OXOPYRROLIDINE FPR2 AGONISTS

20230348426 · 2023-11-02

    Inventors

    Cpc classification

    International classification

    Abstract

    The disclosure relates to compounds of Formula (I), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.

    ##STR00001##

    Claims

    1. A compound of Formula (I): ##STR00850## or a pharmaceutically acceptable salt thereof, wherein: * is an asymmetric carbon atom; Ar.sup.1 is aryl or pyridyl, each substituted with 1-3 R.sup.1; Ar.sup.2 is C.sub.3-6 cycloalkyl, aryl, or 5- to 12-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.2a, and each substituted with 0-3 R.sup.2; Ar.sup.3 is phenyl or pyridyl, each substituted with 1 R.sup.5a, 1 R.sup.5b, and 1 R.sup.5c; R.sup.1 is halo, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, or C.sub.1-4 haloalkoxy; R.sup.2 is oxo, cyano, halo, C.sub.1-6 alkyl substituted with 0-5 R.sup.e, -OR.sup.b, -NR.sup.3R.sup.4, -NR.sup.4C(O)R.sup.b, -NR.sup.4(CR.sup.dR.sup.d).sub.0-1C(O)NR.sup.3R.sup.4, (C.sub.1-4 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, or 5 to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.a; R.sup.2a is hydrogen, C.sub.1-4 alkyl substituted with 0-5 R.sup.e, -(CR.sup.dR.sup.d).sub.1-4-NR.sup.3R.sup.4, -(CR.sup.dR.sup.d).sub.1-4-OR.sup.b, -(CR.sup.dR.sup.d).sub.1-4-C(O)NR.sup.3R.sup.4, -(CR.sup.dR.sup.d).sub.r-C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, -(CR.sup.dR.sup.d).sub.r-aryl substituted with 0-5 R.sup.e, or -(CR.sup.dR.sup.d).sub.1-heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.a and substituted with 0-5 R.sup.e; R.sup.3 is hydrogen, C.sub.1-4 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.8 and substituted with 0-5 R.sup.e; R.sup.4 is hydrogen or C.sub.1-4 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4 to 9-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.8 and substituted with 1-3 R.sup.6; R.sup.5a is hydrogen or halo; R.sup.5b is hydrogen or halo; R.sup.5c is halo, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, or deuteroalkoxy; R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-4 alkyl substituted with 0-5 R.sup.e; R.sup.7 is hydrogen or C.sub.1-4 alkyl; R.sup.8 is hydrogen, C.sub.1-4 alkyl, or -S(O).sub.pR.sup.c; R.sup.a is hydrogen or C.sub.1-6 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, aryl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, NR.sup.d and substituted with 0-5 R.sup.e; R.sup.b is hydrogen, C.sub.1-6 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, aryl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, NR.sup.d and substituted with 0-5 R.sup.e; R.sup.c is C.sub.1-4 alkyl substituted with 0-5 R.sup.e; R.sup.d is hydrogen or C.sub.1-4 alkyl substituted with 0-5 R.sup.e; R.sup.e is halo, cyano, oxo, -OR.sup.g, -NR.sup.gR.sup.g, -C(O)NR.sup.gR.sup.g, -S(O).sub.pC.sub.1-4 alkyl, C.sub.1-6 alkyl substituted with 0-5 R.sup.f, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.f, -(CH.sub.2).sub.r-aryl substituted with 0-5 R.sup.f, or (CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.g and substituted with 0-5 R.sup.f; R.sup.f is halo, cyano, hydroxy, oxo, C.sub.1-5 alkyl, C.sub.3-6 cycloalkyl, or phenyl; R.sup.g is hydrogen, C.sub.1-5 alkyl, C.sub.3-6 cycloalkyl, aryl, or heterocyclyl; or R.sup.g and R.sup.g together with the nitrogen atom to which they are both attached form a heterocyclyl; n is zero or 1; p is zero, 1, or 2; and r is zero, 1, 2, 3, or 4.

    2. The compound of claim 1, having Formula (II): ##STR00851## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.2 is C.sub.3-6 cycloalkyl, phenyl, 5- to 6-membered heterocyclyl comprising 1-2 N or NR.sup.2a, each substituted with 0-2 R.sup.2; Ar.sup.3 is phenyl substituted with 1 R.sup.5a, 1 R.sup.5b, and 1 R.sup.5c; R.sup.1 is halo, C.sub.1-4 haloalkyl, or C.sub.1-4 haloalkoxy; R.sup.2 is oxo, cyano, halo, C.sub.1-5 alkyl substituted with 0-5 R.sup.e, -OR.sup.b, -NR.sup.3R.sup.4, -NR.sup.4C(O)R.sup.b, (C.sub.1-3 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, or 5- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a; R.sup.2a is hydrogen, C.sub.1-4 alkyl substituted with 0-4 R.sup.e, -(CHR.sup.d).sub.1-3-C(O)NR.sup.3R.sup.4, -(CHR.sup.d).sub.r-C.sub.3-6 cycloalkyl substituted with 0-4 R.sup.e, -(CHR.sup.d).sub.r-aryl substituted with 0-4 R.sup.e, or -(CHR.sup.d).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-4 R.sup.e; R.sup.3 is hydrogen, C.sub.1-4 alkyl substituted with 0-4 R.sup.e, C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-4 R.sup.e; R.sup.4 is hydrogen or C.sub.1-3 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4-to 8-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; R.sup.5a is hydrogen or halo; R.sup.5b is hydrogen or halo; R.sup.5c is halo, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, or C.sub.1-4 alkoxy; R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-4 alkyl substituted with 0-4 R.sup.e; R.sup.7 is hydrogen or C.sub.1-3 alkyl; R.sup.8 is hydrogen, C.sub.1-3 alkyl, or -S(O).sub.pR.sup.c; R.sup.a is hydrogen or C.sub.1-6 alkyl substituted with 0-5 R.sup.e; R.sup.b is hydrogen, C.sub.1-6 alkyl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, NR.sup.d and substituted with 0-5 R.sup.e; R.sup.c is C.sub.1-3 alkyl substituted with 0-5 R.sup.e; R.sup.d is hydrogen or C.sub.1-4 alkyl substituted with 0-1 -OC.sub.1-4 alkyl; R.sup.e is halo, cyano, oxo, -OR.sup.g, -NR.sup.gR.sup.g, -C(O)NR.sup.gR.sup.g, -S(O).sub.pC.sub.1-4 alkyl, C.sub.1-4 alkyl substituted with 0-5 R.sup.f, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.f, -(CH.sub.2).sub.r-aryl substituted with 0-5 R.sup.f, or (CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-5 R.sup.f; R.sup.f is halo, cyano, hydroxy, C.sub.1-5 alkyl, or C.sub.3-6 cycloalkyl; R.sup.g is hydrogen, C.sub.1-5 alkyl, or heterocyclyl; n is zero; and r is zero, 1, 2, or 3.

    3. The compound of claim 2, having Formula (III): ##STR00852## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.2 is ##STR00853## ##STR00854## ##STR00855## ##STR00856## ##STR00857## ##STR00858## ##STR00859## ##STR00860## ##STR00861## ##STR00862## ##STR00863## R.sup.1 is halo, C.sub.1-3 haloalkyl, or C.sub.1-3 haloalkoxy; R.sup.2 is cyano, halo, C.sub.1-4 alkyl substituted with 0-5 R.sup.e, -OR.sup.b, -NR.sup.3R.sup.4, -NR.sup.4C(O)R.sup.b, (C.sub.1-4 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, or 5- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a; R.sup.2a is hydrogen, C1-4 alkyl substituted with 0-3 R.sup.e, -(CHR.sup.d).sub.1-2-C(O)NR.sup.3R.sup.4, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-3 R.sup.e, -(CH.sub.2).sub.r-aryl substituted with 0-3 R.sup.e, or -(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-3 R.sup.e; R.sup.3 is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-3 R.sup.e; R.sup.4 is hydrogen or C.sub.1-2 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4-to 8-membered heterocyclyl comprising 1-3 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; R.sup.5a is hydrogen or halo; R.sup.5b is hydrogen or halo; R.sup.5c is halo or C.sub.1-2 alkoxy; R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-4 alkyl substituted with 0-3 R.sup.e; R.sup.7 is hydrogen or CH.sub.3; R.sup.8 is hydrogen, C.sub.1-2 alkyl, or -S(O).sub.2C.sub.1-4 alkyl; R.sup.a is hydrogen, C.sub.1-5 alkyl substituted with 0-4 R.sup.e; R.sup.b is hydrogen, C.sub.1-5 alkyl substituted with 0-4 R.sup.e, heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, NR.sup.d and substituted with 0-4 R.sup.e; R.sup.d is hydrogen or C.sub.1-3 alkyl substituted with 0-1 -OC.sub.1-4 alkyl; R.sup.e is halo, cyano, oxo, -OR.sup.g, -NR.sup.gR.sup.g, C(O)NR.sup.gR.sup.g, -S(O).sub.pC.sub.1-4 alkyl, C.sub.1-4 alkyl substituted with 0-4 R.sup.f, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-4 R.sup.f, -(CH.sub.2).sub.r-aryl substituted with 0-4 R.sup.f, or (CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-4 R.sup.f; R.sup.f is halo, cyano, hydroxy, or C.sub.1-5 alkyl; R.sup.g is hydrogen or C.sub.1-4 alkyl; and r is zero, 1, or 2.

    4. The compound of claim 3, having Formula (IVa): ##STR00864## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.2 is ##STR00865## ##STR00866## ##STR00867## ##STR00868## R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, halo, C.sub.1-4 alkyl substituted with 0-4 R.sup.e, -OR.sup.b, -NR.sup.3R.sup.4, -NR.sup.4C(O)R.sup.b, (C.sub.1-2 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NRª; R.sup.2a is hydrogen, C.sub.1-4 alkyl substituted with 0-2 R.sup.e, -(CHR.sup.d).sub.1-2-C(O)NR.sup.3R.sup.4, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-2 R.sup.e, -(CH.sub.2).sub.r-aryl substituted with 0-2 R.sup.e, or -(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-2 R.sup.e; R.sup.3 is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-3 R.sup.e; R.sup.4 is hydrogen or C.sub.1-2 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4-to 8-membered heterocyclyl comprising 1-3 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; R.sup.5a is hydrogen, F, or Cl; R.sup.5b is hydrogen, F, or Cl; R.sup.5c is Cl or —OCH.sub.3; R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-3 alkyl substituted with 0-3 R.sup.e; R.sup.8 is hydrogen, C.sub.1-2 alkyl, or S(O).sub.2C.sub.1-3 alkyl; R.sup.a is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e; R.sup.b is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.d and substituted with 0-3 R.sup.e; R.sup.d is hydrogen or C.sub.1-2 alkyl substituted with 0-1 -OC.sub.1-4 alkyl; R.sup.e is halo, cyano, oxo, -OR.sup.g, -NR.sup.gR.sup.g, -C(O)NR.sup.gR.sup.g, -S(O).sub.2C.sub.1-4 alkyl, C.sub.1-6 alkyl substituted with 0-3 R.sup.f, -(CH.sub.2).sub.r-C.sub.3-6 cycloalkyl substituted with 0-3 R.sup.f, or -(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-3 R.sup.f; R.sup.f is halo, cyano, hydroxy, or C.sub.1-4 alkyl; R.sup.g is hydrogen or C.sub.1-3 alkyl; and r is zero or 1.

    5. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.2 is ##STR00869## ##STR00870## R.sup.2 is F, Cl, CH.sub.2OH, CH.sub.3, CF.sub.3, or CHF.sub.2; and R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CHF.sub.2, —CH.sub.2CF.sub.3, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH(CF.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, or —CH.sub.2CH(CF.sub.3)OCH.sub.3.

    6. The compound of claim 4, having Formula (IVb): ##STR00871## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, F, Cl, —CH.sub.3, —CF.sub.3, -CHF.sub.2, —CF.sub.3, or —NHC(O)CH.sub.3; R.sup.2a is —CH.sub.3, CHF.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CF.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, —CH.sub.2CH(CF.sub.3)OCH.sub.3, —CH(CH.sub.2NH.sub.2)CH.sub.2OCH.sub.3, —CH(C(O)N(CH.sub.3).sub.2)CH.sub.2OCH.sub.3, —CH.sub.2C(CH.sub.3)(CH.sub.2OH).sub.2, —CH.sub.2CH.sub.2N(CH.sub.3).sub.2, CH.sub.2CH.sub.2S(O).sub.2C.sub.1-4 alkyl, -CHR.sup.dC(O)NR.sup.3R.sup.4, -(CH.sub.2).sub.0-1-C.sub.3-6 cycloalkyl, -(CH.sub.2).sub.0-3-heterocyclyl selected from ##STR00872## ##STR00873## ##STR00874## R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from ##STR00875## ##STR00876## R.sup.5a is hydrogen or F; R.sup.5b is hydrogen or F; R.sup.5c is Cl or -OCH.sub.3; R.sup.6 is hydrogen, oxo, halo, —CH.sub.3, —CHF.sub.2, —CF.sub.3, or —CH.sub.2OH; R.sup.8 is hydrogen, C.sub.1-2 alkyl, or -S(O).sub.2C.sub.1-3 alkyl; and R.sup.d is -CH.sub.2OCH.sub.3.

    7. The compound of claim 4, having Formula (IVc): ##STR00877## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CH.sub.3, —CHF.sub.2, —CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, —NR.sup.3R.sup.4, (CH.sub.3).sub.2(O)P—, ##STR00878## ##STR00879## ##STR00880## R.sup.3 is hydrogen or C.sub.1-4 alkyl substituted with 0-1 S(O).sub.2C.sub.1-3 alkyl, ##STR00881## ##STR00882## R.sup.4 is hydrogen; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from ##STR00883## ##STR00884## ##STR00885## ##STR00886## ##STR00887## ##STR00888## ##STR00889## ##STR00890## ##STR00891## ##STR00892## R.sup.5a is hydrogen or F; R.sup.5b is hydrogen or F; R.sup.5c is Cl or —OCH.sub.3 R.sup.6 is hydrogen, halo, oxo, —CH.sub.3, —CH.sub.2CH.sub.3, or —CH.sub.2OH; and R.sup.8 is hydrogen, C.sub.1-4 alkyl, or -S(O).sub.2C.sub.1-3 alkyl.

    8. The compound of claim 4, having Formula (IVd): ##STR00893## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is —OR.sup.b or (C.sub.1-2 alkyl).sub.2(O)P-; R.sup.5a is hydrogen or F; R.sup.5b is hydrogen or F; R.sup.5c is Cl or —OCH.sub.3; R.sup.b is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, or ##STR00894## R.sup.e is F, Cl, or —OR.sup.g; and R.sup.g is hydrogen or C.sub.1-3 alkyl.

    9. The compound of claim 4, having Formula (IVe): ##STR00895## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CH.sub.3, —CHF.sub.2, —CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, or —NR.sup.3R.sup.4; R.sup.3 is hydrogen or C.sub.1-4 alkyl; R.sup.4 is hydrogen or C.sub.1-2 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from ##STR00896## ##STR00897## ##STR00898## ##STR00899## ##STR00900## ##STR00901## ##STR00902## ##STR00903## ##STR00904## ##STR00905## R.sup.5a is hydrogen or F; R.sup.5b is hydrogen or F; and R.sup.5c is Cl or -OCH.sub.3.

    10. The compound of claim 1, having Formula (IVf): ##STR00906## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is Cl, —CF.sub.3, —OCH.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CH.sub.3, —CHF.sub.2, or —CF.sub.3; R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, -CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, or —CH.sub.2CH.sub.2CF.sub.3; R.sup.5a is hydrogen, F, or Cl; R.sup.5b is hydrogen, F, or Cl; and R.sup.5c is Cl or -OCH.sub.3.

    11. The compound of claim 4, having Formula (V): ##STR00907## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.2 is C.sub.3-5 cycloalkyl; R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.5a is F or Cl; R.sup.5b is F or Cl; and R.sup.5c is -OCH.sub.3.

    12. The compound of claim 3, having Formula (VI): ##STR00908## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CHF.sub.2, —CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, or (CH.sub.3).sub.2(O)P—; R.sup.5a is F or Cl; R.sup.5b is F or Cl; and R.sup.5c is —OCH.sub.3.

    13. The compound of claim 3, having Formula (VII): ##STR00909## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is F, Cl, or (CH.sub.3).sub.2(O)P—; R.sup.5a is F; R.sup.5b is F; and R.sup.5c is —OCH.sub.3.

    14. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.

    15. A method for the treatment or prophylaxis of inflammatory diseases, heart diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, and immune disorders, comprising administrating a therapeutically effective amount of the pharmaceutical composition of claim 14 to a patient in need thereof.

    16. The method of claim 15, wherein the heart disease is selected from the group consisting of angina pectoris, unstable angina, myocardial infarction, heart failure, acute coronary disease, acute heart failure, chronic heart failure, and cardiac iatrogenic damage.

    17. The method of claim 16, wherein the heart failure results from hypertension, an ischemic heart disease, a non-ischemic heart disease, exposure to a cardiotoxic compound, myocarditis, Kawasaki’s disease, Type I and Type II diabetes, thyroid disease, viral infection, gingivitis, drug abuse, alcohol abuse, pericarditis, atherosclerosis, vascular disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, myocardial infarction, atrial fibrosis, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, coronary bypass surgery, pacemaker implantation surgery, starvation, an eating disorder, muscular dystrophies, and a genetic defect.

    Description

    DESCRIPTION OF THE INVENTION

    [0014] The invention encompasses compounds of Formulae (I)-(VII), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.

    [0015] One aspect of the invention is a compound of Formula (I):

    ##STR00002##

    or a pharmaceutically acceptable salt thereof, wherein: [0016] * is an asymmetric carbon atom; [0017] Ar.sup.1 is aryl or pyridyl, each substituted with 1-3 R.sup.1; [0018] Ar.sup.2 is C.sub.3-6 cycloalkyl, aryl, or 5- to 12-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.2a, and each substituted with 0-3 R.sup.2; [0019] Ar.sup.3 is phenyl or pyridyl, each substituted with 1 R.sup.5a, 1 R.sup.5b, and 1 R.sup.5c; [0020] R.sup.1 is halo, C.sub.1-.sub.4 haloalkyl, C.sub.1-.sub.4 alkoxy, or C.sub.1-.sub.4 haloalkoxy; [0021] R.sup.2 is oxo, cyano, halo, C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.e, —OR.sup.b, —NR.sup.3R.sup.4, —NR.sup.4C(O)R.sup.b, —NR.sup.4(CR.sup.dR.sup.d).sub.0-1C(O)NR.sup.3R.sup.4, (C.sub.1-4 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, 5 to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.a; [0022] R.sup.2a is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.e, —(CR.sup.dR.sup.d).sub.1-4—NR.sup.3R.sup.4, —(CR.sup.dR.sup.d).sub.1-4—OR.sup.b, —(CR.sup.dR.sup.d).sub.1-4—C(O)NR.sup.3R.sup.4, —(CR.sup.dR.sup.d).sub.r—C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, —(CR.sup.dR.sup.d).sub.r-aryl substituted with 0-5 R.sup.e, or —(CR.sup.dR.sup.d).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.a and substituted with 0-5 R.sup.e; [0023] R.sup.3 is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.8 and substituted with 0-5 R.sup.e; [0024] R.sup.4 is hydrogen or C.sub.1-.sub.4 alkyl; [0025] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4- to 9-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.8 and substituted with 1-3 R.sup.6; [0026] R.sup.5a is hydrogen or halo; [0027] R.sup.5b is hydrogen or halo; [0028] R.sup.5c is halo, C.sub.1-.sub.4 alkyl, C.sub.1-.sub.4 haloalkyl, C.sub.1-4 alkoxy, or deuteroalkoxy; [0029] R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.e; [0030] R.sup.7 is hydrogen or C.sub.1-.sub.4 alkyl; [0031] R.sup.8 is hydrogen, C.sub.1-.sub.4 alkyl, or -S(O).sub.pR.sup.c; [0032] R.sup.ais hydrogen or C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, aryl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, NR.sup.d and substituted with 0-5 R.sup.e; [0033] R.sup.b is hydrogen, C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.e, C.sub.3-6 cycloalkyl substituted with 0-5 R.sup.e, aryl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, NR.sup.d and substituted with 0-5 R.sup.e; [0034] R.sup.c is C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.e; [0035] R.sup.d is hydrogen or C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.e; [0036] R.sup.e is halo, cyano, oxo, —OR.sup.g, —NR.sup.gR.sup.g, —C(O)NR.sup.gR.sup.g, —S(O).sub.pC.sub.1-4 alkyl, C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.f, —(CH.sub.2)r—C.sub.3—.sub.6 cycloalkyl substituted with 0-5 R.sup.f, —(CH.sub.2).sub.r-aryl substituted with 0-5 R.sup.f, or —(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S(O).sub.p, N, and NR.sup.g and substituted with 0-5 R.sup.f; [0037] R.sup.fis halo, cyano, hydroxy, oxo, C.sub.1-.sub.5 alkyl, C.sub.3-6 cycloalkyl, or phenyl; [0038] R.sup.gis hydrogen, C.sub.1-.sub.5 alkyl, C.sub.3-6 cycloalkyl, aryl, or heterocyclyl; or R.sup.g and R.sup.g together with the nitrogen atom to which they are both attached form a heterocyclyl; [0039] n is zero or 1; [0040] p is zero, 1, or 2; and [0041] r is zero, 1, 2, 3, or 4.

    [0042] Another aspect of the invention is a compound of Formula (II):

    ##STR00003##

    or a pharmaceutically acceptable salt thereof, wherein: [0043] Ar.sup.2 is C.sub.3-6 cycloalkyl, phenyl, 5- to 6-membered heterocyclyl comprising 1-2 N or NR.sup.2a, each substituted with 0-2 R.sup.2; [0044] Ar.sup.3 is phenyl substituted with 1 R.sup.5a, 1 R.sup.5b, and 1 R.sup.5c; [0045] R.sup.1 is halo, C.sub.1-4 haloalkyl, or C.sub.1-4 haloalkoxy; [0046] R.sup.2 is oxo, cyano, halo, C.sub.1-.sub.5 alkyl substituted with 0-5 R.sup.e, —OR.sup.b, —NR.sup.3R.sup.4, —NR.sup.4C(O)R.sup.b, (C.sub.1-3 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, 5- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a; [0047] R.sup.2a is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-4 R.sup.e, —(CHR.sup.d).sub.1-3—C(O)NR.sup.3R.sup.4, —(CHR.sup.d).sub.r—C.sub.3-6 cycloalkyl substituted with 0-4 R.sup.e, —(CHR.sup.d).sub.r-aryl substituted with 0-4 R.sup.e, or —(CHR.sup.d).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-4 R.sup.e; [0048] R.sup.3 is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-4 R.sup.e, C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-4 R.sup.e; [0049] R.sup.4 is hydrogen or C.sub.1-.sub.3 alkyl; [0050] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4- to 8-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; [0051] R.sup.5a is hydrogen or halo; [0052] R.sup.5b is hydrogen or halo; [0053] R.sup.5c is halo, C.sub.1-.sub.4 alkyl, C.sub.1-.sub.4 haloalkyl, or C.sub.1-4 alkoxy; [0054] R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-.sub.4 alkyl substituted with 0-4 R.sup.e; [0055] R.sup.7 is hydrogen or C.sub.1-.sub.3 alkyl; [0056] R.sup.8 is hydrogen, C.sub.1-.sub.3 alkyl, or -S(O).sub.pR.sup.c; [0057] R.sup.ais hydrogen or C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.e; [0058] R.sup.b is hydrogen, C.sub.1-.sub.6 alkyl substituted with 0-5 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, NR.sup.d and substituted with 0-5 R.sup.e; [0059] R.sup.c is C.sub.1-.sub.3 alkyl substituted with 0-5 R.sup.e; [0060] R.sup.d is hydrogen or C.sub.1-.sub.4 alkyl substituted with 0-1 -OC.sub.1-4 alkyl; [0061] R.sup.e is halo, cyano, oxo, -OR.sup.g, -NR.sup.gR.sup.g, -C(O)NR.sup.gR.sup.g, —S(O).sub.pC.sub.1-4 alkyl, C.sub.1-.sub.4 alkyl substituted with 0-5 R.sup.f, -(CH.sub.2)r-C.sub.3-.sub.6 cycloalkyl substituted with 0-5 R.sup.f, -(CH.sub.2).sub.r-aryl substituted with 0-5 R.sup.f, or -(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-5 R.sup.f; [0062] R.sup.f is halo, cyano, hydroxy, C.sub.1-.sub.5 alkyl, or C.sub.3-6 cycloalkyl; [0063] R.sup.g is hydrogen, C.sub.1-.sub.5 alkyl, or heterocyclyl; [0064] n is zero; and [0065] r is zero, 1, 2, or 3.

    [0066] Another aspect of the invention is a compound of Formula (III):

    ##STR00004##

    or a pharmaceutically acceptable salt thereof, wherein: [0067] Ar.sup.2 is [0068] R.sup.1 is halo, C.sub.1-3 haloalkyl, or C.sub.1-3 haloalkoxy; [0069] R.sup.2 is cyano, halo, C.sub.1-4 alkyl substituted with 0-5 R.sup.e, -OR.sup.b, -NR.sup.3R.sup.4, -NR.sup.4C(O)R.sup.b, (C.sub.1-4 alkyl).sub.2(O)P-, C.sub.3-6 cycloalkyl, aryl, or 5- to 6-membered heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a; [0070] R.sup.2a is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, —(CHR.sup.d).sub.1-2—C(O)NR.sup.3R.sup.4, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl substituted with 0-3 R.sup.e, —(CH.sub.2).sub.r-aryl substituted with 0-3 R.sup.e, or —(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-3 R.sup.e; [0071] R.sup.3 is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-3 R.sup.e, C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-3 R.sup.e; [0072] R.sup.4 is hydrogen or C.sub.1-.sub.2 alkyl; [0073] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4- to 8-membered heterocyclyl comprising 1-3 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; [0074] R.sup.5a is hydrogen or halo; [0075] R.sup.5b is hydrogen or halo; [0076] R.sup.5c is halo or C.sub.1-2 alkoxy; [0077] R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-.sub.4 alkyl substituted with 0-3 R.sup.e; [0078] R.sup.7 is hydrogen or CH.sub.3; [0079] R.sup.8 is hydrogen, C.sub.1-.sub.2 alkyl, or S(O).sub.2C.sub.1-4 alkyl; [0080] R.sup.ais hydrogen or C.sub.1-.sub.5 alkyl substituted with 0-4 R.sup.e; [0081] R.sup.b is hydrogen, C.sub.1-.sub.5 alkyl substituted with 0-4 R.sup.e, heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, NR.sup.d and substituted with 0-4 R.sup.e; [0082] R.sup.d is hydrogen or C.sub.1-.sub.2 alkyl substituted with 0-1 —OC.sub.1-4 alkyl; [0083] R.sup.e is halo, cyano, oxo, —OR.sup.g, —NR.sup.gR.sup.g, C(O)NR.sup.gR.sup.g, —S(O).sub.pC.sub.1-4 alkyl, C.sub.1-.sub.4 alkyl substituted with 0-4 R.sup.f, —(CH.sub.2)r—C.sub.3—.sub.6 cycloalkyl substituted with 0-4 R.sup.f, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sup.f, or —(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-4 R.sup.f; [0084] R.sup.f is halo, cyano, hydroxy, or C.sub.1-.sub.5 alkyl; [0085] R.sup.g is hydrogen or C.sub.1-.sub.4 alkyl; [0086] n is zero; and [0087] r is zero, 1, or 2.

    [0088] Another aspect of the invention is a compound of Formula (IVa):

    ##STR00013##

    or a pharmaceutically acceptable salt thereof, wherein: [0089] Ar.sup.2 is [0090] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0091] R.sup.2 is cyano, halo, C.sub.1-4 alkyl substituted with 0-4 R.sup.e, —OR.sup.b, —NR.sup.3R.sup.4, —NR.sup.4C(O)R.sup.b, (C.sub.1-2 alkyl).sub.2(O)P, -C.sub.3-6 cycloalkyl, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a; [0092] R.sup.2a is hydrogen, C.sub.1-4 alkyl substituted with 0-4 R.sup.e, —(CHR.sup.d).sub.1-2—C(O)NR.sup.3R.sup.4, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl substituted with 0-2 R.sup.e, —CH.sub.2).sub.r-aryl substituted with 0-2 R.sup.e, or —(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.a and substituted with 0-2 R.sup.e; [0093] R.sup.3 is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-3 R.sup.e, or heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 0-3 R.sup.e; [0094] R.sup.4 is hydrogen or C.sub.1-.sub.2 alkyl; [0095] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a 4- to 8-membered heterocyclyl comprising 1-3 heteroatoms selected from O, S, N, and NR.sup.8 and substituted with 1-3 R.sup.6; [0096] R.sup.5a is hydrogen, F, or Cl; [0097] R.sup.5b is hydrogen, F, or Cl; [0098] R.sup.5c is Cl or —OCH.sub.3; [0099] R.sup.6 is hydrogen, halo, oxo, hydroxy, or C.sub.1-.sub.3 alkyl substituted with 0-3 R.sup.e; [0100] R.sup.7 is hydrogen or C.sub.1-.sub.2 alkyl; [0101] R.sup.8 is hydrogen, C.sub.1-.sub.2 alkyl, or S(O).sub.2C.sub.1-3 alkyl; [0102] R.sup.ais hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-3 R.sup.e; [0103] R.sup.b is hydrogen, C.sub.1-.sub.4 alkyl substituted with 0-3 R.sup.e, heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.d and substituted with 0-3 R.sup.e; [0104] R.sup.d is hydrogen or C.sub.1-2 alkyl substituted with 0-1 —OC.sub.1-4 alkyl; [0105] R.sup.e is halo, cyano, oxo, —OR.sup.g, —NR.sup.gR.sup.g, —C(O)NR.sup.gR.sup.g, —S(O).sub.2C.sub.1-4 alkyl, C.sub.1-.sub.6 alkyl substituted with 0-3 R.sup.f, —(CH.sub.2)r—C.sub.3—.sub.6 cycloalkyl substituted with 0-3 R.sup.f, or —(CH.sub.2).sub.r-heterocyclyl comprising 1-4 heteroatoms selected from O, S, N, and NR.sup.g and substituted with 0-3 R.sup.f; [0106] R.sup.f is halo, cyano, hydroxy, or C.sub.1-.sub.4 alkyl; [0107] R.sup.g is hydrogen or C.sub.1-.sub.3 alkyl; and [0108] r is zero or 1.

    [0109] Another aspect of the invention is a compound of Formula (IVa), or a pharmaceutically acceptable salt thereof, wherein: [0110] Ar.sup.2 is [0111] R.sup.2 is F, Cl, —CH.sub.2OH, —CH.sub.3, —CF.sub.3, or —CHF.sub.2; and [0112] R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CHF.sub.2, —CH.sub.2CF.sub.3, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH(CF.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, or —CH.sub.2CH(CF.sub.3)OCH.sub.3; [0113] other variables are as defined in Formula (IVa).

    [0114] Another aspect of the invention is a compound of Formula (IVb):

    ##STR00020##

    or a pharmaceutically acceptable salt thereof, wherein: [0115] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0116] R.sup.2 is cyano, F, Cl, CH.sub.3, CF.sub.3, CHF.sub.2, or —NHC(O)CH.sub.3; [0117] R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CF.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, —CH.sub.2CH(CF.sub.3)OCH.sub.3, —CH(CH.sub.2NH.sub.2)CH.sub.2OCH.sub.3, —CH(C(O)N(CH.sub.3).sub.2)CH.sub.2OCH.sub.3, —CH.sub.2C(CH.sub.3)(CH.sub.2OH).sub.2, —CH.sub.2CH.sub.2N(CH.sub.3).sub.2, —CH.sub.2CH.sub.2S(O).sub.2C.sub.1-4 alkyl, —CHR.sup.dC(O)NR.sup.3R.sup.4, —(CH.sub.2).sub.0-1-C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.0-3-heterocyclyl selected from [0118] R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from [0119] R.sup.5a is hydrogen or F; [0120] R.sup.5b is hydrogen or F; [0121] R.sup.5c is Cl or —OCH.sub.3; [0122] R.sup.6 is hydrogen, oxo, halo, or —CH.sub.3, —CHF.sub.3, —CF.sub.3, or —CH.sub.2OH; [0123] R.sup.7 is hydrogen or C.sub.1-.sub.2 alkyl; [0124] R.sup.8 is hydrogen, C.sub.1-.sub.2 alkyl, or —S(O).sub.2C.sub.1—.sub.3 alkyl; and [0125] R.sup.d is —CH.sub.2OCH.sub.3.

    [0126] Another aspect of the invention is a compound of Formula (IVc):

    ##STR00026##

    or a pharmaceutically acceptable salt thereof, wherein: [0127] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0128] R.sup.2 is cyano, F, Cl, CH.sub.2OH, CH.sub.3, CHF.sub.2, CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, —NR.sup.3R.sup.4, (CH.sub.3).sub.2(O)P—, C.sub.3-6 cycloalkyl [0129] R.sup.3 is hydrogen or C.sub.1-.sub.4 alkyl substituted with 0-2 R.sup.e, [0130] R.sup.4 is hydrogen; [0131] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from [0132] R.sup.5a is hydrogen or F; [0133] R.sup.5b is hydrogen or F; [0134] R.sup.5c is Cl or OCH.sub.3 [0135] R.sup.6 is hydrogen, halo, oxo, CH.sub.3, —CH.sub.2CH.sub.3, or —CH.sub.2OH; [0136] R.sup.7 is hydrogen or C.sub.1-.sub.4 alkyl; and [0137] R.sup.8 is hydrogen, C.sub.1-.sub.4 alkyl, or —S(O).sub.2C.sub.1—.sub.3 alkyl.

    [0138] Another aspect of the invention is a compound of Formula (IVd):

    ##STR00042##

    or a pharmaceutically acceptable salt thereof, wherein: [0139] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0140] R.sup.2 is —OR.sup.b or (C.sub.1-2alkyl).sub.2(O)P-; [0141] R.sup.5a is hydrogen or F; [0142] R.sup.5b is hydrogen or F; [0143] R.sup.5c is Cl or —OCH.sub.3; [0144] R.sup.7 is hydrogen or —CH.sub.3; [0145] R.sup.b is hydrogen, C.sub.1-4 alkyl substituted with 0-3 R.sup.e, or [0146] R.sup.e is F, Cl, or —OR.sup.g; and [0147] R.sup.g is hydrogen or C.sub.1-.sub.3 alkyl.

    [0148] Another aspect of the invention is a compound of Formula (IVe):

    ##STR00044##

    or a pharmaceutically acceptable salt thereof, wherein: [0149] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0150] R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CH.sub.3, —CHF.sub.2, —CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, or —NR.sup.3R.sup.4; [0151] R.sup.3 is hydrogen or C.sub.1-.sub.4 alkyl; [0152] R.sup.4 is hydrogen or C.sub.1-.sub.2 alkyl; [0153] alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from [0154] R.sup.5a is hydrogen or F; [0155] R.sup.5b is hydrogen or F; [0156] R.sup.5c is Cl or —OCH.sub.3; [0157] R.sup.6 is hydrogen, halo, oxo, CH.sub.3, —CH.sub.2CH.sub.3, or —CH.sub.2OH; [0158] R.sup.7 is hydrogen or C.sub.1-.sub.4 alkyl; and [0159] R.sup.8 is hydrogen or C.sub.1-.sub.2 alkyl.

    [0160] Another aspect of the invention is a compound of Formula (IVf):

    ##STR00055##

    or a pharmaceutically acceptable salt thereof, wherein: [0161] R.sup.1 is Cl, —CF.sub.3, —OCH.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0162] R.sup.2 is cyano, F, Cl, —CH.sub.2OH, —CH.sub.3, —CHF.sub.2, or —CF.sub.3; [0163] R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, or —CH.sub.2CH.sub.2CF.sub.3; [0164] .sub.R.sup.5a is hydrogen, F, or Cl; [0165] R.sup.5b is hydrogen, F, or Cl; [0166] R.sup.5c is Cl or —OCH.sub.3; and [0167] R.sup.7 is hydrogen or —CH.sub.3.

    [0168] Another aspect of the invention is a compound of Formula (V):

    ##STR00056##

    or a pharmaceutically acceptable salt thereof, wherein: [0169] Ar.sup.2 is C.sub.3-5 cycloalkyl; [0170] R.sup.1 is Cl, —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0171] R.sup.5a is F or Cl; [0172] R.sup.5b is F or Cl; and [0173] R.sup.5c is —OCH.sub.3.

    [0174] Another aspect of the invention is a compound of Formula (Va):

    ##STR00057##

    or a pharmaceutically acceptable salt thereof, wherein: [0175] R.sup.1 is CF.sub.3, OCHF.sub.2, or OCF.sub.3; [0176] R.sup.5a is F or Cl; [0177] R.sup.5b is F or Cl; and [0178] R.sup.5c is OCH.sub.3.

    [0179] Another aspect of the invention is a compound of Formula (VI):

    ##STR00058##

    or a pharmaceutically acceptable salt thereof, wherein: [0180] R.sup.1 is —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; R.sup.2 is F, Cl, —CH.sub.2OH, —CF.sub.3, —CHF.sub.2, —OCH.sub.3, —OCH(CH.sub.3).sub.2, or (CH.sub.3).sub.2(O)P—; [0181] R.sup.5a is F or Cl; [0182] R.sup.5b is F or Cl; and [0183] R.sup.5c is —OCH.sub.3.

    [0184] Another aspect of the invention is a compound of Formula (VII):

    ##STR00059##

    or a pharmaceutically acceptable salt thereof, wherein: [0185] R.sup.1 is —CF.sub.3, —OCHF.sub.2, or —OCF.sub.3; [0186] R.sup.2 is F, Cl, or (CH.sub.3).sub.2(O)P—; [0187] R.sup.5a is F; [0188] R.sup.5b is F; and [0189] R.sup.5c is —OCH.sub.3.

    [0190] For a compound of Formula (I), (II), (III), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (V), (Va), (VI), or (VII), i.e., Formulae (I-VII), the scope of any instance of a variable substituent, including Ar.sup.1, Ar.sup.2, Ar.sup.3, R.sup.1, R.sup.2, R.sup.2a, R.sup.3, R.sup.4, R.sup.5a, R.sup.5b, R.sup.5c, R.sup.6, R.sup.7, R.sup.8, R.sup.a, R.sup.b, R.sup.c, R.sup.d, R.sup.e, R.sup.f, and R.sup.g can be used independently with the scope of any other instance of a variable substituent. As such, the invention includes combinations of the different aspects.

    [0191] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero or 1; Ar2 is phenyl, pyridinyl, or C.sub.3-6 cycloalkyl, each substituted with 0-2 R.sup.2; R.sup.2 is F, Cl, CH.sub.2OH, CF.sub.3, OCH.sub.3, OCH(CH.sub.3).sub.2, CHF.sub.2, CF.sub.3, or (CH.sub.3).sub.2(O)P; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0192] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is CF.sub.3; n is zero; Ar.sup.2 is phenyl, pyridinyl, or C.sub.3-6 cycloalkyl, each substituted with 0-2 R.sup.2; R.sup.2 is F, Cl, CH.sub.2OH, CF.sub.3, OCH.sub.3, OCH(CH.sub.3).sub.2, CHF.sub.2, CF.sub.3, or (CH.sub.3).sub.2(O)P; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0193] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is OCHF.sub.2; n is zero; Ar.sup.2 is phenyl, pyridinyl, or C.sub.3-6 cycloalkyl, each substituted with 0-2 R.sup.2; R.sup.2 is F, Cl, CH.sub.2OH, CF.sub.3, OCH.sub.3, OCH(CH.sub.3).sub.2, CHF.sub.2, CF.sub.3, or (CH.sub.3).sub.2(O)P; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0194] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is OCF.sub.3; n is zero; Ar.sup.2 is phenyl, pyridinyl, or C.sub.3-6 cycloalkyl, each substituted with 0-2 R.sup.2; R.sup.2 is F, Cl, CH.sub.2OH, CF.sub.3, OCH.sub.3, OCH(CH.sub.3).sub.2, CHF.sub.2, CF.sub.3, or (CH.sub.3).sub.2(O)P; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0195] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is 1; Ar.sup.2 is phenyl substituted with 0-2 R.sup.2; R.sup.2 is halo or alkoxy; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0196] In one non-limiting embodiment, for a compound of Formula (I), (II), or (III), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is 1; Ar.sup.2 is cyclopropyl; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0197] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00060##

    R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CHF.sub.2, —CH.sub.2CF.sub.3, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CF.sub.3)OH, or —CH.sub.2CH.sub.2CF.sub.3; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0198] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1 ; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00061##

    R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CHF.sub.2, —CH.sub.2CF.sub.3, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH(CF.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, or —CH.sub.2CH(CF.sub.3)OCH.sub.3; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0199] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1 ; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00062##

    R.sup.2 is cyano, F, Cl, CH.sub.3 or —NHC(O) CH.sub.3; R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CF.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, —CH.sub.2CH(CF.sub.3)OCH.sub.3, —CH(CH.sub.2NH.sub.2)CH.sub.2OCH.sub.3, —CH(C(O)N(CH.sub.3).sub.2)CH.sub.2OCH.sub.3, —CH.sub.2C(CH.sub.3)(CH.sub.2OH).sub.2, —CH.sub.2CH.sub.2N(CH.sub.3).sub.2, —CH.sub.2CH.sub.2S(O).sub.2C.sub.1-4 alkyl, —(CH.sub.2).sub.0-1—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.0-3-heterocyclyl selected from

    ##STR00063##

    ##STR00064##

    ##STR00065##

    Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0200] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1 ; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00066##

    R.sup.2 is cyano, F, Cl, CH.sub.3 or —NHC(O)CH.sub.3; R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CF.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, —CH.sub.2CH(CF.sub.3)OCH.sub.3, —CH(CH.sub.2NH.sub.2)CH.sub.2OCH.sub.3, —CH(C(O)N(CH.sub.3).sub.2)CH.sub.2OCH.sub.3, —CH.sub.2C(CH.sub.3)(CH.sub.2OH).sub.2, —CH.sub.2CH.sub.2N(CH.sub.3).sub.2, —CH.sub.2CH.sub.2S(O).sub.2C.sub.1-4 alkyl, —(CH.sub.2).sub.0-1—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.0-3—heterocyclyl selected from

    ##STR00067##

    ##STR00068##

    ##STR00069##

    Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0201] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1 ; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00070##

    R.sup.2 is cyano, F, Cl, CH.sub.2OH, CH.sub.3, CF.sub.3, CHF.sub.2, CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, -NR.sup.3R.sup.4, (CH.sub.3).sub.2(O)P-, C.sub.3-6 cycloalkyl,

    ##STR00071##

    ##STR00072##

    ##STR00073##

    ##STR00074##

    is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, or —CH.sub.2CH.sub.2OH; R.sup.3 is hydrogen or C.sub.1-.sub.4 alkyl substituted with 0-2 R.sup.e,

    ##STR00075##

    ##STR00076##

    R.sup.4 is hydrogen or C.sub.1-.sub.2 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from

    ##STR00077##

    ##STR00078##

    ##STR00079##

    ##STR00080##

    ##STR00081##

    ##STR00082##

    ##STR00083##

    ##STR00084##

    ##STR00085##

    ##STR00086##

    Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0202] In one non-limiting embodiment, for a compound of Formula (I), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00087##

    ##STR00088##

    R.sup.2 is alkyl, haloalkyl, hydroxyalkyl, or cycloalkyl; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0203] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00089##

    R.sup.2 is cyano, F, Cl, CH.sub.2OH, CF.sub.3, CHF.sub.2, CF.sub.3, —OCH.sub.3, —OCH(CH.sub.3).sub.2, -NR.sup.3R.sup.4, (CH.sub.3).sub.2(O)P—, C.sub.3-6 cycloalkyl,

    ##STR00090##

    ##STR00091##

    ##STR00092##

    ##STR00093##

    ##STR00094##

    R.sup.3 is hydrogen or C.sub.1-.sub.4 alkyl substituted with 0-2 R.sup.e,

    ##STR00095##

    ##STR00096##

    R.sup.4 is hydrogen or C.sub.1-.sub.2 alkyl; alternatively, R.sup.3 and R.sup.4 together with the nitrogen to which they are both attached form a heterocyclyl selected from

    ##STR00097##

    ##STR00098##

    ##STR00099##

    ##STR00100##

    ##STR00101##

    ##STR00102##

    ##STR00103##

    ##STR00104##

    ##STR00105##

    ##STR00106##

    Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0204] In one non-limiting embodiment, for a compound of Formula (I), (II), (III), or (IVa), Ar.sup.1 is phenyl substituted with 1 R.sup.1 ; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00107##

    ##STR00108##

    ##STR00109##

    ##STR00110##

    R.sup.2 is alkoxy; R.sup.2a is alkyl or haloalkyl; Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0205] In one non-limiting embodiment, for a compound of Formula (I), Ar.sup.1 is phenyl substituted with 1 R.sup.1; R.sup.1 is Cl, CF.sub.3, OCHF.sub.2, or OCF.sub.3; n is zero; Ar.sup.2 is

    ##STR00111##

    R.sup.2 is cyano, F, Cl, CH.sub.3 or —NHC(O) CH.sub.3; R.sup.2a is —CH.sub.3, —CH.sub.2CH.sub.3, —CH.sub.2CN, —CH.sub.2CHF.sub.2, —CH.sub.2CH.sub.2OCH.sub.3, —CH.sub.2CH(OH)CF.sub.3, —CH.sub.2CH(OH)CH.sub.3, —CH.sub.2CH.sub.2OH, —CF.sub.2CH.sub.2OH, —CH.sub.2CH(CH.sub.3)OH, —CH.sub.2CH.sub.2CF.sub.3, —CH(CH.sub.2OH)CH.sub.2OCH.sub.3, —CH(CH.sub.2NH.sub.2)OCH.sub.3, —CH.sub.2CH(CH.sub.3)OCH.sub.3, —CH.sub.2CH(CF.sub.3)OCH.sub.3, —CH(CH.sub.2NH.sub.2)CH.sub.2OCH.sub.3, —CH(C(O)N(CH.sub.3).sub.2)CH.sub.2OCH.sub.3, —CH.sub.2C(CH.sub.3)(CH.sub.2OH).sub.2, —CH.sub.2CH.sub.2N(CH.sub.3).sub.2, —CH.sub.2CH.sub.2S(O).sub.2C.sub.1-4 alkyl, —(CH.sub.2).sub.0-1—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.0-3—heterocyclyl selected from

    ##STR00112##

    ##STR00113##

    ##STR00114##

    Ar.sup.3 is phenyl substituted with R.sup.5a, R.sup.5b, and R.sup.5c; R.sup.5a, R.sup.5b, and R.sup.5c are halo and alkoxy, respectively.

    [0206] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 1 .Math.M.

    [0207] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 0.5 .Math.M.

    [0208] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 0.1 .Math.M.

    [0209] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 0.05 .Math.M.

    [0210] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 0.01 .Math.M.

    [0211] In another embodiment, the compounds of the present invention have FPR2 EC.sub.50 values ≤ 0.001 .Math.M.

    [0212] Unless specified otherwise, these terms have the following meanings.

    [0213] A dash “-” that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, —CONH.sub.2 is attached through the carbon atom.

    [0214] A bond pointing to a wave line, such as

    ##STR00115##

    as used in structural formulas herein, depicts the bond that is the point of attachment of the moiety or substituent to the core or backbone structure.

    [0215] “Cyano” means —CN.

    [0216] “Hydroxy” means —OH.

    [0217] “Alkyl” means a straight or branched hydrocarbon group composed of 1 to 6 carbons. “Alkenyl” means a straight or branched alkyl group composed of 2 to 6 carbons with at least one double bond. “Alkynyl” means a straight or branched alkyl group composed of 2 to 6 carbons with at least one triple bond. Terms with a hydrocarbon moiety (e.g. alkoxy) include straight and branched isomers for the hydrocarbon portion.

    [0218] “Halo” includes fluoro, chloro, bromo, and iodo. “Haloalkyl” and “haloalkoxy” include all halogenated isomers from monohalo to perhalo.

    [0219] “Haloalkoxy” and derivatives such as “C.sub.1-6 haloalkoxy” are used interchangeably and mean halo substituted alkyl groups linked through the oxygen atom. Haloalkoxy include mono-substituted as well as multiple halo substituted alkoxy groups, up to perhalo substituted alkoxy. For example trifluoromethoxy and difluoromethoxy are included.

    [0220] “Alkoxy” means an alkyl group attached via an oxygen linkage to the rest of the molecule. Representative examples of such groups are —OCH.sub.3 and —OC.sub.2H.sub.5. Unless set forth or recited to the contrary, all alkoxy groups described or claimed herein may be straight chain or branched.

    [0221] “Alkoxyalkyl” means an alkoxy group as defined above directly bonded to an alkyl group as defined above, e.g., —CH.sub.2—O—CH.sub.3, —CH.sub.2CH.sub.2—O—CH.sub.3 and the like.

    [0222] “Cycloalkyl” means a non-aromatic mono or multicyclic ring system having 3 to 12 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

    [0223] “Aryl” means a monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms, or a bicyclic fused ring system wherein one or both of the rings is aromatic. Bicyclic fused ring systems consist of a phenyl group fused to a four- to seven-membered aromatic or non-aromatic carbocyclic ring. Representative examples of aryl groups include but are not limited to phenyl, indanyl, indenyl, naphthyl, and tetrahydronaphthyl.

    [0224] “Heterocycle,” “heterocyclyl,” or “heterocyclic ring” means a stable 3-, 4-, 5-, 6-, or 7-membered monocyclic or bicyclic or 7-, 8-, 9-, 10-, 11-, 12-, 13-, or 14-membered polycyclic heterocyclic ring that is saturated, partially unsaturated, or fully unsaturated, and that contains carbon atoms and 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S; and including any polycyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N.fwdarw.O and S(O).sub.p, wherein p is 0, 1 or 2). The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, if defined). The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocyclyl may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocyclyl exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocyclyl is not more than 1. When the term “heterocyclyl” is used, it is intended to include heteroaryl.

    [0225] Bridged rings are also included in the definition of heterocyclyl. A bridged ring occurs when one or more atoms (i.e., C, O, N, or S) link two non-adjacent carbon or nitrogen atoms. Examples of bridged rings include, but are not limited to, one carbon atom, two carbon atoms, one nitrogen atom, two nitrogen atoms, and a carbon-nitrogen group. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge.

    [0226] “Heteroaryl” means a 5 to 7 membered monocyclic or 8 to 11 membered bicyclic aromatic ring system with 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

    [0227] Where a bonding attachment location is not specified, the bonding may be attached at any appropriate location as understood by practitioners in the art. Combinations of substituents and bonding patterns are only those that result in stable compounds as understood by practitioners in the art. Parenthetic and multiparenthetic terms are intended to clarify bonding relationships to those skilled in the art. For example, a term such as ((R)alkyl) means an alkyl substituent further substituted with the substituent R.

    [0228] The invention includes all pharmaceutically acceptable salt forms of the compounds. Pharmaceutically acceptable salts are those in which the counter ions do not contribute significantly to the physiological activity or toxicity of the compounds and as such function as pharmacological equivalents. These salts can be made according to common organic techniques employing commercially available reagents. Some anionic salt forms include acetate, acistrate, besylate, bromide, chloride, citrate, fumarate, glucouronate, hydrobromide, hydrochloride, hydroiodide, iodide, lactate, maleate, mesylate, nitrate, pamoate, phosphate, succinate, sulfate, tartrate, tosylate, and xinofoate. Some cationic salt forms include ammonium, aluminum, benzathine, bismuth, calcium, choline, diethylamine, diethanolamine, lithium, magnesium, meglumine, 4-phenylcyclohexylamine, piperazine, potassium, sodium, tromethamine, and zinc.

    [0229] Some of the compounds of the invention exist in stereoisomeric forms including the structure below with the indicated carbon. The invention includes all stereoisomeric forms of the compounds including enantiomers and diastereomers. Methods of making and separating stereoisomers are known in the art. The invention includes all tautomeric forms of the compounds. The invention includes atropisomers and rotational isomers.

    [0230] The invention is intended to include all isotopes of atoms occurring in the compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium and tritium. Isotopes of carbon include .sup.13C and .sup.14C. Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically-labeled reagent in place of the non-labeled reagent otherwise employed. Such compounds may have a variety of potential uses, for example as standards and reagents in determining biological activity. In the case of stable isotopes, such compounds may have the potential to favorably modify biological, pharmacological, or pharmacokinetic properties.

    BIOLOGICAL METHODS

    [0231] N-formyl peptide receptors (FPRs) are a family of chemo attractant receptors that facilitate leukocyte response during inflammation. FPRs belong to the seven-transmembrane G protein-coupled receptor superfamily and are linked to inhibitory G-proteins (Gi). Three family members (FPR1, FPR2 and FPR3) have been identified in humans and are predominantly found in myeloid cells with varied distribution and have also been reported in multiple organs and tissues. After agonist binding, the FPRs activate a multitude of physiological pathways, such as intra cellular signaling transduction, Ca.sup.2+ mobilization and transcription. The family interacts with a diverse set of ligands that includes proteins, polypeptides and fatty acid metabolites which activate both pro-inflammatory and pro-resolution downstream responses. FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays were used to measure the activity of the compounds in this patent.

    [0232] FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays. A mixture of forskolin (5 .Math.M final for FPR2 or 10 .Math.M final for FPR1) and IBMX (200 .Math.M final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 .Math.M. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham’s) medium supplemented with 10% qualified FBS, 250 .Math.g/ml zeocin and 300 .Math.g/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco’s PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer’s instruction. Solutions of cryptate conjugated anti-cAMP and d2 flurorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 .Math.M to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.

    [0233] The examples disclosed below were tested in the FPR2 and FPR1 cAMP assay described above and found having FPR2 and/or FPR1 agonist activity. Table 1 below lists EC.sub.50 values in the FPR2 and FPR1 cAMP assays measured for the following examples.

    TABLE-US-00001 Example hFPR2 cAMP2 EC.sub.50 (.Math.M) hFPR1 cAMP EC.sub.50 (.Math.M) 1 0.028 4.2 2 0.022 0.086 3 0.029 1.7 4 0.0017 0.29 5 0.0029 0.014 6 0.0051 0.65 7 0.010 1.3 8 0.015 0.28 9 0.0067 4.4 10 0.050 0.29 11 0.031 0.086 12 0.091 >10 13 0.045 0.085 14 0.037 0.043 15 0.022 1.1 16 0.180 0.48 17 0.036 0.069 18 0.037 0.20 19 0.024 0.54 20 0.032 0.56 21 0.035 2.3 22 0.013 3.2 23 0.028 1.5 24 0.045 0.30 25 0.035 >10 26 0.035 0.027 27 0.027 0.57 28 0.007 1.1 29 0.051 0.11 30 0.010 0.75 31 0.010 0.15 32 0.018 0.96 33 0.005 1.61 34 0.0038 0.30 35 0.0031 >10 36 0.0055 0.030 37 0.0089 0.016 38 0.0051 0.018 39 0.0005 0.072 40 0.0006 2.6 41 0.0006 0.11 42 0.0007 0.73 43 0.0008 >5 44 0.001 0.010 45 0.001 0.0043 46 0.001 0.002 47 0.0011 0.15 48 0.0011 0.94 49 0.0011 2.0 50 0.0012 1.7 51 0.0012 5.5 52 0.0013 0.027 53 0.0014 0.0023 54 0.0014 0.82 55 0.0014 0.0086 56 0.0014 0.004 57 0.0014 0.000066 58 0.0015 0.0035 59 0.0015 0.0066 60 0.0016 0.0026 61 0.0016 0.034 62 0.0016 0.11 63 0.0017 0.016 64 0.0017 0.0072 65 0.0017 0.18 66 0.0018 0.049 67 0.0018 0.0044 68 0.0018 0.50 69 0.0019 0.0042 70 0.0019 >10 71 0.0019 0.29 72 0.0019 0.0057 73 0.0019 0.0032 74 0.0019 0.094 75 0.002 0.0028 76 0.002 0.28 77 0.002 0.17 78 0.002 0.0052 79 0.002 0.012 80 0.0021 0.13 81 0.0022 0.0027 82 0.0022 0.0053 83 0.0022 0.0076 84 0.0023 0.12 85 0.0023 0.16 86 0.0023 0.0041 87 0.0023 0.75 88 0.0024 0.0079 89 0.0024 0.045 90 0.0025 0.0035 91 0.0026 0.016 92 0.0026 0.0036 93 0.0026 0.068 94 0.0027 0.095 95 0.0027 0.16 96 0.0027 0.046 97 0.0027 0.35 98 0.0027 0.043 99 0.0027 0.33 100 0.0027 0.022 101 0.0028 0.15 102 0.0028 0.0047 103 0.0028 0.0019 104 0.0029 0.12 105 0.0029 0.065 106 0.0029 0.87 107 0.0029 0.0057 108 0.0029 0.0004 109 0.0029 0.50 110 0.0029 0.020 111 0.003 1.1 112 0.003 0.0028 113 0.003 0.016 114 0.003 0.0059 115 0.0031 0.0024 116 0.0031 0.034 117 0.0031 0.21 118 0.0031 0.0041 119 0.0031 0.067 120 0.0031 0.013 121 0.0031 0.0014 122 0.0032 1.08 123 0.0032 0.041 124 0.0033 0.047 125 0.0033 1.1 126 0.0033 2.3 127 0.0033 0.39 128 0.0033 0.0063 129 0.0033 0.38 130 0.0034 0.34 131 0.0034 0.0008 132 0.0034 0.0008 133 0.0034 0.012 134 0.0035 0.0016 135 0.0035 0.058 136 0.0035 0.0022 137 0.0035 0.19 138 0.0035 0.0017 139 0.0035 0.57 140 0.0035 0.61 141 0.0036 0.029 142 0.0036 0.087 143 0.0036 0.053 144 0.0036 0.0231 145 0.0037 0.0082 146 0.0038 0.15 147 0.0038 0.0022 148 0.0038 0.019 149 0.0038 0.0001 150 0.0039 0.007 151 0.0039 0.0005 152 0.0039 0.46 153 0.004 0.0042 154 0.004 0.0033 155 0.004 0.0093 156 0.004 0.0013 157 0.004 0.10 158 0.0041 0.19 159 0.0041 0.074 160 0.0041 1.1 161 0.0041 0.0034 162 0.0041 0.0094 163 0.0042 1.2 164 0.0042 0.29 165 0.0042 0.0017 166 0.0043 2.3 167 0.0043 >10 168 0.0043 1.6 169 0.0043 0.021 170 0.0044 0.0009 171 0.0044 2.4 172 0.0045 0.039 173 0.0045 0.012 174 0.0045 0.067 175 0.0046 0.0093 176 0.0046 0.0065 177 0.0046 0.015 178 0.0047 0.0001 179 0.0047 0.092 180 0.0047 >10 181 0.0048 0.99 182 0.0048 0.0018 183 0.0048 0.0006 184 0.0048 0.0098 185 0.0048 0.0007 186 0.0049 0.003 187 0.0049 0.038 188 0.0049 0.038 189 0.005 3.4 190 0.005 0.13 191 0.005 0.090 192 0.0051 0.0008 193 0.0051 0.57 194 0.0051 0.15 195 0.0052 0.0013 196 0.0052 0.16 197 0.0052 0.0017 198 0.0052 0.013 199 0.0052 0.13 200 0.0052 0.29 201 0.0053 0.018 202 0.0053 0.062 203 0.0053 0.77 204 0.0053 0.52 205 0.0054 0.22 206 0.0054 0.024 207 0.0054 >5 208 0.0054 0.0014 209 0.0055 0.13 210 0.0055 0.19 211 0.0055 0.025 212 0.0056 0.10 213 0.0056 1.8 214 0.0056 2.4 215 0.0056 0.041 216 0.0057 0.27 217 0.0057 0.042 218 0.0057 0.14 219 0.0058 0.14 220 0.0058 0.99 221 0.006 0.050 222 0.006 1.4 223 0.0061 0.1 224 0.0061 1.9 225 0.0062 0.63 226 0.0062 0.023 227 0.0062 0.24 228 0.0062 0.0012 229 0.0062 0.013 230 0.0062 0.088 231 0.0063 0.46 232 0.0063 0.0032 233 0.0063 >5 234 0.0063 1.1 235 0.0065 0.084 236 0.0065 0.030 237 0.0065 0.44 238 0.0066 1.5 239 0.0066 0.65 240 0.0066 0.13 241 0.0066 0.038 242 0.0067 0.11 243 0.0067 0.17 244 0.0068 0.95 245 0.0068 0.0011 246 0.0069 0.28 247 0.0069 0.25 248 0.0069 0.0007 249 0.0069 0.013 250 0.0069 4.8 251 0.007 >5 252 0.007 0.044 253 0.007 0.011 254 0.007 0.052 255 0.007 0.052 256 0.0072 0.53 257 0.0073 0.0016 258 0.0074 0.083 259 0.0074 0.58 260 0.0075 0.0012 261 0.0075 0.94 262 0.0075 0.018 263 0.0075 1.3 264 0.0075 0.37 265 0.0076 0.0015 266 0.0076 0.41 267 0.0077 1.6 268 0.0077 0.14 269 0.0077 0.027 270 0.0078 0.18 271 0.0078 1.4 272 0.0078 0.014 273 0.0078 1.4 274 0.008 0.019 275 0.008 6.1 276 0.008 0.013 277 0.008 0.21 278 0.0081 0.34 279 0.0081 5.8 280 0.0082 0.026 281 0.0082 0.56 282 0.0083 0.70 283 0.0084 0.019 284 0.0084 0.58 285 0.0029 0.22 286 0.0085 0.13 287 0.0086 4.6 288 0.0086 0.0008 289 0.0086 0.062 290 0.0086 1.8 291 0.0087 0.0066 292 0.0087 0.95 293 0.0087 0.044 294 0.0088 0.0091 295 0.0089 0.0006 296 0.009 0.44 297 0.009 0.0001 298 0.009 0.0085 299 0.0092 1.9 300 0.0093 0.36 301 0.0093 0.15 302 0.010 0.022 303 0.0096 0.39 304 0.0096 0.090 305 0.0096 1.3 306 0.0098 0.25 307 0.0099 0.0018 308 0.0099 0.18 309 0.01 0.41 310 0.01 0.067 311 0.010 1.9 312 0.010 0.0005 313 0.010 5.4 314 0.010 0.0004 315 0.010 0.0096 316 0.010 0.095 317 0.010 0.0026 318 0.010 >10 319 0.010 0.20 320 0.010 0.044 321 0.010 0.57 322 0.01 0.097 323 0.011 0.75 324 0.011 0.13 325 0.011 0.0016 326 0.011 0.035 327 0.012 1.7 328 0.012 0.61 329 0.012 2.5 330 0.013 3.7 331 0.013 5.6 332 0.013 5.8 333 0.014 5.7 334 0.014 0.48 335 0.015 0.45 336 0.017 0.06 337 0.017 4.3 338 0.018 1.8 339 0.023 0.0006 340 0.023 0.0011 341 0.023 4.1 342 0.032 0.83 343 0.033 0.12 344 0.046 2.0 345 0.089 0.0031 346 0.097 1.9 347 0.11 0.84 348 0.1107 1.4 349 0.57 5.5 350 0.0009 0.0006 351 0.008 0.005 352 0.0048 0.003 353 0.0042 0.017 354 0.0032 0.007 355 0.0045 0.004 356 0.0035 0.031 357 0.0031 0.012 358 0.0020 0.014 359 0.0045 0.006 360 0.0032 0.018 361 0.0017 0.003 362 0.0001 0.012 363 0.0008 0.003 364 0.0023 0.001 365 0.0026 0.001 366 0.0030 0.003 367 0.0012 0.003 368 0.0017 0.086 369 0.0037 1.1 370 0.0037 1.4 371 0.0019 0.008 372 0.0028 0.017 373 0.0125 0.233 374 0.0041 0.014 375 0.0016 0.003 376 0.0004 0.004 377 0.0016 0.005 378 0.0046 3.8 379 0.0026 0.32 380 0.0018 0.003 381 0.0040 0.010 382 0.0052 0.002 383 0.0055 0.002 384 0.0019 0.001 385 0.0071 0.001 386 0.0024 0.001 387 0.0022 0.001 388 0.0046 0.002 389 <0.005 <0.005 390 0.0048 0.076 391 0.0055 0.036 392 0.0149 0.005 393 0.0024 0.002 394 0.0019 0.011 395 0.0024 0.001 396 0.0095 0.039 397 0.0027 0.015 398 0.0072 0.011 399 0.0027 0.013 400 0.0029 0.000 401 0.0037 0.007 402 0.0028 0.003 403 0.0040 0.002 404 0.0059 0.003 405 0.0047 0.002 406 0.0029 0.009 407 0.0078 0.64 408 0.0035 0.009 409 0.0063 0.036 410 0.0117 3.3 411 0.0026 0.12 412 0.0076 0.093 413 0.0006 0.12 414 0.0047 0.019 415 0.0068 0.003 416 0.0017 0.001 417 0.0029 0.017 418 0.0027 0.004 419 0.0048 0.11 420 0.0073 0.051 421 0.0033 0.015 422 0.0011 0.003 423 0.0047 1.1 424 0.0022 0.011 425 0.0079 0.001 426 0.0023 0.004 427 0.0044 0.002 428 0.0090 0.008 429 0.0015 0.000 430 0.0033 0.005 431 0.0034 0.008 432 0.0091 3.8 433 0.0018 0.001 434 0.0044 0.010 435 0.0028 0.004 436 <0.005 0.009 437 0.0010 0.001 438 0.0039 0.007 439 0.0055 0.007 440 0.0013 0.011 441 0.0052 0.003 442 0.0096 0.001 443 0.0051 0.002 444 0.0018 0.001 445 0.0042 0.62 446 <0.005 0.003 447 0.0047 2.8 448 0.0080 0.009 449 0.0035 0.0002 450 0.0030 0.003 451 0.002 1.9 452 0.0096 0.004 453 0.0095 2.9 454 0.0044 0.017 455 0.0029 0.010 456 0.0028 0.001 457 0.0032 0.002 458 0.0012 0.0008 459 0.0009 0.0002 460 0.0014 0.001 461 0.0037 0.003 462 0.0006 1.4 463 0.0039 0.006 464 0.0016 0.004 465 0.0029 0.013 466 0.0030 0.004 467 0.0018 1.5 468 0.0021 0.018 469 0.0014 0.002 470 0.0019 0.008 471 0.0011 0.002 472 0.0012 0.0017 473 0.0018 0.002 474 0.0021 0.004 475 0.0020 0.020 476 0.0017 0.014 477 0.0010 0.013 478 0.0059 0.001 479 0.0094 0.005 480 0.0057 0.3 481 0.0012 2.2 482 0.0025 0.001 483 0.0056 0.016 484 0.0030 0.42 485 0.0017 0.002 486 0.0043 0.036 487 0.0019 0.72 488 0.0026 0.79 489 0.0007 0.005 490 0.001 0.001 491 0.0018 >5 492 0.0087 >5 493 0.0022 0.27 494 0.0034 0.44 495 0.0016 0.86 496 0.0030 1.1 497 0.0012 0.72 498 0.0018 >5 499 0.029 0.060 500 0.0022 0.71 501 0.0016 2.5 502 0.0077 0.90 503 0.0043 3.5 504 0.0022 3.3 505 0.10 3.4 506 0.0008 0.068 507 0.0023 0.15 508 0.0064 0.11 509 0.041 0.079 510 0.0035 0.29 511 0.066 0.39 512 0.0037 2.1 513 0.0024 1.5 514 0.0026 0.27 515 0.0021 2.2 516 0.0013 1.7 517 0.0028 1.8 518 0.0020 3.3 519 0.0031 0.48 520 0.0049 1.3 521 0.0090 0.33 522 0.0054 >5 523 0.0014 3.6 524 0.0008 1.4 525 0.0014 0.42 526 0.0011 2.3 527 0.0013 0.77 528 0.0002 0.60 529 0.0067 >5 530 0.0031 0.68 531 0.0016 3.2 532 0.0023 0.63 533 0.0040 0.90 534 0.0034 >5 535 0.0010 0.20 536 0.0021 0.65 537 0.0099 0.035 538 0.0013 2.0 539 0.0068 0.47 540 0.0027 >5 541 0.020 0.81 542 0.0057 1.2 543 0.0069 1.9 544 0.034 1.7 545 0.0060 0.33 546 0.0021 1.8 547 0.0045 2.4 548 0.28 >5 549 0.0041 0.028 550 0.010 0.0035 551 0.0015 0.077 552 0.13 0.44 553 0.0007 1.2 554 0.0043 2.4 555 0.031 0.53 556 0.0022 2.0 557 0.0018 0.13 558 0.0064 2.0 559 0.0066 0.45 560 0.0008 0.12 561 0.0043 0.17 562 0.0016 0.75 563 0.0023 0.0023 564 0.0036 0.0005 565 0.0082 0.72 566 0.0011 0.99 567 0.0096 >5 568 0.0028 0.44 569 0.0012 1.6 570 0.0012 1.5 571 0.0060 0.58 572 0.0035 1.6 573 0.0087 1.3 574 0.015 0.55 575 0.48 >5 576 0.0014 0.0015 577 0.0006 0.0002 578 0.0015 0.006 579 0.0058 0.0055 580 0.0036 0.74 581 0.0013 0.010 582 0.0047 0.55 583 0.0038 0.057 584 0.0218 0.66 585 0.0218 1.2 586 0.0098 1.3 587 0.0011 0.60 588 0.0069 0.41 589 0.13 2.6 590 0.0019 1.6 591 0.0105 0.0085 592 0.0071 0.0062 593 0.0033 0.040 594 0.0024 0.0014 595 0.0024 0.013 596 0.0437 0.86 597 0.0015 0.21 598 0.0062 0.59 599 0.0041 0.040 600 0.0078 0.17 601 0.0020 0.17 602 0.0038 0.088 603 0.0039 0.056 604 0.0005 0.015 605 <0.005 0.0019 606 0.0200 0.053 607 0.0133 0.030 608 0.0041 0.0042 609 0.0018 0.028 610 0.0010 0.0003 611 0.0024 0.0059 612 0.0135 0.033 613 0.0118 0.0093 614 0.0060 0.033 615 0.0087 0.0053 616 0.0094 0.020 617 0.0091 0.018 618 0.0010 0.0095 619 0.0094 0.064 620 0.0074 0.0065 621 0.090 0.064 622 0.0084 0.0022 623 0.0115 0.16 624 0.0015 0.0093 625 0.0019 0.012 626 0.0007 0.013 627 0.0086 0.0020 628 0.0047 0.059 629 0.0099 0.67 630 0.0052 1.1 631 0.0100 0.16 632 0.0009 0.0037 633 0.0014 0.0043 634 0.0020 0.0023 635 0.0037 0.0063 636 0.0016 0.0032 637 0.0066 0.0057 638 0.014 0.29 639 0.0058 0.057 640 0.0022 1.2 641 0.0028 1.0 642 0.015 0.57 643 0.0026 0.075 644 0.0021 0.064 645 0.0028 0.19 646 0.016 0.67 647 0.0015 0.022 648 0.0007 0.0041 649 0.0013 0.0078 650 0.011 1.7 651 0.0035 0.78 652 0.0072 0.70 653 0.0033 0.012 654 0.0010 0.012 655 0.0038 0.0012 656 0.0025 0.013 657 0.0020 0.045 658 0.0034 0.0017 659 0.0010 0.0013 660 0.0014 0.029 661 0.0012 0.11 662 0.0040 0.014 663 0.0011 1.7 664 0.0087 0.19 665 <0.010 0.0074 666 0.015 0.015 667 0.063 0.0077 668 0.0088 0.21 669 0.011 0.27 670 0.0065 671 0.0058 672 0.0079 0.005 673 0.0031 0.012 674 0.0068 0.023 675 0.0055 0.005 676 0.013 0.295 677 0.0053 0.230 678 0.011 0.092 679 0.006 0.028 680 0.0028 0.78 681 0.010 1.000 682 0.015 0.001 683 0.013 684 0.007 0.005 685 0.014 0.0014 686 0.013 0.00070 687 0.0018 0.00028 688 0.012 0.0015 689 0.0045 0.0015 690 0.011 0.024 691 0.011 0.011 692 0.0038 0.0028 693 0.0020 0.0025 694 0.0061 0.056 695 0.0035 0.004 696 0.0072 0.0083 697 0.0036 0.0067 698 0.0057 0.0025 699 0.0066 0.0030 700 0.0030 0.00067 701 0.012 0.027 702 0.0085 0.0075 703 0.057 0.099 704 0.0024 0.001 705 0.0006 0.0039 706 0.0094 0.019 707 0.0054 0.13 708 0.011 >1 709 0.014 0.21 710 0.0040 0.49 711 0.0042 3.4 712 0.0021 2.8 713 0.0040 >5 714 0.0064 3.6 715 0.0055 >5 716 0.0057 >5 717 0.0007 0.15 718 0.0009 0.84 719 0.0014 1.9 720 0.0039 >5 721 0.0056 >5

    PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE

    [0234] The compounds of the present invention may be administered to mammals, preferably humans, for the treatment of a variety of conditions and disorders including atherosclerosis, heart failure, lung diseases including asthma, COPD, and cystic fibrosis; neuroinflammatory diseases including multiple sclerosis, Alzheimer’s disease, and stroke; and chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, psoriasis, sepsis, and kidney fibrosis.

