Tricyclic compound and use thereof as mat2a inhibitor

Abstract

The present application relates to a tricyclic compound and use thereof as an MAT2A inhibitor.

Description

Tricyclic compounds and their use as MAT2A inhibitors

[0001] The present application relates to a tricyclic compound and its use as a MAT2A inhibitor.

[0002] Methionine adenosyltransferase 2A (MAT2A) is the primary enzyme that generates S-adenosylmethionine (SAM) from methionine and adenosine triphosphate (ATP) within cells. Also known as the rate-limiting enzyme in the methionine cycle, MAT2A generates SAM, which methylates nucleic acids, phospholipids, histones, biogenic amines, and proteins, and is involved in the synthesis of polyamines and glutathione. Therefore, MAT2A is known to significantly influence cell growth, differentiation, and function by regulating SAM.

[0003] In particular, MAT2A has been reported as a target that exhibits vulnerability in MTAP (Methylthioadenosine Phosphorylase)-deficient cancers. MTAP is an enzyme that degrades methylthioadenosine (MTA). MTAP deletion leads to the accumulation of MTA in cancer cells, and the increased MTA partially inhibits the activity of PRMT5 (Protein arginine methyl transferase 5). In MTAP-deficient cancers with suppressed PRMT5 activity, MAT2A, which produces SAM, a cofactor for PRMT5, may indirectly influence signaling upstream of PRMT5 and contribute to its vulnerability. Accordingly, MAT2A inhibitors are being developed as targets of MTAP-deficient synthetic lethality. Preclinical studies have demonstrated dose-dependent reductions in tumor SAM levels and tumor growth inhibition in xenograft models. In clinical studies, MAT2A inhibitors have also been shown to reduce plasma SAM across a range of doses in patients with advanced solid tumors with homozygous deletions of MTAP, and are therefore being investigated as treatments for MTAP-deficient cancers.

[0004] However, the initially developed MAT2A inhibitor, AG-270, was observed to cause liver damage due to UGT1A1 inhibition in a phase 1 clinical study, and the MAT2A inhibitors developed later target MTAP-deficient cancers, which are observed at a high rate in glioblastoma (40%) and non-small cell lung cancer (15%), which frequently develop brain metastases. However, the inability to secure blood-brain barrier penetration of the drug remains an unmet medical need in clinical trials.

[0005] The present inventors have confirmed that a tricyclic compound according to an example of the present application, as a MAT2A inhibitor, inhibits MAT2A activity. Accordingly, one object of the present application is to provide a tricyclic ring-based compound of chemical formula 1, an optical isomer, a stereoisomer, an isotopic variant, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, which exhibits an excellent MAT2A activity inhibitory effect.

[0006] Another object of the present application is to provide a pharmaceutical composition comprising the above tricyclic ring-based compound, an optical isomer, a stereoisomer, an isotopic variant, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0007] According to one embodiment of the present application, there is provided a compound of the following formula 1, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof:

[0008] [Chemical Formula 1]

[0009]

[0010] In the above chemical formula 1,

[0011] A is , , , or And,

[0012] R2 is (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 1-6 )alkoxy, (C 1-6 )alkylsulfonyl, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, nitro, amino, acetyl, (C 1-6 )alkylamino, (C 1-6 )alkylcarbonyl, (C 1-6 )alkoxycarbonyl, aminocarbonyl, (C 1-6 )alkylaminocarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )hydroxyalkoxy, (C 1-6 )hydroxyalkylamino, (C 1-6 )alkoxy-(C 1-6 )alkyl, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )alkoxy-(C 1-6 )alkylamino, (C 1-6 )aminoalkyl, (C 1-6 )aminoalkoxy, (C 1-6)aminoalkylamino, 3- to 10-membered heteroaryl containing at least one heteroatom selected from N, O and S, 3- to 10-membered heteroaryloxy containing at least one heteroatom selected from N, O and S, 3- to 10-membered heteroarylamino containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyl containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyloxy containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclylamino containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyloxyalkoxy containing at least one heteroatom selected from N, O and S, or 3- to 10-membered heteroaryl containing at least one heteroatom selected from N, O and S Heterocyclyloxyalkylamino, wherein said heterocyclyl or said heteroaryl is unsubstituted or R a , R b , and R c is substituted with one or more of the R a , R b , and R c is independently (C 1-6 )alkyl, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy, hydroxy, halo, cyano, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy-(C 1-6 )alkyl, and (C 1-6 ) is selected from aminoalkyl;

[0013] R 3 is hydrogen, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 1-6)alkoxy, halo, halo(C 1-6 )alkyl-(C 1-6 )alkoxy, (C 1-6 )alkylsulfonyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, (C 1-6 )alkyloxy, cyano, amino, (C 1-6 )alkylamino, aminocarbonyl-(C 1-6 )alkylaminocarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )hydroxyalkoxy, (C 1-6 )hydroxyalkylamino, (C 2-6 )alkoxyalkyl, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )alkoxy-(C 1-6 )alkylamino, (C 1-6 )aminoalkyl, (C 1-6 )aminoalkoxy, (C 1-6 )aminoalkylamino, 3- to 10-membered heteroaryl containing at least one heteroatom selected from N, O and S, 3- to 10-membered heteroaryloxy containing at least one heteroatom selected from N, O and S, 3- to 10-membered heteroarylamino containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyl containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyloxy containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclylamino containing at least one heteroatom selected from N, O and S, 3- to 10-membered heterocyclyl-(C 1-6 )alkyloxy, 3- to 10-membered heterocyclyloxy-(C containing one or more heteroatoms selected from N, O and S 1-6)alkoxy, or a 3- to 10-membered heterocyclyloxy-(C containing one or more heteroatoms selected from N, O and S 1-6 )alkylamino, and the alkoxy, heterocyclyl or heteroaryl is unsubstituted or R a , R b , and R c is substituted with one or more of the R a , R b , and R c is independently (C 1-6 )alkyl, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy, hydroxy, halo, cyano, (C 1-6 )alkoxycarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy-(C 1-6 )alkyl, and (C 1-6 ) is selected from aminoalkyl;

[0014] R 4 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkenyl, (C 1-6 )alkynyl, (C 1-6 )alkoxy, (C 1-6 )alkyl-(C 1-6 )alkoxy, (C 1-6 )alkylthiol, (C 1-6 )alkylsulfonyl, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, amino, (C 1-6 )alkylamino, aminocarbonyl, or (C 1-6 ) is alkylaminocarbonyl;

[0015] R 1is a 5- to 20-membered mono- or bicyclic aryl or a 3- to 10-membered mono- or bicyclic heteroaryl containing one or more heteroatoms selected from N, O and S, wherein the aryl or heteroaryl is unsubstituted or has one or more substituents R d is replaced by;

[0016] R d is halo, oxo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 3-10 )cycloalkyl-(C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkylsulfonamide, 3- to 10-membered heteroaryl containing at least one heteroatom selected from N, O, and S, 3- to 10-membered heterocycloalkyl containing at least one heteroatom selected from N, O, and S, or phenyl;

[0017] R 5 and R 6 is independently hydrogen, halo, hydroxy, acetyl, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy(C 1-6 )alkyl, -(C 1-6 )alkyl-amino, aminocarbonyl, (C 1-6 )alkylaminocarbonyl, di(C 1-6 )alkylaminocarbonyl, aminocarbonyl(C 1-6 )alkyl, aminosulfonyl(C 1-6 )alkyl, (C 1-6 )alkoxy, -amino(C 1-6 )-alkyl, -amino-di(C 1-6 )alkyl, (C 1-6)alkylcarbonyl, or -(C 1-6 )alkyl-R e And,

[0018] The above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkylamino, or a 3- to 10-membered mono- or bicyclic heterocycle containing one or more heteroatoms selected from N, O and S, wherein R e is not substituted (C 1-6 ) may be substituted with alkyl or hydroxy.

[0019]

[0020] For example, the above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) may be an alkylcarbonyl.

[0021] For example, the above R 2 is (C 1-3 )alkyl, halo, acetyl, cyano, (C 3-6 )cycloalkyl, (C 1-3 )dihaloalkyl, (C 1-3 )trihaloalkyl, (C 1-3 )alkoxy, or (C 1-3 ) may be trihaloalkoxy.

[0022] For example, the above R 3 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C1-6 )haloalkoxy, halo(C 1-6 )alkyl(C 1-6 )alkoxy, halo(C 1-6 )alkyl, (C 1-6 ) may be alkylamino, or pyrrolidine.

[0023] For example, the above R 4 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, or (C 1-6 ) may be haloalkyl.

[0024] For example, the above R 1 is unsubstituted or has one or more, specifically 1 to 3, more specifically 1 or 2 substituents R d can be replaced with

[0025] For example, the above R 1 is one or more R d , specifically 1 to 3, more specifically 1 or 2 R d It may have been replaced with .

[0026] For example, the above R d is halo, oxo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 ) may be haloalkoxy, or (C1-C6)alkylsulfonamide.

[0027] For example, the above R 1 is phenyl, pyrazine, pyrazole, pyridine, indole, dihydrobenzofuran, or benzothiazole, and R 1 is unsubstituted or substituted with halo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6) may be substituted with haloalkoxy, or (C1-C6)alkylsulfonamide.

[0028] For example, the above R 1 is phenyl, pyrazine, pyrazole, pyridine, indole, dihydrobenzofuran, or benzothiazole, and R 1 Silver halo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 ) may be substituted with haloalkoxy, or (C1-C6)alkylsulfonamide.

[0029] For example, the above R 5 and R 6 is independently hydrogen, halo, hydroxy, acetyl, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy(C 1-6 )alkyl, amino(C 1-6 )alkyl, di(C 1-6 )alkylaminocarbonyl, (C 1-6 )alkoxy, (C 1-6 )alkylamino, di(C 1-6 )alkylamino, (C 1-6 )alkylamino(C 1-6 )alkyl, (C 1-6 )alkylamino(C 1-6 )alkylhydroxy, (C 1-6 )alkylamino(C 1-6 )alkyl(C 1-6 )alkoxy, or (C 1-6 ) may be an alkylcarbonyl.

[0030] For example, the above R 5 is hydrogen, halo, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 1-6 )alkyl-amino-, di(C 1-6 )alkyl-amino-, (C1-6 )haloalkyl, acetyl, or -CH2R e and the above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkyl-amino-, or a 3- to 10-membered mono- or bicyclic heterocycle containing one or more heteroatoms selected from N, O and S, wherein R e is unsubstituted or (C 1-6 ) may be substituted with alkyl or hydroxy.

[0031] For example, the above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkyl-amino-, azetidine, morpholine, piperazine, or heterospirocarbocyclyl, wherein R e is unsubstituted or (C 1-6 ) may be substituted with alkyl or hydroxy.

[0032] For example, the above R e may be methoxy, methylamine, hydroxyethylamine, methoxyethylamine, azetidine, 3-hydroxyazetidine, methylpiperazine, morpholine, or 2-oxa-7-azaspiro[3.5]nonane.

[0033] For example, the above R 6 Silver hydrogen, halo, (C1-6 )alkyl, (C 1-6 ) can be haloalkyl, acetyl, or hydroxy.

[0034] For example, the above A , , , , , or It could be.

[0035] Specifically, the above A may be any one selected from the group consisting of:

[0036]

[0037]

[0038]

[0039] More specifically, the above A may be any one selected from the group consisting of:

[0040]

[0041] For example, the above A , , or and the above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) may be alkylcarbonyl. The above R 2 may be fluoro, chloro, bromo, iodo, methyl, isopropyl, acetyl, cyano, nitro, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, or trifluoroethoxy

[0042] For example, the above A , , or and the above R 2is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 )alkylcarbonyl, and the above R 3 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkoxy, halo(C 1-6 )alkyl(C 1-6 )alkoxy, halo(C 1-6 )alkyl, (C 1-6 )alkylamino, or pyrrolidine, and the above R 4 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, or (C 1-6 ) may be haloalkyl.

[0043] For example, representative examples of compounds of formula 1 according to an example of the present application include, but are not limited to, those listed in Table 1 below:

[0044] Example Compound Structure Compound Name 1 7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 2 7-chloro-5-phenylimidazo[1,2-a]quinoxalin-4(5H)-one 3 7-chloro-5-(2-ethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 4 7-chloro-5-(2,3-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 5 7-chloro-5-(2-isopropylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one6 7-chloro-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one7 7-Chloro-5-(2-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one8 7-chloro-5-(4-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one9 7-Chloro-5-(5-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 10 5-(3-Fluoro-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 11 7-chloro-5-(3-chloro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 12 7-chloro-5-(2-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 13 7-Cyclopropyl-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 14 5-(3-Fluoro-2-methylphenyl)-7-methoxyimidazo[1,2-a]quinoxalin-4(5H)-one15 5-(3-Fluoro-2-methylphenyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one16 7-Cyclopropyl-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 17 7-Methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 18 4-Oxo-5-(o-tolyl)-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile19 5-(o-tolyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one20 (R a )-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one21 (S a )-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one22 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 23 7-chloro-5-(2-chlorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 24 7-Acetyl-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 25 7-Iodo-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 26 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one27 5-(3-Fluoro-2-methylphenyl)-4-oxo-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile28 5-(o-tolyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one29 5-(3-Fluoro-2-methylphenyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one30 7-Ethoxy-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 31 7-Ethoxy-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 32 7-Bromo-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 33 7-Chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 34 7-Chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 35 7-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 36 7-Methyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 37 7-chloro-5-(2-methoxyphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 38 5-(2-bromophenyl)-7-chloroimidazo[1,2-a]quinoxalin-4(5H)-one 39 7-Chloro-5-(m-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 40 7-chloro-5-(3-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 41 7-Fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 42 3-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[4,3-e]pyrazin-6(5H)-one 43 2-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)benzonitrile 44 N-(3-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)phenyl)methanesulfonamide 45 7-Chloro-2-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 46 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 47 7-Isopropyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 48 7-Chloro-5-(3-methylpyrazin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 49 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one50 7-chloro-5-(2-(trifluoromethoxy)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 51 7-chloro-5-(2,6-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 52 7-chloro-5-(2-fluoro-6-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 53 7-Chloro-5-(3-methylpyridin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 54 7-Chloro-5-(2-chloropyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 55 2-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 56 5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 57 1-Bromo-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 58 1-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 59 1-Acetyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one60 2-Acetyl-1-hydroxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 61 7-Chloro-2-((4-methylpiperazin-1-yl)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one62 7-Chloro-5-(2-methylpyridin-3-yl)-2-(morpholinomethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 63 2-((2-Oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one64 7-Chloro-2-(((2-methoxyethyl)amino)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 65 5-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 66 2-((methylamino)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one67 2-(Methoxymethyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one68 2-(((2-hydroxyethyl)amino)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one69 2-(azetidin-1-ylmethyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one70 2-((3-hydroxyazetidin-1-yl)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one71 7-Chloro-9-fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 72 8-Bromo-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 73 7-Chloro-8-methyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 74 7-Bromo-8-methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxaline-4(5H)-one 75 7-Bromo-8-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 76 7-Bromo-5-(2-methylpyridin-3-yl)-8-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 77 7-Bromo-8-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 78 7-Bromo-8-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 79 7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 80 (R a )-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one81 (S a)-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one82 7-Bromo-8-(difluoromethyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 83 7-Bromo-8-chloro-5-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 84 7-Bromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 85 7,9-Dibromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one86 7-Bromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 87 7-Bromo-8-chloro-5-(2-cyclopropylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 88 1,7-Dibromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 89 7-Bromo-1,8-dichloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one90 7-Bromo-5-(2-hydroxypyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one 91 7-Bromo-5-(2-chloropyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one 92 2,7-Dibromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one93 8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one94 (R a )-8-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one95 (S a )-8-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one96 8-Chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 97 (R a )-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one98 (S a )-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one99 8-Chloro-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one100 8-Chloro-2-(dimethylamino)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 101 7-Chloro-9-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 102 7-Chloro-9-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 103 7-Chloro-9-(cyclopropylmethoxy)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 104 7-Chloro-5-(2-methylpyridin-3-yl)-9-(pyrrolidin-1-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 105 7-chloro-9-(methylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 106 7-chloro-9-(dimethylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 107 7-Bromo-8-chloro-5-(2-methoxypyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 108 5-(Benzo[d]thiazol-7-yl)-7-bromo-8-chloroimidazo[1,2-a]quinoxalin-4(5H)-one 109 7-Bromo-8-chloro-5-(1H-indol-4-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 110 8-Chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 111 (R a )-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one112 (S a )-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one113 9-Methoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 114 9-Methylamino-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 115 9-(Difluoromethoxy)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 116 5-(2-methylpyridin-3-yl)-9-(trifluoromethoxy)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 117 5-(2-Methylpyridin-3-yl)-9-(2,2,2-trifluoroethoxy)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 118 9-Ethoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 119 8-Chloro-1-methyl-2-(methylamino)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one120 8-Chloro-2-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0045] Unless otherwise defined, all technical terms used in this application have the same meaning as commonly understood by those skilled in the art in the relevant field of this application. Furthermore, while exemplary methods and samples are described herein, similar or equivalent methods are also included within the scope of this application. Furthermore, numerical values ​​described herein are deemed to include the meaning of "about," even if not explicitly stated. The contents of all publications cited as references herein are incorporated herein by reference in their entirety.

