Quinoline derivatives and preparation thereof

Abstract

The patent discloses novel quinoline derivatives of formula (I), (Formula should be inserted here) and process for preparing the same. The compounds of formula (I) can be further used for the synthesis of Inhibitors like Kinase Tyrosine Inhibitors. ##STR00001##

Claims

1. A compound of formula (I), ##STR00040## or pharmaceutically acceptable salts, thereof, wherein: R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, OR.sup.aO, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety; R.sup.3 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, R(O)C, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano; R.sup.4 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano; when R.sup.3 is CO.sub.2R.sup.c and R.sup.4 is H then R.sup.2 is selected from mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety; R represents alkoxy (OR.sup.a), alkyl (linear and branched), cycloalkyl, aryl (which may be further substituted); R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl; and R.sup.c is selected from methyl or ethyl, wherein the compound of formula (I) is: ##STR00041## ##STR00042## ##STR00043## or pharmaceutically acceptable salts, thereof.

2. A process for the preparation of compound of formula (I) as claimed in claim 1, wherein the process is a rhodium (I) catalyzed process for the preparation of novel quinoline derivatives of formula (I) from aniline compounds of formula (IIA) and (IIB), ##STR00044## wherein: R.sup.1 is selected from H or ##STR00045## R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, OR.sup.aO, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety; R.sup.3 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, R(O)C, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano; R.sup.4 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano; R represents alkoxy (OR.sup.a), alkyl (linear and branched), cycloalkyl, aryl (which may be further substituted); R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl; wherein the process is for the preparation of the compound of formula Ia-Ir comprising Rhodium(I)-catalyzed stereo- and regio-selective CH alkenylation of anilines with alkynes followed by the sequential carbonylation to give novel quinoline derivative of formula (Ia-Ir); and wherein the process comprises the steps of: a) mixing Rhodium complexes as catalyst, ligand, an amine of formula IIA or IIB and water as solvent; b) adding paraformaldehyde to the solution of step (a); c) heating the solution of step (b) at the temperature 100 C. with stirring for the period ranging from 12 to 24 hrs under closed conditions; d) cooling to 25-30 C., and the reaction mixture is diluted with water (6 mL) and extracted with organic solvent; and e) removing solvent followed by purification to afford formula of (I).

3. The process as claimed in claim 2, wherein the compound of formula IIB is: (E)-2-(1,2-diphenylvinyl)-5-methoxyaniline (IIBA); (E)-2-(1,2-diphenylvinyl)-4-methoxyaniline (IIBB); (E)-5-methyl-2-(1-phenylprop-1-en-2-yl)aniline (IIBC); (E)-4-methyl-2-(1-phenylprop-1-en-2-yl)aniline (IIBD); (E)-5-chloro-2-(1,2-diphenylvinyl)aniline (IIBE); (E)-5-bromo-2-(1,2-diphenylvinyl)aniline (IIBF); (E)-4-bromo-2-(1-phenylprop-1-en-2-yl)aniline (IIBG); (E)-4-methoxy-2-(1-phenylprop-1-en-2-yl)aniline (IIBH).

4. The process as claimed in claim 2, wherein the process comprises mixing of methyl or ethyl propiolate in step (a).

5. The process as claimed in claim 2, wherein the catalyst is (1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl].sub.2).

6. The process as claimed in claim 2, wherein the ligand is 1,1-bis(diphenylphosphino)methane (dppm).

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

(2) In view of above the present invention provides novel quinoline derivatives and process for preparing the same.

(3) In an embodiment, the present invention provides a novel quinoline derivative of formula (I),

(4) ##STR00012##

(5) wherein: R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, OR.sup.aO, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety;

(6) R.sup.3 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, R(O)C, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(7) R.sup.4 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(8) R.sup.3 is CO.sub.2R.sup.c and R.sup.4 is H then R.sup.2 is selected from mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety;

(9) R represents alkoxy (OR.sup.a), alkyl (linear and branched), cycloalkyl, aryl (which may be further substituted);

(10) R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl;

(11) And R.sup.c is selected from methyl or ethyl.

(12) In a preferred embodiment, the present invention provides novel quinoline derivative of formula (I), wherein the compound of formula I is preferably selected from:

(13) ##STR00013## ##STR00014##

(14) In another embodiment, the present invention provides a rhodium (I) catalyzed process for the preparation of novel quinoline derivatives of formula (I) from aniline compounds of formula (II),

(15) ##STR00015##

(16) wherein:

(17) R.sup.1 is selected from H or

(18) ##STR00016##

(19) R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, OR.sup.aO, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety;

(20) R.sup.3 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, R(O)C, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(21) R.sup.4 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl. and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(22) R represents alkoxy (OR.sup.a), alkyl (linear and branched), cycloalkyl, aryl (which may be further substituted);

(23) R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl.

(24) The above process for preparation of novel quinoline derivative of formula (I) is shown below in Scheme A:

(25) ##STR00017##

(26) wherein:

(27) R.sup.1 is selected from H or

(28) ##STR00018##

(29) If R.sup.1 is H then, X is added selected from R.sup.3CCR.sup.4;

(30) R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, OR.sup.aO, O(R.sup.a).sub.nO (crown ether type and long/short chain poly ethers), NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety;

(31) R.sup.3 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, R(O)C, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(32) R.sup.4 is selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano;

(33) R represents alkoxy (OR.sup.a), alkyl (linear and branched), cycloalkyl, aryl (which may be further substituted);

(34) R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl.

(35) In a preferred embodiment, the present invention provides a process for preparation of novel quinoline derivative of formula (I) from aniline compounds of formula (IIA),

(36) ##STR00019##

(37) wherein R.sup.2 is as described above;

(38) comprising rhodium(I)-catalyzed stereo- and regio-selective CH alkenylation of anilines with alkynes that imparts Heck-type intermediate followed by the sequential carbonylation to give novel quinoline derivative of formula (I).

(39) In a more preferred embodiment, the present invention provides a process for preparation of novel quinoline derivative of formula (Ia-Ir) from aniline compounds of formula (IIAa-IIAr),

(40) ##STR00020##

(41) wherein R.sup.2 is as described above;

(42) comprising rhodium(I)-catalyzed stereo- and regio-selective CH alkenylation of anilines with alkynes that imparts Heck-type intermediate followed by the sequential carbonylation to give novel quinoline derivative of formula (I).

(43) In another more preferred embodiment, the present invention provides a process for preparation of Ia (methyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate) from IIAa as shown below in Scheme B.

(44) ##STR00021##

(45) In another preferred embodiment, the present invention provide a process for preparation of novel quinoline derivative of formula (I) from aniline compounds of formula (IIB),

(46) ##STR00022##

(47) wherein R.sup.2, R.sup.3 and R.sup.4 are as described above;

(48) comprising rhodium (I)-catalyzed sequential carbonylation followed by cyclization to give novel quinoline derivative of formula (I).

(49) The above process for preparation of novel quinoline derivatives of formula (I) is shown below in scheme C:

(50) ##STR00023##

(51) wherein;

(52) R.sup.2 represents mono, di or tri substituents, wherein each such substituent is independently selected from the group consisting of H, alkyl (linear or branched), cycloalkyl, OR.sup.a, NR.sup.aR.sup.b, NHR.sup.a, alkylamino (mono or di), arylamino (mono or di), SR.sup.a, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3) cyano, an inorganic support and a polymeric moiety.