    [0235] Unless otherwise specified, the following terms have the stated meanings. The term “subject” refers to any human or other mammalian species that could potentially benefit from treatment with a FPR2 and/or FPR1 agonist as understood by practioners in this field. Some subjects include human beings of any age with risk factors for cardiovascular disease. Common risk factors include age, sex, weight, family history, sleep apnea, alcohol or tobacco use, physical inactivity arrthymia or signs of insulin resistance such as acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome (PCOS). The term “patient” means a person suitable for therapy as determined by practitioners in the field. “Treating” or “treatment” cover the treatment of a patient or subject as understood by practitioners in this field. “Preventing” or “prevention” cover the preventive treatment (i.e., prophylaxis and/or risk reduction) of a subclinical disease-state in a patient or subject aimed at reducing the probability of the occurrence of a clinical disease-state as understood by practitioners in this field. Patients are selected for preventative therapy based on factors that are known to increase risk of suffering a clinical disease state compared to the general population. “Therapeutically effective amount” means an amount of a compound that is effective as understood by practitioners in this field.

    [0236] Another aspect of the invention are pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formulae (I)-(VII) in combination with a pharmaceutical carrier.

    [0237] Another aspect of the invention are pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formulae (I)-(VII) in combination with at least one other therapeutic agent and a pharmaceutical carrier.

    [0238] “Pharmaceutical composition” means a composition comprising a compound of the invention in combination with at least one additional pharmaceutically acceptable carrier. A “pharmaceutically acceptable carrier” refers to media generally accepted in the art for the delivery of biologically active agents to animals, in particular, mammals, including, i.e., adjuvant, excipient or vehicle, such as diluents, preserving agents, fillers, flow regulating agents, disintegrating agents, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents, perfuming agents, anti-bacterial agents, anti-fungal agents, lubricating agents and dispensing agents, depending on the nature of the mode of administration and dosage forms.

    [0239] Pharmaceutically acceptable carriers are formulated according to a number of factors well within the purview of those of ordinary skill in the art. These include, without limitation: the type and nature of the active agent being formulated; the subject to which the agent-containing composition is to be administered; the intended route of administration of the composition; and the therapeutic indication being targeted. Pharmaceutically acceptable carriers include both aqueous and non-aqueous liquid media, as well as a variety of solid and semi-solid dosage forms. Such carriers can include a number of different ingredients and additives in addition to the active agent, such additional ingredients being included in the formulation for a variety of reasons, e.g., stabilization of the active agent, binders, etc., well known to those of ordinary skill in the art. Descriptions of suitable pharmaceutically acceptable carriers, and factors involved in their selection, are found in a variety of readily available sources such as, for example, Allen, L.V., Jr. et al., Remington: The Science and Practice of Pharmacy (2 Volumes), 22nd Edition, Pharmaceutical Press (2012).

    [0240] Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when the compound of the present invention and a second therapeutic agent are combined in a single dosage unit they are formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced). For example, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a material that affects a sustained-release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a low viscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component.

    [0241] Another aspect of the invention is a method for treating heart disease comprising administering a therapeutically effective amount of a compound of Formulae (I)-(VII) to a patient.

    [0242] Another aspect of the invention is a method for treating heart disease wherein the heart disease is selected from the group consisting of angina pectoris, unstable angina, myocardial infarction, heart failure, acute coronary disease, acute heart failure, chronic heart failure, and cardiac iatrogenic damage.

    [0243] It will be understood that treatment or prophylaxis of heart failure may involve treatment or prophylaxis of a cardiovascular event as well. Treatment or prophylaxis as referred to herein may refer to treatment or prophylaxis of certain negative symptoms or conditions associated with or arising as a result of a cardiovascular event. By way of example, treatment or prophylaxis may involve reducing or preventing negative changes in fractional shortening, heart weight, lung weight, myocyte cross sectional area, pressure overload induced cardiac fibrosis, stress induced cellular senescence, and/or cardiac hypertrophy properties, or any combination thereof, associated with or arising as a result of a cardiovascular event. Treatment may be administered in preparation for or in response to a cardiovascular event to alleviate negative effects. Prevention may involve a pro-active or prophylactic type of treatment to prevent the cardiovascular event or to reduce the onset of negative effects of a cardiovascular event.

    [0244] In one embodiment, the present invention provides the use of a compound of Formulae (I)-(VII) or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for the treatment or prophylaxis of heart failure, for example, heart failure results from hypertension, an ischemic heart disease, a non-ischemic heart disease, exposure to a cardiotoxic compound, myocarditis, Kawasaki’s disease, Type I and Type II diabetes, thyroid disease, viral infection, gingivitis, drug abuse, alcohol abuse, pericarditis, atherosclerosis, vascular disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, myocardial infarction, atrial fibrosis, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, coronary bypass surgery, pacemaker implantation surgery, starvation, an eating disorder, muscular dystrophies, and a genetic defect. Preferably, the heart failure to be treated is diastolic heart failure, heart failure with reduced ejection fraction (HF.sub.REF), heart failure with preserved ejection fraction (HF.sub.PEF), acute heart failure, and chronic heart failure of ischemic and non-ischemic origin.

    [0245] In one embodiment, the present invention provides the use of a compound of Formulae (I)-(VII) to treat systolic and/or diastolic dysfunction, wherein the compound is administered in a therapeutically effective amount to increase the ability of the cardiac muscle cells to contract and relax thereby increasing the filling and emptying of both the right and left ventricles, preferably, the left ventricle.

    [0246] In another embodiment, the present invention provides the use of a compound of Formulae (I)-(VII) to treat heart failure wherein the compound is administered in a therapeutically effective amount to increase ejection fraction in the left ventricle.

    [0247] In still another embodiment, the present invention provides the use of a compound of Formulae (I)-(VII) to treat heart failure wherein the compound is administered in a therapeutically effective amount to reduce fibrosis in heart tissue.

    [0248] Another aspect of the invention is a method for treating heart disease wherein the treatment is post myocardial infarction.

    [0249] Another aspect of the invention is a method for treating heart disease comprising administering a therapeutically effective amount of a compound of Formulae (I)-(VII) to a patient in conjunction with other therapeutic agents.

    [0250] The compounds of this invention can be administered by any suitable means, for example, orally, such as tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions (including nanosuspensions, microsuspensions, spray-dried dispersions), syrups, and emulsions; sublingually; buccally; parenterally, such as by subcutaneous, intravenous, intramuscular, or intrasternal injection, or infusion techniques (e.g., as sterile injectable aqueous or non-aqueous solutions or suspensions); nasally, including administration to the nasal membranes, such as by inhalation spray; topically, such as in the form of a cream or ointment; or rectally such as in the form of suppositories. They can be administered alone, but generally will be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

    [0251] The dosage regimen for the compounds of the present invention will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the species, age, sex, health, medical condition, and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient, and the effect desired.

    [0252] By way of general guidance, the daily oral dosage of each active ingredient, when used for the indicated effects, will range between about 0.01 to about 5000 mg per day, preferably between about 0.1 to about 1000 mg per day, and most preferably between about 0.1 to about 250 mg per day. Intravenously, the most preferred doses will range from about 0.01 to about 10 mg/kg/minute during a constant rate infusion. Compounds of this invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily.

    [0253] Dosage forms (pharmaceutical compositions) suitable for administration may contain from about 1 milligram to about 2000 milligrams of active ingredient per dosage unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.1-95% by weight based on the total weight of the composition. A typical capsule for oral administration contains at least one of the compounds of the present invention (250 mg), lactose (75 mg), and magnesium stearate (15 mg). The mixture is passed through a 60 mesh sieve and packed into a No. 1 gelatin capsule. A typical injectable preparation is produced by aseptically placing at least one of the compounds of the present invention (250 mg) into a vial, aseptically freeze-drying and sealing. For use, the contents of the vial are mixed with 2 mL of physiological saline, to produce an injectable preparation.

    [0254] The compounds of the present invention may be employed in combination with other suitable therapeutic agents useful in the treatment of the aforementioned diseases or disorders including: anti-atherosclerotic agents, anti-dyslipidemic agents, anti-diabetic agents, anti-hyperglycemic agents, anti-hyperinsulinemic agents, anti-thrombotic agents, anti-retinopathic agents, anti-neuropathic agents, anti-nephropathic agents, anti-ischemic agents, anti-hypertensive agents, anti-obesity agents, anti-hyperlipidemic agents, anti-hypertriglyceridemic agents, anti-hypercholesterolemic agents, anti-restenotic agents, anti-pancreatic agents, lipid lowering agents, anorectic agents, memory enhancing agents, anti-dementia agents, cognition promoting agents, appetite suppressants, agents for treating heart failure, agents for treating peripheral arterial disease, agents for treating malignant tumors, and anti-inflammatory agents.

    [0255] The compounds of the invention may be used with at least one of the following heart failure agents selected from loop diuretics, Angiotensin converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNI), beta blockers, mineralocorticoid receptor antagonists, nitroxyl donors, RXFP1 agonists, APJ agonists and cardiotonic agents. These agents include, but are not limited to furosemide, bumetanide, torsemide, sacubitrial-valsartan, thiazide diruetics, captopril, enalapril, lisinopril, carvedilol, metopolol, bisoprolol, serelaxin, spironolactone, eplerenone, ivabradine, candesartan, eprosartan, irbestarain, losartan, olmesartan, telmisartan, and valsartan.

    [0256] The compounds of the present invention may be employed in combination with at least one of the following therapeutic agents in treating atherosclerosis: anti-hyperlipidemic agents, plasma HDL-raising agents, anti-hypercholesterolemic agents, cholesterol biosynthesis inhibitors (such as HMG CoA reductase inhibitors), LXR agonist, probucol, raloxifene, nicotinic acid, niacinamide, cholesterol absorption inhibitors, bile acid sequestrants (such as anion exchange resins, or quaternary amines (e.g., cholestyramine or colestipol)), low density lipoprotein receptor inducers, clofibrate, fenofibrate, benzofibrate, cipofibrate, gemfibrizol, vitamin B.sub.6, vitamin B.sub.12, anti-oxidant vitamins, β-blockers, anti-diabetes agents, angiotensin II antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibitors, fibrinogen receptor antagonists, aspirin and fibric acid derivatives.

    [0257] The compounds of the present invention may be employed in combination at least one of the following therapeutic agents in treating cholesterol biosynthesis inhibitor, particularly an HMG-CoA reductase inhibitor. Examples of suitable HMG-CoA reductase inhibitors include, but are not limited to, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin.

    [0258] The compounds of the invention may be used in combination with at least one of the following anti-diabetic agents depending on the desired target therapy. Studies indicate that diabetes and hyperlipidemia modulation can be further improved by the addition of a second agent to the therapeutic regimen. Examples of anti-diabetic agents include, but are not limited to, sulfonylureas (such as chlorpropamide, tolbutamide, acetohexamide, tolazamide, glyburide, gliclazide, glynase, glimepiride, and glipizide), biguanides (such as metformin), thiazolidinediones (such as ciglitazone, pioglitazone, troglitazone, and rosiglitazone), and related insulin sensitizers, such as selective and non-selective activators of PPARα, PPARβ and PPARγ; dehydroepiandrosterone (also referred to as DHEA or its conjugated sulphate ester, DHEA-SO.sub.4); anti-glucocorticoids; TNFα inhibitors; dipeptidyl peptidase IV (DPP4) inhibitor (such as sitagliptin, saxagliptin), GLP-1 agonists or analogs (such as exenatide), α-glucosidase inhibitors (such as acarbose, miglitol, and voglibose), pramlintide (a synthetic analog of the human hormone amylin), other insulin secretagogues (such as repaglinide, gliquidone, and nateglinide), insulin, as well as the therapeutic agents discussed above for treating atherosclerosis.

    [0259] The compounds of the invention may be used in combination with at least one of the following anti-obesity agents selected from phenylpropanolamine, phentermine, diethylpropion, mazindol, fenfluramine, dexfenfluramine, phentiramine, β.sub.3-adrenoreceptor agonist agents; sibutramine, gastrointestinal lipase inhibitors (such as orlistat), and leptins. Other agents used in treating obesity or obesity-related disorders include neuropeptide Y, enterostatin, cholecytokinin, bombesin, amylin, histamine H.sub.3 receptors, dopamine D.sub.2 receptor modulators, melanocyte stimulating hormone, corticotrophin releasing factor, galanin and gamma amino butyric acid (GABA).

    [0260] The compounds of the present invention are also useful as standard or reference compounds, for example as a quality standard or control, in tests or assays involving the FPR2. Such compounds may be provided in a commercial kit, for example, for use in pharmaceutical research involving FPR2 activity. For example, a compound of the present invention could be used as a reference in an assay to compare its known activity to a compound with an unknown activity. This would ensure the experimenter that the assay was being performed properly and provide a basis for comparison, especially if the test compound was a derivative of the reference compound. When developing new assays or protocols, compounds according to the present invention could be used to test their effectiveness. The compounds of the present invention may also be used in diagnostic assays involving FPR2.

    [0261] The present invention also encompasses an article of manufacture. As used herein, article of manufacture is intended to include, but not be limited to, kits and packages. The article of manufacture of the present invention, comprises: (a) a first container; (b) a pharmaceutical composition located within the first container, wherein the composition, comprises a first therapeutic agent, comprising a compound of the present invention or a pharmaceutically acceptable salt form thereof; and, (c) a package insert stating that the pharmaceutical composition can be used for the treatment of dyslipidemias and the sequelae thereof. In another embodiment, the package insert states that the pharmaceutical composition can be used in combination (as defined previously) with a second therapeutic agent for the treatment of dyslipidemias and the sequelae thereof. The article of manufacture can further comprise: (d) a second container, wherein components (a) and (b) are located within the second container and component (c) is located within or outside of the second container. Located within the first and second containers means that the respective container holds the item within its boundaries. The first container is a receptacle used to hold a pharmaceutical composition. This container can be for manufacturing, storing, shipping, and/or individual/bulk selling. First container is intended to cover a bottle, jar, vial, flask, syringe, tube (e.g., for a cream preparation), or any other container used to manufacture, hold, store, or distribute a pharmaceutical product. The second container is one used to hold the first container and, optionally, the package insert. Examples of the second container include, but are not limited to, boxes (e.g., cardboard or plastic), crates, cartons, bags (e.g., paper or plastic bags), pouches, and sacks. The package insert can be physically attached to the outside of the first container via tape, glue, staple, or another method of attachment, or it can rest inside the second container without any physical means of attachment to the first container. Alternatively, the package insert is located on the outside of the second container. When located on the outside of the second container, it is preferable that the package insert is physically attached via tape, glue, staple, or another method of attachment. Alternatively, it can be adjacent to or touching the outside of the second container without being physically attached. The package insert is a label, tag, marker, etc. that recites information relating to the pharmaceutical composition located within the first container. The information recited will usually be determined by the regulatory agency governing the area in which the article of manufacture is to be sold (e.g., the United States Food and Drug Administration). Preferably, the package insert specifically recites the indications for which the pharmaceutical composition has been approved. The package insert may be made of any material on which a person can read information contained therein or thereon. Preferably, the package insert is a printable material (e.g., paper, plastic, cardboard, foil, adhesive-backed paper or plastic, etc.) on which the desired information has been formed (e.g., printed or applied).

    CHEMISTRY METHODS

    [0262] Abbreviations as used herein, are defined as follows: “1x” for once, “2x” for twice, “3x” for thrice, “°C” for degrees Celsius, “aq” for aqueous, “Col” for column, “eq” for equivalent or equivalents, “g” for gram or grams, “mg” for milligram or milligrams, “L” for liter or liters, “mL” for milliliter or milliliters, “.Math.L” for microliter or microliters, “N” for normal, “M” for molar, “nM” for nanomolar, “mol” for mole or moles, “mmol” for millimole or millimoles, “min” for minute or minutes, “h” for hour or hours, “rt” for room temperature, “RT” for retention time, “ON” for overnight, “atm” for atmosphere, “psi” for pounds per square inch, “conc.” for concentrate, “aq” for “aqueous”, “sat” or “sat’d” for saturated, “MW” for molecular weight, “mw” or “.Math.wave” for microwave, “mp” for melting point, “Wt” for weight, “MS” or “Mass Spec” for mass spectrometry, “ESI” for electrospray ionization mass spectroscopy, “HR” for high resolution, “HRMS” for high resolution mass spectrometry, “LCMS” for liquid chromatography mass spectrometry, “HPLC” for high pressure liquid chromatography, “RP HPLC” for reverse phase HPLC, “TLC” or “tlc” for thin layer chromatography, “NMR” for nuclear magnetic resonance spectroscopy, “nOe” for nuclear Overhauser effect spectroscopy, “.sup.1H” for proton, “δ” for delta, “s” for singlet, “d” for doublet, “t” for triplet, “q” for quartet, “m” for multiplet, “br” for broad, “Hz” for hertz, and “α”, “β”, “R”, “S”, “E”, and “Z” are stereochemical designations familiar to one skilled in the art.

    TABLE-US-00002 Ac acetic AcOH acetic acid Acn (or MeCN) acetonitrile Bn benzyl Boc tert-butyl carbonyl Boc.sub.2O di-tert-butyl dicarbonate Bu butyl Dba as in (Pd.sub.2(dba).sub.3) dibenzylideneacetone Cbz carboxybenzyl DCM dichloromethane DEA diethylamine DIEA or DIPEA diisopropylethylamine DMAP 4-dimethylaminopyridine DMF dimethylformamide DMSO dimethyl sulfoxide dppf 1,1′-bis(diphenylphosphino)ferrocene Et ethyl EtOH ethanol EtOAc ethyl acetate HATU 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroni um hexafluorophosphate HBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate i-Bu isobutyl IPA isopropyl alcohol i-Pr isopropyl LAH lithium aluminum hydride Me methyl MeOH methanol pet petroleum Ph phenyl Pr propyl t-Bu tert-butyl TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran Ts tosyl

    [0263] The disclosed compounds can be made by various methods known in the art including those of the following schemes and in the specific embodiments section. The structure numbering and variable numbering shown in the synthetic schemes are distinct from and should not be confused with the structure or variable numbering in the claims or the rest of the specification. The variables in the schemes are meant only to illustrate how to make some of the compounds of this invention.

    [0264] A consideration in the planning of any synthetic route in this field is the choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene, T.W. et al., Protecting Groups in Organic Synthesis, 4th Edition, Wiley (2007)).

    [0265] Compounds having the general Formula (I): wherein A, B and C are defined above as Ar.sup.1, Ar.sup.2 and Ar.sup.3, respectively and Formula (II): wherein A, B and Y are defined above as Ar.sup.1, Ar.sup.2 and alkyl and/or cycloalkyl groups, respectively and can be prepared by the following one or more of the synthetic Schemes.

    ##STR00116##

    ##STR00117##

    1-Arylpyrrolidinone compounds of this invention (Formula I) wherein ring A is a substituted phenyl or cycloalkyl ring, ring B is phenyl or heteroaryl ring and ring C is a substituted phenyl or heteroaryl ring can be prepared by the general route shown in Scheme 1. Compound 1a was synthesized as per the procedure reported in the patent literature (WO2015079692). Compound 1a was treated with diphenylphosphoryl azide (DPPA) and a tertiary amine such as triethylamine (TEA). Subsequent addition of benzyl alcohol yielded Cbz protected compound 1b. Removal of the Cbz protecting group from 1b with Pd/C in the presence of hydrogen, followed by amide coupling of the resulting free amine with a suitably substituted phenyl acid provided amides 1c. Other deprotection conditions and protecting groups known to those skilled in the art could also be used in this sequence. Copper or Pd-catalyzed coupling of 1c to a substituted iodobenzene or bromobenzene or other suitable halo aryl or heteroaryl compounds in a suitable solvent such as butanol or dioxane or toluene, in the presence of a base such as potassium carbonate or cesium carbonate and a suitable ligand such as N,N′-dimethylethylenediamine, or Xanthphos can afford desired compounds 1d. Suitable aryl or heteroaryl halides are either commercially available or can be readily obtained from the corresponding readily available starting materials by methods known to one skilled in the art. Additional methods for this transformation include other variations of Ullmann, Goldberg, and Buchwald copper-catalyzed amidation or Buchwald Pd-catalyzed C-N coupling depending on the nature of ring B, using methods known to one skilled in the art for these types of couplings (see for example Yin & Buchwald, Organic Lett. 2000, 2, 1101; Klapers et al., JACS, 2001, 123, 7727; Klapars et al., JACS, 2002, 124, 7421; Yin & Buchwald, JACS. 2002, 124, 6043; Kiyomor, Madoux & Buchwald, Tet. Lett., 1999, 40, 2657). Similarly, 1-arylpyrrolidinone compounds of this invention (Formula I) wherein rings A and C are substituted phenyl rings or heteroaryl or cycloalkyl and ring B is phenyl or heteroaryl can be prepared by the general route shown in Scheme 2.

    ##STR00118##

    ##STR00119##

    [0266] 1-Arylpyrrolidinone compounds of this invention (Formula II) wherein rings A and C are phenyl rings and Y is a substituted benzyl, heteroaryl alkyl, alkyl and or cycloalkyl group, can be prepared by the general route shown in Scheme 3, starting from an intermediate 1c, prepared as shown in Scheme 1.

    ##STR00120##

    [0267] In the Scheme 3, Y is a C.sub.1-6 alkyl group, benzyl, and heteroaryl with an alkyl spacer and X is a leaving group such as chloride, bromide, iodide, a methane sulfonyloxy group, a trifluoromethane sulfonyloxy group or the other known groups. Compound 1e can be obtained by reacting compound 1c with alkylating reagent YX in a solvent in the presence of a suitable base with heating in an appropriate solvent such as DMF or DMSO or obtained by other methods known to one skilled in the art.

    [0268] Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments that are given for illustration of the invention and are not intended to be limiting thereof.

    [0269] The following methods were used in the exemplified Examples, except where noted otherwise. Purification of intermediates and final products was carried out via either normal or reverse phase chromatography. Normal phase chromatography was carried out using prepacked SiO.sub.2 cartridges eluting with either gradients of hexanes and ethyl acetate or DCM and MeOH unless otherwise indicated. Reverse phase preparative HPLC was carried out using C18 columns with UV 220 nm or prep LCMS detection eluting with gradients of Solvent A (90% water, 10%MeOH, 0.1% TFA) and Solvent B (10% water, 90% MeOH, 0.1% TFA) or with gradients of Solvent A (95% water, 5% Acn, 0.1% TFA) and Solvent B (5% water, 95% Acn, 0.1% TFA) or with gradients of Solvent A (95% water, 2% Acn, 0.1% HCOOH) and Solvent B (98% Acn, 2% water, 0.1% HCOOH) or with gradients of Solvent A (95% water, 5% Acn, 10 mM NH.sub.4OAc) and Solvent B (98% Acn, 2% water, 10 mMNH.sub.4OAc) or with gradients of Solvent A (98% water, 2% Acn, 0.1%NH.sub.4OH) and Solvent B (98% Acn, 2% water, 0.1% NH.sub.4OH).

    [0270] LC/MS Methods Employed in Characterization of Examples. Reverse phase analytical HPLC/MS was performed on a Waters Acquity system coupled with a Waters MICROMASS.sup.® ZQ Mass Spectrometer. [0271] Method A: Linear gradient of 0 to 100% B over 3 min, with 0.75 min hold time at 100% B; [0272] UV visualization at 220 nm [0273] Column: Waters BEH C18 2.1 × 50 mm [0274] Flow rate: 1.0 mL/min [0275] Solvent A: 0.1% TFA, 95% water, 5% Acn [0276] Solvent B: 0.1% TFA, 5% water, 95% Acn [0277] Method B: Linear gradient of 0 to 100% B over 3 min, with 0.75 min hold time at 100% B; [0278] UV visualization at 220 nm [0279] Column: Waters BEH C18 2.1 × 50 mm [0280] Flow rate: 1.0 mL/min [0281] Solvent A: 10 mM ammonium acetate, 95% water, 5% Acn [0282] Solvent B: 10 mM ammonium acetate, 5% water, 95% Acn

    Analytical HPLC: Methods Employed in Characterization of Examples

    [0283] Products were analyzed by reverse phase analytical HPLC: carried out on a Shimadzu Analytical HPLC: system running Discovery VP software. RT = retention time.

    [0284] Method C: Ascentis Express C18, 2.1 × 50 mm, 2.7 \-.Math.m particles; Solvent A: 95% water, 5% acetonitrile, 0.05% TFA; Solvent B: 95% acetonitrile, 5% water, 0.1% TFA; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a 1-minute hold at 100% B; Flow: 1.1 mL/min.

    [0285] Method D: Ascentis Express C18, 2.1 × 50 mm, 2.7 \-.Math.m particles; Solvent A: 95% water, 5% acetonitrile with 10 mM ammonium acetate; Solvent B: 95% acetonitrile, 5% water with 10 mM ammonium acetate; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a 1-minute hold at 100% B; Flow: 1.1 mL/min.

    [0286] The following representative conditions were used to screen compounds for chiral purity. Other conditions were used as well. [0287] Columns: Chiralpak IA, 250 × 4.6 mm, 5.0 \-.Math.m particles, Chiralpak IB, 250 × 4.6 mm, 5.0 \- .Math.m particles, Chiralpak IC, 250 × 4.6 mm, 5.0 \-.Math.m particles, Chiralpak ID, 250 × 4.6 mm, 5.0 \- .Math.m particles, Chiralpak IE, 250 × 4.6 mm, 5.0 \-.Math.m particles and Chiralpak IF, 250 × 4.6 mm, 5.0 \- .Math.m particles; [0288] Mobile Phase: 0.2% ammonia in Acn—MeOH (1:1). [0289] NMR Employed in Characterization of Examples. .sup.1H NMR spectra were obtained with Bruker or JEOL.sup.® Fourier transform spectrometers operating at frequencies as follows: .sup.1H NMR: 300 MHz (Bruker or JEOL.sup.®) or 400 MHz (Bruker or JEOL.sup.®) or 500 MHz (Bruker or JEOL.sup.®). .sup.13C NMR: 100 MHz (Bruker or JEOL.sup.®). Spectra data are reported in the format: chemical shift (multiplicity, coupling constants, and number of hydrogens). Chemical shifts are specified in ppm downfield of a tetramethylsilane internal standard (δ units, tetramethylsilane = 0 ppm) and/or referenced to solvent peaks, which in .sup.1H NMR spectra appear at 2.49 ppm for CD.sub.2HSOCD.sub.3, 3.30 ppm for CD.sub.2HOD, 1.94 for CD.sub.3CN, and 7.24 ppm for CHCl.sub.3, and which in .sup.13C NMR spectra appear at 39.7 ppm for CD.sub.3SOCD.sub.3, 49.0 ppm for CD.sub.3OD, and 77.0 ppm for CDCl.sub.3. All .sup.13C NMR spectra were proton decoupled.

    Intermediate 1: Benzyl ((3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)carbamate

    [0290] ##STR00121##

    To a stirred solution of (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidine-3-carboxylic acid (6.0 g, 22 mmol), TEA (3.7 mL, 27 mmol) in toluene (60 mL) and acetonitrile (12 mL) was added diphenylphosphoryl azide (5.7 mL, 27 mmol). The mixture was stirred at rt for 3 h, and then at 80° C. for 30 min. After the mixture was cooled to rt, benzyl alcohol (12 mL, 110 mmol) was added, and the mixturewas stirred at 100° C. for 16 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was purified via column chromatography (pet. ether-ethyl acetate) to afford Intermediate 1 (4.0 g, 11 mmol, 50%) as a colorless liquid. MS (ESI) m/z: 377.3 [M+H].sup.+

    Intermediate 2: (3S,4R)-3-amino-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one

    [0291] ##STR00122##

    To a degassed solution of Intermediate 1 (4.0 g, 11 mmol) in EtOH (60 mL) was added Pd—C (0.11 g, 1.1 mmol). The reaction mixture was purged with H.sub.2 and stirred under an H.sub.2 atmosphere for 16 h at rt. The mixture was filtered through a pad of Celite and concentrated under reduced pressure to afford (3S,4R)-3-amino-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one (2.5 g, 10.3 mmol, 97 %) as a white solid. The crude material was used in the next synthetic step without further purification. MS (ESI) m/z: 243.2 [M+H].sup.+

    Intermediate 3: N-((3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-4-(difluoromethoxy)benzamide

    [0292] ##STR00123##

    To a stirred solution of Intermediate 2 (1.2 g, 5.0 mmol) in DMF (10 mL) under argon atmosphere at rt were added DIEA (1.0 mL, 6.0 mmol), 4-(difluoromethoxy)benzoic acid (1.1 g, 6.0 mmol), and HATU (2.3 g, 6.0 mmol). After 16 h, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with water and brine (20 mL each), dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to give the crude product, which was purified via column chromatography (pet. ether-ethyl acetate) to afford Intermediate 3 (1.2 g, 2.9 mmol, 59% yield) as a white solid. MS(ESI) m/z: 413.1 [M+H].sup.+. .sup.1H NMR (300 MHz, DMSO-d6) δ 8.85 (d, J = 8.6 Hz, 1H), 8.19 (s, 1H), 7.86 (d, J= 8.6 Hz, 2H), 7.35 (t, J = 75.0 Hz, 1H), 7.26 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 12.0 Hz, 2H), 4.90 - 4.80 (m, 1H), 4.06 - 3.79 (m, 1H), 3.75 (s, 3H), 3.60 - 3.45 (m, 1H), 3.42 -3.32 (m, 1H).

    Intermediate 4: N-((3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-4-(trifluoromethoxy)benzamide

    [0293] ##STR00124##

    A similar protocol to the above procedure for Intermediate 3 was followed to synthesize Intermediate 4. MS(ESI) m/z: 431.1 [M+H].sup.+. .sup.1H NMR (300 MHz, CDCl.sub.3) δ = 7.77 (d, J= 8.4 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 6.47 (m, 3H), 6.23 (s, 1 H), 5.14 - 4.97 (m, 1H), 4.07 - 3.95 (m, 1H), 3.82 - 3.75 (m, 4H), 3.68 - 3.63 (m, 1H).

    Intermediate 5A and 5B: 3-Bromo-4-methyl-1-(3,3,3-trifluoro-2-hydroxypropyl) pyridin-2(1H)-one:

    [0294] ##STR00125##

    ##STR00126##

    To a stirred solution of 3-bromo-4-methylpyridin-2(1H)-one (1.5 g, 8.0 mmol) in DMF (15 mL) at rt, were added 3-bromo-1,1,1-trifluoropropan-2-ol (2.3 g, 12 mmol) and K.sub.2CO.sub.3 (3.3 g, 24 mmol). The reaction mixture was heated at 90° C. for 16 h. The reaction mixture was cooled, filtered through Celite pad, and concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (pet. ether-ethyl acetate) and the enantiomers were separated via chiral SFC separation to yield Intermediate 5A (0.80 g, 2.7 mmol, 33.4% yield) and Intermediate 5B (0.80 g, 2.7 mmol, 33% yield). SFC prep conditions: Column/dimensions: Whelk (R,R)(250 × 4.6) mm, 5.Math.; CO.sub.2:85%, % Co-solvent: 15% of 0.2% DEA in IPA. Total flow: 3.0 g/min, back pressure: 100 bar, temperature: 40° C., UV: 220 nm. Retention time peak 1= 3.2 min and peak 2= 4.4 min. Enantiomer 1: MS(ESI) m/z: 299.9 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 7.60 (d, J = 7.0 Hz, 1H), 6.62 (d, J = 6.5 Hz, 1H), 6.29 (d, J = 7.0 Hz, 1H), 4.42 - 4.29 (m, 2H), 3.87 - 3.79 (m, 1H), 2.28 (s, 3H). Enantiomer 2: MS(ESI) m/z: 299.9 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 7.60 (d, J = 7.0 Hz, 1H), 6.62 (d, J = 6.5 Hz, 1H), 6.29 (d, J = 7.0 Hz, 1H), 4.42 - 4.29 (m, 2H), 3.87 - 3.79 (m, 1H), 2.28 (s, 3H).

    Intermediate 6: 2-(2-Methoxyethyl)-5-methylpyridazin-3(2H)-one

    [0295] ##STR00127##

    To a stirred solution of 5-methylpyridazin-3(2H)-one (1.0 g, 9.1 mmol) in DMF (10 mL) at rt, were added potassium carbonate (3.8 g, 27 mmol), and 1-bromo-2-methoxyethane (1.5 g, 11 mmol). The reaction mixture was heated at 70° C. for 15 h. Then, the reaction mixture was cooled, filtered through Celite pad, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (pet. ether-ethyl acetate) to yield Intermediate 6 (1.0 g, 6.0 mmol, 66 % yield) as a yellow liquid. MS(ESI) m/z: 169.1 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 7.79 (d, J = 2.0 Hz, 1H), 6.73 (m, 1H), 4.18 (t, J = 5.8 Hz, 2H), 3.64 (t, J = 5.8 Hz, 2H), 3.23 (s, 3H), 2.16 (d, J = 2.0 Hz, 3H).

    Intermediate 7: 4-Bromo-2-(2-methoxyethyl)-5-methylpyridazin-3(2H)-one

    [0296] ##STR00128##

    To a stirred solution of 2-(2-methoxyethyl)-5-methylpyridazin-3(2H)-one (500 mg, 3.0 mmol) in acetonitrile (5 mL) at rt, was added NBS (1060 mg, 5.95 mmol). Then, the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was cooled, filtered through Celite pad and the filtrate was concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (pet. ether-ethyl acetate) to afford theIntermediate 7 (350 mg, 1.4 mmol, 48% yield) as an orange solid. MS(ESI) m/z: 249.1 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 7.86 (s, 1H), 4.26 (t, J = 5.5 Hz, 2H), 3.67 (t, J = 5.5 Hz, 2H), 3.22 (s, 3H), 2.27 (s, 3H).

    Example 1: N-((3S,4R)-1-(2-cyanopyridin-3-yl)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-4-(difluoromethoxy)benzamide

    [0297] ##STR00129##

    To a stirred solution of Intermediate 3 (80 mg, 0.19 mmol) in 1,4-dioxane (2 mL) were added 3-bromopicolinonitrile (43 mg, 0.23 mmol), and Cs.sub.2CO.sub.3 (130 mg, 0.39 mmol). The reaction mixture was purged with nitrogen for 5 min and charged with xanthphos (22 mg, 0.039 mmol) and Pd.sub.2(dba).sub.3 (18 mg, 0.019 mmol). The reaction mixture was again purged with nitrogen for 3 min and heated at 100° C. for 16 h. The reaction mixture was cooled and filtered through a Celite pad. The filtrate was concentrated under reduced pressure, and the crude product was purified by reverse phase HPLC to afford Example 1 (26 mg, 0.051 mmol, 26% yield) as a white solid. MS(ESI) m/z: 515.2 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J= 8.3 Hz, 1H), 8.72 (d, J = 4.6 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.94 - 7.87 (m, 3H), 7.35 (s, 1H), 7.29 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 10.8 Hz, 2H), 5.16 - 5.02 (m, 1H), 4.34 - 4.22 (m, 2H), 4.18 - 4.09 (m, 1H), 3.78 (s, 3H). RT = 1.725 min, 100% (Method D).

    Example 2: N-((3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-oxopyrrolidin-3-yl)-4-(difluoromethoxy)benzamide

    [0298] ##STR00130##

    To a stirred solution of Intermediate 3 (60 mg, 0.15 mmol) in 1,4-dioxane (2 mL) at rt were added 5-bromo-1-methylpyridin-2(1H)-one (33 mg, 0.18 mmol), Cs.sub.2CO.sub.3 (95 mg, 0.29 mmol) and, N,N′-dimethylethylenediamine (2.6 mg, 0.029 mmol). The reaction mixture was purged with nitrogen for 5 min and then charged with copper (I) iodide (5.5 mg, 0.029 mmol), purged with nitrogen for 3 min and heated at 100° C. for 16 h. The reaction mixture was cooled, filtered through Celite pad and concentrated under reduced pressure to give the crude product, which was purified by reverse phase HPLC to afford the Example 2 (32 mg, 0.062 mmol, 42% yield) as a white solid. MS(ESI) m/z: 520.1 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J= 8.6 Hz, 1H), 8.01 (d, J= 2.7 Hz, 1H), 7.93 - 7.81 (m, 3H), 7.55 - 7.13 (m, 3H), 6.80 (d, J= 10.8 Hz, 2H), 6.46 (d, J= 10.0 Hz, 1H), 4.98 (m, 1H), 4.18 - 4.07 (m, 1H), 4.00 (t, J = 8.8 Hz, 1H), 3.93 - 3.85 (m, 1H), 3.78 (s, 3H), 3.45 (s, 3H). RT = 1.677 min, 100% (Method D).

    Example 3: N-((3S,4R)-1-(cyclopropylmethyl)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-4-(difluoromethoxy)benzamide

    [0299] ##STR00131##

    To a stirred solution of Intermediate 3 (60 mg, 0.15 mmol) in DMF (2 mL) under argon atmosphere at 0° C. was added NaH (8.7 mg, 0.22 mmol), and the resulting reaction mixture was stirred for 30 min. Then bromomethyl cyclopropane (24 mg, 0.18 mmol) was added to the reaction mixture, and the mixture was gradually warmed to rt over a period of 2 h. The reaction mixture was quenched with ice/water and extracted with EtOAc (20 mL × 2). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure. The crude product was purified by reverse phase HPLC to afford Example 3 (23 mg, 0.049 mmol, 33 % yield) as a white solid. MS(ESI) m/z: 467.1 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J= 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.26 (d, J = 8.6 Hz, 2H), 6.76 (d, J = 10.8 Hz, 2H), 4.92 (t, J = 9.5 Hz, 1H), 3.97 - 3.88 (m, 1H), 3.77 (s, 3H), 3.75 - 3.70 (m, 1H), 3.65 - 3.55 (m, 1H), 3.31 - 3.24 (m, 1H), 3.07 (m, 1H), 1.01 - 0.93 (m, 1H), 0.51 (d, J = 8.1 Hz, 2H), 0.32 - 0.20 (m, 2H). RT = 1.810 min, 99.2% (Method D).

    Example 4 and 5: N-((3S, 4R)-4-(2, 6-Difluoro-4-methoxyphenyl)-2-oxo-1-(2-oxo-1-(3, 3, 3-trifluoro-2-hydroxypropyl)-1,2-dihydropyridin-3-yl)pyrrolidin-3-yl)-4-(difluoromethoxy)benzamide (Enantiomers 1 and 2)

    [0300] ##STR00132##

    ##STR00133##

    To a stirred solution of N-((3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-4-(difluoromethoxy)benzamide (500 mg, 1.2 mmol) in 1,4-dioxane (10 mL) at rt, were added cesium carbonate (790 mg, 2.4 mmol), and 3-bromo-1-(3,3,3-trifluoro-2-hydroxypropyl)pyridin-2(1H)-one (382 mg, 1.34 mmol). The reaction mixture was purged with nitrogen for 5 min and then charged with N,N-dimethylethane-1,2-diamine (21 mg, 0.24 mmol) and copper (I) iodide (23 mg, 0.12 mmol). The reaction mixture was again purged with nitrogen for 3 min and heated at 100° C. for 16 h. The reaction mixture was cooled, filtered through Celite pad, concentrated under reduced pressure. The crude compound, which was purified reverse phase HPLC followed by chiral SFC to yield Example 4 (68 mg, 0.11 mmol, 9.1% yield), and Example 5 (65 mg, 0.10 mmol, 8.7 % yield). SFC prep condition: Column/dimensions: Luxcellulose (250 × 30) mm, 5.Math.; % CO.sub.2: 60%, % Co-solvent: 40% of 4 M methanolic ammonia in MeOH. Total flow: 120.0 g/min, back pressure: 100 bar, temperature: 30° C., UV: 220 nm; Retention time: peak 1 = 4.6 min and peak 2 = 9.7 min. Enantiomer 1: MS(ESI) m/z: 618.2 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (br d, J = 8.6 Hz, 1H), 7.93 - 7.81 (m, 2H), 7.70 (dd, J = 6.8, 2.0 Hz, 1H), 7.65 (dd, J = 7.3, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.37 (t, J= 7.1 Hz, 1H), 5.16 - 5.04 (m, 1H), 4.45 (dd, J= 13.1, 2.8 Hz, 1H), 4.39 - 4.27 (m, 1H), 4.17 - 4.06 (m, 1H), 4.06 - 3.98 (m, 1H), 3.97 - 3.88 (m, 1H), 3.88 -3.80 (m, 1H), 3.76 (s, 3H), 3.35 (br s, 1H). Enantiomer 2: MS(ESI) m/z: 618.2 [M+H].sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.8 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.69 (dd, J = 6.7, 2.1 Hz, 1H), 7.64 (dd, J= 7.3, 2.1 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (d, J= 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.37 (t, J= 7.0 Hz, 1H), 5.08 (dd, J = 10.9, 8.9 Hz, 1H), 4.44 (dd, J= 13.1, 3.1 Hz, 1H), 4.39 - 4.26 (m, 1H), 4.15 - 3.99 (m, 2H), 3.97 - 3.90 (m, 1H), 3.84 (dd, J = 13.3, 9.4 Hz, 1H), 3.76 (s, 3H), 3.36 (br s, 1H).

    [0301] The following Examples in Table 2 were made by using analogous procedures as shown in Examples 1-5 and/or modifications thereof known to one skilled in the art.