[0046] In the above chemical formula 1, R 1 Inland R 6 , R a , R b , R c , R d , and R e The residues listed as such are used in the same sense as is generally understood by those skilled in the art.

[0047] Unless otherwise stated, the term "halogen" used herein, either alone or in combination with additional terms (e.g., haloalkyl), refers to fluorine, chlorine, bromine, or iodine.

[0048] Unless otherwise stated herein, “hydroxy” or “hydroxyl” alone or in combination with other terms means -OH.

[0049] Unless otherwise stated, the term “amino” as used herein, alone or in combination with other terms, means -NH2.

[0050] Unless otherwise stated, the term “alkylamino” as used herein refers to an alkyl group in which one or more hydrogens are the same or different, e.g., (C 1-6 ) refers to an amino substituted with alkyl, including but not limited to methylamino, dimethylamino, etc.

[0051] Unless otherwise stated, the term “alkoxy” herein means alkyloxy, e.g., alkyloxy having 1 to 6 carbon atoms.

[0052] Unless otherwise stated, the term "haloalkyl" as used herein means an alkyl group, as defined herein, in which one or more hydrogens are replaced by the same or different halogens. Examples of haloalkyl groups include, but are not limited to, -CH2Cl, -CH2CF3, -CH2CCl3, -CF2, -CF3, and the like.

[0053] Unless otherwise stated, the term “hydroxyalkyl” as used herein includes a group in which one or more hydrogen atoms in the alkyl group are replaced by one or more hydroxyl (-OH), e.g., divalent or trivalent hydroxyl.

[0054] Unless otherwise stated, the term “aminoalkyl” as used herein includes replacement of one or more hydrogen atoms in an alkyl group with one or more amino (-NH2), for example, divalent or trivalent amino.

[0055] Unless otherwise stated, the term “oxo” herein means a group of the formula =O (i.e., oxygen having a double bond).

[0056] Unless otherwise stated, the term "alkyl" herein refers to a saturated, straight-chain or branched monovalent hydrocarbon radical, unless otherwise stated. For example, the alkyl may be C 1-10 Alkyl, C 1-8 Alkyl, C 1-6 Alkyl, or C 1-4 It could be an alkyl.

[0057] Unless otherwise stated, the term "alkenyl" herein refers to a monovalent hydrocarbon radical containing at least one carbon-carbon double bond, each of which may have an E- or Z-configuration. For example, the alkenyl may be C 2-10 Alkenyl, C 2-8 Alkenyl, C 2-6 Alkenyl, or C 2-4 It could be alkenyl.

[0058] Unless otherwise stated, the term "alkynyl" herein refers to a monovalent group derived from an unsaturated, straight-chain or branched hydrocarbon moiety having at least one carbon-carbon triple bond, unless otherwise stated. For example, the alkynyl C 2-10 alkynyl, C 2-8 alkynyl, C 2-6 alkynyl, or C 2-4 It could be alkynyl.

[0059] These "alkyl," "alkenyl," and "alkynyl," when used alone or in combination with other additional terms (e.g., haloalkyl), may be straight-chain or branched. By their definition, they mean radicals of a saturated aliphatic hydrocarbon group having 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, or 1 to 3 carbon atoms within the alkyl group. Common examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, and tert-pentyl, 1-methylpentyl, 2-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, n-hexyl, 3,3-dimethylbutyl, and isohexyl. Each of the double bond and triple bond of the alkenyl group and the alkynyl group can be substituted at any position. Examples of alkenyl and alkynyl include, but are not limited to, ethenyl, prop-1-enyl, prop-2-enyl, but-2-enyl, 2-methylprop-2-enyl, 3-methylbut-2-enyl, hex-3-enyl, hex-4-enyl, prop-2-ynyl, but-2-ynyl, but-3-ynyl, hex-4-ynyl, or hex-5-ynyl.

[0060] Unless otherwise stated herein, "cycloalkyl," "cycloalkenyl," or "cycloalkynyl" refers to a cyclic alkyl which may be substituted or unsubstituted and refers to a hydrocarbon radical forming a single or fused cyclic ring having unsaturated or partially or fully saturated (e.g., from 3 to 24) carbon atoms. Specifically, the cycloalkyl, cycloalkenyl, or cycloalkynyl may have 3 to 10, 3 to 8, 3 to 6, 3 to 5, 4 to 10, 4 to 8, 4 to 6, or 4 to 5 carbon atoms. The cycloalkyl may include, but is not limited to, carbocyclyl, spirocarbocyclyl, fused carbocyclyl, and bridged carbocyclyl.

[0061] According to one specific example of the present invention, the cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclohepsenyl, cyclooctyl, cyclooctenyl, 2,5-cyclohexadienyl, spiro[3.5]nonane, spiro[3.3]heptane, bicyclo[1.1.1]pentane, bicyclo[2.2.2]octyl, adamant-1-yl, decahydronaphthyl, oxocyclohexyl, dioxocyclohexyl, thiocyclohexyl, 2-oxobicyclo[2.2.1]hept-1-enyl, benzene, naphthalene, and all possible thereof. It may include, but is not limited to, isomers.

[0062] Unless otherwise stated herein, the term "saturated or unsaturated heterocyclyl" means a 3 to 24 membered hydrocarbon group which may be substituted or unsubstituted and which forms an unsaturated or partially or fully saturated single or fused cyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen (N), oxygen (O), and sulfur (S), for example, 1 to 8 heteroatoms. Specifically, the heterocyclyl may be a 3 to 10 membered, 3 to 8 membered, 3 to 6 membered, 4 to 10 membered, 4 to 8 membered, or 4 to 6 membered hydrocarbon group having one or more, for example, 1 to 3, heteroatoms. The heterocycle may include, but is not limited to, heteroaryl, heterocyclyl, heterospirocarbocyclyl, fused heterocyclyl, and bridged heterocyclyl.

[0063] According to one specific example of the present invention, the heterocyclyl is pyrrolidinyl, morpholinyl, pyrrolizidinyl, quinolizidinyl, azaspirooctanyl, piperidinyl, pyrrolidinyl, imidazolinyl, piperazinyl, piperazinyl-1-oxide, morpholinyl, thiamorpholinyl, tetrahydrofuranyl, diazabicyclooctanyl, diazaspirooctanyl, tetrahydropyridinyl, dihydropyridinyl, dihydropyranyl, tetrahydropyranyl, 2-oxa-6-azaspiroheptanyl, azetidinyl, oxazepanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, pyridyl, tetrahydrofuranyl, 8-azabicyclo[3.2.1]octanyl, 2-azaspiro[3.3]heptanyl, 2-oxa-7-azaspiro[3.4]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-azabicyclo[2.2.1]heptanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, pyrimidinyl, pyrazolyl, oxetane and similar groups, but are not limited thereto. For example, C 2-10In the case of heterocyclyl, the number of carbon atoms is indicated as C 2-10 It means a ring size of three or more members containing one or more heteroatoms.

[0064] As used herein, the term "aryl", unless otherwise stated, refers to an aromatic group which may be substituted or unsubstituted, and may be, for example, 6 to 20 membered. For example, the aryl may include, without limitation, phenyl, biphenyl, naphthyl, toluyl, naphthalenyl, anthracenyl, indenyl, indanyl, or all possible isomers thereof.

[0065] In this application, the term "heteroaryl" means a monocyclic or bicyclic or higher aromatic group containing one or more heteroatoms selected from O, N and S, for example, 1 to 4, 1 to 3, or 1 to 2, unless otherwise stated, and may be, for example, 6 to 20 membered. For example, examples of monocyclic heteroaryl include thiazolyl, oxazolyl, thiophenyl, furanyl, pyrrolyl, imidazolyl, isoxazolyl, pyrazolyl, triazolyl, thiadiazolyl, tetrazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl, benzimidazolyl, indazolyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl or similar groups thereof, but are not limited thereto.For example, examples of bicyclic heteroaryl include pyrrolizidinyl, indolyl, indolinyl, benzothiophenyl, benzofuranyl, dihydrobenzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, azaspirooctanyl, purinyl, furopyridinyl or similar groups. Examples of tricyclic heteroaryls include, but are not limited to, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, or similar groups.

[0066] In this application, the numerical range indicated using the term “to” refers to a range that includes the numerical values ​​described before and after the term “to” as the lower limit and the upper limit, respectively.

[0067] The compounds of the present invention may have an asymmetric carbon center and an asymmetric axis or asymmetric plane, and therefore may exist as all optical and stereoisomers, including substantially pure enantiomers such as R and S enantiomers, as well as mixture racemates, and all such enantiomers and mixtures are encompassed within the scope of the present invention. With respect to pure enantiomers, the optical purity of such enantiomers represented by formula 1 and pharmaceutically acceptable salts thereof is preferably 60%ee or higher, more preferably 95%ee or higher, and most preferably 98%ee or higher.

[0068] The term "ee" above refers to enantiomeric excess. For example, one enantiomeric form in a particular compound is present in a mixture of enantiomeric forms in a greater amount than the other enantiomeric forms in the compound. An enantiomeric enriched form can include an enantiomeric mixture of a particular compound in which the concentration of a single enantiomeric form in the enantiomeric mixture of the particular compound is at least 50%, more typically at least 60%, 70%, 80%, or 90%, or greater (e.g., >95%, >97%, >99%, >99.5%) with respect to the other enantiomeric forms of the compound.

[0069] In this specification, for convenience, unless otherwise specified, the compound of formula 1 is used to mean all of the compound of formula 1, its optical isomers, stereoisomers, racemates, isotopic variants, solvates, hydrates, and pharmaceutically acceptable salts thereof.

[0070] As used herein, the term “isotopic variant” refers to a compound that contains an unusual ratio of isotopes at one or more atoms constituting the compound. For example, an isotopic variant of a compound may be radiolabeled, for example, a hydrogen atom may be selected from hydrogen, deuterium, and tritium, and a carbon-13 ( 13 C), nitrogen-15( 15 N) may contain the following.

[0071] According to an example of the present application, the compound of formula 1, its optical isomer, stereoisomer, racemate, or isotopic variant can form a pharmaceutically acceptable salt. The pharmaceutically acceptable salt includes both acid or base addition salts and stereochemically isomeric forms thereof. The salt includes any salt that maintains the activity of the parent compound in the subject to which it is administered and does not cause undesirable effects, and is not particularly limited thereto. Such salts include inorganic and organic salts, for example, acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, benzoic acid, stearic acid, esylic acid, lactic acid, bicarboxylic acid, bisulfuric acid, bitartaric acid, oxalic acid, butyric acid, calcium idetic acid, camsylic acid, carbonic acid, chlorobenzoic acid, citric acid, idetic acid, toluenesulfonic acid, edicilinic acid, esylinic acid, fumaric acid, gluceptic acid, pamoic acid, gluconic acid, glycolylarsanilic acid, methylnitric acid, polygalacturic acid, hexylisorcinonic acid, malonic acid, Hydrabamic acid, hydrochloric acid, hydroiodoic acid, hydroxynaphtholic acid, isethionic acid, lactobionic acid, mandelic acid, estolinic acid, mucic acid, napsylic acid, muconic acid, p-nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogenphosphoric acid, dihydrogenphosphoric acid, salicylic acid, sulfamic acid, sulfanilinic acid, methanesulfonic acid, teoclic acid. In addition, the basic salt form includes, for example, alkali and alkaline earth metal salts such as ammonium salt, lithium salt, sodium salt, potassium salt, magnesium salt, and calcium salt, salts with organic bases such as benzathine, N-methyl-D-glucamine, hydrabamine salts, and salts with amino acids such as arginine, lysine. In addition, the salt form can be converted into a free form by treatment with a suitable base or acid.The term "additional salt" includes compounds of formula 1 and solvates with which salts thereof can form. Such solvates are, for example, hydrates and alcoholates.

[0072] The compound according to one embodiment of the present application may also be in the form of a solvate thereof. The term "solvate" refers to a complex or aggregate formed by one or more solute molecules, i.e., a compound of formula 1 or a pharmaceutically acceptable salt thereof, and one or more solvent molecules. The solvate may be a complex or aggregate formed with various solvent molecules, such as, for example, water, methanol, ethanol, isopropanol, or acetic acid.

[0073] Solvates in which water is the solvent molecule are called "hydrates." Hydrates include compositions containing stoichiometric amounts of water as well as compositions containing variable amounts of water.

[0074] A compound according to an example of the present application may also exist in the form of its tautomer. The term "tautomer" or "tautomeric form" refers to structural isomers of different energies that are interconvertible via a low energy barrier. Some non-limiting examples of proton tautomers (also known as prototautomers) include interconversions via proton transfer, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions due to rearrangement of some of the bonding electrons.

[0075] A compound according to an example of the present application may also be in the form of an isotopic variant thereof. The term "isotopic variant" means a compound in which at least one atom of any compound has been exchanged for another atom having the same atomic number but a different atomic mass than the atomic mass that normally or predominantly occurs in nature.

[0076] Solvates, stereoisomers, tautomers and isotopic variants of the compound of the above formula 1 can be prepared from the compound using methods known in the art.

[0077] Terms and abbreviations used in this specification have their original meanings unless otherwise defined.

[0078] An example of the present application also provides a method for preparing a compound of the above chemical formula 1. Hereinafter, a method for preparing a compound of the above chemical formula 1 will be described based on an exemplary reaction scheme to help understanding the present application. However, a person having ordinary skill in the art to which the present application pertains can prepare the compound of the above chemical formula 1 by various methods using known compounds or compounds that can be easily prepared therefrom based on the structure of the above chemical formula 1, and all such methods should be interpreted as being included in the scope of the present application. Therefore, the description including the following reaction schemes 1 and 2 related to the method for preparing the compound of the above chemical formula 1 is merely to present exemplary methods, and the order of unit operations, etc. may be selectively changed as needed, and the scope of the preparation method of the present application is not limited thereto.

[0079] [Reaction Formula 1]

[0080]

[0081] In the above reaction formula 1, X 1 can be CH or N.

[0082] For example, the above reaction scheme 1 may be the following reaction scheme 1-1:

[0083] [Reaction Formula 1-1]

[0084]

[0085] Step A: Add ethyl 1H-imidazole-2-carboxylate and cesium carbonate to compound 1 and heat to obtain compound 2.

[0086] Step B: Compound 3 is synthesized from compound 2 in the presence of a boronic acid having the formula Ar-B(OH)2 and a phenyl silane and a 1,2,2,3,4,4-hexamethylphosphetane 1-oxide catalyst.

[0087] Step C: Synthesize compound 4 using a base such as potassium carbonate in a polar solvent such as ethanol.

[0088] [Reaction Formula 2]

[0089]

[0090] In the above reaction formula 2, X 1 can be CH or N.

[0091] For example, the above reaction scheme 2 may be the following reaction scheme 2-1:

[0092] [Reaction Formula 2-1]

[0093]

[0094] Step A: Compound 2 is obtained by reacting compound 1 with an amine to be substituted under appropriate base conditions.

[0095] Step B: Compound 3 is obtained from compound 2 using a reduction reaction.

[0096] Step C: Add diethyl oxalate to compound 3 and heat or add ethyl 2-chloro-2-oxoacetate and then under basic conditions to obtain compound 4.

