (s, 1H), 9.72 (d, J = 1.6 Hz, 1H), 9.20-9.10 (m, 1H), 8.98 (dd, J = 5.1, 1.5 Hz, 1H), 8.45 (s, 1H), 8.21 (s, 1H), 7.91 (dd, J = 8.0, 5.1 Hz, 1H), 7.48-7.40 (m, 1H), 7.08-7.01 (m, 3H), 3.84 (s, DMSO >98 AQ5 3H), 3.26 (d, J = 4.5 Hz, 3H), 2.45 (s, 3H). 1420 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.08-9.71 (m, 1H), 9.58 (d, J = 2.0 Hz, 1H), 8.96-8.83 (m, 2H), 8.31 (s, 1H), 7.94 (s, 1H), 7.87- 7.79 (m, 1H), 7.47-7.39 (m, 2H), 7.10 (d, J = DMSO >98 AQ5 8.8 Hz, 2H), 3.84 (s, 3H), 3.27 (d, J = 4.5 Hz, 3H), 2.47 (s, 3H). 1421 2 HCl 1H NMR (400 MHz, DMSO) 9.69-9.63 (m, 1H), 9.10-8.93 (m, 3H), 8.12 (d, J = 8.4 Hz, 1H), 7.90-7.82 (m, 2H), 7.68-7.58 (m, 1H), 7.56- 7.48 (m, 1H), 7.30-7.22 (m, 1H), 3.35 (d, J = 4.6 Hz, 3H), 2.73 DMSO >98 AQ4 (s, 3H). 1422 2 HCl 1H NMR (400 MHz, DMSO) 9.62 (s, 1H), 8.95 (d, J = 5.0 Hz, 3H), 8.03 (s, 1H), 7.85 (t, J = 9.9 Hz, 2H), 7.44- 7.34 (m, 1H), 7.17 (dd, J = 8.2, 2.2 Hz, 2H), 3.34 (d, J = 4.5 Hz, 3H), 2.73 (s, 3H). DMSO >98 AQ4 1423 0 2 HCl 1H NMR (400 MHz, DMSO) 9.62 (d, J = 2.1 Hz, 1H), 9.00- 8.75 (m, 3H), 8.08-7.99 (m, 1H), 7.99-7.93 (m, 1H), 7.93-7.79 (m, 3H), 7.79- 7.73 (m, 2H), 3.34 (d, J = 4.5 Hz, 3H), 2.70 (s, 3H). DMSO >98 AQ4 1424 2 HCl 1H NMR (400 MHz, DMSO) 9.61 (s, 1H), 8.99- 8.63 (m, 3H), 8.07-7.98 (m, 3H), 7.89-7.78 (m, 2H), 7.65-7.59 (m, 2H), 3.33 (d, J = 4.5 Hz, 3H), 2.70 (s, 3H). DMSO >98 AQ4 1425 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.49 (s, 1H), 9.56 (s, 1H), 9.19 (s, 1H), 8.95 (d, J = 5.3 Hz, 1H), 8.83 (d, J = 5.5 Hz, 1H), 8.73 (d, J = 6.4 Hz, 1H), 8.41 (d, J = 5.6 Hz, 1H), 8.26 DMSO >98 Method AQ3 (s, 1H), 8.09 (s, 1H), 8.02-7.91 (m, 2H), 7.85 (s, 1H), 7.78-7.68 (m, 1H), 7.61- 7.51 (m, 1H), 7.48-7.36 (m, 2H), 5.36 (s, 2H). 1426 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.53 (s, 1H), 9.67 (d, J = 1.8 Hz, 1H), 9.32 (dd, J = 5.8, 4.1 Hz, 1H), 8.97 (dd, J = 5.4, 1.4 Hz, 1H), 8.75 (d, J = 8.7 Hz, 1H), 8.35 (t, J = 7.9 DMSO >98 Method AQ3 Hz, 1H), 8.24 (d, J = 13.5 Hz, 1H), 8.03 (dd, J = 8.1, 5.4 Hz, 1H), 7.92 (dd, J = 13.5, 4.8 Hz, 2H), 7.85-7.73 (m, 2H), 7.53-7.43 (m, 1H), 7.36-7.25 (m, 1H), 5.40 (d, J = 5.6 Hz, 2H), 2.85 (s, 3H). 1427 0 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.42 (s, 1H), 9.64 (d, J = 1.7 Hz, 1H), 9.26 (d, J = 8.1 Hz, 1H), 8.95 (dd, J = 5.3, 1.4 Hz, 1H), 8.71 (d, J = 8.7 Hz, 1H), 8.30 (d, J = 18.0 Hz, 2H), DMSO >98 Method AQ3 8.04-7.84 (m, 3H), 7.74 (dd, J = 7.8, 6.0 Hz, 2H), 7.62-7.33 (m, 3H), 5.38 (d, J = 5.5 Hz, 2H), 2.84 (s, 3H). 1428 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.40 (s, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.24 (d, J = 8.1 Hz, 1H), 8.95 (dd, J = 5.3, 1.4 Hz, 1H), 8.69 (d, J = 8.7 Hz, 1H), 8.41- 8.22 (m, 2H), DMSO >98 Method AQ3 8.09 (dd, J = 8.7, 1.8 Hz, 1H), 8.01- 7.84 (m, 4H), 7.74 (d, J = 7.8 Hz, 1H), 7.46- 7.33 (m, 2H), 5.36 (d, J = 5.5 Hz, 2H), 2.83 (s, 3H). 1429 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.21 (s, 1H), 9.62 (s, 1H), 9.19 (d, J = 7.8 Hz, 1H), 8.93 (d, J = 4.6 Hz, 1H), 8.68 (d, J = 8.6 Hz, 1H), 8.26 (dd, J = 28.0, 20.1 Hz, 2H), 8.04-7.80 DMSO >98 Method AQ3 (m, 3H), 7.72 (d, J = 7.8 Hz, 1H), 7.64-7.50 (m, 2H), 7.46-7.33 (m, 1H), 5.33 (d, J = 5.3 Hz, 2H), 2.81 (s, 3H). 1430 0 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.40 (s, 1H), 9.66 (d, J = 1.8 Hz, 1H), 9.31 (d, J = 8.2 Hz, 1H), 8.96 (dd, J = 5.4, 1.4 Hz, 1H), 8.73 (d, J = 8.7 Hz, 1H), 8.33 (t, J = 7.9 Hz, 1H), DMSO >98 Method AQ3 8.23 (s, 1H), 8.03 (dd, J = 8.1, 5.4 Hz, 1H), 7.93 (dd, J = 11.7, 8.3 Hz, 2H), 7.76 (d, J = 7.9 Hz, 1H), 7.70-7.60 (m, 1H), 7.54- 7.35 (m, 2H), 5.38 (d, J = 5.5 Hz, 2H), 2.85 (s, 3H). 1431 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.15 (s, 1H), 9.61 (s, 1H), 9.22 (t, J = 7.3 Hz, 1H), 8.98-8.90 (m, 1H), 8.65 (dd, J = 8.6, 3.0 Hz, 1H), 8.36- 8.26 (m, 2H), 8.13 (dd, J = 8.7, 1.9 Hz, 1H), 8.05-7.95 (m, DMSO >98 Method AQ3 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.76-7.64 (m, 3H), 7.43-7.33 (m, 1H), 5.33 (s, 2H), 2.82 (s, 3H). 1432 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.26 (s, 1H), 9.62 (d, J = 1.8 Hz, 1H), 9.23 (d, J = 8.2 Hz, 1H), 8.94 (dd, J = 5.4, 1.5 Hz, 1H), 8.78 (s, 1H), 8.30 (t, J = 7.9 Hz, 1H), 8.20-8.15 DMSO >98 Method AQ3 (m, 1H), 8.10 (d, J = 8.7 Hz, 1H), 8.00 (dd, J = 7.9, 5.3 Hz, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.80- 7.71 (m, 2H), 7.59-7.50 (m, 1H), 7.47-7.35 (m, 2H), 5.35 (d, J = 5.5 Hz, 2H), 2.82 (s, 3H). 1433 0 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.39 (s, 1H), 9.61 (d, J = 1.7 Hz, 1H), 9.19 (d, J = 8.2 Hz, 1H), 9.01 (d, J = 1.8 Hz, 1H), 8.93 (dd, J = 5.3, 1.5 Hz, 1H), 8.38 (dd, J = 8.8, 1.9 Hz, 1H), 8.29 (t, J = 7.9 Hz, 1H), DMSO >98 Method AQ3 8.09 (d, J = 8.7 Hz, 1H), 7.97 (dd, J = 8.1, 5.3 Hz, 1H), 7.92-7.80 (m, 3H), 7.72 (d, J = 7.8 Hz, 1H), 7.66-7.57 (m, 1H), 7.35-7.26 (m, 1H), 5.36 (d, J = 5.5 Hz, 2H), 2.81 (s, 3H).

(418) TABLE-US-00035 1434 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.45 (s, 1H), 9.60 (d, J = 1.9 Hz, 1H), 9.19 (d, J = 8.2 Hz, 1H), 9.01-8.89 (m, 2H), 8.36-8.25 (m, 2H), 8.10 (d, J = 8.7 Hz, 1H), 8.05-7.94 (m, DMSO >98 Method AQ3 3H), 7.88 (dd, J = 12.8, 5.4 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.46- 7.35 (m, 2H), 5.36 (d, J = 5.5 Hz, 2H), 2.82 (s, 3H). 1435 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.28 (s, 1H), 9.63 (d, J = 1.8 Hz, 1H), 9.24 (d, J = 8.2 Hz, 1H), 8.95 (d, 1H), 8.83 (s, 1H), 8.30 (t, J = 7.9 Hz, 1H), 8.19 (dd, J = 8.7, 1.8 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 8.00 (dd, DMSO >98 Method AQ3 J = 8.1, 5.4 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.64- 7.51 (m, 2H), 7.46-7.37 (m, 1H), 5.36 (d, J = 5.5 Hz, 2H), 2.82 (s, 3H). 1436 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.02 (s, 1H), 9.56 (d, J = 1.6 Hz, 1H), 9.06 (d, J = 8.0 Hz, 1H), 8.88 (dd, J = 5.2, 1.5 Hz, 1H), 8.75 (s, 1H), 8.25- 8.13 (m, 2H), 8.04 (d, J = 8.7 DMSO >98 Method AQ3 Hz, 1H), 7.89 (dd, J = 7.8, 5.3 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.70-7.60 (m, 2H), 7.53-7.44 (m, 1H), 7.38 (ddd, J = 12.2, 8.4, 3.5 Hz, 1H), 5.27 (d, J = 5.3 Hz, 2H), 2.77 (s, 3H). 1437 0 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.20 (s, 1H), 9.60 (d, J = 1.7 Hz, 1H), 9.19 (d, J = 8.1 Hz, 1H), 8.93 (dd, J = 5.4, 1.5 Hz, 1H), 8.75 (s, 1H), 8.29 (t, J = 7.9 Hz, 1H), 8.17-8.05 DMSO >98 Method AQ3 (m, 2H), 7.98 (dd, J = 8.0, 5.4 Hz, 1H), 7.83 (ddd, J = 15.5, 8.4, 6.0 Hz, 2H), 7.72 (d, J = 7.8 Hz, 1H), 7.54- 7.44 (m, 1H), 7.38-7.28 (m, 1H), 5.33 (d, J = 5.5 Hz, 2H), 2.81 (s, 3H). 1438 4 HCl .sup.1H NMR (400 MHz, DMSO) 10.45 (s, 1H), 9.62 (d, J = 1.7 Hz, 1H), 9.21 (d, J = 8.1 Hz, 1H), 9.03 (d, J = 1.7 Hz, 1H), 8.93 (dd, J = 5.3, 1.4 Hz, 1H), 8.39- 8.26 (m, 2H), DMSO >98 Method AQ3 8.15-8.04 (m, 2H), 8.00-7.81 (m, 3H), 7.76- 7.59 (m, 2H), 5.36 (d, J = 5.5 Hz, 2H), 2.82 (s, 3H). 1439 3 HCl .sup.1H NMR (400 MHz, DMSO) 10.29 (s, 1H), 9.53 (d, J = 1.8 Hz, 1H), 9.12 (d, J = 8.0 Hz, 1H), 8.93 (dd, J = 5.3, 1.4 Hz, 1H), 8.78 (d, J = 2.5 Hz, 2H), 8.31 (t, J = 7.8 Hz, 1H), DMSO >98 Method AQ3 8.13 (q, J = 8.7 Hz, 2H), 8.04- 7.89 (m, 2H), 7.87-7.68 (m, 2H), 7.50 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.33 (td, J = 8.3, 1.9 Hz, 1H), 5.30 (d, J = 5.4 Hz, 2H). 1440 0 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.41 (s, 1H), 9.63 (d, J = 1.7 Hz, 1H), 9.15 (d, J = 8.1 Hz, 1H), 8.97 (dd, J = 5.2, 1.4 Hz, 1H), 8.83 (s, 1H), 8.20 (s, 2H), 7.97 (dd, J = 8.0, 5.3 Hz, 1H), 7.73- 7.56 (m, 2H), DMSO >98 Method AQ3 7.54-7.28 (m, 4H), 5.03 (d, J = 5.7 Hz, 2H). 1441 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.59 (d, J = 1.6 Hz, 1H), 9.07-8.94 (m, 2H), 8.84 (s, 1H), 8.76 (s, 1H), 8.22-8.13 (m, 2H), 7.96 (dd, J = 8.0, 5.3 Hz, 1H), 7.66 (ddd, J = 9.2, 6.1, 3.2 Hz, 1H), 7.53-7.32 (m, DMSO >98 Method AQ3 2H), 1.69 (s, 9H). 1442 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.93 (s, 1H), 9.62 (d, J = 1.6 Hz, 1H), 9.06-8.87 (m, 2H), 8.39 (s, 1H), 8.06-7.98 (m, 3H), 7.87 (dd, J = 8.0, 5.1 Hz, 1H), 7.77-7.67 (m, 2H), 3.26 (d, J = DMSO >98 Method AQ3 4.6 Hz, 3H), 2.45 (s, 3H). 1443 00 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.98 (s, 1H), 9.64 (s, 1H), 8.99 (dd, J = 27.3, 6.4 Hz, 2H), 8.41 (s, 1H), 8.10-7.93 (m, 3H), 7.88 (dd, J = 7.7, 6.0 Hz, 2H), 7.76 (t, J = 7.8 Hz, 1H), 3.27 (d, J = 4.5 Hz, 3H), 2.46 (s, 3H). DMSO >98 Method AQ3 1444 01 02 03 2 HCl .sup.1H NMR (400 MHz, DMSO) 9.76-9.69 (m, 1H), 9.37 (t, J = 5.4 Hz, 1H), 8.99 (dd, J = 11.7, 7.5 Hz, 1H), 8.81 (dt, J = 7.9, 4.0 Hz, 1H), 8.70 (t, J = 7.3 Hz, 1H), 8.52 (d, J = 9.2 Hz, 1H), 8.35-8.27 (m, 1H), 8.10 (dd, J = 12.8, 7.3 DMSO >98 Method AQ3, F, G2 (reflux) Hz, 1H), 8.01- 7.90 (m, 2H), 7.77-7.71 (m, 1H), 7.50-7.37 (m, 3H), 7.06- 7.01 (m, 1H), 5.19 (t, J = 17.9 Hz, 2H), 3.88 (s, 3H). 1445 04 05 06 2 HCl 1H NMR (DMSO- d6) ppm 9.73 (s, 1H), 9.37 (brd, J = 8.08 Hz, 1H), 8.97 (brd, J = 5.24 Hz, 1H), 8.77 (brs, 1H), 8.20 (d, J = 8.48 Hz, 1H), 8.10-8.07 (brm, 1H), 7.63- 7.55 (brm, 2H), DMSO >98 AQ6 7.47 (d, J = 8.48 Hz, 1H), 7.32 (brm, 1H), 3.20 (d, J = 4.20 Hz, 3H), 2.65 (s, 3H). The 1H of 2HCl was not observed. 1446 07 08 09 3 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.76 Hz, 1H), 9.39 (brd, J = 8.16 Hz, 1H), 8.98 (dd, J = 5.44, 1.20 Hz, 1H), 8.80 brs, 1H), 8.22 (d, J = 8.48 Hz, 1H), 8.12-8.08 (brm, 1H), 7.57- DMSO >98 AQ6 7.51 (m, 1H), 7.46-7.35 (m, 4H), 3.21 (d, J = 4.32 Hz, 3H), 2.55 (s, 3H). The 1H of 3HCl was not observed. 1447 0 3 HCl 1H NMR (DMSO- d6) ppm 9.72 (d, J = 1.68 Hz, 1H), 9.26 (brd, J = 8.48 Hz, 1H), 8.91 (dd, J = 5.28, 1.40 Hz, 1H), 8.69 (brs, 1H), 8.18 (d, J = 8.56 Hz, 1H), 8.00-7.96 (brm, 1H), 7.53- DMSO >98 AQ6 7.49 (m, 2H), 7.44 (d, J = 8.56 Hz, 1H), 7.38- 7.33 (m, 2H), 3.20 (d, J = 4.40 Hz, 3H), 2.63 (s, 3H). The 1H of 3HCl was not observed. 1448 2 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.44 Hz, 1H), 9.36 (brd, J = 7.88 Hz, 1H), 8.96 (d, J = 5.04 Hz, 1H), 8.77 (brs, 1H), 8.21 (d, J = 8.56 Hz, 1H), 8.07 (brm, 1H), 7.48 (d, J = 8.56 Hz, 1H), 7.38- 7.32 (m, 1H), DMSO >98 AQ6 7.27-7.22 (m, 2H), 3.20 (d, J = 4.4 Hz, 3H), 2.65 (s, 3H). The 1H of 2HCl was not observed. 1449 3 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.72 Hz, 1H), 9.32 (brd, J = 7.56 Hz, 1H), 8.94 (brd, J = 5.48 Hz, 1H), 8.74 (brs, 1H), 8.20 (d, J = 8.56 Hz, 1H), 8.08-8.02 (m, 1H), 7.60- DMSO >98 AQ6 7.54 (m, 1H), 7.47 (d, J = 7.35-7.27 (m, 3H), 3.20 (d, J = 4.4 Hz, 3H), 2.65 (s, 3H). The 1H of 3HCl was not observed. 1450 0 2 HCl 1H NMR (DMSO- d6) ppm 9.74 (d, J = 1.76 Hz, 1H), 9.37 (brd, J = 8.16 Hz, 1H), 8.97 (brdd, J = 5.44, 1.24 Hz, 1H), 8.79 (brs, 1H), 8.22 (d, J = 8.52 Hz, 1H), 8.10-8.06 (brm, 1H), 7.48-7.35 (m, 4H), 3.21 DMSO >98 AQ6 (d, J = 4.36 Hz, 3H), 2.56 (brs, 3H). The 1H of 2HCl was not observed. 1451 3 HCl 1H NMR (DMSO- d6) ppm 9.74 (d, J = 1.52 Hz, 1H), 9.37 (d, J = 8.08 Hz, 1H), 8.97 (dd, J = 5.54, 1.16 Hz, 1H), 8.80 (brs, 1H), 8.23 (d, J = 8.52 Hz, 1H), 8.10- 8.07 (m, 1H), DMSO >98 AQ6 7.60-7.53 (m, 1H), 7.48 (d, J = 8.52 Hz, 1H), 7.41- 7.36 (m, 1H), 7.30-7.26 (m, 1H), 3.21 (d, J = 4.36 Hz, 3H), 2.56 (s, 3H). The 1H of 3HCl was not observed. 1452 3 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.68 Hz, 1H), 9.26 (brd, J = 7.8 Hz, 1H), 8.91 (brdd, J = 5.28, 1.36 Hz, 1H), 8.71 (brs, 1H), 8.21 (d, J = 8.52 Hz, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.99- 7.95 (m, 1H), DMSO >98 AQ6 7.69 (d, 8.4 Hz, 2H),7.46 (d, J = 8.52 Hz, 1H), 3.20 (d, J = 4.4 Hz, 3H), 2.63 (s, 3H). The 1H of 3HCl was not observed. 1453 0 2 HCl 1H NMR (DMSO- d6) ppm 9.73 (d, J = 1.72 Hz, 1H), 9.33 (brd, J = 7.64 Hz, 1H), 8.95 (brd, J = 5.28 Hz, 1H), 8.76 (brs, 1H), 8.22 (d, J = 8.48 Hz, 1H), 8.05 (brm, J = 7.64, 5.28 Hz, 1H), 7.98-7.93 (m, 2 H), 7.84-7.81 (m, 1H), 7.74 (dd, J = 7.84, DMSO >98 AQ6 7.76 Hz, 1H), 7.49 (d, J = 8.84 Hz, 1H), 3.21 (d, J = 4.4 Hz, 3H), 2.63 (s, 3H). The 1H of 2HCl was not observed. 1454 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.72 (d, J = 1.76 Hz, 1H), 9.42 (brd, J = 8.00 Hz, 1H), 9.00 (d, J = 5.52 Hz, 1H), 8.83 (bsr, 1H), 8.22 (d, J = 8.56 Hz, 1H), 8.13 (brm, 1H), 7.55-7.51 (m, 2H), DMSO >98 AQ6 7.48-7.43 (m, 4H), 3.21 (brd, J = 4.16 Hz, 3H), 2.64 (s, 3H). The 1H of 2HCl was not observed. 1455 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.72 (s, 1H), 9.33 (d, J = 8.24 Hz, 1H), 8.96 (d, J = 5.40 Hz, 1H), 8.75 (brs, 1H), 8.17 (d, J = 8.60 Hz, 1H), 8.06 (brm, 1H), 7.45 (d, J = 8.80 Hz, 1H), 7.40 (d, J = 8.64 Hz, 2H), 7.08 (d, DMSO >98 AQ6 J = 8.64 Hz, 2H), 3.84 (s, 3H), 3.20 (d, J = 4.20 Hz, 3H), 2.66 (s, 3H). The 1H of 2HCl was not observed. 1456 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.72 (d, J = 1.64 Hz, 1H), 9.38 (d, J = 8.04 Hz, 1H), 8.98 (dd, J = 5.48, 1.24 Hz, 1H), 8.79 (brs, 1H), 8.20 (d, J = 8.52 Hz, 1H), 8.12-8.09 (m, 1H), 7.48-7.42 (m, 2H), 7.04-6.97 (m, 3H), 3.82 (s, 3H), 3.21 (d, J = DMSO >98 AQ6 4.28 Hz, 3H), 2.65 (s, 3H). The 1H of 2HCl was not observed. 1457 0 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.71 (d, J = 1.32 Hz, 1H), 9.40 (d, J = 7.64 Hz, 1H), 8.99 (dd, J = 5.52, 1.16 Hz, 1H), 8.82 (brs, 1H), 8.17 (d, J = 8.48 Hz, 1H), 8.13 (m, 1H), 7.47-7.43 (m, DMSO >98 AQ6 1H), 7.37 (d, J = 8.48 Hz, 1H), 7.22-7.16 (m, 2H), 7.11-7.07 (m, 1H), 3.73 (s, 3H), 3.21 (d, J = 4.12 Hz, 3H), 2.47 (s, 3H). The 1H of 2HCl was not observed. 1458 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.57 (d, J = 1.88 Hz, 1H), 8.93 (dd, J = 4.88, 1.56 Hz, 1H), 8.87 (brd, J = 6.52 Hz, 1H), 7.95 (d, J = 8.36 Hz, 1H), 7.84 (d, J = 8.36 Hz, 1H), 7.81 (m, DMSO >98 AQ6 1H), 7.34 (d, J = 8.72 Hz, 2H), 7.11 (d, J = 8.72 Hz, 2H), 3.84 (s, 3H), 3.34 (d, J = 4.56 Hz, 3H), 2.72 (s, 3H). The 1H of 2HCl and NH- were not observed. 1459 2 HCl .sup.1H NMR (DMSO- d.sub.6) ppm 9.59 (s, 1H), 8.94 (dd, J = 4.92, 1.48 Hz, 1H), 8.89 (br, 1H), 7.98 (d, J = 8.48 Hz, 1H), 7.86 (d, J = 8.48 Hz, 1H), 7.82 (m, 1H), 7.46 (t, J = 7.96 Hz, 1H), DMSO >98 AQ6 7.06-7.03 (m, 1H), 6.98-6.94 (m, 2H), 3.83 (s, 3H), 3.34 (d, J = 4.56 Hz, 3H), 2.72 (s, 3H). The 1H of 2HCl and NH- were not observed. 1460 0 .sup.1H NMR (300 MHz, DMSO) 9.60 (s, 1H), 8.84- 8.57 (m, 3H), 8.30 (d, J = 7.0 Hz, 1H), 8.18 (d, J = 8.8 Hz, 1H), 8.12-7.93 (m, 4H), 7.85 (dd, J = 8.7, 1.5 Hz, 1H), 7.60-7.46 (m, 1H), 4.85-4.58 DMSO 100 AQ1 366 (M + 1) Method A (Formic acid) (m, 1H), 1.37 (d, J = 6.5 Hz, 6H). 1461 HCl .sup.1H NMR (300 MHz, DMSO) 9.81 (s, 1H), 9.60 (s, 1H), 8.95 (s, 3H), 8.39 (d, J = 8.9 Hz, 1H), 8.19 (s, 1H), 7.96-7.73 (m, 3H), 7.68- 7.55 (m, 1H), 7.39-7.25 (m, 1H), 4.99-4.81 (m, 1H), 1.42 (d, J = 6.5 Hz, 6H). DMSO 100 AQ1 359 (M + 1) Method A (Formic acid) 1462 .sup.1H NMR (300 MHz, DMSO) 9.43 (s, 1H), 8.75- 8.47 (m, 3H), 8.29 (d, J = 7.2 Hz, 1H), 7.79 (d, J = 7.1 Hz, 1H), 7.72- 7.54 (m, 2H), 7.48 (dd, J = 7.8, 4.9 Hz, 1H), 7.44-7.32 (m, 1H), 7.30-7.12 (m, 1H), 3.32 (s, 3H), 3.16 (d, J = 4.3 Hz, 3H). DMSO 100 AQ1 349 (M + 1) Method A (Formic acid) 1463 1H NMR (300 MHz, DMSO) 9.68 (dd, J = 2.1, 0.8 Hz, 1H), 8.86- 8.78 (m, 1H), 8.74 (dd, J = 4.8, 1.7 Hz, 1H), 8.34-8.25 (m, 2H), 8.09-8.02 (m, 1H), 7.80 (d, J = 8.9 Hz, 2H), 7.60 DMSO 99 Method AQ2 344.0 (M + 1) Method C (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 7.09 (d, J = 8.9 Hz, 2H), 4.31 (s, 3H), 3.83 (s, 3H). 1464 0 1H NMR (300 MHz, DMSO) 9.67 (d, J = 2.1 Hz, 1H), 8.82 (d, J = 7.9 Hz, 1H), 8.74 (dd, J = 4.8, 1.7 Hz, 1H), 8.46 (d, J = 1.7 Hz, 1H), 8.36 (dd, J = 8.8, 2.2 Hz, 1H), 8.15-7.94 (m, 5H), 7.60 (ddd, J = DMSO 99 Method AQ2 338.9 (M + 1) Method C 8.0, 4.8, 0.8 Hz, 1H), 4.31 (s, 3H). 1465 2 HCl 1H NMR (300 MHz, DMSO) 9.71 (d, J = 1.8 Hz, 1H), 9.15 (d, J = 8.0 Hz, 1H), 8.90 (dd, J = 5.2, 1.4 Hz, 1H), 8.58 (s, J = 1.8 Hz, 1H), 8.48 (d, J = 1.6 Hz, 1H), 8.43 DMSO 99 Method AQ2 359.0 (M + 1) Method C (dd, J = 8.7, 2.2 Hz, 1H), 8.32 (dd, J = 7.8, 0.9 Hz, 1H), 8.28 (dd, J = 8.2, 2.2 Hz, 1H), 8.14 (d, J = 8.7 Hz, 1H), 7.92 (dd, J = 8.0, 5.2 Hz, 1H), 7.81 (t, J = 8.0 Hz, 1H), 4.34 (s, 3H). 1466 2 HCl 1H NMR (300 MHz, DMSO) 9.71 (d, J = 2.0 Hz, 1H), 9.12 (dd, J = 8.0, 1.4 Hz, 1H), 8.89 (dd, J = 5.2, 1.5 Hz, 1H), 8.49 (d, J = 1.6 Hz, 1H), 8.42 (dd, J = 8.8, 2.2 Hz, 1H), 8.34 (d, J = 9.0 Hz, 2H), DMSO 99 Method AQ2 359.0 (M + 1) Method C 8.14 (dd, J = 9.2, 2.4 Hz, 3H), 7.88 (dd, J = 7.8, 5.5 Hz, 1H), 4.34 (s, 3H). 1467 2 HCl 1H NMR (300 MHz, DMSO) 9.36 (s, 1H), 9.00 (d, J = 6.5 Hz, 2H), 8.78 (d, J = 4.5 Hz, 2H), 8.58 (s, 1H), 8.06 (s, 2H), 7.75 (dd, J = 15.6, 8.9 Hz, 1H), 7.47 (ddd, J = 11.7, 9.4, 2.6 Hz, DMSO 99 Method AQ2 349.6 (M + 1) Method C 1H), 7.31 (td, J = 8.4, 2.7 Hz, 1H), 3.22 (d, J = 4.2 Hz, 3H).