    TABLE-US-00003 Ex Structure LCMS (M+H) + HPLC Method, RT (min.) & Purity .sup.1H NMR 6 [00134]embedded image 549.1 Method D, RT = 2.022 min, 96.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 8.3 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.70 (d, J = 8.1 Hz, 1H), 7.58 - 7.13 (m, 3H), 6.81 (d, J = 10.8 Hz, 2H), 5.06 (m, 1H), 4.46 - 4.33 (m, 1H), 4.31 - 4.20 (m, 1H), 4.17 - 4.08 (m, 1H), 3.78 (s, 3H). 7 [00135]embedded image 558.1 Method D, RT = 1.907 min, 97.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.6 Hz, 1H), 8.94 - 8.85 (m, 1H), 8.39 (dd, J= 1.6, 7.9 Hz, 1H), 7.95 - 7.83 (m, 2H), 7.73 (dd, J = 5.3, 7.7 Hz, 1H), 7.57 - 7.09 (m, 3H), 6.80 (d, J= 10.8 Hz, 2H), 5.14 (m, 1H), 4.28 (m, 1H), 4.14 (m, J= 9.3 Hz, 1H), 4.02 - 3.94 (m, 1H), 3.77 (s, 3H). 8 [00136]embedded image 555.1 Method D, RT = 2.153 min, 97.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.6 Hz, 1H), 8.05 - 7.87 (m, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.29 (m, 1H), 7.14 (m, 1H), 6.95 (m, 1H), 6.79 (d, J = 10.8 Hz, 2H), 5.13 (m, 1H), 4.24 - 4.13 (m, 1H), 4.05 (t, J = 8.8 Hz, 1H), 4.01 -3.90 (m, 1H), 3.77 (s, 3H), 3.51 (s, 3H). 9 [00137]embedded image 510.2 Method D, RT = 1.931 min, 97.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.35 (d, J = 8.3 Hz, 1H), 8.38 (d, J = 4.6 Hz, 1H), 8.03 (d, J = 8.3 Hz, 2H), 7.96 - 7.82 (m, 3H), 7.49 (m, 1H), 6.81 (d, J = 11.0 Hz, 2H), 5.13 (t, J = 9.3 Hz, 1H), 4.33 -4.16 (m, 2H), 4.15 - 4.03 (m, 1H), 3.78 (s, 3H). 10 [00138]embedded image 520.1 Method D, RT = 1.583 min, 90.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.57 - 7.12 (m, 4H), 6.81 (d, J= 10.5 Hz, 2H), 6.46 (d, J = 9.3 Hz, 1H), 6.40 (m, 1H), 4.87 - 4.73 (m, 1H), 4.37 - 4.24 (m, 1H), 4.04 (t, J = 8.7 Hz, 1H), 3.99 -3.92 (m, 1H), 3.78 (s, 3H), 3.45 (br s, 3H). 11 [00139]embedded image 538.1 Method D, RT = 1.759 min, 99.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J= 8.1 Hz, 1H), 8.03 - 7.88 (m, 2H), 7.57 - 7.45 (m, 3H), 6.82 (d, J= 10.8 Hz, 2H), 6.50 - 6.44 (m, 1H), 6.40 (dd, J = 1.0, 7.1 Hz, 1H), 4.90 - 4.76 (m, 1H), 4.37 - 4.24 (m, 1H), 4.05 (t, J = 8.8 Hz, 1H), 4.00 - 3.92 (m, 1H), 3.78 (s, 3H), 3.44 (br s, 3H). 12 [00140]embedded image 591 Method D, RT = 2.381 min, 92.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.1 Hz, 1H), 8.20 (s, 1H), 8.11 (s, 1H), 7.95 - 7.83 (m, 2H), 7.69 (s, 1H), 7.55 - 7.12 (m, 3H), 6.81 (d, J=10.8 Hz, 2H), 5.04 (m, 1H), 4.33 - 4.23 (m, 1H), 4.21 - 4.10 (m, 2H), 3.79 (s, 3H). 13 [00141]embedded image 584.2 Method D, RT = 1.784 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J= 8.1 Hz, 1H), 8.72 (d, J= 12.7 Hz, 1H), 8.59 (m, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.62 - 7.42 (m, 3H), 6.80 (d, J= 10.5 Hz, 2H), 5.03 (m, 1H), 4.47 (t, J= 9.8 Hz, 1H), 4.18 (m, 1H), 4.09 - 3.99 (m, 1H), 3.79 (s, 3H), 1.75 (s, 3H), 1.70 (s, 3H). 14 [00142]embedded image 583.2 Method D, RT = 1.414 min, 99.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.25 (m, 1H), 7.17 (s, 1H), 6.80 (d, J = 10.5 Hz, 2H), 6.70 - 6.61 (m, 1H), 5.06 (m, 1H), 4.66 (m, 1H), 4.23 - 4.05 (m, 2H), 4.04 -3.94 (m, 1H), 3.78 (s, 3H), 1.28 (d, J = 5.9 Hz, 6H). 15 [00143]embedded image 533.1 Method D, RT = 1.951 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 (d, J = 8.1 Hz, 1H), 8.81 (m, 1H), 8.45 (m, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.57 (m, 1H), 7.51 (d, J= 8.3 Hz, 2H), 6.81 (d, J = 10.8 Hz, 2H), 5.11 (m, 1H), 4.49 -4.37 (m, 1H), 4.26 (q, J = 9.5 Hz, 1H), 4.19 - 4.08 (m, 1H), 3.75 (s, 3H). 16 [00144]embedded image 529.2 Method D, RT = 2.370 min, 100.0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 9.02 (m, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.46 (m, 1H), 7.31 - 7.26 (m, 3H), 7.16 (s, 1H), 6.87 - 6.71 (m, 3H), 5.11 - 4.97 (m, 1H), 4.67 (m, 1H), 4.25 - 4.06 (m, 2H), 4.05 - 3.96 (m, 1H), 3.78 (s, 3H), 1.27 (d, J = 5.9 Hz, 6H). 17 [00145]embedded image 597.2 Method D, RT = 1.763 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.71 - 7.60 (m, 2H), 7.52 - 7.42 (m, 4H), 6.75 (d, J= 10.8 Hz, 2H), 5.13 - 4.98 (m, 2H), 4.95 - 4.87 (m, 1H), 4.02 (m, 1H), 3.75 (s, 3H), 3.61 (m, 1H), 3.52 -3.44 (m, 1H), 1.80 (s, 3H), 1.74 (s, 3H). 18 [00146]embedded image 579.2 Method D, RT = 1.607 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J= 8.1 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.71 - 7.60 (m, 2H), 7.50 - 7.41 (m, 2H), 7.35 (s, 1H), 7.29 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 10.5 Hz, 2H), 5.05 (m, 2H), 4.93 - 4.86 (m, 1H), 4.02 (m, 1H), 3.75 (s, 3H), 3.60 (m, 1H), 3.50 - 3.43 (m, 1H), 1.80 (s, 3H), 1.75 (s, 3H). 19 [00147]embedded image 583.1 Method D, RT = 1.723 min, 93.7% .sup.1H NMR (400 MHz, DMSO-d6) δ = 9.21 - 9.06 (m, 1H), 7.95 (d, J = 8.6 Hz, 2H), 7.89 - 7.79 (m, 1H), 7.74 - 7.66 (m, 1H), 7.60 - 7.52 (m, 1H), 7.52 - 7.44 (m, 3H), 6.85 - 6.72 (m, 2H), 5.12 - 4.90 (m, 1H), 4.31 - 4.16 (m, 1H), 4.13 - 3.89 (m, 2H), 3.77 (s, 3H), 1.86 - 1.58 (m, 6H). 20 [00148]embedded image 485.1 Method D, RT = 1.965 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 6.78 (s, 1H), 6.75 (s, 1H), 4.96 - 4.89 (m, 1H), 3.93 (m, 1H), 3.77 (s, 3H), 3.76 - 3.72 (m, 1H), 3.64 - 3.56 (m, 1H), 3.31 - 3.25 (m, 1H), 3.07 (m, 1H), 1.02 - 0.89 (m, 1H), 0.51 (d, J= 8.1 Hz, 2H), 0.30 - 0.20 (m, 2H). 21 [00149]embedded image 533.1 Method D, RT = 1.897 min, 96.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 (d, J = 8.3 Hz, 1H), 8.72 (m, 1H), 8.25 (m, 1H), 8.02 - 7.93 (m, 2H), 7.90 (m, 1H), 7.51 (d, J = 8.3 Hz, 2H), 6.82 (d, J = 10.8 Hz, 2H), 5.13 (m, 1H), 4.36 - 4.22 (m, 2H), 4.17 - 4.07 (m, 1H), 3.78 (s, 3H). 22 [00150]embedded image 584.1 Method D, RT = 1.620 min, 93.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J = 8.1 Hz, 1H), 8.79 - 8.70 (m, 1H), 8.33-8.31 (m, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.61 (m, 1H), 7.59 - 7.50 (m, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.10 - 4.94 (m, 1H), 4.33 - 4.23 (m, 1H), 4.15 - 4.08 (m, 1H), 4.06 - 3.97 (m, 1H), 3.78 (s, 3H), 1.91 - 1.68 (m, 6H). 23 [00151]embedded image 538.1 Method D, RT = 2.065 min, 94.0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 (d, J = 8.3 Hz, 1H), 8.25 (d, J = 5.9 Hz, 1H), 8.01 - 7.81 (m, 3H), 7.51 (d, J = 8.3 Hz, 2H), 6.85 (m, 1H), 6.79 (d, J = 10.8 Hz, 2H), 5.08 (m, 1H), 4.44 (m, 1H), 4.12 (m, 1H), 4.03 - 3.94 (m, 1H), 3.85 (s, 3H), 3.78 (s, 3H). 24 [00152]embedded image 558.1 Method D, RT = 2.223 min, 92.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 8.3 Hz, 1H), 8.09 (m, 1H), 7.96 (d, J = 8.6 Hz, 2H), 7.54 - 7.48 (m, 3H), 6.9 (s, 1 H), 6.82 - 6.74 (m, 2H), 5.11 (m, 1H), 4.46 (m, 1H), 4.17 (m, 1H), 4.06 - 3.96 (m, 1H), 3.78 (s, 3H). 25 [00153]embedded image 566.2 Method D, RT = 1.594 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 7.8 Hz, 1H), 8.82 - 8.68 (m, 1H), 8.41 - 8.28 (m, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.61 (m, 1H), 7.54 - 7.07 (m, 3H), 6.87 - 6.71 (m, 2H), 5.08 - 4.91 (m, 1H), 4.38 - 4.23 (m, 1H), 4.11 (m, 1H), 4.06 -3.94 (m, 1H), 3.78 (s, 3H), 1.86 - 1.72 (m, 6H). 26 [00154]embedded image 538.1 Method D, RT = 1.677 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.3 Hz, 1H), 8.01 (d, J = 2.9 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.87 (m, 1H), 7.50 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 6.46 (d, J = 9.8 Hz, 1H), 5.08 - 4.91 (m, 1H), 4.12 (m, 1H), 4.00 (m, 1H), 3.94 - 3.87 (m, 1H), 3.78 (s, 3H), 3.45 (s, 3H). 27 [00155]embedded image 538.1 Method D, RT = 1.874 min, 93.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 8.6 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.88 (m, 1H), 7.51 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 7.3 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.40 (m, 1H), 5.10 (m, 1H), 4.52 (d, J = 5.9 Hz, 2H), 4.44 (m, 1H), 4.12 (q, J = 9.9 Hz, 1H), 4.01 - 3.98 (m, 1H), 3.78 (s, 3H). 28 [00156]embedded image 526.1 Method D, RT = 1.926 min, 97.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 (d, J = 8.3 Hz, 1H), 8.38 (d, J = 4.4 Hz, 1H), 8.03 - 7.78 (m, 3H), 7.57 - 7.39 (m, 3H), 6.80 (d, J = 10.8 Hz, 2H), 5.11(m, 1H), 4.32 - 4.17 (m, 2H), 4.15 - 4.06 (m, 1H), 3.78 (s, 3H). 29 [00157]embedded image 565.2 Method D, RT = 2.289 min, 93.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.55 - 7.10 (m, 5H), 6.80 (d, J = 10.8 Hz, 2H), 6.69 - 6.60 (m, 1H), 5.05 (m, 1H), 4.66 (m, 1H), 4.24 - 4.04 (m, 2H), 4.02 - 3.92 (m, 1H), 3.78 (s, 3H), 1.28 (d, J = 5.9 Hz, 6H). 30 [00158]embedded image 566.2 Method D, RT = 1.529 min, 89.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 8.76 (d, J = 4.4 Hz, 1H), 8.01 - 7.94 (m, 1H), 7.92 - 7.87 (m, 2H), 7.74 - 7.67 (m, 1H), 7.31 - 7.21 (m, 3H), 6.79 - 6.71 (m, 2H), 5.14 (dd, J = 8.7, 10.6 Hz, 1H), 4.27 - 4.18 (m, 1H), 4.12 - 4.00 (m, 2H), 3.77 (s, 3H), 1.70-1.63 (m, 6H). 31 [00159]embedded image 565.1 Method D, RT = 1.604 min, 95.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 8.98 (m, 1H), 7.94 - 7.77 (m, 3H), 7.70 (t, J = 7.8 Hz, 1H), 7.61 - 7.52 (m, 1H), 7.46 (dd, J = 3.4, 7.8 Hz, 1H), 7.35 (s, 1H), 7.31 - 7.15 (m, 3H), 6.82 - 6.71 (m, 1H), 5.09 - 4.94 (m, 1H), 4.29 - 4.18 (m, 1H), 4.12 - 3.89 (m, 2H), 3.77 (s, 3H), 1.83 - 1.68 (m, 6H). 32 [00160]embedded image 520.1 Method D, RT = 1.886 min, 94.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.1 Hz, 1H), 8.25 (d, J = 5.9 Hz, 1H), 7.96 (d, J = 2.2 Hz, 1H), 7.92 - 7.86 (m, 2H), 7.36 (s, 1H), 7.29 (d, J = 8.8 Hz, 2H), 6.85 (m, 1H), 6.79 (d, J = 10.5 Hz, 2H), 5.06 (dd, J = 8.1, 11.0 Hz, 1H), 4.47 - 4.40 (m, 1H), 4.17 - 4.08 (m, 1H), 4.03 - 3.94 (m, 1H), 3.86 (s, 3H), 3.78 (s, 3H). 33 [00161]embedded image 508.1 Method D, RT = 1.790 min, 90.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J=8.6 Hz, 1H), 8.38 (d, J=4.6 Hz, 1H), 7.96 - 7.84 (m, 3H), 7.56 - 7.13 (m, 4H), 6.80 (d, J=10.8 Hz, 2H), 5.17 - 5.01 (m, 1H), 4.32 - 4.17 (m, 2H), 4.15 - 4.03 (m, 1H), 3.78 (s, 3H). 34 [00162]embedded image 520.2 Method D, RT = 1.564 min, 99.4% .sup.1H NMR (400 MHz, DMSO-d6) δ = 9.01 (d, J = 8.8 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.76 (m, 1H), 7.59 (m, 1H), 7.55 - 7.11 (m, 3H), 6.77 (d, J = 10.8 Hz, 2H), 6.33 (m, 1H), 5.11 (m, 1H), 4.17 - 4.03 (m, 1H), 3.98 (m, 2H), 3.77 (s, 3H), 3.51 (s, 3H). 35 [00163]embedded image 618.3 Method D, RT = 1.881 min, 94.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.55 - 7.13 (m, 4H), 6.79 (d, J = 10.5 Hz, 2H), 6.14 (d, J = 1.5 Hz, 1H), 5.08 (m, 1H), 4.43 (m, 1H), 4.06 (m, 1H), 3.92 - 3.84 (m, 1H), 3.79 (d, J = 7.6 Hz, 6H), 3.48 (m, 4H), 2.49 - 2.35 (m, 4H), 2.25 (s, 3H). 36 [00164]embedded image 564.2 Method D, RT = 1.640 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.67 (dd, J = 6.8, 2.0 Hz, 1H), 7.60 (dd, J = 7.3, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.20 - 4.03 (m, 3H), 4.02 - 3.94 (m, 2H), 3.77 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 37 [00165]embedded image 582.2 Method D, RT = 1.808 min, 95.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.6 Hz, 1H), 8.00 - 7.87 (m, 2H), 7.67 (dd, J = 6.8, 2.0 Hz, 1H), 7.60 (dd, J = 7.3 Hz, 2.0, 1H), 7.49 (d, J = 7.8 Hz, 2H), 6.78 (d, J= 10.8 Hz, 2H), 6.33 (t, J= 7.0 Hz, 1H), 5.13 (dd, J = 11.0, 8.6 Hz, 1H), 4.19 - 3.93 (m, 5H), 3.77 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 38 [00166]embedded image 534.2 Method D, RT = 1.651 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.77 (dd, J = 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.1, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 (d, J = 8.6 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.16 -4.04 (m, 1H), 4.02 - 3.92 (m, 4H), 3.77 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H). 39 [00167]embedded image 488.1 Method D, RT = 1.73 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.8 Hz, 1H), 8.10 (dd, J= 4.6, 1.2 Hz, 1H), 7.90 - 7.77 (m, 2H), 7.64 (dd, J = 8.4, 1.2 Hz, 1H), 7.61 - 7.53 (m, 2H), 7.44-7.41 (m, 1H), 6.79 (d, J = 10.8 Hz, 2H), 5.22 (dd, J = 11.1, 8.9 Hz, 1H), 4.23 - 4.11 (m, 1H), 4.05 (t, J = 8.9 Hz, 1H), 3.93 - 3.89 (m, 1H), 3.87 (s, 3H) 3.77 (s, 3H). 40 [00168]embedded image 598.2 Method D, RT = 1.68 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.3 Hz, 1H), 7.84 - 7.82 (m, 2H), 7.59 - 7.56 (m, 2H), 7.22 (d, J = 2.0 Hz, 1H), 6.79 (d, J =10.8 Hz, 2H), 5.80 (s, 1H), 5.11 - 5.06 (m, 1H), 4.59 (br s, 1H), 4.45 (t, J= 9.9 Hz, 1H), 4.08 - 3.98 (m, 1H), 3.90 - 3.81 (m, 2H), 3.78 (s, 3H), 3.77 (s, 3H), 3.45 - 3.38 (m, 2H), 3.25 -3.22 - 3.19 (m, 1H), 2.82 - 2.76 (m, 1H), 2.24 (s, 3H), 1.83 - 1.79 (m, 1H), 1.71 -1.63 (m, 1H). 41 [00169]embedded image 593.3 Method D, RT = 1.424 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.8 Hz, 1H), 7.96 - 7.81 (m, 2H), 7.68 (dd, J = 7.0, 1.8, Hz, 1H), 7.55 (dd, J= 7.2, 1.8 Hz, 1H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.34 (t, J = 7.1 Hz, 1H), 5.10 (dd, J = 10.8, 8.6 Hz, 1H), 5.01 -4.88 (m, 1H), 4.15 - 4.03 (m, 1H), 4.03 -3.89 (m, 2H), 3.80 - 3.71 (m, 4H), 3.61 (dd, J= 10.5, 4.4 Hz, 1H), 3.34 (br s, 2H), 3.23 (s, 3H), 2.95 - 2.81 (m, 2H). 42 [00170]embedded image 634.2 Method D, RT = 2.634 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 9.04 (m, 1H), 7.93 - 7.84 (m, 2H), 7.70 - 7.57 (m, 1H), 7.34 (t, J = 72 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.89 - 6.74 (m, 3H), 5.16 - 5.07 (m, 1H), 4.26 - 4.15 (m, 2H), 4.06 - 3.93 (m, 3H), 3.76 (s, 3H), 2.56 -2.47 (m, 2H), 2.17 (s, 3H), 2.16 - 2.10 (m, 2H), 1.12 - 1.03 (d, J = 6 Hz, 6H). 43 [00171]embedded image 529.15 Method D, RT = 1.97 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.6 Hz, 1H), 8.07 (dd, J= 4.6, 1.2 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.61 (d, J = 7.3 Hz, 1 H), 7.57 - 7.49 (m, 2H), 7.37 (dd, J = 8.3, 4.6 Hz, 1H), 6.84 - 6.70 (m, 2H), 5.60 (dd, J = 11.5, 8.8 Hz, 1H), 4.74-4.68 (m, 1H), 4.54 - 4.44 (m, 1H), 4.40-4.35 (m, 1H), 3.77 (s, 3H), 1.28 (d, J= 6.0 Hz, 3H), 1.27 (d, J= 6.0 Hz, 3H), 0.90 (d, J= 6.6 Hz, 3H). 44 [00172]embedded image 593.3 Method D, RT = 1.427 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.68 (dd, J = 7.0, 1.8 Hz, 1H), 7.56 (dd, J= 7.1, 1.8 Hz, 1H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.34 (t, J = 7.1 Hz, 1H), 5.13 (dd, J = 10.8, 8.8 Hz, 1H), 5.02 - 4.90 (m, 1H), 4.15 - 3.88 (m, 3H), 3.81 - 3.70 (m, 4H), 3.61 (dd, J= 10.8, 4.4 Hz, 1H), 3.35 - 3.33 (br s, 2H), 3.20 (s, 3H), 2.96 - 2.84 (m, 2H). 45 [00173]embedded image 570.2 Method D, RT = 1.84 min, 96.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 8.01 - 7.91 (m, 2H), 7.72 (dd, J= 7.0, 1.8 Hz, 1H), 7.66 (dd, J = 7.1, 1.8 Hz, 1H), 7.55 - 7.35 (m, 3H), 6.89 - 6.74 (m, 2H), 6.43 - 6.40 (m, 1H), 6.35 (t, J = 57.6 Hz, 1H), 5.14 (dd, J = 11.4, 8.7 Hz, 1H), 4.49 - 4.43 (m, 2H), 4.20 - 4.09 (m, 1H), 4.07 - 3.97 (m, 1H), 3.76 (s, 3H), 3.75 - 3.67 (m, 1H). 46 [00174]embedded image 577.2 Method D, RT = 1.862 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.3 Hz, 1H), 8.01 - 7.74 (m, 3H), 7.74 - 7.28 (m, 3H), 7.36 (t, J = 72 Hz, 1H), 6.81 (d, J= 10.8 Hz, 2H), 5.11 (m, 1H), 4.33 - 4.15 (m, 2H), 4.12 - 3.98 (m, 1H), 3.78 (s, 3H), 3.76 - 3.57 (m, 2H), 3.13 (t, J = 4.4 Hz, 2H). 47 [00175]embedded image 636.2 Method D, RT = 1.904 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 9.04 (m, 1H), 7.99 - 7.86 (m, 2H), 7.70 (dd, J = 6.8, 2.0 Hz, 1H), 7.66 (dd, J = 7.3, 2.0 Hz, 1H), 7.53 - 7.39 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.16 - 5.02 (m, 1H), 4.45 (dd, J = 13.2, 2.9 Hz, 1H), 4.37 - 4.25 (m, 1H), 4.19 - 3.98 (m, 2H), 3.98 - 3.80 (m, 2H), 3.76 (s, 3H), 3.35 - 3.33 (brs, 1H). 48 [00176]embedded image 616.3 Method D, RT = 1.939 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.3 Hz, 1H), 7.94 - 7.82 (m, 2H), 7.64 - 7.56 (m, 2H), 7.36 (t, J = 72 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.86 - 6.73 (m, 2H), 6.63 (dd, J = 6.1, 2.9 Hz, 1H), 5.07 (dd, J= 11.0, 9.0 Hz, 1H), 4.51 - 4.39 (m, 1H), 4.14 - 3.98 (m, 3H), 3.97 - 3.87 (m, 1H), 3.78 (s, 3H), 3.34 - 3.28 (m, 2H), 2.17 (s, 3H), 2.17 - 2.03 (m, 2H), 1.06 (d, J= 5.9 Hz, 6H). 49 [00177]embedded image 612.3 Method D, RT = 1.74 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.57 (d, J= 8.4 Hz, 2H), 6.90 - 6.69 (m, 3H), 5.85 (s, 1H), 4.99 (dd, J = 10.8, 8.3 Hz, 1H), 4.61 - 4.38 (m, 2H), 3.79 (s, 3H), 3.78 (s, 3H), 3.64-3.61 (m, 2H), 3.45 - 3.42 (m, 1H), 3.23 - 3.21 (m, 1H), 2.80 (dd, J = 9.3, 2.0 Hz, 1H), 2.42-2.44 (m, 1H), 2.25 (s, 3H), 1.92 - 1.77 (m, 1H), 1.71-1.68 (m, 1H), 1.36 (d, J = 5.9 Hz, 3H). 50 [00178]embedded image 618.2 Method D, RT = 2.407 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 - 9.03 (m, 1H), 7.93 - 7.86 (m, 2H), 7.59 - 7.56 (m, 1H), 7.35 (t, J = 72 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.84 - 6.74 (m, 2H), 6.51 - 6.43 (m, 1H), 5.17 - 5.07 (m, 1H), 4.55 - 4.48 (m, 1H), 4.20 - 4.11 (m, 2H), 4.02 - 3.93 (m, 1H), 3.77 (s, 3H), 3.44 -3.38 (m, 3H), 2.83 - 2.76 (m, 1H), 2.47 -2.39 (m, 1H), 2.25 (s, 3H), 1.87 - 1.82 (m, 1H), 1.74 - 1.69 (m, 1H). 51 [00179]embedded image 644.3 Method D, RT = 1.69 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.86 (d, J= 8.6 Hz, 1H), 7.93 - 7.82 (m, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.27 - 7.25 (m, 3H), 6.87 - 6.70 (m, 2H), 5.78 (d, J= 1.7 Hz, 1H), 5.65 (dd, J = 12.8, 8.4 Hz, 1H), 4.94 - 4.83 (m, 1H), 4.58 — 4.53 (m, 1H), 4.26 - 4.21 (m, 1H), 3.77 (s, 3H), 3.76 (s, 3H), 3.43 - 3.37 (m, 1H), 3.40 - 3.36 (m, 1H), 3.26 - 3.24 (m, 1H), 2.79-2.76 (m, 1H), 2.46 - 2.37 (m, 1H), 2.27 (s, 3H), 1.82 - 1.7 (m, 1H), 1.75 - 1.64 (m, 1H), 1.18 (d, J = 6.4 Hz, 3H). 52 [00180]embedded image 556.2 Method D, RT = 1.764 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J= 8.6 Hz, 1H), 7.92 (t, J = 59.2 Hz, 1H) 7.92 (t, J= 67.2 Hz, 1H), 7.89 - 7.74 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H) 7.28 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.56 (t, J = 7.2 Hz, 1H), 5.08 (dd, J = 11.0, 8.6 Hz, 1H), 4.20 - 4.07 (m, 1H), 4.06 - 3.94 (m, 2H), 3.77 (s, 3H). 53 [00181]embedded image 564.3 Method D, RT = 1.70 min, 94.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.64 (d, J= 8.0 Hz, 1H), 7.81 - 7.55 (m, 4H), 7.50 - 7.23 (m, 3H), 6.79 - 6.57 (m, 2H), 6.36 (t, J = 7.0 Hz, 1H), 5.24 - 5.11 (m, 1H), 4.23 - 4.04 (m, 5H), 3.72 (s, 3H), 3.66 - 3.57 (m, 2H), 3.24 (s, 3H). 54 [00182]embedded image 606.2 Method D, RT = 1.805 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (br d, J = 8.1 Hz, 1H), 7.93 - 7.82 (m, 2H), 7.63 (t, J = 9.3 Hz, 1H), 7.34 (t, J = 72 Hz, 1H), 7.29 - 7.6 (m, 2H), 6.86 -6.73 (m, 3H), 5.12 (t, J = 9.4 Hz, 1H), 4.25 - 4.13 (m, 2H), 4.03 - 3.94 (m, 1H), 3.78 (s, 3H), 3.48 - 3.42 (m, 4H), 2.48 -2.36 (m, 4H), 2.25 (s, 3H). 55 [00183]embedded image 584.2 Method D, RT = 1.81 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.8 Hz, 1H), 7.96 - 7.85 (m, 2H), 7.77 (dd, J = 6.8, 2.0 Hz, 1H), 7.63 (dd, J= 7.3, 2.0 Hz, 1H), 7.51 (d, J= 8.1 Hz, 1H), 7.35 (t, J= 72.0 Hz, 1H), 7.32 - 7.23 (m, 2H), 6.86 - 6.74 (m, 2H), 6.38 (t, J = 7.1 Hz, 1H), 5.13 (dd, J = 11.5, 8.8 Hz, 1H), 4.30 - 4.09 (m, 3H), 4.04 - 3.94 (m, 1H), 3.74 (s, 3H), 3.73 - 3.64 (m, 1H), 2.84 - 2.70 (m, 2H). 56 [00184]embedded image 564.2 Method D, RT = 1.75 min, 98.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 8.04 - 7.88 (m, 2H), 7.65 (dd, J= 6.7, 2.1 Hz, 1H), 7.59 (dd, J = 7.1, 2.0 Hz, 1H), 7.55 - 7.37 (m, 3H), 6.90 - 6.70 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.2, 8.8 Hz, 1H), 4.22 - 4.06 (m, 3H), 4.05 - 3.94 (m, 1H), 3.74 (s, 3H), 3.72 - 3.65 (m, 1H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 57 [00185]embedded image 556.3 Method D, RT = 1.881 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (t, J = 8.6 Hz, 1H), 8.06 - 7.91 (m, 2H), 7.75 - 7.60 (m, 1H), 7.57 - 7.42 (m, 2H), 7.42 - 7.22 (m, 2H), 6.91 (dd, J = 13.8, 8.7 Hz, 2H), 6.22 (d, J = 6.8 Hz, 1H), 5.28 - 4.66 (m, 1H), 4.14 - 3.78 (2 s, 3H), 3.77 - 3.64 (m, 5H), 2.21 - 2.07 (2 s, 3H), 1.27 - 1.08 (m, 1H), 0.55 - 0.43 (m, 2H), 0.44 - 0.32 (m, 2H). (mixture of interconvertible atropisomers) 58 [00186]embedded image 625.2 Method D, RT = 1.87 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J= 8.5 Hz, 1H), 8.07 - 8.00 (m, 1H), 7.99 - 7.87 (m, 3H), 7.55 - 7.45 (m, 2H), 6.80 (d, J = 10.5 Hz, 2H), 5.15-5.10 (m, 1H), 4.33 - 4.18 (m, 4H), 4.12 - 4.04 (m, 1H), 4.02 - 3.88 (m, 4H), 3.90 (s, 3H). 59 [00187]embedded image 552.2 Method D, RT = 1.75 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.8 Hz, 1H), 7.96 - 7.86 (m, 2H), 7.72 (dd, J= 6.8, 2.0 Hz, 1H), 7.66 (dd, J = 7.3, 2.0 Hz, 1H), 7.55 - 7.49 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.33 - 7.25 (m, 2H), 6.85 - 6.75 (m, 2H), 6.42 (t, J= 7.2 Hz, 1H), 6.35 (t, J = 57.6 Hz, 1H), 5.13 (dd, J= 11.4, 8.7 Hz, 1H), 4.53 - 4.37 (m, 2H), 4.20 - 4.10 (m, 1H), 4.05 - 3.95 (m, 1H), 3.74 (s, 3H), 3.70 (t, J= 9.5 Hz, 1H). 60 [00188]embedded image 546.2 Method D, RT = 1.69 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 8.08 - 7.91 (m, 2H), 7.64 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.41 - 7.30 (m, 2H), 7.01 - 6.83 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.02 (dd, J = 11.1, 8.7 Hz, 1H), 4.19 - 4.04 (m, 3H), 3.82 - 3.67 (m, 5H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 61 [00189]embedded image 502.1 Method D, RT = 1.606 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.95 (m, 1H), 7.90 - 7.80 (m, 2H), 7.71 - 7.62 (m, 1H), 7.60 - 7.44 (m, 2H), 6.82 - 6.69 (m, 2H), 6.25 - 6.16 (m, 1H), 5.34 - 4.84 (m, 1H), 4.27 - 4.05 (m, 2H), 3.79 - 3.70 (2 s, 3H), 3.53 - 3.38 (m, 4H), 2.22 - 1.98 (2 s, 3H). (Mixture of interconvertible atropisomers) 62 [00190]embedded image 611.2 Method D, RT = 1.99 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.6 Hz, 1H), 8.03 - 7.87 (m, 2H), 7.54 - 7.40 (m, 3H), 6.97 (d, J = 5.6 Hz, 1H), 6.79 (d, J = 11.0 Hz, 2H), 6.47 (dd, J= 8.8, 2.7 Hz, 1H), 5.16 - 5.05 (m, 1H), 4.27 - 4.09 (m, 3H), 4.04 - 3.94 (m, 1H), 3.89 (dd, J = 8.8, 5.9 Hz, 1H), 3.85 - 3.77 (m, 1H), 3.76 (s, 3H), 3.73 - 3.69 (m, 1H), 3.51-3.47 (m, 1H), 2.23 - 2.08 (m, 1H), 1.82 - 1.71 (m, 1H). 63 [00191]embedded image 550.2 Method D, RT = 1.62 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.8 Hz, 1H), 8.05 - 7.84 (m, 2H), 7.64 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.54 - 7.43 (m, 3H), 6.89 - 6.71 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.13 (dd, J= 11.4, 8.7 Hz, 1H), 4.92 (t, J = 5.4 Hz, 1H), 4.18 - 4.09 (m, 1H), 4.05 - 3.92 (m, 1H), 4.07 - 3.92 (m, 2H), 3.74 (s, 3H), 3.71 (br d, J = 9.5 Hz, 1H), 3.68 - 3.59 (m, 2H). 64 [00192]embedded image 532.2 Method D, RT = 2.147 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.5 Hz, 1H), 8.06 - 7.95 (m, 2H), 7.62 (m, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.40 - 7.31 (m, 2H), 6.95 - 6.85 (m, 2H), 6.36 - 6.28 (m, 1H), 5.06 - 4.95 (m, 1H), 4.93- 4.89 (m, 1H), 4.16 - 3.98 (m, 3H), 3.78 - 3.67 (m, 5H), 3.65 - 3.60 (m, 2H). 65 [00193]embedded image 668.2 Method D, RT = 1.68 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (br d, J= 8.1 Hz, 1H), 8.34 (d, J = 4.9 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.36 (t, J= 73.6 Hz, 1H),7.28 (d, J = 8.4 Hz, 2H), 6.86 (br d, J = 4.9 Hz, 1H), 6.80 (br d, J = 10.8 Hz, 2H), 5.09 - 4.89 (m, 1H), 4.23 - 4.12 (m, 1H), 4.09 - 3.98 (m, 1H), 3.98 - 3.86 (m, 1H), 3.77 (s, 3H), 3.57 - 3.41 (m, 2H), 3.30 - 3.20 (m, 2H), 2.85 - 2.69 (m, 2H), 2.30 (br s, 3H), 1.96 - 1.84 (m, 1H), 1.80 - 1.64 (m, 1H). 66 [00194]embedded image 617.2 Method D, RT = 2.009 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J= 8.6 Hz, 1H), 7.97 - 7.81 (m, 3H), 7.58 (dd, J = 2.8, 8.7 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.87 - 6.68 (m, 2H), 5.17 - 5.05 (m, 1H), 4.58 (t, J = 3.7 Hz, 1H), 4.28 - 4.14 (m, 2H), 4.09 - 4.03 (m, 1H), 3.77 (s, 3H), 3.68 -3.62 (m, 1H), 2.27 - 2.21 (m, 1H), 1.97 -1.89 (m, 1H), 1.85 - 1.78 (m, 1H), 1.72 -1.63 (m, 1H), 1.56 - 1.37 (m, 2H). 67 [00195]embedded image 520.2 Method D, RT = 1.899 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 8.03 - 7.91 (m, 2H), 7.75 (dd, J = 6.6, 2.0 Hz, 1H), 7.58 (dd, J = 7.2, 2.1 Hz, 1H), 7.53 - 7.44 (m, 4H), 7.44 - 7.32 (m, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.05 (dd, J= 10.9, 8.7 Hz, 1H), 4.22 - 4.11 (m, 1H), 4.04 - 3.88 (m, 2H), 3.88 - 3.70 (m, 2H), 1.24 (t, J= 7.1 Hz, 3H). 68 [00196]embedded image 613.2 Method D, RT = 1.76 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 (d, J = 8.3 Hz, 1H), 8.43 (d, J = 5.6 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.35 (t, J= 73.2 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 5.4 Hz, 1H), 6.90 - 6.72 (m, 2H), 5.14 - 4.98 (m, 1H), 4.32 - 4.02 (m, 3H), 3.91 (s, 3H), 3.83 - 3.72 (m, 4H), 3.72 - 3.61 (m, 4H), 2.56 (s, 3H). 69 [00197]embedded image 556.2 Method D, RT = 1.970 min, 97.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 8.03 - 7.91 (m, 2H), 7.72 (d, J = 6.8 Hz, 1H), 7.66 (td, J = 1.1, 7.2 Hz, 1H), 7.48 (d, J = 8.6 Hz, 4H), 7.44 - 7.29 (m, 2H), 6.42 (m, 1H), 6.34 (t, J = 3.6 Hz, 1 H), 6.40 (t, J = 59.6 Hz, 1H), 5.05 (dd, J= 8.9, 10.9 Hz, 1H), 4.56 - 4.29 (m, 2H), 4.17 (t, J = 7.7 Hz, 1H), 3.89 - 3.72 (m, 2H) 70 [00198]embedded image 612.3 Method D, RT = 1.74 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.3 Hz, 1H), 7.91 - 7.74 (m, 2H), 7.63 - 7.47 (m, 2H), 7.26 (s,, 1H), 6.90 -6.68 (m, 2H), 5.78 (d, J = 1.7 Hz, 1H), 5.66-5.63 (m, 1H), 4.96 - 4.79 (m, 1H), 4.58 - 4.53 (m, 1H), 4.25 - 4.20 (m, 1H), 3.77 (s, 3H), 3.76 (s, 3H), 3.42 -3.37 (m, 2H), 3.26 - 3.21 (m, 1H), 2.79-2.77 (m, 1H), 2.41 (d, J = 9.0 Hz, 1H), 2.26 (s, 3H), 1.81-1.79 (m, 1H), 1.72-1.69 (m, 1H), 1.18 (d, J = 6.6 Hz, 3H). 71 [00199]embedded image 644.2 Method D, RT = 1.58 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.6 Hz, 1H), 7.96 - 7.80 (m, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.29-7.27 (m, 2H), 6.93 - 6.66 (m, 3H), 5.85 (s, 1H), 4.99 (dd, J = 10.8, 8.3 Hz, 1H), 4.58 -4.39 (m, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.64-3.61 (m, 1H), 3.45 - 3.42 (m, 1H), 3.37 - 3.29 (m, 1H), 3.23-3.21 (m, 1H), 2.80 (dd, J= 9.0, 1.7 Hz, 1H), 2.44 (br d, J= 9.0 Hz, 1H), 2.25 (s, 3H), 1.90 - 1.78 (m, 1H), 1.71-1.68 (m, 1H), 1.36 (d, J= 5.9 Hz, 3H). 72 [00200]embedded image 570.2 Method C, RT = 1.927 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.6 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.77 (dd, J = 6.8, 2.0 Hz, 1H), 7.63 (dd, J= 7.2, 1.8 Hz, 1H), 7.51 - 7.37 (m, 4H), 7.35 (t, J = 73.2 Hz, 1H), 7.30 - 7.32 (m, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.04 (dd, J = 11.1, 8.7 Hz, 1H), 4.26 - 4.11 (m, 3H), 3.88 - 3.72 (m, 2H), 2.83 - 2.70 (m, 2H). 73 [00201]embedded image 588.2 Method D, RT = 2.086 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.6 Hz, 1H), 8.02 - 7.93 (m, 2H), 7.77 (dd, J = 6.8, 2.0 Hz, 1H), 7.63 (dd, J = 7.1, 2.0 Hz, 1H), 7.52 - 7.46 (m, 4H), 7.44 - 7.35 (m, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.05 (dd, J= 11.0, 8.8 Hz, 1H), 4.26 - 4.15 (m, 3H), 3.89 - 3.71 (m, 2H), 2.85 - 2.71 (m, 2H). 74 [00202]embedded image 546.2 Method D, RT = 1.69 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.30 (d, J = 5.5 Hz, 1H), 7.68 (dd, J= 7.0, 2.0 Hz, 1H), 7.64 - 7.56 (m, 2H), 7.49 - 7.33 (m, 3H), 6.75 - 6.59 (m, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 9.0, 5.5 Hz, 1H), 4.90 - 4.87 (m, 1H), 4.63-4.61 (m, 1H), 4.23 - 4.06 (m, 2H), 3.72 (s, 3H), 3.61 (t, J= 5.8 Hz, 2H), 3.25 (s, 3H), 0.70 (d, J= 6.5 Hz, 3H). 75 [00203]embedded image 602.2 Method D, RT = 1.98 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 8.04 - 7.89 (m, 2H), 7.77 (dd, J= 6.8, 2.0 Hz, 1H), 7.63 (dd, J = 7.3, 2.0 Hz, 1H), 7.57 - 7.39 (m, 3H), 6.92 - 6.70 (m, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.14 (dd, J= 11.4, 8.7 Hz, 1H), 4.29 - 4.09 (m, 3H), 4.06 - 3.94 (m, 1H), 3.75 (s, 3H), 3.74 - 3.61 (m, 1H), 2.87 - 2.68 (m, 2H) 76 [00204]embedded image 502.2 Method D, RT = 1.78 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 9.0 Hz, 1H), 8.11 (dd, J= 4.6, 1.5 Hz, 1H), 7.91 - 7.76 (m, 2H), 7.64 (dd, J = 8.3, 1.5 Hz, 1H), 7.59 - 7.49 (m, 2H), 7.42 (dd, J = 4.6, 8.3 Hz, 1H), 6.87 - 6.70 (m, 2H), 5.67 (dd, J = 12.0, 8.6 Hz, 1H), 4.58 - 4.46 (m, 1H), 4.40-4.35 (m, 1H), 3.85 (s, 3H), 3.77 (s, 3H), 0.92 (d, J= 6.8 Hz, 3H). 77 [00205]embedded image 534.2 Method D, RT = 1.76 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.88 (d, J = 8.8 Hz, 1H), 8.11 (dd, J= 4.6, 1.5 Hz, 1H), 7.95 - 7.83 (m, 2H), 7.64 (dd, J = 8.6, 1.5 Hz, 1H), 7.43-7.40 (m, 1 H), 7.35 (t, J = 73.6 Hz, 1H), 7.26-7.24 (m, 2H), 6.85 - 6.72 (m, 2H), 5.67 (dd, J = 11.7, 8.6 Hz, 1H), 4.60 - 4.48 (m, 1H), 4.41-4.36 (m, 1H), 3.86 (s, 3H), 3.77 (s, 3H), 0.92 (d, J = 6.6 Hz, 3H). 78 [00206]embedded image 611.3 Method C, RT = 1.525 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.68 (dd, J = 7.0, 1.7 Hz, 1H), 7.56 (dd, J = 7.1, 1.7 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.34 (t, J= 7.1 Hz, 1H), 5.13 (dd, J = 10.8, 8.8 Hz, 1H), 5.02 - 4.90 (m, 1H), 4.15 - 3.88 (m, 4H), 3.81 - 3.70 (m, 4H), 3.61 (dd, J = 10.8, 4.4 Hz, 1H), 3.24 - 3.18 (m, 4H), 2.96 - 2.84 (m, 2H). 79 [00207]embedded image 514.2 Method D, RT = 1.36 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.93 (d, J= 8.8 Hz, 1H), 7.99 - 7.83 (m, 2H), 7.63 (dd, J= 6.7, 2.1 Hz, 1H), 7.58 (dd, J = 7.1, 2.1 Hz, 1H), 7.33 (t, J = 73.6 Hz, 1H), 7.36 - 7.25 (m, 4H), 6.98 - 6.77 (m, 2H), 6.35 - 6.23 (m, 1H), 5.06 - 4.87 (m, 2H), 4.16 - 3.96 (m, 3H), 3.82 - 3.68 (m, 5H), 3.65 (br s, 2H). 80 [00208]embedded image 548.2 Method D, RT = 1.68 min, 100% 1H NMR (400 MHz, DMSO-d6) δ = 8.86 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 7.2, 1.8 Hz, 1H), 7.57 (dd, J = 7.2, 1.8 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.25 - 7.23 (m, 2H), 6.77 (d, J= 11.5 Hz, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.66 (dd, J = 12.0, 8.8 Hz, 1H), 4.69 - 4.58 (m, 1H), 4.333-4.28 (m, 1H), 4.14 - 3.98 (m, 1H), 3.98 - 3.87 (m, 1H), 3.76 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H). 81 [00209]embedded image 546.2 Method D, RT = 1.57 min, 95.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.8 Hz, 1H), 7.97 - 7.86 (m, 2H), 7.65 (dd, J= 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 7.1, 2.0 Hz, 1H), 7.55 - 7.46 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.32 - 7.23 (m, 2H), 6.87 - 6.74 (m, 2H), 6.36 - 6.26 (m, 1H), 5.13 (dd, J= 11.4, 8.9 Hz, 1H), 4.19 - 4.05 (m, 3H), 4.04 - 3.95 (m, 1H), 3.74 (s, 3H), 3.73 - 3.65 (m, 1H), 3.60 (t, J = 5.4 Hz, 2H), 3.25 (s, 3H). 82 [00210]embedded image 534.2 Method D, RT = 1.77 min, 98.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.8 Hz, 1H), 8.00 - 7.92 (m, 2H), 7.75 (dd, J= 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.3, 2.0 Hz, 1H), 7.54 - 7.43 (m,3H), 6.86 - 6.73 (m, 2H), 6.39 - 6.29 (m, 1H), 5.13 (dd, J = 11.4, 8.9 Hz, 1H), 4.19 -4.09 (m, 1H), 4.04 - 3.93 (m, 3H), 3.74 (s, 3H), 3.73 - 3.64 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H). 83 [00211]embedded image 516.2 Method D, RT = 1.58 min, 96.07% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.8 Hz, 1H), 7.98 - 7.84 (m, 2H), 7.75 (dd, J = 6.6, 2.0 Hz, 1H), 7.58 - 7.51 (m, 1H), 7.35 (t, 72.0 Hz, 1H), 7.28 - 7.19 (m, 3H), 6.91 - 6.69 (m, 2H), 6.39 - 6.31 (m, 1H), 5.13 (dd, J = 11.5, 8.8 Hz, 1H), 4.20 - 4.08 (m, 1H), 4.06 - 3.89 (m, 3H), 3.74 (s, 3H), 3.73 - 3.61 (m, 1H), 1.24 (t, J= 7.1 Hz, 3H). 84 [00212]embedded image 611.2 Method D, RT = 1.99 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.6 Hz, 1H), 7.99 - 7.86 (m, 2H), 7.54 - 7.41 (m, 3H), 6.96 (d, J = 5.9 Hz, 1H), 6.79 (d, J = 10.8 Hz, 2H), 6.47 (dd, J= 8.9, 2.6 Hz, 1H), 5.16 - 5.05 (m, 1H), 4.28 - 4.18 (m, 1H), 4.18 - 4.07 (m, 2H), 4.03 - 3.94 (m, 1H), 3.89-3.86 (m, 1H), 3.84 - 3.77 (m, 1H), 3.76 (s, 3H), 3.70 (dt, J= 8.1, 5.7 Hz, 1H), 3.51-3.49 (m, 1H), 2.19-2.16 (m, 1H), 1.83 - 1.73 (m, 1H). 85 [00213]embedded image 595.3 Method D, RT = 1.651 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 8.01 - 7.89 (m, 2H), 7.70 (dd, J= 2.0, 6.8 Hz, 1H), 7.58 (dd, J = 7.3, 2.0 Hz, 1H), 7.49 (dd, J = 8.8, 1.0 Hz, 2H), 6.84 - 6.72 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 8.6, 11.0 Hz, 1H), 4.14 - 3.91 (m, 5H), 3.77 (s, 3H), 2.18 (s, 6H), 2.14 - 1.73 (m, 2H). 86 [00214]embedded image 602.2 Method D, RT = 1.93 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 8.96 (m, 1H), 8.04 - 7.84 (m, 2H), 7.74 - 7.58 (m, 1H), 7.55 - 7.37 (m, 2H), 6.90 - 6.68 (m, 2H), 6.51 - 6.12 (m, 2H), 5.38 - 4.83 (m, 1H), 4.52 - 4.31 (m, 2H), 4.30 - 4.00 (m, 2H), 3.82 - 3.73 (m, 3H), 3.59 - 3.49 (m, 1H), 2.26 - 1.97 (2 s, 3H). (mixture of interconvertible atropisomers) 87 [00215]embedded image 474.1 Method D, RT = 1.491 min, 95.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 12.03 (br dd, J = 3.8, 2.3 Hz, 1H), 9.06 (br d, J = 8.8 Hz, 1H), 7.88 - 7.80 (m, 2H), 7.61 (dd, J = 7.1, 2.0 Hz, 1H), 7.59 - 7.51 (m, 2H), 7.40 (dd, J = 1.3, 6.2 Hz, 1H), 6.77 (d, J = 10.8 Hz, 2H), 6.30 (t, J = 6.8 Hz, 1H), 5.12 (dd, J= 10.5, 8.8 Hz, 1H), 4.15 - 3.87 (m, 3H), 3.77 (s, 3H). 88 [00216]embedded image 498.2 Method D, RT = 1.519 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.8 Hz, 1H), 7.98 - 7.86 (m, 2H), 7.74 (dd, J= 6.7,2.1 Hz, 1H), 7.57 (dd, J = 7.3, 2.0 Hz, 1H), 7.34 (t, J = 80.0 Hz, 1H), 7.35 - 7.27 (m, 4H), 6.97 - 6.83 (m, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.01 (dd, J = 11.2, 8.8 Hz, 1H), 4.18 - 4.08 (m, 1H), 4.04 - 3.90 (m, 2H), 3.83 - 3.63 (m, 5H), 1.24 (t, J= 7.2 Hz, 3H). 89 [00217]embedded image 582.2 Method D, RT = 1.693 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 8.00 - 7.85 (m, 2H), 7.62 (dd, J= 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.2, 2.1 Hz, 1H), 7.53 - 7.39 (m, 2H), 6.76 (d, J= 10.8 Hz, 2H), 6.31 (t, J= 7.1 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.94 (br d, J = 5.4 Hz, 1H), 4.16 - 3.88 (m, 5H), 3.76 (s, 3H), 3.65 (dd, J = 13.0, 8.1 Hz, 1H), 1.09 (d, J = 6.1 Hz, 3H). 90 [00218]embedded image 584.2 Method D, RT = 1.765 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.90 (m, 1H), 7.99 - 7.83 (m, 2H), 7.74 - 7.59 (m, 1H), 7.35 (t, J = 68 Hz, 1 H), 7.56 - 7.07 (m, 2H), 6.84 - 6.69 (m, 2H), 6.54 - 6.11 (m, 2H), 5.39 - 4.80 (m, 1H), 4.51 - 4.02 (m, 4H), 3.82 - 3.71 (m, 3H), 3.58 - 3.41 (m, 1H), 2.25 - 1.95 (2 s, 3H). (mixture of interconvertible atropisomers) 91 [00219]embedded image 534.2 Method D, RT = 1.597 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.93 (d, J = 8.8 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.72 (dd, J = 7.0, 2.1 Hz, 1H), 7.66 (dd, J = 7.3, 2.0 Hz, 1H), 7.35 (t, J = 72.4 Hz, 1 H), 7.34 - 7.25 (m, 4H), 6.94 - 6.85 (m, 2H), 6.34 (tt, J = 52.2, 4 Hz, 1H), 6.41 (t, J = 8 Hz, 1H), 5.02 (dd, J= 11.1, 8.9 Hz, 1H), 4.54 - 4.41 (m, 2H), 4.17 - 4.08 (m, 1H), 3.79 - 3.70 (m, 5H). 92 [00220]embedded image 635.2 Method D, RT = 1.615 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.94 - 7.83 (m, 2H), 7.72 (dd, J= 7.1, 2.0 Hz, 1H), 7.61 (dd, J = 7.2, 1.8 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 1H), 6.76 (d, J = 11.0 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 6.07 (dd, J = 8.7, 5.3 Hz, 1H), 5.09 (dd, J= 11.1, 8.7 Hz, 1H), 4.13 - 4.04 (m, 1H), 4.03 - 3.79 (m, 5H), 3.76 (s, 3H), 3.26 (s, 3H), 3.11 (s, 3H), 2.84 (s, 3H). 93 [00221]embedded image 566.2 Method D, RT = 1.86 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.8 Hz, 1H), 8.02 - 7.88 (m, 2H), 7.78 (dd, J= 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 6.8, 2.0 Hz, 1H), 7.45 (d, J = 8.3 Hz, 2H), 6.81 - 6.67 (m, 2H), 6.34 (t, J= 7.0 Hz, 1H), 5.67 (dd, J = 12.0, 8.8 Hz, 1H), 4.71 - 4.56 (m, 1H), 4.33-4.28 (m, 1H), 4.13 - 3.99 (m, 1H), 3.98 - 3.89 (m, 1H), 3.76 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H), 0.91 (d, J= 6.6 Hz, 3H). 94 [00222]embedded image 524.1 Method D, RT = 1.789 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (br d, J = 8.3 Hz, 1H), 7.92 (t, J = 59.6 Hz, 1H), 7.84 (m, 2H), 7.74 (m, 2H), 7.56 (d, J = 8.3 Hz, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.56 (t, J = 7.1 Hz, 1H), 5.08 (dd, J = 11.0, 8.8 Hz, 1H), 4.20 - 4.06 (m, 1H), 4.04 - 3.93 (m, 2H), 3.77 (s, 3H). 95 [00223]embedded image 506.1 Method D, RT = 1.509 min, 96.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 12.03 (br s, 1H), 9.00 (br d, J = 7.8 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.61 (dd, J = 7.2, 2.1 Hz, 1H), 7.40 - 7.25 (m, 3H), 7.33 (t, J= 73.6 Hz, 1H), 6.77 (d, J= 10.8 Hz, 2H), 6.30 (t, J = 6.7 Hz, 1H), 5.12 (dd, J= 10.8, 8.6 Hz, 1H), 4.15 - 3.92 (m, 3H), 3.77 (s, 3H). 96 [00224]embedded image 610.2 Method D, RT = 1.856 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.8 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.79 (dd, J = 6.8, 2.0 Hz, 1H), 7.61 (dd, J = 7.3, 2.0 Hz, 1H), 7.33 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.36 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 10.8, 8.8 Hz, 1H), 4.18 - 4.03 (m, 3H), 4.03 - 3.88 (m, 2H), 3.77 (s, 3H), 2.68 -2.55 (m, 5H). 97 [00225]embedded image 577.3 Method D, RT = 1.464 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.8 Hz, 1H), 7.92 - 7.83 (m, 2H), 7.70 (dd, J = 6.7, 2.1 Hz, 1H), 7.58 (dd, J = 7.2, 2.1 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.12 - 3.92 (m, 7H), 3.76 (s, 3H), 2.18 (s, 6H). 98 [00226]embedded image 502.1 Method D, RT = 1.680 min, 99.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (br d, J = 8.3 Hz, 1H), 7.94 - 7.80 (m, 2H), 7.76 (dd, J = 6.8, 1.7 Hz, 1H), 7.64 - 7.44 (m, 3H), 6.77 (d, J= 10.5 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 10.9, 8.7 Hz, 1H), 4.18 - 4.05 (m, 1H), 4.05 - 3.92 (m, 4H), 3.78 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H). 99 [00227]embedded image 619.2 Method D, RT = 1.569 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.94 - 7.80 (m, 2H), 7.71 (dd, J = 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 7.1, 2.0 Hz, 1H), 7.34 (t, J= 76.0 Hz, 1 H), 7.27 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.12 (dd, J= 10.9, 8.7 Hz, 1H), 4.14 - 3.92 (m, 5H), 3.76 (s, 3H), 3.54 (t, J= 4.5 Hz, 4H), 2.58 (t, J = 6.4 Hz, 2H), 2.43 (m, 4H). 100 [00228]embedded image 596.2 Method D, RT = 1.84 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.8 Hz, 1H), 8.01 - 7.89 (m, 2H), 7.68 (dd, J= 6.7, 2.0 Hz, 1H), 7.60 (dd, J = 6.7, 2.0 Hz, 1H), 7.52 - 7.38 (m, 2H), 6.84 - 6.71 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.67 (dd, J= 12.1, 8.7 Hz, 1H), 4.69 - 4.57 (m, 1H), 4.32 - 4.27 (m 1H), 4.23-4.18 (m, 1H), 4.10 - 3.99 (m, 1H), 3.76 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H), 0.91 (d, J = 6.8 Hz, 3H). 101 [00229]embedded image 620.1 Method D, RT = 1.82 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.3 Hz, 1H), 8.08 - 7.77 (m, 4H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.79 (d, J= 10.8 Hz, 2H), 5.18 - 5.04 (m, 1H), 4.30 (s, 1H), 4.27 - 4.20 (m, 3H), 4.11 - 3.97 (m, 3H), 3.77 (s, 3H), 3.55 - 3.46 (m, 1H), 1.26 (d, J = 6.1 Hz, 3H). 102 [00230]embedded image 536.2 Method D, RT = 1.730 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 8.04 - 7.88 (m, 2H), 7.64 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.52 - 7.44 (m, 4H), 7.43 - 7.34 (m, 2H), 6.32 (t, J = 7.1 Hz, 1H), 5.04 (dd, J= 10.9, 8.7 Hz, 1H), 4.98 - 4.88 (m, 1H), 4.16 (t, J = 7.6 Hz, 1H), 4.05 - 3.95 (m, 2H), 3.88 - 3.71 (m, 2H), 3.70 - 3.59 (m, 2H). 103 [00231]embedded image 596.2 Method D, RT = 1.889 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.67 - 7.55 (m, 2H), 7.48 (d, J= 8.8 Hz, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.32 (t, J= 7.0 Hz, 1H), 5.12 (dd, J = 10.8, 8.6 Hz, 1H), 4.15 - 3.92 (m, 4H), 3.92 - 3.82 (m, 1H), 3.76 (s, 3H), 3.65 (dt, J = 6.5, 4.6 Hz, 1H), 3.19 (s, 3H), 1.09 (d, J= 6.1 Hz, 3H). 104 [00232]embedded image 564.2 Method D, RT = 1.512 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.6 Hz, 1H), 7.94 - 7.82 (m, 2H), 7.62 (dd, J= 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.2, 2.1 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.30 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 11.1, 8.7 Hz, 1H), 4.93 (d, J = 5.6 Hz, 1H), 4.17 - 4.04 (m, 2H), 4.04 - 3.83 (m, 3H), 3.76 (s, 3H), 3.63 (dd, J = 12.8, 8.2 Hz, 1H), 1.09 (d, J= 6.4 Hz, 3H). 105 [00233]embedded image 578.3 Method D, RT = 1.66 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.87 (d, J= 8.6 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.68 (dd, J = 7.1, 2.0 Hz, 1H), 7.59 (dd, J= 7.1, 2.0 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.25 - 7.35 (m, 2H), 6.84 - 6.65 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.66 (dd, J = 12.0, 8.6 Hz, 1H), 4.69 -4.58 (m, 1H), 4.33-4.29 (m, 1H), 4.24-4.18 (m, 1H), 4.09 - 4.03 (m, 1H), 3.76 (s, 3H), 3.60 (t, J = 5.1 Hz, 2H), 3.25 (s, 3H), 0.91 (d, J = 6.6 Hz, 3H). 106 [00234]embedded image 547.2 Method D, RT = 1.808 min, 97.5% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (br d, J = 8.3 Hz, 1H), 7.91 - 7.75 (m, 2H), 7.58 (d, J = 8.6 Hz, 2H), 7.16 (d, J = 2.0 Hz, 1H), 6.79 (d, J = 10.8 Hz, 2H), 6.45 (br dd, J = 0.7, 2.4 Hz, 1H), 5.87 (d, J = 1.7 Hz, 1H), 5.08 (dd, J = 10.9, 8.4 Hz, 1H), 4.67 - 4.56 (m, 1H), 4.40 (t, J = 9.8 Hz, 1H), 4.14 - 3.98 (m, 1H), 3.94 -3.85 (m, 1H), 3.78 (s, 3H), 3.73 (s, 3H), 3.50 (q, J = 5.7 Hz, 2H), 3.31 - 3.25 (m, 1H), 3.18 (d, J= 5.1 Hz, 1H). 107 [00235]embedded image 550.2 Method D, RT = 1.891 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 8.04 - 7.89 (m, 2H), 7.65 (dd, J= 6.8, 2.0 Hz, 1H), 7.60 (dd, J = 7.1, 2.0 Hz, 1H), 7.54 - 7.44 (m, 4H), 7.44 - 7.29 (m, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.05 (dd, J= 10.8, 8.8 Hz, 1H), 4.25 - 4.04 (m, 3H), 3.88 - 3.69 (m, 2H), 3.60 (t, J = 5.4 Hz, 2H), 3.25 (s, 3H). 108 [00236]embedded image 546.2 Method D, RT = 1.78 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.93 (m, 1H), 8.07 - 7.91 (m, 3H), 7.57 - 7.26 (m, 4H), 7.05 - 6.79 (m, 3H), 5.27 - 4.71 (m, 2H), 4.54 - 4.01 (m, 3H), 3.98 - 3.84 (m, 2H), 3.81 - 3.67 (m, 5H), 2.31 - 2.19 (2 s, 3H). (mixture of interconvertible atropisomers) 109 [00237]embedded image 684.3 Method D, RT = 2.00 min, 100% 1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.90 (m, 1H), 8.46 - 8.35 (m, 1H), 7.96 - 7.78 (m, 2H), 7.35 (t, J = 73 Hz, 1H), 7.31 - 7.25 (m, 3H), 6.79 (d, J=11.0 Hz, 2H), 5.18 - 4.97 (m, 1H), 4.44 - 4.35 (m, 1H), 4.28 - 4.13 (m, 1H), 3.76 - 3.74 (m, 1H), 3.73 (s, 3H), 3.00 - 2.70 (m, 3H), 2.35 - 2.26 (m, 3 H) 2.19 (s, 3H), 1.04 (d, J = 6.4 Hz, 6H). 110 [00238]embedded image 518.2 Method D, RT = 1.547 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J= 9.0 Hz, 1H), 7.99 - 7.84 (m, 2H), 7.64 (dd, J= 7.0, 2.0 Hz, 1H), 7.60 (dd, J = 7.0, 2.0 Hz, 1H), 7.55 - 7.38 (m, 4H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.24 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.09 - 5.00 (m, 1H), 4.93 (t, J = 5.3 Hz, 1H), 4.16 (t, J= 7.8 Hz, 1H), 4.05 - 3.96 (m, 2H), 3.89 - 3.72 (m, 2H), 3.68 - 3.60 (m, 2H). 111 [00239]embedded image 490.1 Method D, RT = 1.932 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.80 - 7.72 (m, 1H), 7.58 (d, J= 8.6 Hz, 2H), 7.31 (dd, J = 8.2, 3.3 Hz, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.15 - 5.04 (m, 1H), 4.31 - 4.16 (m, 2H), 4.12 - 4.01 (m, 1H), 3.78 (s, 3H), 2.47 (s, 3H). 112 [00240]embedded image 608.3 Method D, RT = 1.602 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.89 (m, 1H), 7.98 - 7.84 (m, 2H), 7.67 - 7.56 (m, 1H), 7.55 - 7.05 (m, 2H), 7.34 (t, J = 73.6 Hz, 1H), 6.76 (dd, J = 5.0, 10.9 Hz, 2H), 6.29 - 6.12 (m, 1H), 5.36 -4.85 (m, 2H), 4.28 - 4.08 (m, 2H), 3. 76 (s, 3H), 3.74 - 3.59 (m, 4H), 3.50 (br s, 1H), 3.25 - 3.21 (2 s, 3H), 2.25 - 2.02 (2 s, 3H), 1.98 - 1.80 (m, 1H). (mixture of interconvertible atropisomers) 113 [00241]embedded image 564.2 Method D, RT = 2.304 min, 99.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.5 Hz, 1H), 7.93 - 7.86 (m, 2H), 7.67 (dd, J= 7.0, 2.0 Hz, 1H), 7.62 - 7.57 (m, 1H), 7.35 (t, J = 72.6 Hz, 1H), 7.30 -7.24 (m, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 9.0 Hz, 1H), 4.17 - 4.04 (m, 3H), 4.02 - 3.93 (m, 2H), 3.77 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 114 [00242]embedded image 597.2 Method D, RT = 1.88 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 (d, J = 8.8 Hz, 1H), 8.05 - 7.83 (m, 3H), 7.57 (dd, J = 2.6, 8.9 Hz, 1H), 7.50 (d, J = 8.3 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.10 (br dd, J = 8.8, 10.3 Hz, 1H), 4.30 -4.16 (m, 2H), 4.09-4.03 (m, 1H), 3.77 (s, 3H), 3.27 (s, 3H), 2.07 (s, 3H). 115 [00243]embedded image 582.3 Method D, RT = 2.369 min, 99.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 9.02 (m, 1H), 8.02 - 7.89 (m, 2H), 7.61 - 7.42 (m, 3H), 6.83 - 6.71 (m, 2H), 6.27 - 6.14 (m, 1H), 5.41 - 4.85 (m, 2H), 4.33 - 3.87 (m, 4H), 3.83 - 3.72 (m, 3H), 3.70 - 3.58 (m, 2H), 3.56 - 3.44 (m, 1H), 2.24 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 116 [00244]embedded image 548.2 Method D, RT = 1.787 min, 99.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J = 8.6 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.88 (d, J= 8.3 Hz, 2H), 7.62 - 7.57 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.30 (t, J = 7.1 Hz, 1H), 5.14 (dd, J= 11.0, 8.8 Hz, 1H), 4.18 - 4.06 (m, 1H), 4.04 - 3.94 (m, 2H), 3.77 (s, 3H), 3.43 - 3.38 (m, 1H), 1.10 - 0.98 (m, 2H), 0.93 - 0.80 (m, 2H). 117 [00245]embedded image 599.2 Method D, RT = 2.095 min, 93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 9.0 Hz, 2H), 7.74 (t, J = 9.0 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1 H), 7.29 - 7.26 (m, 2H), 6.79 (d, J = 10.5 Hz, 2H), 6.59 (dd, J = 8.5, 2.5 Hz, 1H), 5.16 - 5.03 (m, 1H), 4.46 -4.33 (m, 4H), 4.25 - 4.14 (m, 2H), 4.02 -3.90 (m, 1H), 3.77 (s, 3H). 118 [00246]embedded image 562.2 Method D, RT = 1.612 min, 95.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 9.0 Hz, 2H), 7.69 (dd, J= 7.1, 2.0 Hz, 1H), 7.56 (dd, J= 7.3, 2.0 Hz, 1H), 7.50 - 7.37 (m, 4H), 7.34 (t, J= 73.6 Hz, 1H), 7.32 - 7.19 (m, 2H), 6.34 (t, J = 7.1 Hz, 1H), 5.13 -5.00 (m, 3H), 4.16 (t, J = 7.9 Hz, 1H), 3.86 - 3.60 (m, 6H), 3.23 (s, 3H). 119 [00247]embedded image 617.2 Method D, RT = 2.014 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.3 Hz, 1H), 7.97 - 7.80 (m, 3H), 7.59 (dd, J = 8.7, 2.8 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.13 - 5.09 (m, 1H), 4.60 - 4.58 (m, 1H), 4.30 - 4.18 (m, 2H), 4.05 - 3.98 (m, 1H), 3.77 (s, 3H), 3.67 -3.64 (m, 1H), 2.31 - 2.22 (m, 1H), 1.95 -1.88 (m, 1H), 1.85 - 1.79 (m, 1H), 1.69 -1.64 (m, 1H), 1.56 - 1.35 (m, 2H). 120 [00248]embedded image 552.3 Method D, RT = 1.777 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.6 Hz, 1H), 8.03 - 7.93 (m, 2H), 7.72 (dd, J= 6.8, 2.0 Hz, 1H), 7.66 (dd, J = 7.3, 2.0 Hz, 1H), 7.48 (d, J = 7.8 Hz, 2H), 7.39 - 7.26 (m, 2H), 6.97 - 6.82 (m, 2H), 6.42 (t, J = 7 Hz, 1H), 6.35 (tt, J = 56.2, 3.5 Hz, 1H), 5.03 (dd, J= 11.1, 8.7 Hz, 1H), 4.53 - 4.35 (m, 2H), 4.19 - 4.09 (m, 1H), 3.81 - 3.68 (m, 5H). 121 [00249]embedded image 566.2 Method D, RT = 1.817 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (dd, J= 16.0, 8.7 Hz, 1H), 8.04 - 7.91 (m, 2H), 7.77 - 7.18 (m, 5H), 7.01 - 6.67 (m, 2H), 6.48 - 6.10 (m, 2H), 5.35 - 4.62 (m, 1H), 4.53 - 4.26 (m, 2H), 4.12 - 3.77 (m, 2H), 3.77 - 3.62 (m, 4H), 3.57 - 3.36 (m, 1H), 2.27 - 1.98 (2 s, 3H). (mixture of interconvertible atropisomers) 122 [00250]embedded image 593.3 Method D, RT = 1.82 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J= 8.6 Hz, 1H), 7.95 - 7.81 (m, 2H), 7.53 - 7.48 (m, 1H), 7.35 (t, J= 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H) 6.96 (d, J = 5.9 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 6.46 (dd, J= 2.6, 8.9 Hz, 1H), 5.19 - 5.03 (m, 1H), 4.31 - 4.19 (m, 1H), 4.19 - 4.07 (m, 2H), 4.04 - 3.94 (m, 1H), 3.87-3.86 (m, 1H), 3.84 - 3.77 (m, 1H), 3.76 (s, 3H), 3.70 (dt, J = 5.7, 8.1 Hz, 1H), 3.50-3.49 (m, 1H), 2.19-2.16 (m, 1H), 1.83 - 1.70 (m, 1H). 123 [00251]embedded image 524.1 Method D, RT = 1.794 min, 94.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.93 (t, J = 59.6 Hz, 1H), 7.86 - 7.66 (m, 4H), 7.63 - 7.47 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.56 (t, J = 7.1 Hz, 1H), 5.09 (dd, J= 10.9, 8.7 Hz, 1H), 4.19 - 4.06 (m, 1H), 4.03 - 3.92 (m, 2H), 3.77 (s, 3H). 124 [00252]embedded image 639.2 Method D, RT = 2.01 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 (br d, J = 8.6 Hz, 1H), 8.02 - 7.87 (m, 4H), 7.49 (d, J = 8.3 Hz, 2H), 6.80 (d, J = 11.0 Hz, 2H), 5.17 - 5.07 (m, 1H), 4.33 - 4.20 (m, 4H), 4.12 - 3.98 (m, 3H), 3.77 (s, 3H), 3.57 - 3.49 (m, 1H), 1.26 (d, J = 6.1 Hz, 3H). 125 [00253]embedded image 611.2 Method D, RT = 1.88 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.8 Hz, 1H), 8.32 - 8.21 (m, 1H), 7.91 - 7.78 (m, 2H), 7.65 - 7.51 (m, 2H), 6.97 - 6.85 (m, 1H), 6.78 (d, J= 10.8 Hz, 2H), 6.13 - 5.95 (m, 1H), 5.21 - 5.02 (m, 1H), 4.37 - 4.11 (m, 3H), 3.95 - 3.83 (m, 2H), 3.82 (s, 3H), 3.79 - 3.64 (m, 3H), 2.31 - 2.19 (m, 1H), 2.04 - 1.89 (m, 1H). 126 [00254]embedded image 562.2 Method D, RT = 1.95 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J= 8.6 Hz, 1H), 8.07 (dd, J = 4.6, 1.2 Hz, 1H), 7.99 - 7.81 (m, 2H), 7.61 (d, J= 7.3 Hz, 1H), 7.39 - 7.35 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.27 - 7.24 (m, 2H), 6.87 - 6.67 (m, 2H), 5.60 (dd, J = 11.5, 8.6 Hz, 1H), 4.77-4.68 (m, 1H), 4.56 -4.43 (m, 1H), 4.40-4.35 (m, 1H), 3.77 (s, 3H), 1.30 (d, J = 5.5 Hz, 3H), 1.26 (d, J = 5.5 Hz, 3H), 0.90 (d, J = 6.4 Hz, 3H). 127 [00255]embedded image 578.3 Method D, RT = 1.67 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J = 8.6 Hz, 1H), 7.93 - 7.82 (m, 2H), 7.69 (dd, J = 6.8, 2.0 Hz, 1H), 7.48-7.45 (m, 1H ),7.35 (t, J = 73.6 Hz, 1H), 7.28 -7.26 (m, 2H), 6.87 - 6.70 (m, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 11.1, 8.4 Hz, 1H), 4.53- 5.09 (m, 1H), 4.17 - 4.08 (m, 2H), 3.77 (s, 3H), 3.76-3.74 (m, 1H), 3.63 - 3.57 (m, 2H), 3.24 (s, 3H), 0.99 (d, J= 6.1 Hz, 3H). 128 [00256]embedded image 516.2 Method D, RT = 1.7 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.8 Hz, 1H), 8.05 - 7.92 (m, 2H), 7.75 (dd, J = 6.6, 2.0 Hz, 1H), 7.58 (dd, J = 7.3, 2.0 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7.39 - 7.28 (m, 2H), 7.00 - 6.83 (m, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.02 (dd, J = 11.1, 8.7 Hz, 1H), 4.18 - 4.08 (m, 1H), 4.05 - 3.92 (m, 2H), 3.83 - 3.68 (m, 5H), 1.25 (t, J= 7.1 Hz, 3H). 129 [00257]embedded image 631.2 Method D, RT = 1.75 min, 98.77% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.99 (m, 1H), 8.24 - 8.14 (m, 1H), 7.94 - 7.81 (m, 2H), 7.33 (t, J = 73.6 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.93 - 6.81 (m, 1H), 6.77 (d, J = 10.5 Hz, 2H), 6.28 (br d, J = 4.9 Hz, 1H), 5.16 - 4.93 (m, 2H), 4.32 -4.10 (m, 2H), 3.92 - 3.82 (m, 1H), 3.76 (s, 3H), 3.75 - 3.68 (m, 1H), 3.47 - 3.39 (m, 2H), 1.18 - 1.04 (m, 3H). (mixture of interconvertible atropisomers) 130 [00258]embedded image 518.2 Method D, RT = 1.467 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.65 (dd, J = 6.8, 2.0 Hz, 1H), 7.62 - 7.43 (m, 3H), 6.77 (d, J= 10.8 Hz, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.8 Hz, 1H), 5.02 - 4.88 (m, 1H), 4.19 - 3.88 (m, 5H), 3.76 (s, 3H), 3.69 -3.60 (m, 2H). 