[0097] Step D: Compound 5 is obtained by using thionyl chloride on compound 4 to obtain compound 5 in which the hydroxyl group is substituted with chlorine.

[0098] Step E: Compound 6 is obtained by replacing the chlorine substituent of compound 5 with an amine using ammonia.

[0099] Step F: Compound 7 is obtained by using a cyclization reaction on compound 6.

[0100]

[0101] Another example of the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula 1 according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0102] Specifically, the compound of formula 1 according to an example of the present application can prevent, improve or treat a disease or condition related to a MAT2A mutant protein, specifically a disease or condition caused by the MAT2A protein. For example, the compound of formula 1 according to the present application can effectively suppress the growth of MTAP-deficient cancer cells as an inhibitor of the MAT2A protein, and thus can be usefully used as a pharmaceutical composition for preventing or treating cancer. The cancer may be a cancer with reduced or deficient MTAP activity. Accordingly, the pharmaceutical composition may be a pharmaceutical composition for preventing or treating a disease related to the MAT2A protein.

[0103] More specifically, the pharmaceutical composition may inhibit the activity of the MAT2A protein to prevent or treat a disease associated with the MAT2A protein. The disease associated with the MAT2A protein may be, for example, cancer. Accordingly, the pharmaceutical composition may act as a selective inhibitor for MTAP-deficient cancers associated with MAT2A, and the pharmaceutical composition may be a composition for the prevention or treatment of MTAP-deficient cancers.

[0104] In addition, the pharmaceutical composition may be used to treat cancer by additionally comprising a compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof, and at least one different therapeutic agent. The compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof, may exhibit synergistic effects when used in combination with different therapeutic agents. The term "synergistic" refers to a therapeutic combination that is more effective than the additive effect of two or more single agents. A combination therapy provides "synergistic" and demonstrates "synergistic" effects, i.e., the effect achieved when the active ingredients are used together is greater than the sum of the effects resulting from the use of the compounds separately. A synergistic effect can be achieved when the active ingredients are: (1) co-formulated and administered or delivered simultaneously in a combined unit dosage form; or (2) delivered as separate formulations by substitution. When delivered in substitution therapy, a synergistic effect can be achieved when the compounds are administered or delivered sequentially, for example, by different injections in separate syringes. Typically, during substitution therapy, effective doses of each active ingredient are administered sequentially, i.e., serially in time. In some embodiments, synergy is evidenced by lower toxicity of the combination compared to the same dose of any single ingredient at the same total dosage. For example, when a compound of formula 1 according to one example of the present application is co-administered with a different therapeutic agent, the toxicity of a 50:50 (w / w) combination comprising the compound of formula 1 and the different therapeutic agent may be less than the toxicity of 100% (w / w) the compound of formula 1, and / or the toxicity of 100% (w / w) the different therapeutic agent, wherein the combination has about the same level of efficacy or greater.That is, the toxicity of the compound of formula 1 and a different therapeutic agent in combination is less than that of either agent alone, and the efficacy of the combination is greater than that of either agent alone. Furthermore, the purpose of combining the compound of formula 1 and a different therapeutic agent is not only to reduce toxicity and provide greater safety, but also to enhance efficacy significantly beyond that provided by either agent alone. Increased efficacy is one of the benefits of combination therapy.

[0105] Another example of the present application relates to a pharmaceutical combination for treating and / or preventing cancer in a subject, comprising a compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof; and a cytotoxic anticancer agent.

[0106] Another example of the present application relates to a pharmaceutical combination for treating and / or preventing cancer in a subject, comprising a combination of a compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent.

[0107] Among the active ingredients of the above pharmaceutical combination, the cytotoxic anticancer agent may include at least one selected from the group consisting of an alkylating agent, an antimetabolite, a DNA polymerase inhibitor, and a microtubule inhibitor.

[0108] Among the active ingredients of the pharmaceutical combination, the targeted anticancer agent may include at least one selected from the group consisting of a monoclonal antibody, a small molecule targeted therapeutic agent, an antibody-drug conjugate, and an immune checkpoint inhibitor.

[0109] One of the effective ingredients of the pharmaceutical combination according to an example of the present application is a cytotoxic anticancer agent or a targeted anticancer agent, which is a compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof, in a ratio of 1:0.0001 to 1:10,000, 1:0.0001 to 1:1,000, 1:0.0001 to 1:100, 1:0.001 to 1:10,000, 1:0.001 to 1:1,000, 1:0.001 to 1:100, 1:0.01 to 1:10,000, 1:0.01 to 1:1,000, 1:0.01 to 1:100, 1:0.1 to It can be used in combination at a weight ratio of 1:10,000, 1:0.1 to 1:1,000, or 1:0.1 to 1:100.

[0110] An example of the alkylating agent may be selected from the group consisting of Cisplatin, Carboplatin, Oxaliplatin, Mechlorethamine, Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil, Carmustine (BCNU), Lomustine (CCNU), Nimustine, Altretamine, Busulfan, Dacarbazine, Procarbazine, Temozolomide, Thiotepa, and Lurbinectedin.

[0111] An example of the above-mentioned metabolic antagonist may be selected from the group consisting of pemetrexed, fluorouracil (5-FU), capecitabine, cytarabine, gemcitabine, methotrexate, and mercaptopurine (6-MP).

[0112] An example of the above DNA polymerase inhibitor may be selected from the group consisting of Etoposide, Teniposide, Topotecan, Irinotecan, SN-38, Dactinomycin, Doxorubicin, Daunorubicin, Mitomycin and Bleomycin.

[0113] An example of the above microtubule inhibitor may be selected from the group consisting of Vinblastine, Vincristine, Vinorelbine, Paclitaxel and Docetaxel.

[0114] An example of the monoclonal antibody may be selected from the group consisting of Trastuzumab, Rituximab, and Bevacizumab. An example of the small molecule targeted therapeutic agent may be selected from the group consisting of kinase inhibitors, hormone receptor antagonists, EGFR / VEGR inhibitors, PARP inhibitors, PI3K / AKT / mTOR pathway inhibitors, and epigenetics inhibitors.

[0115] The above epigenetic inhibitor may include a Type I PRMT inhibitor and a Type II PRMT inhibitor, and the Type II PRMT inhibitor may be at least one selected from the group consisting of a PRMT5 inhibitor, a PRMT7 inhibitor, and a PRMT9 inhibitor.

[0116] The above PRMT5 inhibitor may be an inhibitor that inhibits PRMT5 non-competitively and / or cooperatively with MTA.

[0117] For example, MTA-cooperative PRMT5 inhibitors can have a potent PRMT5 enzyme inhibition effect when used together with MAT2A inhibitors in MTAP-deficient cancers because they preferentially inhibit PRMT5 in an environment where high concentrations of MTA are present due to the mechanism by which binding to PRMT5 is increased in the presence of MTA.

[0118] The above MTA-cooperative PRMT5 inhibitor may include, but is not limited to, one or more selected from the group consisting of AMG-193, MRTX1719, TNG908, and TNG462.

[0119] Examples of the antibody-drug conjugate may include, but are not limited to, CD33, CD22, CD20, or Trop2 antibody-drug conjugates.

[0120] Examples of the above immune checkpoint inhibitors may include, but are not limited to, CD20 antibodies, CTLA-4 inhibitors, PD-1 / PDL-1 antibodies, or LAG-3 antibodies.

[0121] In another aspect of the present application, a method for preventing or treating a disease associated with the methionine adenosyltransferase 2A (MAT2A) protein, such as cancer, is provided, comprising administering to a subject in need thereof a pharmaceutical composition or pharmaceutical combination according to an example of the present application. The cancer may be a cancer in which MTAP activity or expression is reduced, or a cancer in which all or part of the MTAP gene is deleted.

[0122] The above cancers include, for example, acoustic neuroma, adenocarcinoma, adrenal cancer, anal cancer, angiosarcoma, benign monoclonal gammopathy, cholangiocarcinoma, bladder cancer, breast cancer, brain cancer, lymphoma, multiple myeloma, lacrimal gland tumor, bronchial cancer, cervical cancer, craniopharyngioma, colorectal cancer, epithelial carcinoma, ependymoma, endothelial sarcoma, endometrial cancer, esophageal cancer, Barrett's adenocarcinoma, Ewing's sarcoma, eye cancer, gallbladder cancer, stomach cancer, colon cancer, gastrointestinal stromal tumor (GIST), head and neck cancer, oral cancer (OSCC), throat cancer, hematopoietic cancer, hemangioblastoma, inflammatory myofibroblastic tumor, immunocytotoxic amyloidosis, kidney cancer, renal cell carcinoma, liver cancer, lung cancer, melanoma, uveal melanoma, acute myeloid leukemia (AML), It may be at least one selected from the group consisting of myelodysplastic syndrome (MDS), mesothelioma, myeloproliferative disorder (MPD), chronic idiopathic myelofibrosis, chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), neuroblastoma, neurofibroma, neuroendocrine cancer, osteosarcoma, ovarian cancer, papillary adenocarcinoma, pancreatic cancer, penile cancer, prostate cancer, rectal cancer, rhabdomyosarcoma, salivary gland cancer, skin cancer, small intestine cancer, soft tissue sarcoma, thyroid cancer, urethral cancer, vaginal cancer, glioblastoma multiforme (GBM), glioma, peripheral nerve sheath tumor, thymic cancer, adenoid cystic carcinoma (ACC), and vulvar cancer.

[0123] For example, the cancer may be one or more selected from the group consisting of lung cancer, bladder cancer, stomach cancer, esophageal cancer, head and neck cancer, pancreatic cancer, colon cancer, biliary tract cancer, mesothelioma, peripheral nerve sheath tumor, thymic cancer, and adenoid cystic carcinoma (ACC).

[0124] The above brain cancer may be, for example, one or more selected from the group consisting of meningioma, glioma, medulloblastoma, glioblastoma, and brain metastasis.

[0125] According to an example of the present application, a compound of formula 1, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof has a high binding capacity to MAT2A protein. Accordingly, another example of the present application relates to a composition for binding to MAT2A protein, and more specifically, to a composition for inhibiting MAT2A protein activity, comprising a compound according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

[0126] Another example of the present application relates to a method for inhibiting the activity of a MAT2A protein, comprising administering to a subject in need thereof a pharmaceutical composition, or a pharmaceutical combination, according to an example of the present application.

[0127] The present application can provide a compound comprising a tricyclic ring useful as a preventive or therapeutic agent for cancer caused by MAT2A, a method for preparing the same, a pharmaceutical composition containing the same, and a use thereof as a pharmaceutical agent.

[0128] A tricyclic derivative compound exhibiting an excellent MAT2A inhibitory effect according to an example of the present application, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof, acts as a MAT2A (methionine adenosyltransferase 2A) inhibitor and can be effectively used for the prevention or treatment of diseases related to the MAT2A protein, such as cancer.

[0129] Additionally, compounds according to one embodiment of the present application, optical isomers, stereoisomers, racemates, isotopic variants, solvates, hydrates, or pharmaceutically acceptable salts thereof may have improved MTAP-deficient cancer selectivity and blood-brain barrier penetration ability.

[0130] Below, the present application is described in more detail through examples. However, the examples are intended only to exemplify the present application and are not intended to limit the scope of the present application.

[0131]

[0132] Example 1: 7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0133] Example 1 Reaction scheme for the preparation of compounds:

[0134]

[0135] Example 1-1: Ethyl 1-(4-chloro-2-nitrophenyl)-1H-imidazole-2-carboxylate

[0136] 4-Chloro-1-fluoro-2-nitrobenzene (20.0 g, 113 mmol, 1 equiv) and ethyl 1H-imidazole-2-carboxylate (15.9 g, 113 mmol, 1.00 equiv) were dissolved in dimethylformamide (100 mL), and cesium carbonate (48.2 g, 148 mmol, 1.3 equiv) was added. The reaction was stirred at 55 °C for 2 h. The exhaustion of the starting material was observed via TLC, and when the reaction was complete, the mixture was cooled to room temperature, 500 mL of water was added, the precipitate was filtered, washed with water (30 mL X 3), and dried to obtain ethyl 1-(4-chloro-2-nitrophenyl)-1H-imidazole-2-carboxylate (26.0 g, 84.9 mmol, 74.4% yield, 96.6% purity) as a light yellow solid.

[0137] 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.38 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 0.8 Hz, 1H), 7.32 (d, J = 1.2 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 1.11 (t, J = 7.2 Hz, 3H).

[0138]

[0139] Example 1-2: Ethyl 1-(4-chloro-2-(o-tolylamino)phenyl)-1H-imidazole-2-carboxylate

[0140] The compound obtained in Example 1-1 (6.00 g, 20.2 mmol, 1 equiv.), o-tolylboronic acid (5.52 g, 40.60 mmol, 2 equiv.), and 1,2,2,3,4,4-hexamethylphosphitene 1-oxide (530 mg, 3.04 mmol, 0.15 equiv.) were dissolved in toluene (45 mL), and phenylsilane (4.39 g, 40.5 mmol, 5.01 mL, 2 equiv.) was added. The reaction mixture was purged with nitrogen three times to remove gas from the solution, and then stirred at 120 °C for 2 hours under nitrogen. After the reaction mixture was cooled to room temperature, water (100 mL) was added, and then extracted with ethyl acetate (150 mL × 2). The organic layer was washed with a saturated sodium chloride solution (100 mL × 2), dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (stationary phase: silica, mobile phase: petroleum ether / ethyl acetate = 50 / 1 to 10 / 1) to obtain the title compound as a white solid (4.70 g, 10.5 mmol, 51.9% yield, 79.7% purity).

[0141] 1H NMR (400 MHz, DMSO-d6, ppm) δ 7.49 (d, J = 1.2 Hz, 1H), 7.20-7.18 (m, 2H), 7.16-7.09 (m, 3H), 7.05-7.00 (m, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 6.47 (d, J = 2.4 Hz, 1H), 4.15 (d, J = 6.8 Hz, 2H), 2.07 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H).

[0142]

[0143] Example 1-3: 7-Chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0144] The compound obtained in Example 1-2 (3.10 g, 8.71 mmol, 1 equivalent) was dissolved in ethanol (45 mL), and potassium carbonate (1.33 g, 9.60 mmol, 1.1 equivalent) was added. The mixture was stirred at 80 o C and stirred for 2 hours. After confirming the completion of the reaction through TLC, the reaction mass was cooled to room temperature and concentrated under reduced pressure. The residue was purified by column chromatography (stationary phase: silica, mobile phase: dichloromethane / methanol = 100 / 1 to 20 / 1) to obtain the title compound (2.50 g, 7.76 mmol, 89.0% yield, 96.2% purity) as a light yellow solid.

[0145] 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.68 (d, J = 1.3 Hz, 1H), 8.32 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 1.3 Hz, 1H), 7.63 - 7.44 (m, 4H), 7.38 (d, J = 7.7 Hz, 1H), 6.36 (d, J = 2.2 Hz, 1H), 2.02 (s, 3H).

[0146]

[0147] Example 2: 7-Chloro-5-phenylimidazo[1,2-a]quinoxalin-4(5H)-one

[0148]

[0149] In Example 1-2, the title compound was synthesized in the same manner by changing o-tolylboronic acid to phenylboronic acid.

[0150] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.89 (d, J = 1.3 Hz, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.69 - 7.56 (m, 4H), 7.37 - 7.28 (m, 3H), 6.72 (d, J = 2.1 Hz, 1H).

[0151]

[0152] Example 3: 7-chloro-5-(2-ethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0153]

[0154] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (2-ethylphenyl)boronic acid.

[0155] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.3 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.49 - 7.42 (m, 1H), 7.29 (d, J = 2.2 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 6.61 (d, J = 2.2 Hz, 1H), 2.71 - 2.23 (m, 2H), 1.13 (t, J = 7.6 Hz, 3H).

[0156]

[0157] Example 4: 7-chloro-5-(2,3-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0158]

[0159] In Example 1-2, the title compound was synthesized in the same manner by changing o-tolylboronic acid to (2,3-dimethylphenyl)boronic acid.

[0160] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (s, 1H), 7.72 (s, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.42 - 7.28 (m, 3H), 7.04 (d, J = 7.5 Hz, 1H), 6.63 (d, J) = 2.1 Hz, 1H), 2.41 (s, 3H), 1.98 (s, 3H).