(53) R.sup.3 and R.sup.4 are each independently selected from the group consisting of H, alkyl (linear or branched), alkenyl, allyl, proporgyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, and alkylheteroaryl, alkenyl, alkynyl, halogen, trifluromethyl, nitro, amide, ester (CO.sub.2R.sup.a, OC(O)R.sup.a, OC(O)CF.sub.3, OSO.sub.2R.sup.a, OSO.sub.2CF.sub.3), and cyano.

(54) R.sup.a and R.sup.b are each independently selected from the group consisting of alkyl (linear and branched), alkenyl, alkynyl, cycloalkyl, aryl (which may be further substituted), heteroaryl, and alkylaryl.

(55) In a more preferred embodiment, the present invention provides a process for the preparation quinoline compounds of formula (IA-H) from aniline compound of formula (IIBA-H).

(56) The above process is shown below in Scheme D.

(57) ##STR00024##

(58) wherein R.sup.2, R.sup.3 and R.sup.4 are as described above.

(59) In yet another preferred embodiment, the present invention provide a process for preparation of .sup.13C labeled quinoline derivative of formula (I) by using .sup.13C labeled paraformaldehyde which shows .sup.13C label carbon at the 2-position of quinoline product and implies the involvement of paraformaldehyde in the final product.

(60) The reaction is as shown below in Scheme E:

(61) ##STR00025##

(62) In an aspect, the present invention provides a process for the preparation of compound of formula (I) selected from the following:

(63) ##STR00026## ##STR00027## ##STR00028##

(64) In another aspect the present invention provides a three-step synthetic process for 6,7-dihydroxyquinoline-3-carboxamide (8), a tyrosine kinase inhibitors (a potential drug molecule) with 54% (overall) yield using compound of formula Ij as shown below in Scheme F:

(65) ##STR00029##

(66) A one pot method for the synthesis of 3-substituted quinoline by using Rh (I) precursor which proceed through heck intermediate and also CO proxy is shown. In the reaction, use of paraformaldehyde as a CO proxy leads to the quinoline products with more effective yield.

(67) Moreover these one pot sequential methods only proceed by using water as a solvent, which is a green approach for synthetic purpose. The postulated mechanism for this sequential feeler proceeds through a region selective heck intermediate supported by CH activated Rh (III) hydride complex.

Synthesis of Compounds Ia-Ir

(68) A novel process for the synthesis of quinoline derivatives of formula Ia-Ir comprising the steps of: a. mixing Rhodium complexes as catalyst, ligand, an amine (formula II), a terminal alkyne (methyl or ethyl propiolate), and water as solvent; b. adding paraformaldehyde to step (a) solution; c. heating the solution of step (b) at the temperature 100 C. with stirring for 12-24 hrs under closed condition; d. cooling to 25-30 C., reaction mixture was diluted with water (6 mL) and extracted with organic solvent. e. removal of solvent followed by purification to afford formula of 1.

(69) The process as described above, wherein said catalyst is (1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl].sub.2)

(70) The process as described above, wherein said ligand is 1,1-bis(diphenylphosphino)methane (dppm)

Synthesis of compounds IA-IH

(71) A novel process for the synthesis of quinoline derivatives IA-IH comprising the steps of: a. mixing Rhodium complexes as catalyst, ligand, an amine (formula IIB-H), and water as solvent; b. adding paraformaldehyde to step (a) solution; c. heating the solution of step (b) at the temperature 100 C. with stirring for 24-48 hrs under closed condition; d. cooling to 25-30 C., reaction mixture was diluted with water (6 mL) and extracted with organic solvent. e. removal of solvent followed by purification to afford formula of 1.

(72) The process as described above, wherein said catalyst is (1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl].sub.2)

(73) The process as described above, wherein said ligand is 1,1-bis(diphenylphosphino)methane (dppm)

(74) The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

EXAMPLES

Example 1: General Procedure for this Rhodium-Catalysed Auto-Tandem Reaction

(75) To a 10 mL clean, oven-dried screw cap reaction tube was added [Rh(cod)Cl].sub.2 (2.5 mol %), dppm (10 mol %), an aniline (0.25 mmol), CO surrogate (paraformaldehyde) (0.75 mmol), an alkyne (0.275 mmol) and water (250 L) under argon atm. The reaction mixture was kept for heating at 100 C. for 12-24 hrs. After cooling to room temperature, reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

Example 2: General Procedure for Rhodium-Catalysed Carbonylation of Ortho-Vinylanilines

(76) To a 10 mL clean, oven-dried screw cap reaction tube was added [Rh(cod)Cl].sub.2 (2.5 mol %), dppm (10 mol %), ortho-vinylaniline (IIBA-H) (0.25 mmol), paraformaldehyde (0.75 mmol, 2.5 equiv) and water (250 L) under argon atm. The reaction mixture was heated at 100 C. for 24-48 hrs. After cooling at room temperature reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The combined organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated. The crude product was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluent to obtain desired compound (IA-H).

Example 3

(a) Synthetic Procedure for Synthesis of Compound Ia

(77) ##STR00030##

(78) To a 10 mL clean, oven-dried screw cap reaction tube was added chloro(1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl].sub.2) (2.5 mol %), 1,1-bis(diphenylphosphino)methane (dppm) (10 mol %), benzo[d][1,3]dioxol-5-amine (0.25 mmol), paraformaldehyde (0.75 mmol), methyl propiolate (0.275 mmol) and water (250 L) under argon atm. The reaction mixture was kept for heating at 100 C. for 12 hrs. After cooling to 25-30 C., reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under rotary evaporator. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system to obtain desired compound methyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate (Ia) with 95% isolated yield.

(b) Synthetic Procedure for Synthesis of Compound 1A

(79) ##STR00031##

(80) To a 10 mL clean, oven-dried screw cap reaction tube was added chloro(1,5-cyclooctadiene)rhodium(I) dimer (2.5 mol %), 1,1-bis(diphenylphosphino)methane (dppm) (10 mol %). (E)-2-(1,2-diphenylvinyl)-5-methoxyaniline (IIBA) (0.25 mmol), paraformaldehyde (0.75 mmol, 2.5 equiv) and water (250 L) under argon atm. The reaction mixture was heated at 100 C. for 24 hrs. After cooling 25-30 C., reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The combined organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under rotary evaporator. The crude product was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluent to obtain desired compound 7-methoxy-3,4-diphenylquinoline (IA) with 86% of isolated yield.

Example 4

a. Synthesis of IIAh and IIAi

(81) ##STR00032##

(82) Procedure (Method A): A mixture of IIAg (5 mmol), allyl or propargyl bromide (15 mmol), K.sub.2CO.sub.3 (20 mmol), EtOH (25 mL), and water (5 mL) was added to a 100 mL round bottom flask and stirred at 70 C. for 24 hrs until complete consumption of IIAg as judged by TLC. Then, the solvent was removed under reduced pressure and the product was extracted with ethyl acetate (10 mL3), and the combined organic layers were dried over anhydrous Na.sub.2SO.sub.4. The solvent was removed by evaporation under reduced pressure to afford the crude products of both mono- and bis-alkylated derivatives of IIAg. The crude products were subjected for hydrolysis of acetyl group without further purification.