131 [00259]embedded image 691.2 Method D, RT = 1.732 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.91 (m, 1H), 7.97 - 7.80 (m, 2H), 7.69 - 7.55 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 (m, 1H), 6.86 - 6.69 (m, 2H), 6.40 -6.25 (m, 1H), 6.08 - 5.99 (m, 1H), 5.37 -4.87 (m, 2H), 3.91 - 3.77 (m, 4H), 3.77 -3.73 (m, 3H), 3.63 - 3.37 (m, 4H), 3.30 -3.22 (m, 3H), 2.83 - 2.58 (m, 3H), 2.26 -2.03 (m, 3H), 1.81 (br s, 2H). (mixture of interconvertible atropisomers) 132 [00260]embedded image 572.3 Method D, RT = 1.72 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.91 (m, 1H), 8.06 - 7.96 (m, 2H), 7.53 (td, J = 3.5, 7.1 Hz, 1H), 7.50 - 7.43 (m, 2H), 7.43 - 7.34 (m, 1H), 7.32 (d, J= 8.8 Hz, 1H), 7.01 - 6.79 (m, 2H), 6.28 (dd, J = 3.1, 7.2 Hz, 1H), 5.43 - 5.31 (m, 1H), 5.28 - 4.61 (m, 1H), 4.16 - 4.02 (m, 1H), 3.97 - 3.64 (m, 5H), 3.47 (t, J = 9.4 Hz, 1H), 2.98 - 2.83 (m, 2H), 2.19 - 2.05 (2 s, 3H), 2.03 - 1.83 (m, 1H), 1.19 - 1.13 (m, 2H). (mixture of interconvertible atropisomers) 133 [00261]embedded image 594.2 Method D, RT = 1.526 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.95 - 7.83 (m, 2H), 7.70 (dd, J = 6.8, 2.0 Hz, 1H), 7.56 (dd, J = 7.2, 1.8 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.5 Hz, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.17 - 5.04 (m, 3H), 4.14 - 4.03 (m, 1H), 4.03 - 3.92 (m, 2H), 3.81 - 3.65 (m, 6H), 3.65 - 3.56 (m, 1H), 3.23 (s, 3H). 134 [00262]embedded image 653.3 Method D, RT = 1.790 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.3 Hz, 1H), 8.00 - 7.88 (m, 2H), 7.72 (dd, J= 7.0, 1.8 Hz, 1H), 7.61 (dd, J = 7.2, 1.8 Hz, 1H), 7.48 (dd, J= 1.0, 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.41 (t, J = 7.2 Hz, 1H), 6.08 (dd, J = 8.8, 5.1 Hz, 1H), 5.10 (dd, J = 11.0, 8.6 Hz, 1H), 4.16 - 4.04 (m, 1H), 4.02 - 3.91 (m, 2H), 3.89 - 3.80 (m, 2H), 3.76 (s, 3H), 3.27 (s, 3H), 3.11 (s, 3H), 2.85 (s, 3H). 135 [00263]embedded image 607.2 Method D, RT = 1.66 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J= 8.6 Hz, 1H), 8.28 (dd, J= 9.0, 3.2 Hz, 1H), 7.94 (t, J = 9.0 Hz, 1H), 7.91 -7.83 (m, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 5.86 (br d, J = 6.1 Hz, 1H), 5.17 -5.05 (m, 1H), 4.46 - 4.35 (m, 1H), 4.30 -4.17 (m, 2H), 4.12 - 3.90 (m, 2H), 3.77 (s, 3H), 3.75 - 3.60 (m, 1H), 2.43 - 2.34 (m, 1H), 1.88 - 1.75 (m, 1H). 136 [00264]embedded image 576.3 Method D, RT = 1.606 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.98 (m, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.70 - 7.65 (m, 1H), 7.61 - 7.52 (m, 1H), 7.51 - 7.39 (m, 2H), 7.34 (d, J = 8.3 Hz, 2H), 6.90 (d, J= 8.3 Hz, 2H), 6.34 (t, J= 6.8 Hz, 1H), 5.12 - 4.96 (m, 3H), 4.15 -4.06 (m, 1H), 3.79 - 3.60 (m, 9H), 3.23 (s, 3H). (NMR not clean) 137 [00265]embedded image 532.1 Method D, RT = 1.666 min, 99.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 7.93 - 7.76 (m, 2H), 7.66 (dd, J= 6.8, 2.0 Hz, 1H), 7.63 - 7.48 (m, 3H), 6.77 (d, J = 10.5 Hz, 2H), 6.33 (t, J= 7.0 Hz, 1H), 5.12 (dd, J= 11.0, 8.6 Hz, 1H), 4.23 - 4.04 (m, 2H), 4.02 - 3.94 (m, 2H), 3.93 - 3.89 (m, 1H), 3.77 (s, 3H), 3.61 (t, J= 5.3 Hz, 2H), 3.26 (s, 3H). 138 [00266]embedded image 596.2 Method D, RT = 1.869 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 8.00 - 7.83 (m, 2H), 7.61 (dt, J = 2.0, 7.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 10.6, 8.7 Hz, 1H), 4.15 - 3.97 (m, 3H), 3.97 - 3.81 (m, 2H), 3.76 (s, 3H), 3.68 -3.59 (m, 1H), 3.18 (s, 3H), 1.09 (d, J = 6.1 Hz, 3H). 139 [00267]embedded image 536.3 Method D, RT = 1.386 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 11.94 - 11.70 (m, 1H), 9.00 (d, J = 8.6 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.63 - 7.55 (m, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.26 (dt, J= 1.1, 2.9 Hz, 1H), 5.56 - 5.43 (m, 1H), 5.17 - 5.03 (m, 1H), 4.41 - 4.23 (m, 2H), 4.12 - 3.88 (m, 3H), 3.76 (s, 3H). 140 [00268]embedded image 502.2 Method D, RT = 1.605 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 7.89 - 7.78 (m, 2H), 7.62 - 7.52 (m, 2H), 7.46 (d, J = 7.3 Hz, 1H), 6.77 (d, J= 10.5 Hz, 2H), 6.28 - 6.18 (m, 1H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.16 - 4.02 (m, 1H), 3.99 - 3.86 (m, 2H), 3.76 (s, 3H), 3.49 (s, 3H), 2.39 (s, 3H) 141 [00269]embedded image 564.2 Method D, RT = 1.508 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.6 Hz, 1H), 7.97 - 7.81 (m, 2H), 7.62 (dd, J= 6.7, 2.1 Hz, 1H), 7.58 (dd, J = 7.1, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.31 (t, J = 7.1 Hz, 1H), 5.11 (dd, J = 10.9, 8.7 Hz, 1H), 4.94 (d, J = 5.4 Hz, 1H), 4.15 - 3.85 (m, 5H), 3.76 (s, 3H), 3.64 (dd, J = 12.8, 8.2 Hz, 1H), 1.09 (d, J = 6.4 Hz, 3H). 142 [00270]embedded image 594.3 Method D, RT = 1.528 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.8 Hz, 1H), 7.94 - 7.82 (m, 2H), 7.70 (dd, J = 2.0, 7.1 Hz, 1H), 7.56 (dd, J = 2.0, 7.1 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.17 - 4.98 (m, 3H), 4.15 - 4.04 (m, 1H), 4.01 - 3.91 (m, 2H), 3.77(s, 3H), 3.77 - 3.58 (m, 4H), 3.23 (s, 3H). 143 [00271]embedded image 532.2 Method D, RT = 1.44 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J= 9.0 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.63 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.1, 2.0 Hz, 1H), 7.51 (d, J = 9.3 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.88 - 6.75 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.12 (dd, J= 11.2, 8.8 Hz, 1H), 4.93 (t, J = 5.4 Hz, 1H), 4.17 -4.09 (m, 1H), 4.06 - 3.93 (m, 3H), 3.74 (s, 3H), 3.72 - 3.58 (m, 3H). 144 [00272]embedded image 612.3 Method D, RT = 1.698 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 8.07 - 7.89 (m, 2H), 7.70 (dd, J = 6.8, 2.0 Hz, 1H), 7.56 (dd, J = 7.1, 2.0 Hz, 1H), 7.52 - 7.41 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.34 (t, J= 7.1 Hz, 1H), 5.22 - 4.95 (m, 3H), 4.20 - 4.03 (m, 1H), 4.03 - 3.90 (m, 2H), 3.83 - 3.61 (m, 4H), 3.76 (s, 3H), 3.23 (s, 3H). 145 [00273]embedded image 570.2 Method D, RT = 1.708 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.74 (dd, J = 6.8, 1.7 Hz, 1H), 7.66 (dd, J= 7.2, 1.7 Hz, 1H), 7.34 (t, J= 76.0 Hz, 1 H), 7.28 - 7.25 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.53 - 6.18 (m, 2H), 6.42 (t, J = 7 Hz, 1H), 6.35 (tt, J = 56.2, 3.5 Hz, 1H), 5.11 (dd, J = 10.6, 8.7 Hz, 1H), 4.56 - 4.34 (m, 2H), 4.16 - 4.06 (m, 1H), 4.03 - 3.92 (m, 2H), 3.77 (s, 3H). 146 [00274]embedded image 565.2 Method D, RT = 1.70 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 10.61 (s, 1H), 9.11 (d, J = 8.6 Hz, 1H), 8.04 (br d, J = 3.4 Hz, 1H), 7.93 - 7.70 (m, 3H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 -7.27 (m, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.06 (dd, J = 10.5, 8.6 Hz, 1H), 4.27 -4.04 (m, 3H), 3.77 (s, 3H), 2.09 (s, 3H). 147 [00275]embedded image 650.2 Method D, RT = 2.091 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.73 - 6.67 (m, 2H), 7.48 (d, J= 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.39 (t, J = 7.1 Hz, 1H), 5.13 (dd, J= 10.5, 8.8 Hz, 1H), 4.42 (dd, J = 13.2, 3.4 Hz, 1H), 4.33 - 4.19 (m, 1H), 4.16 - 3.87 (m, 4H), 3.76 (s, 3H), 3.34 (s, 3H). 148 [00276]embedded image 588.2 Method D, RT = 1.883 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.74 (dd, J = 7.0, 1.6 Hz, 1H), 7.67 (dd, J = 7.2, 1.8 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.42 (t, J = 7 Hz, 1H), 6.35 (tt, J = 56.2, 3.5 Hz, 1H), 5.12 (dd, J = 8.6, 11.0 Hz, 1H), 4.54 - 4.36 (m, 2H), 4.18 - 4.05 (m, 1H), 4.03 - 3.93 (m, 2H), 3.77 (s, 3H). 149 [00277]embedded image 631.3 Method D, RT = 1.716 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 8.96 (m, 1H), 8.03 - 7.89 (m, 2H), 7.54 - 7.44 (m, 2H), 7.40 - 7.20 (m, 2H), 6.90 (m, 2H), 6.28 (d, J = 7.3 Hz, 1H), 6.09 -6.03 (m, 1H), 5.23 - 4.73 (m, 1H), 4.13 -4.03 (m, 1H), 3.94 - 3.78 (m, 4H), 3.74 -3.61 (2 s, 3H), 3.60 - 3.52 (m, 1H), 3.27 -3.24 (2 s, 3H), 3.14 - 3.07 (m, 3H), 2.82 -2. 37 (2 s, 3H), 2.86 - 2.81 (2 s, 3H). (mixture of interconvertible atropisomers) 150 [00278]embedded image 502.2 Method D, RT = 1.715 min, 98.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.5 Hz, 1H), 8.00 - 7.84 (m, 2H), 7.75 (dd, J= 6.8, 1.8 Hz, 1H), 7.59 (dd, J = 7.5, 1.8 Hz, 1H), 7.51 - 7.39(m, 4H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 (d, J = 8.2HZ, 2H), 6.35 (t, J = 6.8 Hz, 1H), 5.04 (dd, J= 8.8, 10.8 Hz, 1H), 4.17 (t, J= 7.8 Hz, 1H), 4.07 - 3.93 (m, 2H), 3.90 - 3.64 (m, 2H), 1.25 (t, J = 7.3 Hz, 3H). 151 [00279]embedded image 592.3 Method D, RT = 2.017 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.95 (m, 1H), 8.05 - 7.86 (m, 2H), 7.76 - 7.62 (m, 1H), 7.53 - 7.38 (m, 2H), 6.77 (dd, J= 10.8, 5.9 Hz, 2H), 6.30 - 6.15 (m, 1H), 5.40 - 4.84 (m, 1H), 4.29 - 4.08 (m, 2H), 3.90 - 3.65 (m, 5H), 3.53 - 3.49(m, 1H), 2.19 - 1.06 (2 s, 3H), 1.23 - 1.18 (m, 1H), 0.53 - 0.43 (m, 2H), 0.42 - 0.30 (m, 2H). (mixture of interconvertible atropisomers) 152 [00280]embedded image 684.3 Method D, RT = 1.97 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.3 Hz, 1H), 8.49 (br d, J= 4.6 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.13 -7.08 (m, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.08 - 4.94 (m, 1H), 4.22 (q, J= 10.0 Hz, 1H), 4.14 - 4.01 (m, 1H), 3.97 - 3.87 (m, 1H), 3.76 (s, 3H), 3.53 (br d, J = 12.5 Hz, 2H), 2.88 - 2.69 (m, 2H), 2.31 - 2.16 (m, 2H), 2.15 (s, 3H), 1.05 (s, 3H), 1.03 (s, 3H). 153 [00281]embedded image 612.2 Method D, RT = 1.702 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 8.02 - 7.86 (m, 2H), 7.70 (dd, J= 7.1, 2.0 Hz, 1H), 7.57 (dd, J = 7.3, 2.0 Hz, 1H), 7.52 - 7.41 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.34 (t, J= 7.1 Hz, 1H), 5.22 - 4.97 (m, 3H), 4.19 - 4.03 (m, 1H), 4.03 - 3.88 (m, 2H), 3.83 - 3.57 (m, 4H), 3.76 (s, 3H), 3.23 (s, 3H). 154 [00282]embedded image 580.2 Method D, RT = 1.794 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.69 (dd, J = 6.8, 2.0 Hz, 1H), 7.57 (dd, J= 7.1, 2.0 Hz, 1H), 7.48 (d, J = 8.3 Hz, 4H), 7.43 - 7.35 (m, 2H), 6.34 (t, J = 7.0 Hz, 1H), 5.11 - 4.95 (m, 3H), 4.17 (t, J = 8.1 Hz, 1H), 3.85 - 3.62 (m, 6H), 3.23 (s, 3H). 155 [00283]embedded image 636.2 Method D, RT = 1.887 min, 96.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 8.00 - 7.88 (m, 2H), 7.70 (dd, J = 6.8, 2.0 Hz, 1H), 7.64 (dd, J = 7.2, 2.0 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.10 (dd, J = 10.4, 8.9 Hz, 1H), 4.44 (dd, J= 2.8, 13.1 Hz, 1H), 4.39 - 4.27 (m, 1H), 4.16 - 3.99 (m, 2H), 3.97 - 3.89 (m, 2H), 3.85 (dd, J = 13.1, 9.4 Hz, 1H), 3.76 (s, 3H). 156 [00284]embedded image 650.2 Method D, RT = 2.067 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.6 Hz, 1H), 8.01 - 7.86 (m, 2H), 7.71 (dd, J = 6.8, 2.0 Hz, 1H), 7.67 (dd, J = 7.3, 2.0 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.39 (t, J = 7.1 Hz, 1H), 5.12 (dd, J= 10.9, 8.7 Hz, 1H), 4.42 (dd, J = 13.4, 3.4 Hz, 1H), 4.38 - 4.26 (m, 1H), 4.15 - 3.93 (m, 4H), 3.76 (s, 3H), 3.34 (S, 3H). 157 [00285]embedded image 576.2 Method D, RT = 1.815 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J= 8.5 Hz, 1H), 8.15 (dd, J = 5.0, 2.0 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.79 (dd, J = 7.5, 2.0 Hz, 1H), 7.35 (t, J = 72.0 Hz, 1H), 7.28 - 7.26 (m, 2H), 7.12 (dd, J = 7.8, 4.8 Hz, 1H), 6.80 (d, J = 10.5 Hz, 2H), 5.60 (dt, J = 4.4, 2.3 Hz, 1H), 5.05 (dd, J= 8.5, 11.0 Hz, 1H), 4.19 - 4.12 (m, 1H), 4.05 - 3.94 (m, 2H), 3.94 - 3.81 (m, 3H), 3.80 - 3.72 (m, 4H), 2.31 - 2.20 (m, 1H), 2.11 - 2.01 (m, 1H). 158 [00286]embedded image 626.2 Method D, RT = 1.81 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.97 - 7.78 (m, 3H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 7.13 (dd, J = 8.9, 2.6 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.19 - 5.04 (m, 1H), 4.29 - 4.14 (m, 2H), 4.09 - 3.97 (m, 1H), 3.92 m3.85 (m, 2H), 3.77 (s, 3H), 3.59 (t, J = 7.2 Hz, 2H), 2.41 - 2.37 (m, 2H). 159 [00287]embedded image 536.2 Method D, RT = 1.791 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.24 (d, J = 8.8 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.88 (d, J= 8.3 Hz, 2H), 7.77 (dd, J = 6.7, 2.1 Hz, 1H), 7.59 (dd, J = 7.1, 2.1 Hz, 1H), 6.78 (d, J = 10.5 Hz, 2H), 6.36 (t, J= 7.0 Hz, 1H), 5.15 (dd, J= 11.1, 8.7 Hz, 1H), 4.17 - 4.06 (m, 1H), 4.04 - 3.94 (m, 4H), 3.77 (s, 3H), 1.25 (t, J= 7.2 Hz, 3H). 160 [00288]embedded image 593.2 Method D, RT = 1.61 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 (d, J = 8.8 Hz, 1H), 8.12 (d, J = 6.4 Hz, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H), 6.84 - 6.69 (m, 3H), 5.16 (dd, J = 8.8, 10.5 Hz, 1H), 4.77(br s, 1H), 4.24 - 4.04 (m, 3H), 3.76 (s, 3H), 3.72 -3.70(m, 1H), 3.56 - 3.51 (m, 2H), 2.85 (d, J = 9.0 Hz, 1H), 2.58 (d, J= 9.0, Hz, 1H), 2.30 (s, 3H), 1.94 (br d, J= 9.5 Hz, 1H), 1.83 (br d, J= 9.5 Hz, 1H). 161 [00289]embedded image 632.2 Method D, RT = 1.930 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.73 - 7.68 (m, 2H), 7.34 (t, J= 73.6 Hz, 1H), 7.29 -7.26 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.39 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 10.5, 8.8 Hz, 1H), 4.42 (dd, J = 13.4, 3.4 Hz, 1H), 4.35 - 4.22 (m, 1H), 4.15 - 3.92 (m, 4H), 3.76 (s, 3H), 3.36 (s, 3H). 162 [00290]embedded image 532.2 Method D, RT = 1.711 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.6 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.65 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.52 - 7.39 (m, 4H), 7.34 (t, J = 73.6 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.10 -4.95 (m, 1H), 4.20 - 4.08 (m, 3H), 3.86 -3.71 (m, 2H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 163 [00291]embedded image 581.2 Method D, RT = 2.03 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.8 Hz, 1H), 8.32 - 8.21 (m, 1H), 7.91 - 7.78 (m, 2H), 7.65 - 7.51 (m, 2H), 7.14 (t, J = 5.6 Hz, 1H), 6.93 - 6.84 (m, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.21 - 5.02 (m, 1H), 4.34 - 4.26 (m, 1H), 4.22 - 4.09 (m, 1H), 3.78 (s, 3H), 3.77 - 3.66 (m, 1H), 2.27 - 2.23 (m, 1H), 0.85 - 0.76 (m, 2H), 0.62 - 0.55 (m, 2H). 164 [00292]embedded image 631.3 Method D, RT = 1.459 min, 98.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.69 - 7.55 (m, 2H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.31 (t, J = 7.1 Hz, 1H), 5.11 (dd, J = 10.9, 8.7 Hz, 1H), 4.57 (s, 4H), 4.15 - 4.05 (m, 1H), 4.00 - 3.92 (m, 2H), 3.90 - 3.82 (m, 2H), 3.76 (s, 3H), 3.29 (s, 4H), 2.65 - 2.57 (m, 2H). 165 [00293]embedded image 530.2 Method D, RT = 1.67 min, 98.58% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 - 8.94 (m, 1H), 8.00 - 7.83 (m, 2H), 7.68 - 7.74 (tm, 1H), 7.37 - 7.52 (m, 1H), 7.27 - 7.22 (m, 1H), 7.57 - 7.10 (m, 2H), 6.90 - 6.71 (m, 2H), 6.22 (d, J = 6.8 Hz, 1H), 5.43 - 4.74 (m, 1H), 4.21 - 3.85 (m, 5H), 3.74 (2 s, 3H), 2.21 - 2.05 (2 s, 3H), 1.31 -1.11 (m, 3H). (mixture of interconvertible atropisomers) 166 [00294]embedded image 613.2 Method D, RT = 1.87 min, 98.43% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.8 Hz, 1H), 8.25 - 8.13 (m, 1H), 7.90 - 7.75 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 6.96 - 6.84 (m, 1H), 6.78 (d, J= 10.8 Hz, 2H), 5.95 (br s, 1H), 5.14 (br dd, J = 11.0, 8.8 Hz, 1H), 4.35 - 4.28 (m, 1H), 4.26 - 4.14 (m, 2H), 3.77 (s, 3H), 3.76 -3.71 (m, 1H), 3.25 - 3.13 (m, 2H), 1.17 (s, 3H), 1.15 (s, 3H). 167 [00295]embedded image 609.3 Method D, RT = 1.88 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 10.08 (br s, 1H), 9.20 (d, J = 8.6 Hz, 1H), 8.43 (d, J = 5.9 Hz, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.10 (dd, J = 10.8, 8.8 Hz, 1H), 4.40 - 4.28 (m, 1H), 4.26 -4.18 (m, 1H), 4.13 - 4.01 (m, 3H), 3.77 (s, 3H), 3.55 - 3.50 (m, 2H), 3.33 - 3.23 (m, 2H), 2.78 (s, 3H), 1.45 - 1.21 (m, 6H). 168 [00296]embedded image 588.2 Method D, RT = 1.850 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 (br d, J= 8.6 Hz, 1H), 8.46 (s, 1H), 7.95 - 7.73 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H), 7.30 - 7.24 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.10 (dd, J = 10.8, 8.6 Hz, 1H), 4.22 - 3.95 (m, 3H), 3.77 (s, 3H), 3.58 (s, 3H). 169 [00297]embedded image Method D, RT = 1.424 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.5 Hz, 1H), 7.93 - 7.85 (m, 2H), 7.76 (dd, J= 6.5, 2.0 Hz, 1H), 7.58 (dd, J = 7.5, 2.0 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.77 (d, J= 11.0 Hz, 2H), 6.35 (t, J=7.0 Hz, 1H), 5.11 (dd, J = 10.8, 8.8 Hz, 1H), 4.14 - 4.05 (m, 1H), 4.03 - 3.94 (m, 4H), 3.77 (s, 3H), 1.25 (t, J= 7.3 Hz, 3H). 170 [00298]embedded image 530.2 Method D, RT = 1.749 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 9.89 (m, 1H), 8.12 - 7.89 (m, 2H), 7.75 - 7.52 (m, 1H), 7.52 - 7.42 (m, 2H), 7.42 - 7.16 (m, 2H), 6.99 - 6.65 (m, 2H), 6.31 - 6.09 (m, 1H), 5.32 - 4.68 (m, 1H), 4.16 - 3.77 (m, 4H), 3.76 - 3.51 (m, 4H), 2.23 - 1.94 (2 s, 3H), 1.34 - 1.15 (m, 3H). (mixture of interconvertible atropisomers) 171 [00299]embedded image 522.1 Method D, RT = 1.88 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.92 (m, 1H), 8.41 (br d, J = 4.9 Hz, 1H), 7.98 - 7.78 (m, 3H), 7.52-7.49 (m, 1H), 7.35 (t, J= 73.6 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.86 - 6.72 (m, 2H), 5.61 - 5.48 (m, 1H), 4.86 - 4.77 (m, 1H), 4.40-4.35 (m, 1H), 3.78 (s, 3H), 0.99 (d, J= 6.8 Hz, 3H). 172 [00300]embedded image 635.3 Method D, RT = 1.614 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.94 - 7.83 (m, 2H), 7.72 (dd, J = 7.1, 2.0 Hz, 1H), 7.61 (dd, J = 7.2, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.24 (m, 1H), 6.76 (d, J= 11.0 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 6.07 (dd, J = 8.7, 5.3 Hz, 1H), 5.09 (dd, J = 11.1, 8.7 Hz, 1H), 4.13 - 4.04 (m, 1H), 4.03 - 3.79 (m, 5H), 3.76 (s, 3H), 3.26 (s, 3H), 3.11 (s, 3H), 2.84 (s, 3H). 173 [00301]embedded image 582.2 Method D, RT = 1.690 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 7.99 - 7.86 (m, 2H), 7.63 - 7.58 (m, 2H), 7.53 - 7.37 (m, 2H), 6.76 (d, J= 10.8 Hz, 2H), 6.31 (t, J= 7.1 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.94 (br d, J = 5.1 Hz, 1H), 4.17 - 4.03 (m, 2H), 4.03 - 3.83 (m, 3H), 3.76 (s, 3H), 3.63 (dd, J= 12.8, 8.2 Hz, 1H), 1.09 (d, J= 6.4 Hz, 3H). 174 [00302]embedded image 568.1 Method D, RT = 2.171 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.5 Hz, 1H), 7.99 - 7.90 (m, 2H), 7.65 (dd, J= 6.5, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 6.77 (d, J= 10.5 Hz, 2H), 6.35 - 6.29 (m, 1H), 5.12 (dd, J = 11.3, 8.8 Hz, 1H), 4.97 - 4.92 (m, 1H), 4.14 - 4.05 (m, 1H), 4.03 - 3.95 (m, 4H), 3.77 (s, 3H), 3.67 -3.62 (m, 2H). 175 [00303]embedded image 626.2 Method D, RT = 1.72 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (br d, J= 8.1 Hz, 1H), 7.96 (d, J= 8.6 Hz, 2H), 7.74 - 7.66 (m, 1H), 7.56 (dd, J = 7.0, 1.3 Hz, 1H), 7.45 (d, J = 8.6 Hz, 2H), 6.77 (d, J = 11.5 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.71 - 5.61 (m, 1H), 5.14 - 4.97 (m, 2H), 4.67 - 4.56 (m, 1H), 4.29 (dd, J = 8.3, 11.7 Hz, 1H), 3.83 - 3.69, (m, 5H), 3.65 (td, J = 5.4, 10.9 Hz, 2H), 3.23 (s, 3H), 0.91 (br d, J = 6.8 Hz, 3H). 176 [00304]embedded image 578.2 Method D, RT = 1.584 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.92 (m, 1H), 7.88 (d, J = 9.0 Hz, 2H), 7.52 (s, 1H), 7.34 (t, J= 72 Hz, 1H), 7.28 - 7.11 (m, 1H), 6.77 (br d, J = 10.8 Hz, 2H), 6.24 - 6.14 (m, 1H), 5.40 - 5.28 (m, 1H), 4.97 - 4.84 (m, 2H), 4.30 - 3.98 (m, 3H), 3.93 - 3.84 (m, 1H), 3.80 - 3.71 (2 s, 3H), 3.62 - 3.43 (m, 2H), 2.23 - 2.01 (2 s, 3H), 1.08 (d, J = 6.4 Hz, 3H). (mixture of interconvertible atropisomers) 177 [00305]embedded image 579.3 Method D, RT = 1.69 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.96 (t, J = 8.9 Hz, 1H), 7.92 - 7.84 (m, 2H), 7.56 (dd, J = 8.4, 2.6 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.79 (d, J= 10.8 Hz, 2H), 5.14 - 5.04 (m, 1H), 4.29 - 4.13 (m, 2H), 4.11 - 4.01 (m, 1H), 3.77 (s, 3H), 3.27 (s, 3H), 2.07 (s, 3H). 178 [00306]embedded image 560.3 Method D, RT = 1.738 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 8.98 (m, 1H), 8.06 - 7.91 (m, 2H), 7.59 - 7.52 (m, 1H), 7.51 - 7.48 (m, 2H), 7.41 - 7.35 (m, 1H), 7.32 (d, J = 8.6 Hz, 1H), 6.93 - 6.89 (m, 2H), 6.20 (d, J= 7.1 Hz, 1H), 5.27 - 4.66 (m, 1H), 4.19 - 3.99 (m, 2H), 3.95 - 3.80 (m, 2H), 3.74 - 3.68 (2 s, 3H), 3.66 - 3.45 (m, 3H), 3.24 (s, 3H), 2.23 - 2.03 (2 s, 3H). (mixture of interconvertible atropisomers) 179 [00307]embedded image 608.2 Method D, RT = 1.506 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.98 (m, 1H), 7.93 - 7.85 (m, 2H), 7.69 - 7.61 (m, 2H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.40 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.1, 8.4 Hz, 1H), 4.74 (t, J = 5.4 Hz, 2H), 4.15 - 4.04 (m, 1H), 4.03 - 3.89 (m, 4H), 3.76 (s, 3H), 3.24 - 3.11 (m, 4H), 0.78 (s, 3H). 180 [00308]embedded image 614.2 Method C, RT = 1.75 min, 89.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (br d, J = 8.3 Hz, 1H), 7.91 - 7.75 (m, 2H), 7.58 (br d, J = 8.6 Hz, 2H), 7.43 (s, 1H), 6.90 - 6.71 (m, 2H), 6.34 (s, 1H), 5.08 - 4.97 (m, 1H), 4.55 - 4.38 (m, 1H), 4.15 - 4.00 (m, 1H), 3.94 - 3.83 (m, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 3.45 - 3.37 (m, 2H), 3.33 - 3.28 (m, 2H), 2.93 - 2.82 (m, 2H), 2.79 (s, 3H) 1.34 (d, J= 6.4 H, 6H). 181 [00309]embedded image 652.2 Method D, RT = 2.04 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.6 Hz, 1H), 8.49 - 8.35 (m, 1H), 7.81 (br d, J = 6.8 Hz, 2H), 7.60 -7.51 (m, 2H), 7.18 (br d, J= 5.9 Hz, 1H), 6.78 (d, J= 10.8 Hz, 2H), 5.18 - 5.00 (m, 1H), 4.44 - 4.05 (m, 2H), 3.88 - 3.75 (m, 1H) 3.74 (s, 3H), 3.44 - 3.37 (m, 2H), 2.92 - 2.69 (m, 2H), 2.37 -2.22 (m, 2H), 2.21 (s, 3H), 1.05 (d, J= 6.4 Hz, 6H). 182 [00310]embedded image 584.2 Method D, RT = 1.91 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 9.89 (m, 1H), 8.06 - 7.89 (m, 2H), 7.69 - 3.61 (m, 1H), 7.58 - 7.40 (m, 3H), 6.91 - 6.71 (m, 2H), 6.38 - 6.35 (m, 1H), 6.32 (t, J= 57.2 Hz, 1H), 5.40 - 4.78 (m, 1H), 4.54 - 4.33 (m, 2H), 4.17 - 3.98 (m, 1H), 3.74 - 3.70 (2 s, 3H), 3.65 - 3.56 (m, 1H), 3.47 - 3.38 (m, 1H), 2.24 - 2.08 (2 s, 3H). (mixture of interconvertible atropisomers) 183 [00311]embedded image 548.2 Method D, RT = 1.81 min, 94.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 -9.02 (m, 1H), 8.02 - 7.88 (m, 2H), 7.69 -7.62 (m, 1H), 7.57 - 7.39 (m, 3H), 6.88 -6.70 (m, 2H), 6.26 - 6.21 (m, 1H), 5.40 -4.78 (m, 1H), 4.17 - 3.89 (m, 3H), 3.74 -3.70 (2 s, 3H), 3.61 - 3.58 (m, 1H), 3.42 -3.37 (m, 1H), 2.22 - 2.02 (2 s, 3H), 1.28 -1.18 (m, 3H). (mixture of interconvertible atropisomers) 184 [00312]embedded image 573.1 Method D, RT = 2.24 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J= 8.6 Hz, 1H), 7.95 (d, J= 8.6 Hz, 2H), 7.71 (s, 1H), 7.62 - 7.55 (m, 1H), 7.51 - 7.46 (m, 3H), 7.26 (t, J= 76.2 Hz, 1H), 7.02 - 6.96 (m, 1H), 6.80 (d, J= 10.8 Hz, 2H), 5.11 - 4.98 (m, 1H), 4.24 - 4.07 (m, 2H), 4.05 - 3.96 (m, 1H), 3.78 (s, 3H). 185 [00313]embedded image 596.2 Method D, RT = 1.850 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 9.01 (m, 1H), 8.06 - 7.89 (m, 2H), 7.64 - 7.52 (m, 1H), 7.52 - 7.38 (m, 2H), 6.77 (dd, J= 10.8, 5.9 Hz, 2H), 6.26 - 6.12 (m, 1H), 5.39 - 4.84 (m, 1H), 4.30 - 3.99 (m, 4H), 3.79 - 3.71 (m, 3H), 3.62 - 3.54 (m, 2H), 3.54 - 3.44 (m, 1H), 3.26 - 3.21 (2 s, 3H), 2.23 - 1.99 (m, 3H). (mixture of interconvertible atropisomers) 186 [00314]embedded image 632.3 Method C, RT = 1.911 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.76 - 7.61 (m, 2H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.39 (t, J = 7.1 Hz, 1H), 5.17 -5.03 (m, 1H), 4.42 (dd, J= 13.4, 3.4 Hz, 1H), 4.38 - 4.26 (m, 1H), 4.16 - 3.92 (m, 4H), 3.76 (s, 3H), 3.36 (s, 3H). 187 [00315]embedded image 626.2 Method D, RT = 1.788 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 9.09 (m, 1H), 8.00 - 7.92 (m, 2H), 7.71 - 7.62 (m, 2H), 7.53 - 7.46 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.40 (t, J = 7.1 Hz, 1H), 5.15 (dd, J= 11.1, 8.4 Hz, 1H), 4.74 (br t, J= 5.4 Hz, 2H), 4.17 - 4.04 (m, 1H), 4.02 - 3.88 (m, 4H), 3.76 (s, 3H), 3.23 -3.10 (m, 4H), 0.78 (s, 3H). 188 [00316]embedded image 574.2 Method D, RT = 1.940 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J= 8.6 Hz, 1H), 7.95 - 7.70 (m, 4H), 7.92 (t, J= 59.6 Hz, 1H), 7.49 (d, J= 8.3 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.56 (t, J= 7.2 Hz, 1H), 5.09 (dd, J= 11.0, 8.6 Hz, 1H), 4.18 - 4.08 (m, 1H), 4.06 - 3.94 (m, 2H), 3.77 (s, 3H). 189 [00317]embedded image 522 Method D, RT = 1.730 min, 99.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.3 Hz, 1H), 8.07 (d, J= 2.9 Hz, 1H), 7.88 - 7.78 (m, 2H), 7.70 (d, J= 2.9 Hz, 1H), 7.63 - 7.50 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.10 (dd, J= 10.5, 8.8 Hz, 1H), 4.15 - 3.92 (m, 3H), 3.76 (s, 3H), 3.49 (s, 3H). 190 [00318]embedded image 588.2 Method D, RT = 1.803 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J= 8.6 Hz, 1H), 7.94 - 7.83 (m, 2H), 7.78 - 7.72 (m, 1H), 7.68 (dd, J= 7.2, 1.8 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.46 (t, J= 7.1 Hz, 1H), 5.12 (dd, J= 11.2, 8.6 Hz, 1H), 5.03 - 4.86 (m, 2H), 4.17 - 4.06 (m, 1H), 4.03 - 3.90 (m, 2H), 3.76 (s, 3H). 191 [00319]embedded image 606.2 Method D, RT = 1.972 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J= 8.6 Hz, 1H), 7.99 - 7.84 (m, 2H), 7.80 - 7.71 (m, 1H), 7.68 (dd, J= 7.1, 2.0 Hz, 1H), 7.55 - 7.36 (m, 2H), 6.78 (d, J= 10.8 Hz, 2H), 6.46 (t, J = 7.1 Hz, 1H), 5.13 (dd, J = 11.1, 8.7 Hz, 1H), 5.03 -4.84 (m, 2H), 4.17 - 4.05 (m, 1H), 4.04 -3.88 (m, 2H), 3.77 (s, 3H). 192 [00320]embedded image 556.3 Method D, RT = 1.81 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 9.86 (m, 1H), 8.01 - 7.84 (m, 2H), 7.72 - 8.65 (m, 1H), 7.60 - 7.39 (m, 1H), 7.35 (t, J = 73 Hz, 1H), 7.26 - 7.19 (m, 2H), 6.90 - 6.72 (m, 2H), 6.22 (d, J = 6.8 Hz, 1H), 5.43 - 4.76 (m, 1H), 4.20 - 3.93 (m, 2H), 3.90 - 3.74 (m, 2H), 3.72 - 3.66 (2 s, 3H), 3.42 - 3.37 (m, 1H), 2.23 - 1.99 (2 s, 3H), 1.31 - 1.15 (m, 1H), 0.55 - 0.45 (m, 2H), 0.41 - 0.30 (m, 2H). (mixture of interconvertible atropisomers) 193 [00321]embedded image 488.2 Method D, RT = 2.126 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.0 Hz, 1H), 7.92 - 7.71 (m, 3H), 7.61 - 3.52 (m, 3H), 6.78 (br d, J = 11.0 Hz, 2H), 6.33 (br t, J= 6.8 Hz, 1H), 5.12 (br t, J= 9.3 Hz, 1H), 4.09 (br d, J= 8.5 Hz, 1H), 3.97 (br d, J= 8.5 Hz, 2H), 3.77 (s, 3H), 3.51 (br s, 3H). 194 [00322]embedded image 611.3 Method C, RT = 1.510 min, 96.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (br d, J = 7.6 Hz, 1H), 7.98 - 7.91 (m, 2H), 7.68 (br d, J = 7.1 Hz, 1H), 7.56 (dt, J= 1.1, 6.9 Hz, 1H), 7.51 - 7.41 (m, 2H), 6.81 - 6.70 (m, 2H), 6.40 - 6.31 (m, 1H), 5.12 - 4.97 (m, 2H), 4.12 - 4.07 (m, 2H), 4.02 - 3.92 (m, 2H), 3.76 (s, 3H), 3.65 -3.61 (m, 1H), 3.34 - 3.31 (m, 1H), 3.25 -3.16 (m, 4H), 3.06 - 3.01 (m, 2H). 195 [00323]embedded image 574.3 Method D, RT = 1.86 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.77 (m, 1H), 8.02 - 7.63 (m, 3H), 7.33 (t, J = 76 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.81 - 6.72 (m, 2H), 6.32 - 6.10 (m, 1H), 5.42 - 4.80 (m, 1H), 4.32 - 4.04 (m, 2H), 3.93 - 3.66 (m, 5H), 3.55 - 3.43 (m, 1H), 2.24 - 1.99 (2 s, 3H), 1.29 - 1.11 (m, 1H), 0.55 - 0.42 (m, 2H), 0.42 - 0.30 (m, 2H). (mixture of atrop isomsers) 196 [00324]embedded image 522.2 Method D, RT = 1.680 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 9.00 (m, 1H), 7.92 - 7.75 (m, 3H), 7.64 - 7.47 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.53 (dd, J= 7.3, 8.6 Hz, 1H), 5.37 - 5.09 (m, 1H), 4.25 - 4.11 (m, 1H), 4.04 - 3.89 (m, 1H), 3.76 (s, 3H), 3.64 - 3.56 (m, 1H), 3.52 - 3.47 (2 s, 3H). (mixture of interconvertible atropisomers) 197 [00325]embedded image 548.2 Method D, RT = 1.695 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.88 (m, 1H), 7.96 - 7.76 (m, 2H), 7.71 - 7.64 (m, 1H), 7.34 (t, J = 76 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.84 - 6.66 (m, 2H), 6.31 - 6.16 (m, 1H), 5.36 - 4.82 (m, 1H), 4.29 - 4.07 (m, 2H), 4.02 - 3.83 (m, 2H), 3.80 - 3.72 (2 s, 3H), 3.53 - 3.45 (m, 1H), 2.23 - 1.99 (2 s, 3H), 1.26 - 1.17 (m, 3H). (mixture of interconvertible atropisomers) 198 [00326]embedded image 529.3 Method D, RT = 2.851 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 9.03 (m, 1H), 8.02 - 7.87 (m, 2H), 7.83 - 7.73 (m, 1H), 7.68 - 7.57 (m, 1H), 7.52 - 7.42 (m, 2H), 6.83 - 6.71 (m, 2H), 6.46 - 6.30 (m, 1H), 5.15 - 5.06 (m, 1H), 4.26 - 4.17 (m, 2H), 4.14 - 4.05 (m, 1H), 4.02 - 3.94 (m, 2H), 3.76 (s, 3H), 2.84 - 2.69 (m, 2H). 199 [00327]embedded image 607.2 Method D, RT = 1.66 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.3 Hz, 1H), 8.29 (dd, J = 8.9, 3.1 Hz, 1H), 7.94 (t, J = 9.2 Hz, 1H), 7.91 -7.83 (m, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 5.94 - 5.77 (m, 1H), 5.10 (dd, J = 10.5, 8.6 Hz, 1H), 4.39 (br t, J = 8.4 Hz, 1H), 4.30 - 4.17 (m, 2H), 4.12 - 3.96 (m, 2H), 3.77 (s, 3H), 3.68-3.66 (m, 1H), 2.44 - 2.34 (m, 1H), 1.89 - 1.74 (m, 1H). 200 [00328]embedded image 596.3 Method D, RT = 1.86 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J= 8.6 Hz, 1H), 8.01 - 7.85 (m, 2H), 7.69 (dd, J= 6.8, 2.0 Hz, 1H), 7.53 - 7.39 (m, 3H), 6.87 - 6.71 (m, 2H), 6.34 (t, J= 7.0 Hz, 1H), 5.12 (dd, J = 11.2, 8.6 Hz, 1H), 4.53-4.49 (m, 1H), 4.19 - 4.04 (m, 2H), 3.77 (s, 3H), 3.67 - 3.54 (m, 3H), 3.24 (s, 3H), 0.99 (d, J = 6.1 Hz, 3H). 201 [00329]embedded image 576.2 Method D, RT = 1.591 min, 100% .sup.1H NMR (400 MHz, DMSO-d6) δ = 7.94 - 7.85 (m, 2H), 7.64 (dd, J= 6.8, 2.0 Hz, 1H), 7.59 (dd, J= 7.2, 2.0 Hz, 1H), 7.36 (t, J= 72.2 Hz, 1H), 7.27 - 7.25 (m, 3H), 6.77 (d, J= 10.8 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 5.47 - 5.38 (m, 1H), 5.10 (d, J = 11.2 Hz, 1H), 4.18 - 3.92 (m, 4H), 3.90 -3.82 (m, 2H), 3.81 - 3.73 (m, 4H), 2.47 -2.42 (m, 1H), 2.04 - 1.92 (m, 1H). 202 [00330]embedded image 631.3 Method D, RT = 1.580 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J= 8.6 Hz, 1H), 8.13 (dd, J = 5.0, 2.0 Hz, 1H), 7.95 - 7.86 (m, 2H), 7.79 (dd, J = 7.6, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 7.10 (dd, J= 7.6, 5.1 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.12 (dd, J= 11.2, 8.6 Hz, 1H), 4.58 (s, 4H), 4.33 - 4.12 (m, 4H), 3.99 (br d, J= 10.0 Hz, 2H), 3.77 (s, 3H), 3.36 (m, 3H), 2.71 (t, J = 5.5 Hz, 2H). 203 [00331]embedded image 502.2 Method D, RT = 1.79 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J= 9.0 Hz, 1H), 8.12 (dd, J= 4.6, 1.2 Hz, 1H), 7.92 - 7.79 (m, 2H), 7.65 (dd, J = 8.3, 4.6 Hz, 1H), 7.60 - 7.52 (m, 2H), 7.44 (dd, J= 8.3, 4.6 Hz, 1H), 6.88 - 6.68 (m, 2H), 5.29 (dd, J= 11.5, 8.8 Hz, 1H), 4.37 - 4.24 (m, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.70 (t, J= 10.6 Hz, 1H), 1.01 (d, J = 6.1 Hz, 3H). 204 [00332]embedded image 572.1 Method D, RT = 2.12 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.87 (m, 1H), 8.10 - 7.99 (m, 1H), 7.80 (br d, J = 8.1 Hz, 1H), 7.66 (br d, J= 8.6 Hz, 2H), 7.35 (t, J = 72.0 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 6.71 - 6.57 (m, 2H), 5.28 - 5.18 (m, 1H), 4.44 - 4.26 (m, 3H), 3.70 (s, 3H), 2.39 (s, 3H). 205 [00333]embedded image 552.2 Method D, RT = 1.708 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J= 8.6 Hz, 1H), 8.05 (dd, J= 4.4, 3.3 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.78 (dd, J = 8.4, 3.3 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.12 (dd, J= 10.6, 8.7 Hz, 1H), 4.18 - 4.04 (m, 2H), 4.03 - 3.88 (m, 3H), 3.77 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H). 206 [00334]embedded image 583.2 Method C, RT = 1.87 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 10.61 (s, 1H), 9.21 (d, J = 8.3 Hz, 1H), 8.11 - 7.98 (m, 1H), 7.97 - 7.90 (m, 2H), 7.86 (t, J= 8.9 Hz, 1H), 7.50 (d, J= 8.6 Hz, 2H), 6.80 (d, J= 11.0 Hz, 2H), 5.07 (dd, J= 10.3, 8.6 Hz, 1H), 4.29 - 4.03 (m, 3H), 3.77 (s, 3H), 2.09 (s, 3H). 207 [00335]embedded image 513.1 Method D, RT = 1.650 min, 99.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.3 Hz, 1H), 8.66 (d, J= 2.4 Hz, 1H), 7.88 (d, J= 2.4 Hz, 1H), 7.86 - 7.75 (m, 2H), 7.62 - 7.53 (m, 2H), 6.82 - 6.68 (m, 2H), 5.10 (dd, J= 11.1, 8.7 Hz, 1H), 4.16 - 4.06 (m, 1H), 4.03 - 3.97 (m, 1H), 3.96 - 3.89 (m, 1H), 3.77 (s, 3H), 3.53 (s, 3H) 208 [00336]embedded image 560.2 Method D, RT = 1.65 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 - 8.93 (t, J= 8.4 Hz, 1H), 8.00 -7.81 (m, 2H), 7.61 - 7.50 (m, 2H), 7.35 (t, J = 72 Hz, 1H), 7.28 - 7.23 (m, 2H), 6.90 - 6.73 (m, 2H), 6.20 (d, J= 6.8 Hz, 1H), 5.42 -4.74 (m, 1H), 4.21 - 3.92 (m, 4H), 3.74 -3.70 (2S, 3H), 3.61 - 3.55 (m, 3H), 3.24 (s, 3H), 2.22 - 2.03 (2 s, 3H). (mixture of interconvertible atropisomers) 209 [00337]embedded image 605.2 Method D, RT = 1.845 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.64 (t, J = 9.2 Hz, 1H), 7.35 (t, J = 76 Hz, 1H),7.29 - 7.27 (m, 2H), 6.80 (br d, J= 10.8 Hz, 2H), 6.40 (dd, J= 9.0, 2.2 Hz, 1H), 5.17 - 5.05 (m, 1H), 4.71 (s, 4H), 4.24 - 4.02 (m, 6H), 4.00 - 3.94 (m, 1H), 3.78 (s, 3H). 210 [00338]embedded image 649.3 Method D, RT = 1.626 min, 95.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J= 8.6 Hz, 1H), 8.00 - 7.88 (m, 2H), 7.64 (dd, J= 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.1, 2.0 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.12 (dd, J= 11.1, 8.7 Hz, 1H), 4.57 (s, 4H), 4.15 - 4.04 (m, 1H), 4.01 - 3.92 (m, 2H), 3.88 - 3.84 (m, 2H), 3.77 (s, 3H), 3.29 (s, 4H), 2.61 (t, J= 6.0 Hz, 2H). 211 [00339]embedded image 587.2 Method D, RT = 1.964 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.75 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.68 - 7.61 (m, 1H), 7.61 - 7.54 (m, 1H), 7.33 (t, J= 72.6 Hz, 1H), 7.19 - 7.15 (m, 2H), 6.62 (d, J = 11.0 Hz, 2H), 6.31 (d, J = 7.8 Hz, 1H), 5.28 (t, J = 8.4 Hz, 1H), 4.85 - 4.81 (m, 1H), 4.67 - 4.62 (m, 1H), 4.40 - 4.19 (m, 3H), 3.82 - 3.68 (m, 4H), 3.65 (d, J= 7.6 Hz, 1H), 3.44 (br d, J= 9.8 Hz, 1H), 3.24 (m, 1H), 1.94 - 1.76 (m, 2H). 212 [00340]embedded image 611.2 Method D, RT = 2.05 min, 95.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.1 Hz, 1H), 7.83 - 7.77 (m, 3H), 7.59 - 7.55 (m, 2H), 7.13 (d, J = 8 Hz, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.39 - 5.25 (m, 1H), 5.11 - 5.06 (m, 1H), 4.97 (d, J = 3.2 Hz, 1H), 4.39 (br d, J= 2.7 Hz, 1H), 4.30 - 4.20 (m, 1H), 3.90 - 3.79 (m, 1H), 3.76 (s, 3H), 3.65 - 3.50 (m, 4H), 2.02 -1.83 (m, 2H). 213 [00341]embedded image 616.2 Method D, RT = 1.903 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.74 (d, J= 7.8 Hz, 1H), 7.78 - 7.63 (m, 3H), 7.63 - 7.55 (m, 1H), 7.33 (t, J = 76 Hz, 1H), 7.18 - 7.14 (m, 2H), 6.70 - 6.54 (m, 3H), 5.29 (t, J = 8.4 Hz, 1H), 4.42 - 4.24 (m, 4H), 4.12 - 3.98 (m, 2H), 3.70 (s, 3H), 2.17 (s, 3H), 2.16 - 2.08 (m, 3H), 1.07 (d, J= 6.1 Hz, 6H). 214 [00342]embedded image 646.3 Method D, RT = 1.97 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J= 8.3 Hz, 1H), 7.88 (d, J= 9.2 Hz, 2H), 7.35 (t, J= 73.6 Hz, 1H), 7.33 -7.27 (m, 4H), 6.79 (d, J= 10.8 Hz, 2H), 5.08 - 5.03 (m, 1H), 4.49 - 4.38 (m, 1H), 4.17 - 3.98 (m, 3H), 3.93 - 3.84 (m, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 2.48 (s, 3H), 2.30 -2.01 (m, 4H), 1.15 - 1.02 (m, 6H). 215 [00343]embedded image 482.2 Method D, RT = 1.557 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.89 (d, J= 8.8 Hz, 1H), 7.76 (dd, J= 6.7, 2.1 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.57 (dd, J= 7.2, 2.1 Hz, 1H), 7.28 (d, J= 8.1 Hz, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.35 (t, J= 7.0 Hz, 1H), 5.12 (dd, J= 11.1, 8.7 Hz, 1H), 4.18 - 4.04 (m, 1H), 4.04 - 3.89 (m, 4H), 3.76 (s, 3H), 2.35 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H). 216 [00344]embedded image 621.2 Method D, RT = 2.24 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J= 8.6 Hz, 1H), 8.02 - 7.81 (m, 4H), 7.34 (t, J= 73.6 Hz, 1H),7.29 - 7.27 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 5.16 - 5.03 (m, 1H), 4.33 - 4.19 (m, 4H), 4.10 - 3.96 (m, 3H), 3.77 (s, 3H), 3.60 - 3.48 (m, 1H), 1.26 (d, J = 6.1 Hz, 3H). 217 [00345]embedded image 608.3 Method D, RT = 1.54 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.87 (br d, J = 8.3 Hz, 1H), 7.96 - 7.84 (m, 2H), 7.71 (dd, J= 7.1, 2.0 Hz, 1H), 7.56 (dd, J= 7.1, 2.0 Hz, 1H), 7.33 (t, J= 73.6 Hz, 1H), 7.25- 7.23 (m, 2H),6.77 (d, J = 11.5 Hz, 2H), 6.33 (t, J = 7.1 Hz, 1H), 5.65 (dd, J = 11.7, 8.6 Hz, 1H), 5.14 -4.93 (m, 2H), 4.70 - 4.52 (m, 1H), 4.32 -4.27 (m, 1H), 3.76 (s, 3H), 3.75 - 3.69 (m, 4H), 3.23 (s, 3H), 0.91 (br d, J= 6.6 Hz, 3H). 218 [00346]embedded image 608.3 Method D, RT = 1.522 min, 97.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.98 (m, 1H), 7.93 - 7.85 (m, 2H), 7.69 - 7.61 (m, 2H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.40 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.1, 8.4 Hz, 1H), 4.74 (t, J = 5.4 Hz, 2H), 4.15 - 4.04 (m, 1H), 4.03 - 3.89 (m, 4H), 3.76 (s, 3H), 3.24 - 3.11 (m, 4H), 0.78 (s, 3H). 219 [00347]embedded image 550.2 Method D, RT = 1.700 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 (br d, J = 8.6 Hz, 1H), 8.02 - 7.83 (m, 2H), 7.65 (dd, J= 6.6, 2.0 Hz, 1H), 7.59 (dd, J= 7.1, 2.0 Hz, 1H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.12 (dd, J= 10.9, 8.7 Hz, 1H), 4.93 (t, J = 5.3 Hz, 1H), 4.17 - 4.05 (m, 1H), 4.05 - 3.90 (m, 4H), 3.77 (s, 3H), 3.70 - 3.59 (m, 2H). 220 [00348]embedded image 546.2 Method D, RT = 1.71 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J= 8.6 Hz, 1H), 7.88 - 7.77 (m, 2H), 7.68 (dd, J= 6.7, 1.8 Hz, 1H), 7.58 - 7.49 (m, 2H), 7.46 (dd, J= 6.7, 1.8 Hz, 1H), 6.87 - 6.72 (m, 2H), 6.34 (t, J= 7.1 Hz, 1H), 5.18 - 5.00 (m, 1H), 4.57 - 4.42 (m, 1H), 4.23 - 4.05 (m, 2H), 3.78 (s, 3H), 3.67 - 3.56 (m, 3H), 3.25 (m, 3H), 0.99 (d, J = 6.4 Hz, 3H). 221 [00349]embedded image 570.2 Method D, RT = 1.801 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J= 8.6 Hz, 1H), 8.03 - 7.87 (m, 2H), 7.72 (dd, J= 6.7, 1.8 Hz, 1H), 7.64 (dd, J = 7.3, 1.8 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.13 (dd, J= 10.9, 8.7 Hz, 1H), 4.71 (dt, J= 48.6, 4.6 Hz, 2H), 4.38 - 4.29 (m, 1H), 4.29 - 4.20 (m, 1H), 4.16 - 4.05 (m, 1H), 4.04 - 3.94 (m, 2H), 3.77 (s, 3H). 222 [00350]embedded image 526.1 Method D, RT = 1.94 min, 95.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (br d, J= 8.1 Hz, 1H), 8.90 (dd, J= 4.6, 1.2 Hz, 1H), 8.39 (dd, J = 7.8, 1.2 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.73 (dd, J = 7.7, 4.8 Hz, 1H), 7.62 - 7.51 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 5.14 (dd, J= 11.1, 8.7 Hz, 1H), 4.29 - 4.23 (m, 1H), 4.18 - 4.06 (m, 1H), 4.02 - 3.94 (m, 1H), 3.78 (s, 3H). 223 [00351]embedded image 617.2 Method D, RT = 1.75 min,93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J= 8.6 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.57 - 7.52 (m, 1H), 7.34 (t, J = 76 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.44 (d, J = 8.8 Hz, 1H), 5.22 (dd, J = 11.1, 8.9 Hz, 1H), 4.71 (s, 4H), 4.18 - 3.91 (m, 6H), 3.88 - 3.81 (m, 1H), 3.76 (s, 3H), 3.75 (s, 3H). 224 [00352]embedded image 688.2 Method D, RT = 1.94 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (br d, J= 8.1 Hz, 1H), 8.53 (br d, J= 6.6 Hz, 1H), 7.94 - 7.75 (m, 2H), 7.62 - 7.50 (m, 2H), 7.29 (br d, J= 5.4 Hz, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.20 - 5.03 (m, 1H), 4.46 - 4.12 (m, 2H), 3.90 - 3.74 (m, 1H), 3.72 (s, 3H), 3.32 - 3.18 (m, 6H), 2.95 (s, 3H), 2.64 - 2.53 (m, 2H). 225 [00353]embedded image 646.3 Method D, RT = 1.81 min,97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (br d, J = 9.0 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.54 - 7.52 (m, 1H), 7.34 (t, J= 76.0 Hz, 1H), 7. 28 - 7.26 (m, 2H), 6.88 (d, J = 8.8 Hz, 1H), 6.77 (d, J= 10.8 Hz, 2H), 5.21 (dd, J = 11.1, 8.9 Hz, 1H), 4.23 -4.10 (m, 1H), 4.10 - 3.93 (m, 3H), 3.89 -3.82 (m, 1H), 3.77 (s, 3H), 3.76 (s, 3H), 2.49 - 2.43 (m, 1H), 2.39 - 2.06 (m, 6H), 1.11 (br d, J= 6.4 Hz, 6H). 226 [00354]embedded image 516.2 Method D, RT = 1.53 min, 95.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.51 (d, J= 8.5 Hz, 1H), 7.93 (d, J = 9.0 Hz, 1H), 7.78 (dd, J= 6.5, 2.0 Hz, 1H), 7.76 - 7.66 (m, 2H), 7.64 (dd, J= 7.0, 2.0 Hz, 1H), 7.35 (t, J= 72.0 Hz, 1H), 7.23 - 7.16 (m, 2H), 6.82 - 6.63 (m, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.15 - 5.05 (m, 1H), 4.17 -4.06 (m, 1H), 4.04 - 3.94 (m, 3H), 3.82 -3.74 (m, 1H), 3.72 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H). 227 [00355]embedded image 568.2 Method D, RT = 1.64 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J= 8.6 Hz, 1H), 8.02 - 7.86 (m, 2H), 7.56 (d, J= 7.6 Hz, 1H), 7.52 - 7.36 (m, 2H), 6.85 - 6.68 (m, 2H), 6.40 (d, J= 7.6 Hz, 1H), 5.67 (t, J = 5.6 Hz, 1H), 5.12 (dd, J= 11.1, 8.7, Hz, 1H), 4.49 (d, J= 5.4 Hz, 2H), 4.18 - 4.04 (m, 1H), 4.02 -3.89 (m, 2H), 3.76 (s, 3H), 3.49 (s, 3H). 228 [00356]embedded image 566.2 Method D, RT = 1.886 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 8.95 (m, 1H), 8.02 - 7.83 (m, 2H), 7.76 - 7.60 (m, 1H), 7.56 - 7.33 (m, 2H), 6.79 - 6.72 (m, 2H), 6.30 - 6.14 (m, 1H), 5.38 - 4.79 (m, 1H), 4.30 - 4.06 (m, 2H), 4.04 - 3.84 (m, 2H), 3.80 - 3.69 (2 s, 3H), 3.53 - 3.44 (m, 1H), 2.22 - 1.97 (2 s, 3H), 1.29 - 1.15 (m, 3H). (mixture of interconvertible atropisomers). 229 [00357]embedded image 560.2 Method D, RT = 1.78 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J= 8.6 Hz, 1H), 7.96 - 7.85 (m, 2H), 7.79 (dd, J= 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.34 (t, J = 72 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.12 (dd, J= 10.9, 8.7 Hz, 1H), 4.17 - 4.04 (m, 1H), 4.04 - 3.91 (m, 2H), 3.87 - 3.78 (m, 2H), 3.77 (s, 3H), 1.31 - 1.16 (m, 1H), 0.55 - 0.43 (m, 2H), 0.43 - 0.33 (m, 2H). 230 [00358]embedded image 570.2 Method D, RT = 1.89 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J= 8.6 Hz, 1H), 8.05 (dd, J= 4.5, 3.3 Hz, 1H), 7.98 - 7.90 (m, 2H), 7.78 (dd, J = 8.4, 3.3 Hz, 1H), 7.49 (d, J = 8.9 Hz, 2H), 6.78 (d, J= 10.8 Hz, 2H), 5.14 (m, 1H), 4.19 - 4.04 (m, 2H), 4.03 - 3.88 (m, 3H), 3.77 (s, 3H), 1.25 (t, J= 7.1 Hz, 3H) 231 [00359]embedded image 668.2 Method D, RT = 1.69 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 9.00 (m, 1H), 8.24 - 8.06 (m, 1H), 7.95 - 7.78 (m, 2H), 7.35 (t, J= 72 Hz, 1H), 7.31 - 7.25 (m, 2H), 7.01 - 6.83 (m, 1H), 6.82 - 6.68 (m, 2H), 5.16 - 5.01 (m, 1H), 4.58 - 4.43 (m, 1H), 4.38 - 4.27 (m, 1H), 4.25 - 4.08 (m, 1H), 3.86 - 3.77 (m, 1H), 3.76 (s, 3H), 3.64 - 3.55 (m, 1H), 3.50 -3.40 (m, 1H), 3.28 - 3.21 (m, 1H), 2.83 -2.63 (m, 2H), 2.27 (s, 3H), 2.00 - 1.87 (m, 1H), 1.81 (m, 1H). 232 [00360]embedded image 578.2 Method D, RT = 1.686 min, 99.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.82 (m, 1H), 8.02 - 7.83 (m, 2H), 7.66 - 7.48 (m, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.88 - 6.61 (m, 2H), 6.28 -6.12 (m, 1H), 5.38 - 4.81 (m, 1H), 4.32 -3.94 (m, 4H), 3.82 - 3.72 (2 s, 3H), 3.62 -3.44 (m, 3H), 3.27 - 3.19 (2 s, 3H), 2.25 -2.02 (m, 3H). (mixture of interconvertible atropisomers) 233 [00361]embedded image 586.2 Method D, RT = 1.92 min, 97.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (br d, J= 8.1 Hz, 1H), 7.83 (br d, J = 8.6 Hz, 2H), 7.58 (br d, J = 8.3 Hz, 2H), 7.41 (s, 1H), 6.80 (br d, J= 10.8 Hz, 2H), 6.28 (s, 1H), 5.10 - 4.98 (m, 1H), 4.50 - 4.23 (m, 3H), 4.13 - 4.04 (m, 1H), 3.93 - 3.85 (m, 2H), 3.82 (s, 3H), 3.75 (s, 3H), 3.15 - 2.95 (m, 5H), 2.83 (s, 3H). 234 [00362]embedded image 631.3 Method D, RT = 1.74 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.99 (m, 1H), 8.24 - 8.14 (m, 1H), 7.94 -7.81 (m, 2H), 7.33 (t, J= 73.6 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.93 - 6.81 (m, 1H), 6.77 (d, J= 10.5 Hz, 2H), 6.28 (br d, J= 4.9 Hz, 1H), 5.16 - 4.93 (m, 2H), 4.32 -4.10 (m, 2H), 3.92 - 3.82 (m, 1H), 3.76 (s, 3H), 3.75 - 3.68 (m, 1H), 3.47 - 3.39 (m, 2H), 1.18 - 1.04 (m, 3H). (mixture of interconvertible atropisomers) 235 [00363]embedded image 594.2 Method D, RT = 1.972 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 (d, J = 8.6 Hz, 1H), 8.15 (dd, J = 5.0, 1.8 Hz, 1H), 8.02 - 7.88 (m, 2H), 7.79 (dd, J = 7.7, 1.8 Hz, 1H), 7.56 - 7.42 (m, 2H), 7.12 (dd, J = 7.6, 4.9 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.60 (br dd, J = 6.2, 4.5 Hz, 1H), 5.07 (dd, J = 11.0, 8.3 Hz, 1H), 4.16 (br d, J = 10.0 Hz, 1H), 4.05 - 3.88 (m, 3H), 3.87 - 3.80 (m, 2H), 3.77 (s, 3H), 3.76 - 3.73 (m, 1H), 2.30 - 2.21 (m, 1H), 2.12 - 2.03 (m, 1H). 236 [00364]embedded image 538.2 Method D, RT = 1.793 min, 96.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.5 Hz, 1H), 7.98 - 7.85 (m, 2H), 7.72 (dd, J= 2.0, 7.0 Hz, 1H), 7.67 (dd, J = 2.0, 7.5 Hz, 1H), 7.59 - 7.07 (m, 5H), 7.38 (t, J= 58.4 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 6.42 (t, J = 8.0 Hz, 1H), 6.35 (tt, J= 56.2 Hz, 1H), 5.05 (dd, J = 8.8, 10.8 Hz, 1H), 4.54 - 4.36 (m, 2H), 4.18 (t, J = 7.8 Hz, 1H), 3.91 - 3.65 (m, 2H). 237 [00365]embedded image 506.2 Method D, RT = 1.655 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.3 Hz, 1H), 7.95 - 7.75 (m, 3H), 7.65 - 7.55 (m, 2H), 7.50 (dd, J = 8.3, 3.4 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.55 (t, J = 5.9 Hz, 1H), 5.19 - 4.98 (m, 1H), 4.54 (d, J = 5.9 Hz, 2H), 4.27 - 4.13 (m, 2H), 4.11 - 4.00 (m, 1H), 3.77 (s, 3H). 238 [00366]embedded image 556.2 Method D, RT = 2.691 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.3 Hz, 1H), 8.47 (d, J = 1.2 Hz, 1H), 7.92 - 7.80 (m, 3H), 7.65 - 7.53 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 8.6, 10.8 Hz, 1H), 4.19 - 3.96 (m, 3H), 3.77 (s, 3H), 3.57 (s, 3H). 239 [00367]embedded image 645.2 Method D, RT = 1.84 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.8 Hz, 1H), 8.26 - 8.14 (m, 1H), 7.94 - 7.81 (m, 2H), 7.35 (t, J = 72.2 Hz, 1H), 7.34 - 7.25 (m, 2H), 6.94 - 6.83 (m, 1H), 6.78 (d, J= 10.5 Hz, 2H), 5.98 - 5.91 (m, 1H), 5.16 - 5.05 (m, 1H), 4.87 (s, 1H), 4.36 - 4.14 (m, 2H), 3.76 (s, 3H), 3.75 - 3.67 (m, 1H) 3.22 - 3.13 (m, 2H), 1.17 (s, 3H), 1.15 (s, 3H). 240 [00368]embedded image 554.2 Method D, RT = 1.572 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 11.91 - 11.48 (m, 1H), 9.11 (d, J = 8.8 Hz, 1H), 8.03 - 7.84 (m, 2H), 7.57 (d, J = 7.3 Hz, 1H), 7.48 (dd, J = 9.0, 1.0 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.26 (d, J = 7.3 Hz, 1H), 5.56 - 550 (brs, 1H), 5.13 (dd, J = 11.0, 8.6 Hz, 1H), 4.31 (s, 2H), 4.15 - 3.87 (m, 3H), 3.76 (s, 3H). 241 [00369]embedded image 602.2 Method D, RT = 1.838 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 8.95 (m, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.82 - 7.59 (m, 2H), 7.34 (t, J = 76.0 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.38 (t, J = 8.2 Hz, 1H), 5.19 -5.05 (m, 1H), 4.27 - 4.17 (m, 2H), 4.14 -4.03 (m, 1H), 4.03 - 3.92 (m, 2H), 3.77 (s, 3H), 2.85 - 2.69 (m, 2H). 242 [00370]embedded image 566.2 Method D, RT = 1.87 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.6 Hz, 1H), 7.99 - 7.87 (m, 2H), 7.79 (dd, J = 6.8, 2.0 Hz, 1H), 7.53 - 7.37 (m, 3H), 6.84 - 6.71 (m, 2H), 6.36 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 11.2, 8.6 Hz, 1H), 4.54 - 4.44 (m, 1H), 4.04 - 3.90 (m, 2H), 3.77 (s, 3H), 3.62 (t, J = 10.5 Hz, 1H), 1.24 (t, J= 7.1 Hz, 3H), 0.99 (d, J = 6.1 Hz, 3H). 243 [00371]embedded image 550.2 Method D, RT = 1.455 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.6 Hz, 1H), 7.96 - 7.81 (m, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.27 - 7.16 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.40 (d, J = 7.6 Hz, 1H), 5.67 (br s, 1H), 5.11 (dd, J= 11.0, 8.6 Hz, 1H), 4.49 (s, 2H), 4.15 - 3.90 (m, 3H), 3.76 (s, 3H), 3.49 (s, 3H). 244 [00372]embedded image 534.2 Method D, RT = 1.669 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 (br d, J = 8.3 Hz, 1H), 7.97 - 7.78 (m, 2H), 7.56 (s, 1H), 7.54 - 7.03 (m, 3H), 7.34 (t, J= 73.6 Hz, 1H), 6.77 (d, J = 10.5 Hz, 2H), 5.09 (dd, J = 11.0, 8.6 Hz, 1H), 4.11 (q, J= 10.3 Hz, 1H), 3.97 (br d, J = 9.5 Hz, 2H), 3.77 (s, 3H), 3.46 (s, 3H), 2.08 (s, 3H). 245 [00373]embedded image 621.2 Method D, RT = 1.876 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (br d, J = 8.3 Hz, 1H), 8.06 - 7.89 (m, 2H), 7.75 - 7.66 (m, 1H), 7.61 (dd, J = 7.2, 1.8 Hz, 1H), 7.52 - 7.44 (m, 3H), 7.43 - 7.34 (m, 2H), 6.41 (t, J = 7.2 Hz, 1H), 6.07 (dd, J = 8.8, 5.1 Hz, 1H), 5.08 - 4.94 (m, 1H), 4.14 - 4.05 (m, 2H), 3.91 - 3.75 (m, 4H), 3.26 (s, 3H), 3.10 (s, 3H), 2.84 (s, 3H). 246 [00374]embedded image 639.2 Method D, RT = 1.86 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 (d, J = 8.6 Hz, 1H), 8.25 (dd, J = 9.0, 3.2 Hz, 1H), 8.00 - 7.82 (m, 3H), 7.50 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.09 (dd, J = 10.3, 8.6 Hz, 1H), 4.86 (t, J = 5.6 Hz, 1H), 4.63-4.61 (m, 1H), 4.27-4.20 (m, 2H), 4.08 - 3.97 (m, 1H), 3.77 (s, 3H), 3.73-3.71 (m, 1H), 3.61-3.59 (m, 1H), 2.80 - 2.67 (m, 1H), 2.46 - 2.35 (m, 1H), 2.24 - 2.09 (m, 1H), 2.09 - 1.96 (m, 1H). 247 [00375]embedded image 572.2 Method D, RT = 1.99 min, 94.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.6 Hz, 1H), 8.25 (d, J = 8.3 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.69 (d, J = 8.8 Hz, 1H), 7.35 (t, J = 76.2 Hz, 1H), 7.28 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.16 (dd, J = 11.0, 8.8 Hz, 1H), 4.26 (q, J = 9.9 Hz, 1H), 4.10 (br t, J = 8.6 Hz, 1H), 3.99 - 3.88 (m, 1H), 3.77 (s, 3H), 2.61 (s, 3H). 248 [00376]embedded image 667.3 Method D, RT = 1.839 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.87 (m, 1H), 8.05 - 7.84 (m, 2H), 7.75 - 7.57 (m, 1H), 7.54 - 7.34 (m, 2H), 6.77 (dd, J= 5.6, 10.8 Hz, 1H), 6.35 - 6.19 (m, 1H), 6.11 - 5.92 (m, 1H), 5.39 - 4.82 (m, 1H), 4.30 - 3.96 (m, 3H), 3.92 - 3.68 (m, 5H), 3.59 - 3.45 (m, 1H), 3.29 - 3.23 (2 s, 3H), 3.16 - 3.06 (m, 3H), 2.86 - 2.80 (2 s, 3H), 2.22 - 1.95 (2 s, 3H). (Mixture of interconvertible atropisomers) 249 [00377]embedded image 534.2 Method D, RT = 1.77 min, 98.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.8 Hz, 1H), 8.00 - 7.92 (m, 2H), 7.75 (dd, J = 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.3, 2.0 Hz, 1H), 7.54 - 7.43 (m, 3H), 6.86 - 6.78 (m, 2H), 6.39 - 6.29 (m, 1H), 5.13 (dd, J = 11.4, 8.9 Hz, 1H), 4.19 -4.11 (m, 1H), 4.04 - 3.93 (m, 3H), 3.75 (s, 3H), 3.73 - 3.64 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H). 250 [00378]embedded image 624.2 Method D, RT = 1.89 min, 96.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (br d, J = 7.8 Hz, 1H), 8.45 - 8.41 (m, 1H), 7.89 - 7.79 (m, 2H), 7.59 - 7.54 (m, 2H), 7.20 (br d, J = 5.9 Hz, 1H), 6.79 (br d, J = 10.8 Hz, 2H), 5.18 - 5.02 (m, 1H), 4.41 - 4.15 (m, 2H), 3.78 (s, 3H), 3.77 -3.71 (m, 1H), 3.27 - 3.01 (m, 4H), 2.49 -2.37 (m, 4H), 2.22 (s, 3H). 251 [00379]embedded image 513.2 Method D, RT = 1.653 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.8 Hz, 1H), 8.02 (d, J = 7.1 Hz, 1H), 7.92 - 7.81 (m, 2H), 7.65 - 7.48 (m, 2H), 6.79 (d, J = 11.0 Hz, 2H), 6.70 (d, J = 7.1 Hz, 1H), 5.23 (dd, J = 11.5, 8.6 Hz, 1H), 4.26 - 4.11 (m, 2H), 3.77 (s, 3H), 3.75 - 3.70 (m, 1H), 3.56 (s, 3H). 