(419) TABLE-US-00036 1468 3 HCl 1H NMR (300 MHz, DMSO) 9.97 (s, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 7.0 Hz, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.76 (d, J = 0.7 Hz, 1H), 8.41-8.05 (m, DMSO 99 Method AQ2 332.4 (M + 1) Method C 4H), 7.89 (dd, J = 7.1, 4.8 Hz, 1H), 7.59 (ddd, J = 7.1, 4.9, 1.8 Hz, 1H), 3.27 (d, J = 4.3 Hz, 3H). 1469 0 2 HCl 1H NMR (300 MHz, DMSO) 10.04 (s, 1H), 9.65 (d, J = 1.5 Hz, 1H), 9.06 (d, J = 7.3 Hz, 1H), 8.95 (dd, J = 5.1, 1.5 Hz, 1H), 8.71 (s, 1H), 8.19 (s, 2H), 7.89 (dd, J = 7.6, 5.1 DMSO 95 Method AQ2 365.3 (M + 1) Method C Hz, 1H), 7.76- 7.61 (m, 2H), 7.42 (td, J = 7.9, 0.9 Hz, 1H), 3.27 (d, J = 4.4 Hz, 3H). 1470 2 HCl 1H NMR (300 MHz, DMSO) 10.03 (s, 1H), 9.63 (d, J = 1.5 Hz, 1H), 9.04 (d, J = 7.9 Hz, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.68 (s, 1H), 8.16 (s, 2H), 7.88 (dd, J = 7.6, 5.1 DMSO 94 Method AQ2 365.3 (M + 1) Method C Hz, 1H), 7.74 (t, J = 8.5 Hz, 1H), 7.67 (dd, J = 10.8, 2.0 Hz, 1H), 7.51 (dd, J = 8.3, 1.6 Hz, 1H), 3.27 (d, J = 4.4 Hz, 3H). 1471 2 HCl 1H NMR (300 MHz, DMSO) 9.95 (s, 1H), 9.64 (d, J = 1.6 Hz, 1H), 9.07 (d, J = 7.9 Hz, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.75 (s, 1H), 8.18 (s, 2H), 8.09 (d, J = 11.1 Hz, 1H), 7.92 DMSO 96 Method AQ2 356.4 (M + 1) Method C (d, J = 4.0 Hz, 3H), 3.27 (d, J = 4.4 Hz, 3H). 1472 2 HCl 1H NMR (300 MHz, DMSO) 10.01 (s, 1H), 9.63 (d, J = 1.5 Hz, 1H), 9.03 (d, J = 7.8 Hz, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.73 (s, 1H), 8.25- 8.12 (m, 3H), 7.93-7.76 (m, 4H), 7.63 (d, J = DMSO 95 Method AQ2 374.4 (M + 1) Method C 0.8 Hz, 1H), 3.28 (d, J = 4.4 Hz, 3H). 1473 2 HCl 1H NMR (300 MHz, DMSO) 9.97 (s, 1H), 9.61 (d, J = 2.1 Hz, 1H), 8.98 (d, J = 4.6 Hz, 1H), 8.93 (dd, J = 5.1, 1.5 Hz, 1H), 8.68- 8.60 (m, 1H), 8.13 (d, J = 6.1 Hz, 2H), 7.85 (dd, DMSO 95 Method AQ2 377.5 (M + 1) Method C J = 7.7, 5.2 Hz, 1H), 7.63 (t, J = 8.3 Hz, 1H), 7.37- 7.23 (m, 2H), 3.27 (d, J = 4.5 Hz, 3H), 2.56 (s, J = 5.2 Hz, 3H). 1474 0 2 HCl 1H NMR (300 MHz, DMSO) 9.98 (s, 1H), 9.64 (d, J = 1.6 Hz, 1H), 9.06 (d, J = 8.8 Hz, 1H), 8.94 (dd, J = 5.1, 1.5 Hz, 1H), 8.75 (s, 1H), 8.26-8.11 (m, 2H), 8.04- 7.85 (m, 5H), 3.35 (s, 3H), 3.27 (d, J = 4.1 Hz, DMSO 96 Method AQ2 409.5 (M + 1) Method C 3H). 1475 2 HCl 1H NMR (300 MHz, DMSO) 10.25 (s, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.00 (d, J = 7.1 Hz, 1H), 8.93 (dd, J = 5.0, 1.5 Hz, 1H), 8.79 (s, 1H), 8.31 (dd, J = 8.8, 1.5 Hz, 1H), 8.17 DMSO 99 Method AQ2 357.5 (M + 1) Method C (d, J = 8.5 Hz, 1H), 7.84 (dd, J = 7.5, 4.8 Hz, 1H), 7.51 (d, J = 1.8 Hz, 1H), 7.40 (dd, J = 8.2, 1.9 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.10 (s, 2H), 3.29 (d, J = 4.3 Hz, 3H). 1476 2 HCl 1H NMR (300 MHz, DMSO) 10.26 (s, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.01 (d, J = 8.6 Hz, 1H), 8.93 (dd, J = 5.0, 1.5 Hz, 1H), 8.77 (s, 1H), 8.31 (dd, J = 8.8, 1.4 Hz, 1H), 8.18 DMSO 99 Method AQ2 371.5 (M + 1) Method C (d, J = 8.6 Hz, 1H), 7.84 (dd, J = 6.9, 5.8 Hz, 1H), 7.44 (d, J = 2.2 Hz, 1H), 7.39 (dd, J = 8.4, 2.3 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H), 4.30 (s, 4H), 3.29 (d, J = 4.4 Hz, 3H). 1477 2 HCl 1H NMR (300 MHz, DMSO) 10.19 (s, 1H), 9.61 (d, J = 1.6 Hz, 1H), 8.98 (d, J = 8.8 Hz, 1H), 8.93 (dd, J = 5.0, 1.5 Hz, 1H), 8.82 (s, 1H), 8.35 (dd, J = 8.8, DMSO 99 Method AQ2 357.5 (M + 1) Method C 1.3 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.85 (dd, J = 8.1, 5.2 Hz, 1H), 7.76-7.66 (m, 2H), 7.46 (t, J = 7.6 Hz, 1H), 7.31 (d, J = 7.7 Hz, 1H), 3.69 (t, J = 7.0 Hz, 2H), 3.31 (d, J = 4.4 Hz, 3H), 2.84 (t, J = 7.0 Hz, 2H). 1478 2 HCl 1H NMR (300 MHz, DMSO) 10.11 (s, 1H), 9.60 (d, J = 1.9 Hz, 1H), 8.93 (dd, J = 10.3, 5.4 Hz, 2H), 8.80 (d, J = 0.6 Hz, 1H), 8.34 (dd, J = 8.0, 0.5 Hz, 1H), DMSO 99 Method AQ2 357.5 (M + 1) Method C 8.10 (d, J = 8.3 Hz, 1H), 7.88- 7.75 (m, 3H), 7.40 (d, J = 8.3 Hz, 2H), 3.65 (t, J = 6.9 Hz, 2H), 3.30 (d, J = 4.4 Hz, 3H), 2.79 (t, J = 6.9 Hz, 2H). 1479 0 2 HCl 1H NMR (300 MHz, DMSO) 10.27 (s, 1H), 9.62 (d, J = 1.5 Hz, 1H), 8.99 (s, 1H), 8.96-8.88 (m, 2H), 8.37 (d, J = 8.9 Hz, 1H), 8.18 (d, J = 8.6 Hz, 1H), 7.96 (d, J = 8.5 Hz, 2H), DMSO 99 Method AQ2 380.5 (M + 1) Method C 7.85 (s, 1H), 7.70 (d, J = 8.5 Hz, 2H), 3.30 (d, J = 4.3 Hz, 3H), 1.74 (s, 6H). 1480 2 HCl 1H NMR (300 MHz, DMSO) 10.23 (s, 1H), 9.62 (d, J = 1.8 Hz, 1H), 9.02 (d, J = 6.6 Hz, 1H), 8.93 (dd, J = 5.0, 1.5 Hz, 1H), 8.88 (d, J = 0.5 Hz, 1H), 8.33 (d, DMSO 99 Method AQ2 393.4 (M + 1) Method C J = 8.5 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 1.7 Hz, 1H), 7.86 (dd, J = 7.4, 5.1 Hz, 1H), 7.75 (dd, J = 8.5, 1.8 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 3.29 (d, J = 4.3 Hz, 3H). 1481 1H NMR (300 MHz, DMSO) 9.63 (d, J = 1.4 Hz, 1H), 8.81-8.73 (m, 1H), 8.68 (dd, J = 4.7, 1.7 Hz, 1H), 8.61 (d, J = 4.3 Hz, 1H), 8.45 (s, 1H), 7.97 (d, J = 8.6 Hz, DMSO 99 Method AQ2, fol- lowed by hydrol- ysis with 30% H.sub.2O.sub.2 374.5 (M + 1) Method C 1H), 7.86 (d, J = and 8.7 Hz, 2H), NAOH 7.77-7.61 (m, in 3H), 7.53 (dd, J = ethanol 7.9, 4.8 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 3.15 (d, J = 4.3 Hz, 3H). 1482 2 HCl 1H NMR (300 MHz, DMSO) 10.60 (s, 1H), 10.29 (s, 1H), 9.62 (d, J = 1.5 Hz, 1H), 9.00 (d, J = 7.1 Hz 1H), 8.92 (dd, J = 4.9, 1.4 Hz, 1H), 8.76 (s, 1H), 8.29 (d, J = DMSO 94 Method AQ1, except that dioxane water was replaced with DME/ 368.5 (M + 1) Method C 8.9 Hz, 1H), 8.20 water/ (d, J = 8.4 Hz, EtOH in 1H), 7.84 (dd, J = the 7.8, 4.8 Hz, micro- 1H), 7.79-7.68 wave (m, 2H), 6.95 (d, at 120 J = 8.0 Hz, 1H), C. for 3.57 (s, 2H), 10 min 3.29 (d, J = 4.3 Hz, 3H). 1483 2 HCl 1H NMR (300 MHz, DMSO) 10.67 (s, 1H), 9.60 (d, J = 2.4 Hz, 1H), 8.99-8.88 (m, 2H), 8.73 (d, J = 1.0 Hz, 1H), 8.27 (d, J = 9.2 Hz, 1H), 8.10 (d, J = 7.5 Hz, 1H), DMSO 99 Method AQ1, except that dioxane water was replaced with DME/ 368.5 (M + 1) Method C 7.83 (dd, J = 6.9, water/ 4.3 Hz, 1H), EtOH in 7.40 (q, J = 8.3 the Hz, 2H), 7.20 (s, micro- 1H), 3.56 (s, 2H), wave 3.29 (d, J = 4.1 at 120 Hz, 3H). C. for 10 min 1484 2 HCl 1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.61 (d, J = 1.9 Hz, 1H), 9.04-8.89 (m, 2H), 8.84 (d, J = 1.2 Hz, 1H), 8.36 (dd, J = 8.7, 1.3 Hz, 1H), 8.14 (d, J = 8.1 DMSO 99 Method AQ1, except that dioxane water was replaced with DME/ 357.5 (M + 1) Method C Hz, 1H), 7.94- water/ 7.78 (m, 3H), 7.50 EtOH in (d, J = 8.3 Hz, the 2H), 4.49 (s, 2H), micro- 3.39-3.23 (m, 6H). wave at 120 C. for 10 min 1485 00 1H-NMR (400 MHz, DMSO-d6): 9.63 (s, 1H), 8.76 (td, J = 8.0, 1.6 Hz, 1H), 8.71 (dd, J = 4.8, 1.6 Hz, 1H), 8.37 (s, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.59-7.54 (m, 1H), DMSO 95 Method G1, AQ1 377.0 379.0 (M + 1) Method C 7.43 (t, J = 8.0 Hz, 1H), 7.06- 6.98 (m, 3H), 3-82 (s, 3H), 1486 01 2HCl 1H-NMR (400 MHz, DMSO-d6): 9.81 (s, 1H), 9.38 (d, J = 8.4 Hz, 1H), 9.15 (d, J = 5.2 Hz, 1H), 8.69 (d, J = 1.6 Hz, 1H), 8.41 (dd, J = 8.8, 2.0 DMSO 95 Method G1, AQ1 401.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 1H), 8.29- 8.26 (m, 1H), 8.14 (d, J = 8.8 Hz, 1H), 7.50-7.41 (m, 3H), 7.11- 7.08 (m, 1H), 4.80-4.76 (m, 1H), 3.66-3.57 (m, 2H), 3.50 (s, 3H), 3.44 (s, 3H), 1.35 (d, J = 6.4 Hz, 3H). 1487 02 2HCl 1H-NMR (400 MHz, CD3OD): 9.55 (s, 1H), 8.92 (d, J = 4.9 Hz, 1H), 8.89 (dt, J = 8.2, 1.8 Hz, 1H), 8.62 (s, 1H), 8.37 (d, J = 8.8 Hz, 1H), 8.03 (d, MeOD 95 Method G1, AQ1 415.1 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 8.7 Hz, 1H), 7.83 (dd, J = 8.0, 5.0 Hz, 1H), 7.49 (t, J = 8.1 Hz, 1H), 7.43 (s, 2H), 7.10 (d, J = 7.6 Hz, 1H), 4.01 (s, 2H), 3.46 (s, 3H), 3.35 (s, 3H), 1.37 (s, 6H). 1488 03 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.34 (s, 1H), 9.65 (s, 1H), 9.04 (d, J = 6.9 Hz, 1H), 8.99-8.87 (m, 2H), 8.39 (d, J = 9.2 Hz, 1H), DMSO 95 Method G1, AQ1 400.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.24 (d, J = 8.2 Hz, 1H), 7.86 (s, 1H), 7.47-7.43 (m, 3H), 7.05 (d, J = 6.8 Hz, 1H), 4.26-4.22 (m, 2H), 3.77-3.73 (m, 2H), 3.56- 3.50 (m, 2H), 3.32 (d, J = 4.3 Hz, 3H), 1.15 (t, J = 7.0 Hz, 3H). 1489 04 1H-NMR (400 MHz, DMSO-d6): 9.68 (s, 1H), 8.81- 8.78 (m, 2H), 8.71 (d, J = 3.6 Hz, 1H), 8.54 (s, 1H), 8.32 (d, J = 1.2 Hz, 1H), 7.57 (dd, J = 7.6, 4.8 Hz, 1H), 7.46-7.42 (m, DMSO 95 Method G1, AQ1 377.1, 379.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H), 7.04-7.01 (m, 1H), 3.88 (s, 3H), 3.19 (d, J = 4.0 Hz, 3H). 1490 05 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.50 (brs, 1H), 9.68 (d, J = 2.0 Hz, 1H), 9.09 (d, J = 8.0 Hz, 1H), 8.96 (dd, J = 5.2, 1.2 Hz, 1H), 8.94 (s, 1H), DMSO 95 Method G1, AQ1 427.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.40 (d, J = 9.2 Hz, 1H), 8.29 (d, J = 8.8 Hz, 1H), 7.89 (dd, J = 8.0, 1.6 Hz, 1H), 7.48-7.43 (m, 3H), 7.03 (d, J = 7.2 Hz, 1H), 4.06- 4.05 (m, 2H), 3.92 (d, J = 11.6 Hz, 1H), 3.69- 3.66 (m, 1H), 3.42-3.39 (m, 1H), 3.32 (d, J = 4.4 Hz, 3H), 1.86-1.83 (m, 1H), 1.69 (d, J = 12.4 Hz, 1H), 1.52-1.51 (m, 3H), 1.38-1.35 (m, 1H). 1492 06 3HCl 1H-NMR (400 MHz, DMSO-d6): 10.80 (s, 1H), 9.70 (s, 1H), 9.13 (d, J = 8.0 Hz, 1H), 9.07 (s, 1H), 8.97 (d, J = 4.4 Hz, 1H), 8.94 (s, DMSO 95 Method G1, AQ1 488.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.32 (d, J = 8.8 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.98 (t, J = 8.0 Hz, 1H), 7.90 (t, J = 6.2 Hz, 1H), 7.68 (s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 5.50 (s, 2H), 3.30 (d, J = 2.4 Hz, 3H). 1493 07 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.58 (s, 1H), 9.71 (s, 1H), 9.14 (d, J = 7.6 Hz, 1H), 8.98 (d, J = 8.0 Hz, 2H), 8.40 (d, J = 8.8 Hz, 1H), 8.31 (d, J = DMSO 95 Method G1, AQ1 496.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.8 Hz, 1H), 7.92 (t, J = 6.2 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.47-7.43 (m, 3H), 7.02 (d, J = 7.2 Hz, 1H), 4.10 (t, J = 6.0 Hz, 2H), 3.53 (d, J = 6.4 Hz, 1H), 3.32 (d, J = 2.4 Hz, 3H), 2.26 (t, J = 7.0 Hz, 2H), 2.00-1.93 (m, 2H), 1.73-1.63 (m, 4H), 1.55- 1.51 (m, 1H), 1.28-1.02 (m, 5H). 1494 08 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.07 (s, 1H), 9.60 (s, 1H), 8.92 (d, J = 4.4 Hz, 2H), 8.76 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.85-7.83 (m, DMSO 95 Method G1, AQ1 428.1, 429.1, (M + 1) Method B (NH.sub.4HCO.sub.3) 4H), 7.11 (d, J = 8.8 Hz, 2H), 4.04 (t, J = 6.4 Hz, 2H), 3.30 (d, J = 4.0 Hz, 3H), 2.58 (d, J = 4.0 Hz, 3H), 2.26 (t, J = 7.4 Hz, 2H), 2.00-1.93 (m, 2H). 1495 09 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.63 (s, 1H), 9.73 (s, 1H), 9.17 (d, J = 7.6 Hz, 1H), 8.99 (s, 1H), 8.91 (s, 1H), 8.34 (s, 2H), 7.93 (t, J = 6.0 Hz, 1H), 7.88 (d, J = 7.2 DMSO 95 Method G1, AQ1 442.1, 443.1, (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 2H), 7.09 (d, J = 7.6 Hz, 2H), 4.08-4.06 (m, 2H), 3.32 (s, 3H), 2.98 (s, 3H), 2.84 (s, 3H), 2.47- 2.46 (m, 2H), 1.98-1.94 (m, 2H). 1496 0 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.26 (s, 1H), 9.64 (s, 1H), 9.01 (d, J = 7.0 Hz, 1H), 8.94 (s, 1H), 8.89 (s, 1H), 8.39 (d, J = 8.2 Hz, 1H), 8.19 (d, J = DMSO 95 Method G1, AQ1 413.1, 414.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.1 Hz, 1H), 7.85 (s, 1H), 7.47 (d, J = 5.8 Hz, 3H), 7.05 (d, J = 3.4 Hz, 1H), 4.21 (dt, J = 10.8, 5.5 Hz, 1H), 4.08 (qd, J = 10.1, 5.2 Hz, 2H), 3.82 (dd, J = 14.4, 7.0 Hz, 1H), 3.71 (dd, J = 14.1, 7.4 Hz, 1H), 3.31 (d, J = 4.2 Hz, 3H), 2.08- 2.00 (m, 1H), 1.98-1.79 (m, 2H), 1.72-1.68 (m, 1H). 1497 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.53 (s, 1H), 9.68 (s, 1H), 9.09 (d, J = 7.7 Hz, 1H), 8.96 (d, J = 5.9 Hz, 2H), 8.39 (d, J = 8.7 Hz, 1H), 8.30 (d, J = 8.3 Hz, 1H), 7.94-7.79 (m, 1H), 7.48-7.45 (m, 3H), 7.04 (d, J = 7.5 Hz, 1H), DMSO- d.sub.6 95 Method G1, AQ1 415.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 4.30-4.18 (m, 2H), 3.80-3.70 (m, 2H), 3.44 (t, J = 6.6 Hz, 2H), 3.31 (d, J = 4.2 Hz, 3H), 1.56- 1.54 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H). 1498 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.07 (s, 1H), 9.67 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 8.95 (d, J = 4.5 Hz, 1H), 8.51 (s, 1H), 7.85 (s, 2H), 7.41 (t, J = 7.9 Hz, 1H), 7.18 (dd, J = 7.8, 5.1 DMSO 95 Method G1, AQ1 373.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 2H), 7.02 (dd, J = 8.2, 2.3 Hz, 1H), 3.97 (s, 3H), 3.84 (s, 3H), 1499 2HCl 1H-NMR (400 MHz, DMSO-d6): 10.06 (s, 1H), 9.66 (s, 1H), 9.02 (d, J = 7.5 Hz, 1H), 8.95 (s, 1H), 8.89 (s, 1H), 8.39 (d, 2 = 8.5 Hz, 1H), 8.22 (d, J = DMSO 95 Method G1, AQ1 415.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.6 Hz, 1H), 7.85 (dd, J = 7.0, 5.4 Hz, 1H), 7.52-7.43 (m, 3H), 7.09-7.01 (m, 1H), 4.17- 4.15 (m, 2H), 3.32-3.30 (m, 4H), 3.25 (s, 3H), 1.98-1.82 (m, 2H), 1.17 (d, J = 6.1 Hz, 3H). 1500 2HCl 1H-NMR (400 MHz, CD3OD): 9.80 (s, 1H), 9.37 (d, J = 8.2 Hz, 1H), 9.13 (d, J = 5.3 Hz, 1H), 8.90 (s, 1H), 8.45 (d, J = 8.4 Hz, CD.sub.3OD 95 Method G1, AQ1 468.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 8.25 (dd, J = 7.9, 5.6 Hz, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.64 (s, 1H), 7.54 (d, J = 5.1 Hz, 2H), 7.17 (dd, J = 7.5, 3.6 Hz, 1H), 4.70-4.62 (m, 2H), 4.42 (q, J = 9.0 Hz, 2H), 3.93-3.86 (m, 2H), 3.51 (s, 3H), 3.24 (s, 3H). 1501 2HCl 1H-NMR (400 MHz, DMSO): 10.45 (brs, 1H), 9.72 (s, 1H), 9.12 (d, J = 7.6 Hz, 1H), 8.97 (d, J = 4.0 Hz, 1H), 8.70 (s, 1H), 8.35 (d, J = 8.8 Hz, 1H), DMSO 95 Method G1, AQ1 428.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.23 (d, J = 8.4 Hz, 1H), 7.90- 7.87 (m, 2H), 7.49 (d, J = 7.2 Hz, 1H), 7.43 (t, J = 7.2 Hz, 1H), 7.18 (d, J = 8.4 Hz, 1H), 7.11 (t, J = 7.2 Hz, 1H), 4.03 (t, J = 6.4 Hz, 2H), 3.30 (d, J = 4.4 Hz, 3H), 2.54 (d, J = 4.0 Hz, 3H), 2.19 (t, J = 7.4 Hz, 2H),1.93-1.86 (m, 2H).