[0161]

[0162] Example 5: 7-chloro-5-(2-isopropylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0163]

[0164] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (2-isopropylphenyl)boronic acid.

[0165] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.91 (d, J = 1.3 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.63 - 7.54 (m, 2H), 7.47 - 7.38 (m, 1H), 7.29 (d, J = 2.2 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 6.62 (d, J = 2.1 Hz, 1H), 2.79 - 2.52 (m, 1H), 1.20 (d, J = 6.8 Hz, 3H), 1.08 (d, J = 6.9 Hz, 3H).

[0166]

[0167] Example 6: 7-chloro-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0168]

[0169] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (3-fluoro-2-methylphenyl)boronic acid.

[0170] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.91 (d, J = 1.2 Hz, 1H), 7.73 (d, J = 1.2 Hz, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.47 - 7.38 (m, 1H), 7.36 - 7.27 (m, 2H), 7.05 (d, J = 7.9 Hz, 1H), 6.62 (d, J = 2.1 Hz, 1H), 2.02 (d, J = 1.9 Hz, 3H).

[0171]

[0172] Example 7: 7-Chloro-5-(2-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0173]

[0174] In Example 1-2, the title compound was synthesized in the same manner by changing o-tolylboronic acid to (2-(trifluoromethyl)phenyl)boronic acid.

[0175] 1H NMR (400 MHz, CDCl3, ppm) δ 7.97 (d, J = 7.8 Hz, 1H), 7.90 (s, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.75 (t, J = 7.8 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.29 (dd, J = 8.7, 2.1 Hz, 1H), 6.49 (d, J = 2.1 Hz, 1H).

[0176]

[0177] Example 8: 7-chloro-5-(4-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0178]

[0179] In Example 1-2, the title compound was synthesized in the same manner by changing o-tolylboronic acid to (4-fluoro-2-methylphenyl)boronic acid.

[0180] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.3 Hz, 1H), 7.72 (d, J = 1.3 Hz, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.30 (dd, J = 8.6, 2.1 Hz, 1H), 7.23 - 7.10 (m, 3H), 6.62 (d, J = 2.1 Hz, 1H), 2.10 (s, 3H).

[0181]

[0182] Example 9: 7-chloro-5-(5-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0183]

[0184] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (5-fluoro-2-methylphenyl)boronic acid.

[0185] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.2 Hz, 1H), 7.72 (d, J = 1.3 Hz, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.50 - 7.41 (m, 1H), 7.31 (dd, J = 8.7, 2.1 Hz, 1H), 7.24 - 7.17 (m, 1H), 7.00 - 6.95 (m, 1H), 6.62 (d, J = 2.1 Hz, 1H), 2.06 (s, 3H).

[0186]

[0187] Example 10: 5-(3-Fluoro-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0188]

[0189] The title compound was synthesized using 1-fluoro-2-nitro-4-(trifluoromethyl)benzene as the starting material in the same manner as in Example 6.

[0190] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.98 (d, J = 1.3 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 1.2 Hz, 1H), 7.59 (d, J = 8.5 Hz, 1H), 7.44 (q, J = 7.8 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H), 7.06 (d, J = 7.9 Hz, 1H), 6.87 (s, 1H), 2.02 (d, J = 2.0 Hz, 3H).

[0191]

[0192] Example 11: 7-chloro-5-(3-chloro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0193]

[0194] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (3-chloro-2-methylphenyl)boronic acid.

[0195] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.91 (d, J = 1.2 Hz, 1H), 7.73 (d, J = 1.3 Hz, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.39 (t, J = 8.1 Hz, 1H), 7.30 (dd, J = 8.7, 2.1 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 6.60 (d, J = 2.1 Hz, 1H), 2.14 (s, 3H).

[0196]

[0197] Example 12: 7-Chloro-5-(2-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0198]

[0199] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (2-fluorophenyl)boronic acid.

[0200] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.89 (d, J = 1.4 Hz, 1H), 7.72 (d, J = 1.4 Hz, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.63 - 7.56 (m, 1H), 7.47 - 7.34 (m, 3H), 7.30 (dd, J = 8.7, 2.1 Hz, 1H), 6.74 (d, J = 1.8 Hz, 1H).

[0201]

[0202] Example 13: 7-Cyclopropyl-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0203]

[0204] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 4-cyclopropyl-1-fluoro-2-nitrobenzene.

[0205] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.95 - 7.87 (m, 1H), 7.72 - 7.68 (m, 1H), 7.67 - 7.62 (m, 1H), 7.46 - 7.36 (m, 1H), 7.27 - 7.21 (m, 1H), 7.10 - 7.03 (m, 1H), 6.98 - 6.90 (m, 1H), 6.36 (d, J = 1.6 Hz, 1H), 2.08 - 1.98 (m, 3H), 1.88 - 1.75 (m, 1H), 1.03 - 0.91 (m, 2H), 0.64 - 0.54 (m, 2H).

[0206]

[0207] Example 14: 5-(3-Fluoro-2-methylphenyl)-7-methoxyimidazo[1,2-a]quinoxalin-4(5H)-one

[0208]

[0209] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 1-fluoro-4-methoxy-2-nitrobenzene.

[0210] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.89 (s, 1H), 7.73 - 7.66 (m, 2H), 7.43 - 7.35 (m, 1H), 7.27 - 7.21 (m, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.90 - 6.85 (m, 1H), 6.12 (d, J = 2.4 Hz, 1H), 3.72 (s, 3H), 2.03 (q, J = 1.6 Hz, 3H).

[0211]

[0212] Example 15: 5-(3-Fluoro-2-methylphenyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one

[0213]

[0214] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 1-fluoro-2-nitro-4-(trifluoromethoxy)benzene.

[0215] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.70 (d, J = 1.2 Hz, 1H), 8.41 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.57 - 7.40 (m, 3H), 7.29 (d, J = 8.0 Hz, 1H), 6.38 (d, J = 2.0 Hz, 1H), 1.95 (d, J = 2.0 Hz, 3H).

[0216]

[0217] Example 16: 7-Cyclopropyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0218]

[0219] The title compound was synthesized in the same manner as in Example 1, changing the starting material to 4-cyclopropyl-1-fluoro-2-nitrobenzene.

[0220] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.63 (d, J = 1.2 Hz, 1H), 8.18 - 8.08 (m, 1H), 7.68 - 7.62 (m, 1H), 7.57 - 7.43 (m, 3H), 7.38 - 7.31 (m, 1H), 7.07 - 6.97 (m, 1H), 6.24 - 6.11 (m, 1H), 2.01 - 1.97 (m, 3H), 1.86 - 1.74 (m, 1H), 0.94 - 0.86 (m, 2H), 0.56 - 0.46 (m, 2H).

[0221]

[0222] Example 17: 7-Methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0223]

[0224] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-fluoro-4-methoxy-2-nitrobenzene.

[0225] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 7.89 (s, 1H), 7.01 (s, 1H), 7.68 (s, 1H), 7.46 - 7.41 (m, 3H), 7.22 (d, 1H), 6.86 (dd, J = 2.4 Hz, 1H), 6.12 (d, J = 2.4 Hz, 1H), 3.71 (s, 3H), 2.13 (s, 3H).

[0226]

[0227] Example 18: 4-Oxo-5-(o-tolyl)-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile

[0228]

[0229] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 4-fluoro-3-nitrobenzonitrile.

[0230] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.98 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.65-7.58 (m, 1H), 7.55-7.45 (m, 3H), 7.20 (d, J = 7.6) Hz, 1H), 6.93-6.92 (m, 1H), 2.10 (s, 3H).

[0231]

[0232] Example 19: 5-(o-tolyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one

[0233]

[0234] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-fluoro-2-nitro-4-(trifluoromethoxy)benzene.

[0235] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.70 (d, J = 1.2 Hz, 1H), 8.41 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.59 - 7.36 (m, 5H), 6.27 (d, J = 1.6 Hz, 1H), 2.04 - 1.98 (m, 3H).

[0236]

[0237] Example 20: (Ra)-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0238]

[0239] The title compound obtained in Example 1 was separated using DAICEL CHIRALPAK IC (250 mm*20 mm, 5 μm); mobile phase: [hexane-ethanol]; B%: 70%, isocratic transfer conditions (retention time: 8.55 min) to obtain the title compound as a white solid (ee%>99.9%).

[0240] 1 H NMR (400 MHz, CDCl3, ppm) 7.90 (s, 1H), 7.72 (s, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.53 - 7.40 (m, 3H), 7.31 - 7.28 (m, 1H), 7.20 (d, J = 7.6) Hz, 1H), 6.61 (d, J = 2.0 Hz, 1H), 2.10 (s, 3H).

[0241]

[0242] Example 21: (Sa)-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0243]

[0244] The title compound obtained in Example 1 was separated (ee%>99.9%) using DAICEL CHIRALPAK IC (250 mm*20 mm, 5 μm); mobile phase: [hexane-ethanol]; B%: 70%, isocratic transfer conditions (retention time: 10.55 min) to obtain the title compound as a white solid.

[0245] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.3 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.51 - 7.46 (m, 2H), 7.46 - 7.41 (m, 1H), 7.32 - 7.27 (m, 1H), 7.20 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 2.1 Hz, 1H), 2.10 (s, 3H).

[0246]

[0247] Example 22: 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0248]

[0249] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 4-(difluoromethyl)-1-fluoro-2-nitrobenzene.

[0250] 1H NMR (400 MHz, CDCl3, ppm) δ 7.97 (d, J = 1.3 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 1.3 Hz, 1H), 7.64 - 7.37 (m, 4H), 7.22 (d, J = 7.6 Hz, 1H), 6.74 (s, 1H), 6.54 (t, J = 56.1 Hz, 1H), 2.10 (s, 3H).

[0251]

[0252] Example 23: 7-Chloro-5-(2-chlorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0253]

[0254] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (2-chlorophenyl)boronic acid.

[0255] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.3 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.71 - 7.66 (m, 2H), 7.61 - 7.50 (m, 2H), 7.43 - 7.38 (m, 1H), 7.30 (dd, J = 8.7, 2.1 Hz, 1H), 6.59 (d, J = 2.1 Hz, 1H).

[0256]

[0257] Example 24: 7-Acetyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0258]

[0259] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-(4-fluoro-3-nitrophenyl)ethan-1-one.

[0260] 1H NMR (400 MHz, CDCl3, ppm) δ 7.97 (d, J = 1.3 Hz, 1H), 7.90 (dd, J = 8.4, 1.7 Hz, 1H), 7.83 (d, J = 8.5 Hz, 1H), 7.75 (d, J = 1.3 Hz, 1H), 7.53 - 7.48 (m, 2H), 7.47 - 7.41 (m, 1H), 7.24 - 7.19 (m, 2H), 2.47 (s, 3H), 2.10 (s, 3H).

[0261]

[0262] Example 25: 7-Iodo-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0263]

[0264] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-fluoro-4-iodo-2-nitrobenzene.

[0265] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.3 Hz, 1H), 7.71 (d, J = 1.3 Hz, 1H), 7.62 (dd, J = 8.6, 1.7 Hz, 1H), 7.51 - 7.41 (m, 4H), 7.19 (d, J = 7.6 Hz, 1H), 6.93 (d, J = 1.7 Hz, 1H), 2.10 (s, 3H).

[0266]

[0267] Example 26: 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0268]

[0269] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-fluoro-2-nitro-4-(trifluoromethyl)benzene.

[0270] 1H NMR (400 MHz, CDCl3, ppm) δ 7.97 (d, J = 1.3 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.76 (d, J = 1.3 Hz, 1H), 7.57 (d, J = 8.5 Hz, 1H), 7.53 - 7.48 (m, 2H), 7.46 (dd, J = 7.9, 3.8 Hz, 1H), 7.21 (d, J = 7.7 Hz, 1H), 6.87 (s, 1H), 2.10 (s, 3H).

[0271]

[0272] Example 27: 5-(3-Fluoro-2-methylphenyl)-4-oxo-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile

[0273]

[0274] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 4-fluoro-3-nitrobenzonitrile.

[0275] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.98 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.81 - 7.76 (m, 1H), 7.66 - 7.60 (m, 1H), 7.50 - 7.42 (m, 1H), 7.36 - 7.29 (m, 1H), 7.07 - 7.02 (m, 1H), 6.96 - 6.92 (m, 1H), 2.03 (s, 3H).

[0276]

[0277] Example 28: 5-(o-tolyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one

[0278]

[0279] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1-fluoro-2-nitro-4-(2,2,2-trifluoroethoxy)benzene.

[0280] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.90 (d, J = 0.8 Hz, 1H), 7.73 (d, J = 9.2 Hz, 1H), 7.71 (s, 1H), 7.51 - 7.48 (m, 2H), 7.47 - 7.41 (m, 1H), 7.24 - 7.19 (m, 1H), 6.92 - 6.86 (m, 1H), 6.19 (d, J = 2.4 Hz, 1H), 4.28 - 4.19 (m, 2H), 2.11 (s, 3H).

[0281]

[0282] Example 29: 5-(3-Fluoro-2-methylphenyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one

[0283]

[0284] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 1-fluoro-2-nitro-4-(2,2,2-trifluoroethoxy)benzene.

[0285] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.94 - 7.88 (m, 1H), 7.77 - 7.70 (m, 2H), 7.46 - 7.38 (m, 1H), 7.32 - 7.27 (m, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.95 - 6.88 (m, 1H), 6.21 (d, J = 2.4 Hz, 1H), 4.31 - 4.22 (m, 2H), 2.07 - 2.00 (m, 3H).

[0286]

[0287] Example 30: 7-Ethoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0288]

[0289] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 4-ethoxy-1-fluoro-2-nitrobenzene.

[0290] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.79 (d, J = 1.6 Hz, 1H), 8.30 (d, J = 9.2 Hz, 1H), 7.91 (d, J = 1.6 Hz, 1H), 7.57 - 7.45 (m, 3H), 7.36 - 7.32 (m, 1H), 7.09 - 7.05 (m, 1H), 5.88 (d, J = 2.4 Hz, 1H), 3.95 - 3.90 (m, 2H), 2.05 - 2.01 (m, 3H), 1.24 (t, J = 6.8 Hz, 3H).

[0291]

[0292] Example 31: 7-Ethoxy-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0293]

[0294] The title compound was synthesized in the same manner as in Example 6, except that the starting material was changed to 4-ethoxy-1-fluoro-2-nitrobenzene.

[0295] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.61 (d, J = 1.6 Hz, 1H), 8.30 (d, J = 9.2 Hz, 1H), 7.91 (d, J = 1.6 Hz, 1H), 7.57 - 7.45 (m, 2H), 7.36 - 7.32 (m, 1H), 7.09 - 7.05 (m, 1H), 5.88 (d, J = 2.4 Hz, 1H), 3.95 - 3.90 (m, 2H), 2.05 - 2.01 (m, 3H), 1.24 (t, J = 6.8 Hz, 3H).

[0296]

[0297] Example 32: 7-Bromo-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0298]

[0299] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 4-bromo-1-fluoro-2-nitrobenzene.

[0300] 1 H NMR (400 MHz, CDCl3, ppm) δ 7.90 (d, J = 1.4 Hz, 1H), 7.72 (d, J = 1.3 Hz, 1H), 7.62 (d, J = 8.7 Hz, 1H), 7.55 - 7.39 (m, 4H), 7.20 (d, J = 7.6 Hz, 1H), 6.76 (d, J = 2.0 Hz, 1H), 2.10 (s, 3H).

[0301]

[0302] Example 33: 7-Chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0303] Example 33 Reaction scheme for the preparation of compound:

[0304]

[0305] Example 33-1: N-(5-chloro-2-nitrophenyl)-2-methylpyridin-3-amine

[0306] 4-Chloro-2-fluoro-1-nitrobenzene (10 g, 56.97 mmol, 1 equiv), 2-methylpyridin-3-amine (6.47 g, 59.81 mmol, 1.05 equiv), and lithium bis(trimethylsilyl)amide (1 M, 68.36 mL, 1.2 equiv) were added to tetrahydrofuran (200 mL) and purged with nitrogen three times. The mixture was cooled to -60 oC and stirred for 2 hours. After confirming the formation of a new product by TLC, the reaction was terminated by adding a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate (200 mL X 3). The organic layer was washed with a saturated aqueous ammonium chloride solution (100 mL), dried over ammonium sulfate, filtered, and concentrated. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain the title compound (15 g, 56.89 mmol, 99.8% yield) as a yellow solid.