252 [00380]embedded image 558.3 Method D, RT = 1.421 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 - 8.87 (m, 1H), 7.93 (d, J = 8.6 Hz, 2H), 7.68 (dd, J= 6.7, 1.8 Hz, 1H), 7.56 (dd, J = 7.5, 1.8 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.33 - 7.27 (m, 2H), 7.29 - 7.22 (m, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.34 (t, J = 7.1 Hz, 1H), 5.10 - 4.99 (m, 3H), 4.13 -4.06 (m, 2H), 3.79 - 3.64 (m, 7H), 3.23 (s, 3H), 3.17 (d, J = 4.9 Hz, 1H). 253 [00381]embedded image 578.3 Method D, RT = 1.692 min, 93.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.93 - 7.81 (m, 2H), 7.61 (dt, J = 7.2, 1.7 Hz, 2H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.14 -3.79 (m, 5H), 3.76 (s, 3H), 3.68 - 3.61 (m, 1H), 3.18 (s, 3H), 1.09 (d, J = 6.1 Hz, 3H). 254 [00382]embedded image 626.2 Method D, RT = 1.700 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.98 (m, 1H), 7.93 - 7.85 (m, 2H), 7.69 - 7.61 (m, 2H), 7.56 - 7.13 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.40 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.1, 8.4 Hz, 1H), 4.74 (t, J = 5.4 Hz, 2H), 4.15 - 4.04 (m, 1H), 4.03 - 3.89 (m, 4H), 3.76 (s, 3H), 3.24 -3.11 (m, 4H), 0.78 (s, 3H). 255 [00383]embedded image 548.2 Method D, RT = 1.70 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.78 (dd, J = 6.6, 2.0 Hz, 1H), 7.46-7.44 (m, 1H) 7.34 (t, J = 73.6 Hz, 1H), 7.27- 7.25 (m, 2H), 6.78 (d, J = 11.0 Hz, 2H), 6.36 (t, J = 7.0 Hz, 1H), 5.14-5.09 (m, 1H), 4.54 - 4.47 (m, 1H), 4.04 - 3.91 (m, 2H), 3.77 (s, 3H), 3.67-3.60 (m, 1H), 1.24 (t, J= 7.1 Hz, 3H), 0.98 (d, J = 6.1 Hz, 3H). 256 [00384]embedded image 605.2 Method D, RT = 1.904 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.6 Hz, 1H), 7.96 - 7.81 (m, 2H), 7.61 (t, J = 9.2 Hz, 1H), 7.34 (t, J = 72 Hz, 1 H), 7.29 - 7.26 (m, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.53 (dd, J= 2.2, 9.0 Hz, 1H), 5.20 - 5.08 (m, 1H), 4.83 - 4.78 (m, 1H), 4.68 - 4.62 (m, 1H), 4.25 - 4.13 (m, 2H), 4.04 - 3.92 (m, 1H), 3.78 (s, 4H), 3.64 (d, J = 7.3 Hz, 1H), 3.44 (d, J = 9.5 Hz, 1H), 3.23 (d, J = 10.3 Hz, 1H), 1.95 - 1.78 (m, 2H). 257 [00385]embedded image 649.3 Method D, RT = 1.672 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.91 (m, 1H), 7.98 - 7.80 (m, 2H), 7.69 - 7.56 (m, 1H), 7.55 - 6.92 (m, 2H), 7.34 (t, J = 73.6 Hz, 1H), 6.78 - 6.70 (m, 1H), 6.38 - 6.25 (m, 1H), 6.10 - 5.92 (m, 1H), 5.39 - 4.81 (m, 1H), 4.31 - 4.04 (m, 2H), 3.90 - 3.73 (m, 5H), 3.56 - 3.49 (m, 1H), 3.28 - 3.24 (2 s, 3H), 3.19 - 3.03 (m, 3H), 2.99 - 2.89 (m, 1H), 2.86 - 2.81 (2 s, 3H), 2.23 - 2.04 (2 s, 3H). (mixture of interconvertible atropisomers) 258 [00386]embedded image 552.2 Method D, RT = 1.625 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 7.83-7.95 (m, 2H), 7.72 (dd, J = 6.8, 2.0 Hz, 1H), 7.63 (dd, J = 7.1, 2.0 Hz, 1H), 7.35 (t, J = 72 Hz, 1 H), 7.28-7.26 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.71 (dt, J = 48.6, 4.6 Hz, 2H), 4.29 - 4.37 (m, 1H), 4.26 (dt, J = 4.6, 2.2 Hz, 1H), 4.04 - 4.14 (m, 1H), 3.94 - 4.02 (m, 2H), 3.76 (s, 3H). 259 [00387]embedded image 598.3 Method D, RT = 1.48 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.49 (d, J = 9.0 Hz, 1H), 6.84 - 6.70 (m, 2H), 6.51 (d, J = 9.0 Hz, 1H), 5.22 (dd, J = 11.4, 8.9 Hz, 1H), 4.48 - 7.43 (m, 1H), 4.17 -4.05 (m, 1H), 4.01 (br t, J = 8.8 Hz, 1H), 3.90 - 3.83 (m, 1H), 3.76 (s, 3H), 3.74 (s, 3H), 3.44 - 3.33 (m, 2H), 3.25-3.24 (m, 1H), 2.83 - 2.78 (m, 1H), 2.46-2.43 (m, 1H), 2.25 (s, 3H), 1.87-1.82 (m, 1H), 1.71-1.69 (m, 1H). 260 [00388]embedded image 542.3 Method D, RT = 1.56 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 - 8.90 (m, 1H), 8.00 - 7.85 (m, 2H), 7.58 - 7.51 (m, 1H), 7.41 - 7.16 (m, 5H), 6.97 - 6.85 (m, 2H), 6.24 - 6.18 (m, 1H), 5.27 - 4.60 (m, 1H), 4.20 - 3.97 (m, 3H), 3.93 - 3.79 (m, 2H), 3.75 - 3.71 (2 s, 3H), 3.61 - 3.53 (m, 2H), 3.24 (s, 3H), 2.20 - 2.07 (2 s, 3H). (mixture of interconvertible atropisomers isomsers) 261 [00389]embedded image 587.2 Method D, RT = 1.83 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (br d, J = 8.8 Hz, 1H), 8.29 - 8.13 (m, 1H), 7.99 - 7.78 (m, 2H), 7.35 (t, J = 72 Hz, 1H), 7.31 - 7.25 (m, 2H), 6.85 - 6.65 (m, 4H), 5.22 - 5.02 (m, 1H), 4.34 - 4.05 (m, 2H), 3.82 (s, 3H), 3.80 - 3.68 (s, 1H), 2.85 (d, J = 4.4 Hz, 3H). 262 [00390]embedded image 564.3 Method D, RT = 1.508 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.88 (m, 1H), 7.96 - 7.91 (m, 2H), 7.64 -7.07 (m, 4H), 6.77 (dd, J = 10.8, 4.9 Hz, 2H), 6.29 - 6.13 (m, 1H), 5.38 - 4.79 (m, 2H), 4.31 - 3.87 (m, 3H), 3.81 - 3.58 (m, 5H), 3.55 - 3.44 (m, 2H), 2.27 - 1.93 (2 s, 3H). (mixture of interconvertible atropisomers) 263 [00391]embedded image 611.2 Method D, RT = 1.88 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.8 Hz, 1H), 8.32 - 8.21 (m, 1H), 7.91 - 7.78 (m, 2H), 7.65 - 7.51 (m, 2H), 6.97 - 6.85 (m, 1H), 6.78 (d, J= 10.8 Hz, 2H), 6.13 - 5.95 (m, 1H), 5.21 - 5.02 (m, 1H), 4.37 - 4.11 (m, 3H), 3.95 - 3.83 (m, 2H), 3.82 (s, 3H), 3.79 - 3.64 (m, 3H), 2.31 - 2.19 (m, 1H), 2.04 - 1.89 (m, 1H). (mixture of interconvertible atropisomers). 264 [00392]embedded image 582.3 Method D, RT = 1.80 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.68 (dd, J = 6.6, 2.0 Hz, 1H), 7.53 - 7.39 (m, 3H), 6.79 (d, J = 11.0 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 11.4, 8.4 Hz, 1H), 4.99 - 4.90 (m, 1H), 4.55 - 4.44 (m, 1H), 4.06 - 3.98 (m, 2H), 3.77 (s, 3H), 3.68 - 3.56 (m, 3H), 0.99 (d, J = 5.9 Hz, 3H). 265 [00393]embedded image 554.3 Method D, RT = 1.541 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.81 (m, 1H), 7.98 - 7.83 (m, 2H), 7.58 - 7.48 (m, 1H), 7.42 - 7.07 (m, 5H), 6.99 - 6.80 (m, 2H), 6.32 - 6.24 (m, 1H), 5.43 - 5.30 (m, 1H), 5.26 - 4.63 (m, 1H), 4.14 - 3.99 (m, 2H), 3.94 - 3.63 (m, 7H), 3.46 (t, J = 9.7 Hz, 1H), 2.47 - 2.38 (m, 1H), 2.22 - 2.07 (2 s, 3H), 2.02 - 1.88 (m, 1H). (mixture of interconvertible atropisomers). 266 [00394]embedded image 621.1 Method D, RT = 1.80 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.0 Hz, 1H), 8.25 (dd, J = 9.0, 3.0 Hz, 1H), 7.92 - 7.87 (m, 3H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.79 (d, J = 11.0 Hz, 2H), 5.08 (dd, J = 10.0, 8.5 Hz, 1H), 4.85 (t, J = 5.8 Hz, 1H), 4.61- 4.58 (m, 1H), 4.32 - 4.14 (m, 2H), 4.05 - 3.96 (m, 1H), 3.77 (s, 3H), 3.75 -3.66 (m, 1H), 3.64 - 3.60 (m, 1H), 2.74 -2.67 (m, 1H), 2.42 - 2.40 (m, 1H), 2.33 -2.30 (m,1H), 2.10 - 2.04 (m, 1H). 267 [00395]embedded image 533.2 Method D, RT = 1.989 min, 93.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 9.08 (m, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.63 - 7.48 (m, 4H), 7.11 (dd, J = 10.4, 1.3 Hz, 1H), 6.81 (d, J = 10.8 Hz, 2H), 5.18 (d, J = 1.5 Hz, 1H), 5.06 (dd, J= 8.1, 10.0 Hz, 1H), 4.24 - 4.05 (m, 2H), 4.04 -3.99 (m, 1H), 3.79 (s, 3H), 1.44 (s, 6H). 268 [00396]embedded image 582.2 Method D, RT = 1.640 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.93 (dd, J = 4.5, 3.3 Hz, 1H), 7.91 - 7.85 (m, 2H), 7.80 (dd, J = 8.4, 3.3 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 10.8, 8.6 Hz, 1H), 4.18 - 4.03 (m, 4H), 3.97 (s, 1H), 3.77 (s, 3H), 3.61 (t, J= 5.4 Hz, 2H), 3.26 (s, 3H). 269 [00397]embedded image 628.2 Method D, RT = 2.016 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.6 Hz, 1H), 8.01 - 7.89 (m, 2H), 7.79 (dd, J = 6.6, 2.0 Hz, 1H), 7.61 (dd, J = 7.1, 2.0 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.36 (t, J = 7.0 Hz, 1H), 5.13 (dd, J= 10.8, 8.6 Hz, 1H), 4.20 - 4.05 (m, 3H), 4.05 - 3.91 (m, 2H), 3.77 (s, 3H), 2.69 - 2.55 (m, 4H), 2.48 - 2.41 (m, 1H). 270 [00398]embedded image 641.2 Method D, RT = 1.698 min, 94.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.8 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.1 Hz, 1H), 7.54 - 7.11 (m, 3H), 7.34 J= 73.6 Hz, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.23 - 5.12 (m, 1H), 4.31 - 4.19 (m, 1H), 4.13 (br t, J = 9.8 Hz, 1H), 3.96 (br t, J = 9.8 Hz, 1H), 3.77 (s, 3H), 3.08 (br d, J= 12.0 Hz, 2H), 2.95 - 3.90 (m, 1H), 2.68 - 2.61 (m, 2H), 1.85 - 2.80 (m, 2H), 1.72 - 1.60 (m, 2H). 271 [00399]embedded image 593.3 Method D, RT = 1.83 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 7.93 - 7.83 (m, 2H), 77.53 - 7.48 (m, 1H), 7.35 (t, J= 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.96 (d, J= 5.9 Hz, 1H), 6.87 - 6.64 (m, 2H), 6.46 (dd, J = 8.9, 2.6 Hz, 1H), 5.17 - 5.05 (m, 1H), 4.29 - 4.19 (m, 1H), 4.19 - 4.08 (m, 2H), 4.02 - 3.93 (m, 1H), 3.90 - 3.88 (m, 1H), 3.85 - 3.77 (m, 1H), 3.76 (s, 3H), 3.73-3.71 (m, 1H), 3.51-3.49 (m, 1H), 2.18-2.13 (m, 1H), 1.86 - 1.70 (m, 1H). 272 [00400]embedded image 578.2 Method D, RT = 1.946 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.8 Hz, 1H), 8.03 - 7.87 (m, 2H), 7.79 (dd, J = 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 7.1, 2.0 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.0, 8.6 Hz, 1H), 4.17 - 4.05 (m, 1H), 4.05 - 3.92 (m, 2H), 3.89 - 3.73 (m, 2H), 3.72 (s, 3H), 1.31 - 1.18 (m, 1H), 0.55 - 0.45 (m, 2H), 0.43 - 0.34 (m, 2H). 273 [00401]embedded image 498.3 Method D, RT = 1.692 min, 93.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.87 (d, J = 8.5 Hz, 1H), 7.79 - 7.69 (m, 2H), 7.65 (dd, J= 6.8, 1.8 Hz, 1H), 7.58 (dd, J = 7.5, 2.0 Hz, 1H), 7.28 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 10.5 Hz, 2H), 6.35 - 6.27 (m, 1H), 5.11 (dd, J = 11.0, 8.5 Hz, 1H), 4.98 - 4.89 (m, 1H), 4.14 - 4.06 (m, 1H), 4.03 - 3.94 (m, 4H), 3.76 (s, 3H), 3.65 (d, J = 5.5 Hz, 2H), 2.35 (s, 3H). 274 [00402]embedded image 626.2 Method D, RT = 1.700 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.63 - 7.58 (m, 2H), 7.34 (t, J= 73.6 Hz, 1H), 7.28 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.10 (dd, J = 10.9, 8.9 Hz, 1H), 4.15 - 3.82 (m, 5H), 3.76 (s, 3H), 3.67 - 3.63 (m, 1H), 3.19 (s, 3H), 1.09 (d, J = 6.1 Hz, 3H). 275 [00403]embedded image 626.2 Method D, RT = 1.77 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.5 Hz, 1H), 8.39 - 8.25 (m, 1H), 8.23 - 8.13 (m, 1H), 7.90 - 7.75 (m, 2H), 7.62 - 7.49 (m, 2H), 6.79 (d, J = 10.5 Hz, 2H), 6.73 -6.61 (m, 1H), 6.43 - 6.27 (m, 1H), 5.21 - 5.02 (m, 1H), 4.38 - 4.05 (m, 3H), 3.85 - 3.79 (m, 1H), 3.77 (s, 3H), 2.66 (d, J = 8 Hz, 3H), 1.32 (d, J = 4.2 Hz, 3H). 276 [00404]embedded image 528.3 Method D, RT = 1.509 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.6 Hz, 1H), 7.99 - 7.90 (m, 2H), 7.64 (dd, J = 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.2, 2.0 Hz, 1H), 7.33 (t, J = 80.0 Hz, 1H), 7.36 - 7.27 (m, 4H), 6.96 - 6.80 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.01 (dd, J = 10.9, 8.9 Hz, 1H), 4.18 - 4.06 (m, 3H), 3.81 - 3.68 (m, 5H), 3.60 (t, J = 5.4 Hz, 2H), 3.25 (s, 3H). 277 [00405]embedded image 566.2 Method D, RT = 1.782 min, 99.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 8.1 Hz, 2H), 7.88 (d, J = 8.1 Hz, 2H), 7.67 (dd, J = 6.8, 2.0 Hz, 1H), 7.61 (dd, J = 7.3, 2.0 Hz, 1H), 6.77 (d, J = 10.8 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.15 (dd, J = 11.0, 8.6 Hz, 1H), 4.22 - 4.06 (m, 3H), 4.04 - 3.94 (m, 2H), 3.77 (s, 3H), 3.61 (t, J= 5.3 Hz, 2H), 3.26 (s, 3H). 278 [00406]embedded image 637.3 Method D, RT = 1.504 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 7.86 - 8.00 (m, 2H), 7.72 (dd, J = 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.49 (dd, J = 8.9, 0.9 Hz, 2H), 6.69 - 6.84 (m, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 11.1, 8.7 Hz, 1H), 3.91 - 4.15 (m, 5H), 3.76 (s, 3H), 3.54 (t, J= 4.5 Hz, 4H), 2.57 (s, 2H), 2.36 - 2.48 (m, 4H). 279 [00407]embedded image 656.3 Method D, RT = 1.71 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (br d, J = 8.8 Hz, 1H), 8.62 - 8.51 (m, 1H), 7.92 - 7.80 (m, 2H), 7.35 (t, J = 72 Hz, 1H), 7.34 - 7.23 (m, 3H), 6.80 (d, J = 10.8 Hz, 2H), 5.15 - 4.99 (m, 1H), 4.46 - 4.38 (m, 1H), 4.32 - 4.16 (m, 1H), 3.90 - 3.78 (m, 1H), 3.77 (s, 3H), 3.49 - 3.37 (m, 4H), 3.30 - 3.05 (m, 4H), 2.89 (s, 3H). 280 [00408]embedded image 591.2 Method D, RT = 1.82 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 8.27 (dd, J = 9.2, 3.1 Hz, 1H), 7.95 - 7.85 (m, 3H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 5.11 (br dd, J= 10.4, 8.2 Hz, 1H), 4.31 - 4.17 (m, 2H), 4.10 -3.91 (m, 3H), 3.78 (s, 3H), 2.59 (t, J= 8.1 Hz, 2H), 2.09 - 1.98 (m, 2H). 281 [00409]embedded image 638.3 Method C, RT = 1.71 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.95 (m, 1H), 8.29 - 8.20 (m, 2H), 7.91 - 7.75 (m, 2H), 7.61 - 7.56 (m, 2H), 6.81 - 6.76 (m, 2H), 6.75 - 6.68 (m, 1H), 6.58 - 6.51 (m, 1H), 5.19 - 4.98 (m, 1H), 4.35 - 4.26 (m, 1H), 4.25 - 4.10 (m, 1H), 3.89 - 3.75 (m, 2H), 3.80 (s, 3H), 3.78 - 3.74 (m, 1H), 2.64 - 2.68 (m, 1H), 0.68 - 0.62 (m, 2H), 0.46 - 0.42 (m, 2H). 282 [00410]embedded image 720.2 Method D, RT = 1.88 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 8.98 (m, 1H), 8.57 - 8.49 (m, 1H), 7.87 (td, J = 7.4, 0.9 Hz, 2H), 7.35 (t, J = 72 Hz, 1H), 7.32 - 7.25 (m, 3H), 6.79 (d, J = 10.8 Hz, 2H), 5.17 - 5.06 (m, 1H), 4.45 -4.35 (m, 1H), 4.29 - 4.18 (m, 1H), 3.90 -3.80 (m, 1H), 3.77 (s, 3H), 3.41 - 3.25 (m, 8H), 2.96 (s, 3H). 283 [00411]embedded image 653.3 Method D, RT = 1.790 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.8 Hz, 1H), 8.00 - 7.87 (m, 2H), 7.72 (dd, J = 7.1, 2.0 Hz, 1H), 7.62 (dd, J = 7.2, 2.0 Hz, 1H), 7.54 - 7.40 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.4 (t, J = 7.1 Hz, 1H), 6.06 (dd, J = 8.6, 5.1 Hz, 1H), 5.13 (dd, J = 11.1, 8.7 Hz, 1H), 4.15 -3.96 (m, 2H), 3.96 - 3.79 (m, 3H), 3.76 (s, 3H), 3.27 (s, 3H), 3.12 (s, 3H), 2.85 (s, 3H). 284 [00412]embedded image 614.3 Method D, RT = 1.53 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 9.0 Hz, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.61 - 7.54 (m, 2H), 7.52 (d, J = 8.8 Hz, 1H), 6.86 (d, J = 8.8 Hz, 1H), 6.82 -6.71 (m, 2H), 5.21 (dd, J = 9.2, 10.9 Hz, 1H), 4.18 - 4.01 (m, 2H), 3.99 - 3.90 (m, 2H), 3.88 - 3.82 (m, 1H), 3.76 (s, 6H), 2.47 - 2.39 (m, 2H), 2.23 - 2.11 (m, 5H), 1.12 - 1.01 (m, 6H). 285 [00413]embedded image 630.2 Method D, RT = 1.73 min, 96.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.36 (t, J = 73.6 Hz, 1H), 7.30 - 7.26 (m, 3H), 6.80 (d, J = 10.8 Hz, 2H), 5.84 (s, 1H), 5.08 (dd, J = 11.1, 8.4 Hz, 1H), 4.70 - 4.60 (m, 1H), 4.52 - 4.40 (m, 1H), 4.12 - 4.01 (m, 1H), 3.91 - 3.83 (m, 2H), 3.81 (s, 3H) 3.78 (s, 3H), 3.67 - 3.56 (m, 1H), 3.46 (m, 1H), 2.92 - 2.85 (m, 1H), 2.46 - (s, 3H), 1.97 - 1.85 (m, 2H), 1.79 - 1.75 (m, 1H). 286 [00414]embedded image 554.1 Method D, RT = 1.659 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.93 (m, 1H), 7.97 - 7.78 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.53 (dd, J = 7.3, 8.6 Hz, 1H), 5.35 - 5.07 (m, 1H), 4.24 -4.09 (m, 1H), 4.05 - 3.89 (m, 1H), 3.76 (s, 3H), 3.64 - 3.53 (m, 1H), 3.50 (d, J = 5.6 Hz, 3H). (mixture of interconvertible atropisomers) 287 [00415]embedded image 581.3 Method D, RT = 1.76 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 (d, J = 8.6 Hz, 1H), 8.33 (d, J = 5.9 Hz, 1H), 7.87 - 7.78 (m, 2H), 7.61 - 7.53 (m, 2H), 7.00 (d, J = 6.4 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.10 (dd, J = 10.8, 8.6 Hz, 1H), 4.38 - 4.30 (m, 1H), 4.20 (q, J = 9.9 Hz, 1H), 4.06 - 3.96 (m, 1H), 3.77 (s, 3H), 3.57 - 3.45 (m, 4H),2.51 - 2.44 (m, 4H), 2.26 (s, 3H). 288 [00416]embedded image 578.2 Method D, RT = 1.83 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 9.00 (m, 1H), 8.09 - 7.87 (m, 2H), 7.66 - 7.35 (m, 4H), 6.94 - 6.66 (m, 2H), 6.20 (d, J = 6.8 Hz, 1H), 5.41 - 4.78 (m, 1H), 4.22 - 3.89 (m, 4H), 3.78 - 3.72 (2 s, 3H), 3.63 - 3.37 (2 s, 3H), 3.24 (s, 3H), 2.21 -2.06 (2 s, 3H). (mixture of interconvertible atropisomers isomers) 289 [00417]embedded image 644.1 Method D, RT = 1.99 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 (d, J = 8.3 Hz, 1H), 7.99 - 7.82 (m, 3H), 7.50 (d, J= 8.8 Hz, 2H), 7.13 (dd, J= 9.3, 2.4 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.17 - 5.07 (m, 1H), 4.28 - 4.16 (m, 2H), 4.09 - 3.99 (m, 1H), 3.94 - 3.82 (m, 2H), 3.77 (s, 3H), 3.59 (t, J= 7.2 Hz, 2H), 2.43 - 2.38 (m, 2H). 290 [00418]embedded image 626.2 Method D, RT = 1.77 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.5 Hz, 1H), 8.39 - 8.25 (m, 1H), 8.23 - 8.13 (m, 1H), 7.90 - 7.75 (m, 2H), 7.62 - 7.49 (m, 2H), 6.79 (d, J = 10.5 Hz, 2H), 6.73 -6.61 (m, 1H), 6.43 - 6.27 (m, 1H), 5.21 - 5.02 (m, 1H), 4.38 - 4.05 (m, 3H), 3.85 - 3.79 (m, 1H), 3.77 (s, 3H), 2.69 - 2.64 (2 s, 3H), 1.43 - 1.32 (m, 3H). (mixture of interconvertible atropisomers) 291 [00419]embedded image 552.2 Method D, RT = 1.761 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.95 (m, 1H), 8.01 - 7.86 (m, 2H), 7.73 - 7.57 (m, 1H), 7.54 - 7.36 (m, 2H), 6.88 - 6.66 (m, 2H), 6.28 - 6.15 (m, 1H), 5.38 - 4.84 (m, 1H), 4.30 - 4.05 (m, 2H), 3.80 - 3.72 (2 s, 3H), 3.55 - 3.40 (m, 4H), 2.23 - 2.01 (2 s, 3H). (mixture of interconvertible atropisomers) 292 [00420]embedded image 512.3 Method D, RT = 1.560 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.89 (d, J = 8.8 Hz, 1H), 7.77 - 7.69 (m, 2H), 7.66 (dd, J = 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.28 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 8.7, 11.1 Hz, 1H), 4.20 - 4.04 (m, 3H), 3.97 (br d, J = 9.5 Hz, 2H), 3.76 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H), 2.35 (s, 3H). 293 [00421]embedded image 626.2 Method D, RT = 1.72 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (br d, J = 8.1 Hz, 1H), 7.96 (d, J= 8.6 Hz, 2H), 7.74 - 7.66 (m, 1H), 7.56 (dd, J = 7.0, 1.3 Hz, 1H), 7.45 (d, J = 8.6 Hz, 2H), 6.77 (d, J = 11.5 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.71 - 5.61 (m, 1H), 5.14 - 4.97 (m, 2H), 4.67 - 4.56 (m, 1H), 4.29 (dd, J = 11.7, 8.3 Hz, 1H), 3.83 - 3.69, (m, 4H), 3.65 (td, J= 5.4, 10.9 Hz, 2H), 3.34 - 3.32 (m, 1H), 3.23 (s, 3H), 0.91 (br d, J = 6.8 Hz, 3H). 294 [00422]embedded image 632.2 Method D, RT = 1.808 min, 98.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.84 (m, 1H), 8.00 - 7.82 (m, 2H), 7.73 - 7.06 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H), 6.79 - 6.73 (m, 2H), 6.35 - 6.11 (m, 1H), 5.37 - 4.75 (m, 1H), 4.49 - 4.03 (m, 5H), 3.88 - 3.74 (m, 4H), 3.55 - 3.48 (m, 1H), 2.25 - 2.01 (2 s, 3H). (mixture of interconvertible atropisomers) 295 [00423]embedded image 613.3 Method D, RT = 1.563 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 (d, J = 9.0 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.65 - 7.56 (m, 1H), 7.52 - 7.15 (m, 4H), 6.95 - 6.80 (m, 2H), 6.28 (d, J = 7.6 Hz, 1H), 6.02 (s, 1H), 5.21 - 4.73 (m, 1H), 4.11 - 4.03 (m, 1H), 3.93 - 3.75 (m, 5H), 3.74 - 3.67 (2 s, 3H), 3.28 - 3.22 (2 s, 3H), 3.16 - 3.05 (m, 3H), 2.90 - 2.80 (2 s, 3H), 2.24 - 2.06 (2 s, 3H). (mixture of interconvertible atropisomers) 296 [00424]embedded image 518.2 Method D, RT = 1.656 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J = 8.6 Hz, 1H), 7.78 - 7.70 (m, 3H), 7.66 (dd, J= 7.3, 2.0 Hz, 1H), 7.28 (d, J = 8.1 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.42 (t, J = 8.0 Hz, 1H), 6.35 (tt, J = 56.2 Hz, 1H), 5.11 (dd, J = 8.6, 11.0 Hz, 1H), 4.55 - 4.35 (m, 2H), 4.16 - 4.05 (m, 1H), 3.98 (br d, J = 9.3 Hz, 2H), 3.76 (s, 3H), 2.35 (s, 3H). 297 [00425]embedded image 664.2 Method D, RT = 2.100 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 - 8.88 (m, 1H), 8.04 - 7.82 (m, 2H), 7.71 - 7.54 (m, 1H), 7.54 - 7.26 (m, 2H), 6.77 (dd, J = 10.6, 5.5 Hz, 2H), 6.44 - 6.10 (m, 1H), 5.40 - 4.80 (m, 1H), 4.43 - 3.89 (m, 5H), 3.83 - 3.69 (m, 3H), 3.61 - 3.46 (m, 1H), 3.38 - 3.33 (m, 3H), 2.26 - 2.03 (m, 3H). (mixture of interconvertible atropisomers) 298 [00426]embedded image 594.2 Method D, RT = 1.773 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.6 Hz, 1H), 7.98 - 7.89 (m, 2H), 7.64 (dd, J = 7.1, 2.0 Hz, 1H), 7.59 (dd, J = 7.2, 2.0 Hz, 1H), 7.49 (dd, J = 1.0, 8.8 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 5.45 - 5.39 (m, 1H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.17 -4.02 (m, 2H), 3.98 (br d, J= 8.8 Hz, 2H), 3.87 (d, J = 4.4 Hz, 2H), 3.82 - 3.69 (m, 4H), 2.48 - 2.40 (m, 1H), 1.98 (m, 1H). 299 [00427]embedded image 545.2 Method D, RT = 1.397 min, 94.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.83 (s, 1H), 9.07 (d, J = 8.6 Hz, 1H), 8.14 (d, J= 2.7 Hz, 1H), 7.84 (d, J= 8.6 Hz, 2H), 7.66 (d, J = 2.7 Hz, 1H), 7.58 - 7.52 (m, 3H), 6.78 (d, J = 10.8 Hz, 2H), 5.01 (br dd, J = 8.2, 9.9 Hz, 1H), 4.16 - 3.94 (m, 3H), 3.74 (s, 3H), 3.49 (s, 3H), 2.00 (s, 3H). 300 [00428]embedded image 491.1 Method D, RT = 1.65 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 9.01 (m, 2H), 8.66 - 8.51 (m, 1H), 7.89 (d, J = 8.6 Hz, 2H), 7.78 (dd, J = 9.3, 4.6 Hz, 1H), 7.35 (t, J = 76 Hz, 1H), 7.30-7.29 (m, 2H), 6.80 (br d, J = 10.5 Hz, 2H), 5.06 (br t, J = 9.4 Hz, 1H), 4.58 (br t, J = 8.8 Hz, 1H), 4.30 - 4.05 (m, 2H), 3.78 (s, 3H). 301 [00429]embedded image 582.1 Method D, RT = 1.73 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.8 Hz, 1H), 8.02 - 7.91 (m, 2H), 7.67 (dd, J = 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 6.6, 2.0 Hz, 1H), 7.45 (d, J = 8.1 Hz, 2H), 6.82 - 6.70 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.67 (dd, J = 12.0, 8.6 Hz, 1H), 4.65 - 4.59 (m, 1H), 4.32 - 4.27 (m, 1H), 4.12 - 4.06 (m, 2H), 3.97 - 3.92 (m, 2H), 3.76 (s, 3H), 3.34 - 3.30 (m, 1H), 0.92 (d, J = 6.8 Hz, 3H). 302 [00430]embedded image 582.2 Method D, RT = 1.808 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.5 Hz, 1H), 7.99 - 7.90 (m, 2H), 7.67 (dd, J= 6.8, 1.8 Hz, 1H), 7.60 (dd, J = 7.0, 2.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 10.8, 8.8 Hz, 1H), 4.17 - 4.04 (m, 3H), 4.03 - 3.93 (m, 2H), 3.77 (s, 3H), 3.60 (t, J= 5.3 Hz, 2H), 3.25 (s, 3H). 303 [00431]embedded image 618.2 Method D, RT = 1.76 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (br d, J = 9.0 Hz, 1H), 7.95 - 7.83 (m, 2H), 7.62 (d, J = 9.0 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.97 (d, J = 9.0 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.21 - 5.16 (m, 1H), 4.34 - 4.12 (m, 3H), 4.11 - 4.05 (m, 1H), 3.93 - 3.83 (m, 1H), 3.79 (s, 3H), 3.77 (s, 3H), 3.58 -3.47 (m, 2H), 3.18 - 2.96 (m, 4H), 2.86 (s, 3H). 304 [00432]embedded image 562.2 Method D, RT = 1.527 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.82 (dd, J = 7.0, 1.6 Hz, 1H), 7.64 (dd, J = 7.2, 1.6 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.45 (t, J = 7.1 Hz, 1H), 5.54 (m, 1H), 5.09 (dd, J = 10.6, 8.7 Hz, 1H), 4.89 (t, J = 7.2 Hz, 2H), 4.77 (q, J = 7.2 Hz, 2H), 4.15 - 4.03 (m, 1H), 3.99 -3.95 (m, 2H), 3.76 (s, 3H). 305 [00433]embedded image 534.1 Method D, RT = 1.55 min, 95.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 -9.07 (m, 1H), 8.76 - 8.75 (d, J = 4.4 Hz, 1H), 7.98 -7.97 (m, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.78 - 7.74 (m, 1H), 7.57 - 7.51 (m, 2H), 6.76 - 6.74 (d, J = 10.8 Hz, 1 H), 6.63 - 6.60 (d, J = 11.2 Hz, 1H), 5.17 -5.13 (m, 1H), 4.22 - 4.19 (m, 1H), 4.1 -4.03 (m, 2H), 3.77 (s, 3H), 1.85 - 1.65 (m, 6H). 306 [00434]embedded image 667.2 Method D, RT = 1.524 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.8 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.75 (dd, J = 6.7, 2.0 Hz, 1H), 7.60 (dd, J = 7.1, 2.0 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 10.9, 8.4 Hz, 1H), 4.14 - 4.01 (m, 3H), 3.98 (br d, J = 8.6 Hz, 2H), 3.76 (s, 3H), 3.14 - 3.05 (m, 4H), 3.04 - 2.90 (m, 4H), 2.85 - 2.77 (m, 2H). 307 [00435]embedded image 562.2 Method D, RT = 1.618 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 9.0 Hz, 2H), 7.68 (dd, J = 7.2, 1.8 Hz, 1H), 7.58 - 7.54 (m, 1H), 7.53 - 7.32 (m, 5H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 - 7.22 (m, 1H), 6.34 (t, J = 7.1 Hz, 1H), 5.12 - 4.99 (m, 3H), 4.20 - 4.13 (m, 1H), 3.88 - 3.59 (m, 6H), 3.22 (s, 3H). 308 [00436]embedded image 578.2 Method D, RT = 1.575 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.8 Hz, 1H), 7.95 - 7.81 (m, 2H), 7.65 (dd, J = 6.8, 2.0 Hz, 1H), 7.60 (dd, J = 7.3, 2.0 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.32 (t, J = 7.1 Hz, 1H), 5.15 (dd, J = 10.9, 8.7 Hz, 1H), 4.79 (br s, 1H), 4.12 - 4.03 (m, 1H), 4.02 - 3.88 (m, 4H), 3.76 (s, 3H), 1.09 (d, J = 5.1 Hz, 6H). 309 [00437]embedded image 592.2 Method D, RT = 1.86 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.5 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.73 - 7.60 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.32 - 7.29 (m, 2H), 6.89 - 6.73 (m, 3H), 5.12 (dd, J = 8.5, 10.5 Hz, 1H), 4.25 - 4.14 (m, 2H), 4.03-3.95 (m, 1H), 3.77 (s, 3H), 3.74 - 3.66 (m, 4H), 3.43-3.41 (m, 4H). 310 [00438]embedded image 534.2 Method D, RT = 1.575 min, 99.1 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.90 (m, 1H), 7.98 - 7.79 (m, 2H), 7.74 - 7.58 (m, 1H), 7.53 -7.16 (m, 3H), 6.85 - 6.70 (m, 2H), 6.26 - 6.16 (m, 1H), 5.38 - 4.83 (m, 1H), 4.31 - 4.06 (m, 2H), 3.81 - 3.71 (2 s, 3H), 3.53 - 3.41 (m, 4H), 2.23 - 1.97 (2 s, 3H). (mixture of interconvertible atropisomers) 311 [00439]embedded image 588.2 Method D, RT = 1.792 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.89 (m, 1H), 8.15 - 8.01 (m, 1H), 7.89 (dd, J = 8.7, 5.0 Hz, 2H), 7.34 - 7.16 (m, 3H), 6.80 - 6.68 (m, 2H), 6.57 (dd, J = 7.0, 5.3 Hz, 1H), 5.36 - 5.10 (m, 1H), 4.26 - 4.12 (m, 1H), 4.03 - 3.86 (m, 1H), 3.75 (s, 3H), 3.61 - 3.40 (m, 4H). (mixture of interconvertible atropisomers). 312 [00440]embedded image 574.3 Method C, RT = 1.94 min, 98.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 9.89 (m, 1H), 8.02 - 7.89 (m, 2H), 7.72 - 7.66 (m, 1H), 7.57 - 7.41 (m, 3H), 6.87 - 6.74 (m, 2H), 6.22 (d, J = 6.8 Hz, 1H), 5.42 - 4.75 (m, 1H), 4.18 - 3.95 (m, 1H), 3.86 - 3.81 (m, 1H), 3.78 -3.74 (2 s, 3H) 3.76 - 3.65 (m, 1H), 3.42 - 3.35 (m, 2H), 2.20 - 2.10 (2 s, 3H), 1.27 - 1.18 (m, 1H), 0.53 - 0.44 (m, 2H), 0.42 - 0.34 (m, 2H) (mixture of interconvertible atropisomers isomers) 313 [00441]embedded image 534.2 Method D, RT = 1.85 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.6 Hz, 1H), 7.91 - 7.75 (m, 3H), 7.65 (dd, J = 8.4, 3.5 Hz, 1H), 7.61 - 7.49 (m, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.34 (br s, 1H), 5.16 (dd, J = 10.6, 8.7 Hz, 1H), 4.32 - 4.15 (m, 2H), 4.11 - 4.02 (m, 1H), 3.77 (s, 3H), 1.43 (s, 3H), 1.42 (s, 3H). 314 [00442]embedded image 646.3 Method D, RT = 1.943 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.87 (m, 1H), 8.04 - 7.81 (m, 2H), 7.73 - 7.57 (m, 1H), 7.36 - 7.16 (m, 3H), 6.82 - 6.63 (m, 2H), 6.36 - 6.16 (m, 1H), 5.42 - 4.81 (m, 1H), 4.46 - 3.90 (m, 5H), 3.84 - 3.72 (2 s, 3H), 3.61 - 3.50 (m, 1H), 3.37 - 3.34 (2 s, 3H), 2.24 - 2.08 (2 s, 3H). (mixtrue of interconvertible atropisomers) 315 [00443]embedded image 558.3 Method D, RT = 1.424 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 - 8.88 (m, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.71 - 7.64 (m, 1H), 7.56 (d, J = 7.3 Hz, 1H), 7.33 (t, J = 80 Hz, 1H), 7.54 - 7.13 (m, 4H), 6.90 (d, J = 8.3 Hz, 2H), 6.34 (t, J = 6.8 Hz, 1H), 5.11 - 4.97 (m, 3H), 4.16 - 4.08 (m, 2H), 3.80 - 3.62 (m, 8H), 3.23 (s, 3H). 316 [00444]embedded image 592.2 Method D, RT = 1.95 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (br d, J = 8.6 Hz, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.86 - 7.72 (m, 1H), 7.35 (t, J = 70 Hz, 1H), 7.37 - 7.29 (m, 3H), 6.79 (d, J = 10.8 Hz, 2H), 5.14-5.11 (m, 1H), 4.32 - 4.17 (m, 2H), 4.16 - 4.03 (m, 1H), 3.99 - 3.88 (m, 2H), 3.78 (s, 3H), 3.45 - 3.42 (m, 2H), 3.02 - 2.91 (m, 1H), 1.86 - 1.61 (m, 4H). 317 [00445]embedded image 603.2 Method D, RT = 1.696 min, 96.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.90 (m, 1H), 7.97 - 7.86 (m, 2H), 7.70 (dd, J = 7.0, 1.8 Hz, 1H), 7.61 (dd, J = 7.2, 1.8 Hz, 1H), 7.50 - 7.37 (m, 4H), 7.34 (t, J = 73.6 Hz, 1H), 7.27 (d, J = 8.2 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 6.07 (dd, J = 8.4, 5.0 Hz, 1H), 5.07 - 4.95 (m, 1H), 4.13 - 4.08 (m, 1H), 3.91 - 3.77 (m, 4H), 3.26 (s, 3H), 3.10 (s, 3H), 2.84 (s, 3H). 318 [00446]embedded image 609.3 Method D, RT = 1.95 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 (d, J = 8.3 Hz, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 9.0 Hz, 1H), 6.82 (d, J = 10.8 Hz, 2H), 5.05 (dd, J = 10.9, 8.4 Hz, 1H), 4.67 - 4.52 (m, 2H), 4.49 - 4.40 (m, 1H), 4.27 - 4.16 (m, 1H), 4.05 - 3.96 (m, 1H), 3.78 (s, 3H), 3.40 -3.28 (m, 2H), 3.16 - 3.02 (m, 2H), 2.85 (s, 3H), 1.37 (d, J = 6.8 Hz, 6H). 319 [00447]embedded image 493.2 Method D, RT = 1.458 min, 100% .sup.1H NMR (400 MHz, DMSO-d6) δ = 9.27 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 1.2 Hz, 4H), 7.77 (dd, J = 6.6, 2.0 Hz, 1H), 7.58 (dd, J= 7.1, 2.0 Hz, 1H), 6.78 (d, J= 10.8 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.14 (dd, J = 11.0, 8.6 Hz, 1H), 4.17 - 4.04 (m, 1H), 4.04 - 3.86 (m, 4H), 3.76 (s, 3H), 1.25 (t, J= 7.2 Hz, 3H). 320 [00448]embedded image 576.2 Method D, RT = 1.591 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 7.93 - 7.84 (m, 2H), 7.64 (dd, J = 1.8, 7.0 Hz, 1H), 7.59 (dd, J = 2.0, 7.1 Hz, 1H), 7.34 (t, J = 76 Hz, 1H), 7.27 - 7.28 (m, 3H), 6.77 (d, J = 11.0 Hz, 2H), 6.41 (t, J = 7.1 Hz, 1H), 5.44 - 5.40 (m, 1H), 5.13 - 5.09 (m, 1H), 4.16 - 3.91 (m, 4H), 3.87 (d, J = 4.4 Hz, 2H), 3.80 - 3.72 (m, 4H), 2.47 -2.40 (m, 1H), 2.06 - 1.93 (m, 1H). 321 [00449]embedded image 529.2 Method D, RT = 1.542 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 (d, J = 8.6 Hz, 1H), 8.05 - 7.90 (m, 4H), 7.74 (dd, J = 6.8, 2.0 Hz, 1H), 7.67 (dd, J = 7.3, 2.0 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 6.35 (t, J = 56.2 Hz, 1H), 6.43 - 6.4 (m, 1H), 5.13 (dd, J = 11.0, 8.6 Hz, 1H), 4.56 - 4.34 (m, 2H), 4.16 - 4.05 (m, 1H), 4.05 - 3.90 (m, 2H), 3.77 (s, 3H). 322 [00450]embedded image 600.2 Method D, RT = 1.824 min, 97.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.8 Hz, 1H), 7.99 - 7.88 (m, 3H), 7.81 (dd, J= 8.4, 3.3 Hz, 1H), 7.54 - 7.40 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.14 (dd, J= 8.6, 10.8 Hz, 1H), 4.20 - 4.03 (m, 4H), 4.02 - 3.91 (m, 1H), 3.77 (s, 3H), 3.61 (t, J = 5.4 Hz, 2H), 3.26 (s, 3H). 323 [00451]embedded image 577.2 Method D, RT = 1.382 min, 99.03% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ =9.83 (s, 1H), 9.01 (d, J= 8.1 Hz, 1H), 8.14 (d, J= 2.7 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.66 (d, J = 2.7 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.07 - 4.94 (m, 1H), 4.19 - 3.91 (m, 3H), 3.77 (s, 3H), 3.49 (s, 3H), 2.01 (s, 3H). 324 [00452]embedded image 534.2 Method D, RT = 1.589 min, 99.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 9.0 Hz, 1H), 7.92 - 7.83 (m, 2H), 7.55 - 7.14 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H), 6.77 (d, J= 11.0 Hz, 2H), 6.28 - 6.20 (m, 1H), 5.11 (dd, J = 10.8, 8.6 Hz, 1H), 4.12 - 4.03 (m, 1H), 3.97 - 3.92 (m, 2H), 3.76 (s, 3H), 3.49 (s, 3H), 2.40 (s, 3H). 325 [00453]embedded image 626.3 Method D, RT = 1.762 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 - 8.91 (m, 1H), 8.02 - 7.84 (m, 2H), 7.70 - 7.54 (m, 1H), 7.54 - 7.34 (m, 2H), 6.79 - 3.72 (m, 2H), 6.31 - 6.13 (m, 1H), 5.38 - 4.83 (m, 3H), 4.27 - 4.05 (m, 2H), 3.81 - 3.55 (m, 7H), 3.55 - 3.45 (m, 1H), 3.24 - 3.16 (2 s, 3H), 2.23 - 1.94 (2 s, 3H). (mixture of interconvertible atropisomers) 326 [00454]embedded image 625.2 Method D, RT = 1.85 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 (d, J = 8.3 Hz, 1H), 8.29 (dd, J = 9.0, 2.9 Hz, 1H), 8.03 - 7.88 (m, 3H), 7.55 - 7.41 (m, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.86 (d, J = 6.1 Hz, 1H), 5.12 (dd, J = 10.5, 8.3 Hz, 1H), 4.44 - 4.38 (m, 1H), 4.29 -4.16 (m, 2H), 4.13 - 3.93 (m, 2H), 3.77 (s, 3H), 3.73-3.69 (m, 1H), 2.44 - 2.33 (m, 1H), 1.88 - 1.75 (m, 1H). 327 [00455]embedded image 597.2 Method C, RT = 1.73 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.8 Hz, 1H), 8.26 - 8.21 (m, 1H), 7.89 -7.80 (m, 2H), 7.63 - 7.55 (m, 2H), 6.98 - 6.89 (m, 1H), 6.79 (d, J = 10.8 Hz, 2H), 6.51 - 6.45 (m, 1H), 5.19 - 5.11 (m, 1H), 4.86 - 4.81(m, 2H), 4.77 - 4.69 (m, 1H), 4.65 - 4.60 (m, 2H), 4.35 - 4.26 (m, 1H), 4.22 - 4.15 (m, 1H), 3.76 (s, 3H), 3.75 - 3.63 (m, 1H). 328 [00456]embedded image 630.3 Method C, RT = 1.47 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.8 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.50 - 7.48 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 - 7.27 (m, 2H), 6.84 - 6.69 (m, 2H), 6.52 (d, J = 9.0 Hz, 1H), 5.22-5.198 (m, 1H), 4.48 - 4.42 (m, 1H), 4.18 - 4.08 (m, 1H), 4.04 - 3.96 (m, 1H), 3.91 - 3.82 (m, 1H), 3.76 (s, 3H), 3.74 (s, 3H), 3.47 - 3.40 (br s, 2H), 3.25 - 3.230 (m, 1H), 2.89 - 2.74 (m, 1H), 2.47 - 2.43 (m, 1H), 2.30 (s, 3H), 1.88 - 1.81 (m, 1H), 1.71-1.68 (m, 1H). 329 [00457]embedded image 509.2 Method D, RT = 1.268 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.28 (br d, J = 8.8 Hz, 1H), 8.07 - 7.87 (m, 4H), 7.65 (dd, J = 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 6.77 (d, J = 10.8 Hz, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.16 - 5.11 (m, 2H), 4.14 - 3.93 (m, 5H), 3.76 (s, 3H), 3.64 (t, J = 5.5 Hz, 2H). 330 [00458]embedded image 545.2 Method D, RT = 1.621 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 8.65 (d, J = 2.2 Hz, 1H), 7.98 - 7.79 (m, 3H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.10 (dd, J = 8.6, 11.0 Hz, 1H), 4.17 - 4.07 (m, 1H), 4.01 (br t, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.53 (s, 3H). 331 [00459]embedded image 636.1 Method D, RT = 1.555 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.1 Hz, 1H), 8.01 - 7.93 (m, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.34 (t, J = 72.6 Hz,1H), 7.28 (d, J = 8.6 Hz, 2H), 6.83 -6.75 (m, 2H), 5.14 - 5.06 (m, 2H), 4.35 -4.19 (m, 4H), 4.13 - 3.91 (m, 3H), 3.77 (s, 3H), 3.68 - 3.47 (m, 3H). 332 [00460]embedded image 641.3 Method D, RT = 1.94 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 9.0 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H), 7.90 - 7.87 (d, J = 8.8 Hz, 2H), 7.35 (t, J= 73.6 Hz, 1H), 7.30 - 7.28 (m, 2H), 7.06 - 7.04 (m, 1H), 6.81 (d, J= 10.8 Hz, 2H), 5.04 (dd, J = 10.8, 8.3 Hz, 1H), 4.66 - 4.54 (m, 2H), 4.49 - 4.43 (m, 1H), 4.24 - 4.21 (m, 1H), 4.03 - 4.01 (m, 1H), 3.78 (s, 3H), 3.13 - 3.02 (m, 2H), 2.91 - 2.79 (m, 2H), 2.48 (s, 3H) 1.39 - 1.30 (m, 6H). 333 [00461]embedded image 606.2 Method C, RT = 1.88 min, 90.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (br d, J = 8.1 Hz, 1H), 8.50 - 8.37 (m, 1H), 7.91 - 7.72 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.47 (t, J = 64.2 Hz, 1H), 7.19 (br d, J = 5.6 Hz, 1H), 6.78 (br d, J = 10.8 Hz, 2H), 5.17 - 5.04 (m, 1H), 4.42 - 4.10 (m, 2H), 3.88 - 3.78 (m, 1H), 3.77 (s, 3H), 3.47 - 3.36 (m, 2H), 3.21 - 3.09 (m, 2H), 2.47 - 2.34 (m, 4H), 2.22 (s, 3H). 334 [00462]embedded image 636.2 Method D, RT = 1.72 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.8 Hz, 1H), 8.18 - 8.07 (m, 1H), 7.85 (br d, J = 7.6 Hz, 2H), 7.57 (d, J = 8.6 Hz, 2H), 7.02 - 6.84 (m, 1H), 6.79 (d, J = 10.8 Hz, 2H), 5.15 - 5.04 (m, 1H), 4.46 (br s, 1H), 4.39 - 4.26 (m, 1H), 4.21 - 4.06 (m, 1H), 3.88 - 3.75 (m, 1H), 3.71 (s, 3H), 3.62 - 3.53 (m, 1H), 3.26 - 3.21 (m, 2H), 3.49 - 3.41 (m, 1H), 2.81 - 2.73 (m, 1H), 2.25 (s, 3H), 1.98 - 1.87 (m, 1H), 1.83 - 1.66 (m, 1H). 335 [00463]embedded image 485.2 Method D, RT = 2.003 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.8 Hz, 1H), 8.00 - 7.89 (m, 2H), 7.48 (d, J = 8.3 Hz, 2H), 6.76 (d, J = 10.8 Hz, 2H), 4.92 (dd, J = 10.4, 8.7 Hz, 1H), 3.93 - 3.89(m, 1H), 3.76 (s,3H), 3.75 -3.68 (m, 1H), 3.66 - 3.54 (m, 1H), 3.29 -3.24 (m, 1H), 3.06 (dd, J = 13.9, 7.1 Hz, 1H), 1.01 - 0.89 (m, 1H), 0.50 (d, J = 8.1 Hz, 2H), 0.29 - 0.11 (m, 2H). 336 [00464]embedded image 578.2 Method D, RT = 1.709 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J= 8.6 Hz, 1H), 7.94 - 7.81 (m, 2H), 7.34 (t, J = 76 Hz, 1H), 7.48 - 7.25 (m, 3H), 6.77 (d, J= 10.5 Hz, 2H), 6.26 - 6.17 (m, 1H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.17 (t, J = 5.5 Hz, 2H), 4.13 - 4.01 (m, 1H), 3.94 (br d, J = 9.8 Hz, 2H), 3.76 (s, 3H), 3.59 (t, J = 5.6 Hz, 2H), 3.24 (s, 3H), 2.44 (s, 3H). 337 [00465]embedded image 556.2 Method D, RT = 1.832 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.90 (m, 1H), 8.13 - 7.98 (m, 1H), 7.91 - 7.72 (m, 2H), 7.61 - 7.45 (m, 2H), 6.77 (dd, J = 2.1, 10.6 Hz, 2H), 6.62 - 6.48 (m, 1H), 5.33 - 5.12 (m, 1H), 4.27 - 4.07 (m, 1H), 4.03 - 3.89 (m, 2H), 3.75 (s, 3H), 3.59 - 3.54 (2 s, 3H). (mixture of interconvertible atropisomers) 338 [00466]embedded image 459.1 Method D, RT = 1.65 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 (d, J = 8.1 Hz, 1H), 9.08 (dd, J= 4.6, 1.5 Hz, 1H), 8.59 (dd, J = 9.0, 1.5 Hz, 1H), 7.91 - 7.74 (m, 3H), 7.64 - 7.51 (m, 2H), 6.81 (d, J = 10.8 Hz, 2H), 5.07 (dd, J = 10.8, 8.2 Hz, 1H), 4.59 (t, J = 9.0 Hz, 1H), 4.27 - 4.05 (m, 2H), 3.78 (s, 3H). 339 [00467]embedded image 564.2 Method D, RT = 1.961 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.98 (m, 1H), 8.05 - 7.89 (m, 2H), 7.56 (dd, J = 7.0, 4.3 Hz, 1H), 7.54 - 7.42 (m, 5H), 7.42 - 7.32 (m, 1H), 6.23 - 6.19 (m, 1H), 5.31 - 5.28 (m, 1H), 4.17 - 3.85 (m, 5H), 3.73 - 3.52 (m, 2H), 3.24 (s, 3H), 2.22 - 2.09 (2 s, 3H). 340 [00468]embedded image 546.2 Method D, RT = 1.776 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 8.88 (m, 1H), 7.95 - 7.90 (m, 2H), 7.60 - 7.48 (m, 2H), 7.45 - 7.16 (m, 5H), 6.24 - 6.14 (m, 1H), 5.27 - 4.67 (m, 1H), 4.06 (br s, 3H), 3.96 - 3.89 (m, 2H), 3.72 - 3.70 (m, 2H), 3.24 (s, 3H), 2.22 - 2.09 (2 s, 3H). (mixture of interconvertible atropisomers) 341 [00469]embedded image 500.1 Method D, RT = 1.91 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 - 9.17 (m, 1H), 7.93 - 7.78 (m, 4H), 7.73 - 7.63 (m, 1H), 7.62 - 7.53 (m, 2H), 6.81 (d, J= 10.8 Hz, 2H), 5.26 - 5.06 (m, 1H), 4.34 - 4.24 (m, 1H), 4.13 - 4.04 (m, 1H), 4.00 - 3.90 (m, 1H), 3.78 (s, 3H). 342 [00470]embedded image 528.2 Method D, RT = 1.468 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.82 (d, J = 8.8 Hz, 1H), 7.88 - 7.75 (m, 2H), 7.66 (dd, J = 6.8, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.08 - 6.93 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 11.0, 8.8 Hz, 1H), 4.22 - 4.01 (m, 3H), 4.01 - 3.88 (m, 2H), 3.81 (s, 3H), 3.76 (s, 3H), 3.60 (t, J = 5.3 Hz, 2H), 3.25 (s, 3H). 343 [00471]embedded image 617.2 Method D, RT = 1.65 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.45-7.43 (m, 1H), 7.44 (d, J = 8.2 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 -7.16 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.19 (dd, J = 11.4, 8.9 Hz, 1H), 4.28 -4.15 (m, 1H), 4.13 - 4.03 (m, 1H), 4.01 -3.90 (m, 3H), 3.76 (s, 3H), 3.43 - 3.39 (m, 2H), 2.85 - 2.84 (m, 1H), 2.75 (s, 6H), 1.80 - 1.63 (m, 4H). 344 [00472]embedded image 527.1 Method C, RT = 1.67 min, 94.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.36 (d, J = 8.6 Hz, 1H), 8.90 (dd, J = 4.8, 1.3 Hz, 1H), 8.84 - 8.78 (m, 1H), 8.40 (dd, J = 7.9, 1.3 Hz, 1H), 8.22 (dd, J = 8.3, 2.4 Hz, 1H), 7.80 - 7.61 (m, 2H), 6.90 - 6.71 (m, 2H), 5.15 (dd, J = 11.0, 8.6 Hz, 1H), 4.29- 4.21 (m, 1H), 4.17 - 4.14 (m, 1H), 4.01 - 3.99 (m, 1H), 3.78 (s, 3H). 345 [00473]embedded image 498.2 Method D, RT = 1.502 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 6.8, 1.5 Hz, 1H), 7.58 (dd, J = 7.3, 1.5 Hz, 1H), 7.48 - 7.30 (m, 3H), 7.19 - 7.03 (m, 1H), 6.77 (d, J = 10.8 Hz, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 10.8, 9.0 Hz, 1H), 4.19 - 4.04 (m, 1H), 4.04 - 3.89 (m, 4H), 3.79 (s, 3H), 3.77 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H). 346 [00474]embedded image 507.1 Method D, RT = 1.41 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 13.11 - 12.82 (m, 1H), 9.08 - 8.96 (m, 1H), 8.30 - 8.01 (m, 2H), 7.97 - 7.81 (m, 2H), 7.35 (t, J = 70 Hz, 1H), 7.31- 7.26 (m, 2H), 6.78 (d, J = 11.0 Hz, 2H), 5.15-5.11 (m, 1H), 4.15 - 3.89 (m, 3H), 3.77 (s, 3H). 347 [00475]embedded image 556.3 Method D, RT = 1.639 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.79 (d, J = 8.6 Hz, 1H), 7.84 - 7.72 (m, 2H), 7.65 (dd, J = 6.8, 2.0 Hz, 1H), 7.58 (dd, J = 7.3, 2.0 Hz, 1H), 7.04 - 6.90 (m, 2H), 6.76 (d, J = 10.5 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.10 (dd, J = 11.0, 8.6 Hz, 1H), 4.70 (m, 1H), 4.21 - 4.03 (m, 3H), 4.02 -3.89 (m, 2H), 3.76 (s, 3H), 3.60 (t, J= 5.3 Hz, 2H), 3.25 (s, 3H), 1.27 (d, J = 5.9 Hz, 6H). 348 [00476]embedded image 656.3 Method C, RT = 1.66 min, 95.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.4 Hz, 1H), 7.89 - 7.87 (m, 2H), 7.42 (d, J = 8.4 Hz, 1H), 7.35 (t, J= 73.6 Hz, 1H), 7.28 (d, J = 8.2 Hz, 2H), 6.95 -6.92 (m, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 10.8, 8.6 Hz, 1H), 4.46 -4.35 (m, 3H), 4.26 - 4.05 (m, 2H), 4.01 -3.92 (m, 1H), 3.77 (s, 3H), 3.08 - 2.71 (m, 6H), 1.97 - 1.87 (m, 1H), 1.36 (d, J = 6.8 Hz, 6 H), 0.96 - 0.76 (m, 2H), 0.62 - 0.43 (m, 2H). 349 [00477]embedded image 576.3 Method D, RT = 1.95 min, 100% 1H NMR (400 MHz, DMSO-d6) δ = 8.89 - 8.82 (m, 1H), 8.50 (t, J = 7.9 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H), 7.73 - 7.70 (m, 1H), 6.94 - 6.84 (m, 1H), 6.84 - 6.80 (m, 2H), 6.67 - 6.59 (m, 2H), 4.98 - 4.81 (m, 1H), 4.18 - 4.02 (m, 2H), 4.01 - 3.89 (m, 1H), 3.78 (s, 3H), 3.69 (s, 3H), 2.78 -2.56 (m, 4H), 2.51 - 2.54 (m, 1H), 1.93 -1.77 (m, 1H), 1.66 - 1.48 (m, 1H). 350 [00478]embedded image 608.3 Method F, RT = 1.84 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.01 (m, 1H), 8.01 - 7.85 (m, 2H), 7.60 - 7.51 (m, 1H), 7.51 - 7.38 (m, 2H), 6.79-6.75 (m, 2H), 6.36 - 6.21 (m, 1H), 5.43 -4.87 (m, 2H), 4.31 - 4.00 (m, 3H), 3.90 -3.81 (m, 2H), 3.81 - 3.69 (m, 4H), 3.54 -3.48 (m, 1H), 2.47 - 2.39 (m, 1H), 2.22 -2.04 (2 s, 3H), 2.00 - 1.86 (m, 1H). (mixture of interconvertible atropisomers) 351 [00479]embedded image 560.2 Method D, RT = 1.7 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 8.82 (m, 1H), 8.01 - 7.81 (m, 2H), 7.59 - 7.09 (m, 4H), 6.86 - 6.77 (m, 2H), 6.26 - 6.07 (m, 1H), 5.38 - 4.82 (m, 2H), 4.32 - 4.05 (m, 2H), 3.79 - 3.74 (2 s, 3H), 3.51 - 3.46 (m, 1H), 2.22 - 2.00 (2 s, 3H), 1.07 - 0.92 (m, 2H), 0.92 - 0.72 (m, 2H). (mixture of interconvertible atropisomers) 352 [00480]embedded image 578.2 Method D, RT = 1.87 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 8.88 (m, 1H), 8.03 - 7.83 (m, 2H), 7.58 - 7.35 (m, 3H), 6.81 - 6.73 (m, 2H), 6.25 - 6.08 (m, 1H), 5.35 - 4.85 (m, 2H), 4.27 - 4.05 (m, 2H), 3.78 - 3.74 (2 s, 3H), 3.54 - 3.47 (m, 1H), 2.22 - 1.99 (2 s, 3H), 1.06 - 0.92 (m, 2H), 0.92 - 0.70 (m, 2H). (mixture of interconvertible atropisomers) 353 [00481]embedded image 572.2 Method D, RT = 1.732 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.3 Hz, 1H), 7.92 (d, J = 8.6 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 10.8 Hz, 2H), 4.96 (dd, J = 10.8, 8.8 Hz, 1H), 4.84 (t, J = 9.3 Hz, 1H), 3.97 -3.89 (m, 1H), 3.75 (s, 3H), 3.67 - 3.61 (m, 1H), 3.46 - 3.39 (m, 7H), 3.22 (s, 3H), 2.28 - 2.19 (m, 1H), 2.13 - 2.04 (m, 1H). 354 [00482]embedded image 600.2 Method D, RT = 1.813 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.6 Hz, 1H), 8.03 - 7.90 (m, 2H), 7.66 (m, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.05 -4.94 (m, 1H), 4.44 (dd, J = 13.2, 2.7 Hz, 1H), 4.38 - 4.29 (m, 1H), 4.14 - 4.04 (m, 1H), 3.92 - 3.74 (m, 3H), 3.72 (s, 3H), 3.34 -3.30 (m, 1H). 355 [00483]embedded image 604.2 Method D, RT = 2.015 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (br d, J = 8.6 Hz, 1H), 8.04 - 7.90 (m, 2H), 7.73 - 7.57 (m, 2H), 7.51 - 4.45 (m, 4H), 7.44 - 7.32 (m, 2H), 6.81 - 6.73 (brs, 1H), 6.41 - 6.31 (m, 1H), 5.08 - 5.01 (m, 1H), 4.48 - 4.42 (m, 1H), 4.37 - 4.30 (m, 1H), 4.14 - 4.04 (m, 1H), 3.90 - 3.79 (m, 3H). 356 [00484]embedded image 569.2 Method D, RT = 1.69 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (br d, J = 8.1 Hz, 1H), 8.00 (d, J= 4.6 Hz, 1H), 7.94 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 4.6 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 6.78 (d, J= 10.8 Hz, 2H), 5.07 - 5.05 (m, 1H), 4.84 (t, J = 5.9 Hz, 1H), 4.36 - 4.27 (m, 1H), 4.22 - 4.01 (m, 4H), 3.77 (s, 3H), 3.73 (ABq, J = 5.9 Hz, 2H). 357 [00485]embedded image 553.2 Method D, RT = 1.95 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 4.6 Hz, 1H), 7.99 - 7.82 (m, 2H), 7.70 (d, J = 4.4 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 6.78 (d, J= 10.8 Hz, 2H), 5.01 - 5.05 (m, 1H), 4.42 - 4.27 (m, 1H), 4.25 - 4.05 (m, 4H), 3.77 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H). 358 [00486]embedded image 535.3 Method D, RT = 1.77 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 8.01 (d, J = 4.4 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 4.4 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.05 (dd, J = 10.8, 8.6 Hz, 1H), 4.37 - 4.26 (m, 1H), 4.23 - 4.05 (m, 4H), 3.77 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). 359 [00487]embedded image 596.2 Method D, RT = 1.75 min, 98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.28 - 8.97 (m, 1H), 8.07 - 7.82 (m, 2H), 7.61 - 7.34 (m, 3H), 6.79 - 6.75 (m, 2H), 6.28 - 6.09 (m, 1H), 5.41 - 4.80 (m, 2H), 4.31 - 3.97 (m, 3H), 3.95 - 3.85 (m, 1H), 3.82 - 3.73 (2 s, 3H), 3.63 - 3.45 (m, 2H), 2.23 - 2.01 (2 s, 3H), 1.09 (d, J = 6.4 Hz, 3H). (mixture of interconvertible atropisomers) 360 [00488]embedded image 578.3 Method C, RT = 1.57 min, 99 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.81 (m, 1H), 7.99 - 7.77 (m, 2H), 7.63 - 7.09 (m, 4H), 6.79 - 6.72 (m, 2H), 6.30 - 6.09 (m, 1H), 5.40 - 4.82 (m, 2H), 4.35 - 3.98 (m, 3H), 3.94 - 3.84 (m, 1H), 3.81 - 3.72 (2 s, 3H), 3.63 - 3.45 (m, 2H), 2.23 - 2.02 (2 s, 3H), 1.09 (d, J = 6.1 Hz, 3H). (mixture of interconvertible atropisomers) 361 [00489]embedded image 596.2 Method C, RT = 1.80 min, 93 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 9.05 (m, 1H), 7.97 - 7.91 (m, 2H), 7.57 - 7.46 (m, 3H), 6.77 - 6.73 (m, 2H), 6.30 - 6.17 (m, 1H), 5.40 - 4.88 (m, 2H), 4.35 - 3.98 (m, 3H), 3.94 - 3.84 (m, 1H), 3.81 - 3.72 (2 s, 3H), 3.63 - 3.45 (m, 2H), 2.19 - 2.02 (2 s, 3H), 1.11 - 1.06 (m, 3H). (mixture of interconvertible atropisomers) 362 [00490]embedded image 546.2 Method D, RT = 1.61 min, 97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.90 (m, 1H), 7.91 - 7.74 (m, 2H), 7.64 - 7.36 (m, 3H), 6.82 - 6.64 (m, 2H), 6.27 - 6.07 (m, 1H), 5.36 - 4.81 (m, 2H), 4.28 - 3.82 (m, 4H), 3.80 - 3.73 (2 s, 3H), 3.69 - 3.46 (m, 2H), 2.23 - 2.04 (2 s, 3H), 1.09 - 1.06 (m, 3H). (mixture of interconvertible atropisomers) 363 [00491]embedded image 707.3 Method D, RT = 1.78 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.78 - 3.73 (m, 1H), 7.67 - 7.57 (m, 1H), 7.52 -7.41 (m, 2H), 6.76 (d, J= 10.8 Hz, 2H), 6.41 (t, J = 7.2 Hz, 1H), 6.05 -5.64 (m, 1H), 5.16 - 5.00 (m, 1H), 4.74 -4.54 (m, 2H), 4.15 - 3.78 (m, 6H), 3.76 (s, 3H), 3.68 - 3.51 (m, 3H), 3.27 (s, 3H), 1.90 - 1.69 (m, 2H). 364 [00492]embedded image 632.2 Method D, RT = 2.06 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.74 - 7.63 (m, 2H), 7.54 - 7.41 (m, 3H), 6.87 - 6.73 (m, 2H), 6.39 (t, J = 7.0 Hz, 1H), 5.13 (dd, J = 11.1, 9.2 Hz, 1H), 4.41 (dd, J = 13.0, 3.4 Hz, 1H), 4.35 -4.26 (m, 1H), 4.16 - 4.08 (m, 1H), 4.06 -3.95 (m, 1H), 3.78 - 3.72 (m, 4H) 3.77 -3.69 (m, 1H), 3.36 (s, 3H). 365 [00493]embedded image 510.2 Method D, RT = 1.588 min, 89% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.97 (m, 1H), 7.92 - 8.86 (m, 2H), 7.60 - 7.49 (m, 3H), 7.43 - 7.24 (m, 2H), 6.97 - 6.80 (m, 2H), 6.22 - 6.18 (m, 1H), 5.27 - 4.64 (m, 1H), 4.18 - 3.96 (m, 3H), 3.93 - 3.80 (m, 2H), 3.75 - 3.70 (2 s, 3H), 3.66 - 3.53 (m, 2H), 3.24 (s, 3H), 2.21 - 2.04 (2 s, 3H). (mixture of interconvertible atropisomers) 366 [00494]embedded image 516.2 Method D, RT = 1.67 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 8.98 (m, 1H), 7.91 - 7.76 (m, 2H), 7.65 - 7.61 (m, 1H), 7.57 - 7.51 (m, 2H), 7.44 - 7.25 (m, 2H), 6.94 - 6.98 (m, 2H), 6.48 - 6.12 (m, 2H), 5.31 - 4.61 (m, 1H), 4.51 - 4.31 (m, 2H), 4.10 - 3.78 (m, 2H), 3.74 - 3.70 (2 s, 3H), 3.71 - 3.64 (m, 1H), 2.23 - 2.09 (2 s, 3H). (mixture of interconvertible atropisomers) 367 [00495]embedded image 546.2 Method D, RT = 1.51 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 - 8.94 (m, 1H), 7.99 - 7.84 (m, 2H), 7.61 - 7.52 (m, 2H), 7.37 - 7.33 (m, 1H), 7.31 - 7.22 (m, 2H), 6.90 - 6.70 (m, 2H), 6.22 - 6.17 (m, 1H), 5.41 - 4.73 (m, 1H), 4.15 - 3.87 (m, 5H), 3.74 - 3.71(2 s, 3H), 3.64 - 3.54 (m, 3H), 2.25 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 368 [00496]embedded image 586.1 Method D, RT = 1.852 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.8 Hz, 1H), 7.96 - 7.85 (m, 2H), 7.69 (dd, J = 6.8, 2.0 Hz, 1H), 7.65 (dd, J = 7.3, 2.0 Hz, 1H), 7.49 - 7.39 (m, 4H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.79 - 6.70 (m, 1H), 6.37 (t, J = 7.0 Hz, 1H), 5.03 (dd, J = 11.0, 8.8 Hz, 1H), 4.45 (dd, J = 13.1, 2.8 Hz, 1H), 4.37 -4.29 (m, 1H), 4.20 (t, J = 8.8 Hz, 1H), 3.89 - 3.79 (m, 2H), 3.75 - 3.67 (m, 1H). 369 [00497]embedded image 535.2 Method D, RT = 1.60 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 8.54 (s, 1H), 8.13 (s, 1H), 7.97 - 7.84 (m, 2H), 7.34 (t, J = 73.0 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.19 - 4.05 (m, 1H), 4.05 - 3.90 (m, 4H), 3.76 (s, 3H), 1.28 (t, J= 7.1 Hz, 3H). 370 [00498]embedded image 565.2 Method D, RT = 1.61 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.8 Hz, 1H), 8.40 (s, 1H), 8.14 (s, 1H), 7.88 (d, J = 8.6 Hz, 2H), 7.34 (t, J = 73.0 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 10.9, 8.9 Hz, 1H), 4.23 - 4.03 (m, 3H), 4.03 -3.88 (m, 2H), 3.76 (s, 3H), 3.60 (t, J= 5.1 Hz, 2H), 3.26 (s, 3H). 371 [00499]embedded image 582.2 Method D, RT = 1.644 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.93 (d, J = 8.6 Hz, 1H), 7.94 - 7.92 (m, 2H), 7.68 (dd, J= 6.7, 1.8 Hz, 1H), 7.63 (dd, J = 7.2, 1.8 Hz, 1H), 7.33 (t, J = 72.0 Hz, 1H), 7.35 - 7.10 (m, 4H), 6.97 - 6.87 (m, 2H), 6.84 - 6.61 (m, 1H), 6.37 (t, J 7.0 Hz, 1H), 4.99 (dd, J = 10.9, 8.9 Hz, 1H), 4.44 (dd, J = 13.2, 2.9 Hz, 1H), 4.38 -4.29 (m, 1H), 4.12 - 4.05 (m, 1H), 3.85 (dd, J= 13.1, 9.2 Hz, 1H), 3.82 - 3.73 (m, 2H), 3.72 (s, 3H). 372 [00500]embedded image 542.2 Method D, RT = 1.77 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.8 Hz, 1H), 8.00 - 7.86 (m, 2H), 7.47 (d, J = 8.1 Hz, 2H), 6.75 (d, J 10.8 Hz, 2H), 4.97 (dd, J = 10.8, 8.6 Hz, 1H), 4.84 (t, J = 9.4 Hz, 1H), 4.01 - 3.85 (m, 1H), 3.75 (s, 3H), 3.64 (br t, J = 8.7 Hz, 1H), 3.36 (m, 3H), 3.23 (dt, J 13.7, 6.6 Hz, 2H), 2.28 - 2.18 (m, 1H), 2.15 - 2.03 (m, 1H), 1.03 (t, J 7.2 Hz, 3H). 373 [00501]embedded image 552.2 Method D, RT = 1.717 min, 94.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 9.01 (m, 1H), 8.01 - 7.85 (m, 3H), 7.53 - 7.23 (m, 3H), 6.84 - 6.72 (m, 2H), 6.50 - 6.46 (m, 1H), 5.07 - 4.99 (m, 1H), 4.27 - 4.10 (m, 1H), 4.06 - 3.92 (m, 4H), 3.79 - 3.75 (2 s, 3H), 1.31 - 1.19 (m, 3H). (mixture of interconvertible atropisomers) 374 [00502]embedded image 498.2 Method D, RT = 1.68 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 9.0 (m, 1H), 7.92 - 7.79 (m, 2H), 7.68 -7.61 (m, 1H), 7.59 - 7.35 (m, 3H), 6.89 -6.72 (m, 2H), 6.25 - 6.20 (m, 1H), 5.41 -4.74 (m, 1H), 4.18 - 3.85 (m, 4H), 3.76 -3.72 (2 s, 3H), 3.62 -3.36 (m, 1H), 2.22 -2.04 (2 s, 3H), 1.22 (m, 3H). (Mixture of interconvertible atropisomers) 375 [00503]embedded image 564.2 Method D, RT = 1.61 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 9.06 (m, 1H), 8.03 - 7.87 (m, 2H), 7.62 - 7.37 (m, 4H), 6.89 - 6.68 (m, 2H), 6.22 - 6.18 (m, 1H), 5.41 - 4.78 (m, 2H), 4.16 - 3.89 (m, 4H), 3.78 - 3.74 (2 s, 3H), 3.64 - 3.60 (m, 3H), 2.21 - 2.03 (2 s, 3H). (Mixture of interconvertible atropisomers) 376 [00504]embedded image 566.2 Method D, RT = 1.74 min, 94.