(420) TABLE-US-00037 1502 1H-NMR (400 MHz, DMSO-d6): 9.65 (s, 1H), 8.88 (s, 1H), 8.81 (d, J = 8 Hz, 1H), 8.73 (s, 1H), 8.62 (s, 1H), 8.19 (d, J = 8 Hz, 1H), 788 (d, J = 9.2 Hz, 1H), 7.61- DMSO 95 Method G1, AQ1 413.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.58 (m, 1H), 7.47-7.44 (m, 3H), 7.06-7.04 (m, 1H), 4.56- 4.54 (m, 1H), 3.87 (dd, J = 11.2, 2.0 Hz, 1H), 3.68- 3.64 (m, 1H), 3.56-3.53 (m, 2H), 3.21 (d, J = 4.4 Hz, 3H), 2.09- 2.05 (m, 1H), 1.83-1.72 (m, 2H), 1.61-1.55 (m, 1H). 1503 2HCl 1H-NMR (400 MHz, CD3OD): 9.77 (s, 1H), 9.43 (d, J = 8.1 Hz, 1H), 9.08 (d, J = 5.6 Hz, 1H), 8.46 (s, 1H), 8.34- 8.25 (m, 1H), CD.sub.3OD 95 Method G1, AQ1 496.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.20 (d, J = 8.7 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 7.00 (t, J = 7.5 Hz, 1H), 3.98 (t, J = 6.1 Hz, 2H), 3.44 (t, J = 11.1 Hz, 1H), 3.35 (s, 3H), 2.17 (t, J = 7.3 Hz, 2H), 1.93-1.89 (m, 2H), 1.70- 1.53 (m, 4H), 1.48 (d, J = 12.5 Hz, 1H), 1.22- 1.12 (m, 2H), 1.08-1.02 (m, 3H). 1504 1H-NMR (400 MHz, DMSO-d6): 9.63 (s, 1H), 8.76 (d, J = 8.0 Hz, 1H), 8.67 (d, J = 3.6 Hz, 1H), 8.50 (d, J = 4.0 Hz, 1H), 8.10 (s, 1H), 7.56-7.53 (m, 2H), 7.46- DMSO 95 Method G1, AQ1 372.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.42 (m, 3H), 7.03-7.01 (m, 1H), 4.07 (s, 3H), 3.88 (s, 3H), 3.17 (d, J = 4.0 Hz, 1H). 1505 1H-NMR (400 MHz, DMSO): 9.28 (s, 1H), 8.94 (t, J = 7.6 Hz, 1H), 8.62 (d, J = 4.2 Hz, 1H), 8.42 (s, 1H), 7.94 (d, 7 = 8.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.73-7.71 (m, DMSO 95 Method G1, AQ1 367.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 7.46 (t, J = 10.0 Hz, 1H), 7.33-7.27 (m, 2H), 3.16 (d, J = 4.4 Hz, 3H). 1506 0 1H-NMR (400 MHz, DMSO): 8.77 (s, 1H), 8.66 (t, J = 8.6 Hz, 1H), 8.52 (s, 1H), 8.44-8.31 (m, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 8.6 Hz, 1H), 7.62- 7.49 (m, 3H), DMSO 95 Method G1, AQ1 366.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.42-7.37 (m, 1H), 3.12 (d, J = 3.0 Hz, 3H). 1507 1H-NMR (400 MHz, DMSO): 9.29 (d, J = 2.0 Hz, 1H), 8.95 (dt, J = 8.4, 2.4 Hz, 1H), 8.65 (d, J = 4.4 Hz, 1H), 8.49 (s, 1H), 7.94- 7.93 (m, 2H), 7.60-7.26 (m, 4H), 3.16 (d, DMSO 95 Method G1, AQ1 367.1 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 4.4 Hz, 3H). 1508 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.46 (s, 1H), 8.77 (s, 1H), 8.65 (t, J = 8.5 Hz, 1H), 8.55 (s, 1H), 8.19 (d, J = 8.7 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H), 7.79 (dd, J = 15.8, 7.8 Hz, DMSO 95 Method G1, AQ1 367.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 7.71-7.66 (m, 1H), 7.51 (t, J = 10.2 Hz, 1H), 7.34 (t, J = 8.5 Hz, 1H), 3.23 (d, J = 3.3 Hz, 3H). 1509 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.98 (s, 1H), 9.55 (d, J = 1.8 Hz, 1H), 9.07 (d, J = 7.2 Hz, 1H), 8.67 (s, 1H), 8.16 (dd, J = 18.0, 8.4 Hz, 2H), 7.84 (d, J = 8.3 Hz, 1H), 7.78 (td, J = DMSO 95 Method G1, AQ1 363.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.9, 6.6 Hz, 1H), 7.55-7.45 (m, 1H), 7.33 (td, J = 8.4, 2.0 Hz, 1H), 3.28 (d, J = 4.4 Hz, 3H), 2.74 (s, 3H). 1510 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.17 (s, 1H), 8.82 (dd, J = 7.9, 6.7 Hz, 2H), 8.65 (s, 1H), 8.21 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H), 7.80 (s, 1H), 7.65-7.50 (m, 2H), 7.42 (dd, DMSO 95 Method G1, AQ1 363.0 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 12.7, 7.6 Hz, 1H), 3.20 (d, J = 4.4 Hz, 3H), 2.94 (s, 3H). 1511 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.24 (s, 1H), 8.84 (d, J = 4.0 Hz, 1H), 8.77 (s, 1H), 8.64 (s, 1H), 8.18 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.6 Hz, 1H), 7.79 (td, J = 8.9, 6.6 Hz, 2H), 7.57- DMSO 95 Method G1, AQ1 362.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.46 (m, 1H), 7.34 (td, J = 8.5, 2.2 Hz, 1H), 3.20 (d, J = 4.5 Hz, 3H), 2.93 (s, 3H). 1512 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.57 (s, 1H), 8.83 (dd, J = 8.0, 1.6 Hz, 1H), 8.63 (dd, J = 4.8, 2.0 Hz, 1H), 8.38 (s, 1H), 7.95-7.86 (m, 2H), 7.67- 7.57 (m, 2H), 7.15-7.09 (m, 2H), 4.44 (brs, 1H), 2.17 (t, J = 7.6 Hz, 1H), DMSO 95 Method G1, AQ1 417.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1.91-1.89 (m, 1H), 1.78 (d, J = 12.0 Hz, 1H), 1.56-1.48 (m, 4H), 1.32-1.28 (m, 1H). 1513 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.55 (s, 1H), 8.94-8.89 (m, 2H), 8.58 (s, 1H), 8.23 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.85 (t, J = 6.8 Hz, 1H), 7.73 (dd, J = 14.4, 8.0 Hz, 1H), 7.25-7.19 (m, 2H), 4.01 (q, DMSO 95 Method G1, AQ1 363.1 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 7.2 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H). 1514 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.71 (s, 1H), 9.21 (d, J = 8.4 Hz, 1H), 9.08 (d, J = 4.4 Hz, 1H), 8.68 (s, 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.15-8.12 (m, 2H), 7.50- 7.38 (m, 3H), 4.04 (q, J = 7.2 Hz, 2H), 1.49 (t, J = DMSO 95 Method G1, AQ1 363.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.2 Hz, 3H). 1515 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.67 (s, 1H), 9.25 (d, J = 8.0 Hz, 1H), 9.03 (d, J = 5.2 Hz, 1H), 8.60 (s, 1H), 8.21- 8.14 (m, 2H), 8.06 (d, J = 8.4 Hz, 1H), 7.40- 7.26 (m, 3H), 4.26 (brs, 4H), 2.14 (brs, 4H). DMSO- d.sub.6 95 Method G1, AQ1 389.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1516 0 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.60 (s, 1H), 9.14 (d, J = 8.0 Hz, 1H), 9.10 (d, J = 5.2 Hz, 1H), 8.69 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.09 (dd, J = 8.0, 5.2 Hz, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.39-7.27 (m, 3H), 4.60-4.50 DMSO 95 Method G1, AQ1 417.1 (M + 1) Method B (NH.sub.4HCO.sub.3) (m, 1H), 2.08 (d, J = 11.6 Hz, 2H), 1.84 (d, J = 12.0 Hz, 2H), 1.69 (d, J = 8.4 Hz, 1H), 1.57- 1.45 (m, 4H), 1.18-1.10 (m, 1H). 1517 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.04 (brs, 1H), 9.58 (s, 1H), 9.38 (brs, 1H), 8.84 (d, J = 5.6 Hz, 2H), 8.72 (s, 1H), 8.28 (d, J = 9.2 Hz, 1H), 7.75 (t, J = 6.8 Hz, 1H), 7.51-7.41 (m, DMSO 95 Method G1, AQ1 428.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H), 7.07-7.03 (m, 1H), 3.88 (s, 3H), 3.80 (q, J = 5.6 Hz, 2H), 2.32 (t, J = 7.2 Hz, 2H), 1.86-1.74 (m, 2H), 1.73- 1.64 (m, 2H). 1518 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.74 (td, J = 8.0, 1.6 Hz, 1H), 8.71- 8.66 (m, 1H), 8.31 (d, J = 1.6 Hz, 1H), 8.08 (dd, J = 8.8, 2.0 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), DMSO 95 Method G1, AQ1 345.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.87-7.81 (m, 2H), 7.58-7.49 (m, 1H), 7.39- 7.30 (m, 2H), 3.49 (s, 6H). 1519 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.74 (d, J = 7.2 Hz, 1H), 8.69 (d, J = 3.6 Hz, 1H), 8.32 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 7.6 DMSO 95 Method G1, AQ1 361.1 363.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 2H), 7.62- 7.48 (m, 3H), 3.48 (s, 6H). 1520 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.74 (td, J = 8.0, 1.6 Hz, 1H), 8.69 (dd, J = 4.8, 1.6 Hz, 1H), 8.42 (d, J = 2.0 Hz, 1H), 8.16 (dd, J = 8.8, 2.0 Hz, 1H), 8.04-7.89 (m, 5H), 7.54 (q, J = DMSO 95 Method G1, AQ1 352.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 5.2 Hz, 1H), 3.51 (s, 6H). 1521 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.76 (d, J = 8.0 Hz, 1H), 8.68-8.60 (m, 2H), 8.15 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.56 (q, J = 4.8 Hz, 1H), 7.49-7.40 (m, DMSO 95 Method G1, AQ1 428.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H), 7.30 (s, 1H), 7.06-6.97 (m, 1H), 6.73 (s, 1H), 3.87 (s, 5H), 2.14 (t, J = 7.2 Hz, 2H), 1.80- 1.71 (m, 2H), 1.71-1.62 (m, 2H). 1522 2 HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.67 (s, 1H), 9.39 (d, J = 8.2 Hz, 1H), 9.02 (d, J = 5.3 Hz, 1H), 8.31 (d, J = 9.3 Hz, 2H), 8.24- 8.10 (m, 3H), 7.88 (d, J = 7.7 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 3.54 (s, 6H), 2.78 (s, 3H). DMSO 95 Method G1, AQ1 366.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1523 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (d, J = 1.7 Hz, 1H), 8.88- 8.32 (m, 4H), 8.16 (dd, J = 8.7, 1.8 Hz, 1H), 7.86 (t, J = 9.2 Hz, 1H), 7.55 (dd, J = 7.9, 4.8 Hz, 1H), 7.50-7.34 (m, 3H), 7.01 (dt, J = 7.3, 2.1 Hz, 1H), 3.96- 3.84 (m, 5H), 2.78 (t, J = 6.9 Hz, DMSO 95 Method G1, AQ1 400.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 2H). 1524 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (s, 1H), 8.77 (d, J = 8 Hz, 1H), 8.66-8.63 (m, 3H), 8.15 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.45- 7.41 (m, 3H), DMSO 95 Method G1, AQ1 414.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.33 (s, 1H), 7.01 (d, J = 7.0 Hz, 1H), 6.79 (s, 1H), 3.88 (s, 3H), 3.72 (d, J = 6.0 Hz, 2H), 2.24 (t, J = 7.2 Hz, 2H), 2.04-1.94 (m, 2H). 1525 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.58 (d, J = 1.2 Hz, 1H), 8.73- 8.68 (m, 3H), 8.37 (s, 1H), 8.27- 8.22 (m, 4H), 7.89-7.87 (m, 2H), 7.75 (t, J = 8.0 Hz, 1H), 7.55 (dd, J = 8.0, 5.2 DMSO 95 Method G1, AQ1 324.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 1H). 1526 0 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.57 (d, J = 1.6 Hz, 1H), 8.72- 8.66 (m, 2H), 8.57 (d, J = 1.6 Hz, 1H), 8.19-7.91 (m, 3H), 7.83 (d, J = 8.0 Hz, 3H), 7.54 (dd, J = 7.6, 4.8 Hz, 1H), DMSO 95 Method G1, AQ1 329.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.10 (d, J = 8.4 Hz, 2H), 3.83 (s, 3H). 1527 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.58 (s, 1H), 8.72- 8.66 (m, 3H), 8.16 (d, J = 8.4 Hz, 3H), 7.91 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.54 (dd, J = 7.6, DMSO 95 Method G1, AQ1 333.1, 335.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 4.8 Hz, 1H). 1528 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.59 (s, 1H), 9.28 (d, J = 8.0 Hz, 1H), 9.01 (d, J = 5.6 Hz, 1H), 8.65 (s, 2H), 8.37 (s, 2H), 8.25 (d, J = 8.0 Hz, 1H), 8.22 (s, 1H), 8.13 (t, J = 6.8 DMSO 95 Method G1, AQ1 338.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.74 (t, J = 8.0 Hz, 1H), 2.77 (s, 3H). 1529 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.78 (s, 1H), 9.72 (d, J = 1.8 Hz, 1H), 9.18 (d, J = 8.1 Hz, 1H), 8.98 (dd, J = 5.1, 1.2 Hz, 1H), 8.78 (s, 1H), 8.29 (d, J = 8.6 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.95 (dd, J = 7.9, 5.3 Hz, 1H), 7.80 (td, J = 8.9, 6.6 Hz, 1H), DMSO 95 Method G1, AQ1 434.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.55-7.45 (m, 1H), 7.34 (td, J = 8.4, 2.3 Hz, 1H), 7.26 (s, 1H), 6.96 (s, 1H), 3.98 (d, J = 6.1 Hz, 2H), 1.24 (s, 6H). 1530 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.58 (s, 1H), 9.04- 8.89 (m, 2H), 8.71-8.66 (m, 1H) 8.15- 8.11 (m, 2H), 7.82-7.76 (m, 2H), 7.51 (t, J = 9.2 Hz, 1H), 7.34 (t, J = 8.8 Hz, 1H), 4.64 (s, 2H), 3.19 (s, 3H), 2.91 (s, DMSO 95 Method G1, AQ1 420.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H). 1531 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (s, 1H), 8.78 (d, J = 7.9 Hz, 1H), 8.72 (d, J = 3.2 Hz, 1H), 8.19 (s, 2H), 8.08-7.97 (m, 2H), 7.80 (dd, J = 15.5, 8.9 Hz, 1H), 7.58 (dd, J = 7.6, 4.9 Hz, 1H), 7.52-7.41 (m, 1H), 7.29 (td, J = 8.3, 1.9 Hz, 1H), DMSO 95 Method G1, AQ1 418.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 4.48 (s, 2H), 4.15 (s, 2H), 3.48 (s, 2H). 1532 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.65 (s, 1H), 8.87 (s, 1H), 8.79 (d, J = 7.7 Hz, 1H), 8.70 (s, 1H), 8.59 (s, 1H), 8.23 (s, 1H), 8.05- 7.89 (m, 3H), 7.75 (dd, J = 15.1, 7.6 Hz, 1H), 7.56 (s, 1H), 7.48 (t, J = 9.9 Hz, 1H), 7.32 (t, J = 8.1 Hz, 1H), 4.46 (t, DMSO 95 Method G1, AQ1 442.0 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 13.4 Hz, 2H). 1533 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.63 (s, 1H), 8.95- 9.03 (m, 2H), 8.78 (s, 1H), 8.14- 8.24 (m, 2H), 7.88 (t, J = 6.0 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.54-7.48 (m, 1H), 7.35-7.32 (m, 1H), 4.89 (m, 1H), 1.39 (d, DMSO 95 Method G1, AQ1 377.1 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 1.2 Hz, 6H). 1534 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.69- 8.74 (m, 2H), 8.59 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.71-7.77 (m, 1H), 7.66 (s, 1H), 7.56-7.60 (m, 1H), 7.42-7.48 (m, 1H), 7.27- 7.32 (m, 1H), DMSO 95 Method G1, AQ1 391.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1.66 (s, 9H). 1535 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74 (s, 1H), 9.66 (s, 1H), 9.22 (d, J = 7.6 Hz, 1H), 8.99 (d, J = 4.8 Hz, 1H), 8.83 (s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.95 (t, J = 6.2 Hz, 1H), 7.58 (q, J = 8.6 Hz, 1H), 7.51 (t, J = 7.0 Hz, 1H), 7.46-7.41 (m, 1H), 7.25 (s, DMSO 95 Method G1, AQ1 446.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 6.72 (s, 1H), 5.13-5.06 (m, 1H), 3.21 (q, J = 7.3 Hz, 1H), 2.22-1.92 (m, 5H), 1.68-1.57 (m, 1H). 1536 0 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.81 (s, 2H), 9.32 (d, J = 8.0 Hz, 1H), 9.02 (d, J = 5.2 Hz, 1H), 8.81 (s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.00 (dd, J = 7.8, 5.8 Hz, 1H), 7.76 (dd, J = 15.4, 8.6 Hz, 1H), 7.51 (t, J = 10.0 Hz, 1H), 7.35 (t, J = 8.2 Hz, 1H), DMSO 95 Method G1, AQ1 446.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.29 (s, 1H), 6.73 (s, 1H), 5.15- 5.07 (m, 1H), 3.21 (q, J = 7.3 Hz, 1H), 2.23- 1.87 (m, 5H), 1.68-1.57 (m, 1H). 1537 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.66 (s, 1H), 8.79 (d, J = 7.6 Hz, 1H), 8.69 (dd, J = 4.4, 1.2 Hz, 1H), 8.61 (d, J = 1.6 Hz, 1H), 8.40 (d, J = 7.2 Hz, 1H), 8.13 (dd, J = 8.6, 1.4 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 7.6, 4.8 Hz, 1H), 7.49-7.40 (m, 3H), 7.11 (s, 1H), DMSO 95 Method G1, AQ1 Method B (NH.sub.4HCO.sub.3) 7.02 (d, J = 7.2 Hz, 1H), 6.69 (s, 1H), 5.03-4.96 (m, 1H), 3.87 (s, 3H), 3.20 (dd, J = 15.0, 7.4 Hz, 1H), 2.22-1.88 (m, 5H), 1.70-1.56 (m, 1H). 1538 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.60 (s, 1H), 8.86 (d, J = 7.7 Hz, 1H), 8.74 (d, J = 8.0 Hz, 1H), 8.69 (d, J = 3.3 Hz, 1H), 8.65 (s, 1H), 8.19 (d, J = 7.4 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.54 (dd, J = 7.8, 4.8 Hz, 1H), 7.50- 7.40 (m, 3H), DMSO 95 Method G1, AQ1 426.1, 427.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.01 (dd, J = 7.3, 3.9 Hz, 1H), 4.85 (dd, J = 16.9, 8.7 Hz, 1H), 3.88 (s, 3H), 2.16 (s, 2H), 1.96 (s, 2H).