(83) ##STR00033##

(84) Procedure (Method B): To a 15 mL oven dried screw capped tube were added alkylated products of IIAg and 17% of HCl (H.sub.2O:THF=1:1 by v/v) at room temperature. This reaction mixture was heated to 70 C. for 15 h. After cooling to room temperature the reaction mixture was neutralised with saturated NaHCO.sub.3 followed by extraction with ethyl acetate (10 mL3). The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and the solvent was removed by evaporation under reduced pressure. The crude products were isolated by silica gel column chromatography using petroleum ether and ethyl acetate as an eluent.

(85) ##STR00034##

(86) Procedure (Method C): In a 15 mL oven dry screw cap tube [RuCl.sub.2(p-cymene)].sub.2 (0.25 mmol, 5 mol %) and AgSbF.sub.6 (1 mmol, 20 mol %) were added under argon atmosphere. To that tube acetanilide (5 mmol), alkyne (5.5 mmol), pivolic acid (25 mmol, 5 equiv) and isopropanol (2.5 mL) were added. After that the reaction mixture was heated up to 100 C. for 12 h. Then the reaction mixture was cooling to room temperature and diluted by dichloromethane.

(87) Diluted reaction mixture then passed through celite pad and concentrated on rotavapor under reduce pressure. The crude product was purified through silica gel column chromatography by using pet ether and ethyl acetate as an eluent.

b

(88) ##STR00035##

(89) Procedure: Method-B was followed for hydrolysis of acetanilides (IIBA-H) to get ortho-alkenylated anilines (IIBA-H).

(90) ##STR00036##

(91) Procedure: A 100 mL Fischer-Porter tube was charged under nitrogen with [Rh(cod)Cl].sub.2 (2.5 mol %), dppm (10 mol %), IIAa (0.1 mmol), methyl propiolate 2a (0.11 mmol), and 250 L of solvent (THF or water). The Fischer-Porter tube was purged by three successive cycles of pressurization/venting with CO (5 psi), then pressurized with CO (3 atm). The solution was heated at 100 C. with stirring for 12 h. After cooling to 5 C. (ice/water), the excess CO was vented carefully and the reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The combined organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated. The crude product was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluent.

(92) ##STR00037##

(93) Procedure: A 100 mL Fischer-Porter tube was charged under nitrogen with [Rh(cod)Cl].sub.2 (2.5 mol %), dppm (10 mol %), IIBA (0.25 mmol), and water (500 L). The Fischer-Porter tube was purged by three successive cycles of pressurization/venting with CO (5 psi), then pressurized with CO (3 atm). The solution was heated at 100 C. with stirring for 24 h. After cooling to 5 C. (ice/water), the excess CO was vented carefully and the reaction mixture was diluted with water (6 mL) and extracted with ethyl acetate (35 mL). The combined organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated. The crude product was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluent.

(94) ##STR00038##

(95) Procedure: To an oven dried 15 mL screw cap reaction vial were added Ir (264 mg, 1 mmol), NH.sub.4Cl (53 mg, 1 mmol) followed by a saturated solution of NH.sub.3 in methanol. The reaction mixture was heated at 70 C. for 72 h. After cooling to ambient temperature and triturated with water to get analytically pure compound 7.

(96) ##STR00039##

(97) Procedure: To an oven dried 25 mL round bottle flask 87 mg of 6,7-dimethoxyquinoline-3-carboxamide (7) and 850 mg of pyridine.HCl were added and then the reaction mixture was kept for heating at 170 C. for 30 minutes. After heating the excess amount of pyridine.HCl was removed under high vacuum and the resulting solid was washed with ice cold water. The crude mixture was subjected for HRMS analysis (Supplementary Fig 92) to confirm the formation of 6,7-Dihydroxyquinoline-3-carboxamide (8).

Example 4: benzo[d][1,3]dioxol-5-amine (D[IIAa])

(98) Light brown liquid. .sup.1H NMR (400 MHz, Chloroform-d) 6.60 (s, 1H), 6.27 (s, IH), 6.11 (dt, J=8.0 Hz and 4.0 Hz, 0.23H), 5.84 (s, 2H), 3.44 (s, 2H). .sup.13C NMR (125.8 MHz) 148.14, 141.34, 141.27, 140.30, 108.52, 108.43, 106.82, 100.60, 98.02. HRMS (ESI) calcd. for C.sub.7H.sub.6DNO.sub.2 [M].sup.+: 138.0539; found: 138.0540.

Example 5: (E)-methyl 3-(6-aminobenzo[d][1,3]dioxol-5-yl)acrylate (3a)

(99) Yellow solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.77 (d, J=14.1 Hz, 1H), 6.87 (s, 1H), 6.26 (s, 1H), 6.17 (d, J=16.0 Hz, 1H), 5.91 (s, 2H), 3.87 (s, 2H), 3.79 (s, 3H). .sup.13C NMR (125.8 MHz) 168.04, 150.77, 142.33, 141.38, 139.47, 114.48, 112.15, 105.80, 101.19, 98.14, 51.54. HRMS (ESI) calcd. for C.sub.11H.sub.12NO.sub.4 [M+H].sup.+: 222.0688; found: 222.0692.

Example 6: Dimethyl 2-(6-aminobenzo[d][1,3]dioxol-5-yl)maleate (3c)

(100) Compound 3c was isolated by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 80:20) as eluent (both 4p and 3c are having same Rf value). Thus we obtained as an inseparable mixture (3c+4p; 1:1.16 by .sup.1H NMR). Combined yield: 28%. .sup.1H NMR (500 MHz, Chloroform-d) 8.55 (s, 1H), 7.47 (s, 1H), 7.16 (s, 1H), 6.21 (s, 2H), 4.1 (s, 3H), 4.0 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 167.36, 165.87, 153.22, 149.69, 148.60, 147.1, 124.72, 120.87, 120.52, 106.2, 103.2, 102.49, 53.18, 52.79. Due to mixture of 3c and 4p HRMS (ESI) was not recorded.

Example 7: Methyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate (Ia)

(101) Light yellow solid. Yield: 95% (54.8 mg) by procedure (a) and 61% (35.2 mg) by procedure (b). .sup.1H NMR (400 MHz, Chloroform-d) 9.22 (s, 1H), 8.61 (s, 1H), 7.41 (s, 1H), 7.12 (s, 1H), 6.14 (s, 2H), 3.98 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 166.10, 152.70, 148.76, 148.56, 148.10, 137.01, 124.02, 121.47, 106.0, 103.59, 102.18, 52.31. HRMS (ESI) calcd. for C.sub.12H.sub.10NO.sub.4 [M+H].sup.+: 232.0632; found: 232.0634.

Example 8: Methyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate ([13C]Ia)

(102) Eluent: petroleum ether/ethyl acetate (v/v 85:15). Colourless solid. Yield: 87% (50.4 mg). .sup.1H NMR (400 MHz, Chloroform-d) 9.25 (d, J=200.0 Hz, 1H), 8.64 (s, 1H), 7.43 (s, 1H), 7.13 (s, 1H), 6.17 (s, 2H), 4.01 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 166.17, 160.01, 152.72, 148.42, 148.15 (major), 147.86, 137.03, 105.96, 103.36, 102.22, 52.36. HRMS (ESI) calcd. for C.sub.11.sup.13CH.sub.10NO.sub.4 [M+H].sup.+: 233.0523, found: 233.0522. (The ratio of 4a: [.sup.13C]4a=7:93 based on .sup.1H NMR analysis).