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.93 (m, 1H), 7.99 - 7.83 (m, 2H), 7.69 - 7.61 (m, 1H), 7.56 - 7.45 (m, 1H), 7.51 - 7.21 (m, 3H), 6.88 - 6.69 (m, 2H), 6.36 - 6.13 (m, 2H), 5.41 - 4.74 (m, 1H), 4.50 - 4.32 (m, 2H), 4.18 - 3.89 (m, 2H), 3.74 (2 s, 3H), 3.62 - 3.36 (m, 1H), 2.22 - 2.10 (2 s, 3H). (mixture of interconvertible atropisomers) 377 [00505]embedded image 534.2 Method D, RT = 1.76 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 8.96 (m, 1H), 7.99 - 7.83 (m, 2H), 7.66 - 7.61 (m, 1H), 7.59 - 7.35 (m, 3H), 6.89 - 6.71 (m, 2H), 6. 51 - 6.26 (m, 2H), 5.41 - 4.74 (m, 1H), 4.50 - 4.32 (m, 2H), 4.18 - 3.89 (m, 2H), 3.74 (2 s, 3H), 3.62 - 3.36 (m, 1H), 2.23 - 2.03 (2 s, 3H). (mixture of interconvertible atropisomers) 378 [00506]embedded image 503.2 Method D, RT = 1.62 min, 97.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.6 Hz, 1H), 8.54 (s, 1H), 8.13 (s, 1H), 7.88 - 7.77 (m, 2H), 7.60 - 7.50 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.16 - 4.05 (m, 1H), 4.03 - 3.90 (m, 4H), 3.76 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). 379 [00507]embedded image 615.2 Method F, RT = 1.63 min, 96.0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.89 (m, 1H), 7.91 - 7.71 (m, 2H), 7.66 - 7.34 (m, 3H), 6.84 - 6.64 (m, 2H), 6.31 - 6.12 (m, 1H), 5.33 - 4.73 (m, 3H), 4.30 - 4.01 (m, 2H), 3.76 (s, 3H), 3.70 - 3.62 (m, 2H), 3.61 - 3.36 (m, 7H), 2.25 - 1.99 (2 s, 3H). (mixture of interconvertible atropisomers) 380 [00508]embedded image 582.2 Method D, RT = 1.92 min, 95.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.6 Hz, 1H), 7.93 - 7.78 (m, 2H), 7.72 - 7.65 (m, 2H), 7.61 - 7.43 (m, 3H), 6.89 - 6.75 (m, 2H), 6.39 (t, J = 7.1 Hz, 1H), 5.14 (dd, J = 11.2, 8.8 Hz, 1H), 4.42 (dd, J = 13.6, 3.5 Hz, 1H), 4.36 - 4.25 (m, 1H), 4.18 - 4.09 (m, 1H), 4.08 - 3.95 (m, 2H), 3.78 (s, 3H), 3.77 - 3.71 (m, 1H), 3.25 (s, 3H). 381 [00509]embedded image 570.2 Method D, RT = 1.812 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 8.94 (m, 1H), 8.05 - 7.68 (m, 4H), 7.51 - 7.24 (m, 3H), 6.87 - 6.69 (m, 2H), 6.52 - 6.39 (m, 1H), 5.33 - 4.74 (m, 1H), 4.35 - 4.00 (m, 2H), 3.79 - 3.74 (2 s, 3H), 3.62 - 3.51 (m, 1H), 2.28 - 2.00 (2 s, 3H). (mixture of interconvertible atropisomers) 382 [00510]embedded image 480.2 Method D, RT = 1.685 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.97 (m, 1H), 7.90 - 7.86 (m, 2H), 7.68 - 7.63 (m, 1H), 7.60 - 7.47 (m, 2H), 7.41 - 7.18 (m, 2H), 6.93 - 6.89 (m, 2H), 6.24 - 6.17 (m, 1H), 5.29 - 4.64 (m, 1H), 4.13 - 3.80 (m, 4H), 3.74 - 3.71 (2 s, 3H), 3.47 - 3.42 (m, 1H), 2.24 - 2.02 (2 s, 3H), 1.32 - 1.13 (m, 3H). (mixture of interconvertible atropisomers) 383 [00511]embedded image 552.2 Method D, RT = 1.884 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.94 (m, 1H), 8.05 - 7.67 (m, 4H), 7.57 - 7.42 (m, 2H), 7.42 - 7.25 (m, 2H), 7.04 - 6.79 (m, 2H), 6.47 - 6.41 (m, 1H), 5.32 - 4.54 (m, 1H), 4.08 - 3.79 (m, 2H), 3.79 - 3.51 (m, 4H), 2.28 - 2.10 (2 s, 3H). (mixture of interconvertible atropisomers) 384 [00512]embedded image 534.2 Method D, RT = 1.726 min, 93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 8.82 (m, 1H), 8.08 - 7.68 (m, 4H), 7.57 - 7.06 (m, 5H), 6.97 - 6.76 (m, 2H), 6.47 - 6.42 (m, 1H), 5.31 - 4.56 (m, 1H), 4.07 - 3.78 (m, 2H), 3.76 - 3.49 (m, 4H), 2.30 - 2.10 (2 s, 3H). (mixture of interconvertible atropisomers) 385 [00513]embedded image 506.2 Method D, RT = 1.758 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.98 (m, 1H), 7.94 - 7.79 (m, 2H), 7.70 - 7.66 (m, 1H), 7.60 - 7.47 (m, 2H), 7.42 - 7.23 (m, 2H), 7.00 - 6.80 (m, 2H), 6.24 - 6.20 (m, 1H), 5.28 - 4.62 (m, 1H), 4.15 - 3.78 (m, 3H), 3.75 - 3.70 (m, 4H), 3.51 - 3.40 (m, 1H), 2.23 - 2.02 (2 s, 3H), 1.28 - 1.08 (m, 1H), 0.55 - 0.44 (m, 2H), 0.42 - 0.30 (m, 2H). (mixture of interconvertible atropisomers) 386 [00514]embedded image 548.2 Method D, RT = 1.794 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 8.98 (m, 1H), 7.90 - 7.86 (m, 2H), 7.70 - 7.66 (m, 1H), 7.63 - 7.50 (m, 2H), 7.46 - 7.21 (m, 2H), 6.94 - 6.88 (m, 2H), 6.28 - 6.23 (m, 1H), 5.32 - 4.58 (m, 1H), 4.27 - 3.77 (m, 4H), 3.74 - 3.70 (2 s, 3H) 3.48 - 3.46 (m, 1H), 2.85 - 2.66 (m, 2H), 2.24 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 387 [00515]embedded image 580.2 Method D, RT = 1.766 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 - 8.92 (m, 1H), 7.95 - 7.91 (m, 2H), 7.70 - 7.65 (m, 1H), 7.55 - 7.07 (m, 5H), 6.93 - 6.87 (m, 2H), 6.28 - 6.23 (m, 1H), 5.30 - 4.64 (m, 1H), 4.29 - 3.78 (m, 4H), 3.74 - 3.70 (2 s, 3H) 3.48 - 3.46 (m, 1H), 2.86 - 2.64 (m, 2H), 2.23 - 2.06 (2 s, 3H). (mixture of interconvertible atropisomers) 388 [00516]embedded image 512.3 Method D, RT = 1.572 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 - 8.92 (m, 1H), 8.00 - 7.88 (m, 2H), 7.67 - 7.62 (m, 1H), 7.55 - 7.05 (m, 5H), 6.93 - 6.88 (m, 2H), 6.24 - 6.18 (m, 1H), 5.32 - 4.63 (m, 1H), 4.14 - 3.77 (m, 4H), 3.74 - 3.70 (2 s, 3H), 3.47 - 3.42 (m, 1H), 2.25 - 2.04 (2 s, 3H), 1.25- 1.19 (m, 3H). (mixture of interconvertible atropisomers) 389 [00517]embedded image 572.3 Method D, RT = 1.517 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 - 8.88 (m, 1H), 7.96 - 7.90 (m, 2H), 7.62 - 7.56 (m, 1H), 7.53 - 7.12 (m, 5H), 6.93 - 6.95 (m, 2H), 6.26 - 6.18 (m, 1H), 5.27 - 5.16 (m, 1H), 5.10 - 4.94 (m, 2H), 4.75 - 4.65 (m, 1H), 4.14 - 4.05 (m, 1H), 3.95 - 3.82 (m, 2H), 3.77 - 3.57 (m, 6H), 3.24 - 3.20 (2 s, 3H), 2.20 - 2.08 (2 s, 3H). (mixture of atrop and diastereomers) 390 [00518]embedded image 524.2 Method D, RT = 1.603 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.6 Hz, 1H), 7.91 - 7.75 (m, 2H), 7.33 (t, J = 73.6 Hz, 1H), 7.27 - 7.24 (m, 2H), 6.74 (d, J = 10.8 Hz, 2H), 4.96 (dd, J = 10.9, 8.9 Hz, 1H), 4.84 (t, J = 9.4 Hz, 1H), 3.97 - 3.86 (m, 1H), 3.75 (s, 3H), 3.64 (br t, J = 8.7 Hz, 1H), 3.37 - 3.31 (m, 3H), 3.26 - 3.20 (m, 2H), 2.26 - 2.17 (m, 1H), 2.13 - 2.03 (m, 1H), 1.03 (t, J= 7.2 Hz, 3H). 391 [00519]embedded image 496.1 Method D, RT = 1.467 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J = 8.6 Hz, 1H), 7.92 - 7.81 (m, 2H), 7.64 - 7.49 (m, 4H), 7.38 - 7.27 (m, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.30 (t, J = 7.0 Hz, 1H), 5.05 - 4.96 (m, 1H), 4.96 - 4.88 (m, 1H), 4.12 - 4.04 (m, 2H), 3.96 - 3.90 (m, 1H), 3.79 - 3.70 (m, 2H), 3.72 (s, 3H), 3.70 - 3.61 (m, 1H), 1.08 (d, J= 6.1 Hz, 3H). 392 [00520]embedded image 532.2 Method D, RT = 1.606 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.95 (m, 1H), 7.98 - 7.90 (m, 2H), 7.58 - 7.49 (m, 2H), 7.46 - 7.15 (m, 6H), 6.23 - 6.18 (m, 1H), 5.33 - 4.97 (m, 1H), 5.05 - 4.97 (m, 1H), 4.94 - 4.90 (m, 1H), 4.06 - 3.86 (m, 4H), 3.67 - 3.58 (m, 2H), 2.22 - 2.10 (2 s, 3H). (mixture of interconvertible atropisomers) 393 [00521]embedded image 564.2 Method D, RT = 1.848 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J= 9.3 Hz, 1H), 7.89 - 7.81 (m, 2H), 7.73 - 7.63 (m, 2H), 7.59 - 7.51 (m, 2H), 7.34 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.05 -4.98 (m, 1H), 4.44 - 4.37 (m, 1H), 4.32 -4.26 (m, 1H), 4.13 - 4.02 (m, 3H), 3.80 -3.74 (m, 1H), 3.72 (s, 3H), 3.36 (s, 3H). 394 [00522]embedded image 514.2 Method D, RT = 1.52 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.98 (m, 1H), 7.88 - 7.75 (m, 2H), 7.59 - 7.43 (m, 4H), 6.86 - 6.74 (m, 2H), 6.21 - 6.18 (m, 1H), 5.42 - 4.74 (m, 2H), 4.15 - 3.92 (m, 4H), 3.76 - 3.72 (2 s, 3H), 3.66 - 3.56 (m, 3H), 2.22 - 2.05 (2 s, 3H). (mixture of interconvertible atropisomers) 395 [00523]embedded image 578.2 Method D, RT = 1.85 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.63 - 7.56 (m, 2H), 7.53 - 7.43 (m, 3H), 6.85 - 6.76 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.15 - 5.10 (m, 1H), 4.13 - 3.93 (m, 3H), 3.91 (br d, J = 7.1 Hz, 2H), 3.76 (s, 3H), 3.74 - 3.64 (m, 1H), 3.25 (s, 3H), 1.08 (d, J = 6.1 Hz, 3H). 396 [00524]embedded image 568.2 Method D, RT = 1.84 min, 94.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.6 Hz, 1H), 8.13 (dd, J = 4.9, 2.0 Hz, 1H), 7.98 - 7.90 (m, 2H), 7.79 (dd, J = 7.6, 1.7 Hz, 1H), 7.49 (d, J = 8.6 Hz, 2H), 7.09 (dd, J = 7.6, 4.9 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.08 (dd, J = 10.9, 8.4 Hz, 1H), 4.74 (t, J = 5.5 Hz, 1H), 4.38 (td, J= 5.5, 2.6 Hz, 2H), 4.15 (q, J = 9.8 Hz, 1H), 4.05 - 4.96 (m, 2H), 3.76 (s, 3H), 3.75 - 3.69 (m, 2H). 397 [00525]embedded image 526.2 Method D, RT = 1.471 min, 91% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 - 8.94 (m, 1H), 7.91 - 7.83 (m, 2H), 7.68 (dd, J = 6.8, 2.0 Hz, 1H), 7.58 - 7.49 (m, 3H), 7.34 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.33 (t, J = 7.1 Hz, 1H), 5.11 - 4.97 (m, 3H), 4.13 - 4.10 (m, 1H), 3.78 - 3.65 (m, 8H), 3.65 - 3.60 (m, 1H), 3.23 (s, 3H). 398 [00526]embedded image 565.2 Method D, RT = 1.73 min, 97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 8.01 (d, J = 4.6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.69 (d, J = 4.6 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.28 -7.26 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.05 (dd, J = 10.9, 8.4 Hz, 1H), 4.37 -4.22 (m, 3H), 4.21 - 4.05 (m, 2H), 3.77 (s, 3H), 3.70 (t, J = 5.5 Hz, 2H), 3.24 (s, 3H). 399 [00527]embedded image 538.1 Method D, RT = 1.88 min, 94 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 -9.04 (m, 1H), 8.07 - 7.68 (m, 4H), 7.64 - 7.45 (m, 2H), 6.87 - 6.65 (m, 2H), 6.51 - 6.36 (m, 1H), 5.36 - 4.78 (m, 1H), 4.35 - 3.99 (m, 2H), 3.83 - 3.73 (2 s, 3H), 3.66 - 3.52 (m, 1H), 2.29 - 2.05 (2 s, 3H). (mixture of interconvertible atropisomers) 400 [00528]embedded image 596.3 Method D, RT = 1.721 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.24 - 8.92 (m, 1H), 7.99 - 7.86 (m, 1H), 7.96 -7.91 (m, 1H), 7.60 - 7.42 (m, 3H), 6.83 - 6.69 (m, 2H), 6.26 - 6.16 (m, 1H), 5.00 - 4.84 (m, 2H), 4.30 - 3.96 (m, 4H), 3.80 - 3.74 (2 s, 3H), 3.62 - 3.47 (m, 2H), 2.24 - 2.02 (2 s, 3H), 1.14 - 1.03 (m, 3H). (mixture of interconvertible atropisomers) 401 [00529]embedded image 566.2 Method D, RT = 1.87 min, 94.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 9.00 (m, 1H), 7.99 - 7.81 (m, 2H), 7.70 - 7.65 (m, 1H), 7.62 - 7.50 (m, 2H), 7.45 - 7.40 (m, 1H), 6.90 - 6.72 (m, 2H), 6.28 - 6.24 (m, 1H), 5.42 - 4.74 (m, 1H), 4.30 - 3.94 (m, 3H), 3.76 - 3.70 (2 s, 3H), 3.49 - 3.34 (m, 2H), 2.81 - 2.68 (m, 2H), 2.22 - 2.06 (2 s, 3H). (mixture of interconvertible atropisomers) 402 [00530]embedded image 598.2 Method D, RT = 1.83 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 - 8.95 (m, 1H), 7.99 - 7.84 (m, 2H), 7.61 - 7.52 (m, 1H), 7.58 - 7.12 (m, 4H), 6.90 - 6.70 (m, 2H), 6.21 - 6.17 (m, 1H), 5.42 - 4.74 (m, 1H), 4.30 - 3.94 (m, 3H), 3.76 - 3.70 (2 s, 3H), 3.49 - 3.34 (m, 2H), 2.81 - 2.68 (m, 2H), 2.22 - 2.06 (2 s, 3H). (mixture of interconvertible atropisomers) 403 [00531]embedded image 566.2 Method D, RT = 1.87 min, 94.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 9.01 (m, 1H), 7.99 - 7.82 (m, 2H), 7.71 - 7.67 (m, 1H), 7.63 - 7.52 (m, 2H), 7.49 - 7.37 (m, 1H), 6.90 - 6.73 (m, 2H), 6.25 - 6.21 (m, 1H), 5.42 - 4.74 (m, 1H), 4.22 - 3.95 (m, 2H), 3.95 - 3.82 (m, 1H), 3.79 -3.75 (2 s, 3H), 3.74 - 3.54 (m, 2H), 2.23 - 2.03 (2 s, 3H), 1.32 - 1.09 (m, 1H), 0.58 - 0.45 (m, 2H), 0.42 - 0.26 (m, 2H) (mixture of interconvertible atropisomers) 404 [00532]embedded image 598.2 Method D, RT = 1.83 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 9.01 (m, 1H), 7.99 - 7.82 (m, 2H), 7.71 - 7.67 (m, 1H), 7.63 - 7.52 (m, 2H), 7.49 - 7.37 (m, 1H), 6.90 - 6.73 (m, 2H), 6.25 - 6.21 (m, 1H)), 5.42 - 4.69 (m, 1H), 4.19 - 3.90 (m, 4H), 3.78 - 3.72 (2 s, 3H), 3.63 - 3.35 (m, 3H), 3.24 (s, 3H), 2.23 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 405 [00533]embedded image 560.3 Method D, RT = 1.885 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.99 (m, 1H), 7.99 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 7.1 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.32 (d, J = 7.1 Hz, 1H), 5.05 - 4.97 (m, 1H), 4.12 - 4.08 (m, 1H), 4.08 - 4.02 (m, 1H), 3.93 - 3.86 (m, 1H), 3.78 - 3.73 (m, 2H), 3.72 (s, 3H), 3.68 - 3.62 (m, 1H), 3.2 (s, 3H), 1.09 (d, J = 6.4 Hz, 3H). 406 [00534]embedded image 530.2 Method D, RT = 1.681 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 8.96 (m, 1H), 7.90 - 7.84 (m, 2H), 7.68 (dd, J= 7.0, 1.8 Hz, 1H), 7.59 - 7.52 (m, 3H), 7.50 - 7.44 (m, 2H), 7.43 - 7.38 (m, 2H), 6.37 - 6.31 (m, 1H), 5.13 - 4.98 (m, 2H), 4.20 - 4.12 (m, 1H), 3.88 - 3.58 (m, 7H), 3.23 (s, 3H). 407 [00535]embedded image 564.2 Method D, RT = 1.59 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J = 8.6 Hz, 1H), 7.94 - 7.81 (m, 2H), 7.67 (dd, J = 6.6, 2.2 Hz, 1H), 7.47 -7.45 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.85 - 6.67 (m, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.11 (dd, J = 11.4, 8.7 Hz, 1H), 4.55 - 4.47 (m, 1H), 4.03 - 3.97 (m, 3H), 3.77 (s, 3H), 3.67 -3.61 (m, 3H), 0.99 (d, J = 5.9 Hz, 3H). 408 [00536]embedded image 582.2 Method D, RT = 2.052 min, 95.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.3 Hz, 1H), 8.13 (dd, J = 4.9, 2.0 Hz, 1H), 8.01 - 7.88 (m, 2H), 7.79 (dd, J = 7.6, 1.7 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 7.11 (dd, J = 7.6, 4.9 Hz, 1H), 6.78 (d, J = 10.5 Hz, 2H), 5.11 (dd, J = 11.0, 8.6 Hz, 1H), 4.47 - 4.40 (m, 2H), 4.19 -4.09 (m, 1H), 4.03 (t, J = 9.7 Hz, 1H), 3.97 - 3.91 (m, 1H), 3.77 (s, 3H), 3.72 -3.67 (m, 2H), 3.30 (s, 3H). 409 [00537]embedded image 532.2 Method D, RT = 1.618 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (br d, J = 8.6 Hz, 1H), 7.96 - 7.83 (m, 2H), 7.62 - 7.57 (m, 2H), 7.50 - 7.37 (m, 4H), 7.34 (t, J= 73.6 Hz, 1H), 7.29 - 7.25 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.08 -4.98 (m, 2H), 4.98 - 4.86 (m, 1H), 4.17 (t, J= 8.3 Hz, 1H), 4.08 (dd, J = 12.7, 3.7 Hz, 1H), 3.96 - 3.88 (m, 1H), 3.81 (dd, J = 10.5, 8.3 Hz, 1H), 3.76 - 3.69 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H). 410 [00538]embedded image 599.2 Method D, RT = 1.94 min, 95.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.85 (d, J = 7.6 Hz, 1H), 8.25 - 8.13 (m, 1H), 7.61 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 6.1 Hz, 1H), 6.69 -6.56 (m, 2H), 6.40 - 6.30 (m, 1H), 4.99 (dd, J = 9.2, 7.7 Hz, 1H), 4.59 - 4.53 (m, 1H), 4.32 - 4.23 (m, 1H), 3.99 (br t, J= 8.9 Hz, 1H), 3.70 (s, 3H), 3.53 - 3.44 (m, 4H), 3.28 (s, 3H). 411 [00539]embedded image 526.2 Method D, RT = 1.465 min, 93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J = 8.6 Hz, 1H), 7.93 - 7.81 (m, 2H), 7.67 (dd, J= 6.8, 1.7 Hz, 1H), 7.59 - 7.48 (m, 3H), 7.34 (d, J= 8.8 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.33 (t, J = 7.0 Hz, 1H), 5.12 - 4.93 (m, 3H), 4.13 - 4.05 (m, 1H), 3.80 - 3.73 (m, 4H), 3.72 (s, 3H), 3.69 -3.58 (m, 2H), 3.23 (s, 3H). 412 [00540]embedded image 564.2 Method D, RT = 1.78 min, 99.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.6 Hz, 1H), 8.13 (dd, J = 4.9, 1.7 Hz, 1H), 7.94 - 7.83 (m, 2H), 7.79 (dd, J = 7.6, 1.7 Hz, 1H), 7.34 (t, J = 73.0 Hz, 1H), 7.28 - 7.26 (m, 2H), 7.14 - 7.14 (m, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.09 (dd, J = 10.9, 8.7 Hz, 1H), 4.44 (dd, J = 5.4, 3.9 Hz, 2H), 4.20 - 4.09 (m, 1H), 4.03 (t, J = 9.5 Hz, 1H), 3.97 - 3.90 (m, 1H), 3.77 (s, 3H), 3.73 - 3.65 (m, 2H), 3.30 (s, 3H). 413 [00541]embedded image 532.2 Method D, RT = 1.87 min, 98.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.8 Hz, 1H), 8.13 (dd, J = 5.0, 1.8 Hz, 1H), 7.89 - 7.81 (m, 2H), 7.79 (dd, J = 7.6, 2.0 Hz, 1H), 7.61 - 7.50 (m, 2H), 7.11 (dd, J= 7.6, 5.1 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.10 (dd, J = 11.0, 8.8 Hz, 1H), 4.51 - 4.40 (m, 2H), 4.19 - 4.08 (m, 1H), 4.02 (t, J = 9.7 Hz, 1H), 3.97 -3.91 (m, 1H), 3.77 (s, 3H), 3.73 - 3.67 (m, 2H), 3.30 (s, 3H). 414 [00542]embedded image 530.2 Method D, RT = 1.670 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.68 (dd, J = 1.6, 7.0 Hz, 1H), 7.61 - 7.52 (m, 3H), 7.51 - 7.44 (m, 2H), 7.44 - 7.30 (m, 2H), 6.34 (t, J = 7.1 Hz, 1H), 5.11 - 4.97 (m, 3H), 4.14 (t, J = 7.3 Hz, 1H), 3.86 - 3.61 (m, 6H), 3.23 (s, 3H). 415 [00543]embedded image 552.2 Method D, RT = 1.838 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 8.88 (m, 1H), 8.01 - 7.87 (m, 2H), 7.71 - 7.57 (m, 1H), 7.55 - 7.10 (m, 7H), 6.48 - 6.12 (m, 2H), 5.32 - 4.71 (m, 1H), 4.45 - 4.31 (m, 2H), 4.15 - 3.69 (m, 3H),2.23 - 2.11 (2 s, 3H). (mixture of interconvertible atropisomers) 416 [00544]embedded image 596.2 Method D, RT = 1.824 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.3 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.69 (dd, J = 6.7, 1.8 Hz, 1H), 7.66 (dd, J = 7.3, 1.8 Hz, 1H), 7.37 - 7.22 (m, 4H), 7.33 (t, J = 76.0 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.07 - 4.94 (m, 1H), 4.41 (dd, J = 13.3, 3.5 Hz, 1H), 4.36 - 4.26 (m, 1H), 4.16 -3.95 (m, 2H), 3.82 - 3.73 (m, 2H), 3.72 (s, 3H), 3.36 (s, 3H). 417 [00545]embedded image 600.2 Method D, RT = 1.95 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 7.89 - 7.77 (m, 2H), 7.71 (dd, J= 6.8, 2.0 Hz, 1H), 7.68 (dd, J = 2.0, 7.1 Hz, 1H), 7.60 - 7.48 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.39 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 10.8, 8.8 Hz, 1H), 4.42 (dd, J = 13.3, 3.3 Hz, 1H), 4.33 -4.24 (m, 1H), 4.15 - 3.92 (m, 4H), 3.76 (s, 3H), 3.36 (s, 3H). 418 [00546]embedded image 560.3 Method D, RT = 1.67 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.8 Hz, 1H), 7.97 - 7.83 (m, 2H), 7.66 - 7.56 (m, 2H), 7.54 - 7.48 (m, 1H), 7.35 (t, J = 76.0 Hz, 1H), 7.31 - 7.24 (m, 2H), 6.87 - 6.73 (m, 2H), 6.31 (t, J= 7.0 Hz, 1H), 5.13 (dd, J = 11.5, 8.8 Hz, 1H), 4.22 - 4.12 (m, 1H), 4.08 (dd, J = 13.2, 3.7 Hz, 1H), 4.04 - 3.94 (m, 1H), 3.84 (dd, J = 13.3, 7.7 Hz, 1H), 3.74 (s, 3H), 3.70 - 3.60 (m, 2H), 3.18 (s, 3H), 1.09 (d, J= 6.4 Hz, 3H). 419 [00547]embedded image 585.2 Method D, RT = 1.79 min, 92.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.96 (m, 1H), 8.34 (d, J = 5.1 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.61 - 7.50 (m, 2H), 6.87 - 6.73 (m, 2H), 6.71 (d, J= 5.1 Hz, 1H), 6.43 (br t, J = 6.1 Hz, 1H), 5.08 - 4.91 (m, 1H), 4.81 - 4.71 (m, 1H), 4.27 - 4.00 (m, 2H), 3.81 -3.77 (m, 1H), 3.76 (s, 3H), 3.61 - 3.47 (m, 4H). 420 [00548]embedded image 611.2 Method D, RT = 1.94 min, 97.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (br d, J = 8.1 Hz, 1H), 8.55 - 8.41 (m, 1H), 7.82 (br d, J = 8.1 Hz, 2H), 7.66 -7.39 (m, 2H), 7.22 (d, J = 5.6 Hz, 1H), 6.87 - 6.59 (m, 2H), 5.19 - 5.01 (m, 1H), 4.42 - 4.11 (m, 2H), 3.80 (s, 3H), 3.79 -3.56 (m, 5H), 3.28 - 3.19 (m, 2H), 3.17 -3.05 (m, 2H). 421 [00549]embedded image 552.2 Method D, RT = 1.77 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.91 (m, 1H), 7.91 - 7.76 (m, 2H), 7.72 - 7.44 (m, 3H), 6.87 - 6.68 (m, 2H), 6.51 - 6.03 (m, 2H), 5.38 - 4.75 (m, 1H), 4.51 - 4.32 (m, 2H), 4.30 - 4.02 (m, 2H), 3.79 - 3.73 (2 s, 3H), 3.60 - 3.44 (m, 1H), 2.25 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 422 [00550]embedded image 546.3 Method D, RT = 1.69 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.89 (m, 1H), 7.98 - 7.74 (m, 2H), 7.68 - 7.41 (m, 3H), 6.79 - 6.74 (m, 2H), 6.28 - 6.09 (m, 1H), 5.44 - 4.77 (m, 1H), 4.29 - 3.96 (m, 4H), 3.77 - 3.74 (2 s, 3H), 3.63 - 3.42 (m, 3H), 3.27 - 3.23 (2 s, 3H), 2.23 - 1.99 (2 s, 3H). (mixture of interconvertible atropisomers) 423 [00551]embedded image 599.2 Method D, RT = 1.94 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 9.07 (m, 1H), 8.25 - 8.13 (m, 1H), 7.88 - 7.82 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 6.91 - 6.85 (m, 1H), 6.69 - 6.56 (d, J = 10.8 Hz, 2H), 6.46 - 6.33 (m, 1H), 5.16 -5.11 (m, 1H), 4.35 - 4.13 (m, 2H), 3.79 (s, 3H), 3.78 - 3.71 (m,1H), 3.53 - 3.44 (m, 4H), 3.28 (s, 3H). (mixture of interconvertible atropisomers) 424 [00552]embedded image 500.2 Method D, RT = 1.635 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.8 Hz, 1H), 7.90 - 7.82 (m, 2H), 7.65 - 7.52 (m, 4H), 7.50 - 7.44 (m, 2H), 7.43 - 7.36 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.07 - 5.00 (m, 1H), 4.98 - 4.88 (m, 1H), 4.17 - 4.10 (m, 1H), 4.06 (dd, J = 12.7, 3.7 Hz, 1H), 3.96 - 3.88 (m, 1H), 3.84 - 3.74 (m, 2H), 3.68 - 3.64 (m, 1H), 1.08 (d, J = 6.4 Hz, 3H). 425 [00553]embedded image 510.2 Method D, RT = 1.937 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 9.02 (m, 1H), 7.90 - 7.86 (m, 2H), 7.71 - 7.67 (m, 1H), 7.60 - 7.47 (m, 3H), 7.46 - 7.31 (m, 3H), 6.24 - 6.20 (m, 1H), 5.36 - 4.62 (m, 1H), 4.15 - 3.82 (m, 3H), 3.81 - 3.47 (m, 2H), 2.22 - 2.07 (2 s, 3H), 1.31 - 1.16 (m, 1H), 0.54 - 0.41 (m, 2H), 0.41 - 0.28 (m, 2H). (mixture of interconvertible atropisomers) 426 [00554]embedded image 608.3 Method D, RT = 1.539 min, 97.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 8.79 (m, 1H), 8.01 - 7.80 (m, 2H), 7.68 - 7.56 (m, 1H), 7.56 - 7.05 (m, 3H), 6.79 - 6.74 (m, 2H), 6.30 - 6.10 (m, 1H), 5.39 - 4.78 (m, 3H), 4.32 - 4.00 (m, 2H), 3.78 - 3.75 (2 s, 3H), 3.74 - 3.58 (m, 3H), 3.51 - 3.48 (m, 1H), 3.53 - 3.44 (m, 1H), 3.25 - 3.18 (2 s, 3H), 2.26 - 1.91 (2 s, 3H). (mixture of interconvertible atropisomers) 427 [00555]embedded image 626.2 Method D, RT = 1.759 min, 98.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.88 (m, 1H), 8.04 - 7.87 (m, 2H), 7.71 - 7.55 (m, 1H), 7.55 - 7.35 (m, 2H), 6.85 - 6.62 (m, 2H), 6.29 - 6.12 (m, 1H), 5.39 - 4.82 (m, 3H), 4.32 - 4.02 (m, 2H), 3.77 - 3.74 (2 s, 3H), 3.74 - 3.57 (m, 4H), 3.53 - 3.50 (m, 1H), 3.23 - 3.19 (2 s, 3H), 2.23 - 2.00 (2 s, 3H). (mixture of interconvertible atropisomers) 428 [00556]embedded image 617.7 Method D, RT = 1.58 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J= 8.8 Hz, 1H), 7.97 - 7.83 (m, 2H), 7.66 - 7.56 (m, 2H), 7.54 - 7.48 (m, 1H), 7.35 (t, J = 76.0 Hz, 1H), 7.31 - 7.24 (m, 2H), 6.87 - 6.73 (m, 2H), 6.31 (t, J= 7.0 Hz, 1H), 5.16 - 5.04 (m, 1H), 4.15 - 3.98 (m, 2H), 3.93 - 3.80 (m, 2H), 3.78 (s, 3H), 3.68 - 3.51 (m, 2H), 3.27 (s, 3H), 3.01 (s, 3H), 2.99 (s, 3H). 429 [00557]embedded image 626.3 Method D, RT = 1.775 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.27 - 9.01 (m, 1H), 8.05 - 7.81 (m, 2H), 7.69 - 7.53 (m, 1H), 7.53 - 7.32 (m, 2H), 6.79 - 6.75 (m, 2H), 6.32 - 6.13 (m, 1H), 5.40 - 4.81 (m, 3H), 4.32 - 4.01 (m, 2H), 3.76 - 3.74 (2 s, 3H), 3.74 - 3.57 (m, 3H), 3.51 - 3.49 (m, 1H), 3.55 - 3.46 (m, 1H), 3.22 (s, 3H), 2.24 - 1.96 (2 s, 3H). (mixture of interconvertible atropisomers) 430 [00558]embedded image 584.2 Method D, RT = 1.89 min, 99 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.84 (m, 1H), 7.92 - 7.78 (m, 2H), 7.76 - 7.64 (m, 1H), 7.61 - 7.43 (m, 2H), 6.79 - 6.75 (m, 2H), 6.34 - 6.17 (m, 1H), 5.37 - 4.78 (m, 1H), 4.31 - 4.00 (m, 4H), 3.78 - 3.75 (2 s, 3H), 3.55 - 3.40 (m, 1H), 2.83 - 2.66 (m, 2H), 2.24 - 1.98 (2 s, 3H). (mixture of interconvertible atropisomers) 431 [00559]embedded image 516.2 Method D, RT = 1.69 min, 94 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.89 (m, 1H), 7.91 - 7.76 (m, 2H), 7.73 - 7.61 (m, 1H), 7.61 - 7.39 (m, 2H), 6.79 - 6.75 (m, 2H), 6.29 - 6.13 (m, 1H), 5.38 - 4.77 (m, 1H), 4.30 - 3.82 (m, 4H), 3.77 - 3.75 (2 s, 3H), 3.55 - 3.44 (m, 1H), 2.21 - 2.01 (2 s, 3H), 1.30 - 1.13 (m, 3H). (mixture of interconvertible atropisomers) 432 [00560]embedded image 502.2 Method D, RT = 2.02 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J = 8.6 Hz, 1H), 8.26 (d, J = 5.9 Hz, 1H), 7.97 (d, J= 2.2 Hz, 1H), 7.93 - 7.80 (m, 2H), 7.58 - 7.08 (m, 2H), 6.93 - 6.71 (m, 3H), 5.72-5.67 (m, 1H), 5.02 - 4.88 (m, 1H), 4.32 - 4.27 (m, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 1.17 (d, J = 6.6 Hz, 3H). 433 [00561]embedded image 614.2 Method D, RT = 1.97 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.3 Hz, 1H), 8.05 - 7.86 (m, 2H), 7.72 - 7.59 (m, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 6.39 (t, J = 7.1 Hz, 1H), 5.08 - 4.97 (m, 1H), 4.46 - 4.38 (m, 1H), 4.33 - 4.24 (m, 1H), 4.16 (t, J = 7.8 Hz, 1H), 4.02 (dd, J= 13.3, 8.7 Hz, 1H), 3.81 - 3.72 (m, 2H), 3.72 (s, 3H), 3.36 (s, 3H). 434 [00562]embedded image 528.3 Method D, RT = 1.412 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 - 8.89 (m, 1H), 7.96 - 7.89 (m, 2H), 7.64 - 7.55 (m, 2H), 7.35 - 7.33 (m, 2H), 7.33 (t, J= 76.0 Hz, 1H), 7.25 - 7.20 (m, 2H), 6.95 - 6.88 (m, 2H), 6.34 - 6.26 (m, 1H), 5.05 - 4.91 (m, 2H), 4.12 - 4.01 (m, 2H), 3.95 - 3.88 (m, 1H), 3.80 - 3.62 (m, 6H), 1.09 (d, J = 6.4 Hz, 3H). 435 [00563]embedded image 564.2 Method D, RT = 1.66 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J= 8.8 Hz, 1H), 8.03 - 7.86 (m, 2H), 7.62 - 7.57 (m, 2H), 7.55 - 7.38 (m, 3H), 6.88 - 6.71 (m, 2H), 6.31 (t, J = 7.1 Hz, 1H), 5.12 (dd, J= 11.2, 8.8 Hz, 1H), 4.95 - 4.91 (m, 1H), 4.16 - 3.87 (m, 4H), 3.78 (s, 3H), 3.77 - 3.61 (m, 2H), 1.08 (d, J = 6.4 Hz, 3H). 436 [00564]embedded image 546.2 Method D, RT = 1.48 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.87 (m, 1H), 7.91 (d, J = 7.8 Hz, 2H), 7.66 - 7.55 (m, 2H), 7.53 - 7.46 (m, 1H), 7.35 (t, J = 72.0 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.89 - 6.70 (m, 2H), 6.31 (t, J= 7.1 Hz, 1H), 5.17 - 5.02 (m, 1H), 4.95 - 4.91 (m, 1H), 4.14 - 3.86 (m, 4H), 3.77(s, 3H), 3.76 - 3.63 (m, 2H), 1.09 (d, J= 6.1 Hz, 3H). 437 [00565]embedded image 594.3 Method D, RT = 1.68 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (br d, J = 8.8 Hz, 1H), 7.97 (d, J= 8.8 Hz, 2H), 7.69 (br d, J = 7.1 Hz, 1H), 7.57 (br d, J = 7.3 Hz, 1H), 7.54 - 7.38 (m, 3H), 6.90 - 6.73 (m, 2H), 6.41 - 6.26 (m, 1H), 5.19 - 4.98 (m, 3H), 4.18 - 4.10 (m, 1H), 4.04 - 3.94 (m, 1H), 3.79 (s, 3H) 3.77 -3.59 (m, 5H), 3.23 (s, 3H). 438 [00566]embedded image 576.2 Method D, RT = 1.50 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 (d, J = 8.6 Hz, 1H), 7.96 - 7.86 (m, 2H), 7.68 (dd, J= 7.0, 1.8 Hz, 1H), 7.56 (dd, J = 7.2, 1.8 Hz, 1H), 7.53 - 7.48 (m, 1H), 7.33 (t, J = 74.0 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.86 - 6.70 (m, 2H), 6.34 (t, J= 7.1 Hz, 1H), 5.19 - 4.98 (m, 3H), 4.18 - 4.10 (m, 1H), 4.04 - 3.94 (m, 1H), 3.79 (s, 3H) 3.78 - 3.59 (m, 5H), 3.23 (s, 3H). 439 [00567]embedded image 550.2 Method D, RT = 1.788 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.99 (m, 1H), 7.98 (d, J = 8.6 Hz, 2H), 7.68 - 7.55 (m, 2H), 7.51 - 7.45 (m, 4H), 7.44 - 7.34 (m, 2H), 6.31 (t, J = 7.1 Hz, 1H), 5.10 - 4.99 (m, 1H), 4.99 - 4.84 (m, 1H), 4.18 - 4.01 (m, 2H), 3.96 - 3.86 (m, 1H), 3.84 - 3.75 (m, 2H), 3.71 - 3.61 (m, 1H), 1.08 (d, J = 6.4 Hz, 3H). 440 [00568]embedded image 546.2 Method D, RT = 1.596 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.8 Hz, 1H), 8.05 - 7.85 (m, 2H), 7.67 - 7.55 (m, 2H), 7.47 (d, J = 7.8 Hz, 2H), 7.40 - 7.25 (m, 2H), 6.90 (d, J= 8.8 Hz, 2H), 6.30 (t, J = 7.0 Hz, 1H), 5.01 (dd, J= 11.0, 8.8 Hz, 1H), 4.97 - 4.86 (m, 1H), 4.20 - 4.03 (m, 2H), 3.98 - 3.86 (m, 1H), 3.72 (s, 3H), 3.82 - 3.56 (m, 3H), 1.09 (d, J = 6.4 Hz, 3H). 441 [00569]embedded image 641.3 Method D, RT = 1.505 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 - 8.84 (m, 1H), 7.93 (d, J = 8.1 Hz, 2H), 7.72 - 7.59 (m, 2H), 7.36 - 7.34 (m, 2H), 7.33 (t, J = 74.0 Hz, 1H), 7.27 - 7.25 (m, 2H), 6.90 (d, J= 8.8 Hz, 2H), 6.47 - 6.33 (m, 1H), 6.07 - 6.04 (m, 1H), 5.05 - 4.93 (m, 1H), 4.12 - 4.04 (m, 1H), 3.93 - 3.74 (m, 3H), 3.72 (s, 3H), 3.64 - 3.44 (m, 6H), 3.28 (s, 3H), 3.38 - 3.19 (m, 3H). 442 [00570]embedded image 542.2 Method D, RT = 1.901 min, 97.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.97 (m, 1H), 7.99 - 7.85 (m, 2H), 7.71 - 7.67 (m, 1H), 7.56 - 7.47 (m, 1H), 7.45 - 7.12 (m, 6H), 6.25 - 6.21 (m, 1H), 5.33 - 4.62 (m, 1H), 4.17 - 3.94 (m, 1H), 4.17 - 3.82 (m, 2H), 3.81 - 3.47 (m, 2H), 2.21 - 2.07 (2 s, 3H), 1.28 - 1.16 (m, 1H), 0.52 - 0.45 (m, 2H), 0.42 - 0.34 (m, 2H). (mixture of interconvertible atropisomers) 443 [00571]embedded image 570.2 Method D, RT = 2.006 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 9.03 (m, 1H), 8.03 - 7.94 (m, 2H), 7.67 - 7.63 (m, 1H), 7.55 - 7.37 (m, 6H), 6.50 - 6.15 (m, 1H), 6.33 - 6.29 (m, 1H) 5.36 - 4.67 (m, 1H), 4.51 - 4.35 (m, 2H), 4.16 - 3.50 (m, 3H), 2.26 - 2.12 (2 s, 3H). (mixture of interconvertible atropisomers) 444 [00572]embedded image 625.3 Method D, RT = 1.594 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J= 9.0 Hz, 1H), 7.95 - 7.88 (m, 2H), 7.76 - 7.72 (m, 1H), 7.64 - 7.59 (m, 1H), 7.35 - 7.33 (m, 2H), 7.33 (t, J = 72.0 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.94 - 6.83 (m, 2H), 6.43 - 6.35 (m, 1H), 5.95 - 5.87 (m, 1H), 5.03 - 4.94 (m, 1H), 4.05 (br d, J = 1.2 Hz, 1H), 3.92 - 3.84 (m, 1H), 3.80 -3.75 (m, 2H), 3.72 (s, 3H), 3.66 - 3.59 (m, 2H), 3.57 - 3.49 (m, 2H), 3.35 - 3.29 (m, 1H), 3.27 (s, 3H), 1.96 - 1.84 (m, 2H), 1.82 - 1.70 (m, 2H). 445 [00573]embedded image 564.2 Method D, RT = 1.49 min, 100 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.86 (d, J = 8.6 Hz, 1H), 7.95 - 7.82 (m, 2H), 7.66 (dd, J = 6.6 Hz, 2.0, 1H), 7.58 (dd, J = 6.6, 2.0, Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 - 7.26 (m, 2H), 6.85 - 6.65 (m, 2H), 6.31 (t, J = 7.0 Hz, 1H), 5.66 (dd, J = 11.9, 8.7 Hz, 1H), 4.94 (t, J = 5.3 Hz, 1H), 4.69 - 4.56 (m, 1H), 4.30 (dd, J = 12.0, 8.1 Hz, 1H), 4.16 - 4.03 (m, 1H), 3.99 - 3.89 (m, 1H), 3.76 (s, 3H), 3.71 -3.57 (m, 2H), 0.91 (d, J = 6.6 Hz, 3H). 446 [00574]embedded image 604.3 Method D, RT = 1.792 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 - 8.96 (m, 1H), 7.91 - 7.85 (m, 2H), 7.34 (t, J = 73.2 Hz, 1H), 7.34 (s, 1H), 7.29 -7.21 (m, 2H), 6.80 - 6.72 (m, 2H), 5.14 -5.06 (m, 1H), 5.00 - 4.92 (m, 1H), 4.14 -4.01 (m, 3H), 3.98 - 3.90 (m, 2H), 3.76 (s, 3H), 3.66 - 3.58 (m, 2H), 2.86 - 2.79 (m, 2H), 2.56 - 2.47 (m, 2H), 1.81 - 1.71 (m, 2H), 1.70 - 1.60 (m, 2H). 447 [00575]embedded image 625.2 Method D, RT = 2.1 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.95 (m, 1H), 8.33 - 8.14 (m, 1H), 7.89 - 7.76 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 6.96 - 6.86 (m, 1H), 6.78 (d, J= 11.0 Hz, 2H), 6.44 - 6.29 (m, 1H), 5.17 - 5.05 (m, 1H), 4.33 - 4.02 (m, 3H), 3.80 (s, 3H), 3.79 - 3.68 (m, 1H), 3.68 - 3.57 (m, 1H), 3.46 - 3.36 (m, 2H), 1.98 - 1.76 (m, 2H), 1.68 - 1.54 (m, 1H), 1.21 - 1.04 (m, 2H). 448 [00576]embedded image 677.2 Method D, RT = 1.71 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.98 (m, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.83 - 7.73 (m, 1H), 7.63 - 7.59 (m, 1H), 7.33 (t, J = 74.0 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.84 - 6.67 (m, 2H), 6.40 (dt, J= 7.2, 1.6 Hz, 1H), 5.89 - 5.81 (m, 1H), 5.14 -4.91 (m, 2H), 4.39 - 4.20 (m, 1H), 4.15 -4.05 (m, 1H), 4.02 - 3.81 (m, 4H), 3.78 (s, 3H), 3.76 - 3.68 (m, 1H), 3.51 - 3.38 (m, 3H), 3.27 (2 s, 3H), 2.02 - 1.66 (m, 2H). 449 [00577]embedded image 590.3 Method D, RT = 1.72 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 7.02 (m, 1H), 8.07 - 7.90 (m, 2H), 7.67 - 7.54 (m, 1H), 7.54 - 7.41 (m, 2H), 7.38 (d, J = 8.5 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 6.98 - 6.78 (m, 2H), 6.21 (d, J= 7.5 Hz, 1H), 5.23 - 4.64 (m, 3H), 4.14 - 3.81 (m, 2H), 3.78 - 3.70 (m, 4H), 3.64 - 3.42 (m, 4H), 3.23 - 3.20 (2 s, 3H), 2.20 - 2.08 (2 s, 3H). (mixture of interconvertible atropisomers) 450 [00578]embedded image 542.2 Method D, RT = 1.87 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.96 (m, 1H), 7.91 - 7.78 (m, 2H), 7.73 - 7.65 (m, 1H), 7.59 - 7.52 (m, 2H), 6.79-6.75 (m, 2H), 6.27 - 6.19 (m, 1H), 5.36 -4.89 (m, 1H), 4.28 - 4.03 (m, 3H), 3.86 -3.80 (m, 1H), 3.77 - 3.74 (2 s, 3H), 3.58 -3.45 (m, 1H), 2.26 - 1.96 (2 s, 3H), 1.28 -1.15 (m, 1H), 0.50 - 0.46 (m, 2H), 0.40 -0.37 (m, 2H). (mixture of interconvertible atropisomers) 451 [00579]embedded image 647.2 Method C, RT = 1.88 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.8 Hz, 1H), 8.33 - 8.22 (m, 1H), 7.90 - 7.75 (m, 2H), 7.58 - 7.54 (m, 2H), 6.94 - 6.85 (m, 1H), 6.85 - 6.68 (m, 3H), 5.17 - 5.06 (m, 1H), 4.32 - 4.18 (m, 2H), 3.82 - 3.67 (m, 6H), 3.45 (t, J = 6.7 Hz, 2H), 3.07 (s, 3H). 452 [00580]embedded image 613.2 Method D, RT = 2.002 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (br s, 1H), 8.05 (d, J = 4.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 4.4 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.34 - 5.22 (m, 1H), 5.08 (br d, J= 10.8 Hz, 1H), 4.98 - 4.81 (br s, 1H), 4.37 - 4.28 (m, 1H), 4.21 - 4.04 (m, 2H), 3.77 (s, 3H), 3.72 - 3.56 (m, 4H), 3.21 (s, 3H). 453 [00581]embedded image 490.2 Method D, RT = 1.84 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.3 Hz, 1H), 8.41 (d, J = 4.6 Hz, 1H), 7.94-7.84 (m, 3H), 7.57 - 7.48 (m, 3H), 6.89 - 6.73 (m, 2H), 5.53 (dd, J = 10.8, 8.6 Hz, 1H), 4.84 - 4.70 (m, 1H), 4.37 (dd, J = 10.8, 8.6 Hz, 1H), 3.78 (s, 3H), 1.03 (d, J = 6.6 Hz, 3H). 454 [00582]embedded image 600.2 Method D, RT = 1.846 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.94 (m, 1H), 7.97 - 7.78 (m, 2H), 7.72 - 7.61 (m, 1H), 7.54 - 7.11 (m, 3H), 6.85 - 6.66 (m, 2H), 6.42 - 6.30 (m, 1H), 6.02 - 5.89 (m, 1H), 5.36 - 4.84 (m, 1H), 4.32 - 3.99 (m, 4H), 3.76 (2 s, 3H), 3.59 - 3.52 (m, 1H), 2.26 - 2.08 (2 s, 3H). (mixture of interconvertible atropisomers) 455 [00583]embedded image 577.2 Method D, RT = 2.02 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 9.01 (m, 1H), 8.04 - 7.86 (m, 2H), 7.81 - 7.65 (m, 1H), 7.57 - 7.40 (m, 2H), 6.90 - 6.66 (m, 2H), 6.44 - 6.27 (m, 1H), 5.39 - 4.81 (m, 3H), 4.30 - 4.05 (m, 2H), 3.77 (s, 3H), 3.62 - 3.47 (m, 1H), 2.25 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 456 [00584]embedded image 636.3 Method D, RT = 1.904 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.30 - 8.92 (m, 1H), 8.10 - 7.83 (m, 2H), 7.73 - 7.53 (m, 1H), 7.53 - 7.23 (m, 2H), 6.84 - 6.60 (m, 2H), 6.30 - 6.13 (m, 1H), 5.43 - 4.78 (m, 1H), 4.34 - 4.02 (m, 2H), 3.95 - 3.69 (m, 4H), 3.70 (s, 3H), 3.56 - 3.43 (m, 1H), 3.27 - 3.13 (m, 2H), 2.22 - 2.04 (2 s, 3H), 2.04 - 1.83 (m, 1H), 1.44 - 1.38 (m, 2H), 1.35 - 1.11 (m, 2H). (mixture of interconvertible atropisomers) 457 [00585]embedded image 618.3 Method D, RT = 1.732 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.79 (m, 1H), 8.01 - 7.76 (m, 2H), 7.71 - 7.55 (m, 1H), 7.55 - 7.00 (m, 3H), 6.78 - 6.73 (m, 2H), 6.30 - 6.06 (m, 1H), 5.42 - 4.82 (m, 1H), 4.33 - 4.01 (m, 2H), 3.93 - 3.78 (m, 4H), 3.78 - 3.76 (2 s, 3H), 3.55 - 3.43 (m, 1H), 3.27 - 3.15 (m, 2H), 2.23 - 2.03 (2 s, 3H), 2.03 - 1.88 (m, 1H), 1.43 (m, 2H), 1.36 - 1.13 (m, 2H). (mixture of interconvertible atropisomers) 458 [00586]embedded image 592.2 Method D, RT = 2.021 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.28 - 8.95 (m, 1H), 8.05 - 7.90 (m, 2H), 7.84 - 7.64 (m, 1H), 7.57 - 7.38 (m, 2H), 6.78 - 6.73 (m, 2H), 6.35 - 6.15 (m, 1H), 5.37 - 4.79 (m, 2H), 4.33 - 3.91 (m, 2H), 3.78 - 3.77 (2 s, 3H), 3.74 - 3.63 (m, 1H), 3.59 - 3.37 (m, 1H), 2.40 - 2.20 (m, 3H), 2.20 - 1.97 (2 s, 3H), 1.83 - 1.13 (m, 1H), 0.59 - 0.27 (m, 1H). (mixture of interconvertible atropisomers) 459 [00587]embedded image 538.3 Method D, RT = 1.714 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 8.82 (m, 1H), 7.99 - 7.89 (m, 2H), 7.70 - 7.66 (m, 1H), 7.55 - 7.06 (m, 5H), 6.92 - 6.89 (m, 2H), 6.24 - 6.21 (m, 1H), 5.29 - 4.62 (m, 1H), 4.13 - 3.81 (m, 2H), 3.79 - 3.59 (m, 5H), 3.48 - 3.44 (m, 1H), 2.25 - 2.04 (2 s, 3H), 1.25 - 1.20 (m, 1H), 0.56 - 0.27 (m, 4H). (mixture of interconvertible atropisomers) 460 [00588]embedded image 588.3 Method D, RT = 2.136 min, 100% 1H NMR (400 MHz, DMSO-d6) δ = 8.99 (d, J= 8.8 Hz, 1H), 7.93 - 7.81 (m, 2H), 7.34 (t, J = 73.6 Hz, 1H), 7.34 (s, 1H), 7.27 - 7.25 (m, 2H), 6.76 (d, J= 10.8 Hz, 2H), 5.11 (dd, J= 11.1, 8.7 Hz, 1H), 4.16 - 3.99 (m, 3H), 3.94 (br d, J = 9.3 Hz, 2H), 3.76 (s, 3H), 2.75 (br t, J = 6.0 Hz, 2H), 2.52 - 2.47 (m, 2H), 1.85 - 1.72 (m, 2H), 1.70 - 1.54 (m, 2H), 1.18 (t, J = 7.0 Hz, 3H). 461 [00589]embedded image 586.2 Method D, RT = 2.146 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J= 8.6 Hz, 1H), 7.91 - 7.73 (m, 2H), 7.62 - 7.44 (m, 2H), 7.34 (s, 1H), 6.76 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.22 - 4.03 (m, 3H), 3.98 - 3.90 (m, 2H), 3.76 (s, 3H), 3.55 (t, J= 5.6 Hz, 2H), 3.23 (s, 3H), 2.86 - 2.70 (m, 2H), 2.52 - 2.47 (m, 2H), 1.87 - 1.69 (m, 2H), 1.69 - 1.49 (m, 2H). 462 [00590]embedded image 639.2 Method D, RT = 1.707 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.6 Hz, 1H), 8.50 (s, 1H), 8.18 (s, 1H), 7.89 - 7.76 (m, 2H), 7.61 - 7.48 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.40 (tt, J = 52.0, 4.2 Hz, 1H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.62 - 4.36 (m, 2H), 4.18 -4.04 (m, 1H), 4.04 - 3.86 (m, 2H), 3.76 (s, 3H). 463 [00591]embedded image 594.2 Method D, RT = 1.777 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.24 - 9.01 (m, 1H), 8.02 - 7.85 (m, 2H), 7.78 - 7.74 (m, 1H), 7.54 - 7.39 (m, 2H), 6.86 - 6.65 (m, 2H), 6.41 - 6.26 (m, 1H), 5.58 - 5.41 (m, 1H), 5.37 - 4.65 (m, 5H), 4.30 - 4.00 (m, 2H), 3.77 - 3.74 (2 s, 3H), 3.53 - 3.50 (m, 1H), 2.25 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 464 [00592]embedded image 556.2 Method D, RT = 2.145 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.32 (s, 1H), 6.76 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 11.1, 8.7 Hz, 1H), 4.15 - 3.98 (m, 3H), 3.94 (br d, J = 9.0 Hz, 2H), 3.76 (s, 3H), 2.81 - 2.66 (m, 2H), 2.52 - 2.47 (m, 2H), 1.87 - 1.70 (m, 2H), 1.70 - 1.56 (m, 2H), 1.18 (t, J = 7.0 Hz, 3H). 465 [00593]embedded image 600.2 Method D, RT = 1.85 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.3 Hz, 1H), 7.97 - 7.85 (m, 2H), 7.69 (dd, J= 6.8, 2.0 Hz, 1H), 7.65 (dd, J = 7.3, 2.0 Hz, 1H), 7.52 (d, J = 9.8 Hz, 1H), 7.35 (t, J= 73.6 Hz, 1H), 7.29 - 7.2 (m, 2H), 6.88 - 6.76 (m, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.12 (dd, J = 11.2, 8.8 Hz, 1H), 4.45 (dd, J = 13.0, 2.7 Hz, 1H), 4.39 - 4.30 (m, 1H), 4.13 - 4.06 (m, 1H), 4.05 - 3.97 (m, 1H), 3.90 - 3.82 (m, 1H), 3.77 - 3.72 (m, 4H). 466 [00594]embedded image 637.2 Method D, RT = 2.07 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 4.6 Hz, 1H), 7.99 - 7.85 (m, 2H), 7.74 (d, J = 4.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.06 (br dd, J= 4.6, 1.7 Hz, 1H), 5.10 - 4.98 (m, 1H), 4.55 -4.45 (m, 1H), 4.42 - 4.23 (m, 3H), 4.23 -4.02 (m, 2H), 3.77 (s, 3H). 467 [00595]embedded image 565.2 Method D, RT = 1.619 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 8.34 (s, 1H), 8.12 (s, 1H), 7.96 - 7.80 (m, 2H), 7.34 (t, J= 72.6 Hz, 1H), 7.30 - 7.24 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.13 - 5.02 (m, 2H), 4.17 -4.04 (m, 2H), 4.04 - 3.83 (m, 3H), 3.76 (s, 3H), 3.66 (dd, J = 13.1, 8.7 Hz, 1H), 1.11 (d, J = 6.4 Hz, 3H). 468 [00596]embedded image 603.1 Method D, RT = 1.97 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.3 Hz, 1H), 8.04 (d, J = 4.6 Hz, 1H), 7.92 - 7.83 (m, 2H), 7.74 (d, J = 4.6 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 -7.27 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.05 (dd, J = 11.0, 8.3 Hz, 1H), 4.40 -4.28 (m, 3H), 4.25 - 4.15 (m, 1H), 4.15 -4.04 (m, 1H), 3.77 (s, 3H), 2.86 - 2.74 (m, 2H). 469 [00597]embedded image 644.2 Method D, RT = 2.00 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 8.90 (m, 1H), 8.06 - 7.85 (m, 2H), 7.76 - 7.61 (m, 1H), 7.55 - 7.35 (m, 2H), 6.86 - 6.63 (m, 2H), 6.36 - 6.19 (m, 1H), 5.39 - 4.81 (m, 1H), 4.38 - 4.06 (m, 4H), 3.82 - 3.69 (2 s, 3H), 3.61 - 3.46 (m, 3H), 3.10 - 2.97 (2 s, 3H), 2.25 - 1.96 (2 s, 3H). (mixture of interconvertible atropisomers) 470 [00598]embedded image 626.2 Method D, RT = 1.84 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.87 (m, 1H), 7.99 - 7.80 (m, 2H), 7.73 - 7.63 (m, 1H), 7.56 - 7.05 (m, 3H), 6.87 - 6.56 (m, 2H), 6.34 - 6.17 (m, 1H), 5.39 - 4.84 (m, 1H), 4.44 - 4.05 (m, 4H), 3.84 - 3.73 (2 s, 3H), 3.64 - 3.42 (m, 3H), 3.10 - 2.98 (2 s, 3H), 2.24 - 1.98 (2 s, 3H). (mixture of interconvertible atropisomers) 471 [00599]embedded image 597.2 Method D, RT = 2.12 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 9.00 (m, 1H), 8.08 - 7.76 (m, 3H), 7.59 - 7.35 (m, 2H), 6.90 - 6.64 (m, 2H), 5.38 - 4.75 (m, 1H), 4.42 - 4.10 (m, 4H), 3.81 - 3.74 (2 s, 3H), 3.74 - 3.50 (m, 3H), 3.23 (s, 3H), 2.28 - 2.03 (2 s, 3H). (mixture of interconvertible atropisomers) 472 [00600]embedded image 579.2 Method D, RT = 1.89 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 8.93 (m, 1H), 8.05 - 7.93 (m, 1H), 7.93 - 7.77 (m, 2H), 7.56 - 7.09 (m, 3H), 6.88 - 6.66 (m, 2H), 5.36 - 4.74 (m, 1H), 4.45 - 4.12 (m, 4H), 3.82 - 3.72 (2 s, 3H), 3.72 - 3.51 (m, 3H), 3.23 (s, 3H), 2.26 - 2.02 (2 s, 3H). (mixture of interconvertible atropisomers) 473 [00601]embedded image 589.2 Method D, RT = 2.17 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J = 8.3 Hz, 1H), 8.07 (d, J = 4.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 4.6 Hz, 1H), 7.50 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.40 (tt, J = 56.0, 4.0 Hz, 1H), 5.07 (dd, J = 11.0, 8.3 Hz, 1H), 4.56 (td, J = 14.4, 4.0 Hz, 2H), 4.42 - 4.30 (m, 1H), 4.27 - 4.16 (m, 1H), 4.16 - 4.03 (m, 1H), 3.77 (s, 3H). 474 [00602]embedded image 571.3 Method D, RT = 2.00 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.1 Hz, 1H), 8.06 (d, J = 4.6 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 4.6 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.26 (m, 2H), 6.78 (d, J= 10.8 Hz, 2H), 6.40 (tt, J= 56.0, 4.0 Hz, 1H), 5.05 (dd, J = 11.0, 8.3 Hz, 1H), 4.55 (td, J = 14.3, 4.2 Hz, 2H), 4.39 - 4.29 (m, 1H), 4.26 - 4.15 (m, 1H), 4.15 - 4.02 (m, 1H), 3.76 (s, 3H). 475 [00603]embedded image 619.2 Method D, RT = 1.95 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.1 Hz, 1H), 8.04 (d, J = 4.4 Hz, 1H), 7.87 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 4.6 Hz, 1H), 7.34 (t, J = 73.6 Hz, 1H), 7.29 - 7.26 (m, 2H), 6.78 (d, J= 11.0 Hz, 2H), 6.70 - 6.50 (brs, 1H), 5.04 (dd, J = 11.2, 7.8 Hz, 1H), 4.56 - 4.46 (m, 1H), 4.39 - 4.06 (m, 5H), 3.77 (s, 3H). 476 [00604]embedded image 595.2 Method D, RT = 1.74 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.3 Hz, 1H), 8.05 (d, J = 4.4 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.65 (d, J= 4.6 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 -7.26 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.32 - 5.22 (m, 1H), 5.05 (dd, J = 11.2, 8.6 Hz, 1H), 4.91 (t, J = 5.9 Hz, 1H), 4.33 - 4.25 (m, 1H), 4.19 - 4.12 (m, 1H), 4.15 - 4.06 (m, 1H), 3.77 (s, 3H), 3.71 - 3.57 (m, 4H), 3.20 (s, 3H). 477 [00605]embedded image 563.2 Method C, RT = 1.76 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 4.6 Hz, 1H), 7.86 - 7.75 (m, 2H), 7.65 (d, J = 4.4 Hz, 1H), 7.57 (d, J = 8.6 Hz, 2H), 6.78 (d, J= 10.8 Hz, 2H), 5.35 - 5.24 (m, 1H), 5.07 (dd, J = 10.9, 8.4 Hz, 1H), 4.89 (t, J = 5.7 Hz, 1H), 4.37 - 4.27 (m, 1H), 4.22 - 4.04 (m, 2H), 3.77 (s, 3H), 3.72 - 3.57 (m, 4H), 3.21 (s, 3H). 478 [00606]embedded image 622.3 Method D, RT = 1.86 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.93 (m, 1H), 8.05 - 7.84 (m, 2H), 7.80 - 7.65 (m, 1H), 7.56 - 7.35 (m, 2H), 6.87 - 6.63 (m, 2H), 6.37 - 6.16 (m, 1H), 5.38 - 4.80 (m, 2H), 4.31 - 4.07 (m, 2H), 4.04 - 3.93 (m, 2H), 3.77 - 3.69 (2 s, 3H), 3.55 - 3.39 (m, 3H), 2.25 - 2.05 (2 s, 3H), 1.99 - 1.84 (m, 2H), 1.77 - 1.60 (m, 2H). (mixture of interconvertible atropisomers) 479 [00607]embedded image 590.2 Method D, RT = 1.66 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.87 (m, 1H), 7.94 - 7.79 (m, 2H), 7.61 - 7.47 (m, 1H), 7.46 - 7.05 (m, 3H), 6.78 - 6.75 (m, 2H), 6.35 - 6.20 (m, 1H), 5.41 - 5.24 (m, 1H), 4.88 - 4.86 (m, 1H), 4.28 - 4.00 (m, 3H), 3.89 - 3.82 (m, 3H), 3.79 - 3.76 (2 s, 3H) 3.50 - 3.47 (m, 1H), 2.47 - 2.37 (m, 1H), 2.24 - 2.04 (2 s, 3H), 2.02 - 1.88 (m, 1H). (mixture of interconvertible atropisomers) 480 [00608]embedded image 625.3 Method D, RT = 2.03 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (br d, J = 8.6 Hz, 1H), 8.13 (d, J = 6.1 Hz, 1H), 7.81 (br d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 6.89 - 6.67 (m, 3H), 5.20 - 5.11 (m, 1H), 4.88 (br s, 1H), 4.51 - 4.41 (m, 1H), 4.24 - 4.16 (m, 1H), 3.77 (s, 3H), 3.76 - 3.66 (m, 2H), 3.48 - 3.43 (m, 1H), 3.39 - 3.09 (m, 2H), 1.94 - 1.83 (m, 2H), 1.36 (s, 3H). 481 [00609]embedded image 650.3 Method D, RT = 2.15 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 9.00 (m, 1H), 8.40 (d, J = 5.6 Hz, 1H), 7.82 (br d, J = 6.8 Hz, 2H), 7.56 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 5.6 Hz, 1H), 6.78 (d, J = 11.0 Hz, 2H), 5.18 - 5.02 (m, 1H), 4.42 - 4.31 (m, 1H), 4.28 - 4.14 (m, 1H), 3.83 - 3.70 (m, 4H), 3.67 - 3.41 (m, 2H), 3.13 - 2.96 (m, 3H), 2.89 - 2.70 (m, 1H), 2.18 - 1.94 (m, 3H), 1.83 - 1.62 (m, 3H), 1.40 - 1.25 (m, 1H). 482 [00610]embedded image 707.2 Method D, RT = 1.83 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.0 Hz, 1H), 8.11 (dd, J = 4.8, 1.8 Hz, 1H), 8.01 - 7.94 (m, 2H), 7.84 (dd, J = 7.8, 1.8 Hz, 1H), 7.53 - 7.44 (m, 2H), 7.16 (dd, J = 7.5, 5.0 Hz, 1H), 6.80 (d, J = 10.5 Hz, 2H), 5.41 (dd, J = 6.0, 3.5 Hz, 1H), 5.12 - 5.05 (m, 1H), 4.70 - 4.59 (m, 4H), 4.29 - 4.14 (m, 2H), 4.10 - 3.98 (m, 4H), 3.80 - 3.74 (m, 5H), 3.51 - 3.69 (m, 1H), 3.30 (s, 3H). 483 [00611]embedded image 600.2 Method D, RT = 1.84 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.89 (m, 1H), 7.94 - 7.75 (m, 2H), 7.67 - 7.42 (m, 3H), 6.87 - 6.60 (m, 3H), 6.38 - 6.16 (m, 1H), 5.39 - 4.80 (m, 1H), 4.48 - 4.03 (m, 4H), 3.86 - 3.78 (m, 1H), 3.77-3.74 (2 s, 3H), 3.58 - 3.45 (m, 1H), 2.26 -1.96 (2 s, 3H). (mixture of interconvertible atropisomers) 484 [00612]embedded image 586.2 Method D, RT = 2.007 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.97 (m, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 6.78 - 6.70 (m, 2H), 5.02 - 4.94 (m, 1H), 4.66 - 4.57 (m, 1H), 3.96 - 3.85 (m, 1H), 3.75 (s, 3H), 3.59 - 3.52 (m, 1H), 3.46 - 3.41 (m, 4H), 3.41 - 3.35 (m, 3H), 3.23 (s, 3H), 2.04 -1.82 (m, 4H). 485 [00613]embedded image 661.3 Method D, RT = 1.93 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 6.8, 1.7 Hz, 1H), 7.60 (dd, J = 7.2, 1.7 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.30 - 7.23 (m, 2H), 6.80 - 6.74 (m, 2H), 6.40 (t, J = 7.0 Hz, 1H), 5.92 (dd, J = 8.6, 5.1 Hz, 1H), 5.09 (dd, J = 10.9, 8.4 Hz, 1H), 4.13 - 4.05 (m, 1H), 4.03 - 3.95 (m, 1H), 3.95 - 3.83 (m, 3H), 3.76 (s, 3H), 3.65 - 3.53 (m, 2H), 3.34 -3.28 (m, 2H), 3.27 (s, 3H), 1.96 - 1.85 (m, 2H), 1.82 - 1.68 (m, 2H). 486 [00614]embedded image 587.2 Method D, RT = 1.862 min, 98.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (br s, 1H), 8.45 (s, 1H), 8.19 (s, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 10.5 Hz, 2H), 5.10 (d, J = 11.2 Hz, 1H), 4.43 - 4.29 (m, 2H), 4.12 (br dd, J = 10.3, 9.5 Hz, 1H), 4.05 - 3.87 (m, 3H), 3.76 (s, 3H), 3.35 - 3.32 (m, 1H). 487 [00615]embedded image 603.2 Method D, RT = 1.791 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.6 Hz, 1H), 8.56 (s, 1H), 8.17 (s, 1H), 7.96 - 7.79 (m, 2H), 7.34 (t, J = 74.0 Hz, 1H), 7.29 - 7.24 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.12 (dd, J = 11.2, 8.6 Hz, 1H), 4.23 (t, J = 7.2 Hz, 2H), 4.17 - 4.05 (m, 1H), 4.05 - 3.87 (m, 2H), 3.76 (s, 3H), 2.92 - 2.72 (m, 2H). 488 [00616]embedded image 551.2 Method D, RT = 1.441 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.6 Hz, 1H), 8.37 (s, 1H), 8.13 (s, 1H), 7.95 - 7.83 (m, 2H), 7.34 (t, J = 73.0 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.76 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 11.0, 8.6 Hz, 1H), 4.17 - 4.06 (m, 1H), 4.02 (t, J = 5.1 Hz, 2H), 3.99 - 3.91 (m, 3H), 3.76 (s, 3H), 3.68 - 3.60 (m, 2H). 489 [00617]embedded image 632.3 Method D, RT = 1.77 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 8.89 (m, 1H), 7.99 - 7.79 (m, 2H), 7.61-7.52 (m, 1H), 7.55 - 7.09 (m, 3H), 6.86 -6.55 (m, 3H), 6.235 - 6.25 (m, 1H), 5.34 - 4.77 (m, 1H), 4.47 - 4.23 (m, 3H), 4.19 -4.10 (m,1H), 3.82 - 3.79(m, 1H), 3.77 -3.73 (2 s, 3H), 3.57 - 3.47 (m, 1H), 2.24 -2.00 (2 s, 3H). (mixture of interconvertible atropisomers) 490 [00618]embedded image 618.2 Method F, RT = 1.999 min, 93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.03 (m, 1H), 8.01 - 7.87 (m, 2H), 7.71 - 7.62 (m, 1H), 7.54 - 7.41 (m, 2H), 6.85 - 6.68 (m, 2H), 6.42 - 6.28 (m, 1H), 6.01 - 5.86 (m, 1H), 5.33 - 4.77 (m, 1H), 4.32 - 4.17 (m, 3H), 4.14 - 4.02 (m, 1H), 3.78 - 3.76 (2 s, 3H), 3.61 - 3.54 (m, 1H), 2.26 - 2.08 (2 s, 3H). (mixture of interconvertible atropisomers) 491 [00619]embedded image 675.2 Method-D, RT = 1.742 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.89 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 2.0 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.27 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 11.5 Hz, 2H), 6.75 (d, J = 2.0 Hz, 1H), 5.66 (dd, J = 12.6, 8.4 Hz, 1H), 4.97 (quin, J = 7.1 Hz, 1H), 4.31 (dd, J = 12.6, 7.9 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 3.53 - 3.40 (m, 2H), 3.25 (s, 3H), 3.09 - 2.87 (m, 2H), 2.65 - 2.54 (m, 2H), 2.47 - 2.38 (m, 1H), 2.16 - 1.95 (m, 2H), 1.88 - 1.67 (m, 4H), 1.20 (br d, J = 6.3 Hz, 3H). 492 [00620]embedded image 649.2 Method-D, RT = 1.963 min, 94.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.3 Hz, 1H), 7.92 - 7.86 (m, 2H), 7.84 (d, J = 2.0 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.29 (d, J = 8.3 Hz, 2H), 6.81 (d, J = 10.8 Hz, 2H), 6.75 (d, J = 2.0 Hz, 1H), 5.06 (dd, J = 10.5, 8.3 Hz, 1H), 4.86 (dt, J = 47.2, 4.5 Hz, 2H), 4.44 - 4.43 (m, 1H), 4.47 (br t, J = 9.9 Hz, 1H), 4.15 (q, J = 9.9 Hz, 1H), 3.97 (br t, J = 10.5 Hz, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 3.67 -3.51 (m, 4H), 3.20 - 3.04 (m, 1H), 2.96 -2.83 (m, 1H), 2.15 - 1.96 (m, 4H). 493 [00621]embedded image 511.2 Method C, RT = 1.465 min, 98.3 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.5 Hz, 1H), 8.43 (d, J = 6.8 Hz, 1H), 7.86 (d, J = 8.5 Hz, 2H), 7.77 (s, 1H), 7.58 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 7.5 Hz, 1H), 6.90 (t, J = 7.1 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.20 (dd, J = 11.0, 8.5 Hz, 1H), 4.55 - 4.46 (m, 1H), 4.33 (br t, J = 9.9 Hz, 1H), 4.25 - 4.13 (m, 1H), 3.78 (s, 3H), 2.36 (s, 3H). 494 [00622]embedded image 527.12 Method C, RT = 1.387 min, 95.6%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.5 Hz, 1 H), 8.49 (d, J = 6.5 Hz, 1H), 7.92 - 7.82 (m, 3H), 7.58 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 7.25 Hz, 1H), 6.93 (t, J = 7.1 Hz, 1H), 6.85 - 6.75 (m, 2H), 5.26 - 5.17 (m, 2H), 4.62 (d, J = 4.7 Hz, 2H), 4.59 - 4.48 (m, 1H), 4.37 - 4.17 (m, 2H), 3.78 (s, 3 H). 495 [00623]embedded image 537.14 Method C, RT = 1.635 min, 100 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.8 Hz, 1H), 8.38 (dd, J = 6.8, 1.0 Hz, 1H), 7.90 - 7.81 (m, 2H), 7.77 (s, 1H), 7.62 - 7.49 (m, 2H),7.39 (dd, J = 7.3, 1.0 Hz, 1H), 6.92 - 6.86 (m, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.17 (dd, J = 11.0, 8.8 Hz, 1H), 4.51 - 4.42 (m, 1H), 4.35 (t, J = 11.0 Hz, 1H), 4.25 - 4.13 (m, 1H), 3.78 (s, 3H), 2.08 - 1.96 (m, 1H), 0.96 - 0.89 (m, 2H), 0.84 - 0.76 (m, 2H). 