[0307] 1 H NMR (400 MHz, CDCl 3, ppm) δ 9.38 (br s, 1H), 8.52 (d, J = 4.0 Hz, 1H), 8.21 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.31 - 7.28 (m, 1H), 6.81 - 6.76 (m, 1H), 6.72 (d, J = 2.0 Hz, 1H), 2.54 (s, 3H).

[0308]

[0309] Example 33-2: 5-Chloro-N 1 -(2-methylpyridin-3-yl)benzene-1,2-diamine

[0310] The compound obtained in Example 33-1 (15 g, 56.89 mmol, 1 equivalent) was dissolved in methanol (300 mL), and Raney-nickel (4.87 g, 56.89 mmol, 1 equivalent) was added. The reaction mixture was stirred at 25 °C under hydrogen (15 Psi). o Stirred for 2 hours at C. Starting material disappeared on LCMS and m / z ([M + H]) of title compound + = 234.1) was observed, and the reaction mixture was filtered and concentrated to obtain the title compound (13 g, crude mixture) as a yellow solid.

[0311] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 7.95 - 7.86 (m, 1H), 7.08 - 7.01 (m, 1H), 6.91 - 6.87 (m, 1H), 6.85 (s, 1H), 6.80 (d, J = 2.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 2H), 5.39 - 4.56 (m, 2H), 2.44 (s, 3H).

[0312]

[0313] Example 33-3:7-Chloro-1-(2-methylpyridin-3-yl)-1,4-dihydroquinoxaline-2,3-dione

[0314] The compound obtained in Example 33-2 (12 g, 51.35 mmol, 1 equivalent) was dissolved in diethyl oxalate (128.40 g, 878.60 mmol, 120.00 mL, 17.11 equivalent) and 140 o Stirred for 6 hours at C. The m / z of the title compound ([M + H]) on LCMS + = 288.5) was observed. The reaction mixture was concentrated and purified by chromatography (stationary phase: silica, mobile phase: dichloromethane: methanol = 1 / 0 to 10 / 1), and then solidified with ethyl acetate (100 mL). The title compound (11.5 g, 39.57 mmol, 77.0% yield, 99% purity) was obtained as a yellow solid.

[0315] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 12.30 (s, 1H), 8.79 - 8.50 (m, 1H), 7.87 - 7.74 (m, 1H), 7.61 - 7.47 (m, 1H), 7.33 - 7.16 (m, 2H), 6.18 (d, J = 1.2 Hz, 1H), 2.25 (s, 3H).

[0316]

[0317] Example 33-4: 3,7-Dichloro-1-(2-methylpyridin-3-yl)quinoxalin-2(1H)-one

[0318] The compound obtained in Example 33-3 (1 g, 3.48 mmol, 1 equivalent), phosphoryl chloride (1.60 g, 10.43 mmol, 969.01 uL, 3 equivalents), N,N-dimethylaniline (1.26 g, 10.43 mmol, 1.32 mL, 3 equivalents) were dissolved in toluene (10 mL) and stirred at 110 o The mixture was stirred for 12 hours at C. The reaction mixture was concentrated to obtain the title compound (1 g, crude mixture) as a yellow oil, which was used in the next reaction without further purification.

[0319]

[0320] Example 33-5: 3-Amino-7-chloro-1-(2-methylpyridin-3-yl)quinoxalin-2(1H)-one

[0321] The compound obtained in Example 33-4 (1 g, 3.27 mmol, 1 equivalent) was dissolved in tetrahydrofuran (1 mL) and aqueous ammonia solution (3.82 g, 32.66 mmol, 4.19 mL, 30% purity, 10 equivalent) was added. The reaction mixture was stirred at 25 o Stirred for 12 hours at C. The m / z of the title compound ([M + H]) was determined by LCMS. + = 287.3) was observed, and the reaction mixture was concentrated under reduced pressure and filtered. The filter cake was concentrated to obtain the title compound (936 mg, crude mixture) in the form of a yellow solid.

[0322]

[0323] Example 33-6: 7-Chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0324]

[0325] The compound obtained in Example 34-5 (300 mg, 1.05 mmol, 1 equivalent) and 2-chloroacetaldehyde (164.27 mg, 2.09 mmol, 134.65 uL, 2 equivalents) were added to ethanol (3 mL). The reaction mixture was stirred at 80 oStirred for 12 hours at C. The desired m / z ([M + H]) was determined by LCMS. + = 311.3) was detected. The reaction mixture was concentrated under reduced pressure and purified by prep-HPLC (column: 3_Phenomenex Luna C18 75*30mm*3μm; mobile phase: [water (0.1% ammonium hydrocarbon)-acetonitrile], B%: 41%-71%, 10 min). The purified product was neutralized with aqueous sodium bicarbonate solution and extracted to obtain the title compound (140 mg, 450.09 μmol, 43.0% yield, 99.9% purity) as a yellow solid.

[0326] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.72 - 8.67 (m, 2H), 8.33 (d, J = 8.8 Hz, 1H), 7.92 - 7.85 (m, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.57 - 7.46 (m, 2H), 6.43 (d, J = 2.0 Hz, 1H), 2.25 (s, 3H).

[0327]

[0328] Example 34: 7-Chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0329]

[0330] In Example 33-6, the title compound was synthesized using the same method by changing 2-chloroacetaldehyde to 2-chloropropanal.

[0331] 1 H NMR (400 MHz, DMSO-d 6,ppm): δ 8.69 (br d, J = 4.0 Hz, 1H), 8.29 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.57 - 7.50 (m, 1H), 7.48 - 7.36 (m, 2H), 6.44 (d, J = 2.0 Hz, 1H), 2.86 (s, 3H), 2.23 (s, 3H).

[0332]

[0333] Example 35: 7-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0334]

[0335] The title compound was synthesized in the same manner as in Example 33, except that the starting material was changed to 2,6-dichloro-3-nitropyridine.

[0336] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.72 (d, J = 8.4 Hz, 1H), 8.69 (d, J = 1.2 Hz, 1H), 7.73 - 7.70 (m, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.46 - 7.33 (m, 3H), 7.32 - 7.27 (m, 1H), 2.00 (s, 3H).

[0337]

[0338] Example 36: 7-Methyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0339]

[0340] The title compound of Example 35 (400 mg, 1.29 mmol, 1 equiv), methylboronic acid (154.11 mg, 2.57 mmol, 2 equiv), Pd(dppf)Cl2 (94.19 mg, 128.73 μmol, 0.1 equiv), and cesium carbonate (1.05 g, 3.22 mmol, 2.5 equiv) were dissolved in dioxane (3.2 mL) and water (0.8 mL), and stirred at 100°C for 12 hours under nitrogen. After confirming the reaction, it was cooled to 15°C, quenched with 10 mL of water, and extracted with ethyl acetate. The extracted organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification was performed by Prep-HPLC (Column: Waters Xbridge 150*25mm* 5μm; Mobile phase: [Water (10 mM ammonium carbonate)-ACN]; B%: 26%-56%, 8 min) to obtain 110 mg of a white solid.

[0341] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.64 (d, J = 1.2 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 1.2 Hz, 1H), 7.44 - 7.31 (m, 3H), 7.31 - 7.23 (m, 2H), 2.31 (s, 3H), 1.97 (s, 3H).

[0342]

[0343] Example 37: 7-Chloro-5-(2-methoxyphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0344]

[0345] The title compound was synthesized using the same method as in Example 33-1, using 2-methoxyaniline instead of 2-methylpyridin-3-amine.

[0346] 1 H NMR (400 MHz, DMSO-d 6,ppm): δ 8.68 (d, J = 1.2 Hz, 1H), 8.32 - 8.26 (m, 1H), 7.70 (d, J = 1.2 Hz, 1H), 7.65 - 7.59 (m, 1H), 7.49 - 7.41 (m, 2H), 7.37 - 7.32 (m, 1H), 7.24 - 7.19 (m, 1H), 6.46 - 6.45 (m, 1H), 3.72 (s, 3H).

[0347]

[0348] Example 38: 5-(2-Bromophenyl)-7-chloroimidazo[1,2-a]quinoxalin-4(5H)-one

[0349]

[0350] In Example 1-2, the title compound was synthesized in the same manner by changing o-tolylboronic acid to (2-bromophenyl)boronic acid.

[0351] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.90 (d, J = 1.3 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.72 (s, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.43 - 7.37 (m, 1H), 7.30 (dd, J = 8.7, 2.2 Hz, 1H), 6.57 (d, J = 2.1 Hz, 1H).

[0352]

[0353] Example 39: 7-Chloro-5-(m-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0354]

[0355] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to m-tolylboronic acid.

[0356] 1H NMR (400 MHz, CDCl 3, ppm): δ 7.88 (d, J = 1.3 Hz, 1H), 7.71 (d, J = 1.3 Hz, 1H), 7.67 (d, J = 8.7 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.30 - 7.26 (m, 1H), 7.11 (d, J = 8.2 Hz, 2H), 6.74 (d, J = 2.1 Hz, 1H), 2.46 (s, 3H).

[0357]

[0358] Example 40: 7-Chloro-5-(3-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0359]

[0360] In Example 1-2, the title compound was synthesized using the same method by changing o-tolylboronic acid to (3-fluorophenyl)boronic acid.

[0361] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.90 (d, J = 1.3 Hz, 1H), 7.72 (d, J = 1.3 Hz, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.63 (td, J = 8.2, 6.1 Hz, 1H), 7.37 - 7.28 (m, 2H), 7.19 - 7.12 (m, 1H), 7.09 (dt, J = 8.7, 2.2 Hz, 1H), 6.73 (d, J = 2.1 Hz, 1H).

[0362]

[0363] Example 41: 7-Fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0364]

[0365] The title compound was synthesized in the same manner as in Example 1, except that the starting material was changed to 1,4-difluoro-2-nitrobenzene.

[0366] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.89 (d, J = 1.3 Hz, 1H), 7.77 - 7.62 (m, 2H), 7.55 - 7.39 (m, 3H), 7.21 (d, J = 7.5 Hz, 1H), 7.03 (t, J = 6.9 Hz, 1H), 6.35 (dd, J = 10.1, 2.7 Hz, 1H), 2.10 (s, 3H).

[0367]

[0368] Example 42: 3-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[4,3-e]pyrazin-6(5H)-one

[0369]

[0370] The title compound was synthesized in the same manner as in Example 33, except that the starting material was changed to 2,4-dichloro-5-nitropyridine.

[0371] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 9.38 - 9.26 (m, 1H), 8.82 - 8.66 (m, 1H), 7.83 - 7.70 (m, 1H), 7.60 - 7.45 (m, 3H), 7.43 - 7.34 (m, 1H), 6.33 - 6.24 (m, 1H), 2.05 (s, 3H).

[0372]

[0373] Example 43: 2-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)benzonitrile

[0374] Example 43 Reaction scheme for the preparation of compound:

[0375]

[0376] Example 43-1: 2-((5-chloro-2-nitrophenyl)amino)benzonitrile

[0377] 4-Chloro-2-fluoro-1-nitrobenzene (500 mg, 2.85 mmol, 1 equiv), 2-aminobenzonitrile (606.04 mg, 5.13 mmol, 1.8 equiv), and lithium hydroxide monohydrate (215.27 mg, 5.13 mmol, 1.8 equiv) were dissolved in dimethyl sulfoxide (5 mL), and stirred at 55 o C and stirred for 12 hours. When the reaction confirmed the formation of a new substance through TLC, water (50 mL) was added to the reaction mass and extracted with ethyl acetate (50 mL X 3). The organic layer was washed with saturated aqueous sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (stationary phase: silica, mobile phase: petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain the title compound (500 mg, 1.83 mmol, 64.1% yield) as a yellow solid.

[0378] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 9.69 (br s, 1H), 8.22 (d, J = 9.2 Hz, 1H), 7.79 - 7.74 (m, 1H), 7.71 - 7.65 (m, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.38 - 7.32 (m, 1H), 7.15 (d, J = 2.0 Hz, 1H), 6.93 - 6.89 (m, 1H).

[0379]

[0380] Example 43-2: 2-((2-amino-5-chlorophenyl)amino)benzonitrile

[0381] The compound obtained in Example 43-1 (400 mg, 1.46 mmol, 1 equivalent) was dissolved in ethanol (10 mL) and water (2 mL), and iron (652.98 mg, 11.69 mmol, 8 equivalents) and ammonium chloride (312.73 mg, 5.85 mmol, 4 equivalents) were added. The reaction mixture was stirred at 80 o Stirred for 12 hours at C. The desired m / z ([M + H]) was determined on LCMS. + = 244.4) was detected. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The title compound (350 mg, crude mixture) in the form of a yellow solid was used in the next reaction without further purification.

[0382]

[0383] Example 43-3: 2-(7-chloro-2,3-dioxo-3,4-dihydroquinoxalin-1(2H)-yl)benzonitrile

[0384] The compound obtained in Example 43-2 was used as a starting material and the title compound was obtained in the same manner as in Example 33-3.

[0385] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 12.44 (br s, 1H), 8.22 - 8.17 (m, 1H), 8.08 - 7.99 (m, 1H), 7.86 - 7.80 (m, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.38 - 7.20 (m, 2H), 6.27 (s, 1H).

[0386]

[0387] Example 43-4: 2-(3,7-dichloro-2-oxoquinoxalin-1(2H)-yl)benzonitrile

[0388] The compound obtained in Example 43-3 was used as a starting material and the title compound was obtained in the same manner as in Example 33-4.

[0389]

[0390] Example 43-5: 2-(3-amino-7-chloro-2-oxoquinoxalin-1(2H)-yl)benzonitrile

[0391] The compound obtained in Example 43-4 was used as a starting material and the title compound was obtained in the same manner as in Example 33-5.

[0392]

[0393] Example 43-6: 2-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)benzonitrile

[0394]

[0395] The compound obtained in Example 43-5 was used as a starting material and the title compound was obtained in the same manner as in Example 33-6.

[0396] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.74 (s, 1H), 8.37 (d, J = 8.8 Hz, 1H), 8.25 - 8.19 (m, 1H), 8.09 - 8.02 (m, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.58 - 7.51 (m, 1H), 6.52 (d, J = 2.0 Hz, 1H).

[0397]

[0398] Example 44: N-(3-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)phenyl)methanesulfonamide

[0399] Example 44 Reaction scheme for the preparation of compound:

[0400]

[0401] Example 44-1: N-(3-((5-chloro-2-nitrophenyl)amino)phenyl)methanesulfonamide

[0402] 4-Chloro-2-fluoro-1-nitrobenzene (3 g, 17.09 mmol, 1 equiv) and N-(3-aminophenyl)methanesulfonamide (3.50 g, 18.80 mmol, 3.54 mL, 1.1 equiv) were dissolved in dimethylsulfonamide (35 mL), and N,N-diisopropylethylamine (4.42 g, 34.18 mmol, 5.95 mL, 2 equiv) was added. The reaction mixture was 110 o C for 15 hours. Water (150 mL) was added to the reaction mixture and extracted with ethyl acetate (100 mL X 3). The organic layer was washed with saturated aqueous sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (stationary phase: silica, mobile phase: petroleum ether / ethyl acetate = 1 / 0 to 10 / 1) to obtain the title compound (2 g, 5.85 mmol, 34.2% yield) as a red solid.

[0403] 1 H NMR (400 MHz, CDCl 3, ppm): δ 9.51 (br s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 2.0Hz, 1H), 7.19 (s, 1H), 7.14 - 7.05 (m, 2H), 6.79 (dd, J = 2.0, 9.2 Hz, 1H), 6.57 (s, 1H), 3.10 (s, 3H).

[0404]

[0405] Example 44-2: N-(3-((2-amino-5-chlorophenyl)amino)phenyl)methanesulfonamide

[0406] The title compound was synthesized in the same manner as in Example 33-2 using the compound obtained in Example 44-1 as a starting material.

[0407] 1 H NMR (400 MHz, DMSO-d 6,ppm): δ 9.57 (s, 1H), 7.35 (s, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.85 - 6.80 (m, 1H), 6.74 - 6.69 (m, 2H), 6.58 (br d, J = 7.6 Hz, 1H), 6.50 (br d, J = 8.0 Hz, 1H), 5.15 - 4.75 (m, 2H), 2.96 (s, 3H).