(421) TABLE-US-00038 1539 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.34 (s, 1H), 9.67 (s, 1H), 9.07 (s, 1H), 8.97 (d, J = 5.0 Hz, 1H), 8.92 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.25 (d, J = 7.4 Hz, 1H), 7.99 (s, 1H), 7.90 (s, 1H), 7.48 DMSO 95 Method G1, AQ1 414.0, 415.0 (M + 1) Method B (NH.sub.4HCO.sub.3) (d, J = 5.8 Hz, 3H), 7.09-6.99 (m, 1H), 4.03 (d, J = 6.1 Hz, 2H), 3.89 (s, 3H), 2.65 (t, J = 6.8 Hz, 2H), 2.56 (d, J = 4.4 Hz, 3H). 1540 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.48 (s, 1H), 9.64 (s, 1H), 9.05 (d, J = 7.9 Hz, 1H), 9.01-8.92 (m, 2H), 8.38 (d, J = 8.8 Hz, 1H), 8.28 (d, J = 8.6 Hz, 1H), 7.93- 7.83 (m, 1H), 7.55-7.43 (m, DMSO 95 Method G1, AQ1 428.1, 429.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H), 7.08-6.98 (m, 1H), 4.04 (dd, J = 12.4, 6.6 Hz, 2H), 3.89 (s, 3H), 2.98 (s, 3H), 2.89 (t, J = 7.0 Hz, 2H), 2.84 (s, 3H). 1541 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.02 (brs, 1H), 9.75 (d, J = 1.6 Hz, 1H), 9.07 (dd, J = 8.0, 1.6 Hz, 1H), 8.83 (s, 1H), 8.35 (d, J = 9.2 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.14 (d, J = DMSO 95 Method G1, AQ1 411.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.8 Hz, 1H), 7.48-7.46(m, 3H), 7.06-7.03 (m, 1H), 3.89 (s, 3H), 3.30 (d, J = 4.0 Hz, 3H). 1542 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.22 (brs, 1H), 9.64 (s, 1H), 9.01 (d, J = 6.4 Hz, 1H), 8.95 (d, J = 4.0 Hz, 1H), 8.89 (s, 1H), 8.39 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.85 (t, J = 5.2 Hz, 1H), 7.52-7.42 (m, 4H), 7.08-7.05 (m, 1H), 6.89 (s, 1H), 3.89 (s, 4H), 3.83-3.76 (m, 2H), 2.83- 2.79 (m, 1H), 1.65-1.56 (m, DMSO 95 Method G1, AQ1 510.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 7H), 1.24-1.07 (m, 6H), 0.89- 0.81 (m, 2H). 1543 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.67 (d, J = 1.6 Hz, 1H), 8.80 (dt, J = 8.0, 2.0 Hz, 1H), 8.70 (dd, J = 4.4, 2.0 Hz, 1H), 8.15 (s, 1H), 7.87 (s, 1H), 7.71- 7.67 (m, 1H), 7.58-7.55 (m, DMSO 95 Method G1, AQ1 359.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 7.47 (d, J = 2.4 Hz, 1H), 7.34 (m, 2H), 3.45 (s, 6H), 2.76 (s, 3H). 1544 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.66 (s, 1H), 8.82-8.79 (m, 1H), 8.70 (d, J = 4.0 Hz, 1H), 8.20 (d, J = 1.6 Hz, 1H), 8.02 (s, 1H), 7.86-7.84 (m, 2H), 7.58-7.55 (m, 3H), 3.48 (s, DMSO 95 Method G1, AQ1 375.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 6H), 2.77 (s, 3H). 1545 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.68 (s, 1H), 9.01 (d, J = 8.0 Hz, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.18 (d, J = 1.6 Hz, 1H), 8.03 (s, 1H), 7.88-7.84 (m, 2H), 7.80- 7.77 (m, 1H), DMSO 95 Method G1, AQ1 359.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.37-7.33 (m, 2H), 3.50 (s, 6H), 2.78 (s, 3H). 1546 0 .sup.1H-NMR (400 MHz, CD.sub.3OD): 9.51 (s, 1H), 8.81 (d, J = 7.8 Hz, 1H), 8.54 (s, 1H), 8.35 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.29 (dt, J = 11.2, 4.8 CD3OD 95 Method G1, AQ1 416.1 (M + 1) Method B (NH.sub.4HCO.sub.3) Hz, 3H), 6.88 (d, J = 7.5 Hz, 1H), 4.43 (dd, J = 7.1, 4.0 Hz, 1H), 4.16 (dd, J = 13.8, 4.0 Hz, 1H), 3.86 (dd, J = 13.7, 7.4 Hz, 1H), 3.80 (s, 3H). 1547 2HCl .sup.1H-NMR (400 MHz, CD.sub.3OD): 9.74 (s, 1H), 9.44 (d, J = 8.2 Hz, 1H), 9.02 (d, J = 5.5 Hz, 1H), 8.50 (s, 1H), 8.24 (dd, J = 8.0, 5.9 Hz, 1H), 8.16 (q, J = 8.7 Hz, 2H), 7.70-7.58 (m, 1H), 7.12- 7.00 (m, 2H), 6.13 (s, 1H), 4.44- CD.sub.3OD 95 Method G1, AQ1 457.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 4.41 (m, 1H), 4.29-4.27 (m, 1H), 2.37-2.16 (m, 3H), 2.09- 2.07 (m, 1H). 1548 2HCl .sup.1H-NMR (400 MHz, CD.sub.3OD): 9.85 (s, 1H), 9.57 (d, J = 8.0 Hz, 1H), 9.10 (d, J = 4.8 Hz, 1H), 8.64 (s, 1H), 8.34-8.22 (m, 3H), 7.51 (t, J = 6.9 Hz, 1H), 7.47- 7.33 (m, 2H), 6.23 (s, 1H), 4.53- 4.51 (m, 1H), 4.38-4.36 (m, CD.sub.3OD 95 Method G1, AQ1 457.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 2.51-2.30 (m, 3H), 2.19- 2.18 (m, 1H). 1549 2HCl .sup.1H-NMR (400 MHz, DMSO): 10.38 (brs, 1H), 9.63 (d, J = 1.6 Hz, 1H), 9.00 (d, J = 8.0 Hz, 1H), 8.95-8.94 (m, 2H), 8.39 (d, J = 9.2 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.88-7.85 (m, 1 H), 7.49- 7.48 (m, 3H), 7.07-7.04 (m, 1H), 3.94-3.89 (m, 5H), 3.60- DMSO 95 Method G1, AQ1 387.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3.57 (m, 2H), 1.96-1.93 (m, 2H). 1550 .sup.1H-NMR (400 MHz, DMSO): 9.62 (s, 1H), 8.72- 8.70 (m, 2H), 8.40 (s, 1H), 8.11- 7.94 (m, 2H), 7.91-7.74 (m, 3H), 7.54 (dd, J = 7.6, 4.8 Hz, 1H), 7.09 (d, J = 8.6 Hz, 2H), 3.83 (s, DMSO 95 Method G1, AQ1 343.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3H), 2.74 (s, 3H). 1551 .sup.1H-NMR (400 MHz, DMSO): 9.64 (s, 1H), 8.76 (d, J = 8.0 Hz, 1H), 8.70 (d, J = 4.4 Hz, 1H), 8.46 (s, 1H), 8.12-7.83 (m, 5H), 7.57 (dd, J = 7.8, 4.8 Hz, 1H), 7.39 (t, J = 8.7 Hz, 2H), DMSO 95 Method G1, AQ1 331.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 2.84 (s, 3H). 1552 1H-NMR (400 MHz, DMSO): 9.62 (s, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.71 (d, J = 4.4 Hz, 1H), 8.23 (s, 1H), 8.20 (s, 1H), 8.07- 8.00 (m, 2H), 7.60-7.50 (m, 3H), 7.40-7.37 (m, 1H), 4.48 (s, 2H), 4.12-4.10 (m, 2H), 3.48- 3.46 (m, 2H). DMSO 95 Method G1, AQ1 418.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1553 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74 (s, 1H), 9.45 (s, 1H), 9.27 (d, J = 8.8 Hz, 1H), 8.97 (s, 1H), 8.69 (s, 1H), 8.12- 8.00 (m, 3H), 7.83-7.76 (m, 1H), 7.51-7.32 (m, 2H), 480- 4.64 (m, 2H). DMSO 95 Method G1, AQ1 417.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1554 2HCl .sup.1H-NMR (400 MHz, CD3OD): 9.86 (s, 1H), 9.48 (d, J = 8.8 Hz, 1H), 9.18 (d, J = 5.2 Hz, 1H), 8.72 (s1H), 8.92 (s, 1H), 8.37-8.31 (m, 2H), 8.22 (d, J = 8.8 Hz, 1H), 7.80-7.55 (m, 1H), 7.26- 7.20 (m, 2H), 4.92 (d, J = 4.8 Hz, CD3OD 95 Method G1, AQ1 380.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 4.81 (t, J = 4.8 Hz, 1H), 4.39-4.30 (m, 2H). 1555 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.62 (s, 1H), 8.7-8.68 (m, 2H), 8.32 (s, 1H), 7.97- 7.93 (m, 2H), 7.91-7.36 (m, 5H), 347 (s, 6H). DMSO 95 Method G1, AQ1 345.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1556 0 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.61 (s, 1H), 8.75 (d, J = 8.0 Hz, 1H), 8.67 (d, J = 3.6 Hz, 1H), 8.48 (s, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.59-7.49 (m, 3H), 7.45-7.30 (m, 5H), 7.02- 6.92 (m, 1H), 4.50 (q, J = 3.2 Hz, 1H), 4.39- 4.20 (m, 2H), 4.14-4.09 (m, DMSO 95 Method G1, AQ1 493.0 495.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 3.98-3.83 (m, 1H), 3.38 (s, 3H), 2.49-2.40 (m, 1H), 2.35- 2.18 (m, 1H). 1557 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.60 (s, 1H), 8.73 (dd, J = 7.6, 1.2 Hz, 1H), 8.67 (dd, J = 8.4, 1.2 Hz, 1H), 8.47 (s, 1H), 8.11 (dd, J = 8.4, 1.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.54- 7.50 (m, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.38- 7.32 (m, 2H), 7.32-7.23 (m, 2H), 7.05 (d, J = DMSO 95 Method G1, AQ1 489.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.4 Hz, 1H), 7.00-6.92 (m, 2H), 4.45 (t, J = 8.4 Hz, 1H), 4.24 (s, 2H), 4.08- 3.95 (m, 1H), 3.88-3.80 (m, 7H), 2.44-2.33 (m, 1H), 2.29- 2.15 (m, 1H). 1558 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.56 (s, 1H), 9.02 (s, 1H), 8.19 (d, J = 7.5 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.58 (dd, J = 7.7, 4.9 Hz, 1H), 7.52- 7.37 (m, 3H), 7.37-7.24 (m, 3H), 7.12 (t, J = 8.8 Hz, 2H), 7.02 (d, J = 7.5 Hz, 1H), 6.84 (s, DMSO 95 Method G1, AQ1 506.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 3.89-3.78 (m, 4H), 3.72-3.66 (m, 1H), 3.13 (s, 1H), 2.97-2.90 (m, 1H), 2.86- 2.78 (m, 1H). 1559 2 HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.48-10.00 (m, 1H), 9.70 (s, 1H), 9.12-8.77 (m, 3H), 8.42- 8.32 (m, 1H), 8.30-8.17 (m, 1H), 7.95-7.79 (m, 1H), 7.55- 7.44 (m, 6H), 7.26 (d, J = 7.2 Hz, 1H), 7.05 (s, 1H), 6.94 (s, 1H), 3.89 (s, 5H), 3.22 (s, 1H), 2.97- 2.81 (m, 2H). DMSO 95 Method G1, AQ1 558.1 560.0 562.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1560 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.25 (s, 1H), 9.61 (d, J = 1.5 Hz, 1H), 8.96 (d, J = 4.0 Hz, 1H), 8.87 (s, 1H), 8.39 (d, J = 8.5 Hz, 1H), 8.25 (d, J = 7.7 Hz, 1H), 7.87 (s, 1H), 7.52- 7.44 (m, 4H), 7.36 (t, J = 7.6 Hz, 1H), 7.28 (dd, J = 13.5, 6.0 Hz, 1H), 7.22-7.10 (m, 2H), 7.06 (d, J = 7.5 Hz, 1H), 6.89 (s, 1H), 3.95- DMSO 95 Method G1, AQ1 508.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 3.81 (m, 5H), 3.21 (d, J = 9.0 Hz, 1H), 2.94 (d, J = 7.3 Hz, 2H). 1561 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.64 (s, 1H), 8.74 (m, 2H), 8.69 (d, J = 3.5 Hz, 1H), 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.58-7.49 (m, 1H), 7.43 (m, 4H), 7.28-7.18 (m, 4H), 7.15 (m, 1H), 7.01 (d, DMSO 95 Method G1, AQ1 503.9 (M + 1) Method B (NH.sub.4HCO.sub.3) J = 7.2 Hz, 1H), 6.94 (s, 1H), 3.82- 3.73 (m, 5H), 2.90-2.87 (m. 1H), 2.68-2.65 (m, 2H), 1.89- 1.86 (m, 2H). 1562 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.85 (s, 1H), 8.76 (s, 1H), 8.65 (d, J = 3.6 Hz, 1H), 8.64 (s, 1H), 8.53 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 8.7 Hz, 1H), 7.51 (dd, J = 8.0, 4.7 Hz, 1H), 7.45 (d, J = 6.7 Hz, 2H), 7.40 (s, 1H), DMSO 95 Method G1, AQ1 489.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.31-7.27 (m, 5H), 7.24 (d, J = 6.6 Hz, 1H), 7.00 (d, J = 6.9 Hz, 1H), 6.80 (s, 1H), 3.77-3.70 (m, 5H), 3.17-3.15 (m, 1H), 2.98- 2.81 (m, 2H). 1563 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.57 (s, 1H), 8.74-8.68 (m, 2H), 8.21 (s, 1H), 8.15 (dd, J = 8.7, 1.6 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.56-7.52 (m, 2H), 7.46- 7.31 (m, 4H), 7.12 (d, J = 6.5 Hz, 2H), 6.95-6.93 (m, 1H), 5.16 (s, 2H), 3.78 (s, 3H), 3.53 (s, 3H). DMSO 95 Method G1, AQ1 467.1, 469.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1564 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.64 (d, J = 1.4 Hz, 1H), 8.75 (d, J = 7.9 Hz, 1H), 8.70 (d, J = 4.6 Hz, 1H), 8.32 (s, 1H), 8.12 (d, J = 8.7 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.55 (dd, J = DMSO 95 Method G1, AQ1 507.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.9, 4.8 Hz, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.36- 7.29 (m, 2H), 7.01-6.98 (m, 1H), 6.88 (s, 1H), 6.83 (s, 2H), 4.12-4.03 (m, 2H), 3.85 (s, 3H), 3.69 (s, 3H), 3.62 (s, 3H), 3.56 (d, J = 8.0 Hz, 3H), 3.16-3.02 (m, 2H). 1565 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.64 (d, J = 2.0 Hz, 1H), 8.77- 8.69 (m, 2H), 8.68 (d, J = 1.6 Hz, 1H), 8.64 (d, J = 1.6 Hz, 1H), 8.16 (dd, J = 8.8, 1.6 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.55- 7.52 (m, 1H ), 7.46-7.41 (m, 4H), 7.29 (t, J = 7.2 Hz, 1H), 7.23-7.19 (m, 1H), 7.14-7.06 (m, 2H), 7.01 (dt, J = DMSO 95 Method G1, AQ1 522.3 (M + 1) Method B (NH.sub.4HCO.sub.3) 9.2, 2.0 Hz, 1H), 6.96 (s, 1H), 3.87-3.76 (m, 5H), 2.94- 2.93 (m, 1H), 2.68 (t, J = 7.8 Hz, 2H), 1.89- 1.83 (m, 2H). 1566 0 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.59 (s, 1H), 8.76 (t, J = 5.2 Hz, 1H), 8.69 (dd, J = 4.4, 1.2 Hz, 1H), 8.63 (s, 1H), 8.56 (d, J = 8.4 Hz, 1H), 8.15 (dd, J = 8.8, 1.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.53-7.50 (m, 1H), 7.48-7.40 (m, 3H), 7.36- 7.32 (m, 3H), 7.30-7.24 (m, 2H), 7.02-7.00 (m, 1H), 6.85 (s, DMSO 95 Method G1, AQ1 524.2, 526.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 3.92-3.83 (m, 4H), 3.72- 3.69 (m, 1H), 3.18-3.14 (m, 1H), 2.96-2.84 (m, 2H). 1567 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.64 (s, 1H), 9.08 (s, 1H), 8.79- 8.69 (m, 2H), 8.51 (s, 1H), 8.31 (s, 1H), 8.00- 7.89 (m, 2H), 7.85- 7.69 (m, 1H), 7.67-7.42 (m, 2H), 7.30-7.21 (m, 2H), 5.00 (d, J = 5.1 Hz, 2H). DMSO 95 Method G1, AQ1 416.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1568 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.58 (s, 1H), 10.09 (d, J = 4.4 Hz, 1H), 9.65 (s, 1H), 9.05-9.02 (m, 2H), 8.95 (d, J = 4.4 Hz, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.30- 8.27 (m, 1H), DMSO 95 Method G1, AQ1 504.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.85 (t, J = 6.2 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.49-7.43 (m, 3H), 7.24 (t, J = 7.8 Hz, 2H), 7.03-6.97 (m, 2H), 3.89 (s, 3H), 3.86- 3.84 (m, 2H), 2.44 (t, J = 7.0 Hz, 2H), 1.87- 1.77 (m, 4H). 1569 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.62 (s, 1H), 9.67 (s, 1H), 9.08 (d, J = 7.2 Hz, 1H), 9.03 (s, 1H), 8.97 (d, J = 5.2 Hz, 1H), 8.44 (t, J = 5.6 Hz, 1H), DMSO 95 Method G1, AQ1 518.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 8.40 (dd, J = 8.8, 0.8 Hz, 1H), 8.32 (dd, J = 9.2, 2.8 Hz, 1H), 7.89 (t, J = 6.4 Hz, 1H), 7.50-7.44 (m, 3H), 7.25-7.14 (m, 5H), 7.03 (d, J = 7.2 Hz, 1H), 4.24 (d, J = 6.0 Hz, 2H), 3.89 (s, 3H), 3.87-3.82 (m, 2H), 2.26 (t, J = 7.0 Hz, 2H), 1.84-1.69 (m, 4H). 1570 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.55 (s, 1H), 8.69 (dd, J = 11.3, 6.2 Hz, 2H), 8.23 (s, 1H), 8.15 (d, J = 8.7 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.59- 7.50 (m, 2H), 7.44-7.26 (m, 3H), 7.23 (t, J = 7.5 Hz, 1H), 7.15 (s, 1H), 7.12 (d, J = 7.7 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.18 DMSO 95 Method G1, AQ1 451.2, 452.2, 453.2 (M + 1) Method B (NH.sub.4HCO.sub.3) (s, 2H), 3.79 (s, 3H), 3.54 (s, 3H). 1571 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.62 (s, 1H), 9.60 (s, 1H), 8.88 (d, J = 4.3 Hz, 1H), 8.82 (s, 1H), 8.78 (d, J = 8.1 Hz, 1H), 8.31 (d, J = 8.6 Hz, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.75 (dd, J = 7.8, 5.1 Hz, 1H), 7.53-7.39 (m, 4H), 7.33 (dd, J = 14.3, 7.9 Hz, 1H), 7.12 (t, J = 7.8 Hz, 2H), 7.03 (dd, J = 11.0, 6.3 Hz, DMSO 95 Method G1, AQ1 508.1, 509.1, 510.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 2H), 6.90 (s, 1H), 3.97-3.90 (m, 4H), 3.82 (dd, J = 18.0, 9.5 Hz, 1H), 3.19 (dd, J = 13.4, 7.5 Hz, 1H), 2.98 (dd, J = 13.6, 7.9 Hz, 1H), 2.87 (dd, J = 13.6, 6.7 Hz, 1H). 1572 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.20 (s, 1H), 9.61 (s, 1H), 8.94 (d, J = 4.8 Hz, 1H), 8.86 (s, 2H), 8.37 (d, J = 8.4 Hz, 1H), 8.22 (s, 1H), 7.83 (s, 1H), 7.56-7.32 (m, 6H), 7.31-7.19 (m, 2H), 7.06 (d, J = 7.2 Hz, 1H), 6.89 (s, 1H), 4.03-3.93 (m, 1H), 3.88 (s, 3H), 3.82 (dd, J = 14.4, 5.5 Hz, 1H), 3.22 (s, 1H), 3.02 DMSO 95 Method G1, AQ1 524.1, 525.1, 526.0 (M + 1) Method B (NH.sub.4HCO.sub.3) (d, J = 7.2 Hz, 2H). 1573 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.31 (s, 1H), 9.63 (s, 1H), 8.96 (d, J = 4.4 Hz, 1H), 8.90 (s, 1H), 8.84 (d, J = 7.7 Hz, 1H), 8.39 (d, J = 8.7 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 7.91- 7.80 (m, 1H), 7.48 (dd, J = 15.6, 7.7 Hz, 3H), 7.36 (s, 1H), 7.24-7.03 (m, 5H), 6.85 (s, 1H), 4.03-3.93 (m, 1H), 3.88 (s, 3H), DMSO 95 Method G1, AQ1 504.1, 505.2, 506.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 3.83 (dd, J = 14.7, 7.6 Hz, 1H), 3.15 (s, 1H), 2.94 (dd, J = 13.8, 8.0 Hz, 1H), 2.84 (dd, J = 13.8, 6.6 Hz, 1H), 2.29 (s, 3H). 1574 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.43 (s, 1H), 9.71 (s, 1H), 9.05 (d, J = 4.7 Hz, 1H), 9.01 (d, J = 7.6 Hz, 1H), 8.96 (s, 1H), 8.45 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 7.99- 7.89 (m, 1H), 7.61-7.41 (m, 4H), 7.23 (d, J = 7.8 Hz, 2H), 7.13 (d, J = 7.6 Hz, 3H), 6.93 (s, 1H), 4.01-3.84 (m, 5H), 3.31-3.21 (m, 1H), 3.02- 2.97 (m, 7.5 Hz, DMSO 95 Method G1, AQ1 504.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1H), 2.87-2.81 (m, 1H), 2.29 (s, 3H).