Example 9: Methyl 6,7-dimethoxyquinoline-3-carboxylate (Ib)

(103) Pale yellow solid. Yield: 87% (53.7 mg). .sup.1H NMR (500 MHz, Chloroform-d) 9.29 (s, 1H), 8.71 (s, 1H), 7.50 (s, 1H), 7.16 (s, 1H), 4.09 (s, 3H), 4.06 (s, 3H), 4.02 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 166.22, 154.43, 150.42, 148.03, 147.36, 136.58, 122.54, 121.36, 107.88, 105.91, 56.32, 56.13, 52.29. HRMS (ESI) calcd. for C.sub.13H.sub.13NO.sub.4 [M].sup.+: 247.0845, found: 247.0849.

Example 10: Methyl 7-methoxyquinoline-3-carboxylate (Ic)

(104) Yield: 84% (21.8 mg, 0.12 mmol scale). .sup.1H NMR (200 MHz, Chloroform-d) 9.38 (s, 1H), 8.76 (s, 1H), 7.82 (d, J=10.0 Hz, 1H), 7.48 (s, 1H), 7.27 (dd, J=10.4 Hz and 4.2 Hz, 1H), 4.01 (s, 3H), 3.99 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 166.12, 162.73, 151.93, 150.51, 138.24, 130.17, 129.97, 122.05, 120.98, 120.86, 110.41, 107.45, 55.72, 52.33. HRMS (ESI) calcd. for C.sub.12H.sub.11NO.sub.3 [M+H].sup.+: 218.0817, found: 218.0823.

Example 11: Ethyl 6-methoxyquinoline-3-carboxylate (Id)

(105) Greenish yellow liquid. Yield: 32% (19 mg). .sup.1H NMR (500 MHz, Chloroform-d) 9.33 (s, 1H), 8.77 (s, 1H), 8.08 (d, J=10.1 Hz, 1H), 7.50 (dd, J=10.3 Hz and 3.2 Hz, 1H), 7.20 (s, 1H), 4.50 (q, J=7.2 Hz, 2H), 3.98 (s, 3H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 165.60, 158.32, 147.70, 146.10, 137.26, 130.83, 128.58, 124.72, 123.55, 106.02, 61.46, 55.66, 14.36. HRMS (ESI) calcd. for C.sub.13H.sub.13NO.sub.3 [M].sup.+: 231.0895, found: 231.0890.

Example 12: Methyl 7-(benzyloxy)quinoline-3-carboxylate(Ie)

(106) Compound Ie was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 90:10) as an eluent. Yellow solid. Yield: 85% (62.5 mg). .sup.1H NMR (400 MHz, Chloroform-d) 9.40 (s, 1H), 8.78 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.58 (s, 1H), 7.52 (d, J=8.2 Hz, 2H), 7.44 (m, 2H), 7.38 (t, J=8.0 Hz, 2H), 5.27 (s, 2H), 4.03 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 166.09, 161.78, 151.83, 150.51, 138.25, 135.96, 130.27, 128.74, 127.73, 122.17, 121.16, 121.09, 108.62, 70.43, 52.34. HRMS (ESI) calcd. for C.sub.18H.sub.16NO.sub.3 [M+H].sup.+: 294.1120, found: 294.1125.

Example 13: Methyl 2,3,5,6,8,9,11,12-octahydro-[1,4,7,10,13]pentaoxacyclopentadeca[2,3-g] quinoline-17-carboxylate (If)

(107) Compound If was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 20:80) as an eluent. Gray solid. Yield: 82% (77.4 mg). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.16 (s, 1H), 7.12 (s, 1H), 6.80 (s, 1H), 6.63 (s, 1H), 3.33 (s, 2H), 3.27 (s, 2H), 2.97 (s, 2H), 2.91 (s, 4H), 2.71 (s, 8H). .sup.13C NMR (100.6 MHz, DMSO-d.sub.6) 165.66, 153.65, 149.39, 147.12, 146.97, 136.24, 132.01, 130.54, 128.89, 122.29, 120.68, 108.24, 107.79, 70.31, 69.17, 68.15, 52.32. HRMS (ESI) calcd. for C.sub.19H.sub.24NO.sub.7 [M+H].sup.+: 378.1538, found: 378.1547.

Example 14: Methyl 7-acetamidoquinoline-3-carboxylate (Ig)

(108) Compound Ig was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 50:50) as an eluent. Pale yellow solid. Yield: 79% (48.2 mg). .sup.1H NMR (500 MHz, CDCl.sub.3/DMSO-d.sub.6 (1:1)) 9.48 (s, 1H), 8.39 (s, 1H), 7.92 (s, 1H), 7.62 (s, 1H), 7.10 (d, J=10.0 Hz, 1H), 6.95 (d, J=10.0 Hz, 1H), 3.09 (s, 3H), 1.30 (s, 3H). .sup.13C NMR (125.8 MHz, CDCl.sub.3/DMSO-d.sub.6) 167.23, 163.47, 148.57, 147.89, 140.60, 135.89, 127.76, 120.84, 119.27, 119.10, 113.76, 50.20, 22.36. HRMS (ESI) calcd. for C.sub.13H.sub.13N.sub.2O.sub.3 [M+H].sup.+: 245.0916, found: 245.0921.

Example 15: Methyl 7-(diprop-2-ynylamino)quinoline-3-carboxylate (Ih)

(109) Compound Ih was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 50:50) as an eluent. Gummy solid. Yield: 80% (55.7 mg). .sup.1H NMR (500 MHz, CDCl.sub.3) 9.35 (s, IH), 8.71 (s, 1H), 7.87 (d, J=10.1 Hz, 1H), 7.51 (s, 1H), 7.38 (dd, J=10.0 and 5.2 Hz, 1H), 4.33 (d, J=2.0 Hz, 4H), 4.01 (s, 3H), 2.33 (t, J=2.0 Hz, 2H). .sup.13C NMR (125.8 MHz, CDCl.sub.3) 166.24, 151.38, 150.73, 150.21, 138.20, 130.24, 120.57, 120.13, 118.01, 109.78, 78.33, 73.22, 52.25, 40.30. HRMS (ESI) calcd. for C.sub.17H.sub.15N.sub.2O.sub.2 [M+H].sup.+: 279.1124, found: 279.1128.

Example 16: Methyl 7-(allylamino)quinoline-3-carboxylate (Ii)

(110) Compound Ii was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 85:15) as an eluent. Viscous liquid. Yield: 73% (44.2 mg). .sup.1H NMR (200 MHz, Chloroform-d) 9.26 (s, 1H), 8.61 (s, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.08 (s, 1H), 6.97 (d, J=8.2 Hz, 1H), 5.95 (m, 1H), 5.35 (d, J=18.1 Hz, IH), 5.24 (d, J=8.0 Hz, IH), 3.97 (s, 3H), 3.75 (m, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 166.38, 152.12, 150.97, 150.54, 150.32, 138.17, 133.84, 130.11, 120.24, 119.14, 117.21, 104.93, 52.09, 45.95. HRMS (ESI) calcd. for C.sub.14H.sub.15N.sub.2O.sub.2 [M+H].sup.+: 243.1123, found: 243.1128.