[0408]

[0409] Example 44-3: N-(3-(7-chloro-2,3-dioxo-3,4-dihydroquinoxalin-1(2H)-yl)phenyl)methanesulfonamide

[0410] The compound obtained in Example 44-2 was used as a starting material and the title compound was obtained in the same manner as in Example 33-3.

[0411] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 12.18 (br s, 1H), 10.13 (br s, 1H), 7.60 (br t, J = 7.6 Hz, 1H), 7.37 (br d, J = 7.8 Hz, 1H), 7.21 (br s, 3H), 7.12 (br d, J = 7.6 Hz, 1H), 6.28 (s, 1H), 3.08 (s, 3H).

[0412]

[0413] Example 44-4: N-(3-(3,7-dichloro-2-oxoquinoxalin-1(2H)-yl)phenyl)methanesulfonamide

[0414] The compound obtained in Example 44-3 was used as a starting material and the title compound was obtained in the same manner as in Example 33-4.

[0415]

[0416] Example 44-5: N-(3-(3-amino-7-chloro-2-oxoquinoxalin-1(2H)-yl)phenyl)methanesulfonamide

[0417] The compound obtained in Example 44-4 was used as a starting material and the title compound was obtained in the same manner as in Example 32-5.

[0418]

[0419] Example 44-6: N-(3-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)phenyl)methanesulfonamide

[0420]

[0421] The compound obtained in Example 44-5 was used as a starting material and the title compound was obtained in the same manner as in Example 33-6.

[0422] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 10.18 - 10.08 (m, 1H), 8.64 (s, 1H), 8.28 (d, J = 8.8 Hz, 1H), 7.67 (s, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.47 - 7.38 (m, 2H), 7.26 (s, 1H), 7.19 (br d, J = 7.6 Hz, 1H), 6.52 (d, J = 2.0 Hz, 1H), 3.10 (s, 3H).

[0423]

[0424] Example 45: 7-Chloro-2-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0425]

[0426] The compound obtained in Example 33-5 (210 mg, 732.43 μmol, 1 equivalent) and 1-bromo-2,2-dimethoxypropane (670.33 mg, 3.66 mmol, 492.89 μL, 5 equivalents) were dissolved in isopropyl alcohol (5 mL), and pyridinium para-toluenesulfonic acid (18.41 mg, 73.24 μmol, 0.1 equivalent) was added. The reaction mixture was stirred at 95 oC for 16 hours. The reaction mixture was concentrated under reduced pressure to remove isopropyl alcohol, water (10 mL) was added, and then extracted with dichloromethane (10 mL X 3). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge C18 150*50mm* 10μm; mobile phase: [water (10 mM ammonium carbonate)-acetonitrile]; B%: 22%-52%, 10 min) to obtain the title compound (164.77 mg, 492.13 μmol, 67.2% yield, 97% purity) as a white solid.

[0427] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.69 (m, 1H), 8.42 (s, 1H), 8.22 (d, J = 8.8 Hz, 1H), 7.92 - 7.78 (m, 1H), 7.57 (s, 1H), 7.49 - 7.45 (m, 1H), 6.42 (d, J = 2.0 Hz, 1H), 2.37 (s, 3H), 2.23 (s, 3H).

[0428]

[0429] Example 46: 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0430] Example 46 Reaction scheme for the preparation of compound:

[0431]

[0432] Example 46-1: 5-(o-tolyl)-7-vinylimidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0433] The compound of Example 35 (300 mg, 965.45 μmol, 1 equiv) and vinyltrifluoroborane calcium salt (258.64 mg, 1.93 mmol, 2 equiv), Pd(dppf)Cl2 (70.64 mg, 96.54 μmol, 0.1 equiv), and Cs2CO3 (786.40 mg, 2.41 mmol, 2.5 equiv) were dissolved in dioxane (6 mL) and water (1.5 mL), and stirred at 100°C for 12 hours under nitrogen. After confirming the reaction, the mixture was quenched with water (20 mL) and extracted with ethyl acetate. The extracted organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (260 mg, 842.79 μmol, 87.30% yield, 98% purity) was obtained as a yellow solid by purification using column chromatography (petroleum ether / ethyl acetate = 100 / 0 to 0 / 100).

[0434] 1 H NMR (400 MHz, CDCl 3, ppm): δ 9.51 (br s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 2.0Hz, 1H), 7.19 (s, 1H), 7.14 - 7.05 (m, 2H), 6.79 (dd, J = 2.0, 9.2 Hz, 1H), 6.57 (s, 1H), 3.10 (s, 3H).

[0435]

[0436] Example 46-2: 4-Oxo-5-(o-tolyl)-4,5-dihydroimidazo[1,2-a]pyrido[2,3-e]pyrazine-7-carbaldehyde

[0437] The compound of Example 46-1 (170 mg, 562.30 μmol, 1 equiv) was dissolved in dioxane (2 mL) and water (2 mL). Sodium periodate (601.36 mg, 2.81 mmol, 155.79 μL, 5 equiv) and potassium osmium(VI) oxide dihydrate (41.44 mg, 112.46 μmol, 0.2 equiv) were added dropwise, and the mixture was stirred at room temperature for 2 hours. After confirming the reaction, the mixture was quenched with 10 mL of water, and the organic layer was extracted with ethyl acetate. The extracted organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (185 mg, crude mixture) as a yellow solid was obtained without further purification.

[0438] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 9.62 - 9.51 (m, 1H), 8.91 - 8.82 (m, 1H), 8.80 - 8.72 (m, 1H), 8.02 - 7.93 (m, 1H), 7.78 - 7.73 (m, 1H), 7.47 - 7.30 (m, 4H), 2.06 - 2.01 (m, 3H).

[0439]

[0440] Example 46-3: 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0441]

[0442] The compound of Example 46-2 (155 mg, 509.36 μmol, 1 equivalent) was dissolved in dichloromethane (2.6 mL), and diethylaminosulfur trifluoride (246.31 mg, 1.53 mmol, 201.89 μL, 3 equivalents) was added dropwise at 0°C. The mixture was stirred at room temperature for 12 hours, and after confirming the reaction, it was quenched with 10 mL of aqueous sodium bicarbonate solution, and the organic layer was extracted with dichloromethane. The extracted organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (27 mg, 81.09 μmol, 15.9% yield, 98% purity) was obtained as a yellow solid by purification through prep-HPLC (column: Waters Xbridge 150*25mm* 5um; mobile phase: [water (10 mM ammonium carbonate)-acetonitrile]; B%: 30%-60%, 8 min).

[0443] 1 H NMR (400 MHz, DMSO-d6, ppm): 8.82 (d, J=8.4 Hz, 1 H), 8.67 - 8.78 (m, 1 H), 7.69 - 7.77 (m, 2 H), 7.24 - 7.46 (m, 4 H), 6.53 - 6.87 (m, 1 H), δ ppm 1.99 (s, 3 H).

[0444]

[0445] Example 47: 7-Isopropyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0446] Example 47 Reaction scheme for the preparation of compound:

[0447]

[0448] Example 47-1: 7-(Propenyl)-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-a]pyrazin-4(5H)-one

[0449] The compound of Example 35 (200 mg, 643.63 μmol, 1 equiv), isopropenyltrifluoroborane calcium salt (190.48 mg, 1.29 mmol, 2 equiv), Pd(dppf)Cl2 (47.10 mg, 64.36 μmol, 0.1 equiv), and cesium carbonate (524.27 mg, 1.61 mmol, 2.5 equiv) were dissolved in dioxane (4 mL) / water (1 mL), and stirred at 100 o C and stirred. After confirming the reaction, the mixture was quenched with water and extracted with ethyl acetate. The extracted organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 100 / 0 to 0 / 100) (ethyl acetate: methanol = 10:1) to obtain the title compound (190 mg, 510.50 μmol, 79.32% yield, 85% purity) as a yellow solid.

[0450] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.69 (d, J = 1.2 Hz, 1H), 8.65 - 8.58 (m, 1H), 7.70 (d, J = 1.2 Hz, 1H), 7.68 - 7.62 (m, 1H), 7.43 - 7.39 (m, 2H), 7.39 - 7.36 (m, 1H), 7.35 - 7.32 (m, 1H), 7.30 - 7.27 (m, 1H), 5.66 (s, 1H), 5.22 - 5.14 (m, 1H), 1.98 (s, 3H), 1.86 - 1.82 (m, 3H).

[0451]

[0452] Example 47-2: 7-Isopropyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0453]

[0454] The compound of Example 47-1 (165 mg, 521.56 μmol, 1 equivalent) was dissolved in methanol (5 mL), palladium / carbon (20 mg, 10% purity) was added, hydrogen was injected, and the mixture was stirred at room temperature for 2 hours. The residue was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5μm; mobile phase: [water (10 mM ammonium carbonate)-acetonitrile]; B%: 41%-71%, 8 min) to obtain the title compound (93.96 mg, 292.18 μmol, 56.02% yield, 99% purity) as a white solid.

[0455] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.67 - 8.61 (m, 1H), 8.59 - 8.52 (m, 1H), 7.70 - 7.65 (m, 1H), 7.45 - 7.22 (m, 5H), 1.96 (s, 3H), 1.05 - 0.93 (m, 6H).

[0456]

[0457] Example 48: 7-Chloro-5-(3-methylpyrazin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0458] Example 48 Reaction scheme for the preparation of compound:

[0459]

[0460] Example 48-1: N-(5-chloro-2-nitrophenyl)-3-methylpyrazin-2-amine

[0461] 4-Chloro-2-fluoro-1-nitrobenzene (4 g, 22.79 mmol, 1 equiv) and 3-methylpyrazin-2-amine (2.98 g, 27.34 mmol, 1.2 equiv) were dissolved in dimethylformamide (40 mL), and potassium tert-butoxide (3.07 g, 27.34 mmol, 1.2 equiv) was added dropwise. The reaction mixture was 55 oC and stirred for 15 hours. When the reaction was completed as shown by TLC, the mixture was diluted with water (200 mL) and extracted with ethyl acetate (100 mL X 3). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 1 / 0 to 10 / 1) to obtain the title compound (1.6 g, 6.05 mmol, 26.53% yield) as a yellow solid.

[0462]

[0463] Example 48-2: 5-Chloro-N 1 -(3-methylpyrazin-2-yl)benzene-1,2-diamine

[0464] The title compound was synthesized in the same manner as in Example 33-2 using the compound of Example 48-1 as a starting material.

[0465]

[0466] Example 48-3: Ethyl 2-((4-chloro-2-((3-methylpyrazin-2-yl)amino)phenyl)amino)-2-oxoacetate

[0467] The compound of Example 48-2 (2 g, 8.52 mmol, 1 eq) and ethyl 2-chloro-2-oxo-acetate (1.40 g, 10.23 mmol, 1.14 mL, 1.2 eq) were added to water (8 mL) and dichloromethane (32 mL), and sodium carbonate (993.58 mg, 9.37 mmol, 1.1 eq) was added dropwise. The reaction mixture was stirred at room temperature for 12 hours. When the reaction was complete through TLC, it was diluted with water (50 mL) and extracted with dichloromethane (50 mL X 3). The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting yellow oily title compound (2 g, crude mixture) was used in the next reaction without further purification.

[0468]

[0469] Example 48-4: 7-Chloro-1-(3-methylpyrazin-2-yl)-1,4-dihydroquinoxaline-2,3-dione

[0470] The compound of Example 48-3 (1.5 g, 4.48 mmol, 1 equiv) was dissolved in tetrahydrofuran (20 mL), and sodium hydride (896.09 mg, 22.40 mmol, 60% purity, 5 equiv) was added dropwise. The reaction mixture was stirred at room temperature for 12 hours. After the reaction was terminated by adding water (50 mL) to the reaction mixture, the mixture was extracted with ethyl acetate (50 mL X 3). The organic layer was washed with a saturated aqueous sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 3 / 1 to 1 / 1) to obtain the title compound (0.4 g, 1.39 mmol, 30.92% yield) as a yellow solid.

[0471] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 12.38 (br s, 1H), 8.82 (d, J = 2.4 Hz, 1H), 8.67 (d, J = 2.0 Hz, 1H), 7.28 (s, 2H), 6.45 (s, 1H), 2.39 (s, 3H).

[0472]

[0473] Example 48-5: 3,7-Dichloro-1-(3-methylpyrazin-2-yl)quinoxalin-2(1H)-one

[0474] The title compound was synthesized in the same manner as in Example 33-4 using the compound of Example 48-4 as a starting material.

[0475]

[0476] Example 48-6: 3-Amino-7-chloro-1-(3-methylpyrazin-2-yl)quinoxalin-2(1H)-one

[0477] The compound of Example 48-5 (400 mg, 1.30 mmol, 1 equiv) was dissolved in isopropyl alcohol (30 mL), and ammonia (2 M, 6.51 mL, 10 equiv) was added dropwise. The reaction mixture was stirred at room temperature for 12 hours. The desired m / z ([M + H]) was determined by LCMS. + = 288.4) was detected. The reaction mixture was concentrated. The title compound (350 mg, crude mixture) as a black oil was used in the next reaction without further purification.

[0478]

[0479] Example 48-7: 7-Chloro-5-(3-methylpyrazin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0480]

[0481] The title compound was synthesized using the compound of Example 48-6 as a starting material in the same manner as in Example 33-6.

[0482] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.83 (d, J = 2.4 Hz, 1H), 8.73 - 8.68 (m, 2H), 8.34 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 1.2 Hz, 1H), 7.54 - 7.50 (m, 1H), 6.68 (d, J = 2.0 Hz, 1H), 2.38 (s, 3H).

[0483]

[0484] Example 49: 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one

[0485]

[0486] The title compound was synthesized in the same manner as in Example 48 using 2-chloro-3-nitro-6-(trifluoromethyl)pyridine as a starting material.

[0487] 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.84 - 8.92 (m, 1 H), 8.77 (d, J = 1.2 Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.75 (d, J = 1.2 Hz, 1 H), 7.27 - 7.45 (m, 4 H), 1.96 - 2.02 (m, 3 H).

[0488]

[0489] Example 50: 7-Chloro-5-(2-(trifluoromethoxy)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0490]

[0491] The title compound was synthesized using the same method as in Example 33-1 by changing 2-methylpyridin-3-amine to 2-(trifluoromethoxy)aniline.

[0492] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.71 (d, J = 0.8 Hz, 1H), 8.34 (d, J = 8.8 Hz, 1H), 7.80 - 7.69 (m, 5H), 7.53 - 7.47 (m, 1H), 6.50 (d, J = 2.0) Hz, 1H).

[0493]

[0494] Example 51: 7-Chloro-5-(2,6-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0495]

[0496] The title compound was synthesized using the same method as in Example 33-1, but the 2-methylpyridin-3-amine was changed to 2,6-dimethylaniline.

[0497] 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.71 (d, J = 1.0 Hz, 1H), 8.36 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.53 - 7.48 (m, 1H), 7.46 - 7.40 (m, 1H), 7.39 - 7.34 (m, 2H), 6.34 (d, J = 2.0 Hz, 1H), 1.95 (s, 6H).

[0498]

[0499] Example 52: 7-Chloro-5-(2-fluoro-6-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0500]

[0501] The title compound was synthesized in the same manner as in Example 33-1 by changing 2-methylpyridin-3-amine to 2-fluoro-6-methylaniline.

[0502] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.75 - 8.69 (m, 1H), 8.35 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.63 - 7.56 (m, 1H), 7.55 - 7.50 (m, 1H), 7.43 - 7.35 (m, 2H), 6.49 (d, J = 2.0 Hz, 1H), 2.08 - 2.05 (m, 3H).

[0503]

[0504] Example 53: 7-Chloro-5-(3-methylpyridin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0505]

[0506] The title compound was synthesized using the same method as in Example 33-1, but the 2-methylpyridin-3-amine was changed to 3-methylpyridin-2-amine.

[0507] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.75 - 8.67 (m, 1H), 8.59 (br d, J = 3.5 Hz, 1H), 8.40 - 8.29 (m, 1H), 8.05 (br d, J = 7.3 Hz, 1H), 7.76 - 7.71 (m, 1H), 7.66 - 7.58 (m, 1H), 7.54 - 7.46 (m, 1H), 6.38 - 6.29 (m, 1H), 2.17 - 2.06 (m, 3H).