(422) TABLE-US-00039 1575 .sup.1H-NMR (400 MHz, CD.sub.3OD): 9.39 (s, 1H), 8.69 (d, J = 8.0 Hz, 1H); 8.65 (s, 1H), 8.38 (s, 1H), 8.07 (d, J = 7.9 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.60-7.53 (m, 1H), 7.35-7.25 (m, 5H), 7.18 (dd, J = 13.6, 7.2 Hz, 2H), 7.12 (s, 1H), 6.88 (dd, J = 7.9, 2.1 Hz, 1H), 4.49 (dd, J = 11.3, 7.9 Hz, 1H), 4.36-4.17 (m, 2H), 4.04 (t, J = CD3OD 95 Method G1, AQ1 459.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 10.4 Hz, 1H), 3.74 (s, 3H), 3.60- 3.49 (m, 1H), 2.50- 2.39 (m, 1H), 2.27- 2.14 (m, 1H). 1576 0 .sup.1H-NMR (400 MHz, DMSO- d.sub.6): 9.67 (d, J = 1.7 Hz, 1H), 9.05 (s, 1H), 8.94 (d, J = 3.7 Hz, 1H), 8.59 (s, 1H), 8.40-8.22 (m, 2H), 7.85 (s, 1H), 7.79 (d, J = 1.9 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H), 7.52- DMSO 95 Method G1, AQ1 527.0, 529.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.36 (m, 4H), 7.04 (d, J = 7.6 Hz, 1H), 4.74-4.72 (m, 2H), 4.48-4.43 (m, 3H), 3.85 (s, 3H), 3.74-3.60 (m, 1H), 2.25-2.23 (m, 1H). 1577 2HCl .sup.1H-NMR (400 MHz, DMSO): 9.69 (d, J = 1.6 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.79 (d, J = 1.6 Hz, 1H), 8.73 (s, 1H), 8.21 (d, J = 9.2 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.67 (dd, J = 7.6, 4.8 Hz, 1H), 7.56- 7.38 (m, 7H), 7.05- 7.02 (m, 1H), 5.59 (s, 4H), 3.89 (s, 3H). DMSO 95 Method G1, AQ1 431.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1578 .sup.1H-NMR (400 MHz, DMSO): 9.59 (d, J = 1.6 Hz, 1H), 8.81-8.64 (m, 2H), 8.28- 8.10 (m, 2H), 7.96 (d, J = 8.6 Hz, 1H), 7.55 (td, J = 8.5, 5.0 Hz, 3H), 7.40-7.06 (m, 5H), 6.94 (dd, J = 8.2, 2.0 Hz, 1H), 5.15 (s, 2H), 3.78 (s, 3H), 3.51 (s, 3H). DMSO 95 Method G1, AQ1 451.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 1579 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 10.61 (s, 1H), 9.66 (s, 1H), 9.00 (d, J = 13.5 Hz, 3H), 8.43-8.31 (m, 2H), 7.89 (s, 1H), 7.48 (dd, J = 14.6, 7.2 Hz, 3H), 7.33-7.22 (m, 4H), 7.21- 7.14 (m, 1H), DMSO 95 Method G1, AQ1 491.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 7.05 (d, J = 7.2 Hz, 1H), 4.10- 3.85 (m, 2H), 3.90 (s, 3H), 3.37- 3.27 (m, 1H), 3.07-2.91 (m, 2H). 1580 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.91 (s, 1H), 9.60 (s, 1H), 9.11 (s, 1H), 8.95 (s, 1H), 8.66 (s, 1H), 8.20-8.02 (m, 3H), 7.97 (s, 1H), 7.78 (dd, J = 13.3, 6.5 Hz, 1H), 7.50 (t, J = 11.3 Hz, 1H), 7.33 (t, J = 8.1 Hz, 1H), 7.21 (s, 1H), 5.08 (d, J = 3.8 Hz, 2H). DMSO 95 Method G1, AQ1 416.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1581 2HCl .sup.1H-NMR (400 MHz, DMSO- d.sub.6): 9.84 (s, 1H), 9.71 (s, 1H), 9.12 (d, J = 6.2 Hz, 1H), 8.96 (d, J = 4.8 Hz, 1H), 8.91 (s, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.30 (s, 1H), 7.88 (s, 1H), 7.57-7.38 (m, 3H), 7.24 (s, 1H), 7.08 (d, J = 7.9 Hz, 1H), 6.73 (s, 1H), 5.18- 5.05 (m, 1H), DMSO 95 Method G1, AQ1 440.2 (M + 1) Method B (NH.sub.4HCO.sub.3) 3.88 (s, 3H), 3.23 (dd, J = 14.8, 7.4 Hz, 1H), 2.31- 2.17 (m, 1H), 2.15-1.89 (m, 4H), 1.71-1.57 (m, 1H). 1583 2HCl 1H-NMR (300 MHz, DMSO): 10.39 (s, 1H), 9.71 (s, 1H), 9.14 (d, J = 8.1 Hz, 1H), 8.98 (d, J = 4.0 Hz, 1H), 8.71 (s, 1H), 8.31 (d, J = 8.8 Hz, 1H), 8.25-8.19 (m, 1H), 7.96-7.89 DMSO 95 Method AQ2, AP 361.7 (M + 1) Method C (m, 1H), 7.38 (dd, J = 9.2, 3.0 Hz, 1H), 7.34- 7.14 (m, 2H), 3.81 (s, 4H), 3.30 (d, J = 4.4 Hz, 4H). 1584 2HCl 1H-NMR (300 MHz, DMSO): 10.84 (s, 1H), 9.01 (s, 1H), 8.95 (d, J = 3.9 Hz, 1H), 8.72 (d, J = 7.8 Hz, 1H), 8.50- 8.40 (m, 1H), 8.33 (d, J = 8.8 Hz, 1H), 8.24 (td, J = 7.8, 1.7 Hz, DMSO 95 Method AQ2, AP 343.5 (M + 1) Method C 1H), 7.85 (dd, J = 6.5, 4.8 Hz, 1H), 7.57-7.43 (m, 3H), 7.09- 7.02 (m, 1H), 3.90 (s, 3H), 3.38 (s, 3H) 1585 2HCl 1H-NMR (300 MHz, DMSO): 10.44-10.13 (m, 1H), 9.66 (s, 1H), 9.08 (d, J = 10.1 Hz, 2H), 8.96 (d, J = 3.7 Hz, 1H), 8.44 (d, J = 8.9 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.13 (dd, J = 13.3, 5.3 DMSO 95 Method AQ2, AP 356.4 (M + 1) Method C Hz, 2H), 8.00 (d, J = 8.2 Hz, 1H), 7.91 (s, 1H), 3.30 (d, J = 4.4 Hz, 3H). 1586 1H-NMR (300 MHz, DMSO): 9.64 (s, 1H), 8.78 (d, J = 8.0 Hz, 1H), 8.73-8.69 (m, 1H), 8.63 (s, 2H), 8.47-8.37 (m, 1H), 8.32- 8.25 (m, 1H), 8.23-8.12 (m, 1H), 7.87 (d, J = DMSO 95 Method AQ2, AP 356.4 (M + 1) Method C 8.6 Hz, 1H), 7.73 (t, J = 9.0 Hz, 1H), 7.55 (dd, J = 7.9, 4.7 Hz, 1H), 3.20 (d, J = 4.3 Hz, 3H). 1587 000 1H-NMR (300 MHz, DMSO): 9.65 (s, 1H), 8.79 (d, J = 8.0 Hz, 1H), 8.72-8.57 (m, 2H), 8.24 (d, J = 8.7 Hz, 1H), 7.88 (d, J = 8.7 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, DMSO 95 Method AQ2, AP 401.5 (M + 1) Method C 1H), 7.53 (t, J = 10.9 Hz, 2H), 7.45-7.36 (m, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.21 (d, J = 4.1 Hz, 3H). 1588 001 2HCl 1H-NMR (300 MHz, DMSO): 10.77 (s, 1H), 9.66 (s, 1H), 9.06 (s, 2H), 8.95 (d, J = 3.8 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 8.26 (d, J = 8.8 Hz, 1H), 7.87 (s, 1H), 7.71 (d, J = 8.1 DMSO 95 Method AQ2, AP 361.5 (M + 1) Method C Hz, 1H), 7.38 (dd, J = 22.8, 11.6 Hz, 2H), 4.03 (s, 3H), 3.31 (d, J = 4.1 Hz, 3H). 1589 002 2HCl 1H-NMR (300 MHz, DMSO): 10.23-10.05 (m, 1H), 9.64 (s, 1H), 9.00 (s, 1H), 8.94 (s, 1H), 8.89 (s, 1H), 8.38 (d, J = 8.6 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 7.85 (s, 1H), 7.36 (d, J = 8.7 Hz, 2H), 6.95 (d, J = DMSO 95 Method AQ2, AP 361.5 (M + 1) Method C 10.9 Hz, 1H), 3.90 (s, 1H), 3.30 (d, J = 4.3 Hz, 3H). 1590 003 2HCl 1H-NMR (300 MHz, DMSO): 10.34 (s, 1H), 9.70 (s, 1H), 9.14 (d, J = 7.4 Hz, 1H) 8.98 (d, J = 3.9 Hz, 1H), 8.75 (s, 1H), 8.32 (d, J = 8.8 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.93 (d, DMSO 95 Method AQ2, AP 361.3 (M + 1) Method C J = 4.8 Hz, 1H), 7.27 (dd, J = 19.5, 6.3 Hz, 3H), 3.88 (s, 3H), 3.28 (d, J = 4.1 Hz, 3H). 1591 004 2HCl 1H-NMR (300 MHz, DMSO): 10.21 (s, 1H), 9.66 (d, J = 1.6 Hz, 1H), 9.04 (d, J = 7.3 Hz, 1H), 8.96 (d, J = 3.5 Hz, 1H), 8.67 (s, 1H), 8.28-8.12 (m, 2H), 7.88 (s, 1H), 7.66 (t, J = DMSO 95 Method AQ2, AP 361.3 (M + 1) Method C 8.8 Hz, 1H), 7.11- 6.97 (m, 2H), 3.86 (s, 3H), 3.30 (d, J = 4.4 Hz, 3H). 1592 005 3HCl 1H-NMR (300 MHz, DMSO): 10.77 (s, 1H), 9.69 (s, 1H), 9.39 (s, 1H), 9.16 (d, J = 7.8 Hz, 1H), 9.04 (s, 1H), 8.97 (d, J = 3.6 Hz, 1H), 8.63 (d, J = 2.5 Hz, 1H), 8.53 (s, 2H), 8.31 DMSO 95 Method AQ2, AP 343.1 (M + 1) Method C (d, J = 8.5 Hz, 1H), 7.91 (d, J = 5.4 Hz, 1H), 4.11 (s, 3H), 3.30 (d, J = 4.4 Hz, 3H). 1593 006 2HCl DMSO 95 Method AQ2, AP 359.1 (M + 1) Method C 1594 007 1H-NMR (300 MHz, DMSO): 9.64 (d, J = 1.3 Hz, 1H), 8.82- 8.75 (m, 1H), 8.68 (dd, J = 4.8, 1.7 Hz, 1H), 8.60 (s, 1H), 8.53 (d, J = 1.7 Hz, 1H), DMSO 95 Method AQ2, AP 371.1 (M + 1) Method C 8.10 (dd, J = 8.7, 1.9 Hz, 1H), 7.86-7.77 (m, 4H), 7.58-7.48 (m, 2H), 7.09 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 1H), 3.99 (d, J = 6.0 Hz, 2H), 3.18 (d, J = 4.4 Hz, 3H), 1.82- 1.69 (m, 2H), 1.07 (d, J = 6.7 Hz, 3H). 1595 008 2HCl 1H-NMR (300 MHz, DMSO): 10.24-10.10 (bs, 1H), 9.65 (s, 1H), 9.02 (s, 1H), 8.96 (d, J = 3.8 Hz, 1H), 8.90 (s, 1H), 8.39 (s, DMSO 95 Method AQ2, AP 443.5 (M + 1) Method C 1H), 8.20 (s, 1H), 8.07 (s, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.54 (t, J = 9.1 Hz, 1H), 3.70 (bs, 4H), 3.59 (bs, 4H), 3.32 (d, J = 4.4 Hz, 3H). 1596 009 2HCl 1H-NMR (300 MHz, DMSO): 10.37 (s, 1H), 9.69 (d, J = 1.7 Hz, 1H), 9.10 (d, J = 7.0 Hz, 1H), 9.03-8.93 (m, 2H), 8.42 (d, J = 8.6 Hz, 1H), DMSO 95 Method AQ2, AP 428.5 (M + 1) Method C 8.28 (d, J = 9.3 Hz, 1H), 8.05 (d, J = 3.5 Hz, 1H), 7.99 (dd, J = 6.2, 2.4 Hz, 2H), 7.52 (t, J = 9.1 Hz, 1H), 3.54-3.43 (m, 4H), 3.30 (t, J = 10.4 Hz, 3H), 1.98-1.81 (m, 4H). 1597 010 2HCl 1H-NMR (300 MHz, DMSO): 10.71 (s, 1H), 8.96 (d, J = 3.9 Hz, 1H), 8.81 (s, 1H), 8.74 (d, J = 7.9 Hz, 1H), 8.36 (d, J = 8.7 Hz, 1H), 8.29-8.19 (m, 2H), 7.87 (dd, J = 6.5, 4.7 Hz, 1H), DMSO 95 Method AQ2, AP 349.4 (M + 1) Method C 7.80 (dd, J = 15.5, 8.9 Hz, 1H), 7.61-7.50 (m, 1H), 7.36 (d, J = 8.1 Hz, 1H), 3.37 (d, J = 4.5 Hz, 3H). 1598 011 1H-NMR (300 MHz, DMSO): 9.27 (d, J = 1.5 Hz, 1H), 8.61 (dd, J = 12.6, 3.0 Hz, 2H), 8.41 (d, J = 2.9 Hz, 1H), 8.34-8.27 (m, 1H), 8.16 (dd, J = 8.7, 1.9 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.45 (dd, J = 16.0, 9.2 Hz, 3H), DMSO 95 Method AQ2, AP 373.4 (M + 1) Method C 7.05-6.97 (m, 1H), 3.96 (s, 3H), 3.87 (s, 3H), 3.19 (d, J = 4.3 Hz, 3H). 1599 012 2HCl 1H-NMR (300 MHz, DMSO): 10.44-10.13 (m, 1H), 9.65 (s, 1H), 9.02 (s, 1H), 8.96 (d, J = 3.5 Hz, 1H), 8.87 (s, 1H), 8.37 (d, J = 9.1 Hz, 1H), 8.24 (s, 1H), 7.86 (s, 2H), 7.78 (d, J = DMSO 95 Method AQ2, AP 343.5 (M + 1) Method C 7.9 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 7.5 Hz, 1H), 4.64 (s, 2H), 3.33 (d, J = 4.2 Hz, 3H), 3.17 (s, 1H). 1600 013 MSA 1H-NMR (300 MHz, DMSO): 9.90 (s, 1H), 9.57 (d, J = 1.6 Hz, 1H), 8.93 (dd, J = 5.0, 1.5 Hz, 2H), 8.73 (s, 1H), 8.32 (d, J = 8.7 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.85 (dd, J = 10.1, DMSO 95 Method AQ2, AP 343.5 (M + 1) Method C 7.0 Hz, 2H), 7.73 (d, J = 7.5 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 4.63 (s, 2H), 3.30 (d, J = 4.3 Hz, 3H), 2.32 (s, 3H). 1601 014 015 016 MsOH .sup.1H NMR (300 MHz, DMSO) 9.72 (brs, 1H), 9.58 (d, J = 1.6 Hz, 1H), 9.03-8.89 (m, 2H), 8.45 (d, J = 8.7 Hz, 1H), 8.11 (s, 1H), 7.99-7.84 (m, 2H), DMSO >98 G2/ AQ3 7.64 (ddd, J = 9.2, 6.1, 3.1 Hz, 1H), 7.58- 7.31 (m, 2H), 3.28 (d, J = 4.5 Hz, 3H), 2.39 (s, 3H). 1602 017 018 019 .sup.1H NMR (300 MHz, DMSO) 9.59 (d, J = 2.0 Hz, 1H), 9.33 (s, 2H), 9.24 (s, 1H), 8.79 (d, J = 1.5 Hz, 1H), 8.76- 8.64 (m, 2H), 8.30 (dd, J = 8.7, 1.5 DMSO >98 G2/ AQ3 Hz, 1H), 8.12 (brs, 2H), 7.91 (d, J = 8.7 Hz, 1H), 7.55 (dd, J = 7.9, 4.8 Hz, 1H). 1603 020 021 022 .sup.1H NMR (300 MHz, DMSO) 9.64-9.53 (m, 1H), 8.77-8.58 (m, 2H), 8.53 (s, 1H), 8.43 (d, J = 1.5 Hz, 1H), 8.11- 7.90 (m, 3H), 7.82 (d, J = 8.7 DMSO >98 G2/ AQ3 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 4.00 (s, 3H), 3.98 (s, 3H). 1604 023 024 025 .sup.1H NMR (300 MHz, DMSO) 9.59 (d, J = 2.0 Hz, 1H), 8.83- 8.66 (m, 2H), 8.55 (s, 1H), 8.27- 7.99 (m, 4H), 7.99- 7.82 (m, 2H), 7.77 (d, J = 7.7 DMSO >98 G2/ AQ3 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.56 (dd, J = 7.9, 4.8 Hz, 1H). 1605 026 027 028 .sup.1H NMR (300 MHz, DMSO) 9.58 (d, J = 2.1 Hz, 1H), 8.80-8.64 (m, 2H), 8.25 (dd, J = 8.7, 1.6 Hz, 1H), 8.10 (d, J = 8.3 Hz, 2H), 8.02 (d, J = 8.3 DMSO >98 G2/ AQ3 Hz, 2H), 7.88 (d, J = 8.7 Hz, 1H), 7.55 (dd, J = 7.9, 4.8 Hz, 1H). 1606 029 030 031 2HCl .sup.1H NMR (300 MHz, DMSO) 9.95-9.43 (m, 3H), 9.05 (d, J = 8.2 Hz, 1H), 8.99 (dd, J = 5.1, 1.5 Hz, 1H), 8.74 (s, 1H), 8.33 (d, J = 8.7 DMSO >98 G2/ AQ3 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 7.93 (dd, J = 8.0, 5.1 Hz, 1H), 7.79 (td, J = 8.9, 6.6 Hz, 1H), 7.51 (ddd, J = 11.5, 9.3, 2.6 Hz, 1H), 7.33 (td, J = 8.3, 1.9 Hz, 1H). 1607 032 033 034 3HCl .sup.1H NMR (300 MHz, DMSO) 11.88 (s, 1H), 9.77 (d, J = 1.7 Hz, 1H), 9.56-9.28 (m, 1H), 9.19- 9.01 (m, 1H), 8.31-8.11 (m, 4H), 7.75-7.47 (m, 2H), 7.47- 7.23 (m, 1H), 4.83-4.67 (m, 2H), 3.96 (t, J = DMSO >98 G2/ AQ3 12.2 Hz, 2H), 3.57 (d, J = 11.9 Hz, 2H), 3.46- 3.19 (m, 2H), 2.83 (d, J = 3.1 Hz, 3H). 1608 035 036 037 HCl .sup.1H NMR (300 MHz, DMSO) 14.45 (s, 1H), 10.36 (s, 1H), 9.31 (d, J = 2.2 Hz, 1H), 8.82 (s, 1H), 8.73 (ddd, J = 8.8, 2.5, 0.9 Hz, DMSO 100 Method AQ2/BF 1H), 8.36 (d, J = 9.0 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.56- 7.36 (m, 3H), 7.11 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 7.1 Hz, 1H), 3.99 (s, 3H), 3.87 (s, 3H), 3.30 (d, J = 3.9 Hz, 3H). 1609 038 039 040 HCl .sup.1H NMR (300 MHz, DMSO) 10.97 (s, 1H), 9.56-9.35 (m, 2H), 9.04-8.81 (m, 2H), 8.66 (t, J = 7.7 Hz, 1H), 8.61-8.45 (m, 2H), 8.15 (d, J = 8.6 Hz, 1H), 8.10-7.96 (m, DMSO 100 Method AQ2/BF 1H), 7.77-7.58 (m, 1H), 3.25 (d, J = 4.1 Hz, 3H). 1610 041 042 043 2 MsOH .sup.1H NMR (300 MHz, CDCl.sub.3) 9.93 (brs, 1H), 9.61 (d, J = 1.8 Hz, 1H), 9.10-8.96 (m, 2H), 8.64 (s, 1H), 8.21 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.99 DMSO >98 G2/ AQ3 Method 3 (dd, J = 8.0, 5.3 Hz, 1H), 7.69- 7.47 (m, 2H), 7.47-7.34 (m, 1H), 3.30 (d, J = 4.5 Hz, 3H), 2.42 (s, 6H). 1611 044 045 046 2HCl .sup.1H NMR (300 MHz, CDCl.sub.3) 10.42 (brs, 1H), 9.71 (d, J = 1.9 Hz, 1H), 9.17 (d, J = 8.1 Hz, 1H), 8.99 (dd, J = 5.1, 1.3 Hz, 1H), 8.78 (s, 1H), 8.33 (d, J = 8.7 Hz, 1H), 8.17 (d, J = DMSO >98 G2/ AQ3 8.7 Hz, 1H), 7.94 (dd, J = 8.1, 5.2 Hz, 1H), 7.79 (td, J = 8.9, 6.7 Hz, 1H), 7.55-7.37 (m, 1H), 7.31 (td, J = 8.4, 2.2 Hz, 1H), 3.29 (d, J = 4.4 Hz, 3H). 1612 047 048 049 HCl .sup.1H NMR (300 MHz, DMSO) 9.95 (brs, 1H), 9.65 (s, 1H), 9.18- 9.02 (m, 1H), 8.95 (d, J = 4.7 Hz, 1H), 8.58 (d, J = 8.7 Hz, 1H), 8.28 (s, 1H), 8.09- 7.70 (m, 4H), 3.29 (d, J = 4.4 Hz, DMSO >98 G2/ AQ3 3H). 1613 050 051 052 .sup.1H NMR (300 MHz, DMSO) 9.64 (d, J = 1.5 Hz, 1H), 8.77 (dt, J = 7.9, 1.9 Hz, 1H), 8.69 (dd, J = 4.8, 1.7 Hz, 1H), 8.61-8.48 (m, 1H), 8.31 (d, J = 8.7 Hz, 1H), 8.11 (d, J = 1.8 Hz, 1H), 8.00- 7.83 (m, 3H), 7.55 DMSO >98 G2/ AQ3 (dd, J = 7.9, 4.8 Hz, 1H), 3.17 (d, J = 4.4 Hz, 3H). 1614 053 054 055 .sup.1H NMR (300 MHz, DMSO) 9.65 (dd, J = 2.1, 0.8 Hz, 1H), 8.78 (dt, J = 8.0, 1.9 Hz, 1H), 8.69 (dd, J = 4.8, 1.7 Hz, 1H), 8.65- 8.50 (m, 1H), 8.33 (d, J = 8.6 Hz, 1H), 8.04-7.85 DMSO >98 G2/ AQ3 Method 3 (m, 1H), 7.69 (dt, J = 8.5, 1.8 Hz, 1H), 7.65- 7.37 (m, 3H), 3.18 (d, J = 4.5 Hz, 3H). 1615 056 057 058 .sup.1H NMR (300 MHz, DMSO) 9.65 (d, J = 1.7 Hz, 1H), 8.84-8.74 (m, 1H), 8.69 (dd, J = 4.7, 1.5 Hz, 1H), 8.65- 8.52 (m, 1H), 8.34 (d, J = 8.6 Hz, 1H), 7.98 (s, 1H), 7.72 (d, J = 8.5 Hz, 1H), 7.69-7.43 (m, 3H), DMSO >98 G2/ AQ3 Method 3 3.18 (d, J = 4.3 Hz, 3H). 1760 059 060 061 2 HCl .sup.1H NMR (400 MHz, DMSO) 10.04 (s, 1H), 9.65 (s, 1H), 9.11- 8.99 (m, 1H), 8.96 (dd, J = 5.0, 1.4 Hz, 1H), 8.41 (s, 1H), 8.13- 8.05 (m, 1H), 7.92- 7.82 (m, 1H), 7.64-7.55 (m, 1H), 7.44- 7.26 (m, 3H), 3.27 DMSO >98 AQ5 ND 4 (d, J = 4.6 Hz, 3H), 2.47 (s, 3H).

(423) ##STR03062##

(424) ##STR03063##

(425) 6-(3-methoxyphenyl)-2-(pyridine-3-yl)quinazoline-4-ol (lix-a) 6-(3-methoxyphenyl)-2-(pyridine-3-yl)quinazoline-4-ol was prepared from 6-bromo-2-(pyridin-3-yl)quinazolin-4-ol (synthesized following Scheme 70 substituting 2-amino-5-bromobenzamide for 2-amino-5-bromo-3-methylbenzamide) and 3-methoxylphenylboronic acid as described in Scheme 72 using method AQ2. The resultant product, 6-(6-methoxypyridin-3-yl)-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine, was a pale yellow solid (19.1 mg, 51%). LCMS m/z=344 (M+1) (Method C) (retention time=2.01 min). .sup.1H NMR (300 MHz, DMSO) 9.64 (d, J=1.3 Hz, 1H), 8.84-8.74 (m, 1H), 8.68 (dd, J=6.2, 1.7 Hz, 2H), 8.57 (d, J=1.6 Hz, 2H), 8.16 (ddd, J=14.4, 8.7, 2.2 Hz, 2H), 7.85 (d, J=8.7 Hz, 1H), 7.54 (dd, J=7.9, 4.8 Hz, 1H), 7.00 (d, J=8.7 Hz, 1H), 3.93 (s, 3H), 3.18 (d, J=4.3 Hz, 3H).

(426) Method AP: 6-(3-methoxyphenyl)-2-(pyridine-3-yl)-4-(pyrrolidin-1-yl)quinazoline (lviii-g)6-(3-methoxyphenyl)-2-(pyridine-3-yl)-4-(pyrrolidin-1-yl)quinazoline was prepared from 6-(3-methoxyphenyl)-2-(pyridine-3-yl)quinazoline-4-ol and pyrrolidine in a manner analogous to that described for 6-bromo-N-methyl-2-(pyridine-3-yl)quinazoline-4-amine using Method AP in Scheme 72. 6-(3-methoxyphenyl)-2-(pyridine-3-yl)-4-(pyrrolidin-1-yl)quinazoline was a pale yellow solid (43 mg, 31%). LCMS m/z=383 (M+1) (Method C) (retention time=2.49 min). .sup.1H NMR (300 MHz, DMSO) 9.62 (s, 1H), 8.94 (d, J=5.0 Hz, 2H), 8.56 (s, 1H), 8.32 (dd, J=19.9, 8.5 Hz, 2H), 7.83 (s, 1H), 7.56-7.30 (m, 3H), 7.04 (d, J=6.8 Hz, 1H), 4.27 (s, 4H), 3.86 (s, 3H), 2.08 (s, 4H).

(427) The compounds in the following table were prepared in a manner analogous to that described in Scheme 76, replacing pyrrolidine with the appropriate amine and 3-methoxyphenylboronic acid with the appropriate boronic acid.