Example 17: Ethyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate (Ik)

(111) Compound Ik was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 85:15) as an eluent. White solid. Yield: 90% (55.2 mg). .sup.1H NMR (400 MHz, Chloroform-d) 9.27 (s, 1H), 8.64 (s, 1H), 7.45 (s, IH), 7.17 (s, IH), 6.18 (s, 2H), 4.48 (q, J=7.4 Hz, 2H), 1.47 (t, J=8.0 Hz, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 165.68, 152.65, 148.79, 148.55, 148.55, 148.23, 124.06, 121.83, 105.96, 103.63, 102.19, 61.33, 14.36. HRMS (ESI) calcd. for C.sub.13H.sub.12NO.sub.4 [M+H].sup.+: 246.0763, found: 246.0761.

Example 18: sec-butyl [1,3]dioxolo[4,5-g]quinoline-7-carboxylate (II)

(112) Compound II was prepared according to the general procedure and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 85:15) as an eluent. Brown coloured solid. Yield: 85% (58.1 mg). .sup.1H NMR (200 MHz, Chloroform-d) 9.25 (s, 1H), 8.60 (s, 1H), 7.43 (s, 1H), 7.15 (s, 1H), 6.16 (s, 2H), 5.17 (q, J=6.2 Hz, 1H), 1.82-1.67 (m, 2H), 1.38 (d, J=6.0 Hz, 3H), 1.0 (t, J=6.0 Hz, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 165.55, 152.83, 148.95, 148.75, 148.49, 137.10, 124.31, 122.45, 106.18, 103.85, 102.40, 73.65, 29.19, 19.84, 10.00. HRMS (ESI) calcd. for C.sub.15H.sub.15NO.sub.4 [M+H].sup.+: 273.2839, found: 273.2843.

Example 19: Dimethyl [1,3]dioxolo[4,5-g]quinoline-7,8-dicarboxylate (In)

(113) Compound In was prepared according to the general procedure (24 h) and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 80:20) as an eluent. Pale yellow solid. Yield: 69% (50 mg). .sup.1H NMR (200 MHz, Chloroform-d) 9.25 (s, 1H), 7.46 (s, 1H), 7.07 (s, 1H), 6.20 (s, 2H), 4.10 (s, 3H), 4.0 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 167.75, 165.13, 152.94, 149.53, 149.11, 147.89, 140.76, 137.52, 117.67, 106.10, 102.57, 100.82, 53.19, 52.78. HRMS (ESI) calcd. for C.sub.14H.sub.12NO.sub.6 [M+H].sup.+: 290.0654, found: 290.0659.

Example 20: Diethyl [1,3]dioxolo[4,5-g]quinoline-7,8-dicarboxylate (Io)

(114) Compound Io was prepared according to the general procedure (24 h) and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 80:20) as an eluent. Yellow solid. Yield: 72% (57 mg). .sup.1H NMR (400 MHz, Chloroform-d) 9.21 (s, 1H), 7.41 (s, 1H), 7.05 (s, 1H), 4.54 (q, J=8.0 Hz, 2H), 4.41 (q, J=8.0 Hz, 2H), 4.13 (t, J=8.2 Hz, 3H), 4.1 (t, J=8.0 Hz, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 166.98, 164.37, 152.50, 149.14, 148.73, 147.74, 140.53, 120.24, 117.65, 105.89, 102.22, 100.48, 62.01, 61.54, 13.93, 13.81. HRMS (ESI) calcd. for C.sub.14H.sub.12NO.sub.6 [M+H].sup.+: 318.0970, found: 318.0972.

Example 21: [1,3]dioxolo[4,5-g]quinolin-7-yl(4-methoxyphenyl)methanone (Ip)

(115) Compound Ip was prepared according to the general procedure (20 h) and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 85:15) as eluent. White solid. Yield: 76% (58.4 mg). .sup.1H NMR (200 MHz, Chloroform-d) 9.06 (s, 1H), 8.37 (s, 1H), 7.87 (d, J=8.0 Hz, 2H), 7.46 (s, 1H), 7.16 (s, 1H), 7.01 (d, J=8.0 Hz, 2H), 6.17 (s, 2H), 3.92 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 193.57, 163.58, 152.59, 148.68, 148.40, 148.14, 136.94, 132.52, 129.92, 129.40, 124.04, 113.87, 105.84, 105.47, 103.64, 102.22, 100.88, 55.58. HRMS (ESI) calcd. for C.sub.18H.sub.14NO.sub.4 [M+H].sup.+: 308.0916, found: 308.0891.

Example 22: [1,3]dioxolo[4,5-g]quinolin-7-yl(2,4-dimethoxyphenyl)methanone (Iq)

(116) Compound Iq was prepared according to the general procedure (24 h) and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 85:15) as eluent. Colourless liquid. Yield: 72% (60.7 mg). .sup.1H NMR (500 MHz, Chloroform-d) 8.98 (s, 1H), 8.46 (s, 1H), 7.57 (d, J=10.0 Hz, 1H), 7.17 (s, 1H), 8.64 (dd, J=10.0 and 5.2 Hz, 1H), 6.55 (s, 1H), 6.19 (s, 2H), 5.88 (d, J=10.0 Hz, 1H), 3.93 (s, 3H), 3.71 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 164.17, 159.70, 137.03, 132.71, 130.27, 105.83, 105.45, 105.28, 103.91, 102.27, 100.94, 98.73, 55.64, 55.57. HRMS (ESI) calcd. for C.sub.19H.sub.16NO.sub.5 [M+H].sup.+: 338.1019, found: 338.1023.

Example 23: Ethyl 6,7-dimethoxyquinoline-3-carboxylate (Ir)

(117) Colourless liquid. Yield: 81% (53 mg). .sup.1H NMR (200 MHz, Chloroform-d) 9.27 (s, 1H), 8.86 (s, 1H), 7.47 (s, 1H), 7.13 (s, 1H), 4.46 (q, J=8.0 Hz, 2H), 4.07 (s, 3H), 4.03 (s, 3H), 1.46 (t, J=8.2 Hz, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 165.65, 154.21, 150.25, 148.04, 147.26, 136.32, 122.40, 121.55, 107.82, 105.82, 61.14, 56.20, 56.04, 14.27. HRMS (ESI) calcd. for C.sub.14H.sub.15NO.sub.4 [M].sup.+: 261.1001, found: 261.0994.

Example 24:7-methoxy-3,4-diphenylquinoline (IA)

(118) Eluent: petroleum ether/ethyl acetate (v/v 90:10). Colourless solid. Yield: 82% (63.8 mg). .sup.1H NMR (500 MHz, Chloroform-d) 8.94 (s, IH), 7.60 (d, J=8.0 Hz, IH), 7.54 (s, 1H), 7.37-7.36 (m, 3H), 7.26-7.24 (m, 3H), 7.23-7.21 (m, 2H), 7.18 (d, J=10.0 Hz, 2H), 7.15-7.17 (m, 1H), 4.02 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 160.42, 151.95.149.32, 145.55, 138.26, 136.45, 131.37, 130.48, 130.17, 128.12, 128.01, 127.76, 127.69, 126.84, 122.28, 119.85, 107.36, 55.59. HRMS (ESI) calcd. for C.sub.22H.sub.18NO [M+H].sup.+: 312.1377, found: 312.1383.