[0508]

[0509] Example 54: 7-Chloro-5-(2-chloropyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0510] Example 54 Reaction scheme for the preparation of compound:

[0511]

[0512] Example 54-1: N-(5-chloro-2-nitrophenyl)-2-methoxypyridin-3-amine

[0513] 2-Methoxypyridin-3-amine (1.86 g, 14.95 mmol, 1.05 equiv) was dissolved in tetrahydrofuran (25 mL), and lithium bis(trimethylsilyl)amide (1 M, 17.09 mL, 1.2 equiv) was added dropwise, and then stirred at 0 o C and stirred for 1 hour. To the resulting reaction mixture, a solution of 4-chloro-2-fluoro-1-nitrobenzene (2.5 g, 14.24 mmol, 1 equivalent) in tetrahydrofuran (5 mL) was added at 0 o C was added. The reaction mixture was stirred at room temperature for 1 hour. The desired m / z ([M + H]) was determined by LC-MS. += 280.2) was observed. A saturated aqueous ammonium chloride solution (60 mL) was added and extracted with ethyl acetate (3 X 40 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (3 X 40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by column chromatography (stationary phase: silica, mobile phase: 0-12% ethyl acetate / petroleum ether) to obtain the title compound (2.81 g, 8.29 mmol, 58.2% yield, 82.5% purity) as a red solid.

[0514] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.41 (s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 8.12 - 8.06 (m, 1H), 7.86 - 7.78 (m, 1H), 7.15 - 7.08 (m, 1H), 6.98 - 6.90 (m, 2H), 3.96 - 3.90 (m, 3H).

[0515]

[0516] Example 54-2: 5-Chloro-N 1 -(2-methoxypyridin-3-yl)benzene-1,2-diamine

[0517] The title compound was synthesized in the same manner as in Example 33-2 using the compound of Example 54-1 as a starting material.

[0518] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 7.55 (dd, J = 1.6, 4.8 Hz, 1H), 6.94 - 6.92 (m, 1H), 6.91 - 6.86 (m, 2H), 6.85 - 6.81 (m, 1H), 6.79 - 6.77 (m, 1H), 6.73 - 6.71 (m, 1H), 5.41 - 4.99 (m, 2H), 3.96 - 3.92 (m, 3H).

[0519]

[0520] Example 54-3: 7-Chloro-1-(2-methoxypyridin-3-yl)-1,4-dihydroquinoxaline-2,3-dione

[0521] The compound of Example 54-2 (1.9 g, 7.61 mmol, 1 equivalent), diethyl oxalate (20.33 g, 139.11 mmol, 19.00 mL, 18.28 equivalent), N,N-diisopropylethylamine (1.97 g, 15.22 mmol, 2.65 mL, 2 equivalent) were dissolved in nitrogen at 160 o C for 4 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Petroleum ether (30 mL) was added to the crude compound, and solidification was achieved by leaving it at room temperature for 30 minutes. The resulting residue was filtered and the filter cake was concentrated under reduced pressure to obtain the title compound (860 mg, 2.83 mmol, 37.1% yield, 99.8% purity) as a green solid.

[0522] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 12.35 (br s, 1H), 8.41 (br d, J = 3.6 Hz, 1H), 7.87 (s, 1H), 7.39 - 7.09 (m, 3H), 6.33 (s, 1H), 3.84 (s, 3H).

[0523]

[0524] Example 54-4: 3,7-Dichloro-1-(2-hydroxypyridin-3-yl)quinoxalin-2(1H)-one

[0525] The title compound was synthesized in the same manner as in Example 33-4 using the compound of Example 54-3 as a starting material.

[0526]

[0527] Example 54-5: 3-Amino-7-chloro-1-(2-hydroxypyridin-3-yl)quinoxalin-2(1H)-one

[0528] The title compound was synthesized in the same manner as in Example 33-5 using the compound of Example 54-4 as a starting material.

[0529] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 10.03 - 8.73 (m, 1H), 7.79 (dd, J = 1.9, 7.2 Hz, 1H), 7.66 (dd, J = 2.0, 6.3 Hz, 1H), 7.53 - 7.38 (m, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.31 - 7.23 (m, 1H), 7.20 (dd, J = 2.4, 8.5 Hz, 1H), 6.63 - 6.57 (m, 1H), 6.45 - 6.39 (m, 1H)

[0530]

[0531] Example 54-6: 7-Chloro-5-(2-hydroxypyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0532] The title compound was synthesized in the same manner as in Example 33-6 using the compound of Example 54-5 as a starting material.

[0533] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 12.34 (br s, 1H), 8.66 (d, J = 1.2 Hz, 1H), 8.29 (d, J = 8.8 Hz, 1H), 7.81 (dd, J = 2.0, 7.1 Hz, 1H), 7.73 - 7.66 (m, 2H), 7.47 (dd, J = 2.2, 8.8 Hz, 1H), 6.85 (d, J = 2.0 Hz, 1H), 6.46 (t, J = 6.8 Hz, 1H)

[0534]

[0535] Example 54-7: 7-Chloro-5-(2-chloropyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0536]

[0537] The compound of Example 54-6 (255 mg, 815.45 μmol, 1 equiv) and phosphoryl chloride (4.13 g, 26.90 mmol, 2.5 mL, 32.99 equiv) and N,N-diisopropylethylamine (158.09 mg, 1.22 mmol, 213.06 μL, 1.5 equiv) were added to 110 o C for 16 h. Saturated aqueous sodium bicarbonate solution (150 mL) was slowly added to the reaction mixture, and extracted with ethyl acetate (40 mL X 3). The organic layer was washed with saturated aqueous sodium chloride solution (50 mL X 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge C18 150*50mm* 10μm; mobile phase: [water (10 mM ammonium bicarbonate)-acetonitrile]; B%: 25%-55%, 10 min) to obtain the title compound (55 mg, 164.45 μmol, 20.2% yield, 99.0% purity) as a white solid.

[0538] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.73 - 8.71 (m, 1H), 8.70 - 8.67 (m, 1H), 8.40 - 8.30 (m, 1H), 8.24 - 8.15 (m, 1H), 7.81 - 7.75 (m, 1H), 7.75 - 7.72 (m, 1H), 7.58 - 7.47 (m, 1H), 6.65 (d, J = 2.0 Hz, 1H).

[0539]

[0540] Example 55: 2-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0541]

[0542] The title compound was synthesized in the same manner as in Example 45, except that the starting material was changed to 2-fluoro-1-nitro-4-(trifluoromethyl)benzene.

[0543] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.73 - 8.69 (m, 1H), 8.53 - 8.47 (m, 1H), 8.42 - 8.37 (m, 1H), 7.92 - 7.87 (m, 1H), 7.80 - 7.74 (m, 1H), 7.58 - 7.52 (m, 1H), 6.61 (s, 1H), 2.40 (s, 3H), 2.23 (s, 3H).

[0544]

[0545] Example 56: 5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0546]

[0547] The title compound was synthesized in the same manner as in Example 33, except that the starting material was changed to 2-fluoro-1-nitro-4-(trifluoromethyl)benzene.

[0548] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.79 (s, 1H), 8.72 - 8.71 (m, 1H), 8.53 - 8.51 (m, 1H), 7.91 - 7.89 (m, 1H), 7.81 - 7.79 (m, 1H), 7.77 - 7.73 (m, 1H), 7.57 - 7.56 (m, 1H), 6.62 (s, 1H), 2.261 (s, 3H).

[0549]

[0550] Example 57: 1-Bromo-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0551]

[0552] The compound of Example 56 (1 g, 2.90 mmol, 1 equivalent) was dissolved in acetonitrile (15 mL), and N-bromosuccinimide (516.95 mg, 2.90 mmol, 1 equivalent) was added. The reaction mixture was stirred at 25°C for 12 hours. The MS [M+H] of the title compound was determined by LCMS. + =424.7 was detected, the reaction mixture was concentrated under reduced pressure to remove the solvent, and the resulting concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm*5μm; mobile phase: [water (10mM ammonium carbonate)-acetonitrile]; B%: 32%-62%, 9 min] to obtain the title compound (270 mg, 625.26 μmol, 21.5% yield, 98% purity) as a yellow solid.

[0553] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.25 (d, J = 8.8 Hz, 1H), 8.73 - 8.71 (m, 1H), 7.88 - 7.84 (m, 3H), 7.58 - 7.54 (m, 1H), 6.66 - 6.65 (m, 1H), 2.27 (s, 3H).

[0554]

[0555] Example 58: 1-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0556] Example 58 Reaction scheme for the preparation of compound:

[0557]

[0558] The compound of Example 57 (150 mg, 354.45 μmol, 1 equiv), 2,4,6-trimethyl-1,3,5,2,4,6-trioxaborinene (3.5 M, 405.09 μL, 4 equiv), potassium carbonate (195.96 mg, 1.42 mmol, 4 equiv), Pd(PPh3)2Cl2 (24.88 mg, 35.45 μmol, 0.1 equiv) were dissolved in dimethylformamide (4 mL) and stirred for 12 hours at 90 o C and stirred. After confirming the reaction, the mixture was quenched at room temperature with saturated ammonium chloride aqueous solution (10 mL), and extracted with ethyl acetate. The extracted organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (75 mg, 205.13 μmol, 57.9% yield, 98% purity) as a yellow solid was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5 μm; mobile phase: [water (10 mM ammonium carbonate)]).

[0559] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.72 - 8.71 (m, 1H), 8.50 - 8.48 (m, 1H), 7.91 - 7.89 (m, 1H), 7.74 - 7.72 (m, 1H), 7.58 - 7.56 (m, 1H), 7.50 (s, 1H), 6.64 - 6.32 (m, 1H), 2.90 (s, 3H), 2.24 (m, 3H).

[0560]

[0561] Example 59: 1-Acetyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0562] Example 59 Reaction scheme for the preparation of compound:

[0563]

[0564] Example 59-1: 1-(1-Ethoxyvinyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0565] The compound of Example 57 (160.00 mg, 378.08 μmol, 1 equivalent), tributyl(1-ethoxyvinyl)staneine (218.47 mg, 604.93 μmol, 204.37 μL, 1.6 equivalent), and Pd(PPh3)2Cl2 (26.54 mg, 37.81 μmol, 0.1 equivalent) were dissolved in dioxane (5 mL) and stirred for 12 hours at 90 o The mixture was stirred at C. The following reaction was carried out without further purification.

[0566] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.72 - 8.71 (m, 1H), 8.50 - 8.48 (m, 1H), 7.91 - 7.89 (m, 1H), 7.74 - 7.72 (m, 1H), 7.58 - 7.56 (m, 1H), 7.50 (s, 1H), 6.64 - 6.32 (m, 1H), 2.90 (s, 3H), 2.24 (m, 3H).

[0567]

[0568] Example 59-2: 1-Acetyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0569]

[0570] To the compound of Example 59-1, 4 mL of hydrochloric acid / dioxane (1 mol / L) was added, and the mixture was stirred at 25°C for 2 hours. 20 mL of aqueous potassium fluoride solution was added to the reaction mixture to terminate the reaction, followed by extraction with ethyl acetate (10 mL X 3). The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5 μm; mobile phase: [water (10 mM ammonium carbonate)-acetonitrile]; B%: 26%-56%, 9 min) to obtain the title compound (52 mg, 129.62 μmol, 34.28% yield, 96.3% purity) as a yellow solid.

[0571] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.82 - 8.73 (m, 1H), 8.71 - 8.67 (m, 1H), 8.67 - 8.64 (m, 1H), 8.04 - 7.93 (m, 1H), 7.79 - 7.70 (m, 1H), 7.68 - 7.59 (m, 1H), 6.73 - 6.64 (m, 1H), 2.80 (s, 3H), 2.30 (m, 3H).

[0572]

[0573] Example 60: 2-Acetyl-1-hydroxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0574] Example 60 Reaction scheme for the preparation of compound:

[0575]

[0576] Example 60-1: tert-Butyl (4-(2-methylpyridin-3-yl)-3-oxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-2-yl)glycinate

[0577] 3-Chloro-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one (1 g, 2.94 mmol, 1 equiv) was dissolved in 10 mL of tetrahydrofuran, and triethylamine (893.64 mg, 8.83 mmol, 1.23 mL, 3 equiv) and tert-butyl 2-aminoacetate (772.29 mg, 5.89 mmol, 2 equiv) were added dropwise. The reaction solution was stirred at room temperature for 12 hours, quenched with water, and extracted with ethyl acetate. The extracted organic layer was washed with aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The title compound (730 mg, 1.44 mmol, 48.8% yield, 85.4% purity) was obtained as a yellow solid by purification using column chromatography (ethyl acetate / petroleum ether 0-50%).

[0578] 1 H NMR (400 MHz, DMSO-d6, ppm) δ 8.77 - 8.69 (m, 1H), 8.46 - 8.36 (m, 1H), 8.03 - 7.92 (m, 1H), 7.66 - 7.46 (m, 3H), 6.56 - 6.45 (m, 1H), 4.09 (dd, J = 2.4, 6.1 Hz, 2H), 2.21 - 2.16 (m, 3H), 1.47 - 1.41 (m, 10H).

[0579]

[0580] Example 60-2: (4-(2-methylpyridin-3-yl)-3-oxo-6-(trifluoro)-3,4-dihydroquinoxalin-2-yl)glycine

[0581] The compound of Example 60-1 (850 mg, 1.96 mmol, 1 equivalent) was dissolved in dichloromethane, and 8.5 mL of 4M hydrogen chloride / dioxane was added dropwise, followed by stirring at room temperature for 3 hours. The reaction was quenched with water, and the mixture was extracted with ethyl acetate. The extracted organic layer was washed with aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (630 mg, crude mixture) as a yellow solid.

[0582] 1 H NMR (400 MHz, DMSO-d6, ppm): δ13.41 - 12.10 (m, 1H), 8.80 - 8.67 (m, 1H), 8.35 - 8.27 (m, 1H), 8.04 - 7.88 (m, 1H), 7.70 - 7.60 (m, 1H), 7.59 - 7.47 (m, 2H), 6.55 - 6.36 (m, 1H), 4.20 (s, 2H), 2.23 - 2.13 (m, 3H).

[0583]

[0584] Example 60-3: 2-Acetyl-1-hydroxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0585]

[0586] The compound of Example 60-2 (200 mg, 482.20 μmol, 1 equivalent) was dissolved in 6 mL of tetrahydrofuran, and acetic anhydride (492.28 mg, 4.82 mmol, 452.88 μL, 10 equivalents) and triethylamine (671.17 μL, 4.82 mmol, 10 equivalents) were added to 0 o C was added dropwise. Afterwards, 4-dimethylaminopyridine (5.89 mg, 48.22 μmol, 0.1 equivalent) was added dropwise and 0 o C and stirred for 1 hour. After confirming the reaction, it was quenched with water (30 mL), adjusted to pH 6-7 with aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The extracted organic layer was washed with aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (methanol / dichloromethane 0-15%), solidified with ethyl acetate, and filtered. The title compound (35 mg, 86.39 μmol, 43.4% yield, 99.3% purity) as a yellow solid was obtained.

[0587] 1H NMR (400 MHz, DMSO-d6, ppm) δ 9.45 - 9.32 (m, 1H), 8.72 - 8.60 (m, 1H), 7.92 - 7.77 (m, 1H), 7.58 - 7.46 (m, 2H), 6.42 - 6.32 (m, 1H), 2.38 (s, 3H), 2.21 (s, 3H)

[0588]

[0589] Example 61: 7-Chloro-2-((4-methylpiperazin-1-yl)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0590] Example 61 Reaction scheme for the preparation of compound:

[0591]

[0592] Example 61-1: 7-Chloro-2-(chloromethyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0593] Using the compound of Example 54-4 (200 mg, 698 μmol, 1 equivalent) as a starting material, 1,3-dichloro-2-propanone (443 mg, 3.49 mmol, 5 equivalents) was dissolved in ethyl acetate and heated to reflux. After the reaction was completed, the mixture was cooled to room temperature and purified by column chromatography (ethyl acetate / hexane 0-100%) to obtain the title compound (50 mg, 139 μmol, 20% yield) as a white solid.