(428) TABLE-US-00040 TABLE 25 Pur- Method .sup.1H- Re- ity for Num- NMR tention LCMS Per- Coup- ber Product Salt .sup.1H-NMR Solvent LCMS Time Protocol cent ling 1616 064 HCl 1H NMR (300 MHz, DMSO) 9.82 (s, 1H), 9.59 (s, 1H), 9.08-8.81 (m, 3H), 8.36 (d, J = 8.8 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.95-7.77 (m, 1H), 7.58- 7.37 (m, 3H), 7.05 (d, J = 6.5 Hz, 1H), 5.01- 4.79 (m, 1H), 3.87 (s, 3H), 1.42 (d, J = 6.5 Hz, 6H). DMSO 371 (M + 1) 2.36 Method C 100 Method AP 1617 065 HCl 1H NMR (300 MHz, DMSO) 10.38 (s, 1H), 9.64 (s, 1H), 9.43 (s, 1H), 9.28 (s, 1H), 9.07 (d, J = 7.9 Hz, 1H), 9.00- 8.76 (m, 3H), 8.48 (d, J = 7.5 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08-7.95 (m, 1H), 7.94- 7.81 (m, 1H), 3.97-3.74 (m, 2H), 1.38 (t, J = 7.2 Hz, 3H). DMSO 328 (M + 1) 1.82 Method C 100 Method AP 1618 066 HCl 1H NMR (300 MHz, DMSO) 10.11 (s, 1H), 9.58 (s, 1H), 9.03-8.79 (m, 3H), 8.35 (d, J = 8.7 Hz, 1H), 8.23-8.09 (m, 1H), 7.90- 7.75 (m, 1H), 7.58-7.36 (m, 3H), 7.04 (d, J = 3.3 Hz, 1H), 3.88 (s, 3H), 3.65 (t, J = 6.0 Hz, 2H), 2.29-2.09 (m, 1H), 1.02 (d, J = 6.7 Hz, 6H). DMSO 385 (M + 1) 1.76 Method D 100 Method AP 1619 067 HCl 1H NMR (300 MHz, DMSO) 9.83-9.52 (m, 2H), 9.27 (d, J = 7.1 Hz, 1H), 8.95 (d, J = 5.1 Hz, 1H), 8.87 (s, 1H), 8.32 (d, J = 8.9 Hz, 1H), 8.15- 7.92 (m, 2H), 7.59-7.33 (m, 3H), 7.04 (d, J = 3.4 Hz, 1H), 4.86-4.57 (m, 2H), 3.88 (s, 3H). DMSO 411 (M + 1) 1.99 Method D 100 Method AP 1620 068 HCl 1H NMR (300 MHz, DMSO) 10.50 (s, 1H), 9.64 (d, J = 1.4 Hz, 1H), 9.12- 8.85 (m, 3H), 8.46-8.33 (m, 1H), 8.27 (d, J = 8.9 Hz, 1H), 7.88 (dd, J = 7.9, 5.1 Hz, 1H), 7.57-7.37 (m, 3H), 7.11- 6.94 (m, 1H), 4.00-3.76 (m, 5H), 1.37 (t, J = 7.2 Hz, 3H). DMSO MS not work 1.56 Method D 100 Method AP 1621 069 1H NMR (300 MHz, DMSO) 9.57 (s, 1H), 8.78-8.50 (m, 3H), 8.33-7.89 (m, 3H), 7.83 (d, J = 8.7 Hz, 1H), 7.53 (dd, J = 7.9, 4.8 Hz, 1H), 7.47-7.32 (m, 3H), 7.04- 6.91 (m, 1H), 3.86 (s, 3H). DMSO 329 (M + 1) 1.47 Method D 100 Method AP 1622 070 HCl 1H NMR (300 MHz, DMSO) 9.56 (s, 1H), 9.14-8.87 (m, 2H), 8.50 (s, 1H), 8.33 (s, 2H), 7.94-7.77 (m, 1H), 7.52- 7.25 (m, 3H), 7.02 (d, J = 7.9 Hz, 1H), 3.84 (s, 3H), 3.71 (s, 6H). DMSO 357 (M + 1) 1.55 Method D 100 Method AP 1623 071 1H NMR (300 MHz, DMSO) 9.60 (d, J = 1.4 Hz, 1H), 8.81-8.55 (m, 3H), 8.42 (d, J = 1.8 Hz, 1H), 8.11 (ddd, J = 18.8, 8.7, 2.2 Hz, 2H), 7.86 (d, J = 8.7 Hz, 1H), 7.52 (dd, J = 7.9, 4.8 Hz, 1H), 6.95 (d, J = 8.6 Hz, 1H), 4.27 (s, 4H), 3.92 (s, 3H), 2.08 (s, 4H). DMSO 384.1 (M + 1) 2.33 Method C 100 Method AP 1624 072 2HCl 1H NMR (300 MHz, DMSO) 9.62 (s, 1H), 8.94 (d, J = 5.0 Hz, 2H), 8.56 (s, 1H), 8.32 (dd, J = 19.9, 8.5 Hz, 2H), 7.83 (s, 1H), 7.56-7.30 (m, 3H), 7.04 (d, J = 6.8 Hz, 1H), 4.27 (s, 4H), 3.86 (s, 3H), 2.08 (s, 4H). DMSO 383.2 (M + 1) 2.47 Method C 95 Method AP 1625 073 1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.4 Hz, 1H), 8.85 (d, J = 7.9 Hz, 1H), 8.80- 8.72 (m, 2H), 8.45 (d, J = 8.7 Hz, 1H), 8.27 (dd, J = 14.9, 5.9 Hz, 3H), 7.63 (dd, J = 7.3, 4.8 Hz, 1H), 7.52-7.33 (m, 4H), 7.04 (d, J = 7.1 Hz, 1H), 3.88 (s, 3H). DMSO 380.1 (M + 1) 2.01 Method C 100 Method AP 1626 074 HCl 1H NMR (300 MHz, DMSO) 9.61 (s, 1H), 8.75 (d, J = 7.7 Hz, 1H), 8.68 (d, J = 4.6 Hz, 1H), 8.30 (s, 1H), 8.08 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.75 (d, J = 8.7 Hz, 2H), 7.54 (dd, J = 7.6, 5.0 Hz, 1H), 7.07 (d, J = 8.7 Hz, 2H), 3.82 (s, 4H), 3.49 (s, 7H). DMSO 358.0 (M + 1) 2.25 Method C 100 Method AP 1627 075 HCl 1H NMR (300 MHz, DMSO) 9.62 (s, 1H), 8.76 (d, J = 7.9 Hz, 1H), 8.73- 8.66 (m, 1H), 8.19-8.09 (m, 2H), 7.97 (d, J = 8.6 Hz, 1H), 7.82-7.73 (m, 2H), 7.61-7.52 (m, 1H), 7.14- 7.05 (m, 2H), 3.94 (s, 5H), 3.89-3.80 (m, 9H). DMSO 399.2 (M + 1) 2.19 Method C 100 Method AP 1628 076 1H NMR (300 MHz, DMSO) 9.55 (dd, J = 2.1, 0.8 Hz, 1H), 8.76-8.62 (m, 3H), 8.60 (d, J = 1.7 Hz, 1H), 8.24-8.10 (m, 2H), 8.02 (s, 2H), 7.83 (d, J = 8.7 Hz, 1H), 7.56-7.46 (m, 1H), 6.98 (d, J = 9.2 Hz, 1H), 3.91 (s, 3H). DMSO 330.1 (M + 1) 1.72 Method C 100 Method AP 1629 077 1H NMR (300 MHz, DMSO) 9.65 (d, J = 2.1 Hz, 1H), 8.79 (d, J = 8.0 Hz, 1H), 8.73 (dd, J = 4.7, 1.6 Hz, 1H), 8.36-8.25 (m, 2H), 8.06 (d, J = 8.7 Hz, 1H), 7.59 (dd, J = 7.6, 4.4 Hz, 1H), 7.48-7.40 (m, 1H), 7.41- 7.29 (m, 2H), 7.01 (dd, J = 8.0, 2.4 Hz, 1H), 4.80 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 1.53 (t, J = 7.0 Hz, 3H). DMSO 358 (M + 1) Method C 99 Method AP 1630 078 2 HCl 1H NMR (300 MHz, DMSO) 9.68 (d, J = 1.8 Hz, 1H), 9.07 (d, J = 5.5 Hz, 1H), 8.96 (d, J = 3.5 Hz, 1H), 8.90 (s, 1H), 8.37 (d, J = 7.5 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.94-7.83 (m, 1H), 7.57-7.39 (m, 3H), 7.22 (d, J = 1.0 Hz, 1H), 7.08 (d, J = 7.3 Hz, 1H), 6.72 (s, 1H), 5.18-5.04 (m, 1H), 3.88 (s, J = 2.7 Hz, 3H), 3.23 (dd, J = 13.7, 6.1 Hz, 1H), 2.31- 2.17 (m, 1H), 2.17-1.88 (m, 4H), 1.74-1.55 (m, 1H). DMSO 440.6 (M + 1) Method C 99 Method AP 1631 079 2 HCl 1H NMR (300 MHz, DMSO) 9.70 (d, J = 1.6 Hz, 1H), 9.24 (d, J = 7.4 Hz, 1H), 8.99 (dd, J = 5.3, 1.4 Hz, 1H), 8.34 (dd, J = 15.7, 6.1 Hz, 3H), 8.21 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 7.7, 5.1 Hz, 1H), 7.51-7.33 (m, 3H), 7.04 (dd, J = 7.8, 2.4 Hz, 1H), 4.67 (s, 2H), 4.33 (s, 2H), 3.87 (s, J = 3.6 Hz, 3H), 3.50 (s, 2H). DMSO 412.4 (M + 1) Method C 99 Method AP 1632 080 2 HCl 1H NMR (300 MHz, DMSO) 9.00 (d, J = 6.5 Hz, 2H), 8.78 (d, J = 6.5 Hz, 2H), 8.46-8.32 (m, 2H), 8.15 (d, J = 8.4 Hz, 1H), 7.53-7.30 (m, 3H), 7.02 (d, J = 7.8 Hz, 1H), 4.34 (s, J = 2.4 Hz, 3H), 3.86 (s, J = 2.5 Hz, 3H). DMSO 344.4 (M + 1) Method C 99 Method AP 1633 081 1H NMR (300 MHz, DMSO) 9.55 (dd, J = 2.1, 0.8 Hz, 1H), 8.76-8.62 (m, 3H), 8.60 (d, J = 1.7 Hz, 1H), 8.24-8.10 (m, 2H), 8.02 (s, 2H), 7.83 (d, J = 8.7 Hz, 1H), 7.56-7.46 (m, 1H), 6.98 (d, J = 9.2 Hz, 1H), 3.91 (s, 3H). DMSO 330.1 (M + 1) Method C 99 Method AP Num- ber Starting Material R.sup.1 Starting Material R.sup.3 Product 1634 082 083 084 1635 085 086 087 1636 088 089 090 1637 091 092 093 1638 094 095 096 1639 097 098 099 1640 00 01 02 1641 03 04 05 1642 06 07 08 1643 09 0 1644 1645 1646 0 1647 1648 1649 1650 0 1651 1652 1653 0 1654 1655 1656 0 1657 1658 1659 1660 0 1661 1662 1663 0 1664 1665 1666 0 1667 1668 1669 1670 0 1671 1672 1673 1674 00 1675 01 1676 02 1677 03 1678 NH3 04 Salt .sup.1HNMR Purity Method Number Type .sup.1H NMR Solvent percent of Coupling 1634 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.78 (d, 2H, J = 5.4 Hz), 6.58 (d, 1H, J = F5, G2 1.1 Hz), 7.00-7.75 (m, 8H), 7.85 (d, (reflux) 1H, J = 8.6 Hz), 8.64-8.97 (m, 4H), 9.64 (s, 1H) 1635 .sup.1H NMR (DMSO-d.sub.6) ppm 3.84-3.95 (m, DMSO >98 Method AQ3, 11H), 7.01 (d, 1H, J = 8.1 Hz), 7.32- F5, G2 7.46 (m, 3H), 7.56 (dd, 1H, J = 6.1, 8.1 (reflux) Hz), 7.97 (d, 1H, J = 8.2 H), 8.16- 8.76 (m, 4H), 9.61 (s, 1H) 1636 .sup.1H NMR (DMSO-d.sub.6) ppm 2.23 (m, 2H), DMSO >98 Method AQ3, 3.85 (s, 3H), 4.71 (br s, 4H), 6.98 (dd, F5, G2 1H, J = 2.1, 8.0 Hz), 7.31-7.55 (m, 4H), (reflux) 7.87 (d, 1H, J = 8.2 Hz), 8.12-8.74 (m, 4H), 9.59 (s, 1H) 1637 1H NMR (DMSO-d6) ppm 1.77 (br s, DMSO >98 Method AQ3, 6H), 3.86-3.89 (br m, 7H), 6.99 (dd, F5, G2 1H, J = 1.4, 8.6 Hz), 7.31-7.57 (m, 4H), (reflux) 7.93 (d, 1H, J = 1.4, 8.6 Hz), 8.11-8.16 (m, 2H), 8.69-8.76 (m, 2H), 9.61 (s, 1H) 1638 1H NMR (DMSO-d6) ppm 2.18-2.22 DMSO >98 Method AQ3, (m, 1H), 3.00-3.09 (m, 1H), 3.11-3.22 F5, G2 (m, 2H), 3.31-3.34 (m, 1H), 3.86 (s, (relux) 3H), 6.29-6.31 (m, 1H), 7.17-8.82 (m, 14H), 9.63 (s, 1H) 1639 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.10-4.13 (m, 2H), 4.35-4.38 (m, 2H), F5, G2 6.92-7.46 (m, 10H), 7.85 (d, 1H, J = (reflux) 8.6 Hz), 8.16 (d, 1H, J = 8.6 Hz), 8.66- 8.75 (m, 4H), 9.61 (s, 1H) 1640 1H NMR (DMSO-d6) ppm 3.07 (t, 2H, DMSO >98 Method AQ3, J = 6.9 Hz), 3.87 (s, 3H), 3.92-3.96 (m, F5, G2 2H), 7.00-7.58 (m, 10H), 7.84 (d, 1H, J = (reflux) 8.6 Hz), 8.14 (d, 1H, J = 8.6 Hz), 8.59-8.78 (m, 4H), 9.64 (s, 1H) 1641 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.95 (d, 2H, J = 5.6 Hz), 7.01-7.51 (m, F5, G2 10H), 7.85 (d, 1H, J = 8.6 Hz), 8.16 (d, (reflux) 1H, J = 8.6 Hz), 8.65-8.73 (m, 4H), 9.56 (s, 1H) 1642 1H NMR (DMSO-d6) ppm 1.66-1.781 DMSO >98 Method AQ3, (m, 6H), 2.16-2.19 (m, 2H), 3.87 (s, F5, G2 3H), 4.78 (br s, 1H), 7.00-7.55 (m, 5H), (reflux) 7.83 (d, 1H, J = 8.6 Hz), 8.12 (d, 1H, J = 8.6 Hz), 8.29 (s, 1H), 8.67-8.77 (m, 3H), 9.62 (s, 1H) 1643 HCl 1H NMR (DMSO-d6) ppm 0.81 (t, 3H, DMSO >98 Method AQ3, J = 7.4 Hz), 1.47-1.54 (m, 2H), 2.00- F5, G2 2.05 (m, 2H), 3.32-3.37 (m, 4H), 3.86- (reflux) 3.91 (m, 5H), 7.03-7.80 (m, 5H), 8.16 (d, 1H, J = 8.7 Hz), 8.34 (d, 1H, J = 8.7 Hz), 8.86-8.96 (m, 3H), 9.61 (s, 1H), 10.03 (s, 1H) 1644 1H NMR (DMSO-d6) ppm 0.38-0.54 DMSO >98 Method AQ3, (m, 4H), 1.30-1.32 (m, 1H), 3.58-3.62 F5, G2 (m, 2H), 3.87 (s, 3H), 7.00-7.54 (m, (reflux) 5H), 7.86 (d, 1H, J = 8.6 Hz), 8.14 (d, 1H, J = 8.6 Hz), 8.64-8.76 (m, 4H), 9.62 (s, 1H) 1645 1H NMR (DMSO-d6) ppm 1.83-1.88 DMSO >98 Method AQ3, (m, 2H), 2.21-2.27 (m, 2H), 2.49 (br s, F5, G2 2H), 3.87 (s, 3H), 4.88-4.91 (m, 1H), (reflux) 7.03-7.57 (m, 5H), 7.83 (d, 1H, J = 8.6 Hz), 8.13 (d, 1H, J = 8.6 Hz), 8.62-8.77 (m, 4H), 9.63 (s, 1H) 1646 1H NMR (DMSO-d6) ppm 3.21 (s, 1H), DMSO >98 Method AQ3, 3.88 (s, 3H), 4.52 (dd, 2H, J = 2.2, 5.2 F5, G2 Hz), 7.01-7.58 (m, 5H), 7.88 (d, 1H, J = (reflux) 8.7 Hz), 8.19 (d, 1H, J = 8.6 Hz), 8.64- 9.01 (m, 4H), 9.66 (s, 1H) 1647 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.37 (br s, 2H), 5.19 (dd, 1H, J = 1.5, F5, G2 10.2 Hz), 5.31 (dd, 1H, J = 1.5, 17.2 (reflux) Hz), 6.01-6.22 (m, 1H), 7.00-7.56 (m, 5H), 7.85 (d, 1H, J = 8.6 Hz), 8.16 (d, 1H, J = 8.6 Hz), 8.67-8.82 (m, 4H), 9.61 (s, 1H) 1648 1H NMR (DMSO-d6) ppm 0.94-0.99 (t, DMSO >98 Method AQ3, 6H, J = 7.4 Hz), 1.68-1.80 (m, 4H), F5, G2 3.87 (s, 3H), 4.49-4.52 (m, 1H), 7.01- (reflux) 7.47 (m, 5H), 7.83 (d, 1H, J = 8.6 Hz), 8.11-8.15 (m, 2H), 8.67-8.75 (m, 3H), 9.63 (s, 1H) 1649 1H NMR (DMSO-d6) ppm 1.68 (s, 9H), DMSO >98 Method AQ3, 3.87 (s, 3H), 7.01-7.70 (m, 6H), 7.82 F5, G2 (d, 1H, J = 8.6 Hz), 8.11 (d, 1H, J = 8.6 (reflux) Hz), 8.67-8.74 (m, 3H), 9.60 (s, 1H) 1650 1H NMR (DMSO-d6) ppm 0.97 (t, 3H, DMSO >98 Method AQ3, J = 7.2 Hz), 1.44-1.48 (m, 2H), 1.74- F5, G2 1.78 (m, 2H), 3.71-3.75 (m, 2H), 3.89 (reflux) (s, 3H), 7.00-7.56 (m, 5H), 7.83 (d, 1H, J = 8.6 Hz), 8.15 (d, 1H, J = 8.6 Hz), 8.59-8.76 (m, 4H), 9.62 (s, 1H) 1651 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.98 (d, 2H, J = 5.6 Hz), 7.02-7.46 (m, F5, G2 7H), 7.87 (d, 1H, J = 8.7 Hz), 8.51 (dd, (reflux) 1H, J = 1.5, 4.5 Hz), 8.50-8.71 (m, 5H), 9.26 (s, 1H), 9.48 (s, 1H) 1652 1H NMR (DMSO-d6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.98 (d, 2H, J = 5.5 Hz), 7.00-7.46 (m, F5, G2 6H), 7.86-7.90 (m, 2H), 8.16 (d, 1H, J = (reflux) 1.7 Hz), 8.46 (d, 1H, J = 1.7 Hz), 8.66-8.76 (m, 4H), 9.22 (s, 1H), 9.56 (s, 1H) 1653 1H NMR (DMSO-d6) ppm 3.22-3.27 DMSO >98 Method AQ3, (m, 2H), 3.87 (s, 3H), 4.04-4.11 (m, F5, G2 2H), 7.02-7.46 (m, 8H), 7.83 (d, 1H, J = (reflux) 8.6 Hz), 8.13 (d, 1H, J = 1.6 Hz), 8.67-8.78 (m, 5H), 9.64 (s, 1H) 1654 1H NMR (DMSO-d6) ppm 1.76-1.88 DMSO >98 Method AQ3, (m, 4H), 2.66 (br s, 1H), 3.37-3.48 (m, F5, G2 2H), 3.86 (s, 3H), 4.39-4.47 (m, 2H), (reflux) 6.95-7.57 (m, 7H), 7.95 (d, 1H, J = 8.7 Hz), 8.15-8.19 (m, 2H), 8.69-8.76 (m, 2H), 9.61 (s, 1H) 1655 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.97 (d, 2H, J = 5.6 Hz), 7.00-7.50 (m, F5, G2 8H), 7.85 (d, 1H, J = 8.7 Hz), 8.16 (s, (reflux) 1H), 8.66-8.77 (m, 3H), 9.11 (s, 1H), 9.61 (s, 1H) 1656 .sup.1H NMR (DMSO-d.sub.6) ppm 2.28 (s, 3H), DMSO >98 Method AQ3, 3.87 (s, 3H), 4.91 (d, 2H, J = 5.5 Hz), F5, G2 7.00-7.52 (m, 9H), 7.86 (d, 1H, J = 8.6 (reflux) Hz), 8.17 (dd, 1H, J = 8.6, 1.8 Hz), 8.66-9.16 (m, 3H), 9.18-9.16 (m, 1H), 9.57 (s, 1H) 1657 .sup.1H NMR (DMSO-d.sub.6) ppm 3.71 (s, 3H), DMSO >98 Method AQ3, 3.87 (s, 3H), 4.91 (d, 2H, J = 5.7 Hz), F5, G2 6.82-7.52 (m, 9H), 7.86 (d, 1H, J = 8.7 (reflux) Hz), 8.17 (dd, 1H, J = 8.7, 1.8 Hz), 8.66-9.15 (m, 3H), 9.17-9.19 (m, 1H), 9.57 (s, 1H) 1658 .sup.1H NMR (DMSO-d.sub.6) ppm 2.25 (s, 3H), DMSO >98 Method AQ3, 3.87 (s, 3H), 4.91 (d, 2H, J = 5.7 Hz), F5, G2 7.00-7.53 (m, 9H), 7.86 (d, 1H, J = 8.6 (reflux) Hz), 8.17 (dd, 1H, J = 8.6, 1.8 Hz), 8.66-9.15 (m, 3H), 9.17-9.19 (m, 1H), 9.57 (s, 1H) 1659 .sup.1H NMR (DMSO-d.sub.6) ppm 2.44 (s, 3H), DMSO >98 Method AQ3, 3.86 (s, 3H), 4.95 (d, 2H, J = 5.7 Hz), F5, G2 7.01-7.53 (m, 9H), 7.86 (d, 1H, J = 8.6 (reflux) Hz), 8.17 (dd, 1H, J = 8.6, 1.8 Hz), 8.65-9.02 (m, 3H), 9.50-9.52 (m, 1H), 9.54 (s, 1H) 1660 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 7.03 (s, 1H), 7.44-7.94 (m, 10H), 8.07- F5, G2 8.70 (m, 4H), 9.41 (s, 1H) (reflux) 1661 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.91 (d, 2H, J = 5.5 Hz), 7.00-7.04 (m, F5, G2 1H), 7.04-7.55 (m, 7H), 7.87 (d, 1H, J = (reflux) 8.6 Hz), 8.18 (dd, 1H, J = 8.6, 1.8 Hz), 8.66-9.18 (m, 3H), 9.18-9.21 (m, 1H), 9.55 (s, 1H) 1662 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.99 (d, 2H, J = 5.5 Hz), 7.01-7.05 (m, F5, G2 2H), 7.15-7.56 (m, 6H), 7.88 (d, 1H, J = (reflux) 8.6 Hz), 8.20 (dd, 1H, J = 8.6, 1.8 Hz), 8.64-9.18 (m, 3H), 9.19-9.21 (m, 1H), 9.50 (s, 1H) 1663 .sup.1H NMR (DMSO-d.sub.6) ppm 3.49 (s, 3H), DMSO >98 Method AQ3, 3.74 (s, 3H), 5.15 (s, 2H), 6.90 (d, J = F5, G2 8.2 Hz, 1H), 7.04-7.29 (m, 2H), 7.33- (reflux) 7.54 (m, 7H), 7.93 (d, 1H, J = 8.6 Hz), 8.15 (dd, 1H, J = 8.6, 1.8 Hz), 8.21 (s, 1H), 8.68-8.75 (m, 2H), 9.59 (s, 1H) 1664 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.94 (d, 2H, J = 5.5 Hz), 7.01-7.03 (m, F5, G2 1H), 7.35-7.57 (m, 7H), 7.88 (d, 1H, J = (reflux) 8.6 Hz), 8.20 (dd, 1H, J = 8.6, 1.8 Hz), 8.66-9.22 (m, 3H), 9.19-9.21 (m, 1H), 9.50 (s, 1H) 1665 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.96 (d, 2H, J = 5.5 Hz), 7.00-7.03 (m, F5, G2 2H), 7.33-7.52 (m, 7H), 7.88 (d, 1H, J = (reflux) 8.6 Hz), 8.19 (dd, 1H, J = 8.6, 1.8 Hz), 8.65-9.20 (m, 3H), 9.19-9.21 (m, 1H), 9.54 (s, 1H) 1666 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.93 (d, 2H, J = 5.5 Hz), 7.00-7.19 (m, F5, G2 3H), 7.41-7.55 (m, 6H), 7.88 (d, 1H, J = (reflux) 8.6 Hz), 8.17 (dd, 1H, J = 8.6, 1.8 Hz), 8.65-9.18 (m, 3H), 9.19-9.21 (m, 1H), 9.57 (s, 1H) 1667 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.92 (d, 2H, J = 5.5 Hz), 7.01-7.03 (d, F5, G2 1H, J = 7.0 Hz), 7.37-7.53 (m, 6H), (reflux) 7.72 (d, 1H, J = 8.6 Hz), 8.18 (dd, 1H, J = 8.6, 1.8 Hz), 8.66-9.19 (m, 3H), 9.20-9.23 (m, 1H), 9.56 (s, 1H) 1668 .sup.1H NMR (DMSO-d.sub.6) ppm 1.68 (d, 3H, J = DMSO >98 Method AQ3, 7.0 Hz), 3.87 (s, 3H), 4.92 (d, 2H, J = F5, G2 5.5 Hz), 5.75-5.78 (m, 1H), 7.02 (d, (reflux) 1H, J = 7.0 Hz), 7.32-7.56 (m, 9H), 7.84 (d, 1H, J = 8.6 Hz), 8.15 (dd, 1H, J = 8.6, 1.8 Hz), 8.64-8.84 (m, 4H), 9.51 (s, 1H) 1669 .sup.1H NMR (DMSO-d.sub.6) ppm 3.70 (s, 3H), DMSO >98 Method AQ3, 3.86 (s, 3H), 4.92 (d, J = 5.1 Hz, 2H), F5, G2 6.89-7.01 (m, 3H), 7.41-7.54 (m, 6H), (reflux) 7.85 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 8.67-8.75 (m, 3H), 9.19 (s, 1H), 9.56 (s, 1H) 1670 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 3.91 (s, 3H), 4.92 (d, J = 5.0 Hz, 2H), F5, G2 6.87-7.52 (m, 9H), 7.85 (d, J = 8.5 Hz, (reflux) 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.64-8.73 (m, 3H), 9.05 (s, 1H), 9.52 (s, 1H) 1671 .sup.1H NMR (DMSO-d.sub.6) ppm 3.87 (s, 3H), DMSO >98 Method AQ3, 4.93 (d, J = 5.6 Hz, 2H), 7.02 (s, 1H), F5, G2 7.41-7.61 (m, 7H), 7.83 (d, J = 8.9 Hz, (reflux) 1H), 8.18 (d, J = 8.9 Hz, 1H), 8.66-8.71 (m, 3H), 9.21 (s, 1H), 9.54 (s, 1H) 1672 .sup.1H NMR (DMSO-d.sub.6) ppm 3.69 (s, 6H), DMSO >98 Method AQ3, 3.87 (s, 3H), 4.93 (d, J = 5.6 Hz, 2H), F5, G2 6.90 (s, 1H), 7.00-7.54 (m, 7H), 7.85 (reflux) (d, J = 8.6 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 8.66-8.78 (m, 3H), 9.14 (s, 1H), 9.63 (s, 1H) 1673 DMSO 95 Method AQ3, AP 1674 2HCl 1H-NMR (300 MHz, DMSO): 9.71 (d, DMSO 95 Method AQ3, J = 1.6 Hz, 1H), 9.16 (d, J = 8.2 Hz, AP 1H), 8.98 (dd, J = 5.1, 1.5 Hz, 1H), 8.58 (s, 1H), 8.48-8.34 (m, 3H), 8.20 (d, J = 8.0 Hz, 1H), 7.98-7.87 (m, 2H), 7.75 (t, J = 7.8 Hz, 1H), 3.73 (s, 6H). 1675 1H-NMR (300 MHz, DMSO): 9.59 (s, DMSO 95 Method AQ3, 1H), 8.78-8.62 (m, 2H), 8.38 (s, 1H), AP 8.05 (dd, J = 8.6, 1.8 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.52 (dd, J = 7.8, 4.7 Hz, 1H), 7.07 (d, J = 8.8 Hz, 2H), 4.04 (s, 4H), 3.82 (s, 3H), 2.02 (s, 4H). 1676 3HCl 1H-NMR (300 MHz, DMSO): 10.40 DMSO 95 Method AQ3, (s, 1H), 9.48 (d, J = 2.0 Hz, 1H), 8.95 AP (s, 2H), 8.88 (d, J = 5.2 Hz, 1H), 8.72 (d, J = 4.3 Hz, 1H), 8.35 (d, J = 8.9 Hz, 1H), 8.18 (s, 1H), 8.08 (d, J = 8.8 Hz, 1H), 7.94-7.81 (m, 2H), 7.64 (s, 1H), 7.54-7.45 (m, 3H), 7.06-7.00 (m, 1H), 5.25 (d, J = 5.1 Hz, 2H), 3.88 (s, 3H). 1677 1H-NMR (300 MHz, DMSO): 12.83 DMSO 95 Method AQ3, (s, 1H), 9.32 (d, J = 2.2 Hz, 1H), 8.77 AP (dd, J = 4.8, 1.5 Hz, 1H), 8.63 (d, J = 2.5 Hz, 1H), 8.56-8.49 (m, 1H), 8.37 (d, J = 2.2 Hz, 1H), 8.23-8.14 (m, 2H), 7.85 (d, J = 8.5 Hz, 1H), 7.60 (dd, J = 8.0, 4.8 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1H), 3.92 (s, 3H). 1678 2HCl .sup.1H NMR (300 MHz, DMSO) 9.79 DMSO >98 Method AQ3, (brs, 1H), 9.60 (s, 2H), 9.07 (d, J = 7.4 F5, G2 Hz, 1H), 9.00 (d, J = 4.5 Hz, 1H), 8.80 (reflux) (s, 1H), 8.35 (d, J = 8.7 Hz, 1H), 8.26 (d, J = 8.6 Hz, 1H), 8.02-7.88 (m, 1H), 7.67-7.48 (m, 2H), 7.49-7.37 (m, 1H).

(429) ##STR03205##
Method AT for Alkylation: Method AT1: NaOMe/MeOH/microwave/150 C. Method AT2: MeOH/microwave/150 C. Method AT3: DIPEA/KI/DMF/microwave/150 C.

(430) ##STR03206##

(431) Method AR: 3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenol (lxi-a) To a suspension of 6-(3-methoxyphenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (prepared in a similar method described for 6-(3-methoxyphenyl)-2-(pyridine-3-yl)-4-(pyrrolidin-1-yl)quinazoline using Scheme 74, substituting N-methylamine for pyrrolidine) (1.00 g, 2.9 mmol) in CH.sub.2Cl.sub.2 (15 mL) and boron tribromide 1M solution in dichloromethane (8.76 ml, 8.76 mmol) was added at 0 C. The reaction mixture was stirred overnight at room temperature after which it was carefully poured into a vigorously stirring mixture of ice and saturated aqueous solution of NaHCO.sub.3. The resultant solid was collected by filtration, dried and then dissolved in a mixture of K.sub.2CO.sub.3 (2 g) and methanol (50 mL). The solution was then acidified using aqueous NH.sub.4Cl solution. (50 mL) and the precipitate which formed was collected by filtration and dried to give 0.95 g of 3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenol as pale yellow solid (99%). LCMS m/z=329 (M+1) (Method D) (retention time=1.30 min). .sup.1H NMR (300 MHz, DMSO) 9.63 (s, 1H), 9.60 (s, 1H), 8.77 (d, J=8.0 Hz, 1H), 8.74-8.59 (m, 2H), 8.54 (s, 1H), 8.05 (d, J=8.7 Hz, 1H), 7.83 (d, J=8.7 Hz, 1H), 7.54 (dd, J=7.9, 4.8 Hz, 1H), 7.38-7.12 (m, 3H), 6.82 (d, J=7.8 Hz, 1H), 3.17 (d, J=4.3 Hz, 3H).

(432) Method AS: 6-(3-(2-chloroethoxyl)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (lxii-a) A suspension of 3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenol (0.30 g, 0.914 mmol), 1-bromo-2-chloroethane (0.38 ml, 4.57 mmol), and potassium carbonate (0.38 g, 2.74 mmol) in DMF (10 mL) was stirred for 2 days at room temperature. Water (10 mL) and ethyl acetate (10 mL) were added to the mixture and extracted. The organic layer was separated and concentrated in vacuo to leave a solid, which was collected by filtration and washed with hexane and dried to give 0.30 g of 6-(3-(2-chloroethoxyl)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine as brown solid (83%). The product was used without further purification.