Example 25:7-methoxy-3,4-diphenylquinoline ([13C]IA)

(119) Eluent: petroleum ether/ethyl acetate (v/v 90:10). Colourless solid. Yield: 71% (55 mg). .sup.1H NMR (400 MHz, Chloroform-d) 8.94 (d, J=180.0 Hz, 1H), 7.6 (d, J=8.0 Hz, 1H), 7.54 (s, IH), 7.37-7.35 (m, 3H), 7.24 (t, J=8.0 Hz, 3H), 7.21 (dd, J=8.0 Hz and 4.0 Hz, 2H), 7.17 (dd, J=10.0 Hz and 4.2 Hz, 3H), 4.01 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 162.98, 160.43, 152.91 (major), 150.72, 149.25, 145.58, 138.24, 136.44, 131.6, 131.07, 130.47, 130.17, 128.13, 128.01, 27.77, 27.69, 126.85, 119.86, 107.35, 107.27, 55.60. HRMS (ESI) calcd. for C.sub.21.sup.13CH.sub.18NO [M+H].sup.+: 313.1416, found: 313.1416. (The ratio of the 6a:[.sup.13C]6a=6:94, based on .sup.1H NMR analysis).

Example 26:6-methoxy-3,4-diphenylquinoline (IB)

(120) Eluent: petroleum ether/ethyl acetate (v/v 95:5). Colourless solid. Yield: 74% (57.6 mg). .sup.1H NMR (500 MHz, Chloroform-d) 8.88 (s, 1H), 8.12 (d, J=10.1 Hz, 1H), 7.41 (dd, J=10.0 and 5.2 Hz, 1H), 7.38-7.35 (m, 3H), 7.26-7.22 (m, 5H), 7.19 (dd, J=10.0 Hz and 5.2 Hz, 2H), 6.97 (s, 1H), 3.76 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 158.06, 149.42, 144.25, 143.71, 138.33, 136.56, 133.43, 130.94, 130.4, 130.13, 128.25, 128, 127.69, 126.98, 121.43, 104.58, 55.38. HRMS (ESI) calcd. for C.sub.22H.sub.18NO [M+H].sup.+: 312.1377, found: 312.1383.

Example 27:4,7-dimethyl-3-phenylquinoline (IC)

(121) Eluent: petroleum ether/ethyl acetate (v/v 97:3). Yellow liquid. Yield: 72% (42 mg). .sup.1H NMR (400 MHz, Chloroform-d) 8.76 (s, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.92 (s, 1H), 7.52 (d, J=8.2 Hz, 2H), 7.49-7.27 (m, 4H), 2.63 (s, 3H), 2.60 (s, 3H). .sup.13C NMR (100.6 MHz, Chloroform-d) 151.49, 147.26, 140.37, 139.08, 138.80, 133.76, 129.98, 129.00, 128.94, 128.42, 127.45, 125.97, 123.93, 21.64, 15.58. HRMS (ESI) calcd. for C.sub.17H.sub.16N [M+H].sup.+: 234.1274, found: 234.1277.

Example 28:4,6-dimethyl-3-phenylquinoline (ID)

(122) Eluent: petroleum ether/ethyl acetate (v/v 97:3). Yellow liquid. Yield: 71% (41.4 mg). .sup.1H NMR (500 MHz, Chloroform-d) 8.76 (s, 1H), 8.06 (s, 1H), 7.88 (s, 1H), 7.60 (s, 1H), 7.52 (d, J=8.3 Hz, 2H), 7.47-7.43 (m, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 150.67, 145.56, 139.84, 138.85, 136.58, 134.46, 131.07, 129.97, 129.71, 128.91, 128.43, 127.92, 127.50, 123.23, 22.02, 15.63. HRMS (ESI) calcd. for C.sub.17H.sub.15N [M].sup.+: 233.1204, found: 233.1204.

Example 29:7-chloro-3,4-diphenylquinoline (IE)

(123) Eluent: petroleum ether/ethyl acetate (v/v 97:3). White solid. Yield: 80% (63.2 mg). .sup.1H NMR (500 MHz, Chloroform-d) 9.02 (s, 1H), 8.21 (s, 1H), 7.67 (s, 1H), 7.46 (s, 1H), 7.44-7.36 (m, 3H), 7.29-7.25 (m, 3H), 7.21-7.17 (m, 4H). .sup.13C NMR (125.8 MHz, Chloroform-d) 152.87, 147.97, 145.52, 137.69, 135.79, 135.03, 130.39, 130.06, 128.39, 128.29, 128.13, 128.04, 127.96, 127.80, 125.74. HRMS (ESI) calcd. for C.sub.21H.sub.14ClN [M].sup.+: 315.0818, found: 315.0815.

Example 30:7-bromo-3,4-diphenylquinoline (IF)

(124) Eluent: petroleum ether/ethyl acetate (v/v 97:3). White solid. Yield: 79% (71 mg). .sup.1H NMR (500 MHz, Chloroform-d) 9.01 (s, 1H), 8.39 (s, 1H), 7.58 (s, 2H), 7.38 (d, J=10.1 Hz, 3H), 7.29-7.26 (m, 3H), 7.20-7.17 (m, 4H). .sup.13C NMR (125.8 MHz, Chloroform-d) 152.32, 148.20, 145.62, 137.70, 135.74, 131.73, 130.42, 130.34, 130.06, 128.30, 128.15, 128.11, 127.99, 127.26, 126.03, 123.32. HRMS (ESI) calcd. for C.sub.21H.sub.14BrN [M].sup.+: 359.0311, found: 359.031.

Example 31:6-bromo-4-methyl-3-phenylquinoline (IG)

(125) Eluent: petroleum ether/ethyl acetate (v/v 95:5). Yield: 58% (from crude mixture by .sup.1H NMR). .sup.1H NMR (500 MHz, Chloroform-d) 8.84 (s, 1H), 8.31 (s, 1H), 8.16 (d, J=10.0 Hz, 1H), 7.87 (d, J=10.0 Hz, 1H), 7.55 (t, J=5.4 Hz, 2H), 7.49 (t, J=10.2 Hz, 1H), 7.42-7.38 (m, 2H), 2.67 (s, 3H). Due to inseparable mixture of (5g and product 6g) .sup.13C NMR was not recorded. HRMS (ESI) calcd. for C.sub.16H.sub.13NBr [M+H].sup.+: 298.0221, found: 298.0226.

Example 32:N,N-di(prop-2-ynyl)benzene-1,3-diamine (IIAh)

(126) Compound IIAh was prepared according to the general procedure as described above (method A and method B) using proporgyl bromide as an alkylating agent and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 90:10) as an eluent.

(127) Brown liquid. Yield: 48%. .sup.1H NMR (400 MHz, Chloroform-d) 7.09 (t, J=8.0 Hz, 1H), 6.42 (dd, J=8.4 Hz and 5.0 Hz, 1H), 6.31 (s, 1H), 6.26 (dd, J=8.4 Hz and 5.1 Hz, 1H), 4.11 (s, 4H), 3.67 (s, 2H, NH.sub.2), 2.28 (s, 2H). .sup.13C NMR (100.6 MHz, Chloroform-d) 149.02, 147.39, 130.01, 107.18, 106.41, 102.58, 79.46, 72.59, 40.36. HRMS (ESI) calcd. for C.sub.12H.sub.13N.sub.2 [M+H].sup.+: 185.1070; found: 185.1073.

Example 33: N-allylbenzene-1,3-diamine (IIAi)

(128) Compound IIAi was prepared according to the general procedure (method A and B) as described above using allyl bromide as an alkylating agent and was purified by silica gel column chromatography using petroleum ether/ethyl acetate (v/v 90:10) as an eluent.