496 [00624]embedded image 539 Method C, RT = 1.685 min, 100 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.8 Hz, 1H), 8.42 (dd, J = 6.6, 1.1 Hz, 1H), 7.92 - 7.80 (m, 2H), 7.76 (s, 1H), 7.62 - 7.51 (m, 2H), 7.42 (dd, J = 7.5, 1.1 Hz, 1H), 6.90 (t, J = 7.0 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.20 (dd, J = 11.1, 8.6 Hz, 1H), 4.60 - 4.48 (m, 1H), 4.37 (t, J = 10.3 Hz, 1H), 4.21 (q, J = 10.3 Hz, 1H), 3.77 (s, 3H), 3.04 - 2.97 (m, 1H), 1.29 (d, J = 6.8 Hz, 6H). 497 [00625]embedded image 565 Method C, RT = 2.034 min, 94.3 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.5 Hz, 1H), 8.65 (d, J = 1.0 Hz, 1H), 8.57 (dd, J = 6.8, 1.0 Hz, 1H), 7.93 - 7.80 (m, 2H), 7.70 (dd, J = 7.5, 1.0 Hz, 1H), 7.62 - 7.51 (m, 2H), 7.21 - 7.09 (m, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.19 (dd, J = 10.8, 8.6 Hz, 1H), 4.54 - 4.45 (m, 1H), 4.37 - 4.29 (m, 1H), 4.29 - 4.19 (m, 1H), 3.77 (s, 3H). 498 [00626]embedded image 617.2 Method D, RT = 1.564 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.80 (d, J = 2.2 Hz, 1H), 7.36 (t, J = 74.1 Hz, 1H), 7.29 (d, J = 8.3 Hz, 2H), 6.80 (d, J = 11.0 Hz, 2H), 6.70 (d, J = 2.2 Hz, 1H), 5.07 (dd, J = 11.0, 8.3 Hz, 1H), 4.47 (t, J = 9.8 Hz, 1H), 4.16 - 4.05 (m, 1H), 4.00 - 3.90 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 2.84 - 2.80 (m, 2H), 2.16 (s, 3H), 1.98 - 1.86 (m, 3H), 1.83 - 1.71 (m, 4H). 499 [00627]embedded image 559.15 Method C, RT = 2.043 min, 100 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.0 Hz, 1H), 8.65 (d, J = 0.8 Hz, 1H), 7.88 - 7.74 (m, 2H), 7.66 (d, J = 0.8 Hz, 1H), 7.62 - 7.52 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.05 (dd, J = 11.1, 8.1 Hz, 1H), 4.45 (t, J = 9.8 Hz, 1H), 4.38 - 4.24 (m, 2H), 4.21 - 4.07 (m, 2H), 4.00 - 3.89 (m,1H), 3.82 - 3.72 (m, 4H), 3.70 - 3.59 (m, 1H), 2.04 - 1.93 (m, 1H), 1.92 - 1.75 (m, 2H), 1.71 - 1.59 (m, 1H). 500 [00628]embedded image 571.2 Method D, RT = 1.489 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.84 (t, J = 8.0 Hz, 1H), 7.35 (t, J = 72.5 Hz, 1H), 7.36 - 7.23 (m, 3H), 6.88 - 6.72 (m, 3H), 5.08 (dd, J = 10.8, 8.3 Hz, 1H), 4.49 (t, J = 9.9 Hz, 1H), 4.13 (q, J = 9.9 Hz, 1H), 4.02 - 3.96 (m, 1H), 3.78 (s, 3H), 3.77 -3.72 (m, 2H), 3.54 - 3.49 (brs, 1H), 2.92 - 1.89 (m, 2H), 2.28 - 2.24 (m, 2H). 501 [00629]embedded image 617.3 Method D, RT = 1.473 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.5 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 9.0 Hz, 2H), 7.80 (t, J = 7.8 Hz, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.12 (d, J = 7.5 Hz, 1H), 6.80 (m, 2H), 5.08 (dd, J = 10.8, 8.3 Hz, 1H), 4.49 (t, J = 9.8 Hz, 1H), 4.34 - 4.30 (m, 1H), 4.12 (q, J = 9.8 Hz, 1H), 4.00 - 3.89 (m, 1H), 3.79 (s, 3H), 3.51 -3.47 (m, 2H), 3.04 - 3.00 (m, 1H), 2.88 -2.84 (m, 2H), 2.43 - 2.39 (m, 2H), 2.17 -2.12 (m, 1H), 2.02 - 1.92 (m, 1H), 1.90 -1.86 (m, 1H), 1.74 - 1.45 (m, 3H). 502 [00630]embedded image 617.2 Method D, RT = 1.494 min, 95%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.5 Hz, 2H), 7.80 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 11.0 Hz, 2H), 5.08 (dd, J = 10.8, 8.3 Hz, 1H), 4.48 (t, J = 9.5 Hz, 2H), 4.13 (q, J = 10.0 Hz, 1H), 4.03 - 3.92 (m, 1H), 3.79 (s, 3H), 3.52 (s, 2H), 3.06 - 3.02 (m, 1H), 2.96 - 2.82 (m, 2H), 2.65 - 2.55 (m, 1H), 2.48 - 2.41 (m, 1H), 2.31 - 2.00 (m, 2H), 1.92 - 1.83 (m, 1H), 1.78 - 1.50 (m, 3H). 503 [00631]embedded image 553.2 Method D, RT = 2.977 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 - 9.07 (d, J = 8.4 Hz, 1H), 8.48 (s, 1H), 8.05 (s, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 11.0 Hz, 2H), 6.36 (t, J = 48.0 Hz, 1H), 5.10 (d, J = 11.5 Hz, 1H), 4.57 - 4.31 (m, 3H), 3.74 (s, 3H), 3.64 (t, J = 10.5 Hz, 1H), 1.03 (d, J = 6.0 Hz, 3H). 504 [00632]embedded image 661.35 Method-D, RT = 1.605 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 - 8.86 (m, 1H), 7.93 - 7.86 (m, 2H), 7.84 - 7.79 (m, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.31 - 7.22 (m, 2H), 6.84 - 6.76 (m, 2H), 6.69 (d, J = 2.0 Hz, 1H), 5.67 (dd, J = 12.8, 8.3 Hz, 1H), 5.02 - 4.92 (m, 1H), 4.39 - 4.26 (m, 2H), 3.82 (s, 3H), 3.79 (s, 3H), 3.55 - 3.47 (m, 2H), 2.99 - 2.92 (m, 2H), 2.63 - 2.55 (m, 2H), 2.42 - 2.36 (m, 2H), 2.09 - 1.97 (m, 1H), 1.82 - 1.66 (m, 4H), 1.19 (d, J = 6.6 Hz, 3H). 505 [00633]embedded image 580.2 Method D, RT = 1.636 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 (d, J = 8.5 Hz, 1H), 8.49 (dd, J = 8.5, 1.3 Hz, 1H), 8.05 (m, 1H), 7.95 - 7.82 (m, 2H), 7.77 - 7.65 (m, 1H), 7.33 (t, J = 74.6 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.86 -6.69 (m, 2H), 5.66 (dd, J = 12.5, 8.3 Hz, 1H), 5.04 - 4.91 (m, 1H), 4.35 (dd, J = 12.5, 7.8 Hz, 1H), 3.78 (s, 3H), 1.68 (d, J = 13.6 Hz, 3H), 1.57 (d, J = 13.6 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H). 506 [00634]embedded image 571.2 Method C, RT = 1.427 min, 92%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.93 (m, 1H), 7.91 - 7.77 (m, 2H), 7.70 - 7.60 (m, 1H), 7.60 - 7.43 (m, 2H), 6.85 - 6.67 (m, 2H), 6.35 - 6.14 (m, 1H), 5.36 - 4.85 (m, 1H), 4.81 - 4.65 (m, 1H), 4.29 - 4.05 (m, 2H), 3.81 - 3.72 (2 s, 3H), 3.52 - 3.48 (m, 2H), 3.15 - 3.06 (m, 2H), 2.66 - 2.56 (m, 2H), 2.48 - 2.44 (m, 1H), 2.24 - 2.01 (2 s, 3H), 1.77 - 1.65 (m, 3H). (Mixture of interconvertible atropisomers) 507 [00635]embedded image 603.2 Method D, RT = 1.531 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.90 (m, 1H), 7.95 - 7.83 (m, 2H), 7.38 - 7.22 (m, 4H), 6.83 - 6.73 (m, 2H), 6.44 - 6.32 (m, 1H), 5.30 - 4.96 (m, 2H), 4.35 - 4.03 (m, 2H), 3.98 - 3.80 (m, 2H), 3.77 (s, 3H), 3.63 - 3.49 (m, 2H), 3.15 - 3.06 (m, 1H), 2.93 - 2.88 (2 s, 3H), 2.24 - 2.09 (2 s, 3H), 1.26 - 1.15 (m, 2H). (Mixture of interconvertible atropisomers) 508 [00636]embedded image 603.2 Method D, RT = 1.503 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 - 8.93 (m, 1H), 7.91 - 7.86 (m, 2H), 7.76 - 7.63 (m, 1H), 7.37 - 7.24 (m, 3H), 6.78 (m, 2H), 6.43 - 6.30 (m, 1H), 5.33 - 4.93 (m, 2H), 4.34 - 4.11 (m, 2H), 3.94 - 3.80 (m, 2H), 3.77 (s, 3H), 3.63 - 3.49 (m, 2H), 3.19 - 3.05 (m, 1H), 2.93 - 2.88 (2 s, 3H), 2.25 - 2.07 (2 s, 3H), 1.27 - 1.14 (m, 2H). (Mixture of interconvertible atropisomers) 509 [00637]embedded image 559.15 Method C, RT = 2.012 min, 100 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (br d, J = 7.8 Hz, 1H), 8.65 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.66 (s, 1H), 7.57 (d, J = 8.5 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.08 - 4.97 (m, 1H), 4.45 (t, J = 9.8 Hz, 1H), 4.39 - 4.31 (m, 1H), 4.29 - 4.22 (m, 1H), 4.14 (q, J = 9.8 Hz, 1H), 3.99 -3.91 (m, 1H), 3.81 - 3.71 (m, 5H), 3.64 (q, J = 7.8 Hz, 1H), 3.53 (dd, J = 8.6, 5.6 Hz, 1H), 2.72 - 2.64 (m, 1H), 2.07 - 1.95 (m, 1H), 1.71 - 1.59 (m, 1H). 510 [00638]embedded image 572.2 Method D, RT = 1.564 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.94 (m, 1H), 7.91 - 7.78 (m, 2H), 7.76 - 7.64 (m, 1H), 7.62 - 7.50 (m, 2H), 6.85 - 6.66 (m, 2H), 6.46 - 6.29 (m, 1H), 5.28 - 4.87 (m, 2H), 4.31 - 4.06 (m, 2H), 3.94 - 3.75 (m, 2H), 3.77 (s, 3H), 3.61 - 3.43 (m, 2H), 3.17 - 3.13 (m, 1H), 2.89 (s, 3H), 2.55 - 2.49 (m, 2H), 2.28 - 1.99 (2 s, 3H). (Mixture of interconvertible atropisomers) 511 [00639]embedded image 534.1 Method D, RT = 1.671 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 (d, J = 8.0 Hz, 1H), 8.47 (dd, J = 8.5, 1.3 Hz, 1H), 8.05 (m, 1H), 7.91 - 7.80 (m, 2H), 7.73 (dd, J = 6.9, 5.9 Hz, 1H), 7.62 - 7.49 (m, 2H), 6.80 (d, J = 10.5 Hz, 2H), 5.09 (dd, J = 10.9, 8.1 Hz, 1H), 4.54 (t, J = 9.5 Hz, 1H), 4.15 (q, J = 9.9 Hz, 1H), 4.03 - 3.89 (m, 1H), 3.78 (s, 3H), 1.68 (d, J = 13.6 Hz, 3H), 1.57 (d, J = 13.6 Hz, 3H). 512 [00640]embedded image 601.2 Method D, RT = 1.661 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.94 - 7.85 (m, 2H), 7.80 (t, J = 7.9 Hz, 1H), 7.34 (t, J = 75.4 Hz, 1H), 7.78 -7.15 (m, 2H), 7.12 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 11.5 Hz, 2H), 5.65 (dd, J = 12.6, 8.4 Hz, 1H), 5.01 - 4.91 (m, 1H), 4.32 (dd, J = 12.5, 8.3 Hz, 1H), 3.78 (s, 3H), 3.09 - 2.79 (m, 3H), 2.36 - 2.28 (m, 4H), 2.11 - 2.01 (m, 1H), 1.91 - 1.87 (m, 1H), 1.78 - 1.71 (m, 1H), 1.68 - 1.44 (m, 2H), 1.21 (d, J = 6.5 Hz, 3H). 513 [00641]embedded image 601.3 Method D, RT = 1.657 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.94 - 7.85 (m, 2H), 7.81 (t, J = 8.0 Hz, 1H), 7.28 - 7.21 (m, 2H), 7.42 (t, J = 73.8 Hz, 1H), 7.17 - 7.07 (m, 1H), 6.89 -6.71 (m, 2H), 5.64 (dd, J = 12.4, 8.1 Hz, 1H), 5.02 - 4.88 (m, 1H), 4.32 (dd, J = 12.6, 7.9 Hz, 1H), 3.78 (s, 3H), 3.08 -2.86 (m, 3H), 2.41 - 2.27 (m, 4H), 2.23 -2.08 (m, 1H), 1.97 - 1.85 (m, 1H), 1.81 -1.42 (m, 3H), 1.22 (d, J = 6.5 Hz, 3H). 514 [00642]embedded image 558.1 Method D, RT = 1.464 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 8.63 (s, 1H), 8.12 (s, 1H), 7.88 - 7.75 (m, 2H), 7.63 - 7.48 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.25 - 5.17 (m, 1H), 5.11 (dd, J = 11.1, 8.4 Hz, 1H), 4.16 - 4.05 (m, 1H), 3.96 (d, J = 9.5 Hz, 2H), 3.76 (s, 3H), 3.13 - 3.03 (m, 1H), 3.00 - 2.88 (m, 1H), 2.63 - 2.50 (m, 2H), 2.47 - 2.38 (m, 1H), 2.33 (s, 3H), 1.93 -1.89 (m, 1H). 515 [00643]embedded image 631.3 Method C, RT = 1.553 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.79 (t, J = 7.9 Hz, 1H), 7.34 (t, J = 73.5 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 7.8 Hz, 1H), 6.86 - 6.74 (m, 2H), 5.66 (dd, J = 12.5, 8.3 Hz, 1H), 5.00 - 4.90 (m, 1H), 4.42 - 4.39 (m, 1H), 4.32 (dd, J = 12.6, 8.4 Hz, 1H), 3.79 (s, 3H), 3.52 - 3.49 (m, 2H), 3.07 (d, J = 10.8 Hz, 1H), 2.94 - 2.83 (m, 2H), 2.47 - 2.44 (m, 2H), 2.21 - 2.13 (m, 1H), 2.06 - 1.98 (m, 1H), 1.92 - 1.85 (m, 1H), 1.72 - 1.68 (m, 1H), 1.64 - 1.46 (m, 2H), 1.22 (d, J = 6.8 Hz, 3H). 516 [00644]embedded image 631.2 Method D, RT = 1.642 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.34 (s, 1H), 8.93 (s, 1H), 8.32 - 8.23 (m, 1H), 7.89 (d, J = 9.0 Hz, 3H), 7.34 (t, J = 72.5 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 11.5 Hz, 2H), 5.65 - 5.60 (m, 1H), 5.33 - 5.29 (m, 1H), 5.01 - 4.95 (m, 1H), 4.37 - 4.33 (m, 1H), 3.79 (s, 3H), 3.76 -3.71 (m, 2H), 3.52 - 3.49 (m, 1H), 3.24 -3.19 (m, 4H), 2.97 - 2.91 (m, 2H), 2.04 -1.84 (m, 4H), 1.22 (d, J = 6.8 Hz, 3H). 517 [00645]embedded image 587.1 Method D, RT = 1.683 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.6 Hz, 1H), 8.45 (s, 1H), 8.18 (s, 1H), 7.89 - 7.76 (m, 2H), 7.63 - 7.46 (m, 2H), 7.15 - 6.85 (br s, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 10.6, 8.7 Hz, 1H), 4.45 - 4.27 (m, 2H), 4.18 - 4.07 (m, 1H), 4.07 - 3.89 (m, 3H), 3.77 (s, 3H). 518 [00646]embedded image 587.1 Method D, RT = 1.684 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 8.46 (s, 1H), 8.20 (s, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.63 - 7.48 (m, 2H), 7.15 - 6.85 (br s, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 10.8, 8.8 Hz, 1H), 4.45 - 4.25 (m, 2H), 4.19 - 4.08 (m, 1H), 4.08 - 3.87 (m, 3H), 3.77 (s, 3H). 519 [00647]embedded image 497.11 Method C, RT = 1.449 min, 98 %. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.5 Hz, 1H), 8.53 (dd, J = 6.8, 1.0 Hz, 1H), 8.04 (d, J = 1.3 Hz, 1H), 7.90 -7.79 (m, 2H), 7.61 (d, J = 1.0 Hz, 1H), 7.60 - 7.52 (m, 2H), 7.48 (dd, J = 7.4, 1.0 Hz, 1H), 6.97 (t, J = 7.0 Hz, 1H), 6.79 (d, J = 10.8 Hz, 2H), 5.20 (dd, J = 11.3, 8.5 Hz, 1H), 4.54 - 4.46 (m, 1H), 4.41 (t, J = 9.9 Hz, 1H), 4.21 (q, J = 10.1 Hz, 1H), 3.77 (s, 3H). 520 [00648]embedded image 517.1 Method D, RT = 1.681 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.97 (m, 1H), 8.52 - 8.39 (m, 1H), 7.88 - 7.77 (m, 2H), 7.60 - 7.50 (m, 2H), 6.81 - 6.71 (m, 2H), 5.30 - 4.85 (m, 1H), 4.29 - 4.02 (m, 2H), 3.99 - 3.87 (m, 2H), 3.80 - 3.74 (2 s, 3H), 3.64 - 3.55 (m, 1H), 2.54 - 2.48 (m, 1H), 2.29 - 2.14 (2 s, 3H), 1.30 - 1.21 (m, 3H). (Mixture of interconvertible atrop isomers) 521 [00649]embedded image 547.1 Method D, RT = 1.686 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.92 (m, 1H), 8.48 - 8.21 (m, 1H), 7.89 - 7.78 (m, 2H), 7.65 - 7.52 (m, 2H), 6.85 - 6.69 (m, 2H), 5.36 - 4.77 (m, 1H), 4.35 - 4.19 (m, 1H), 4.17 - 4.04 (m, 3H), 3.85 - 3.71 (2 s, 3H), 3.65 - 3.53 (m, 2H), 2.47 - 2.38 (m, 1H), 2.36 - 2.24 (2 s, 3H), 2.22 - 2.03 (m, 3H). (Mixture of interconvertible atrop isomers) 522 [00650]embedded image 573.2 Method D, RT = 1.547 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 9.01 (m, 1H), 8.36 - 8.27 (m, 1H), 7.89 - 7.80 (m, 2H), 7.61 - 7.52 (m, 2H), 6.85 - 6.73 (m, 2H), 5.36 - 4.81 (m, 1H), 4.68 (br s, 2H), 4.33 - 3.98 (m, 1H), 3.97 - 3.86 (m, 2H), 3.81 - 3.73 (2 s, 3H), 3.65 - 3.53 (m, 1H), 3.28 - 3.15 (m, 3H), 2.30 - 2.16 (2 s, 3H), 0.79 - 0.70 (2 s, 3H). (Mixture of interconvertible atropisomers) 523 [00651]embedded image 601.2 Method D, RT = 1.942 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J = 8.5 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.92 - 7.87 (m, 2H), 7.78 (dd, J = 8.5, 7.5 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.28 - 7.26 (m, 2H), 7.09 (d, J = 7.0 Hz, 1H), 6.84 - 6.77 (m, 2H), 5.67 (dd, J = 12.5, 8.5 Hz, 1H), 5.03 - 4.92 (m, 1H), 4.32 (dd, J = 12.8, 7.8 Hz, 1H), 3.79 (s, 3H), 2.87 - 2.83 (m, 2H), 2.65 - 2.55 (m, 1H), 2.18 (s, 3H), 1.96 (td, J = 11.4, 2.3 Hz, 2H), 1.85 - 1.68 (m, 4H), 1.21 (d, J = 6.5 Hz, 3H). 524 [00652]embedded image 631.2 Method D, RT = 1.87 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J = 8.3 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 7.9 Hz, 1H), 7.34 (t, J = 72.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 7.4 Hz, 1H), 6.81 (d, J = 10.8 Hz, 2H), 5.67 (dd, J = 12.5, 8.4 Hz, 1H), 5.03 - 4.95 (m, 1H), 4.39 - 4.28 (m, 2H), 3.79 (s, 3H), 3.60 - 3.43 (m, 2H), 3.43 - 3.37 (m, 1H), 3.03- 2.95 (m, 2H), 2.42 - 2.38 (m, 2H), 2.32 - 2.01 (m, 2H), 1.84 - 1.68 (m, 4H), 1.21 (d, J = 6.4 Hz, 3H). 525 [00653]embedded image 587.2 Method D, RT = 1.896 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 7.89 (d, J = 8.9 Hz, 2H), 7.79 (t, J = 7.9 Hz, 1H), 7.35 (t, J = 72.0 Hz, 1H), 7.29 (d, J = 8.9 Hz, 2H), 7.10 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.08 (dd, J = 10.8, 8.3 Hz, 1H), 4.48 (t, J = 9.7 Hz, 1H), 4.12 (q, J = 9.8 Hz, 1H), 4.03 -3.92 (m, 1H), 3.78 (s, 3H), 2.84 (m, 2H), 2.65 - 2.55 (m, 2H), 2.17 (s, 3H), 2.02 -1.87 (m, 2H), 1.87 - 1.69 (m, 3H). 526 [00654]embedded image 614.2 Method D, RT = 1.645 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.88 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.59 - 7.47 (m, 2H), 7.34 (t, J = 72.0 Hz, 1H), 7.28 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 11.5 Hz, 2H), 6.31 - 6.22 (m, 1H), 5.67 (dd, J = 12.6, 8.4 Hz, 1H), 4.98 -4.86 (m, 2H), 4.26 (dd, J = 12.7, 8.1 Hz, 2H), 3.80 - 3.74 (2 s, 3H), 3.52 - 3.41 (m, 2H), 3.12 - 3.15 (m, 2H), 2.89 - 2.75 (2 s, 3H), 2.40 - 2.35 (m, 1H), 2.21 - 2.15 (m, 1H), 1.20 (d, J = 6.4 Hz, 3H). (Mixture of interconvertible atropisomers) 527 [00655]embedded image 617.2 Method D, RT = 1.497 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 7.8 Hz, 1H), 8.16 (d, J = 8.3 Hz, 1H), 7.95 - 7.86 (m, 2H), 7.80 (t, J = 7.9 Hz, 1H), 7.32 - 7.24 (m, 2H), 7.36 (t, J = 73.6 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.08 (dd, J = 11.0, 8.6 Hz, 1H), 4.52 - 4.44 (m, 1H), 4.38 - 4.33 (m, 1H), 4.17 - 4.06 (m, 1H), 4.02 - 3.94 (m, 1H), 3.79 (s, 3H), 3.50 (t, J = 6.5 Hz, 2H), 2.99 - 2.95 (m, 2H), 2.65 - 2.56 (m, 1H), 2.41 (t, J = 6.5 Hz, 2H), 2.12 - 2.02 (m, 2H), 1.84 - 1.68 (m, 4H). 528 [00656]embedded image 587.2 Method D, RT = 1.943 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J = 8.3 Hz, 1H), 8.15 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 7.9 Hz, 1H), 7.33 (t, J = 72.0 Hz, 1H), 7.26 (d, J = 8.6 Hz, 2H), 7.06 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 11.5 Hz, 2H), 5.67 (dd, J = 11.2, 8.3 Hz, 1H), 5.05 - 4.97 (m, 1H), 4.32 (dd, J = 12.5, 8.3 Hz, 1H), 3.79 (s, 3H), 3.05 - 2.97 (m, 2H), 2.77 - 2.70 (m, 1H), 2.62 - 2.54 (m, 3H), 1.80 - 1.71 (m, 2H), 1.66 - 1.52 (m, 2H), 1.20 (d, J = 6.4 Hz, 3H). 529 [00657]embedded image 617.3 Method-D, RT = 1.555 min, 97.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 8.3 Hz, 1H), 7.94 - 7.84 (m, 3H), 7.34 (t, J= 76.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.02 (br s, 1H), 6.84 - 6.79 (m, 2H), 6.70 (d, J= 2.0 Hz, 1H), 5.65 (dd, J = 12.6, 8.2 Hz, 1H), 5.02 - 4.93 (m, 1H), 4.34 (dd, J = 12.7, 7.8 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 3.08 - 2.89 (m, 4H), 2.53 - 2.52 (m, 1H), 2.06 - 1.83 (m, 4H), 1.22 - 1.18 (m, 3H). 530 [00658]embedded image 557.2 Method D, RT = 1.679 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.93 (m, 1H), 7.92 - 7.81 (m, 2H), 7.78 - 7.67 (m, 1H), 7.62 - 7.51 (m, 2H), 6.85 - 6.71 (m, 2H), 6.34 - 6.17 (m, 1H), 5.41 - 4.84 (m, 2H), 4.33 - 4.05 (m, 2H), 3.85 - 3.73 (2 s, 3H), 3.55 - 3.36 (m, 2H), 3.16 - 3.02 (m, 2H), 2.92 - 2.75 (m, 2H), 2.29 - 2.24 (m, 1H), 2.25 - 2.06 (2 s, 3H), 1.80 - 1.63 (m, 1H). (Mixture of interconvertible atropisomers) 531 [00659]embedded image 600.2 Method C, RT = 1.491 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J= 8.3 Hz, 1H), 7.95 - 7.86 (m, 2H), 7.57 - 7.53 (m, 2H), 7.35 (t, J = 72.0 Hz, 1H), 7.34 - 7.16 (m, 2H), 6.80 (d, J= 10.8 Hz, 2H), 6.29 (dd, J = 5.3, 3.5 Hz, 1H), 5.08 (dd, J = 11.0, 8.3 Hz, 1H), 4.65 -4.61 (m, 1H), 4.53 - 4.43 (m, 1H), 4.13 -4.01 (m, 1H), 3.95 - 3.84 (m, 1H), 3.78 (s, 3H), 3.42 - 3.31 (m, 1H), 3.00 - 2.93 (m, 1H), 2.90 - 2.83 (m, 1H), 2.41 (s, 3H), 1.94 - 1.87 (m, 3H), 1.82 - 1.74 (m, 1H). 532 [00660]embedded image 504.1 Method D, RT = 1.771 min, 97%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.3 Hz, 1H), 8.47 (s, 1H), 7.89 -7.79 (m, 2H), 7.63 - 7.52 (m, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.00 (dd, J = 9.9, 8.9 Hz, 1H), 4.24 - 4.06 (m, 2H), 4.02 -3.89 (m, 3H), 3.78 (s, 3H), 2.12 (m, 1H), 0.88 (d, J = 6.6 Hz, 3H), 0.86 (d, J = 6.6 Hz, 3H). 533 [00661]embedded image 553.1 Method D, RT = 1.665 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.96 (m, 1H), 8.51 - 8.30 (m, 1H), 8.00 - 7.73 (m, 2H), 7.63 - 7.41 (m, 2H), 6.85 - 6.70 (m, 2H), 6.42 (t, J = 52.2 Hz, 1H), 5.35 - 4.70 (m, 1H), 4.57 - 4.36 (m, 2H), 4.32 - 3.96 (m, 2H), 3.82 - 3.71 (2 s, 3H), 3.67 - 3.51 (m, 1H), 2.33 - 2.14 (2 s, 3H). (Mixture of interconvertible atropisomers) 534 [00662]embedded image 603.3 Method D, RT = 1.486 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 9.08 (m, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.79 (d, J= 2.0 Hz, 1H), 7.35 (t, J = 72.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 6.68 (d, J= 1.7 Hz, 1H), 5.08 (dd, J= 10.9, 8.2 Hz, 1H), 4.51 - 4.43 (m, 1H), 4.16 - 4.06 (m, 1H), 3.99 - 3.92 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 3.07 - 2.98 (m, 2H), 2.62 - 2.56 (m, 1H), 1.80 - 1.71 (m, 5H), 1.64 (dt, J = 9.4, 1.6 Hz, 2H). 535 [00663]embedded image 608.2 Method D, RT = 1.93 min, 94% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.97 - 7.86 (m, 3H), 7.35 J= 73.2 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 6.85 (dd, J = 8.8, 2.7 Hz, 1H), 6.80 (d, J= 10.8 Hz, 2H), 5.17 - 5.04 (m, 1H), 4.30 - 3.94 (m, 5H), 3.82 - 3.71 (m, 5H), 3.67 - 3.63 (m, 1H), 3.55 - 3.51 (m, 1H), 2.71 - 2.64 (m, 1H), 2.06 - 1.94 (m, 1H), 1.72 - 1.60 (m, 1H). 536 [00664]embedded image 587.2 Method D, RT = 1.521 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.75 (d, J = 7.8 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.79 (t, J = 7.5 Hz, 1H), 7.74 - 7.64 (m, 2H), 7.17 (d, J = 8.8 Hz, 1H), 7.31 (t, J = 73.5 Hz, 2H), 7.09 (d, J = 7.5 Hz, 1H), 6.61 (d, J = 11.0 Hz, 2H), 5.30 (t, J = 8.5 Hz, 1H), 4.47 - 4.24 (m, 3H), 3.70 (s, 3H), 2.97 - 2.87 (m, 2H), 2.65 - 2.58 (m, 1H), 2.25 (s, 3H), 2.15 - 2.00 (m, 2H), 1.90 - 1.67 (m, 4H). 537 [00665]embedded image 651.2 Method D, RT = 2.252 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.91 (d, J = 8.5 Hz, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.83 (d, J= 9.2 Hz, 2H), 7.80 (t, J = 8.0 Hz, 1H), 7.35 (t, J = 75.3 Hz, 1H), 7.27 (d, J = 9.2 Hz, 2H), 7.11 (d, J = 7.5 Hz, 1H), 6.87 - 6.72 (m, 2H), 6.40 - 6.10 (m, 1H), 5.66 (dd, J= 12.5, 8.5 Hz, 1H), 5.06 - 4.91 (m, 1H), 4.33 (dd, J = 12.5, 8.0 Hz, 1H), 3.79 (s, 3H), 3.33 - 3.29 (m, 1H), 3.11 - 2.66 (m, 5H), 2.28 - 2.24 (m, 1H), 1.87 - 1.80 (m, 4H), 1.22 (d, J= 6.5 Hz, 3H). 538 [00666]embedded image 631.2 Method C, RT = 1.499 min, 95.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.88 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.81 (d, J= 2.1 Hz, 1H), 7.34 (t, J= 76.0 Hz, 1H), 7.26 (d, J = 8.6 Hz, 2H), 6.80 (d, J= 11.5 Hz, 2H), 6.69 (d, J= 2.0 Hz, 1H), 5.67 (dd, J = 12.6, 8.4 Hz, 1H), 5.02 - 4.93 (m, 1H), 4.30 (dd, J = 12.6, 7.9 Hz, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 2.84 (br d, J = 10.8 Hz, 2H), 2.18 (s, 3H), 1.99 - 1.96 (m, 1H), 1.97 - 1.92 (m, 2H), 1.82 - 1.70 (m, 4H), 1.19 (br d, J = 6.4 Hz, 3H). 539 [00667]embedded image 618.3 Method C, RT = 1.910 min, 93.3% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 7.8 Hz, 1H), 7.93 - 7.88 (m, 2H), 7.40 - 7.37 (m, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.32 - 7.26 (m, 2H), 6.86 - 6.78 (m, 2H), 6.77 - 6.74 (m, 1H), 5.04 - 4.95 (m, 1H), 4.66 - 4.57 (m, 1H), 3.98 - 3.89 (m, 2H), 3.86 - 3.84 (m, 3H), 3.79 (s, 3H), 3.74 - 3.65 (m, 1H), 3.48 - 3.38 (m, 2H), 2.93 - 2.80 (m, 1H), 1.81 - 1.70 (m, 4H), 1.35 (d, J = 6.6 Hz, 3H). 540 [00668]embedded image 647.2 Method D, RT = 1.552 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.3 Hz, 1H), 7.93 - 7.87 (m, 2H), 7.79 (d, J = 2.2 Hz, 1H), 7.35 (t, J = 74.3 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 6.83 -6.76 (m, 2H), 6.70 (d, J = 2.2 Hz, 1H), 5.07 (dd, J = 10.9, 8.2 Hz, 1H), 4.48 (br t, J = 9.9 Hz, 1H), 4.16 - 4.06 (m, 1H), 4.00 - 3.91 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 3.49 (t, J = 6.4 Hz, 3H), 2.98 - 2.91 (m, 2H), 2.55 (br d, J = 5.1 Hz, 1H), 2.38 (t, J = 6.5 Hz, 2H), 2.08 - 1.98 (m, 2H), 1.81 - 1.72 (m, 4H). 541 [00669]embedded image 512.1 Method D, RT = 1.627 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.3 Hz, 1H), 8.56 (s, 1H), 7.83 (d, J= 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.42 (tt, J = 54.5, 9.1 Hz, 1H), 5.03 - 4.92 (m, 1H), 4.78 - 4.71 (m, 2H), 4.27 - 4.09 (m, 2H), 4.00 - 3.91 (m, 1H), 3.78 (s, 3H). 542 [00670]embedded image 559.1 Method D, RT = 1.574 min, 95%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.5 Hz, 1H), 8.60 (s, 1H), 8.13 (s, 1H), 7.88 - 7.74 (m, 2H), 7.60 - 7.46 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 11.0, 8.5 Hz, 1H), 4.78 (t, J = 12.2, 3.8 Hz, 1H), 4.19 - 4.05 (m, 1H), 4.03 -3.92 (m, 4H), 3.76 (s, 3H), 3.48 - 3.44 (m, 2H), 2.14 - 1.96 (m, 2H), 1.83 - 1.78 (m, 2H). 543 [00671]embedded image 559.2 Method D, RT = 1.7 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J= 8.5 Hz, 1H), 8.74 (s, 1H), 8.63 (s, 1H), 7.90 - 7.76 (m, 2H), 7.62 - 7.44 (m, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.43 (t, J = 7.5 Hz, 1H), 5.09 (d, J = 10.9 Hz, 1H), 4.18 (q, J = 10.0 Hz, 1H), 4.03 - 3.95 (m, 2H), 3.82 (d, J = 11.3 Hz, 2H), 3.77 (s, 3H), 3.64 - 3.52 (m, 2H), 2.10 - 1.92 (m, 2H), 1.80 - 1.61 (m, 2H). 544 [00672]embedded image 476.2 Method D, RT = 2.282 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.4 Hz, 1H), 8.47 (s, 1H), 7.87 -7.79 (m, J = 8.6 Hz, 2H), 7.62 - 7.54 (m, 2H), 6.80 (s, 1H), 6.77 (s, 1H), 4.98 (dd, J = 10.4, 8.4 Hz, 1H), 4.24 - 4.10 (m, 4H), 4.00 - 3.87 (m, 1H), 3.78 (s, 3H), 1.40 (t, J= 7.3 Hz, 3H). 545 [00673]embedded image 557.1 Method D, RT = 1.798 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.5 Hz, 1H), 7.92 - 7.74 (m, 2H), 7.64 - 7.46 (m, 3H), 7.15 (d, J = 7.5 Hz, 1H), 6.82 (d, J= 11.3 Hz, 2H), 6.26 (d, J = 8.3 Hz, 1H), 5.00 (dd, J= 10.8, 8.5 Hz, 1H), 4.92 (d, J= 3.0 Hz, 1H), 4.62 - 4.48 (m, 1H), 4.37 (d, J= 1.3 Hz, 1H), 3.79 (s, 3H), 3.64 (t, J = 9.9 Hz, 1H), 3.50 - 3.30 (m, 4H), 2.06 - 1.96 (m, 1H), 1.91 - 1.79 (m, 1H), 1.38 (d, J = 6.0 Hz, 3H). 546 [00674]embedded image 515.1 Method D, RT = 1.597 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.8 Hz, 1H), 7.90 - 7.73 (m, 2H), 7.66 - 7.50 (m, 3H), 7.25 - 7.12 (m, 1H), 6.77 (d, J = 10.8 Hz, 2H), 5.16 (dd, J = 10.3, 9.0 Hz, 1H), 4.21 - 4.02 (m, 2H), 3.99 - 3.88 (m, 1H), 3.76 (s, 3H), 3.52 -3.41 (m, 1H), 1.09 - 1.01 (m, 2H), 0.99 -0.89 (m, 2H). 547 [00675]embedded image 573.2 Method D, RT = 1.604 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.8 Hz, 1H), 8.50 (s, 1H), 8.15 (s, 1H), 7.86 - 7.81 (m, 2H), 7.60 - 7.54 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.13 (dd, J = 11.2, 8.6 Hz, 1H), 4.16 - 4.04 (m, 1H), 4.03 - 3.92 (m, 2H), 3.90 - 3.81 (m, 4H), 3.77 (s, 3H), 3.24 (t, J = 11.5 Hz, 2H), 2.10 - 1.95 (m, 1H), 1.47 - 1.42 (m, 2H), 1.34 - 1.21 (m, 2H). 548 [00676]embedded image 699.2 Method-D, RT = 2.434 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.93 - 8.87 (m, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.84 - 7.81 (m, 1H), 7.34 (t, J= 76.0 Hz, 1H), 7.28 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 11.0 Hz, 2H), 6.73 - 6.70 (m, 1H), 5.67 (dd, J= 12.7, 8.3 Hz, 1H), 5.02 - 4.92 (m, 1H), 4.30 (dd, J= 12.7, 8.1 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.18 (q, J = 10.2 Hz, 2H), 3.01 (br d, J = 11.5 Hz, 2H), 2.65 -2.54 (m, 1H), 2.46 -2.42 (m, 2H), 1.86 -1.67 (m, 4H), 1.21 (d, J = 6.6 Hz, 3H). 549 [00677]embedded image 655.2 Method D, RT = 2.089 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.80 (t, J = 9.0 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.34 (t, J = 71.7 Hz, 1H), 7.28 (d, J= 8.6 Hz, 2H), 6.79 (d, J = 11.0 Hz, 2H), 6.15 (tt, J= 54.3, 11.5 Hz, 1H), 5.13 (br t, J= 9.4 Hz, 1H), 4.31 - 4.15 (m, 2H), 4.12 - 4.01 (m, 1H), 3.78 (s, 3H), 3.00 (br d, J = 11.5 Hz, 2H), 2.80 - 2.62 (m, 3H), 2.32 - 2.19 (m, 2H), 1.86 - 1.64 (m, 4H). 550 [00678]embedded image 673.2 Method D, RT = 2.24 min, 96% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.80 (dd, J = 8.6, 9.8 Hz, 1H), 7.39 - 7.33 (m, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 (d, J= 8.6 Hz, 2H), 6.79 (d, J= 10.8 Hz, 2H), 5.20 - 5.04 (m, 1H), 4.30 - 4.16 (m, 2H), 4.13 - 4.00 (m, 1H), 3.78 (s, 3H), 3.19 (q, J = 10.3 Hz, 2H), 3.02 (br d, J= 11.2 Hz, 2H), 2.74 - 2.66 (m, 1H), 2.48 - 2.41 (m, 2H), 1.88 - 1.66 (m, 4H). 551 [00679]embedded image 601.1 Method D, RT = 2.257 min, 98.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.28 (d, J = 8.3 Hz, 1H), 8.78 (d, J = 7.8 Hz, 1H), 8.06 (d, J= 8.1 Hz, 1H), 8.01 - 7.88 (m, 2H), 7.51 (d, J= 8.3 Hz, 2H), 6.81 (d, J = 10.8 Hz, 2H), 5.11 (dd, J = 10.5, 8.3 Hz, 1H), 4.51 - 4.39 (m, 1H), 4.36 - 4.24 (m, 1H), 4.22 - 4.12 (m, 1H), 3.78 (s, 3H). 552 [00680]embedded image 649.3 Method-C, RT = 1.916 min, 82.51% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 - 8.91 (m, 1H), 7.97 - 7.92 (m, 2H), 7.51 - 7.45 (m, 2H), 7.29 (d, J = 2.0 Hz, 1H), 6.83 - 6.75 (m, 2H), 5.87 (d, J = 1.5 Hz, 1H), 5.71 - 5.63 (m, 1H), 4.92 - 4.82 (m, 1H), 4.79 - 4.75 (m, 1H), 4.65 - 4.61 (m, 1H), 4.28 - 4.20 (m, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 3.70 - 3.63 (m, 1H), 3.47 -3.41 (m, 1H), 3.25 - 3.15 (m, 2H), 1.90 -1.80 (m, 2H), 1.21 (br d, J = 6.4 Hz, 3H). 553 [00681]embedded image 539.2 Method D, RT = 2.426 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.6 Hz, 1H), 8.51 (s, 1H), 8.19 (s, 1H), 7.86 - 7.81 (m, 2H), 7.60 - 7.54 (m, 2H), 6.77 (d, J= 10.8 Hz, 2H), 6.40 (tt, J = 56.0, 9.2 Hz, 1H), 5.12 (dd, J = 11.0, 8.6 Hz, 1H), 4.58 - 4.42 (m, 2H), 4.17 -4.06 (m, 1H), 4.05 - 3.92 (m, 2H), 3.77 (s, 3H). 554 [00682]embedded image 553.1 Method D, RT = 1.76 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 (d, J = 8.8 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.76 (d, J = 4.4 Hz, 1H), 7.62 - 7.50 (m, 2H), 7.38 (d, J = 4.4 Hz, 1H), 6.80 (d, J = 11.2 Hz, 2H), 6.41 (tt, J= 54.8, 4.3 Hz, 1H), 5.24 (dd, J = 11.2, 8.8 Hz, 1H), 4.56 - 4.42 (m, 3H), 3.78 (s, 3H), 3.69 (t, J = 10.4 Hz, 1H), 1.09 (d, J= 6.1 Hz, 3H). 555 [00683]embedded image 585.1 Method D, RT = 1.793 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 - 8.87 (m, 1H), 8.52 (s, 1H), 7.90 (d, J = 9.9 Hz, 2H), 7.34 (t, J = 72.0 Hz, 1H), 7.27 (m, 3H), 6.80 (d, J = 9.9 Hz, 2H), 6.35 (tt, J= 54.8, 4.3 Hz, 1H), 5.69 - 5.57 (m, 1H), 4.84 (m, 1H), 4.48 - 4.26 (m, 3H), 3.78 (s, 3H), 1.19 (d, J = 6.8 Hz, 3H). 556 [00684]embedded image 605.2 Method D, RT = 1.43 min, 93% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.96 - 7.86 (m, 2H), 7.80 (dd, J = 9.8, 8.6 Hz, 1H), 7.34 (t, J = 74.0 Hz, 1H), 7.32 - 7.27 (m, 3H), 6.79 (d, J = 10.8 Hz, 2H), 5.18 - 5.09 (m, 1H), 4.28 - 4.17 (m, 2H), 4.10 - 4.04 (m, 1H), 3.78 (s, 3H), 2.88 - 2.80 (m, 2H), 2.70 -2.60 (m, 1H), 2.21 (s, 3H), 2.05 - 1.96 (m, 2H), 1.86 - 1.69 (m, 4H). 557 [00685]embedded image 588.1 Method-D, RT = 2.076 min, 94.45% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 9.12 (m, 1H), 7.87 - 7.82 (m, 2H), 7.60 - 7.55 (m, 2H), 6.99 - 6.92 (m, 1H), 6.85 - 6.78 (m, 2H), 6.21 - 6.16 (m, 1H), 5.06 - 4.94 (m, 1H), 4.57 - 4.48 (m, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 3.73 - 3.57 (m, 5H), 3.44 - 3.35 (m, 4H), 1.35 (d, J = 5.9 Hz, 3H). 558 [00686]embedded image 600.2 Method-D, RT = 1.712 min, 98.72% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 9.12 (m, 1H), 7.86 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 2.0 Hz, 1H), 6.85 - 6.79 (m, 2H), 6.76 - 6.73 (m, 1H), 5.04 - 4.97 (m, 1H), 4.65 - 4.57 (m, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 3.72 -3.63 (m, 1H), 2.90 - 2.81 (m, 2H), 2.63 -2.54 (m, 1H), 2.19 (s, 3H), 2.03 - 1.92 (m, 2H), 1.82 - 1.69 (m, 4H), 1.34 (d, J= 5.6 Hz, 3H). 559 [00687]embedded image 564.1 Method D, RT = 1.744 min, 95%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.90 (d, J = 8.3 Hz, 1H), 7.97 - 7.87 (m, 3H), 7.78 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 72.9 Hz, 1H), 7.27 (d, J = 8.6 Hz, 2H), 6.81 (d, J = 11.5 Hz, 2H), 6.61 (d, J = 7.8 Hz, 1H), 5.68 (dd, J= 12.6, 8.2 Hz, 1H), 4.97 - 4.86 (m, 1H), 4.81 (t, J = 5.5 Hz, 1H), 4.39 - 4.18 (m, 3H), 3.79 (s, 3H), 3.71 (q, J= 5.1 Hz, 2H), 1.24 (d, J= 6.6 Hz, 3H). 560 [00688]embedded image 553.1 Method D, RT = 1.727 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.96 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 8.6 Hz, 2H), 7.73 (d, J= 4.4 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.35 (d, J = 4.4 Hz, 1H), 6.85 -6.75 (m, 2H), 6.41 (tt, J = 55.5, 4.5 Hz, 1H), 5.60 (dd, J = 11.7, 8.6 Hz, 1H), 4.73 - 4.60 (m, 1H), 4.49 (tt, J = 14.7, 4.4 Hz, 2H), 4.37 (dd, J= 12.0, 8.3 Hz, 1H), 3.78 (s, 3H), 0.98 (d, J = 6.6 Hz, 3H). 561 [00689]embedded image 589.2 Method C, RT = 1.536 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.86 (d, J= 8.1 Hz, 1H), 7.90 (d, J = 9.0 Hz, 2H), 7.57 - 7.49 (m, 2H), 7.35 (t, J= 73.0 Hz, 1H), 7.26 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 6.24 - 6.19 (m, 1H), 5.68 (m, 1H), 4.93 (t, J = 7.2 Hz, 2H), 4.38 (s, 1H), 4.28 - 4.24 (m, 1H), 3.78 (s, 3H), 3.53 - 3.34 (m, 3H), 3.30 - 3.22 (m, 1H), 2.06 - 1.97 (m, 1H), 1.92 - 1.87 (m, 1H), 1.24 (d, J = 6.1 Hz, 3H). 562 [00690]embedded image 550.1 Method C, RT = 1.687 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 7.92 - 7.88 (m, 3H), 7.78 (t, J = 8.1 Hz, 1H), 7.34 (t, J = 72.9 Hz, 1H), 7.27 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 6.61 (d, J = 8.1 Hz, 1H), 5.11 - 5.07 (m, 1H), 4.78 (t, J = 5.5 Hz, 1H), 4.48 (t, J = 9.8 Hz, 1H), 4.33 -4.22 (m, 2H), 4.12 (q, J = 10.1 Hz, 1H), 4.01 - 3.94 (m, 1H), 3.80 - 3.77 (m, 3H), 3.77 - 3.64 (m, 2H). 563 [00691]embedded image 590.1 Method D, RT = 1.729 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 9.00 (dd, J = 13.8, 8.8 Hz, 1H), 8.03 -7.97 (m, 2H), 7.60 (d, J = 7.0 Hz, 1H), 7.53 - 7.44 (m, 2H), 7.39 (d, J = 8.5 Hz, 1H), 7.35 - 7.31 (m, 1H), 6.96 - 6.87 (m, 2H), 6.22 (dd, J = 7.0, 2.5 Hz, 1H), 5.27 - 4.67 (m, 3H), 4.15 - 3.81 (m, 2H), 3.79 - 3.58 (m, 8H), 3.24 (d, J = 1.0 Hz, 3H), 2.22 - 2.09 (m, 3H). (Mixture of interconvertible atrop isomers) 564 [00692]embedded image 590.1 Method D, RT = 1.675 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 9.00 (dd, J = 13.8, 8.8 Hz, 1H), 8.06 -7.97 (m, 2H), 7.60 (dd, J = 7.0, 6.0 Hz, 1H), 7.56 - 7.44 (m, 2H), 7.42 - 7.30 (m, 2H), 6.98 - 6.88 (m, 2H), 6.22 (d, J= 7.5 Hz, 1H), 5.29 - 4.67 (m, 3H), 4.15 - 3.82 (m, 2H), 3.80 - 3.58 (m, 8H), 3.23 (d, J = 1.0 Hz, 3H), 2.23 - 2.08 (m, 3H). (Mixture of interconvertible atropisomers) 565 [00693]embedded image 649.2 Method-D, RT = 1.792 min, 96.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (d, J = 8.3 Hz, 1H), 7.95 (d, J= 11.5 Hz, 2H), 7.86 (d, J = 2.0 Hz, 1H), 7.48 (br d, J = 8.0 Hz, 2H), 6.82 (d, J = 11.5 Hz, 2H), 6.73 (d, J= 2.0 Hz, 1H), 5.66 (dd, J = 12.8, 8.3 Hz, 1H), 4.97 (quin, J = 7.0 Hz, 1H), 4.33 (dd, J = 12.8, 8.0 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 2.95 - 2.76 (m, 3H), 2.74 - 2.62 (m, 4H), 2.33 (td, J= 3.7, 1.8 Hz, 1H), 2.05 - 1.83 (m, 4H), 1.20 (br d, J = 6.5 Hz, 3H). 566 [00694]embedded image 588.2 Method D, RT = 1.775 min, 93%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.62 - 7.57 (m, 2H), 7.35 (t, J = 73.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.65 - 6.58 (m, 1H), 5.14 - 5.04 (m, 1H), 4.48 - 4.38 (m, 1H), 4.12 - 4.01 (m, 1H), 3.95 - 3.90 (m, 1H), 3.78 (s, 3H), 3.46 (m, 4H), 2.40 - 2.34 (m, 4H), 2.21 (s, 3H). 567 [00695]embedded image 652.1 Method D, RT = 1.866 min, 97%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J= 8.0 Hz, 1H), 7.89 (d, J = 9.0 Hz, 2H), 7.67 - 7.62 (m, 2H), 7.35 (t, J= 73.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.71 - 6.65 (m, 1H), 5.12 - 5.05 (m, 1H), 4.48 - 4.44 (m, 1H), 4.09 (d, J = 10.0 Hz, 1H), 3.95 (d, J = 10.5 Hz, 1H), 3.78 (s, 3H), 3.65 - 360 (m, 4H), 3.20 - 3.16 (m, 4H), 2.89 (s, 3H). 568 [00696]embedded image 589.2 Method D, RT = 1.829 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.86 (d, J= 8.3 Hz, 1H), 7.89 (d, J = 9.0 Hz, 2H), 7.56 - 7.50 (m, 2H), 7.35 (t, J= 73.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.21 (m, 1H), 5.68 (m, 1H), 4.98 - 4.85 (m, 1H), 4.41 - 4.35 (m, 2H), 4.31 - 4.22 (m, 1H), 3.78 (s, 3H), 3.51 - 3.38 (m, 3H), 3.34 - 3.26 (m, 1H), 2.07 - 1.83 (m, 2H), 1.24 (d, J= 6.1 Hz, 3H). 569 [00697]embedded image 618.2 Method D, RT = 1.59 min, 95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.3 Hz, 1H), 7.93 - 7.84 (m, 2H), 7.57 - 7.41 (m, 2H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 5.07 (dd, J = 10.9, 8.4 Hz, 1H), 4.63 - 4.60 (m, 1H), 4.44 (br t, J = 9.9 Hz, 1H), 4.12 - 3.96 (m, 1H), 3.92 - 3.83 (m, 1H), 3.78 (s, 3H), 3.62 (br dd, J= 9.7, 3.5 Hz, 1H), 3.47 - 3.42 (m, 1H), 3.42 - 3.33 (m, 1H), 2.80 (dd, J= 9.4, 1.8 Hz, 1H), 2.60 (br d, J = 10.0 Hz, 1H), 2.29 (s, 3H), 1.85 - 1.80 (m, 1H), 1.74 -1.70 (m, 1H). 570 [00698]embedded image 614.2 Method D, RT = 1.55 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 8.6 Hz, 1H), 7.93 - 7.83 (m, 2H), 7.40 (s, 1H), 7.35 (t, J = 73.6 Hz, 1H), 7.28 (d, J= 8.6 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.12 (s, 1H), 5.05 (dd, J = 11.1, 8.2 Hz, 1H), 4.58 - 4.54 (m, 1H), 4.47 -4.42 (m, 1H), 4.07 - 4.01 (m, 1H), 3.89 -3.80 (m, 2H), 3.78 (s, 3H), 3.45 - 3.40 (m, 1H), 3.26 - 3.19 (m, 1H), 2.79 - 2.77 (m, 1H), 2.45 - 2.41 (m, 1H), ), 2.26 (s, 3H), 2.23 (s, 3H), 1.84 - 1.80 (m, 1H), 1.73 -1.62 (m, 1H). 571 [00699]embedded image 632.2 Method D, RT = 1.77 min,98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 (d, J = 8.3 Hz, 1H), 7.99 - 7.90 (m, 2H), 7.54 - 7.44 (m, 2H), 7.40 (s, 1H), 6.84 -6.71 (m, 2H), 6.12 (s, 1H), 5.06 (dd, J = 11.0, 8.3 Hz, 1H), 4.58 - 4.54 (m, 1H), 4.50 - 4.42 (m, 1H), 4.11 - 4.02 (m, 1H), 3.91 - 3.85 (m, 1H), 3.78 (s, 3H), 3.43 -3.39 (m, 2H), 3.25 - 3.22 (m, 1H), 2.80 (dd, J = 9.4, 2.1 Hz, 1H), 2.43 (d, J= 9.5 Hz, 1H), 2.26 (s, 3H), 2.23 (s, 3H), 1.84 - 1.80 (m, 1H), 1.73 - 1.62 (m, 1H). 572 [00700]embedded image 636.2 Method D, RT = 1.77 min,95% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J = 8.3 Hz, 1H), 7.98 - 7.92 (m, 2H), 7.57 - 7.41 (m, 4H), 6.86 - 6.73 (m, 2H), 5.08 (dd, J = 11.0, 8.1 Hz, 1H), 4.63 -4.60 (m, 1H), 4.45 (br t, J = 9.7 Hz, 1H), 4.12 - 4.03 (m, 1H), 3.92 - 3.86 (m, 1H), 3.78 (s, 3H), 3.65 - 3.58 (m, 1H), 3.45 -3.42 (m, 1H), 3.40 - 3.36 (m, 1H), 2.79 (dd, J = 9.5, 2.0 Hz, 1H), 2.58 (dd, J = 9.5, 2.0 Hz, 1H), 2.28 (s, 3H), 1.85 - 1.77 (m, 1H), 1.74 - 1.66 (m, 1H). 573 [00701]embedded image 502 Method D, RT = 1.695 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J= 7.8 Hz, 1H), 7.94 - 7.81 (m, 3H), 7.78 (d, J = 7.8 Hz, 1H), 7.62 - 7.52 (m, 2H), 7.32 (d, J = 7.6 Hz, 1H), 6.82 (d, J = 11.2 Hz, 2H), 5.03 - 4.99 (m, 1H), 4.68 - 4.46 (m, 3H), 3.79 (s, 3H), 3.74 - 3.67 (m, 1H), 3.51 - 3.15 (m, 1H), 1.30 (d, J= 5.9 Hz, 3H). 574 [00702]embedded image 589.2 Method D, RT = 1.994 min, 97%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.88 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.70 - 7.60 (m, 2H), 7.35 (t, J= 76.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 8.1 Hz, 1H), 5.68 - 5.65 (m, 1H), 4.94 - 4.85 (m, 1H), 4.29 - 4.24 (m, 1H), 3.78 (s, 3H), 3.74 - 3.71 - 3.65 (m, 4H), 3.49 - 3.39 (m, 4H), 1.21 (d, J = 6.4 Hz, 3H). 575 [00703]embedded image 592.1 Method-D, RT = 2.416 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.98 (d, J= 8.3 Hz, 1H), 7.98 - 7.92 (m, 2H), 7.74 (d, J = 2.0 Hz, 1H), 7.48 (br d, J = 8.9 Hz, 2H), 6.83 - 6.81 (m, 1H), 6.80 -6.77 (m, 2H), 5.66 (dd, J = 12.6, 8.4 Hz, 1H), 4.92 - 4.80 (m, 1H), 4.26 (dd, J = 12.8, 8.0 Hz, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 1.77 - 1.57 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H), 1.00 - 0.88 (m, 3H), 0.87 - 0.80 (m, 1H). 576 [00704]embedded image 644.2 Method F, RT = 2.488 min, 99% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.04 (m, 1H), 8.00 - 7.92 (m, 2H), 7.74 - 7.64 (m, 1H), 7.53 - 7.44 (m, 2H), 6.81 - 6.76 (m, 2H), 6.32 - 6.24 (m, 1H), 5.37 - 4.86 (m, 1H), 4.36 - 4.26 (m, 2H), 4.26 - 4.14 (m, 1H), 4.26 - 4.07 (m, 2H), 3.79 - 3.74 (2 s, 3H), 3.61 - 3.53 (m, 2H), 3.07 - 3.04 (2 s, 3H), 2.22 - 2.06 (2 s, 3H). (Mixture of interconvertible atropisomers) 577 [00705]embedded image 538.2 Method D, RT = 2.596 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 - 8.88 (m, 1H), 7.92 - 7.88 (m, 2H), 7.75 - 7.70 (m, 1H), 7.47 - 7.07 (m, 5H), 6.96 - 6.85 (m, 2H), 6.33 - 6.27 (m, 1H), 5.22 - 4.68 (m, 2H), 4.06 - 3.80 (m, 2H), 3.73 - 3.68 (2 s, 3H), 3.60 - 3.39 (m, 1H), 2.37 - 2.21 (m, 4H), 2.19 - 2.07 (2 s, 3H), 1.82 - 1.77 (m, 2H). (Mixture of interconvertible atrop isomers) 578 [00706]embedded image 558.3 Method D, RT = 2.358 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 9.02 (m, 1H), 8.02 - 7.98 (m, 2H), 7.76 - 7.72 (m, 1H), 7.54 - 7.44 (m, 2H), 7.41 - 7.28 (m, 2H), 6.93 - 6.88 (m, 2H), 6.36 - 6.32 (m, 1H), 5.58 - 5.17 (m, 1H), 4.95 - 4.65 (m, 4H), 4.09 - 4.01 (m, 1H), 3.96 - 3.77 (m, 2H), 3.75 - 3.70 (m, 3H), 3.69 - 3.42 (m, 1H), 2.26 - 2.10 (2 s, 3H). (Mixture of interconvertible atropisomers) 579 [00707]embedded image 615.1 Method D, RT = 1.693 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.92 (m, 1H), 7.93 - 7.85 (m, 2H), 7.82 - 7.73 (m, 1H), 7.54 - 7.11 (m, 3H), 6.82 - 6.72 (m, 2H), 6.36 - 6.24 (m, 2H), 5.37 - 4.83 (m, 3H), 4.32 - 4.04 (m, 2H), 3.79 - 3.74 (2 s, 3H), 3.57 - 3.48 (m, 1H), 2.25 - 2.20 (2 s, 3H), 2.21 - 2.08 (2 s, 3H). (Mixture of interconvertible atropisomers) 580 [00708]embedded image 575.1 Method D, RT = 1.977 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.68 - 7.60 (m, 2H), 7.35 (t, J= 73.6 Hz, 1H), 7.28 (d, J = 8.6 Hz, 2H), 6.79 (d, J= 10.8 Hz, 2H), 6.65 - 6.57 (m, 1H), 5.10 (dd, J = 10.9, 8.4 Hz, 1H), 4.50 -4.39 (m, 1H), 4.15 - 4.01 (m, 1H), 3.98 -3.87 (m, 1H), 3.78 (s, 3H), 3.74 - 3.63 (m, 4H), 3.48 - 3.39 (m, 4H). 581 [00709]embedded image 546.2 Method F, RT = 2.40 min, 99%, .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.90 (m, 1H), 7.91 - 7.74 (m, 2H), 7.64 - 7.36 (m, 3H), 6.82 - 6.64 (m, 2H), 6.27 - 6.07 (m, 1H), 5.36 - 4.81 (m, 2H), 4.28 - 3.82 (m, 4H), 3.80 - 3.73 (2 s, 3H), 3.69 - 3.46 (m, 2H), 2.23 - 2.04 (2 s, 3H), 1.16 - 0.98 (m, 3H). (Mixture of interconvertible atropisomers) 582 [00710]embedded image 618.2 Method D, RT = 1.757 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (br d, J= 8.5 Hz, 1H), 7.89 (d, J= 8.5 Hz, 2H), 7.74 - 7.61 (m, 2H), 7.35 (t, J= 76.4 Hz, 1H), 7.27 (d, J= 8.5 Hz, 2H), 6.82 -6.74 (m, 1H), 6.77 (br d, J = 11.0 Hz, 1H), 6.38 (t, J= 7.0 Hz, 1H), 5.09 (br t, J = 9.3 Hz, 1H), 4.49 - 4.42 (m, 1H), 4.37 - 4.33 (m, 1H), 4.15 - 4.01 (m, 3H), 3.99 - 3.90 (m, 1H), 3.87 - 3.84 (m, 1H), 3.77 (s, 3H). 583 [00711]embedded image 618.2 Method D, RT = 1.744 min, 97.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 (br d, J= 8.5 Hz, 1H), 7.89 (d, J= 8.5 Hz, 2H), 7.74 - 7.61 (m, 2H), 7.35 (t, J= 76.4 Hz, 1H), 7.27 (d, J= 8.5 Hz, 2H), 6.82 -6.74 (m, 1H), 6.77 (br d, J = 11.0 Hz, 1H), 6.38 (t, J= 7.0 Hz, 1H), 5.09 (br t, J = 9.3 Hz, 1H), 4.49 - 4.42 (m, 1H), 4.37 - 4.33 (m, 1H), 4.15 - 4.01 (m, 3H), 3.99 - 3.90 (m, 1H), 3.87 - 3.84 (m, 1H), 3.77 (s, 3H). 584 [00712]embedded image 596.1 Method-D, RT = 2.103 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.79 (d, J= 2.0 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.04 - 7.02 (d, J= 2.0 Hz, 1H), 6.80 (d, J= 10.8 Hz, 2H), 5.33 - 5.13 (m, 1H), 5.09 (dd, J= 11.0, 8.3 Hz, 1H), 4.50 (br t, J= 9.9 Hz, 1H), 4.16 - 4.07 (m, 1H), 3.98 - 3.91 (m, 1H), 3.85 (s, 3H), 3.78 (s, 3H), 1.42 (s, 3H), 1.41 (s, 3H). 585 [00713]embedded image 578.1 Method-D, RT = 1.924 min, 93.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.3 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.80 (d, J= 2.2 Hz, 1H), 7.34 (t, J= 76.0 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 2.2 Hz, 1H), 6.80 (d, J= 10.8 Hz, 2H), 5.33 - 5.13 (m, 1H), 5.07 (dd, J = 11.0, 8.1 Hz, 1H), 4.54 - 4.44 (m, 1H), 4.17 - 4.05 (m, 1H), 3.99 - 3.90 (m, 1H), 3.85 (s, 3H), 3.78 (s, 3H), 1.42 (s, 3H), 1.41 (s, 3H). 586 [00714]embedded image 550.1 Method-C, RT = 1.508 min, 98.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.82 (d, J= 2.2 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 6.88 (d, J= 2.2 Hz, 1H), 6.79 (d, J= 10.8 Hz, 2H), 5.43 - 5.39 (m, 1H), 5.08 (dd, J = 11.1, 8.2 Hz, 1H), 4.46 (d, J= 5.9 Hz, 2H), 4.43 - 4.38 (m, 1H), 4.10 (q, J= 10.1 Hz, 1H), 3.98 - 3.91 (m, 1H), 3.86 (s, 3H), 3.78 (s, 3H). 587 [00715]embedded image 568.1 Method-D, RT = 1.895 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 (d, J= 8.1 Hz, 1H), 7.95 (d, J= 8.8 Hz, 2H), 7.81 (d, J= 2.0 Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H), 6.88 (d, J = 2.0 Hz, 1H), 6.80 (d, J= 10.8 Hz, 2H), 5.48 - 5.35 (m, 1H), 5.09 (dd, J= 10.8, 8.3 Hz, 1H), 4.46 (d, J = 5.9 Hz, 2H), 4.44 - 4.39 (m, 1H), 4.15 - 4.04 (m, 1H), 3.98 - 3.90 (m, 1H), 3.87 - 3.84 (m, 3H), 3.78 (s, 3H). 588 [00716]embedded image 534.1 Method-D, RT = 2.060 min, 96.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.1 Hz, 1H), 7.89 (d, J= 8.8 Hz, 2H), 7.78 (d, J= 2.2 Hz, 1H), 7.34 (t, J= 76.0 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 6.79 (d, J= 11.0 Hz, 2H), 6.72 (d, J= 2.2 Hz, 1H), 5.07 (dd, J= 11.0, 8.3 Hz, 1H), 4.46 - 4.39 (m, 1H), 4.14 - 4.04 (m, 1H), 3.99 - 3.92 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 2.39 (s, 3H). 589 [00717]embedded image 560.2 Method-D, RT = 2.253 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J= 8.3 Hz, 1H), 7.92 - 7.84 (m, 2H), 7.72 (d, J = 2.0 Hz, 1H), 7.34 (t, J = 76.0 Hz, 1H), 7.28 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 2.0 Hz, 2H), 6.72 (d, J = 2.2 Hz, 1H), 5.06 (dd, J= 11.1, 8.4 Hz, 1H), 4.40 (t, J = 9.9 Hz, 1H), 4.07 (q, J = 10.0 Hz, 1H), 3.91 - 3.84 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 2.07 - 1.97 (m, 1H), 0.99 -0.92 (m, 2H), 0.91 - 0.85 (m, 2H). 590 [00718]embedded image 635.2 Method D, RT = 1.43 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 9.0 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.78 (dd, J= 9.8, 8.5 Hz, 1H), 7.34 (t, J = 74.0 Hz, 1H), 7.32 - 7.27 (m, 3H), 6.79 (d, J = 10.8 Hz, 2H), 5.12 -5.10 (m, 1H), 4.35 (t, J = 5.4 Hz, 1H), 4.28 - 4.16 (m, 2H), 4.13 - 3.99 (m, 1H), 3.77 (s, 3H), 3.50 (q, J = 6.4 Hz, 2H), 3.17 (d, J= 5.3 Hz, 1H), 2.99 - 2.89 (m, 2H), 2.71 - 2.64 (m, 1H), 2.40 (t, J = 6.4 Hz, 2H), 2.10 -2.00 (m, 2H), 1.85 - 1.64 (m, 3H). 591 [00719]embedded image 604.1 Method D, RT = 1.656 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.84 (m, 1H), 7.99 - 7.82 (m, 2H), 7.55 - 7.15 (2t, J= 74.3 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.80 - 6.74 (m, 2H), 5.41 - 4.85 (m, 2H), 4.30 - 3.88 (m, 4H), 3.80 - 3.72 (2 s, 3H), 3.63 (quin, J= 5.1 Hz, 2H), 3.50 - 3.41 (m, 1H), 3.06 (br t, J= 7.2 Hz, 2H), 2.83 - 2.68 (m, 2H), 2.18 - 1.94 (m, 5H). (Mixture of interconvertible atropisomers) 592 [00720]embedded image 622.1 Method D, RT = 1.788 min, 98.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.33 - 8.91 (m, 1H), 8.04 - 7.82 (m, 2H), 7.60 - 7.33 (m, 2H), 6.81 - 6.75 (m, 2H), 5.41 - 4.85 (m, 2H), 4.30 - 3.88 (m, 4H), 3.80 - 3.72 (2 s, 3H), 3.64 - 3.61 (m, 2H), 3.50 - 3.41 (m, 1H), 3.08 - 3.04 (m, 2H), 2.83 - 2.68 (m, 2H), 2.18 - 1.94 (m, 5H). (Mixture of interconvertible atropisomers) 593 [00721]embedded image 572.1 Method D, RT = 1.649 min, 99.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.91 (m, 1H), 7.91 - 7.70 (m, 2H), 7.64 - 7.42 (m, 2H), 6.81 - 6.75 (m, 2H), 5.41 - 4.81 (m, 2H), 4.29 - 3.84 (m, 4H), 3.80 - 3.71 (2 s, 3H), 3.65 - 3.61 (m, 2H), 3.52 - 3.39 (m, 1H), 3.12 - 2.99 (m, 2H), 2.80 - 2.67 (m, 2H), 2.15 - 1.90 (m, 5H). (Mixture of interconvertible atropisomers) 594 [00722]embedded image 548.2 Method D, RT = 2.609 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 - 8.95 (m, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.64 - 7.59 (m, 1H), 7.56 - 7.49 (m, 2H), 7.38 - 7.29 (m, 2H), 6.93 - 6.84 (m, 2H), 6.30 - 6.26 (m, 1H), 5.21 - 4.74 (m, 1H), 4.18 - 4.10 (m, 1H), 4.21 - 3.98 (m, 1H), 3.96 - 3.81 (m, 2H), 3.72 - 3.68 (2 s, 3H), 3.63 - 3.42 (m, 1H), 2.78 - 2.63 (m, 2H), 2.21 - 2.06 (2 s, 3H). (Mixture of interconvertible atropisomers) 595 [00723]embedded image 577.2 Method D, RT = 2.167 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.35 - 8.94 (m, 1H), 8.02 - 7.91 (m, 2H), 7.78 - 7.71 (m, 1H), 7.54 - 7.44 (m, 2H), 6.85 - 6.73 (m, 2H), 6.43 - 6.32 (m, 1H), 5.39 - 4.82 (m, 3H), 4.33 - 4.22 (m, 1H), 4.20 - 4.05 (m, 1H), 3.81 - 3.74 (2 s, 3H), 3.63 - 3.52 (m, 1H), 2.27 - 2.05 (2S, 3H). (Mixture of interconvertible atropisomers) 596 [00724]embedded image 503.1 Method-D, RT = 1.319 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J= 8.6 Hz, 1H), 8.03 (s, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.56 (d, J= 8.6 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.00 (dd, J = 10.6, 8.7 Hz, 1H), 4.28 - 4.20 (m, 1H), 4.02 (q, J = 9.6 Hz, 1H), 3.91 - 3.84 (m, 1H), 3.79 (t, J= 7.0 Hz, 2H), 3.76 (s, 3H), 3.75 - 3.71 (m, 2H), 2.55 - 2.52 (m, 1H), 2.49 - 2.46 (m, 1H). 597 [00725]embedded image 535.2 Method-D, RT = 1.308 min, 93.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 - 8.94 (m, 1H), 8.03 (s, 1H), 7.88 (d, J = 8.6 Hz, 2H), 7.34 (t, J = 76.0 Hz, 1H), 7.27 (d, J= 8.6 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.00 (dd, J= 10.6, 8.7 Hz, 1H), 4.28 - 4.20 (m, 1H), 4.02 (q, J = 9.6 Hz, 1H), 3.91 - 3.84 (m, 1H), 3.79 (t, J= 7.0 Hz, 2H), 3.76 (s, 3H), 3.75 - 3.71 (m, 2H), 2.55 - 2.52 (m, 1H), 2.49 - 2.46 (m, 1H). 598 [00726]embedded image 553.1 Method-D, RT = 1.412 min, 97% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.6 Hz, 1H), 8.03 (s, 1H), 7.94 (d, J= 8.8 Hz, 2H), 7.49 (d, J= 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.00 (dd, J = 10.6, 8.7 Hz, 1H), 4.28 - 4.20 (m, 1H), 4.02 (q, J = 9.6 Hz, 1H), 3.91 - 3.84 (m, 1H), 3.79 (t, J= 7.0 Hz, 2H), 3.76 (s, 3H), 3.75 - 3.71 (m, 2H), 2.55 - 2.52 (m, 1H), 2.49 - 2.46 (m, 1H). 599 [00727]embedded image 544.1 Method C, RT = 1.557 min, 99.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J= 8.5 Hz, 1H), 8.30 (dd, J= 6.9, 0.9 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.67 (dd, J= 7.3, 0.9 Hz, 1H), 7.35 (t, J= 72.8 Hz, 1H), 7.28 (d, J= 8.8 Hz, 2H), 7.06 (t, J = 7.0 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.16 (dd, J= 11.1, 8.4 Hz, 1H), 4.67 - 4.57 (m, 1H), 4.42 (t, J= 10.3 Hz, 1H), 4.24 (q, J = 10.3 Hz, 1H), 3.78 (s, 3H), 2.71 (s, 3H). 600 [00728]embedded image 683.1 Method D, RT = 1.644 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 8.94 (m, 1H), 7.96 - 7.82 (m, 3H), 7.55 - 7.11 (m, 3H), 6.83 - 6.68 (m, 2H), 6.57 - 6.46 (m, 1H), 5.31 - 4.76 (m, 1H), 4.32 - 3.96 (m, 2H), 3.78 - 3.74 (2 s, 3H), 3.65 - 3.46 (m, 6H), 3.37 - 3.34 (m, 1H), 2.30 - 2.10 (2 s, 3H), 1.66 - 1.60 (m, 1H), 1.31 - 1.16 (m, 1H). (Mixture of interconvertible atrop isomers) 601 [00729]embedded image 589.2 Method D, RT = 1.422 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.89 (m, 1H), 7.96 - 7.83 (m, 2H), 7.77 - 7.67 (m, 1H), 7.54 - 7.10 (m, 3H), 6.84 - 6.70 (m, 2H), 6.33 - 6.22 (m, 1H), 5.36 - 4.84 (m, 2H), 4.27 - 4.10 (m, 2H), 3.78 - 3.75 (2 s, 3H), 3.52 - 3.49 (m, 3H), 3.15 - 3.05 (m, 2H), 2.88 - 2.77 (m, 2H), 2.27 - 2.02 (2 s, 3H), 1.80 - 1.68 (m, 1H). (Mixture of interconvertible atropisomers) 602 [00730]embedded image 607.1 Method D, RT = 1.586 min, 95%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.96 (m, 1H), 8.05 - 7.87 (m, 2H), 7.77 - 7.65 (m, 1H), 7.57 - 7.38 (m, 2H), 6.77 (m, 2H), 6.27 (m, 1H), 5.40 - 5.14 (m, 1H), 4.93 - 4.07 (m, 3H), 3.80 - 3.72 (2 s, 3H), 3.53 - 3.49 (m, 3H), 3.13 - 2.99 (m, 2H), 2.90 - 2.74 (m, 2H), 2.27 - 2.00 (2 s, 3H), 1.81 - 1.60 (m, 1H). (Mixture of interconvertible atropisomers) 603 [00731]embedded image 512.1 Method C, RT = 1.625 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 (d, J= 8.5 Hz, 1H), 8.30 (dd, J = 6.8, 0.8 Hz, 1H), 7.94 - 7.80 (m, 2H), 7.68 (dd, J = 7.3, 0.8 Hz, 1H), 7.62 - 7.51 (m, 2H), 7.07 (t, J = 7.0 Hz, 1H), 6.81 (d, J= 10.8 Hz, 2H), 5.18 (dd, J= 11.1, 8.4 Hz, 1H), 4.70 - 4.55 (m, 1H), 4.42 (t, J = 10.1 Hz, 1H), 4.24 (q, J = 10.1 Hz, 1H), 3.78 (s, 3H), 2.72 (s, 3H). 604 [00732]embedded image 562.1 Method C, RT = 1.728 min, 99.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 (d, J = 8.3 Hz, 1H), 8.31 (dd, J = 6.8, 0.8 Hz, 1H), 8.04 - 7.87 (m, 2H), 7.68 (dd, J = 7.3, 0.8 Hz, 1H), 7.57 - 7.41 (m, 2H), 7.07 (t, J = 7.0 Hz, 1H), 6.81 (d, J= 10.8 Hz, 2H), 5.19 (dd, J= 11.1, 8.4 Hz, 1H), 4.68 - 4.55 (m, 1H), 4.42 (t, J= 10.0 Hz, 1H), 4.25 (q, J = 10.1 Hz, 1H), 3.79 (s, 3H), 2.72 (s, 3H). 605 [00733]embedded image 618.2 Method D, RT = 1.791 min, 99.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.90 (m, 1H), 7.96 - 7.77 (m, 2H), 7.54 - 7.14 (2t, J= 74.3 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.82 - 6.68 (m, 2H), 5.40 - 4.82 (m, 2H), 4.30 - 4.00 (m, 4H), 3.78 - 3.72 (2 s, 3H), 3.61 (quin, J= 5.8 Hz, 2H), 3.51 - 3.41 (m, 1H), 2.85 - 2.80 (m, 2H), 2.47 - 2.40 (m, 2H), 2.14 - 1.93 (2 s, 3H), 1.81 - 1.61 (m, 4H). (Mixture of interconvertible atrop isomers) 606 [00734]embedded image 636.1 Method D, RT = 1.766 min, 94.