(433) Method AT1: 6-(3-(2-methoxyethoxyl)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (lxiii-a) A solution of 6-(3-(2-chloroethoxyl)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (70 mg, 0.18 mmol) and sodium methoxide (97 mg, 1.8 mmol) in methanol (3 mL) was placed in a microwave reaction vial. The mixture was heated under microwave irradiation conditions at 150 C. for 30 minutes after which the solvent was removed in vacuo. The crude product was obtained, which was purified by column chromatography on basic silica gel (eluted with hexane/ethyl acetate 3:1.fwdarw.1:4) to give 20 mg of 6-(3-(2-methoxyethoxyl)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine as an off-white powder (29%). LCMS m/z=387 (M+1) (Method D) (retention time=1.49 min). .sup.1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.77 (d, J=8.2 Hz, 1H), 8.73-8.51 (m, 3H), 8.16 (d, J=8.7 Hz, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.60-7.32 (m, 4H), 7.01 (s, 1H), 4.21 (s, 2H), 3.70 (s, 2H), 3.33 (s, 3H), 3.19 (s, 3H).

(434) Method AT2: N-Methyl-6-(4-(2-morpholinoethoxy)phenyl)-2-(pyridin-3-yl)quinazolin-4-amine (lxiii-b)

(435) ##STR03207##

(436) In a 10 mL microwave vial 6-(4-(2-chloroethoxy)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (70.0 mg, 0.179 mmol) and morpholine (0.155 ml, 1.791 mmol) were added in methanol (3 mL) to give a yellow suspension. The vial was irradiated at 150 C. in the microwave for 30 min. The volatiles were evaporated in vacuo. Water (10 mL) was added to the reaction mixture and extracted with ethyl acetate (210 mL). The organic layers were combined and washed with brine (120 mL), then dried over MgSO.sub.4, filtered and concentrated. The residue was purified by column chromatography on basic silica gel (eluted with hexane/ethyl acetate 3:2 to 0:1). The product was obtained as the parent and converted to the HCl salt by addition of 4 M HCl-dioxane, then crystallized from EtOHH2O to give 55 mg of N-methyl-6-(4-(2-morpholinoethoxyl)phenyl)-2-(pyridin-3-yl)quinazolin-4-amine as a yellow powder (60% yield). LCMS m/z=442 (M+1) (Method D) (retention time=1.12 min). .sup.1H NMR (300 MHz, DMSO) 11.31 (s, 1H), 10.41 (s, 1H), 9.63 (s, 1H), 9.10-8.79 (m, 3H), 8.34 (d, J=8.2 Hz, 1H), 8.28-8.12 (m, 1H), 7.92 (d, J=8.0 Hz, 2H), 7.87-7.74 (m, 1H), 7.18 (d, J=8.0 Hz, 2H), 4.60-4.46 (m, 2H), 4.06-3.91 (m, 2H), 3.91-3.74 (m, 2H), 3.67-3.41 (m, 4H), 3.38-3.09 (m, J=10.1 Hz, 5H).

(437) Method AT3: N-methyl-2-(pyridin-3-yl)-6-(3-(2-(2,2,2 trifluoroethylamino)ethoxy)phenyl)quinazolin-4-amine (lxiii-c)

(438) ##STR03208##

(439) In a 10 mL microwave vial was added 6-(3-(2-chloroethoxy)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (50.0 mg, 0.128 mmol), 2,2,2-trifluoroethylamine (0.100 ml, 1.279 mmol), potassium iodide (42.5 mg, 0.256 mmol), and N,N-diisopropylethylamine (0.045 ml, 0.256 mmol) in DMF (3 mL) to give a yellow suspension. The vial was irradiated at 150 C. in the microwave for 20 min Water (10 mL) was added to the mixture and extracted with ethyl acetate (220 mL). The organic layers were combined and washed with water (120 mL) and brine (120 mL), dried over MgSO.sub.4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with CH.sub.2Cl.sub.2/CH.sub.2Cl.sub.2-MeOHNH.sub.4OH=100:20:1 1:0 to 0:1). The product was converted to the HCl salt by addition of 4 M HCl-dioxane, then crystallization from IPA-H2O to give 30 mg of N-methyl-2-(pyridin-3-yl)-6-(3-(2-(2,2,2-trifluoroethylamino)ethoxy)phenyl)quinazolin-4-amine as a yellow powder (42%). LCMS m/z=454 (M+1) (Method C) (retention time=2.26 min). .sup.1H NMR (300 MHz, DMSO) 10.73-10.36 (m, 1H), 9.65 (s, 1H), 9.13-8.98 (m, 2H), 8.93 (d, J=5.0 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H), 8.24 (d, J=7.7 Hz, 1H), 7.94-7.75 (m, 1H), 7.69-7.41 (m, 3H), 7.09 (d, J=8.1 Hz, 1H), 4.61-4.43 (m, 2H), 4.28-4.07 (m, 2H), 3.59-3.39 (m, 2H), 3.30 (d, J=2.8 Hz, 3H).

(440) Scheme 80: Method AU: N-(2-(4-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenoxy)ethyl)acetamide (lxiv-a)

(441) ##STR03209##

(442) In a 50 mL round-bottomed flask was added 6-(4-(2-aminoethoxy)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (15.0 mg, 0.040 mmol) and triethylamine (0.017 ml, 0.121 mmol) in CH.sub.2Cl.sub.2 (5 mL) to give a yellow solution. Acetic anhydride (4.58 l, 0.048 mmol) was added and the mixture was stirred for 2 h at room temperature. Water (10 mL) was added to the mixture and extracted with ethyl acetate (210 mL). The organic layers were combined and washed with brine (120 mL), dried over Mg.sub.2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with CH.sub.2Cl.sub.2/MeOH 1:0 to 9:1). The product was converted to the HCl salt by addition of 4 M HCl-dioxane, then dissolved in a small amount of methanol, followed by ethyl acetate. The resulting solid was filtered and dried to give 10 mg of N-(2-(4-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenoxy)ethyl)acetamide as a HCl salt as a yellow solid in a 51% yield. LCMS m/z=414 (M+1) (Method C) (retention time=1.28 min). .sup.1H NMR (300 MHz, DMSO) 10.26 (s, 1H), 9.62 (s, 1H), 9.06-8.90 (m, 2H), 8.81 (s, 1H), 8.34 (d, J=9.0 Hz, 1H), 8.17 (d, J=6.6 Hz, 2H), 7.86 (d, J=8.0 Hz, 3H), 7.13 (d, J=7.9 Hz, 2H), 4.06 (t, J=5.4 Hz, 2H), 3.52-3.38 (m, 2H), 3.30 (d, J=4.1 Hz, 3H), 1.84 (s, 3H).

(443) The compounds in the following table were prepared in a manner analogous to that described in Scheme 78, replacing 1-bromo-2-chloroethane with the corresponding alkyl halide.

(444) TABLE-US-00041 TABLE 26 .sup.1H- Re- Pur- Method NMR ten- ity for Num- Sol- tion LCMS per- Coup- ber PRODUCT Salt .sup.1H-NMR vent LCMS Time Protocol cent ling 1679 0 HCl 1H NMR (300 MHz, DMSO) 10.36 (s, 1H), 9.65 (s, 1H), 9.13-8.99 (m, 1H), 8.99- 8.83 (m, 2H), 8.38 (d, J = 8.8 Hz, 1H), 8.30-8.16 (m, 1H), 7.94- 7.80 (m, 1H), 7.55-7.35 (m, 3H), 7.09- 6.97 (m, 1H), 4.16 (q, J = 7.0 Hz, 2H), 3.31 (d, J = 4.3 Hz, 3H), 1.37 (t, J = 6.9 Hz, 3H). DMSO 357 (M + 1) 1.62 Method D 100 Method AR/AS/ AT1 1680 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.77 (d, J = 8.2 Hz, 1H), 8.73-8.51 (m, 3H), 8.16 (d, J = 8.7 Hz, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.60-7.32 (m, 4H), 7.01 (s, 1H), 4.21 (s, 2H), 3.70 (s, 2H), 3.33 (s, 3H), 3.19 (s, 3H). DMSO 387 (M + 1) 1.49 Method D 100 Method AR/AS/ AT1 1681 1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.78 (d, J = 7.9 Hz, 1H), 8.72-8.49 (m, 3H), 8.22-8.01 (m, 2H), 7.85 (d, J = 8.6 Hz, 1H), 7.62-7.36 (m, 4H), 7.01 (s, 1H), 4.59 (s, 2H), 3.19 (d, J = 4.0 Hz, 3H), 2.68 (d, J = 4.5 Hz, 3H). DMSO 400 (M + 1) 1.31 Method D 100 Method AR/W with KI 1682 2HCl 1H NMR (300 MHz, DMSO) d 10.47 (s, 1H), 9.65 (d, J = 1.7 Hz, 1H), 9.05 (d, J = 7.9 Hz, 1H), 9.01- 8.88 (m, 2H), 8.39 (m, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.87 (dd, J = 8.0, 5.3 Hz, 1H), 7.65- 7.39 (m, 3H), 7.09 (m, 1H), 6.44 (m, 1H), 4.47 (td, J = 14.7, 3.4 Hz, 2H), 3.29 (d, J = 4.5 Hz, 3H). DMSO 393.4 (M + 1) Method C NH4HCO3) 100 Method AR/AS (K2CO3, DMF- THF (1:1), 60 C.) then Method AT 1683 HCl .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.60 (s, 1H), 9.03- 8.87 (m, 2H), 8.77 (s, 1H), 8.32 (d, J = 8.5 Hz, 1H), 8.21-8.02 (m, 1H), 7.92-7.69 (m, 3H), 7.20-7.02 (m, 2H), 4.93 (s, 2H), 3.70- 3.40 (m, 8H), 3.29 (d, J = 3.5 Hz, 3H). DMSO 456 (M + 1) 1.73 (M + 1) Method B (Ammon- ium formate) 100 Method AR/W with KI 1684 HCl .sup.1H NMR (300 MHz, DMSO) 10.38 (s, 1H), 9.64 (s, 1H), 9.02 (d, J = 6.7 Hz, 1H), 8.93 (d, J = 4.9 Hz, 1H), 8.84 (s, 1H), 8.34 (d, J = 9.0 Hz, 1H), 8.22 (d, J = 8.7 Hz, 1H), 7.98- 7.70 (m, 3H), 7.11 (d, J = 7.3 Hz, 2H), 4.26-4.05 (m, 2H), 3.78- 3.57 (m, 2H), 3.45-3.19 (m, 6H). DMSO 387 (M + 1) 1.47 Method A (Formic acid) 100 Method AR/AS/ AT1 1685 HCl .sup.1H NMR (300 MHz, DMSO) 11.31 (s, 1H), 10.41 (s, 1H), 9.63 (s, 1H), 9.10-8.79 (m, 3H), 8.34 (d, J = 8.2 Hz, 1H), 8.28-8.12 (m, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.87-7.74 (m, 1H), 7.18 (d, J = 8.0 Hz, 2H), 4.60-4.46 (m, 2H), 4.06- 3.91 (m, 2H), 3.91-3.74 (m, 2H), 3.67-3.41 (m, 4H), 3.38- 3.09 (m, J = 10.1 Hz, 5H). DMSO 442 (M + 1) 1.22 Method A (Formic acid) 100 Method AR/AS/ AT2 1686 HCl .sup.1H NMR (300 MHz, DMSO) 10.32-9.70 (m, 1H), 9.61 (s, 1H), 9.13- 8.70 (m, 5H), 8.29 (d, J = 8.5 Hz, 1H), 8.20-8.01 (m, 1H), 7.89 (d, J = 8.6 Hz, 2H), 7.83- 7.67 (m, 1H), 7.16 (d, J = 8.8 Hz, 2H), 4.38-4.27 (m, 2H), 3.43-3.32 (m, 2H), 3.27 (d, J = 3.7 Hz, 3H), 2.63 (t, J = 4.8 Hz, 3H). DMSO 386 (M + 1) 1.46 Method B (Ammon- ium formate) 100 Method AR/AS/ AT2 1687 HCl .sup.1H NMR (300 MHz, DMSO) 9.95 (s, 1H), 9.62 (s, 1H), 9.13-8.86 (m, J = 5.2 Hz, 3H), 8.39 (d, J = 8.7 Hz, 1H), 8.26 (s, 1H), 7.97-7.80 (m, 1H), 7.61- 7.37 (m, 3H), 7.14- 6.98 (m, 1H), 5.01-4.81 (m, 1H), 4.31- 4.13 (m, 2H), 3.79-3.63 (m, 2H), 1.42 (d, J = 6.5 Hz, 6H). DMSO 415 (M + 1) 1.65 Method A (Formic acid) 100 Method AR/AS/ AT1 1688 HCl .sup.1H NMR (300 MHz, DMSO) 10.12 (s, 1H), 9.63 (s, 1H), 9.10-8.88 (m, 2H), 8.72 (s, 1H), 8.44 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 8.3 Hz, 1H), 7.85 (dd, J = 7.6, 4.8 Hz, 1H), 7.52 (d, J = 6.3 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.22- 7.04 (m, 2H), 4.97 (s, 2H), 3.30 (d, J = 4.1 Hz, 3H), 2.97 (s, 3H), 2.85 (s, 3H). DMSO 414 (M + 1) 1.28 Method A (Formic acid) 100 Method AR/W with KI 1689 0 HCl .sup.1H NMR (300 MHz, DMSO) 10.22 (s, 1H), 9.63 (s, 1H), 9.10-8.87 (m, 2H), 8.75 (s, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.15 (d, J = 8.7 Hz, 1H), 8.01 (d, J = 4.2 Hz, 1H), 7.93- 7.77 (m, 1H), 7.51 (d, J = 7.3 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 8.5 Hz, 1H), 4.54 (s, 2H), 3.29 (d, J = 3.9 Hz, 3H), 2.64 (d, J = 4.4 Hz, 3H). DMSO 400 (M + 1) 1.33 Method A (Formic acid) 100 Method AR/W with KI 1690 HCl .sup.1H NMR (300 MHz, DMSO) 10.09 (s, 1H), 9.62 (s, 1H), 9.05-8.87 (m, 2H), 8.60 (s, 1H), 8.26 (d, J = 8.6 Hz, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.90- 7.77 (m, 1H), 7.54-7.36 (m, 2H), 7.26-7.06 (m, 2H), 4.23- 4.11 (m, 2H), 3.70-3.58 (m, 2H), 3.29 (d, J = 4.4 Hz, 3H), 3.24 (s, 3H). DMSO 387 (M + 1) 1.51 Method A (Formic acid) 100 Method AR/AS/ AT1 1691 HCl .sup.1H NMR (300 MHz, DMSO) 9.65 (s, 1H), 9.04 (d, J = 7.8 Hz, 1H), 8.94 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 8.39-8.22 (m, 2H), 7.97- 7.80 (m, 1H), 7.53-7.31 (m, 3H), 7.03 (d, J = 6.8 Hz, 1H), 4.26- 4.13 (m, 2H), 3.82-3.59 (m, 8H), 3.32 (s, 3H). DMSO 401 (M + 1) 1.47 Method A (Formic acid) 100 Method AR/AS/ AT1 1692 HCl .sup.1H NMR (300 MHz, DMSO) 9.83-9.26 (m, 3H), 9.00- 8.76 (m, 3H), 8.40 (d, J = 8.8 Hz, 1H), 8.18 (d, J = 8.6 Hz, 1H), 7.89-7.72 (m, 1H), 7.58- 7.36 (m, 3H), 7.04 (d, J = 3.4 Hz, 1H), 4.30-4.18 (m, 2H), 3.79- 3.66 (m, 2H), 3.33 (s, 3H). DMSO 373 (M + 1) 1.42 Method A (Formic acid) 100 Method AR/AS/ AT1 1693 HCl .sup.1H NMR (300 MHz, DMSO) 10.73-10.36 (m, 1H), 9.65 (s, 1H), 9.13- 8.98 (m, 2H), 8.93 (d, J = 5.0 Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 7.7 Hz, 1H), 7.94-7.75 (m, 1H), 7.69- 7.41 (m, 3H), 7.09 (d, J = 8.1 Hz, 1H), 4.61-4.43 (m, 2H), 4.28- 4.07 (m, 2H), 3.59-3.39 (m, 2H), 3.30 (d, J = 2.8 Hz, 3H). DMSO 454 (M + 1) 2.26 Method B (Ammon- ium formate) 100 Method AR/AS/ AT3 1694 HCl .sup.1H NMR (300 MHz, DMSO) 10.35 (s, 1H), 9.67 (s, 1H), 9.04 (d, J = 7.3 Hz, 1H), 8.94 (d, J = 5.0 Hz, 1H), 8.78 (s, 1H), 8.24 (s, 2H), 7.96-7.77 (m, 1H), 7.60- 7.40 (m, 2H), 7.33-7.10 (m, 2H), 4.50-4.36 (m, 2H), 4.05- 3.85 (m, 2H), 3.53- 3.37 (m, 2H), 3.28 (d, J = 3.6 Hz, 3H). DMSO 454 (M + 1) 2.11 Method B (Ammon- ium formate) 100 Method AR/AS/ AT3 1695 .sup.1H NMR (300 MHz, DMSO) 9.64 (s, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.73-8.50 (m, 3H), 8.14 (d, J = 8.7 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.48- 7.34 (m, 3H), 6.96 (d, J = 3.2 Hz, 1H), 4.91 (s, 2H), 3.18 (d, J = 4.3 Hz, 3H), 3.03 (s, 3H), 2.86 (s, 3H). DMSO 414 (M + 1) 1.30 Method A (Formic acid) 100 Method AR/W with KI

(445) ##STR03227##

(446) ##STR03228##

(447) Method AV: 1-(Benzyloxy)-7-bromo-3-chloroisoquinoline (lxv-a) To 20 mL of benzylalcohol was slowly added Na (2.00 g, 86.9 mmol) at 0 C., the mixture was then stirred at room temperature for 4 h. 7-bromo-1,3-dichloroisoquinoline (2.00 g, 7.2 mmol) in toluene (50 mL) was added to the mixture with stirring. The reaction mixture was heated at 80 C. overnight. The solvent was removed under reduced pressure, the residue was purified with chromatography on silica gel (petroleum ether) to give 2.00 g xiv-a as a white solid (yield 80%). LCMS m/z=257.9, 259.9 (M+1) (Method B) (retention time=1.62 min)

(448) Method AQ1: 1-(Benzyloxy)-3-chloro-7-(3-methoxyphenyl) isoquinoline (lxvi-a) To a mixture of 1-(benzyloxy)-7-bromo-3-chloroisoquinoline (1.00 g, 2.86 mmol, 1.0 eq), 3-methoxyphenylboronic acid (435 mg, 2.86 mmol, 1.0 eq), K.sub.2CO.sub.3 (2.13 g, 15.4 mmol, 5.4 eq) in dioxane (10 mL) and H.sub.2O (5 mL) was added Pd(PPh.sub.3).sub.2Cl.sub.2 (100 mg, 0.15 mmol, 0.05 eq) under N.sub.2 atmosphere. The resulting mixture was stirred at 110 C. under N.sub.2 atmosphere overnight. The solvent was removed in vacuo and the residue was purified with chromatography on silica gel (hexane/ethyl acetate 250:1) to give 550 mg of lxvi-a as white solid (yield 37%). LCMS m/z=376.0 (M+1) (Method B) (retention time=2.43 min)

(449) Method AQ3: 1-(Benzyloxy)-7-(3-methoxyphenyl)-3-(pyridin-3-yl)isoquinoline (lxvii-a) To a mixture of 1-(benzyloxy)-3-chloro-7-(3-methoxyphenyl)isoquinoline (150 mg, 0.40 mmol, 1.0 eq), pyridin-3-ylboronic acid (74 mg, 0.60 mmol, 1.5 eq), K.sub.2CO.sub.3 (166 mg, 1.20 mmol, 3.0 eq) in dioxane (2 mL) and H.sub.2O (1 mL) was added Pd(PPh.sub.3).sub.2Cl.sub.2 (14 mg, 0.02 mmol, 0.05 eq) under N.sub.2 atmosphere. The sealed tube was irradiated in the CEM microwave at 130 C. for 1 h. After the reaction was completed, the volatiles were removed in vacuo and the residue was purified with chromatography on silica gel (hexane/ethyl acetate 50:1) to give 200 mg of crude lxvii-a as a brown oil, which was used directly in the next step without purification. LCMS m/z=419.0 (M+1) (Method B) (retention time=2.25 min)

(450) Method AW: 7-(3-Methoxyphenyl)-3-(pyridin-3-yl)isoquinolin-1-ol (lxviii-a) A mixture of 1-(benzyloxy)-7-(3-methoxyphenyl)-3-(pyridin-3-yl)isoquinoline (200 mg, 0.48 mmol), and concentrated HCl (10 mL) in ethanol (20 mL) was stirred at room temperature overnight. After the reaction was completed, the mixture was filtered and concentrated to afford 130 mg of lxviii-a as a yellow solid (yield 90% for two steps). LCMS m/z=329.0 (M+1) (Method B) (retention time=1.66 min)

(451) Method AX: 1-Chloro-7-(3-methoxyphenyl)-3-(pyridin-3-yl)isoquinoline (lxix-a) To a mixture of 7-(3-methoxyphenyl)-3-(pyridin-3-yl)isoquinolin-1-ol (130 mg, 0.395 mmol) in phenylphosphonic dichloride (5 mL) was stirred at 120 C. overnight. After the reaction was completed, the mixture was added to ice-water slowly. The pH was adjusted to 7 by slow addition of NH.sub.3H.sub.2O at 0 C. Then the mixture was extracted with dichloromethane (100 mL x 3). The combined organic layer were dried over MgSO.sub.4, filtered and concentrated in vacuo to give 130 mg of crude lxix-a as a white solid, which was used directly in the next step without purification. LCMS m/z=346.9 (M+1) (Method B) (retention time=1.80 min)

(452) Method AY: 7-(3-Methoxyphenyl)-N-methyl-3-(pyridin-3-yl)isoquinolin-1-amine (lxx-a) A mixture of 1-chloro-7-(3-methoxyphenyl)-3-(pyridin-3-yl)isoquinoline (90 mg, 0.26 mmol), methylamine hydrochloride (200 mg, 2.96 mmol, 10.0 eq) and Et.sub.3N (0.5 mL) was added to a sealed tube with i-AmOH (2 mL). The sealed tube was irradiated in the CEM microwave at 160 C. for 1 h. After the reaction was completed, the i-AmOH was removed in vacuo and the residue was dissolved in 10 mL of water and dichloromethane, the mixture was extracted with dichloromethane (350 mL). The combined organic layers were dried over MgSO.sub.4, filtered and concentrated in vacuo and the residue was washed with MeOH to give 5 mg of lxx-a as a brown solid (yield 6%). LCMS m/z=342.1 (M+1) (Method B) (retention time=2.02 min). .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.40 (d, J=0.9 Hz, 1H), 8.67-8.47 (m, 3H), 8.08-7.95 (m, 1H), 7.89-7.84 (m, 2H), 7.66 (s, 1H), 7.57-7.49 (m, 1H), 7.46-7.42 (m, 3H), 7.08-6.95 (m, 1H), 3.88 (s, 3H), 3.14 (d, J=4.3 Hz, 3H).

(453) The compounds in the following table were prepared in a manner analogous to that described in Scheme 81, replacing with the appropriate isoquinoline and aniline.

(454) TABLE-US-00042 TABLE 27 Mole- .sup.1H- Method Num- Salt cular NMR LCMS Purity for ber PRODUCT type Mass .sup.1H-NMR Solvent LCMS Protocol percent Coupling 1697 341.41 1H-NMR (400 MHz, DMSO-d6): 9.40 (d, J = 0.9 Hz, 1H), 8.67- 8.47 (m, 3H), 8.08- 7.95 (m, 1H), 7.89- 7.84 (m, 2H), 7.66 (s, 1H), 7.57-7.49 (m, 1H), 7.46-7.42 (m, 3H), 7.08-6.95 (m, 1H), 3.88 (s, 3H), 3.14 (d, J = 4.3 Hz, 3H). DMSO 342.1 (M + 1) Method B (NH4HCO3) 95 Method AX, H1 1698 0 312.37 1H-NMR (400 MHz, DMSO-d6): 9.40 (d, J = 1.8 Hz, 1H), 9.12 (d, J = 2.1 Hz, 1H), 8.66 (s, 1H), 8.60 (m, 2H), 8.54 (dt, J = 8.0, 1.9 Hz, 1H), 8.29-8.23 (m, 1H), 8.08 (dd, J = 8.5, 1.6 Hz, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 4.5 Hz, 1H), 7.68 (s, 1H), 7.56 (dd, J = 7.8, 4.8 Hz, 1H), 7.51 (dd, J = 7.8, 4.8 Hz, 1H), 3.14 (d, J = 4.4 Hz, 3H). DMSO 312.9 (M + 1) Method B (NH4HCO3) 95 Method AX, H1

(455) ##STR03231##

(456) ##STR03232##

(457) Method BA: Synthesis of 5-[3-(4-Methylamino-2-pyridin-3-yl-quinazolin-6-yl)-phenoxymethyl]-oxazolidin-2-one (lxxi-a) To 5-(chloromethyl)oxazolidin-2-one (45 mol) was added the solution of 3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenol (30 mol) in NMP (200 L). PS-BEMP (90 mol) was added to the vials by resin dispenser. After the reaction mixture was heated at 90 C. for 12 h, the residue was diluted with methanol and purified by PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound whose structure was finally confirmed by LCMS using LCMS Method E.

(458) The compounds in the following table were prepared in a manner analogous to that described in Scheme 80, replacing 5-(chloromethyl)oxazolidin-2-one with the appropriate alkyl halide.