(129) Brown liquid. Yield: 37%. .sup.1H NMR (500 MHz, Chloroform-d) 7.01 (t, J=10.0 Hz, 1H), 6.13 (d, J=10.1 Hz, 2H), 6.01-5.99 (m, 2H), 5.33 (d, J=19.2 Hz, 1H), 5.21 (d, J=10 Hz, 1H), 3.78 (t, 0.1=5.2 Hz, 2H), 3.58 (s, 2H). 13C NMR (125.8 MHz, Chloroform-d) 149.15, 147.39, 135.54, 129.88, 115.90, 104.92, 103.99, 99.59, 46.39. HRMS (ESI) calcd. for C.sub.9H.sub.13N.sub.2 [M+H].sup.+: 149.1073; found: 149.1073.

Example 34: (E)-N-(2-(1,2-diphenylvinyl)-5-methoxyphenyl)acetamide (IIBA)

(130) Compound IIBA was prepared from 3-methoxy acetanilide and diphenylacetylene by Method C. Light brown solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.99 (s, 1H), 7.36-7.30 (m, 6H), 7.19-7.14 (m, 5H), 7.05 (d, J=10 Hz, 2H), 6.68 (d, J=10.2 Hz, 1H), 3.85 (s, 3H), 1.74 (s, 3H). .sup.13C NMR (50.3 MHz, Chloroform-d) 168.25, 159.97, 142.26, 137.48, 136.58, 136.45, 131.57, 130.27, 128.88, 128.73, 128.54, 128.20, 127.92, 127.02, 121.43, 11.05, 106.2, 55.41, 24.57. HRMS (ESI) calcd. for C.sub.23H.sub.21NO.sub.2Na [M+Na].sup.+: 366.1461; found: 366.1465.

Example 35: (E)-N-(2-(1,2-diphenylvinyl)-4-methoxyphenyl)acetamide (IIBB)

(131) Compound IIBB was prepared from 4-methoxy acetanilide and diphenylacetylene by Method C. White solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.77 (d, J=8.0 Hz, 1H), 7.28-7.25 (m, 5H), 7.22-7.16 (m, 5H), 6.96 (s, 1H), 6.89 (dd, J=8.4 Hz, 1H), 6.78 (s, 1H), 6.69 (s, 1H), 3.82 (s, 3H), 1.69 (s, 3H). .sup.13C NMR (100.6 MHz) 167.96, 156.59, 139.79, 139.17, 137.06, 136.60, 132.02, 129.56, 129.51, 129.31, 128.42, 128.18, 128.06, 127.38, 125.01, 116.31, 113.58, 55.55, 23.79. HRMS (ESI) calcd. for C.sub.23H.sub.21NO.sub.2Na [M+Na].sup.+: 366.1454; found: 366.1465.

Example 36: (E)-N-(5-methyl-2-(1-phenylprop-1-en-2-yl)phenyl)acetamide (IIBC)

(132) Compound IIBC was prepared from 3-methyl acetanilide and 1-phenyl-1-propyne by Method C. White solid. .sup.1H NMR (200 MHz, Chloroform-d) 8.07 (s, 1H), 7.45-7.39 (m, 5H), 7.32 (t, J=8.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.97 (d, J=8.0 Hz, 1H), 6.52 (s, 1H), 2.40 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H). .sup.13C NMR (100.6 MHz) 168.10, 137.88, 137.11, 135.61, 133.92, 133.16, 131.14, 128.90, 128.44, 128.07, 127.08, 125.21, 122.14, 24.75, 21.41, 19.91. HRMS (ESI) calcd. for C.sub.18H.sub.19NONa [M+Na].sup.+: 288.1355: found: 288.1359.

Example 37: (E)-N-(4-methyl-2-(1-phenylprop-1-en-2-yl)phenyl)acetamide (IIBD)

(133) Compound IIBD was prepared from 4-methyl acetanilide and 1-phenyl-1-propyne by Method C. White solid. .sup.1H NMR (200 MHz, Chloroform-d) 8.02 (d, J=8.1 Hz, 1H), 7.41-7.25 (m, 6H), 7.09 (d, J=8.0 Hz, 1H), 7.04 (s, 1H), 7.49 (s, 1H), 2.33 (s, 3H), 2.21 (s, 3H), 2.12 (s, 3H). .sup.13C NMR (50.3 MHz) 168.21, 131.11, 136.30, 135.78, 133.97, 131.51, 131.01, 128.95, 128.47, 127.12, 122.03, 24.64, 20.93, 19.83.

Example 38: (E)-N-(5-chloro-2-(1,2-diphenylvinyl)phenyl)acetamide (IIBE)

(134) Compound IIBE was prepared from 3-chloro acetanilide and diphenylacetylene by Method C. White solid. .sup.1H NMR (200 MHz, Chloroform-d) 8.18 (s, 1H), 7.33-7.25 (m, 5H), 7.20 (d, J=8.0 Hz, 2H), 7.19-7.15 (m, 5H), 7.10 (s, 1H), 6.76 (s, 1H), 1.71 (s, 3H). .sup.13C NMR (50.3 MHz) 168.81, 138.62, 138.45, 136.20, 134.31, 132.53, 132.34, 131.57, 129.46, 129.35, 129.12, 128.31, 128.16, 127.51, 124.23, 121.89, 14.06.

Example 39: (E)-N-(5-bromo-2-(1,2-diphenylvinyl)phenyl)acetamide (IIBF)

(135) Compound IIBF was prepared from 3-bromo acetanilide and diphenylacetylene by Method C. Pale white solid. 1H NMR (500 MHz, Chloroform-d) 8.58 (s, 1H), 7.37 (t, J=10.0 Hz, 2H), 7.34 (d, J=10.2 Hz, 2H), 7.29 (s, 1H), 7.25-7.22 (m, 5H), 7.18 (s, 1H), 7.10-7.08 (m, 2H), 7.04 (d, J=10 Hz, 1H), 1.80 (s, 3H). .sup.13C NMR (50.3 MHz) 168.05, 141.22, 136.62, 135.85, 132.02, 130.84, 129.84, 129.39, 129.15, 128.80, 128.59, 128.39, 128.18, 127.56, 126.80, 124.06, 121.28, 117.77, 113.57, 24.35.

Example 40: (E)-N-(4-bromo-2-(1-phenylprop-1-en-2-yl)phenyl)acetamide (IIBG)

(136) Compound IIBG was prepared from 4-bromo acetanilide and 1-Phenyl-1-propyne by Method C. White solid. .sup.1H NMR (500 MHz, Chloroform-d) 8.12 (s, 1H), 7.52 (s, 1H), 7.44 (t, J=10.2 Hz, 2H), 7.40 (d, J=10 Hz, 4H), 7.33 (t, J=6.0 Hz, 1H), 6.53 (s, 1H), 2.23 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (125.8 MHz) 168.26, 137.95, 136.56, 134.19, 133.34, 132.07, 131.13, 130.73, 128.95, 128.55, 127.47, 123.37, 117.01, 24.67, 19.61.

Example 41: (E)-2-(1,2-diphenylvinyl)-5-methoxyaniline (IIBA)

(137) Gray solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.38 (d, J=8.0 Hz, 2H), 7.29-7.26 (m, 3H), 7.17-7.08 (m, 5H), 7.05 (s, 1H), 6.87 (d, J=8.0 Hz, 1H), 6.32 (dd, J=8.1 Hz, 4 Hz, 1H), 6.26 (s, 1H), 3.75 (s, 3H), 3.56 (s, 2H). .sup.13C NMR (50.3 MHz) 160.47, 145.39, 138.73, 137.22, 132.05, 129.52, 129.39, 129.08, 128.59, 128.34, 127.82, 127.31, 126.91, 126.19, 118.34, 101.48, 101.19, 55.17. HRMS(ESI) calcd. for C.sub.21H.sub.20NO [M+H].sup.+: 302.1536; found: 302.1539.