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.26 - 8.98 (m, 1H), 8.02 - 7.84 (m, 2H), 7.56 - 7.37 (m, 2H), 6.84 - 6.66 (m, 2H), 5.41 - 4.80 (m, 2H), 4.28 - 3.99 (m, 4H), 3.81 - 3.73 (2 s, 3H), 3.61 (quin, J = 5.8 Hz, 2H), 3.50 - 3.42 (m, 1H), 2.89 - 2.77 (m, 2H), 2.47 - 2.38 (m, 2H), 2.14 - 1.91 (2 s, 3H), 1.80 - 1.57 (m, 4H). (Mixture of interconvertible atropisomers) 607 [00735]embedded image 586.1 Method D, RT = 1.629 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.93 (m, 1H), 7.92 - 7.76 (m, 2H), 7.67 - 7.46 (m, 2H), 6.83 - 6.69 (m, 2H), 5.41 - 4.87 (m, 2H), 4.29 - 3.99 (m, 4H), 3.79 - 3.72 (2 s, 3H), 3.60 (quin, J = 5.8 Hz, 2H), 3.49 - 3.42 (m, 1H), 2.90 - 2.75 (m, 2H), 2.47 - 2.39 (m, 2H), 2.14 - 1.91 (2 s, 3H), 1.81 - 1.54 (m, 4H). (Mixture of interconvertible atropisomers) 608 [00736]embedded image 604.2 Method D, RT = 2.015 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J= 8.5 Hz, 1H), 8.03 - 7.96 (m, 2H), 7.72 - 7.64 (m, 2H), 7.49 (d, J = 9.0 Hz, 4H), 7.46 - 7.39 (m, 2H), 6.38 (t, J= 7.0 Hz, 1H), 5.04 (dd, J= 11.0, 8.5 Hz, 1H), 4.45 (dd, J = 13.1, 2.5 Hz, 1H), 4.40 -4.28 (m, 1H), 4.19 - 4.09 (m, 1H), 3.92 -3.79 (m, 3H), 3.51 - 3.40 (m, 1H). 609 [00737]embedded image 604.2 Method D, RT = 2.029 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J= 8.5 Hz, 1H), 8.03 - 7.96 (m, 2H), 7.72 - 7.64 (m, 2H), 7.49 (d, J = 9.0 Hz, 4H), 7.46 - 7.39 (m, 2H), 6.38 (t, J= 7.0 Hz, 1H), 5.04 (dd, J= 11.0, 8.5 Hz, 1H), 4.45 (dd, J = 13.1, 2.5 Hz, 1H), 4.40 -4.28 (m, 1H), 4.19 - 4.09 (m, 1H), 3.92 -3.79 (m, 3H), 3.51 - 3.40 (m, 1H). 610 [00738]embedded image 538.2 Method F, RT = 2.51 min, 99%, .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (m, 1H), 7.99 - 7.89 (m, 2H), 7.72 - 7.64 (m, 1H), 7.55 - 7.06 (m, 5H), 6.93 - 6.89 (m, 2H), 6.22 (d, J = 6.8 Hz, 1H), 5.29 -4.62 (m, 1H), 4.13 - 3.81 (m, 2H), 3.79 -3.75 (2 s, 3H) 3.69 - 3.59 (m, 2H), 3.46-3.40 (m, 1H), 2.25 - 2.04 (2 s, 3H), 1.22-120 (m, 1H), 0.49 - 0.47 (m, 4H). (Mixture of interconvertible atropisomers) 611 [00739]embedded image 584.2 Method F, RT = 2.65 min, 99%, .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 9.00 (m, 1H), 7.91 - 7.79 (m, 2H), 7.69 (d, J= 7.0 Hz, 1H), 7.61, - 7.51 (m, 2H), 6.78 (br d, J = 10.5 Hz, 2H), 6.27 (d, J = 7.0 Hz, 1H), 5.40 - 4.85 (m, 1H), 4.33 -4.06 (m, 4H), 3.80 - 3.74 (2 s, 3H), 3.56 -3.47 (m, 1H), 2.83 - 2.68 (m, 2H), 2.25 -2.04 (2 s, 3H). (Mixture of interconvertible atrop isomers) 612 [00740]embedded image 589.1 Method D, RT = 1.34 min, 93%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.86 (m, 1H), 7.95 - 7.80 (m, 2H), 7.78 - 7.66 (m, 1H), 7.56 - 7.12 (m, 3H), 6.82 - 6.65 (m, 2H), 6.32 - 6.17 (m, 1H), 5.36 - 4.89 (m, 2H), 4.30 - 4.07 (m, 3H), 3.80 - 3.72 (2 s, 3H), 3.49 (t, J= 8.4 Hz, 1H), 3.14 - 3.01 (m, 2H), 2.88 - 2.75 (m, 2H), 2.26 - 2.13 (m, 4H), 1.77 - 1.62 (m, 1H). (Mixture of interconvertible atropisomers) 613 [00741]embedded image 607.2 Method D, RT = 1.527 min, 95%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 9.00 (m, 1H), 8.00 - 7.85 (m, 2H), 7.78 - 7.65 (m, 1H), 7.55 - 7.40 (m, 2H), 6.88 - 6.69 (m, 2H), 6.34 - 6.18 (m, 1H), 5.37 - 4.82 (m, 2H), 4.30 - 4.06 (m, 3H), 3.79 - 3.72 (2 s, 3H), 3.50 (t, J = 8.1 Hz, 1H), 3.16 - 2.99 (m, 2H), 2.88 - 2.78 (m, 2H), 2.25 - 2.00 (m, 4H), 1.78 - 1.63 (m, 1H). (Mixture of interconvertible atropisomers) 614 [00742]embedded image 558.1 Method D, RT = 1.611 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.94 (m, 1H), 7.90 - 7.78 (m, 2H), 7.71 - 7.48 (m, 3H), 6.83 - 6.70 (m, 2H), 6.31 - 6.15 (m, 1H), 5.35 - 4.83 (m, 2H), 4.53 - 4.45 (m, 1H), 4.39 (qd, J= 9.1, 5.7 Hz, 1H), 4.30 - 4.06 (m, 4H), 3.82 - 3.70 (2 s, 3H), 3.55 - 3.48 (m, 1H), 2.69 - 2.61 (m, 1H), 2.40 - 2.34 (m, 1H), 2.26 - 2.04 (2 s, 3H). (Mixture of interconvertible atropisomers) 615 [00743]embedded image 608.1 Method D, RT = 1.759 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.28 - 8.90 (m, 1H), 8.03 - 7.84 (m, 2H), 7.70 - 7.56 (m, 1H), 7.52 - 7.37 (m, 2H), 6.86 - 6.65 (m, 2H), 6.30 - 6.15 (m, 1H), 5.41 - 4.80 (m, 2H), 4.55 - 4.45 (m, 1H), 4.43 - 4.33 (m, 1H), 4.31 - 4.06 (m, 4H), 3.82 - 3.70 (2 s, 3H), 3.60 - 3.44 (m, 1H), 2.72 - 2.61 (m, 1H), 2.39 - 2.30 (m, 1H), 2.24 - 1.96 (2 s, 3H). (Mixture of interconvertible atropisomers) 616 [00744]embedded image 590.1 Method D, RT = 1.579 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.84 (m, 1H), 7.97 - 7.78 (m, 2H), 7.71 - 7.57 (m, 1H), 7.34 (t, J = 74.3 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.81 - 6.75 (m, 2H), 6.31 - 6.16 (m, 1H), 5.39 - 4.78 (m, 2H), 4.55 - 4.45 (m, 1H), 4.41 - 4.36 (m, 1H), 4.30 - 4.04 (m, 4H), 3.80 - 3.68 (2 s, 3H), 3.57 - 3.46 (m, 1H), 2.70 - 2.59 (m, 1H), 2.40 - 2.32 (m, 1H), 2.23 - 2.01 (2 s, 3H). (Mixture of interconvertible atropisomers) 617 [00745]embedded image 590.1 Method D, RT = 1.597 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 8.86 (m, 1H), 7.97 - 7.81 (m, 2H), 7.69 - 7.57 (m, 1H), 7.34 (t, J = 74.3 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.81 - 6.75 (m, 2H), 6.31 - 6.14 (m, 1H), 5.38 - 4.82 (m, 2H), 4.54 - 4.43 (m, 1H), 4.41 - 4.33 (m, 1H), 4.31 - 4.08 (m, 4H), 3.81 - 3.74 (2 s, 3H), 3.56 - 3.45 (m, 1H), 2.68 - 2.62 (m, 1H), 2.40 - 2.32 (m, 1H), 2.22 - 2.01 (2 s, 3H). (Mixture of interconvertible atropisomers) 618 [00746]embedded image 558.1 Method D, RT = 1.616 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.86 (m, 1H), 7.93 - 7.76 (m, 2H), 7.71 - 7.38 (m, 3H), 6.81 - 6.75 (m, 2H), 6.32 - 6.12 (m, 1H), 5.41 - 4.78 (m, 2H), 4.57 - 4.44 (m, 1H), 4.42 - 4.31 (m, 1H), 4.29 - 4.06 (m, 4H), 3.81 - 3.70 (2 s, 3H), 3.54 - 3.44 (m, 1H), 2.70 - 2.62 (m, 1H), 2.38 - 2.30 (m, 1H), 2.25 - 1.96 (2 s, 3H). (Mixture of interconvertible atropisomers) 619 [00747]embedded image 619.1 Method D, RT = 1.484 min, 94.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.87 (m, 1H), 7.99 - 7.84 (m, 2H), 7.71 - 7.56 (m, 2H), 7.34 (t, J = 74.3 Hz, 1H), 7.28 - 7.24 (m, 1H), 6.81 - 6.75 (m, 2H), 6.37 - 6.19 (m, 1H), 5.38 - 4.81 (m, 2H), 4.34 - 4.09 (m, 4H), 3.80 - 3.75 (2 s, 3H), 3.64 - 3.50 (m, 3H), 3.27 - 3.19 (m, 1H), 2.25 - 2.06 (2 s, 3H). (Mixture of interconvertible atropisomers) 620 [00748]embedded image 553.1 Method D, RT = 1.75 min,96 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 4.9 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.78 (d, J = 4.6 Hz, 1H), 7.56 - 7.52 (m, 2H), 7.39 (t, J = 74.0 Hz, 1H), 7.27 - 7.25 (m, 1H) 6.85 -6.77 (m, 2H), 6.40 (tt, J = 52.6, 4.8 Hz, 1H), 5.12 - 5.09 (m, 1H), 4.56 - 4.50 (m, 2H), 4.46 (t, J = 8.3 Hz, 1H), 4.07 - 3.90 (m, 2H), 3.74 (s, 3H). 621 [00749]embedded image 574.1 Method D, RT = 1.59 min,97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.94 (m, 1H), 7.90 - 7.75 (m, 2H), 7.63 - 7.35 (m, 3H), 6.86 - 6.69 (m, 2H), 6.35 - 6.22 (m, 1H), 5.36 - 4.84 (m, 2H), 4.37 - 4.04 (m, 5H), 3.91 - 3.83 (m, 1H), 3.86 - 3.82 (2 s, 3H), 3.61 - 3.50 (m, 3H), 2.22 - 2.05 (2 s, 3H). (Mixture of interconvertible atropisomers) 622 [00750]embedded image 624.1 Method D, RT = 1.66 min,99 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.24 - 8.94 (m, 1H), 8.04 - 7.85 (m, 2H), 7.59 - 7.45 (m, 3H), 6.85 - 6.63 (m, 2H), 6.37 - 6.22 (m, 1H), 5.79 - 5.60 (m, 1H), 5.05 - 4.84 (m, 2H), 4.39 - 4.05 (m, 5H), 3.88 - 3.85 (m, 1H), 3.78 - 3.74 (2 s, 3H), 3.59 - 3.50 (m, 2H), 2.24 - 2.00 (2 s, 3H). (Mixture of interconvertible atropisomers) 623 [00751]embedded image 574.1 Method D, RT = 1.53 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 8.90 (m, 1H), 7.92 - 7.76 (m, 2H), 7.65 - 7.53 (m, 2H), 7.53 - 7.38 (m, 1H), 6.85 - 6.69 (m, 2H), 6.36 - 6.23 (m, 1H), 5.50 - 5.30 (m, 1H), 5.0-4.28 (m, 1H), 4.34 -4.03 (m, 4H), 3.89 - 3.80 (m, 1H), 3.78 -3.74 (2 s, 3H), 3.58 - 3.51 (m, 2H), 3.17 (s, 2H), 2.21 - 2.01 (2 s, 3H). (Mixture of interconvertible atropisomers) 624 [00752]embedded image 606.1 Method D, RT = 1.50 min,99 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.83 (m, 1H), 8.00 - 7.76 (m, 2H), 7.53 - 7.46 (m, 1H), 7.35 (t, J = 73.8 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.86 - 6.67 (m, 2H), 6.36 - 6.22 (m, 1H), 5.75 - 5.59 (m, 1H), 5.38 - 4.76 (m, 2H), 4.38 - 4.00 (m, 5H), 3.93 - 3.85 (m, 1H), 3.78 - 3.74 (2 s, 3H), 3.61 - 3.47 (m, 2H), 2.24 - 2.00 (2 s, 3H). (Mixture of interconvertible atropisomers) 625 [00753]embedded image 621 Method D, RT = 1.59 min, 10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 - 8.86 (m, 1H), 7.92 - 7.76 (m, 2H), 7.74 - 7.66 (m, 1H), 7.59 - 7.43 (m, 2H), 6.85 - 6.65 (m, 2H), 6.32 - 6.19 (m, 1H), 5.36 - 4.82 (m, 2H), 4.28 - 4.04 (m, 2H), 3.78 - 3.75 (2 s, 3H), 3.54 - 3.42 (m, 3H), 3.22 - 3.13 (m, 2H), 2.43 - 2.29 (m, 2H), 2.19 - 2.0 (2 s, 3H), 2.15 - 2.05 (m, 2H). (Mixture of interconvertible atropisomers) 626 [00754]embedded image 652.1 Method D, RT = 1.57 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 - 8.81 (m, 1H), 7.96 - 7.81 (m, 2H), 7.75 - 7.62 (m, 1H), 7.28 - 7.23 (m, 2H), 7.35 (t, J= 73.8 Hz, 1H), 6.81 - 6.74 (m, 2H), 6.38 - 6.20 (m, 1H), 5.37 - 4.77 (m, 2H), 4.32 - 4.04 (m, 2H), 3.78 - 3.75 (2 s, 3H), 3.56 - 3.40 (m, 3H), 3.23 - 3.11 (m, 2H), 2.43 - 2.25 (m, 2H), 2.19 - 2.0 (2 s, 3H), 2.15 - 2.05 (m, 2H). (Mixture of interconvertible atropisomers) 627 [00755]embedded image 670.1 Method D, RT = 1.74 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.24 - 8.96 (m, 1H), 8.04 - 7.85 (m, 2H), 7.77 - 7.64 (m, 1H), 7.56 - 7.38 (m, 2H), 6.88 - 6.65 (m, 2H), 6.34 - 6.20 (m, 1H), 5.36 - 4.79 (m, 2H), 4.33 - 4.00 (m, 2H), 3.82 - 3.68 (m, 3H), 3.57 - 3.39 (m, 3H), 3.22 - 3.09 (m, 2H), 2.45 - 2.28 (m, 2H), 2.19 - 2.0 (2 s, 3H), 2.15 - 2.05 (m, 2H). (Mixture of interconvertible atropisomers) 628 [00756]embedded image 577.1 Method D, RT = 1.56 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.1 Hz, 1H), 7.95 - 7.82 (m, 2H), 7.28 (d, J= 8.6 Hz, 2H), 7.35 (t, J = 73.8 Hz, 1H), 6.96 (d, J = 1.2 Hz, 1H), 6.81 (d, J = 10.8 Hz, 2H), 5.77 (quin, J = 7.0 Hz, 1H), 4.91 (dd, J= 10.6, 8.2 Hz, 1H), 4.87 - 4.70 (m, 4H), 4.29 (q, J= 9.7 Hz, 1H), 4.15 - 3.97 (m, 2H), 3.77 (s, 3H), 2.24 (s, 3H). 629 [00757]embedded image 491.1 Method D, RT = 1.70 min,97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J= 8.6 Hz, 1H), 7.85 (s, 1H), 7.82 (d, J= 8.3 Hz, 2H), 7.56 (d, J= 8.3 Hz, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.06 - 4.93 (m, 1H), 4.11 - 3.92 (m, 2H), 3.85 - 3.78 (m, 4H), 3.76 (s, 3H), 3.69 (s, 3H). 630 [00758]embedded image 523.1 Method D, RT = 1.67 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J= 8.8 Hz, 1H), 7.92 - 7.81 (m, 3H), 7.34 (t, J= 72.9 Hz, 1H), 7.27 (d, J= 8.8 Hz, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.00 (dd, J= 10.3, 8.8 Hz, 1H), 4.13 - 3.92 (m, 2H), 3.87 - 3.79 (m, 4H), 3.76 (s, 3H), 3.69 (s, 3H). 631 [00759]embedded image 541.1 Method D, RT = 1.84 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.86 (s, 1H), 7.48 (d, J = 8.6 Hz, 2H), 6.77 (d, J= 10.8 Hz, 2H), 5.01 (t, J = 9.4 Hz, 1H), 4.12 - 3.94 (m, 2H), 3.87 - 3.79 (m, 4H), 3.76 (s, 3H), 3.69 (s, 3H). 632 [00760]embedded image 548.3 Method D, RT = 2.482 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.01 - 8.95 (m, 1H), 7.97 - 7.90 (m, 2H), 7.67 - 7.61 (m, 1H), 7.55 - 7.13 (m, 5H), 6.96 - 6.86 (m, 2H), 6.48 - 6.16 (m, 2H), 5.28 - 4.63 (m, 1H), 4.50 - 4.34 (m, 2H), 4.11 - 3.79 (m, 2H), 3.72 - 3.67 (2 s, 3H), 3.52 - 3.44 (m, 1H), 2.25 - 2.10 (2 s, 3H). (Mixture of interconvertible atropisomers) 633 [00761]embedded image 546.3 Method D, RT = 1.68 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.85 (m, 1H), 7.86 - 7.81 (m, 2H), 7.57 - 7.54 (m, 3H), 6.78 - 6.74 (m, 2H), 6.23 - 6.18 (m, 1H), 5.38 - 4.87 (m, 1H), 4.44 - 4.07 (m, 4H), 3.78 - 3.74 (2 s, 3H), 3.52 - 3.50 (m, 3H), 3.24 (s, 3H), 2.23 - 2.05 (2 s, 3H). (Mixture of interconvertible atropisomers) 634 [00762]embedded image 632.2 Method D, RT = 1.82 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.85 (m, 1H), 7.97 - 7.81 (m, 2H), 7.67 - 7.54 (m, 1H), 7.34 (t, J = 74.0 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.83 - 6.61 (m, 3H), 6.33 - 6.18 (m, 1H), 5.38 - 4.81 (m, 1H), 4.44 - 4.07 (m, 4H), 3.86 - 3.71 (m, 4H), 3.52 - 3.50 (m, 1H), 2.23 - 2.05 (2 s, 3H). (Mixture of interconvertible atropisomers) 635 [00763]embedded image 528.2 Method F, RT = 1.991 min, 99.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 - 9.03 (m, 1H), 7.91 - 7.83 (m, 2H), 7.61 - 7.50 (m, 3H), 7.44 (t, J= 9.0 Hz, 1H), 6.87 - 6.77 (m, 2H), 6.21 (d, J = 7.0 Hz, 1H), 5.40 - 5.31 (m, 1H), 4.82 (dd, J = 11.0, 8.5 Hz, 1H), 4.20 - 3.91 (m, 4H), 3.77 - 3.72 (2 s, 3H), 3.63 - 3.55 (m, 2H), 3.25 (s, 3H), 2.22 - 2.07 (2 s, 3H). (Mixture of interconvertible atropisomers) 636 [00764]embedded image 564.2 Method F, RT = 2.338 min, 99.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 - 9.07 (m, 1H), 8.01 - 7.95 (m, 2H), 7.60 - 7.38 (m, 4H), 6.87 - 6.75 (m, 2H), 6.20 (d, J = 7.0 Hz, 1H), 5.38 (dd, J = 11.5, 9.5 Hz, 1H), 4.94 (br t, J= 4.5 Hz, 1H), 4.83 - 4.80 (m, 1H), 4.19 - 3.87 (m, 4H), 3.80 - 3.70 (2 s, 3H), 3.68 - 3.54 (m, 2H), 2.22 - 2.07 (2 s, 3H). (Mixture of interconvertible atrop isomers) 637 [00765]embedded image 594.2 Method F, RT = 2.526 min, 99.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.05 (m, 1H), 8.00 - 7.91 (m, 2H), 7.76 (d, J= 7.1 Hz, 1H), 7.53 - 7.45 (m, 2H), 6.83 - 6.73 (m, 2H), 6.39 - 6.32 (m, 1H), 5.51 (t, J = 7.3 Hz, 1H), 4.93 - 4.83 (m, 3H), 4.82 - 4.70 (m, 2H), 4.32 - 4.20 (m, 1H), 4.20 - 4.01 (m, 2H), 3.79 - 3.74 (2 s, 3H), 2.25 - 2.07 (2 s, 3H). (Mixture of interconvertible atropisomers) 638 [00766]embedded image 580.2 Method-D, RT = 1.890 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.03 (m, 1H), 7.97 - 7.90 (m, 2H), 7.58 - 7.42 (m, 3H), 6.80 - 6.72 (m, 2H), 5.38 - 4.84 (m, 1H), 4.29 - 4.02 (m, 2H), 3.99 - 3.80 (m, 2H), 3.76 - 3.71 (2 s, 3H), 3.51 - 3.40 (m, 1H), 2.12 (s, 3H), 2.02 - 1.96 (2 s, 3H), 1.24 - 1.16 (m, 3H). (Mixture of interconvertible atropisomers) 639 [00767]embedded image 580.1 Method-D, RT = 1.891 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 9.04 (m, 1H), 7.99 - 7.90 (m, 2H), 7.60 - 7.43 (m, 3H), 6.81 - 6.73 (m, 2H), 5.40 - 4.83 (m, 1H), 4.30 - 4.05 (m, 2H), 4.00 - 3.82 (m, 2H), 3.77 - 3.74 (2 s, 3H), 3.53 - 3.42 (m, 1H), 2.13 (s, 3H), 2.03 - 1.97 (2 s, 3H), 1.25 - 1.17 (m, 3H). (Mixture of interconvertible atropisomers) 640 [00768]embedded image 560.1 Method-D, RT = 1.737 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.20 - 8.98 (m, 1H), 7.88 - 7.80 (m, 2H), 7.60 7.43 (m, 3H), 6.81 - 6.73 (m, 2H), 5.39 -4.88 (m, 1H), 4.30 - 3.96 (m, 4H), 3.77 -3.75 (2 s, 3H), 3.60 - 3.54 (m, 2H), 3.52 -3.43 (m, 1H), 3.24 (2 s, 3H), 2.15 (s, 3H), 2.03 - 1.98 (2 s, 3H). (Mixture of interconvertible atropisomers) 641 [00769]embedded image 560.1 Method-D, RT = 1.739 min, 98.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 8.99 (m, 1H), 7.87 - 7.80 (m, 2H), 7.58 - 7.42 (m, 3H), 6.81 - 6.73 (m, 2H), 5.37 - 4.86 (m, 1H), 4.28 - 3.94 (m, 4H), 3.76 - 3.74 (2 s, 3H), 3.60 - 3.54 (m, 2H), 3.51 - 3.40 (m, 1H), 3.23 (2 s, 3H), 2.13 (s, 3H), 2.02 - 1.97 (2 s, 3H). (Mixture of interconvertible atropisomers) 642 [00770]embedded image 562.1 Method-D, RT = 1.725 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.96 (m, 1H), 7.94 - 7.86 (m, 2H), 7.60 - 7.50 (m, 1H), 7.51 - 7.13 (m, 3H), 6.81 - 6.72 (m, 2H), 5.40 - 4.86 (m, 1H), 4.31 - 4.05 (m, 2H), 4.01 - 3.82 (m, 2H), 3.78 - 3.73 (2 s, 3H), 3.53 - 3.40 (m, 1H), 2.14 - 2.04 (2 s, 3H), 2.04 - 1.98 (2 s, 3H), 1.26 - 1.17 (m, 3H). (Mixture of interconvertible atrop isomers) 643 [00771]embedded image 582.1 Method D, RT = 1.603 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.92 (d, J = 9.0 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.69 (dd, J = 6.8, 2.0 Hz, 1H), 7.64 (dd, J = 7.3, 2.0 Hz, 1H), 7.35 (t, J = 74.6 Hz, 1H), 7.35 - 7.33 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.94 - 6.84 (m, 2H), 6.37 (t, J = 7.1 Hz, 1H), 5.01 (dd, J = 11.2, 8.8 Hz, 1H), 4.46 - 4.42 (m, 1H), 4.33 - 4.29 (m, 1H), 4.16 (t, J = 8.4 Hz, 1H), 3.88 - 3.73 (m, 3H), 3.72 (s, 3H), 3.69 - 3.64 (m, 1H). 644 [00772]embedded image 582.1 Method D, RT = 1.59 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.6 Hz, 2H), 7.68 (dd, J = 6.6, 1.7 Hz, 1H), 7.64 (dd, J = 7.6, 1.7 Hz, 1H), 7.35 (t, J = 74.6 Hz, 1H), 7.35 - 7.33 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.37 (t, J = 7.0 Hz, 1H), 5.04 - 4.95 (m, 1H), 4.44 (dd, J = 12.8, 2.6 Hz, 1H), 4.38 - 4.29 (m, 1H), 4.12 - 4.04 (m, 1H), 3.91 - 3.72 (m, 4H), 3.72 (s, 3H). 645 [00773]embedded image 567.1 Method D, RT = 1.81 min,95 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.65 - 8.53 (m, 1H), 8.07 (d, J = 4.8 Hz, 1H), 7.77 (d, J = 4.8 Hz, 1H), 7.74 - 7.62 (m, 4H), 7.32 (t, J = 76.0 Hz, 1H), 7.19 (dd, J = 8.5, 2.5 Hz, 2H), 6.82 (d, J = 8.3 Hz, 2H), 5.08 - 4.99 (m, 1H), 4.48 - 4.32 (m, 4H), 4.00 - 3.88 (m, 1H), 3.70 (s, 3H), 2.89 - 2.74 (m, 2H). 646 [00774]embedded image 604.2 Method D, RT = 1.649 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 8.87 (m, 1H), 8.01 - 7.81 (m, 2H), 7.47 - 7.43 (m, 1H), 7.34 (t, J = 74.3 Hz, 1H), 7.28 - 7.24 (m, 2H), 6.83 - 6.69 (m, 2H), 5.38 - 4.87 (m, 2H), 4.26 - 3.87 (m, 5H), 3.78 - 3.74 (2 s, 3H), 3.67 - 3.59 (m, 2H), 3.53 - 3.43 (m, 1H), 2.71 - 2.65 (m, 1H), 2.55 - 2.50 (m, 1H), 1.83 - 1.49 (m, 5H). 647 [00775]embedded image 475.1 Method C, RT = 1.824 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 9.0 Hz, 2H), 7.72 (d, J = 2.4 Hz, 1H), 7.60 - 7.48 (m, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.64 (d, J = 2.2 Hz, 1H), 4.97 (dd, J = 10.1, 8.7 Hz, 1H), 4.25 - 4.16 (m, 1H), 4.15 -4.03 (m, 3H), 3.92 - 3.81 (m, 1H), 3.77 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). 648 [00776]embedded image 507.1 Method C, RT = 1.780 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 9.0 Hz, 2H), 7.72 (d, J = 2.4 Hz, 1H), 7.34 (t, J = 72.6 Hz, 1H), 7.28 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.65 (d, J = 2.4 Hz, 1H), 4.97 (dd, J = 10.3, 8.6 Hz, 1H), 4.27 - 4.16 (m, 1H), 4.16 - 4.01 (m, 3H), 3.90 - 3.81 (m, 1H), 3.77 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). 649 [00777]embedded image 525.1 Method C, RT = 1.961 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.3 Hz, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 2.4 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 6.65 (d, J = 2.4 Hz, 1H), 4.98 (dd, J = 10.3, 8.3 Hz, 1H), 4.28 - 4.16 (m, 1H), 4.16 - 3.98 (m, 3H), 3.86 (t, J = 9.7 Hz, 1H), 3.77 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). 650 [00778]embedded image 505.1 Method D, RT = 1.658 min, 97.5% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.3 Hz, 1H), 7.89 - 7.75 (m, 2H), 7.64 - 7.47 (m, 2H), 7.19 (d, J = 1.2 Hz, 1H), 6.88 (d, J = 1.2 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 4.87 (dd, J = 10.8, 8.1 Hz, 1H), 4.32 - 4.21 (m, 1H), 4.17 - 4.00 (m, 2H), 3.95 (br d, J = 10.0 Hz, 2H), 3.77 (s, 3H), 3.67 - 3.58 (m, 2H), 3.27 (s, 3H). 651 [00779]embedded image 537.2 Method D, RT = 1.622 min, 95.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.1 Hz, 1H), 7.94 - 7.81 (m, 2H), 7.34 (t, J = 73.4 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 1.5 Hz, 1H), 6.88 (d, J = 1.5 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 4.86 (dd, J = 10.8, 8.1 Hz, 1H), 4.32 - 4.20 (m, 1H), 4.17 - 4.00 (m, 2H), 3.98 - 3.89 (m, 2H), 3.77 (s, 3H), 3.67 - 3.56 (m, 2H), 3.27 (s, 3H). 652 [00780]embedded image 555.1 Method D, RT = 1.809 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.18 (d, J = 8.1 Hz, 1H), 7.99 - 7.77 (m, 2H), 7.55 - 7.39 (m, 2H), 7.19 (d, J = 1.2 Hz, 1H), 6.88 (d, J = 1.2 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 4.88 (dd, J = 10.8, 8.1 Hz, 1H), 4.33 - 4.21 (m, 1H), 4.18 - 3.90 (m, 4H), 3.77 (s, 3H), 3.69 - 3.54 (m, 2H), 3.27 (s, 3H). 653 [00781]embedded image 552.2 Method D, RT = 1.77 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 9.02 (m, 1H), 7.89 - 7.79 (m, 2H), 7.68 - 7.51 (m, 3H), 6.83 - 6.70 (m, 2H), 6.32 - 6.31(m, 1H), 6.29 (tt, J = 54.8, 5.1 Hz, 1H), 5.32 - 4.85 (m, 1H), 4.40 - 4.05 (m, 4H), 3.78 - 3.74 (2 s, 3H), 3.51 - 3.50 (m, 1H), 2.49 - 2.07 (2 s, 3H). (Mixture of interconvertible atropisomers) 654 [00782]embedded image 558.2 Method D, RT = 1.69 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 - 8.98 (m, 1H), 7.87 - 7.82 (m, 2H), 7.59 - 7.52 (m, 3H), 6.81 - 6.57 (m, 2H), 6.32 - 6.27 (m, 1H), 5.41 - 5.32 (m, 1H), 4.90 (dd, J = 10.5, 8.5 Hz, 1H), 4.21 - 4.02 (m, 3H), 3.90 - 3.72 (m, 6H), 3.53 - 3.48 (m, 1H), 2.54 - 2.52 (m, 1H), 2.24 - 2.20 (2 s, 3H), 2.01 - 1.94 (m, 1H). (Mixture of interconvertible atropisomers) 655 [00783]embedded image 608.2 Method D, RT = 1.846 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.25 - 9.05 (m, 1H), 8.02 - 7.91 (m, 2H), 7.60 - 7.45 (m, 3H), 6.84 - 6.73 (m, 2H), 6.35 - 6.26 (m, 1H), 5.43 - 4.86 (m, 2H), 4.32 - 4.01 (m, 3H), 3.91 - 3.71 (m, 6H), 3.53 - 3.48 (m, 1H), 2.46 - 2.38 (m, 1H), 2.23 - 2.04 (2 s, 3H), 2.01 - 1.90 (m, 1H). (Mixture of interconvertible atrop isomers) 656 [00784]embedded image 600.2 Method D, RT = 1.813 min, 98.2% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 9.0 Hz, 2H), 7.69 - 7.65 (m, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.06 - 4.98 (m, 1H), 4.45 (dd, J = 12.8, 2.8 Hz, 1H), 4.40 - 4.28 (m, 1H), 4.16 - 4.03 (m, 1H), 3.91 - 3.70 (m, 4H), 3.73 (s, 3H). 657 [00785]embedded image 600.2 Method D, RT = 1.828 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.69 - 7.65 (m, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 6.38 (t, J = 7.0 Hz, 1H), 5.02 (dd, J = 11.3, 8.8 Hz, 1H), 4.46 (dd, J = 13.1, 2.5 Hz, 1H), 4.39 - 4.28 (m, 1H), 4.17 (t, J = 8.3 Hz, 1H), 3.91 - 3.70 (m, 4H), 3.73 (s, 3H). 658 [00786]embedded image 579.2 Method D, RT = 1.89 min, 10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 8.93 (m, 1H), 8.05 - 7.93 (m, 1H), 7.93 - 7.77 (m, 2H), 7.34 (t, J = 74.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.88 - 6.66 (m, 2H), 5.36 - 4.74 (m, 1H), 4.45 - 4.12 (m, 4H), 3.82 - 3.72 (2 s, 3H), 3.72 - 3.51 (2 s, 3H), 3.23 - 3.18 (2 s, 3H), 2.26 - 2.02 (2 s, 3H). (Mixture of interconvertible atrop isomers) 659 [00787]embedded image 618.2 Method D, RT = 2.709 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 9.04 (m, 1H), 8.00 - 7.91 (m, 2H), 7.72 - 7.61 (m, 1H), 7.53 - 7.44 (m, 2H), 6.83 - 6.73 (m, 2H), 6.39 - 6.32 (m, 1H), 5.98 - 5.91 (m, 1H), 5.37 - 4.82 (m, 1H), 4.34 - 4.00 (m, 4H), 3.80 - 3.75 (2 s, 3H), 3.63 - 3.52 (m, 1H), 2.28 - 2.07 (2 s, 3H). (Mixture of interconvertible atropisomers) 660 [00788]embedded image 511.1 Method C, RT = 1.895 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 2.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.75 (d, J = 2.4 Hz, 1H), 6.34 (tt, J = 55.0, 8.6 Hz, 1H), 4.96 (dd, J = 10.1, 8.4 Hz, 1H), 4.62 - 4.56 (m, 2H), 4.26 - 4.03 (m, 2H), 3.86 (t, J = 9.3 Hz, 1H), 3.77 (s, 3H). 661 [00789]embedded image 543.1 Method C, RT = 1.852 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 2.4 Hz, 1H), 7.35 (t, J = 74.6 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.75 (d, J = 2.2 Hz, 1H), 6.34 (tt, J = 55.0, 8.6 Hz, 1H), 4.95 (dd, J = 10.0, 8.6 Hz, 1H), 4.62 -4.56 (m, 2H), 4.27 - 4.07 (m, 2H), 3.86 (t, J = 9.3 Hz, 1H), 3.77 (s, 3H). 662 [00790]embedded image 561.1 Method C, RT = 2.041 min, 97.1% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ =9.16 (d, J = 8.3 Hz, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 2.4 Hz, 1H), 7.50 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 10.8 Hz, 2H), 6.75 (d, J = 2.4 Hz, 1H), 6.34 (tt, J = 58.2, 11.0 Hz, 1H), 4.97 (dd, J = 10.0, 8.6 Hz, 1H), 4.62 - 4.56 (m, 2H), 4.28 - 4.06 (m, 2H), 3.86 (t, J = 9.5 Hz, 1H), 3.77 (s, 3H). 663 [00791]embedded image 588.1 Method D, RT = 1.849 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.91 (m, 1H), 7.94 - 7.85 (m, 2H), 7.61 - 7.54 (m, 1H), 7.34 (t, J = 73.4 Hz, 1H), 7.30 - 7.22 (m, 2H), 6.78 - 6.74 (m, 2H), 5.40 - 4.92 (m, 1H), 4.25 - 3.84 (m, 4H), 3.78 - 3.74 (m, 3H), 3.53 - 3.43 (m, 1H), 2.71 - 2.52 (m, 3H), 1.82 - 1.53 (m, 5H), 1.22 (2t, J = 6.8 Hz, 3H). (Mixture of interconvertible atropisomers) 664 [00792]embedded image 588.1 Method D, RT = 1.849 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 8.91 (m, 1H), 7.94 - 7.85 (m, 2H), 7.61 - 7.54 (m, 1H), 7.34 (t, J = 73.4 Hz, 1H), 7.30 - 7.22 (m, 2H), 6.78 - 6.74 (m, 2H), 5.40 - 4.92 (m, 1H), 4.25 - 3.84 (m, 4H), 3.78 - 3.74 (m, 3H), 3.53 - 3.43 (m, 1H), 2.71 - 2.52 (m, 3H), 1.82 - 1.53 (m, 5H), 1.22 (2t, J = 6.8 Hz, 3H). (Mixture of interconvertible atropisomers) 665 [00793]embedded image 619.1 Method D, RT = 1.485 min, 95.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.87 (m, 1H), 8.01 - 7.81 (m, 2H), 7.73 - 7.58 (m, 1H), 7.55 - 7.11 (m, 4H), 6.87 - 6.66 (m, 2H), 6.35 - 6.20 (m, 1H), 5.37 - 4.79 (m, 2H), 4.33 - 4.05 (m, 3H), 3.81 - 3.78 (2 s, 3H), 3.63 - 3.51 (m, 2H), 3.26 - 3.22 (m, 2H), 2.23 - 2.06 (2 s, 3H). (Mixture of interconvertible atropisomers) 666 [00794]embedded image 467.1 Method D, RT = 1.62 min,97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 8.63 (m, 1H), 8.09 - 7.96 (m, 1H), 7.91 - 7.61 (m, 3H), 7.60 - 7.44 (m, 2H), 7.39 - 7.16 (m, 2H), 6.96 - 6.75 (m, 2H), 5.12 - 4.97 (m, 1H), 4.53 - 4.27 (m, 1H), 4.24 - 4.08 (m, 2H), 3.98 - 3.87 (m, 1H), 3.77 (s, 3H), 3.80 - 3.74 (m, 1H), 1.30 (t, J = 7.2 Hz, 3H). 667 [00795]embedded image 594 Method D, RT = 1.751 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 9.0 Hz, 2H), 7.83 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 9.0 Hz, 2H), 7.25 (d, J = 7.8 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.11 - 5.00 (m, 1H), 4.68 (t, J = 5.3 Hz, 2H), 4.28 - 4.19 (m, 2H), 4.14 - 4.10 (m, 3H), 3.77 (s, 3H). 668 [00796]embedded image 576.1 Method D, RT = 1.568 min, 97.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.5 Hz, 1H), 7.99 - 7.85 (m, 2H), 7.83 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 74.8 Hz, 1H), 7.27 (t, J = 7.9 Hz, 3H), 6.79 (d, J = 10.8 Hz, 2H), 5.12 - 4.98 (m, 1H), 4.68 (t, J = 5.2 Hz, 2H), 4.32 - 4.19 (m, 2H), 4.17 - 4.04 (m, 3H), 3.77 (s, 3H). 669 [00797]embedded image 598.2 Method D, RT = 1.57 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.62 - 7.58 (m, 2H), 7.49 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 6.9 Hz, 1H), 5.13 (dd, J =10.8, 8.5 Hz, 1H), 4.30 (dd, J =12.9, 3.4 Hz, 1H), 4.16 - 3.91 (m, 4H), 3.77 (s, 3H), 3.63 -3.59 (m, 2H), 3.41 - 3.33 (m, 3H). 670 [00798]embedded image 467.1 Method D, RT = 1.62 min,97 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 8.63 (m, 1H), 8.09 - 7.96 (m, 1H), 7.91 - 7.61 (m, 3H), 7.60 - 7.44 (m, 2H), 7.39 - 7.16 (m, 2H), 6.96 - 6.75 (m, 2H), 5.12 - 4.97 (m, 1H), 4.53 - 4.27 (m, 2H), 4.24 - 4.08 (m, 2H), 3.96 - 3.89 (m, 1H), 3.77 (s, 3H), 1.36 - 1.20 (t, J = 7.2 Hz, 3H). 671 [00799]embedded image 535.1 Method D, RT = 1.84 min,92 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 - 8.61 (m, 1H), 8.04 (dd, J = 13.4, 4.9 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 5.08 - 4.99 (m, 1H), 4.48 - 4.32 (m, 3H), 4.00 - 3.88 (m, 1H), 3.77 (s, 3H), 3.80 - 3.72 (m, 1H), 2.89 - 2.74 (m, 2H). 672 [00800]embedded image 567.1 Method D, RT = 1.81 min,95 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 4.6 Hz, 1H), 7.97 - 7.86 (m, 2H), 7.77 (d, J = 4.6 Hz, 1H), 7.59 - 7.14 (m, 5H), 7.01 - 6.79 (m, 2H), 5.04 (dd, J = 11.7, 8.4 Hz, 1H), 4.54 - 4.42 (m, 1H), 4.37 (t, J = 6.8 Hz, 2H), 3.97 (t, J = 10.4 Hz, 1H), 3.84 - 3.75 (m, 1H), 3.73 (s, 3H), 2.88 - 2.72 (m, 2H). 673 [00801]embedded image 553.2 Method D, RT = 1.95 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 4.6 Hz, 1H), 7.99 - 7.82 (m, 2H), 7.70 (d, J = 4.4 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 6.78 (d, J = 10.8 Hz, 2H), 5.07 (dd, J = 10.8, 8.4 Hz, 1H), 4.42 - 4.27 (m, 1H), 4.25 -4.05 (m, 4H), 3.77 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H). 674 [00802]embedded image 499.2 Method D, RT = 1.66 min,96 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.94 (br d, J = 8.6 Hz, 1H), 8.00 (d, J = 4.6 Hz, 1H), 7.95 - 7.85 (m, 2H), 7.72 (d, J = 4.6 Hz, 1H), 7.37 (t, J = 74.5 Hz, 1H), 7.36 -734 (m, 2H), 7.26 - 7.16 (m, 2H), 6.91 (d, J = 8.6 Hz, 2H), 5.03 (dd, J = 11.5, 8.3 Hz, 1H), 4.46 (dd, J = 9.8, 8.3 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 3.96 (t, J = 10.4 Hz, 1H), 3.81 - 3.68 (m, 1H), 3.77 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). 675 [00803]embedded image 517.2 Method D, RT = 1.84 min,96 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.03 (d, J = 8.3 Hz, 1H), 8.06 - 7.89 (m, 3H), 7.72 (d, J = 4.6 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 5.04 (dd, J = 11.9, 8.4 Hz, 1H), 4.51 - 4.38 (m, 1H), 4.14 (q, J = 7.3 Hz, 2H), 3.97 (t, J = 10.3 Hz, 1H), 3.79 - 3.75 (m, 1H), 3.73 (s, 3H), 1.28 (t, J = 7.3 Hz, 3H). 676 [00804]embedded image 614.2 Method-D, RT = 2.004 min, 93.7% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.15 - 9.10 (m, 1H), 8.51 - 8.47 (m, 1H), 7.86 - 7.78 (m, 2H), 7.58 - 7.52 (m, 2H), 7.28 - 7.23 (m, 1H), 6.83 - 6.74 (m, 2H), 5.14 - 4.96 (m, 1H), 4.65 (s, 1H), 4.43 - 4.18 (m, 1H), 4.14 (s, 2H), 3.99 - 3.82 (m, 1H), 3.77 (s, 3H), 3.75 - 3.71 (m, 1H), 1.22 (s, 3H), 1.17 (s, 3H). 677 [00805]embedded image 548.2 Method D, RT = 1.42 min, 10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.5 Hz, 2H), 7.63 - 7.53 (m, 4H), 6.77 (d, J = 10.5 Hz, 2H), 6.32 (t, J = 6.9 Hz, 1H), 5.12 (dd, J = 10.5, 8.6 Hz, 1H), 5.00 (br s, 1H), 4.65 (br s, 1H), 4.30 - 4.27 (m, 1H), 4.15 - 3.92 (m, 4H), 3.77 (s, 3H), 3.67-3.61 (m, 1H), 3.38 - 3.35 (m, 2H). 678 [00806]embedded image 580.2 Method D, RT = 1.40 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.61 (dd, J = 13.0, 7.0 Hz, 2H), 7.34 (t, J = 74.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.11 (t, J = 9.6 Hz, 1H), 5.04 - 4.94 (m, 1H), 4.83 - 4.68 (m, 1H), 4.30 - 4.31(m, 1H), 4.15 - 3.87 (m, 4H), 3.77 (s, 3H), 3.65 - 3.63 (m, 1H), 3.38 -3.35 (m, 2H). 679 [00807]embedded image 598.2 Method D, RT = 1.57 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.5 Hz, 1H), 8.02 - 7.89 (m, 2H), 7.63 (dd, J = 6.5, 1.9 Hz, 1H), 7.60 (dd, J = 7.1, 1.9 Hz, 1H), 7.49 (d, J = 8.5 Hz, 2H), 6.77 (d, J = 10.8 Hz, 2H), 6.32 (t, J = 7.1 Hz, 1H), 5.13 - 5.09 (dd, J = 10.8, 8.9 Hz, 1H), 5.00 (d, J = 5.8 Hz, 1H), 4.74 (t, J = 5.8 Hz, 1H), 4.30 (dd, J = 12.9, 2.9 Hz, 1H), 4.15 - 3.92 (m, 4H), 3.76 (s, 3H), 3.64 - 3.60 (m, 1H), 3.41 -3.36 (m, 2H). 680 [00808]embedded image 548.2 Method D, RT = 1.42 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.5 Hz, 1H), 7.92 - 7.78 (m, 2H), 7.63 (dd, J = 6.6, 2.0 Hz, 1H), 7.59 (dd, J = 7.3, 2.0 Hz, 1H), 7.58 - 7.43 (m, 2H), 6.77 (d, J = 10.5 Hz, 2H), 6.32 (t, J = 7.3 Hz, 1H), 5.12 - 5.07 (m, 1H), 5.04 - 4.94 (m, 1H), 4.80 - 4.69 (m, 1H), 4.30 - 4.27 (m, 1H), 4.14 - 3.90 (m, 4H), 3.77 (s, 3H), 3.64 - 3.60 (m, 1H), 3.41 - 3.36 (m, 2H). 681 [00809]embedded image 580.3 Method D, RT = 1.40 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.00 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.63 (dd, J = 6.8, 2.0 Hz, 2H), 7.34 (t, J = 74.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.78 - 6.75 (m, 2H), 6.32 (t, J = 7.0 Hz, 1H), 5.13 - 5.08 (m, 1H), 4.32 - 4.28 (m, 1H), 4.15 - 3.92 (m, 4H), 3.77 (s, 3H), 3.63 - 3.60 (m, 2H), 3.38 - 3.33 (m, 3H). 682 [00810]embedded image 604.3 Method D, RT = 1.69 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.87 (m, 1H), 7.96 - 7.84 (m, 2H), 7.62 - 7.50 (m, 1H), 7.28 (t, J = 75.1 Hz, 1H), 7.37 - 7.13 (m, 2H), 6.81 - 6.68 (m, 2H), 6.26 - 6.12 (m, 1H), 5.36 - 4.84 (m, 2H), 4.30 - 4.04 (m, 3H), 3.81 - 3.72 (2 s, 3H), 3.66 - 3.62 (m, 1H), 3.51 - 3.45 (m, 1H), 3.12 - 3.10 (m, 1H), 2.22 - 2.05 (2 s, 3H), 0.92 - 0.68 (m, 1H), 0.48 - 0.32 (m, 2H), 0.32 - 0.04 (m, 2H). (Mixture of interconvertible atropisomers) 683 [00811]embedded image 622.3 Method D, RT = 1.85 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.31 - 8.93 (m, 1H), 8.06 - 7.83 (m, 2H), 7.67 - 7.52 (m, 1H), 7.52 - 7.41 (m, 2H), 6.86 - 6.68 (m, 2H), 6.27 - 6.12 (m, 1H), 5.38 - 4.84 (m, 2H), 4.32 - 4.07 (m, 3H), 3.80 - 3.71 (2 s, 3H), 3.66 - 3.60 (m, 1H), 3.51 - 3.45 (m, 1H), 3.18 - 3.10 (m, 2H), 2.21 - 1.96 (2 s, 3H), 0.93 - 0.75 (m, 1H), 0.48 - 0.33 (m, 2H), 0.30 - 0.04 (m, 2H). (Mixture of interconvertible atropisomers) 684 [00812]embedded image 573.2 Method D, RT = 1.67 min,98 % .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.21 - 8.85 (m, 1H), 7.92 - 7.79 (m, 2H), 7.69 - 7.45 (m, 3H), 6.81 - 6.68 (m, 2H), 6.28 - 6.08 (m, 1H), 5.38 - 4.82 (m, 2H), 4.32 - 4.04 (m, 3H), 3.80 - 3.75 (2 s, 3H), 3.72 - 3.60 (m, 1H), 3.51 - 3.45 (m, 1H), 3.21 - 3.02 (m, 1H), 2.20 - 1.99 (2 s, 3H), 0.91 - 0.74 (m, 1H), 0.47 - 0.33 (m, 2H), 0.29 - 0.20 (m, 1H), 0.20 - 0.07 (m, 1H). (Mixture of interconvertible atropisomers) 685 [00813]embedded image 604.3 Method D, RT = 1.72 min,10 0% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.17 - 8.82 (m, 1H), 8.01 - 7.81 (m, 2H), 7.33 (t, J = 75.1 Hz, 1H), 7.58 - 7.16 (m, 3H), 6.77 (dd, J = 10.6, 4.9 Hz, 2H), 6.19 (dd, J = 12.3, Hz, 1H), 5.39 - 4.78 (m, 2H), 4.31 - 4.03 (m, 3H), 3.81 - 3.72 (2 s, 3H), 3.67 - 3.60 (m, 1H), 3.51 - 3.45 (m, 1H), 3.20 - 3.06 (m, 1H), 2.23 - 1.99 (2 s, 3H), 0.91 - 0.71 (m, 1H), 0.48 - 0.33 (m, 2H), 0.31 - 0.21 (m, 1H), 0.19 - 0.07 (m, 1H). (Mixture of interconvertible atrop isomers) 686 [00814]embedded image 622.3 Method D, RT = 1.87 min, 98% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.22 - 8.95 (m, 1H), 8.03 - 7.86 (m, 2H), 7.58 - 7.54 (m, 1H), 7.53 - 7.37 (m, 2H), 6.79 - 6.75 (m, 2H), 6.22 - 6.17 (m, 1H), 5.37 - 4.95 (m, 1H), 4.94 - 4.84 (m, 1H), 4.29 - 4.04 (m, 3H), 3.77 - 3.76 (2 s, 3H), 3.72 - 3.61 (m, 1H), 3.55 - 3.46 (m, 1H), 3.18 - 3.10 (m, 1H), 2.22 - 2.04 (2 s, 3H), 0.88 - 0.78 (m, 1H), 0.46 - 0.33 (m, 2H), 0.30 - 0.22 (m, 1H), 0.19 - 0.09 (m, 1H). (Mixture of interconvertible atropisomers) 687 [00815]embedded image 556.2 Method D, RT = 1.881 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.91 (m, 1H), 8.08 - 7.92 (m, 2H), 7.79 - 7.62 (m, 1H), 7.50 - 7.46 (m, 2H), 7.42 - 7.23 (m, 2H), 6.93 - 6.89 (m, 2H), 6.34 - 6.14 (m, 1H), 5.28 - 4.65 (m, 2H), 4.12 - 3.82 (m, 3H), 3.78 - 3.48 (m, 4H), 2.36 - 2.24 (m, 3H), 2.21 - 2.08 (2 s, 3H), 1.84 - 1.65 (m, 1H), 0.58 - 0.21 (m, 1H). (Mixture of interconvertible atropisomers) 688 [00816]embedded image 574.2 Method D, RT = 2.072 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.16 - 8.97 (m, 1H), 8.07 - 7.92 (m, 2H), 7.82 - 7.67 (m, 1H), 7.65 - 7.38 (m, 3H), 6.90 - 6.70 (m, 2H), 6.32 - 6.15 (m, 1H), 5.82 - 5.32 (m, 1H), 5.11 - 4.81 (m, 2H), 4.32 - 3.73 (m, 4H), 3.70 - 3.55 (m, 2H), 2.44 - 2.24 (m, 3H), 2.22 - 2.05 (2 s, 3H), 1.99 - 1.72 (m, 1H), 0.54 - 0.22 (m, 1H). (Mixture of interconvertible atropisomers) 689 [00817]embedded image 556.3 Method D, RT = 1.819 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 8.85 (m, 1H), 8.00 - 7.87 (m, 2H), 7.81 - 7.65 (m, 1H), 7.59 - 7.39 (m, 1H), 7.38 - 6.92 (m, 3H), 6.87 - 6.66 (m, 2H), 6.33 - 6.19 (m, 1H), 5.42 - 4.81 (m, 2H), 4.20 3.89 (m, 3H), 3.78 - 3.74 (2 s, 3H), 3.63 - 3.54 (m, 1H), 2.39 - 2.23 (m, 3H), 2.22 - 2.08 (2 s, 3H), 1.84 - 1.70 (m, 1H), 0.56 - 0.30 (m, 1H). (Mixture of interconvertible atropisomers) 690 [00818]embedded image 503.1 Method D, RT = 1.71 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.99 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 4.6 Hz, 1H), 7.91 - 7.83 (m, 2H), 7.78 (d, J = 4.6 Hz, 1H), 7.59 - 7.50 (m, 2H), 7.40 - 7.31 (m, 2H), 6.95 - 6.86 (m, 2H), 6.39 (tt, J = 54.8, 4.4 Hz, 1H), 5.04 (dd, J = 11.6, 8.4 Hz, 1H), 4.55 (dt, J = 14.5, 4.0 Hz, 2H), 4.46 (dd, J = 9.9, 8.2 Hz, 1H), 3.98 (t, J = 10.4 Hz, 1H), 3.82 - 3.74 (m, 1H), 3.73 (s, 3H). 691 [00819]embedded image 535.1 Method D, RT = 1.86 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.93 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 4.9 Hz, 1H), 7.94 - 7.86 (m, 2H), 7.79 (d, J = 4.6 Hz, 1H), 7.40 - 7.34 (m, 2H), 7.33 (t, J = 75.1 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.95 - 6.86 (m, 2H), 6.39 (tt, J = 55.8, 4.4 Hz, 1H), 5.03 (dd, J = 11.6, 8.4 Hz, 1H), 4.56 (dt, J = 14.4, 4.2 Hz, 2H), 4.46 (dd, J = 9.9, 8.2 Hz, 1H), 3.98 (t, J = 10.4 Hz, 1H), 3.82 - 3.74 (m, 1H), 3.73 (s, 3H). 692 [00820]embedded image 553.1 Method D, RT = 1.86 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.04 (d, J = 8.3 Hz, 1H), 8.05 (d, J = 4.6 Hz, 1H), 8.01 - 7.92 (m, 2H), 7.79 (d, J = 4.6 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7.41 -7.29 (m, 2H), 6.96 - 6.85 (m, 2H), 6.40 (tt, J = 55.8, 4.3, Hz, 1H), 5.05 (dd, J = 11.6, 8.4 Hz, 1H), 4.56 (dt, J = 14.5, 4.3 Hz, 2H), 4.46 (dd, J = 9.9, 8.4 Hz, 1H), 3.98 (t, J = 10.4 Hz, 1H), 3.81 - 3.73 (m, 1H), 3.72 (s, 3H). 693 [00821]embedded image 604.3 Method D, RT = 1.629 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.81 (m, 1H), 7.96 - 7.82 (m, 2H), 7.74 - 7.58 (m, 1H), 7.58 - 7.08 (m, 3H), 6.76 (m, 2H), 6.32 - 6.18 (m, 1H), 5.39 - 4.77 (m, 1H), 4.32 - 4.02 (m, 2H), 4.00 - 3.85 (m, 2H), 3.83 - 3.71 (m, 4H), 3.68 - 3.57 (m, 2H), 3.54 - 3.43 (m, 2H), 2.71 - 2.61 (m, 1H), 2.22 - 2.02 (2 s, 3H), 1.93 - 1.78 (m, 1H), 1.68 - 1.51 (m, 1H). (Mixture of interconvertible atrop isomers) 694 [00822]embedded image 521 Method D, RT = 1.78 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.02 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 4.6 Hz, 1H), 7.91 - 7.80 (m, 2H), 7.78 (d, J = 4.6 Hz, 1H), 7.61 - 7.43 (m, 3H), 6.90 - 6.75 (m, 2H), 6.39 (tt, J = 56.2, 5.1 Hz, 1H), 5.13 (dd, J = 11.1, 8.4 Hz, 1H), 4.55 (dt, J = 14.4, 4.3, Hz, 2H), 4.46 (t, J = 7.9 Hz, 1H), 4.09 - 3.88 (m, 2H), 3.75 (s, 3H). 695 [00823]embedded image 604.3 Method D, RT = 1.619 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.81 (m, 1H), 7.98 - 7.81 (m, 2H), 7.73 - 7.58 (m, 1H), 7.56 - 7.04 (m, 3H), 6.78 - 6.74 (m, 2H), 6.31 - 6.11 (m, 1H), 5.41 - 4.81 (m, 1H), 4.32 - 3.97 (m, 3H), 3.94 - 3.72 (m, 5H), 3.69 - 3.57 (m, 2H), 3.55 - 3.42 (m, 2H), 2.70 - 2.61 (m, 1H), 2.21 - 1.97 (2 s, 3H), 1.93 - 1.80 (m, 1H), 1.71 - 1.54 (m, 1H). (Mixture of interconvertible atropisomers) 696 [00824]embedded image 571.1 Method D, RT = 1.92 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 4.9 Hz, 1H), 8.00 - 7.89 (m, 2H), 7.78 (d, J = 4.9 Hz, 1H), 7.54 (t, J = 8.8 Hz, 1H), 7.48 (d, J = 8.3 Hz, 2H), 6.86 - 6.75 (m, 2H), 6.39 (tt, J = 54.8, 5.1 Hz, 1H), 5.13 (dd, J = 11.0, 8.6 Hz, 1H), 4.55 (dt, J = 14.4, 4.2 Hz, 2H), 4.47 (t, J = 7.9 Hz, 1H), 4.08 - 3.92 (m, 2H), 3.75 (s, 3H). 697 [00825]embedded image 622.2 Method D, RT = 1.788 min, 97%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.23 - 8.92 (m, 1H), 8.05 - 7.87 (m, 2H), 7.78 - 7.61 (m, 1H), 7.55 - 7.37 (m, 2H), 6.78 - 6.73 (m, 2H), 6.30 - 6.13 (m, 1H), 5.38 - 4.81 (m, 1H), 4.31 - 3.95 (m, 3H), 3.93 - 3.83 (m, 2H), 3.75 - 3.70 (s, 3H), 3.67 -3.58 (m, 2H), 3.53 - 3.43 (m, 2H), 2.72 -2.64 (m, 1H), 2.24 - 2.02 (2 s, 3H), 1.93 -1.82 (m, 1H), 1.68 - 1.54 (m, 1H). (Mixture of interconvertible atropisomers) 698 [00826]embedded image 600.2 Method D, RT = 1.642 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.97 - 8.92 (m, 1H), 7.98 - 7.83 (m, 2H), 7.60 - 7.58 (m, 1H), 7.56 - 7.13 (m, 2H), 7.10 (m, 2H), 6.87 - 6.70 (m, 2H), 6.22 - 6.19 (m, 1H), 5.43 - 4.74 (m, 1H), 4.19 - 3.87 (m, 3H), 3.87 - 3.70 (m, 5H), 3.62 - 3.37 (m, 1H), 3.26 - 3.15 (m, 3H), 2.23 - 2.06 (2 s, 3H), 2.04 - 1.93 (m, 1H), 1.49 - 1.38 (m, 2H), 1.34 - 1.19 (m, 2H). (Mixture of interconvertible atrop isomers) 699 [00827]embedded image 582.3 Method D, RT = 1.565 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.95 - 8.93 (m, 1H), 7.95 - 7.92 (m, 2H), 7.61 - 7.59 (m, 1H), 7.39 - 7.22 (m, 5H), 6.92 - 6.90 (m, 2H), 6.21 (d, J = 6.8 Hz, 1H), 5.32 - 4.58 (m, 1H), 3.94 - 3.69 (m, 9H), 3.67 - 3.38 (m, 1H), 3.30 - 3.18 (m, 2H), 2.23 - 2.06 (2 s, 3H), 2.03 - 1.90 (m, 1H), 1.51 - 1.36 (m, 2H), 1.34 - 1.16 (m, 2H). (Mixture of interconvertible atropisomers) 700 [00828]embedded image 600.3 Method D, RT = 1.75 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.05 - 9.03 (m, 1H), 8.02 - 7.97 (m, 2H), 7.61 -7.59 (m, 1H),7.49 - 7.47 (m, 2H), 7.40 -7.30 (m, 2H), 6.93 - 6.90 (m, 2H), 6.21 (d, J = 6.8 Hz, 1H), 5.31 - 4.63 (m, 1H), 3.93 - 3.69 (m, 10H), 3.23 (m, 2H), 2.18 - 2.06 (2 s, 3H), 2.03 - 1.89 (m, 1H), 1.51 - 1.36 (m, 2H), 1.32 - 1.21 (m, 2H). (Mixture of interconvertible atropisomers) 701 [00829]embedded image 638.3 Method D, RT = 1.61 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.10 - 8.90 (m, 1H), 7.94 - 7.84 (m, 2H), 7.79 - 7.68 (m, 1H), 7.33 (t, J = 73.6 Hz, 1H), 7.26 - 7.24 (m, 2H), 6.81 - 6.68 (m, 2H), 6.40 - 6.29 (m, 1H), 5.49 - 4.75 (m, 2H), 4.31 - 4.04 (m, 3H), 3.78 - 3.74 (2 s, 3H), 3.62 - 3.47 (m, 4H), 3.29 - 3.23 (m, 1H), 2.48 - 2.39 (m, 1H), 2.24 - 2.02 (2 s, 3H). (Mixture of interconvertible atropisomers) 702 [00830]embedded image 656.2 Method D, RT = 1.78 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.19 - 9.00 (m, 1H), 8.00 - 7.88 (m, 2H), 7.77 - 7.67 (m, 1H), 7.52 - 7.41 (m, 2H), 6.82 - 6.70 (m, 2H), 6.40 - 6.28 (m, 1H), 5.46 - 4.81 (m, 2H), 4.29 - 4.05 (m, 3H), 3.78 - 3.74 (2 s, 3H), 3.62 - 3.45 (m, 4H), 3.27 - 3.21 (m, 1H), 2.47 - 2.38 (m, 1H), 2.24 - 2.04 (2 s, 3H). (Mixture of interconvertible atrop isomers) 703 [00831]embedded image 612.2 Method D, RT = 1.412 min, 95.6% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.12 (dd, J = 14.9, 8.4 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.84 - 7.67 (m, 1H), 7.49 (t, J = 7.3 Hz, 2H), 7.26 (d, J = 7.5 Hz, 1H), 6.78 (t, J = 10.1 Hz, 2H), 5.20 - 4.98 (m, 1H), 4.68 (t, J = 5.1 Hz, 1H), 4.26 - 4.21 (m, 1H), 4.17 - 4.03 (m, 2H), 4.01 - 3.90 (m, 1H), 3.77 (s, 3H), 3.75 - 3.70 (m, 1H), 3.34 - 3.30 (m, 1H). 704 [00832]embedded image 572.2 Method D, RT = 3.00 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 - 9.01 (m, 1H), 8.05 - 7.94 (m, 2H), 7.63 - 7.44 (m, 3H), 7.42 - 7.28 (m, 2H), 6.98 - 6.84 (m, 2H), 6.31 - 6.27 (m, 1H), 5.38 - 5.34 (m, 1H), 5.25 - 4.67 (m, 1H), 4.14 - 3.99 (m, 2H), 3.95 - 3.81 (m, 3H), 3.79 - 3.74 (m, 1H), 3.75 - 3.70 (2 s, 3H), 3.67 - 3.45 (m, 1H), 2.48 - 2.39 (m, 1H), 2.26 - 2.08 (2 s, 3H), 2.04 - 1.90 (m, 1H). (Mixture of interconvertible atropisomers) 705 [00833]embedded image 594.2 Method F, RT = 2.526 min, 99.9% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.06 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.69 (dd, J = 7.0, 1.6 Hz, 1H), 7.57 (dd, J = 7.3, 1.6 Hz, 1H), 7.54 - 7.46 (m, 3H), 6.85 - 6.78 (m, 2H), 6.35 (t, J = 7.0 Hz, 1H), 5.20 - 5.01 (m, 3H), 4.19 - 4.12 (m, 1H), 4.06 - 3.96 (m, 1H), 3.80 - 3.64 (m, 5H), 3.75 (s, 3H), 3.24 (s, 3H). 706 [00834]embedded image 632.2 Method D, RT = 1.765 min, 98.8% .sup.1H NMR (400 MHz, DMSO-d.sub.6) 6 = 9.15 - 8.83 (m, 1H), 7.97 - 7.79 (m, 2H), 7.69 - 7.56 (m, 1H), 7.35 (t, J = 74.8 Hz, 1H), 7.31 - 7.27 (m, 2H), 6.84 - 6.66 (m, 3H), 6.34 - 6.19 (m, 1H), 5.36 - 4.80 (m, 1H), 4.46 - 4.08 (m, 4H), 3.91 - 3.69 (m, 4H), 3.52 - 3.49 (m, 1H), 2.26 - 1.97 (2 s, 3H). (Mixture of interconvertible atropisomers) 707 [00835]embedded image 632.3 Method C, RT = 1.720 min, 100% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 8.86 (m, 1H), 7.97 - 7.77 (m, 2H), 7.69 - 7.56 (m, 1H), 7.35 (t, J = 74.8 Hz, 1H), 7.31 - 7.27 (m, 2H), 6.85 - 6.53 (m, 3H), 6.34 - 6.15 (m, 1H), 5.38 - 4.78 (m, 1H), 4.47 - 4.01 (m, 4H), 3.91 - 3.69 (m, 4H), 3.56 - 3.47 (m, 1H), 2.25 - 2.04 (2 s, 3H). (Mixture of interconvertible atropisomers) 708 [00836]embedded image 612.2 Method-D, RT = 1.918 min, 98.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.13 - 9.07 (m, 1H), 8.66 - 8.59 (m, 1H), 7.86 - 7.79 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.39 - 7.32 (m, 1H), 6.78 (d, J = 11.5 Hz, 2H), 5.39 - 5.34 (m, 1H), 5.14 - 5.04 (m, 1H), 4.48 - 4.13 (m, 2H), 4.01 - 3.73 (m, 7H), 3.33 - 3.30 (m, 1H), 2.35 - 2.27 (m, 1H), 2.12 - 1.91 (m, 1H). (Mixture of interconvertible atropisomers) 709 [00837]embedded image 612.2 Method-D, RT = 1.918 min, 97.4% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 - 9.07 (m, 1H), 8.67 - 8.58 (m, 1H), 7.87 - 7.76 (m, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.36 (br d, J = 5.6 Hz, 1H), 6.78 (d, J = 10.8 Hz, 2H), 5.39 - 5.31 (m, 1H), 5.13 -5.02 (m, 1H), 4.47 - 4.13 (m, 2H), 4.01 -3.73 (m, 7H), 3.33 - 3.30 (m, 1H), 2.37 -2.22 (m, 1H), 2.09 - 1.94 (m, 1H). (Mixture of interconvertible atropisomers) 710 [00838]embedded image 544.2 Method D, RT = 1.207 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.8 Hz, 1H), 8.53 (s, 1H), 8.12 (s, 1H), 7.89 - 7.74 (m, 2H), 7.62 - 7.50 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.17 - 5.04 (m, 2H), 4.17 - 4.06 (m, 1H), 4.00 - 3.92 (m, 2H), 3.76 (s, 3H), 3.19 - 3.06 (m, 3H), 2.97 (dd, J = 11.8, 3.8 Hz, 1H), 2.89 - 2.79 (m, 1H), 2.30 - 2.18 (m, 1H), 1.92 - 1.88 (m, 1H). 711 [00839]embedded image 663.3 Method-C, RT = 1.606 min, 97.14% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 8.88 (d, J = 8.3 Hz, 1H), 7.93 - 7.86 (m, 2H), 7.85 - 7.80 (m, 1H), 7.35 (t, J = 72 Hz, 1H), 7.30 - 7.23 (m, 2H), 6.84 - 6.76 (m, 2H), 6.72 - 6.68 (m, 1H), 5.67 (dd, J = 12.5, 8.3 Hz, 1H), 5.03 - 4.90 (m, 1H), 4.49 (dt, J = 47.2, 4.5 Hz, 2H), 4.35 - 4.26 (m, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 2.98 (br d, J = 10.8 Hz, 2H), 2.69 - 2.63 (m, 1H), 2.62 - 2.55 (m, 2H), 2.15 - 2.05 (m, 2H), 1.84 - 1.68 (m, 4H), 1.21 (d, J = 6.2 Hz, 3H). 712 [00840]embedded image 522.1 Method C, RT = 1.594 min, 96.0%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.33 (d, J = 1.0 Hz, 1H), 9.15 (d, J = 8.3 Hz, 1H), 8.14 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.77 (d, J = 6.5 Hz, 2H), 7.58 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 10.8 Hz, 2H), 5.17 (dd, J = 11.1, 8.6 Hz, 1H), 4.64 -4.54 (m, 1H), 4.41 (t, J = 10.1 Hz, 1H), 4.23 (q, J = 10.0 Hz, 1H), 3.78 (s, 3H). 713 [00841]embedded image 558.2 Method D, RT = 1.623 min, 99.7%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.5 Hz, 1H), 8.64 (s, 1H), 8.13 (s, 1H), 7.88 - 7.79 (m, 2H), 7.60 - 7.53 (m, 2H), 6.78 (d, J = 11.0 Hz, 2H), 5.26 - 5.17 (m, 1H), 5.12 (dd, J = 11.3, 8.8 Hz, 1H), 4.17 - 4.05 (m, 1H), 3.96 (d, J = 9.5 Hz, 2H), 3.77 (s, 3H), 3.06 (td, J = 8.8, 3.5 Hz, 1H), 2.92 (d, J = 9.0 Hz, 1H), 2.59 -2.53 (m, 1H), 2.47 - 2.38 (m, 1H), 2.32 (s, 3H), 2.24 (m, 1H), 1.98 - 1.83 (m, 1H). 714 [00842]embedded image 544.1 Method D, RT = 1.204 min, 98%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.07 (d, J = 8.5 Hz, 1H), 8.53 (s, 1H), 8.13 (s, 1H), 7.89 - 7.76 (m, 2H), 7.64 - 7.46 (m, 2H), 6.77 (d, J = 10.8 Hz, 2H), 5.18 - 5.02 (m, 2H), 4.15 - 4.04 (m, 1H), 3.99 - 3.91 (m, 2H), 3.76 (s, 3H), 3.17 - 3.09 (m, 3H), 3.01 (dd, J = 12.0, 3.8 Hz, 1H), 2.91 - 2.82 (m, 1H), 2.30 - 2.20 (m, 1H), 1.94 - 1.86 (m, 1H). 715 [00843]embedded image 631.2 Method D, RT = 1.51 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.3 Hz, 1H), 8.05 (s, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.36 (t, J = 72.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.97 (s, 1H), 6.81 (d, J = 10.8 Hz, 2H), 5.34 (d, J = 3.5 Hz, 1H), 5.02 (dd, J = 8.0, 10.8 Hz, 1H), 4.46 (t, J = 10.0 Hz, 1H), 4.16 (q, J = 9.8 Hz, 1H), 4.03 - 3.93 (m, 1H), 3.78 (s, 3H), 3.78 - 3.66 (m, 2H), 3.59 (d, J = 12.0 Hz, 2H), 3.22 - 3.14 (m, 2H), 3.12 - 3.01 (m, 2H), 2.93 - 2.84 (m, 1H), 2.36 (s, 3H), 2.13 - 1.95 (m, 4H). 716 [00844]embedded image 587.2 Method D, RT = 1.485 min, 99%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.11 (d, J = 8.1 Hz, 1H), 8.05 (s, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.36 (t, J = 72.0 Hz, 1H), 7.29 (d, J = 8.6 Hz, 2H), 6.96 (s, 1H), 6.81 (d, J = 10.8 Hz, 2H), 5.01 (dd, J = 10.8, 8.3 Hz, 1H), 4.45 (t, J = 9.7 Hz, 1H), 4.16 (q, J = 9.8 Hz, 1H), 4.04 - 3.87 (m, 1H), 3.79 (s, 3H), 3.39 - 3.31 (m, 3H), 3.09 - 2.89 (m, 3H), 2.36 (s, 3H), 2.05 - 1.80 (m, 4H). 717 [00845]embedded image 511.12 Method C, RT = 1.484 min, 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.14 (d, J = 8.5 Hz, 1H), 8.34 (s, 1H), 7.94 (d, J = 1.3 Hz, 1H), 7.91 - 7.79 (m, 2H), 7.63 - 7.48 (m, 3H), 7.37 (d, J = 1.0 Hz, 1H), 6.80 (d, J = 10.8 Hz, 2H), 5.17 (dd, J = 11.0, 8.5 Hz, 1H), 4.56 - 4.45 (m, 1H), 4.40 (t, J = 9.9 Hz, 1H), 4.22 (q, J = 10.0 Hz, 1H), 3.78 (s, 3H), 2.31 (s, 3H). 718 [00846]embedded image 573.2 Method D, RT = 1.429 min, 96%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 6 = 9.08 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 8.3 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 8.0 Hz, 1H), 7.35 (t, J = 73.5 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 7.3 Hz, 1H), 6.79 (d, J = 10.5 Hz, 2H), 5.12 - 5.03 (m, 1H), 4.52 - 4.41 (m, 1H), 4.16 - 4.08 (m, 1H), 3.98 (d, J = 10.0 Hz, 1H), 3.78 (s, 3H), 3.09 - 3.06 (m, 1H), 2.92 -2.87 (m, 1H), 2.64 - 2.59 (m, 1H), 2.29 -2.24 (m, 1H), 1.97 - 1.92 (m, 1H), 1.70 -1.60 (m, 2H), 1.55 - 1.42 (m, 3H). 719 [00847]embedded image 573.2 Method D, RT = 1.439 min, 94%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.09 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 8.3 Hz, 1H), 7.92 - 7.84 (m, 2H), 7.78 (t, J= 7.9 Hz, 1H), 7.35 (t, J = 73.3 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.07 (d, J = 7.5 Hz, 1H), 6.79 (d, J = 10.5 Hz, 2H), 5.07 (dd, J = 11.0, 8.3 Hz, 1H), 4.51 - 4.41 (m, 1H), 4.16 - 4.07 (m, 1H), 3.97 (t, J= 10.8 Hz, 1H), 3.78 (s, 3H), 3.10 - 3.07 (m, 1H), 2.92 - 2.87 (m, 1H), 2.65 - 2.58 (m, 1H), 1.97 - 1.90 (m, 1H), 1.76 (m, 1H), 1.69 - 1.58 (m, 2H), 1.55 - 1.34 (m, 3H). 720 [00848]embedded image 675.2 Method-D, RT = 1.799 min, 93.08% .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.5 Hz, 1H), 7.95 - 7.86 (m, 2H), 7.82 - 7.78 (m, 1H), 7.35 (t, J = 72 Hz, 1H), 7.32 - 7.24 (m, 2H), 6.83 - 6.75 (m, 2H), 6.71 - 6.67 (m, 1H), 5.07 (dd, J = 11.0, 8.5 Hz, 1H), 4.54 - 4.43 (m, 1H), 4.11 (q, J = 10.0 Hz, 1H), 3.99 - 3.92 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 3.07 -2.99 (m, 2H), 2.57 - 2.53 (m, 1H), 2.25 -2.13 (m, 4H), 1.80 - 1.72 (m, 4H), 1.07 (s, 6H). 721 [00849]embedded image 558.2 Method D, RT = 1.608 min, 97%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ = 9.08 (d, J = 8.5 Hz, 1H), 8.64 (s, 1H), 8.13 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 6.78 (d, J = 10.5 Hz, 2H), 5.25 - 5.16 (m, 1H), 5.12 (dd, J = 11.0, 8.5 Hz, 1H), 4.17 - 4.05 (m, 1H), 4.01 -3.92 (m, 2H), 3.77 (s, 3H), 3.06 (td, J = 8.6, 3.3 Hz, 1H), 2.94 (d, J = 11.5 Hz, 1H), 2.58 - 2.53 (m, 1H), 2.47 - 2.38 (m, 1H), 2.32 (s, 3H), 2.28 - 2.19 (m, 1H), 1.94 - 1.79 (m, 1H).

    [0302] It will be evident to one skilled in the art that the present disclosure is not limited to the foregoing illustrative examples, and that it can be embodied in other specific forms without departing from the essential attributes thereof. It is therefore desired that the examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing examples, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.