(459) TABLE-US-00043 TABLE 28 Starting Starting Number Material 1 Material 2 1699 1700 1701 1702 0 1703 1704 1705 1706 1707 0 1708 1709 1710 1711 1712 0 1713 1714 1715 Mass Salt Exact Found Purity Number Product Type Mass (M + 1) (%) 1699 427 428 98 1700 421 422 98 1701 TFA 467 468 98 1702 0 515 516 98 1703 2TFA 468 469 98 1704 TFA 436 437 98 1705 455 456 98 1706 438 439 98 1707 421 422 98 1708 453 454 98 1709 TFA 467 468 98 1710 487 488 98 1711 TFA 515 516 98 1712 0 TFA 436 437 98 1713 TFA 422 423 98 1714 TFA 476 477 98 1715 2TFA 438 439 98

(460) ##STR03284##

(461) ##STR03285##

(462) Method BB: Synthesis of 3-methyl-6-((3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenoxy)methyl)benzo[d]oxazol-2(3H)-one (lxxi-b) To 6-(hydroxymethyl)-3-methylbenzo[d]oxazol-2(3H)-one (45 mol) was added the solution of 3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenol (30 mol) in THF (400 L). After PS-triphenylphosphine (60 mol) was added, the solution of DBAD (di-tert-butyl azodicarboxylate, 66 mol) in THF was dispensed to the vials. The mixture was heated at 50 C. for 8 h. After the solvent was removed, the residue was diluted with methanol and purified by Mass triggered PREP-HPLC Condition D. The target fraction was lyophilized to afford the titled compound whose structure was finally confirmed by LCMS using LCMS Method E.

(463) The compounds in the following table were prepared in a manner analogous to that described in Scheme 85, replacing 6-(hydroxymethyl)-3-methylbenzo[d]oxazol-2(3H)-one with the appropriate alkyl alcohol.

(464) TABLE-US-00044 TABLE 29 Number Starting Material 1 Starting Material 2 1716 1717 1718 0 1719 1720 1721 1722 1723 00 01 1724 02 03 1725 04 05 1726 06 07 1727 08 09 1728 0 1729 1730 1731 1732 1733 0 1734 1735 1736 1737 1738 0 Salt Mass Found Number Product Type Exact Mass (M + 1) Purity (%) 1716 TFA 489 490 100 1717 448 449 100 1718 TFA 422 423 100 1719 TFA 422 423 100 1720 TFA 472 473 100 1721 TFA 489 490 100 1722 TFA 489 490 100 1723 TFA 466 467 100 1724 0 TFA 425 426 94 1725 TFA 453 454 100 1726 TFA 489 490 100 1727 TFA 489 490 100 1728 TFA 448 449 100 1729 TFA 422 423 100 1730 TFA 504 505 100 1731 TFA 424 425 100 1732 TFA 433 434 100 1733 TFA 484 485 100 1734 0 TFA 466 467 100 1735 TFA 425 426 100 1736 TFA 464 465 95 1737 TFA 466 467 100 1738 TFA 489 490 100

(465) ##STR03355##

(466) Synthesis of N-(6-bromo-2-(pyridin-3-yl)quinazolin-4-yl)acetamide (lxxii-a) A 100 mL round bottom flask was fitted with a reflux condenser and charged with 6-bromo-2-(pyridin-3-yl)quinazolin-4-amine (2.45 g, 8.14 mmol), acetic anhydride (5.81 g, 57.0 mmol) and acetic acid (30 mL). The reaction mixture was stirred at 90 C. for 20 min and then cooled to room temperature. A precipitate formed during the reaction and was collected by filtration and washed with water (100 mL). The solid was dried at 60 C. to give N-(6-bromo-2-(pyridin-3-yl)quinazolin-4-yl)acetamide as a white powder (1.83 g, 66%). .sup.1H NMR (300 MHz, CDCl.sub.3) 9.72 (s, 1H), 8.84-8.69 (m, 3H), 8.22 (s, 1H), 8.02-7.90 (m, 2H), 7.53-7.41 (m, 1H), 2.83 (s, 3H).

(467) ##STR03356##

(468) Synthesis of N-(6-bromo-2-(pyridin-3-yl)quinazolin-4-yl)-N-methylacetamide (lxxiii-a) To a solution of 6-bromo-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (1.20 g, 3.81 mmol) in acetic acid (10 mL) was added acetic anhydride (1.94 g, 19.0 mmol) and stirred at 195 C. using microwave for 6 h. The reaction mixture was checked by LC-MS, no starting material was observed, ice was added into the reaction. The precipitate was collected by filtration and washed with water. The product was dried at 60 C. to give N-(6-bromo-2-(pyridin-3-yl)quinazolin-4-yl)-N-methylacetamide (711 mg, 52%) as a light brown powder. .sup.1H NMR (300 MHz, CDCl.sub.3) 9.76 (dd, J=2.2, 0.8 Hz, 1H), 8.85-8.79 (m, 1H), 8.76 (dd, J=4.8, 1.7 Hz, 1H), 8.09 (dd, J=1.8, 0.8 Hz, 1H), 8.05-8.01 (m, 2H), 7.46 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 3.52 (s, 3H), 2.11 (s, 3H).

(469) ##STR03357##

(470) Method BC: Synthesis of 6-(2,3-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (lxxv-a) (Compound 1742) To a solution of the hydroxyl derivative (520 mg, 1.27 mmol) in DMF (20 mL) was added methyl iodide (262 mg, 1.84 mmol) and NaH (55% in oil; 69 mg, 1.9 mmol) at 0 C. The reaction mixture was stirred at room temperature for 1 h and the ice water was added into the reaction mixture. The resulting solution was extracted with ethyl acetate (3 times), dried over Na.sub.2SO.sub.4, concentrated and purified by column chromatography (NH-silica gel, 50% hexane/50% ethyl acetate). The resulting product was dissolved in isopropyl alcohol and 1NHCl (5 mL) was added and a precipitate formed which was collected by filtration and dried at 60 C. to give 6-(2,3-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as an orange powder (130 mg, 21%). .sup.1H NMR (300 MHz, DMSO) 9.66 (d, J=1.6 Hz, 1H), 9.09 (d, J=8.1 Hz, 1H), 8.96 (dd, J=5.1, 1.5 Hz, 1H), 8.51 (s, 1H), 8.33 (d, J=8.7 Hz, 1H), 8.20 (d, J=8.8 Hz, 1H), 7.90 (dd, J=8.1, 5.1 Hz, 1H), 7.66-7.47 (m, 2H), 7.47-7.32 (m, 1H), 4.22-4.07 (m, 2H), 3.70 (s, 3H), 3.48 (t, J=5.8 Hz, 2H), 3.22 (s, 3H), 2.19-2.01 (m, 2H).

(471) ##STR03358##

(472) Method BD: 2-(3-(4-(dimethylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenyl)ethanol, 2HCl (lxxvi-a) To a reaction vial containing 2-(3-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenyl)ethanol (89.0 mg, 0.25 mmol) in DMF (1 mL) was added 60% sodium hydride (13 mg, 0.325 mmol) and iodomethane (0.02 mL, 0.325 mmol). The reaction mixture was allowed to stir at ambient temperature for 12 h. Water (20 mL) was added to the reaction mixture, and the crude product was extracted with ethyl acetate (415 mL). The crude material was purified via ISCO (silica, 4 g column, 95% CH.sub.2Cl.sub.2-5% MeOH-0.1% NH.sub.4OH) to give the product as an off-white solid. The free base was then converted to the HCl salt to yield the final product as a yellow solid (24.6 mg, 0.055 mmol, 22%). LC-MS m/z=371.5 (M+1) (retention time=1.86).sup.1H NMR (300 MHz, DMSO) 9.61 (d, J=2.1 Hz, 1H), 8.99 (d, J=7.5 Hz, 1H), 8.93 (dd, J=5.0, 1.5 Hz, 1H), 8.48 (d, J=1.0 Hz, 1H), 8.28 (dd, J=17.4, 9.4 Hz, 2H), 7.84 (dd, J=7.7, 5.1 Hz, 1H), 7.69-7.60 (m, 2H), 7.44 (t, J=7.5 Hz, 1H), 7.30 (d, J=7.3 Hz, 1H), 3.78-3.61 (m, 9H), 2.82 (t, J=7.0 Hz, 2H).

(473) Synthesis of 6-(2,4-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride (lxxvii-a) (Compound 1744) 6-(2,4-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride was synthesized in a similar manner to that described for 6-(2,3-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride substituting the appropriate hydroxyl derivative. 6-(2,4-difluorophenyl)-N-(3-methoxypropyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine was obtained as the dihydrochloride salt .sup.1H NMR (300 MHz, DMSO) 9.69 (d, J=2.0 Hz, 1H), 9.14 (d, J=8.3 Hz, 1H), 8.97 (dd, J=5.1, 1.2 Hz, 1H), 8.45 (s, 1H), 8.39 (d, J=8.6 Hz, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.92 (dd, J=8.0, 5.2 Hz, 1H), 7.86-7.73 (m, 1H), 7.57-7.38 (m, 1H), 7.36-7.23 (m, 1H), 4.19-4.04 (m, 2H), 3.71 (s, 3H), 3.48 (t, J=5.7 Hz, 2H), 3.23 (s, 3H), 2.21-1.96 (m, 2H).

(474) ##STR03359##

(475) Method BE: 4-(3,4-dichlorophenyl)-1-(6-(3-methoxyphenyl)-2-(pyridin-3-yl)quinazolin-4-yl)pyrrolidin-2-one (lxxviii-a) To a mixture of 4-chloro-6-(3-methoxyphenyl)-2-(pyridin-3-yl)quinazoline (40 mg, 0.12 mmol), 4-(3,4-dichlorophenyl)pyrrolidin-2-one (100 mg, 0.437 mmol) and Cs.sub.2CO.sub.3 (42 mg, 0.127 mmol) in dry toluene (6 mL) was added Pd(OAc).sub.2 (3 mg, 0.01 mmol) and Xantphos (10 mg, 0.02 mmol) under a nitrogen atmosphere. The resulting mixture was stirred at 100 C. for 12 h. After cooling, the mixture was filtered through a pad of celite. The residue was purified by silica gel chromatography, eluted with petroleum ether/ethyl acetate (5:4) to give the desired product as a yellow solid. 14 mg of the desired product was obtained in a 22.5%. yield, LCMS: retention time=1.802 min, [MH].sup.+=541.0, 543.0. .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.73 (s, 1H), 9.05-9.04 (m, 1H), 8.86-8.85 (m, 1H), 8.42-8.38 (m, 2H), 8.19 (d, J=8.8 Hz, 1H), 7.89 (d, J=1.6 Hz, 1H), 7.82-7.81 (m, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.58 (dd, J=8.0, 1.6 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.41-7.36 (m, 2H), 7.07 (dd, J=8.0, 2.0 Hz, 1H), 4.57-4.46 (m, 2H), 4.06-4.03 (m, 1H), 3.20-3.01 (m, 2H), 3.88 (s, 3H).

(476) The compounds in the following table were prepared in a manner analogous to that described in Scheme 91, replacing 4-(3,4-dichlorophenyl)pyrrolidin-2-one with the appropriate amide

(477) TABLE-US-00045 TABLE 30 .sup.1H Method Num- Salt NMR Purity of LCMS ber Product type .sup.1H NMR Solvent percent Coupling LCMS Method 1745 0 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.75 (s, 1H), 8.90 (d, J = 8.0 Hz, 1H), 8.78 (d, J = 4.0 Hz, 1H), 8.35 (s, 1H), 8.28-8.19 (m, 2H), 7.92 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 5.0 Hz, 2H), 7.73-7.70 (m, 1H), 7.68-7.61 (m, 2H), 7.52-7.42 (m, 1H), 7.29 (t, J = 8.4 Hz, 1H), 5.61 (s, 2H). DMSO 95 Method BE 451.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1746 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74 (s, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.77 (d, J = 3.8 Hz, 1H), 8.45 (s, 1H), 8.39 (d, J = 8.7 Hz, 1H), 8.18 (d, J = 8.7 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.83 (s, 2H), 7.72-7.56 (m, 2H), 7.52-7.27 (m, 3H), 7.03 (d, J = 7.9 Hz, 1H), 5.60 (s, 2H), 3.85 (s, 3H). DMSO 95 Method BE 445.1 (M + 1) Method B (NH.sub.4HCO.sub.3) 1747 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.76 (s, 1H), 8.91 (d, J = 6.4 Hz, 1H), 8.79 (s, 1H), 8.41 (s, 1H), 8.30-8.23 (m, 2H), 7.92 (d, J = 8.0 Hz, 1H), 7.83 (s, 2H), 7.65 (d, J = 3.6 Hz, 2H), 7.55-7.49 (m, 2H), 7.40 (s, 1H), 5.61 (s, 2H). DMSO 95 Method BE 451.0, 452.0, (M + 1) Method B (NH.sub.4HCO.sub.3) 1748 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.73 (s, 1H), 9.05-9.04 (m, 1H), 8.86-8.85 (m, 1H), 8.42-8.38 (m, 2H), 8.19 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 1.6 Hz, 1H), 7.82-7.81 (m, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.58 (dd, J = 8.0, 1.6 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.41-7.36 (m, 2H), 7.07 (dd, J = 8.0, 2.0 Hz, 1H), 4.57-4.46 (m, 2H), 4.06-4.03 (m, 1H), 3.20-3.01 (m, 2H), 3.88 (s, 3H). DMSO 95 Method BE 541.0, 543.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1749 2HCl .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.68 (s, 1H), 8.83 (d, J = 8.0 Hz, 1H), 8.76 (s, 1H), 8.39-8.37 (m, 2H), 8.17 (d, J = 10.0 Hz, 1H), 7.63-7.31 (m, 9H), 7.06 (dd, J = 8.4, 2.0 Hz, 1H), 4.56-4.45 (m, 2H), 4.03-3.99 (m, 1H), 3.88 (s, 3H), 3.19-2.97 (m, 2H). DMSO 95 Method BE 472.9 (M + 1) Method B (NH.sub.4HCO.sub.3) 1750 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74 (d, J = 8.4 Hz, 1H), 8.89 (dt, J = 8.4, 1.6 Hz, 1H), 8.78 (dd, J = 4.4, 1.2 Hz, 1H), 8.46 (d, J = 1.6 Hz, 1H), 8.41 (dd, J = 8.8, 1.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.88 (s, 2H), 7.65-7.62 (m, 1H), 7.48-7.44 (m, 1H), 7.41-7.37 (m, 2H), 7.04 (dd, J = 8.0, 1.6 Hz, 1H), 5.59 (s, 2H), 3.86 (s, 3H). DMSO 95 Method BE 479.0 (M + 1) Method B (NH.sub.4HCO.sub.3) 1751 .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.74 (s, 1H), 8.89 (d, J = 8.4 Hz, 1H), 8.78 (d, J = 4.4 Hz, 1H), 8.46 (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.91-7.87 (m, 1H), 7.77-7.62 (m, 3H), 7.48- 7.37 (m, 3H), 7.03 (d, J = 6.4 Hz, 1H), 5.58 (s, 2H), 3.86 (s, 3H). DMSO 95 Method BE 463.1 (M + 1) Method B (NH.sub.4HCO.sub.3)

(478) ##STR03367##

(479) N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (1.51 g, 3.87 mmol) was dissolved in CH.sub.2Cl.sub.2/MeOH (20 mL/20 mL). Methanesulfonic acid (0.251 mL, 3.87 mmol) was added to the solution. The volatiles were evaporated in vacuo. The resultant residue was crystallized from EtOH (30 mL) to give 1.35 g of N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine methanesulfonate as a light yellow powder (72%). LCMS m/z=391 (M+1) (Method D) (Retention time=1.91 min). .sup.1H NMR (300 MHz, DMSO) 9.52 (s, 1H), 9.01-8.83 (m, 2H), 8.75 (s, 1H), 8.58 (s, 1H), 8.09 (d, J=7.2 Hz, 1H), 8.03-7.85 (m, 2H), 7.83-7.68 (m, 1H), 7.59-7.43 (m, 1H), 7.33 (t, J=7.9 Hz, 1H), 2.31 (s, 3H), 1.66 (s, 9H).

(480) ##STR03368##

(481) N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (1.22 g, 3.12 mmol) was dissolved in CH.sub.2Cl.sub.2/MeOH (20 mL/20 mL). Fumaric acid (0.363 g, 3.12 mmol) was added to the solution. The mixture was sonicated until fumaric acid was dissolved. Then, the volatiles were evaporated in vacuo. The resultant solid was washed with MeOH and dried to give 1.28 g of N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine fumarate as a light yellow powder (91%). LCMS m/z=391 (M+1) (Method D) (Retention time=1.95 min). .sup.1H NMR (300 MHz, DMSO) 13.14 (s, 1H), 9.59 (s, 1H), 8.82-8.65 (m, 2H), 8.57 (s, 1H), 7.89 (d, J=8.7 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.79-7.62 (m, 2H), 7.61-7.52 (m, 1H), 7.51-7.38 (m, 1H), 7.28 (t, J=8.6 Hz, 1H), 6.61 (s, 1H), 1.64 (s, 9H).

(482) ##STR03369##

(483) N-methyl-6-(3-(2-propoxyethoxyl)phenyl)-2-(pyridin-3-yl)quinazolin-4-amine fumarate was synthesized in a similar manner to that described N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine fumarate. LCMS m/z=415.5 (M+1) (Method C (NH.sub.4HCO.sub.3) (Retention time=2.43 min). .sup.1H NMR (300 MHz, CD.sub.3OD) 9.57 (s, 1H), 8.84 (m, 1H), 8.63 (s, 1H), 8.35 (m, 1H), 8.07 (m, 1H), 7.88 (d, J=8.7 Hz, 1H), 7.58 (m, 1H), 7.48-7.24 (m, 4H), 7.00 (m, 1H), 6.74 (s, 1H), 4.36-4.05 (m, 2H), 4.00-3.70 (m, 2H), 3.53 (t, J=6.6 Hz, 2H), 3.29-3.13 (m, 3H), 1.75-1.51 (m, 2H), 0.95 (t, J=7.4 Hz, 3H).

(484) ##STR03370##

(485) N-methyl-6-(3-(2-propoxyethoxy)phenyl)-2-(pyridin-3-yl)quinazolin-4-amine methanesulfonate was synthesized in a similar manner to that described N-tert-butyl-6-(2,4-difluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine methanesulfonate. LCMS m/z=415.5 (M+1) (Method C (NH.sub.4HCO.sub.3) (Retention time=2.43 min). .sup.1H NMR (300 MHz, CD.sub.3OD) 9.49 (s, 1H), 9.00-8.72 (m, 1H), 8.53 (s, 1H), 8.29 (m, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.80 (dd, J=8.0, 5.1 Hz, 1H), 7.52-7.25 (m, 3H), 7.02 (m, 1H), 4.38-4.06 (m, 2H), 3.98-3.72 (m, 2H), 3.61-3.48 (m, 2H), 3.42 (d, J=0.6 Hz, 3H), 3.34-3.26 (m, 2H), 2.71 (s, 3H), 1.80-1.47 (m, 2H), 0.96 (t, J=7.4 Hz, 3H).

(486) Biological Testing:

(487) STEP46 Biochemical Assays

(488) Serial dilutions of compounds were performed in 100% DMSO and 1 uL of compounds were dispensed into 384-well black polystyrene plates (Corning, NY). Compounds were incubated with 24 uL of buffer containing 50 mM Hepes, 1 mM DTT, 0.02% Brij35, 1 ng/well purified STEP46 enzyme for 30 min at room temperature. The reaction was initiated by addition of 25 uL of DiFMUP (6, 8-difluoro-4-methylumbelliferyl phosphate) (InVitrogen, CA) with a final concentration of 10 M and incubated at 27 C. for 90 min. Final DMSO concentration is 2%. Plates were read with florescence intensity at excitation/emission of 360/460 nm using a PheraStar plate reader (BMG Labtech, NC).

(489) Data Analysis

(490) Data were expressed as percentage (%) inhibition of enzyme activity. 0% inhibition is defined as the RFUs (relative fluorescence units) in the absence of compounds and 100% inhibition is defined as RFUs in the absence of STEP46 enzyme. IC.sub.50 values of compounds with inhibitory activity against STEP46 were determined by GraphPad Prism (version 4.03) using four parameter logistic equation. Some compounds act as activators. For compounds showing STEP46 enzymatic activation, data are represented as percentage of inhibition but with negative values at three representative concentrations (25, 50 and 100 uM).

(491) Compounds 1-1760 show either inhibition or activation >50% at 100 uM, 50 or 25 uM.

(492) TABLE-US-00046 STEP IC50 Number (M) 73 ++ 296 ++ 297 + 300 + 303 ++ 306 + 309 ++ 312 +++ 313 +++ 314 ++ 315 ++ 316 +++ 317 ++ 318 ++ 320 ++ 322 + 325 +++ 326 ++ 327 ++ 329 +++ 330 ++ 332 +++ 333 +++ 334 ++ 335 +++ 336 +++ 337 +++ 339 ++ 341 ++ 342 ++ 343 + 344 ++ 346 ++ 348 ++ 352 ++ 390 ++ 391 ++ 392 ++ 393 ++ 396 ++ 399 +++ 400 ++ 403 ++ 407 ++ 412 +++ 415 ++ 416 +++ 418 ++ 419 +++ 421 + 423 ++ 424 ++ 425 ++ 426 + 427 ++ 428 ++ 429 +++ 430 +++ 431 +++ 433 ++ 434 ++ 435 +++ 436 ++ 437 ++ 439 +++ 440 ++ 441 ++ 442 +++ 443 +++ 444 +++ 445 +++ 446 ++ 447 ++ 448 +++ 449 ++ 451 +++ 452 +++ 453 +++ 454 ++ 455 ++ 456 +++ 457 ++ 458 +++ 459 +++ 460 ++ 461 ++ 463 ++ 466 ++ 467 ++ 468 +++ 470 ++ 471 ++ 472 ++ 473 ++ 474 ++ 629 ++ 630 ++ 631 ++ 632 +++ 633 ++ 634 ++ 635 +++ 636 + 637 ++ 638 ++ 639 +++ 640 ++ 641 +++ 642 +++ 643 +++ 644 ++ 645 ++ 647 ++ 648 ++ 649 ++ 650 +++ 651 +++ 652 +++ 653 +++ 655 +++ 656 +++ 657 +++ 658 ++ 660 +++ 661 +++ 662 +++ 663 +++ 664 ++ 665 ++ 666 +++ 667 +++ 668 +++ 669 +++ 670 +++ 671 ++ 672 ++ 673 ++ 674 ++ 675 +++ 676 +++ 677 + 678 ++ 679 +++ 680 ++ 681 ++ 682 ++ 683 ++ 684 ++ 685 +++ 686 +++ 687 +++ 688 +++ 689 +++ 690 ++ 691 +++ 692 +++ 693 +++ 694 +++ 695 +++ 696 +++ 697 ++ 698 +++ 699 +++ 700 +++ 701 ++ 702 +++ 703 +++ 704 +++ 705 +++ 706 +++ 707 +++ 708 ++ 709 +++ 846 ++ 847 +++ 884 + 888 + 889 ++ 898 + 899 ++ 900 ++ 901 ++ 923 ++ 932 ++ 933 ++ 934 +++ 962 +++ 1124 +++ 1125 ++ 1126 ++ 1140 +++ 1141 +++ 1142 ++ 1143 ++ 1144 ++ 1145 ++ 1146 ++ 1148 ++ 1150 + 1151 ++ 1152 ++ 1153 ++ 1155 ++ 1157 ++ 1158 ++ 1159 ++ 1160 ++ 1161 ++ 1165 +++ 1167 ++ 1168 ++ 1171 ++ 1172 ++ 1173 + 1176 ++ 1178 ++ 1180 ++ 1181 ++ 1182 ++ 1183 ++ 1184 ++ 1185 ++ 1186 ++ 1187 +++ 1188 ++ 1191 ++ 1192 ++ 1193 ++ 1194 +++ 1198 ++ 1200 ++ 1201 ++ 1202 ++ 1203 ++ 1204 + 1205 ++ 1206 ++ 1208 + 1211 + 1212 ++ 1213 ++ 1214 ++ 1215 +++ 1216 +++ 1217 ++ 1218 ++ 1219 ++ 1220 + 1221 + 1222 ++ 1223 +++ 1225 ++ 1226 ++ 1227 ++ 1228 ++ 1229 ++ 1230 ++ 1234 ++ 1237 ++ 1238 ++ 1239 ++ 1248 ++ 1279 ++ 1280 ++ 1281 +++ 1282 ++ 1283 + 1284 ++ 1285 + 1286 ++ 1324 ++ 1327 + 1328 + 1330 + 1332 ++ 1333 + 1334 + 1335 ++ 1336 ++ 1337 ++ 1339 ++ 1340 ++ 1341 ++ 1346 ++ 1348 + 1350 ++ 1351 ++ 1352 + 1353 ++ 1354 ++ 1356 ++ 1357 ++ 1358 ++ 1359 ++ 1360 ++ 1361 + 1362 ++ 1363 ++ 1364 ++ 1365 ++ 1366 ++ 1369 ++ 1370 ++ 1371 ++ 1372 ++ 1373 ++ 1374 ++ 1375 ++ 1376 ++ 1380 ++ 1381 ++ 1382 +++ 1391 + 1395 ++ 1396 ++ 1400 ++ 1401 ++ 1402 ++ 1403 + 1404 + 1406 ++ 1407 ++ 1408 ++ 1409 ++ 1410 ++ 1411 + 1412 ++ 1413 ++ 1414 ++ 1415 + 1416 ++ 1419 ++ 1420 ++ 1422 ++ 1423 + 1424 + 1425 ++ 1430 ++ 1437 ++ 1445 ++ 1446 ++ 1447 + 1448 ++ 1449 + 1450 ++ 1451 ++ 1452 +++ 1453 ++ 1454 + 1455 ++ 1456 ++ 1458 + 1467 ++ 1497 ++ 1516 + 1601 ++ 1611 ++ 1680 ++ Key + IC.sub.50 > 10 uM ++ IC.sub.50 1-10 uM +++ IC.sub.50 < 1 uM

(493) Having thus described several aspects of at least one embodiment of this invention, it is to be appreciated various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications, and improvements are intended to be part of this disclosure, and are intended to be within the spirit and scope of the invention. Accordingly, the foregoing description and drawings are by way of example only.