Example 42: (E)-2-(1,2-diphenylvinyl)-4-methoxyaniline (IIBB)

(138) Gray solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.26-7.20 (m, 5H), 7.17-7.09 (m, 5H), 6.77 (s, 1H), 6.71 (dd, J=8.4 Hz and 3.7 Hz, 2H), 6.57 (dd, J=9.1 Hz and 3.5 Hz, 1H), 3.72 (s, 3H), 3.28 (s, 2H). .sup.13C NMR (50.3 MHz) 152.33, 140.64, 137.87, 136.96, 130.82, 130.65, 129.61, 129.38, 128.89, 128.55, 128.45, 128.16, 127.94, 127.60, 126.83, 126.62, 117.15, 116.27, 114.52, 55.64. HRMS (ESI) calcd. for C.sub.21H.sub.20NO [M+H].sup.+: 302.1467; found: 302.1468.

Example 43: (E)-5-methyl-2-(1-phenylprop-1-en-2-yl)aniline (IIBC)

(139) Brown coloured liquid. .sup.1H NMR (200 MHz, Chloroform-d) 7.38-7.34 (m, 4H), 7.26 (dt, J=8.4 Hz and 3.8 Hz, 1H), 7.0 (d, J=8.4 Hz and 4.0 Hz, 1H), 6.60 (d, J=8.2 Hz and 4.0 Hz, 1H), 6.57-6.54 (m, 2H), 3.76 (s, 2H), 2.28 (s, 3H), 2.22 (s, 3H). .sup.13C NMR (100.6 MHz) 142.73, 137.78, 137.72, 136.52, 129.72, 129.89, 128.79, 128.54, 126.18, 126.50, 119.21, 116.28, 21.12, 19.25. HRMS (ESI) calcd. for C.sub.18H.sub.18N [M+H].sup.+: 224.1430; found: 224.1434.

Example 44: (E)-4-methyl-2-(1-phenylprop-1-en-2-yl)aniline (IIBD)

(140) Brown coloured liquid. .sup.1H NMR (200 MHz, Chloroform-d) 7.39-7.36 (m, 4H), 7.26 (dd, J=10.1 Hz and 3.8 Hz, 1H), 6.91 (d, J=8.0 Hz, 2H), 6.65 (d, J=8.1 Hz, 1H), 6.54 (s, 1H), 3.66 (s, 2H), 2.26 (s, 3H), 2.23 (s, 3H). .sup.13C NMR (125.8 MHz) 140.30, 137.73, 136.73, 131.62, 129.77, 129.14, 128.92, 128.44, 128.21, 127.59126.57, 115.81, 20.43, 19.18. HRMS (ESI) calcd. for C.sub.16H.sub.17N [M].sup.+: 223.1362; found: 223.1361.

Example 45: (E)-5-chloro-2-(1,2-diphenylvinyl)aniline (IIBE)

(141) White solid. .sup.1H NMR (200 MHz, Chloroform-d) 7.27-7.21 (m, 5H), 7.17-7.13 (m, 3H), 7.13 (d. J=8.0 Hz, 2H), 7.07-7.04 (m, 1H), 6.75 (s, 1H), 6.72 (dd, J=8.0 Hz, 4.1 Hz, 1H), 6.63 (s, 1H), 3.68 (s, 2H). .sup.13C NMR (50.3 MHz) 145.34, 139.61, 139.13, 136.81, 132.10, 130.35, 129.59, 129.45, 128.70, 128.02, 127.81, 127.00, 118.13, 115.40. HRMS (ESI) calcd. for C.sub.20H.sub.16ClN [M].sup.+: 305.0972; found: 305.0971.

Example 46: (E)-5-bromo-2-(1,2-diphenylvinyl)aniline (IIBF)

(142) White solid. .sup.1H NMR (500 MHz, Chloroform-d) 7.41 (d, J=10 Hz, 2H), 7.36 (t, J=10.1 Hz, 3H), 7.25-7.20 (m, 3H), 7.16 (d, J=10.0 Hz, 2H), 6.91 (d, J=10.0 Hz, 2H), 6.89 (s, 1H), 3.69 (s, 2H). .sup.13C NMR (125.8 MHz) 145.54, 141.37, 137.72, 136.68, 132.47, 129.95, 129.65, 128.98, 128.61, 128.35, 127.99, 127.54, 126.70, 124.22, 121.77, 118.28. HRMS (ESI) calcd. for C.sub.20H.sub.16BrN [M].sup.+: 349.0466; found: 349.0469.

Example 47: (E)-4-bromo-2-(1-phenylprop-1-en-2-yl)aniline (IIBG)

(143) Semi-solid. .sup.1H NMR (400 MHz, Chloroform-d) 7.44-7.39 (m, 4H), 7.30 (t, J=8.2 Hz, 1H), 7.25 (s, 1H), 7.21 (dd, J=8.2 Hz and 3.8 Hz, 1H), 6.64 (d, J=8.0 Hz, 1H), 6.58 (s, 1H), 3.81 (s, 2H), 2.23 (s, 3H). .sup.13C NMR (100.6 MHz) 142.09, 137.27, 136.37, 133.35, 131.25, 130.72, 130.58, 128.97, 128.34, 126.94, 117.13, 110.15, 18.98.

Example 48:6,7-dimethoxyquinoline-3-carboxamide (7)

(144) Yellow solid. Yield: 86%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.19 (s, 1H), 7.75 (s, 1H), 7.29 (s, 1H), 6.63 (s, 1H), 6.52 (s, 1H), 6.50 (s, 1H), 3.06 (s, 3H), 3.03 (s, 3H). .sup.13C NMR (100.6 MHz, DMSO-d.sub.6) 166.94, 153.48, 149.95, 146.61, 145.99, 133.94, 125.11, 122.17, 107.43, 106.35, 55.88, 55.80. HRMS (ESI) calcd. for C.sub.12H.sub.13N.sub.2O.sub.3 [M+H].sup.+: 233.0918, found: 233.0937.

Example 49: Methyl 7-methoxy-2-(2-methoxy-2-oxoethyl)quinoline-3-carboxylate (9)

(145) Yellow solid. Yield: 31%. .sup.1H NMR (500 MHz, Chloroform-d) 8.79 (s, 1H), 7.79 (d, J=10.0 Hz, IH), 7.41 (s, 1H), 7.24 (dd, J=10.0 Hz and 5.2 Hz, IH), 4.43 (s, 2H), 3.96 (s, 3H), 3.95 (s, 3H), 3.74 (s, 3H). .sup.13C NMR (125.8 MHz, Chloroform-d) 171.38, 166.46, 162.88, 154.94, 150.73, 140.11, 129.67, 121.48, 120.72, 106.90, 55.68, 52.28, 52.00, 44.51. HRMS (ESI) calcd. for C.sub.15H.sub.16NO.sub.5 [M+H].sup.+: 290.1018, found: 290.1023.

Advantages of the Invention

(146) Effective synthesis of biologically active quinolines derivatives.

(147) Carbon monoxide free carbonyl source.

(148) Water is used as solvent.

(149) One pot, single step simple process.