[0594]

[0595] Example 61-2: 7-Chloro-2-((4-methylpiperazin-1-yl)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0596]

[0597] The compound of Example 61-1 (50 mg, 139 μmol, 1 equivalent) was used as a starting material, and 1-methylpiperazine (20.9 mg, 209 μmol, 1.5 equivalent) was dissolved in ethanol and heated to reflux. Upon completion of the reaction, the mixture was cooled to room temperature and purified by column chromatography (methanol / dichloromethane 0-20%). The title compound (23 mg, 54.4 μmol, 39% yield, 99.77% purity) as a pale yellow solid was obtained.

[0598] 1 H NMR (400 MHz, CDCl 3, ppm): δ 8.75 (d, 1H, J= 3.6 Hz), 7.97 (brs, 1H), 7.71 (d, 1H, J= 8.4Hz), 7.57 (d, 1H, J= 7.6Hz), 7.45 - 7.43 (m, 1H), 7.33 - 7.31 (m, 1H), 6.55(s, 1H), 3.87(s, 2H), 2.82 - 2.68 (m, 8H), 2.42 (s, 3H), 2.36 (s, 3H)

[0599]

[0600] Example 62: 7-Chloro-5-(2-methylpyridin-3-yl)-2-(morpholinomethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0601]

[0602] Using the compound of Example 61-1 (40 mg, 111 μmol, 1 equivalent) as a starting material, the title compound (37 mg, 90.3 μmol, 81% yield, 99.43% purity) was obtained in the same manner as in Example 61-2.

[0603] 1 H NMR (400 MHz, CDCl 3,ppm): δ 8.75 (d, 1H, J= 3.6 Hz), 7.92 (s, 1H), 7.70 (d, 1H, J= 8.8Hz), 7.58 (d, 1H, J= 1.6Hz), 7.56 (d, 1H, J= 1.2Hz), 7.33 - 7.30 (m, 1H), 6.55(s, 1H), 3.82(s, 2H), 3.77 (m, 4H), 2.66 (s, 4H), 2.36 (s, 3H)

[0604]

[0605] Example 63: 2-((2-Oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0606]

[0607] The title compound (16 mg, 35.6 μmol, 42% yield, 97.92% purity) was obtained in the same manner as in Example 61-2 using the compound of Example 61-1 (30 mg, 83.5 μmol, 1 equivalent) as a starting material.

[0608] 1 H NMR (400 MHz, CDCl 3, ppm): δ 8.75 (d, 1H, J= 3.6 Hz), 7.91 (s, 1H), 7.69 (d, 1H, J= 8.8Hz), 7.57 (m, 1H), 7.43 (m, 1H), 7.33 - 7.30 (m, 1H), 6.55 (s, 1H), 4.43 (s, 4H), 3.76 (s, 2H), 2.52 (s, 4H), 2.36 (s, 3H), 1.94 (s, 4H)

[0609]

[0610] Example 64: 7-Chloro-2-(((2-methoxyethyl)amino)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0611]

[0612] Using the compound of Example 61-1 (40 mg, 111 μmol, 1 equivalent) as a starting material, the title compound (6.9 mg, 17.3 μmol, 16% yield, 99.55% purity) was obtained in the same manner as in Example 61-2.

[0613] 1 H NMR (400 MHz, CDCl 3, ppm): δ 8.76 (s, 1H), 8.49 (s, 1H), 7.81 (d, 1H, J= 8.8Hz), 7.61 (d, 1H, J= 7.6Hz), 7.45 (m, 1H), 7.33 - 7.31 (m, 1H), 6.55 (s, 1H), 4.38 (s, 2H), 3.77 (m, 2H), 3.37 (s, 3H), 3.26 (m, 2H), 2.34 (s, 3H)

[0614]

[0615] Example 65: 5-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0616] Example 65 Reaction scheme for the preparation of compound:

[0617]

[0618] Example 65-1: N-(2-nitro-5-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-4-amine

[0619] The title compound (0.6 g, 1.85 mmol, 62.5% yield) as an orange solid was obtained in the same manner as in Example 33-1 using 2,3-dihydrobenzofuran-4-amine (400 mg, 2.96 mmol, 1 equivalent) and 2-fluoro-1-nitro-4-(trifluoromethyl)benzene (928.20 mg, 4.44 mmol, 1.5 equivalent) as starting materials.

[0620] 1 H NMR (400 MHz, CDCl 3,ppm): δ 9.40 (brs, 1H), 8.34 (d, J = 8.8 Hz, 1H), 7.37 - 7.31 (m, 1H), 7.26 - 7.19 (m, 1H), 7.04 - 6.97 (m, 1H), 6.86 - 6.80 (m, 1H), 6.80 - 6.74 (m, 1H), 4.74 - 4.59 (m, 2H), 3.20 - 3.01 (m, 2H).

[0621]

[0622] Example 65-2:N 1 -(2,3-dihydrobenzofuran-4-yl)-5-(trifluoromethyl)benzene-1,2-diamine

[0623] The title compound (515 mg, crude mixture) was obtained in the same manner as in Example 33-2 using the compound of Example 65-1 (600 mg, 1.85 mmol, 1 equivalent) as a starting material.

[0624] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 7.17 - 7.11 (m, 1H), 7.11 - 7.06 (m, 1H), 6.93 - 6.85 (m, 2H), 6.84 - 6.79 (m, 1H), 6.23 (d, J = 8.0 Hz, 1H), 6.08 (d, J = 7.6 Hz, 1H), 5.50 (brs, 2H), 4.49 (t, J = 8.8 Hz, 2H), 2.99 (t, J = 8.8 Hz, 2H).

[0625]

[0626] Example 65-3: 1-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxaline-2,3-dione

[0627] The title compound (692 mg, crude mixture) was obtained in the same manner as in Example 33-3 using the compound of Example 65-2 (515 mg, 1.75 mmol, 1 equivalent) as a starting material.

[0628] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 12.56 - 12.36 (m, 1H), 7.62 - 7.48 (m, 1H), 7.46 - 7.27 (m, 2H), 7.04 - 6.92 (m, 1H), 6.91 - 6.79 (m, 1H), 6.63 - 6.51 (m, 1H), 4.66 - 4.47 (m, 2H), 3.11 - 2.76 (m, 2H).

[0629]

[0630] Example 65-4: 3-Chloro-1-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxalin-2(1H)-one

[0631] The title compound (500 mg, crude mixture) was obtained in the same manner as in Example 33-4 using the compound of Example 65-3 (492 mg, 1.41 mmol, 1 equivalent) as a starting material.

[0632] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 7.62 - 7.52 (m, 1H), 7.52 - 7.42 (m, 1H), 7.37 - 7.25 (m, 1H), 7.00 - 6.87 (m, 1H), 6.86 - 6.72 (m, 1H), 6.64 - 6.43 (m, 1H), 4.64 - 4.41 (m, 2H), 3.07 - 2.70 (m, 2H).

[0633]

[0634] Example 65-5: 3-Amino-1-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxalin-2(1H)-one

[0635] Using the compound of Example 65-4 as a starting material, the title compound (100 mg, 287.94 μmol, 52.8% yield) was obtained in the same manner as in Example 33-5.

[0636] 1H NMR (400 MHz, DMSO-d 6, ppm): δ 7.57 - 7.47 (m, 2H), 7.40 - 7.32 (m, 1H), 7.04 - 6.96 (m, 1H), 6.93 - 6.87 (m, 1H), 6.69 - 6.62 (m, 1H), 4.65 - 4.49 (m, 2H), 3.02 - 2.76 (m, 2H).

[0637]

[0638] Example 65-6: 5-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0639]

[0640] Using the compound of Example 65-5 (140 mg, 403.12 μmol, 1 equivalent) as a starting material, the title compound as a yellowish white substance (33.66 mg, 90.20 μmol, 22.4% yield, 99.5% purity) was obtained in the same manner as in Example 33-6.

[0641] 1 H NMR (400 MHz, DMSO-d 6, ppm): δ 8.79 - 8.71 (m, 1H), 8.53 - 8.44 (m, 1H), 7.82 - 7.70 (m, 2H), 7.42 - 7.34 (m, 1H), 7.04 - 6.98 (m, 1H), 6.94 - 6.90 (m, 1H), 6.85 - 6.82 (m, 1H), 4.67 - 4.47 (m, 2H), 3.08 - 2.77 (m, 2H).

[0642]

[0643] Example 71: 7-Chloro-9-fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0644] Example 71 Reaction scheme for the preparation of compound:

[0645]

[0646] Example 71-1: Ethyl 1-(4-chloro-2-fluoro-6-nitrophenyl)-1H-imidazole-2-carboxylate

[0647] 5-Chloro-1,2-difluoro-3-nitrobenzene (194 g, 1 mmol, 1 equiv) and ethyl 1H-imidazole-2-carboxylate (140 mg, 1 mmol, 1 equiv) were dissolved in N,N-dimethylformamide (5 mL), and cesium carbonate (397 mg, 1.2 mmol, 1.2 equiv) was added. The reaction mixture was stirred at 55°C for 2 h. The consumption of the starting material was observed by TLC, and when the reaction was complete, the mixture was cooled to room temperature, water (500 mL) was added, and the precipitate was filtered, washed with water, and dried (30 mL × 3) to obtain the title compound (250 mg, 767 μmol, 79.7% yield) as a light yellow solid.

[0648] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.00 (t, J = 2.2 Hz, 1H), 7.58 (dd, J = 8.5, 2.3 Hz, 1H), 7.41 (d, J = 1.2 Hz, 1H), 7.13 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H).

[0649]

[0650] Example 71-2: Ethyl 1-(4-chloro-2-fluoro-6-(o-tolylamino)phenyl)-1H-imidazole-2-carboxylate

[0651] The compound obtained in Example 71-1 (100 mg, 319 μmol, 1 equiv.), o-tolylboronic acid (86.7 mg, 638 μmol, 2 equiv.), and 1,2,2,3,4,4-hexamethylphosphetane 1-oxide (12 mg, 63.8 μmol, 0.2 equiv.) were dissolved in toluene (1 mL), and phenylsilane (68.4 mg, 63.8 μmol, 77.9 uL, 2 equiv.) was added. The reaction mixture was purged with nitrogen three times to remove gas in the solution, and then stirred at 120 o C and stirred for 2 hours. After cooling the reaction mixture to room temperature, water (20 mL) was added and extracted with ethyl acetate (30 mL × 2). The organic layer was washed with a saturated aqueous sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (stationary phase: silica, mobile phase: petroleum ether / ethyl acetate = 50 / 1 to 3 / 1) to obtain the title compound (74 mg, 198 μmol, 62.1% yield) as a white solid.

[0652] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.45 (s, 1H), 7.26 - 7.09 (m, 5H), 6.67 (dd, J = 8.9, 2.2 Hz, 1H), 6.54 (s, 1H), 4.35 (q, J = 7.1 Hz, 2H), 2.11 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H).

[0653]

[0654] Example 71-3: 7-Chloro-9-fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0655]

[0656] The compound obtained in Example 71-2 (74 mg, 198 μmol, 1.00 equivalent) was dissolved in ethanol (2 mL), and potassium carbonate (30.1 mg, 218 μmol, 1.1 equivalent) was added. The mixture was stirred at 80 o The mixture was stirred at C for 2 hours. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by column chromatography (stationary phase: silica, mobile phase: dichloromethane / methanol = 100 / 1 to 20 / 1) to obtain the title compound (39.5 mg, 121 μmol, 60.9% yield, 99.1% purity) as a light white solid.

[0657] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.21 (s, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.54 - 7.42 (m, 3H), 7.19 (d, J = 7.6 Hz, 1H), 7.15 (dd, J = 11.5, 2.1 Hz, 1H), 6.42 (d, J = 2.0 Hz, 1H), 2.10 (s, 3H).

[0658]

[0659] Example 72: 8-Bromo-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0660]

[0661] The title compound was synthesized in the same manner as in Example 71, except that the starting material was changed to 1-bromo-2-chloro-5-fluoro-4-nitrobenzene.

[0662] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.99 (s, 1H), 7.87 (s, 1H), 7.73 (s, 1H), 7.56 - 7.37 (m, 3H), 7.19 (d, J = 7.6 Hz, 1H), 6.70 (s, 1H), 2.10 (s, 3H).

[0663]

[0664] Example 73: 7-Chloro-8-methyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0665]

[0666] The title compound was synthesized in the same manner as in Example 71, except that the starting material was changed to 1-chloro-4-fluoro-2-methyl-5-nitrobenzene.

[0667] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.89 (s, 1H), 7.70 (s, 1H), 7.60 (s, 1H), 7.52 - 7.38 (m, 3H), 7.19 (d, J = 7.6 Hz, 1H), 6.60 (s, 1H), 2.48 (s, 3H), 2.09 (s, 3H).

[0668]

[0669] Example 74: 7-Bromo-8-methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0670]

[0671] The title compound was synthesized in the same manner as in Example 71, except that the starting material was changed to 1-bromo-4-fluoro-2-methoxy-5-nitrobenzene.

[0672] 1 H NMR (400 MHz, CDCl 3, ppm): δ 7.90 (s, 1H), 7.73 (s, 1H), 7.50 - 7.41 (m, 3H), 7.23 - 7.16 (m, 2H), 6.82 (s, 1H), 4.03 (s, 3H), 2.09 (s, 3H).

[0673]

[0674] Example 75: 7-Bromo-8-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0675] Example 75 Reaction scheme for the preparation of compound:

[0676]

[0677] Example 75-1: N-(5-Bromo-4-methoxy-2-nitrophenyl)-2-methylpyridin-3-amine

[0678] 1-Bromo-5-fluoro-2-methoxy-4-nitrobenzene (2.0 g, 18.49 mmol, 1 equiv), 2-methylpyridin-3-amine (5.55 g, 22.19 mmol, 1.2 equiv), and lithium bis(trimethylsilyl)amide (1 M, 36.99 mL, 2 equiv) were added to tetrahydrofuran (30 mL) and purged with nitrogen three times. The mixture was cooled to -50 o C and stirred for 2 hours. After confirming the formation of a new product by TLC, the reaction was terminated by adding a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate (200 mL × 3). The organic layer was washed with a saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 10 / 1 to 3 / 1) to obtain the title compound (4.9 g, 13.33 mmol, 72.1% yield) as a yellow liquid.

[0679] 1 H NMR (400 MHz, CDCl3, ppm) δ 9.05 (s, 1H), 8.39 (dd, J = 1.6, 4.8 Hz, 1H), 7.63 (s, 1H), 7.52 (dd, J = 1.2, 8.0 Hz, 1H), 7.19 - 7.16 (m, 1H), 7.02 (s, 1H), 3.85 (s, 3H), 2.46 (s, 3H).

[0680]

[0681] Example 75-2: 5-Bromo-4-methoxy-N 1 -(2-methylpyridin-3-yl)benzene-1,2-diamine

[0682] The compound obtained in Example 75-1 (4.8 g, 14.19 mmol, 1 equivalent) was dissolved in methanol (40 mL), and Raney-nickel (608.06 mg, 7.10 mmol, 0.2 equivalent) was added. The reaction mixture was stirred at room temperature for 12 hours under hydrogen (15 Psi). The starting material disappeared on LCMS and the m / z ([M + H]) of the title compound + = 308.0) was observed, the reaction mixture was filtered and concentrated to obtain the title compound (3.7 g, crude mixture) as a yellow solid. The obtained mixture was used immediately in the next reaction.

[0683]

[0684] Example 75-3: 7-Chloro-6-methoxy-1-(2-methylpyridin-3-yl)-1,4-dihydroquinoxaline-2,3-dione

[0685] The compound obtained in Example 75-2 (3.40 g, 11.03 mmol, 1 equivalent) was dissolved in diethyl oxalate (42.80 g, 109.83 mmol, 40 mL, 26.56 equivalent), N,N-diisopropylethylamine (2.85 g, 22.07 mmol, 3.84 mL, 2 equivalent) was added, and then 160 o The mixture was stirred for 3 hours at C. The m / z ([M + H]+ = 362.0) of the title compound was observed on LCMS. The reaction mixture was concentrated and purified by chromatography (stationary phase: silica, mobile phase: dipetroleum ether: ethyl acetate = 1 / 0 to 1 / 2), and then solidified with ethyl acetate (100 mL). The title compound (1.9 g, 5.25 mmol, 47.5% yield) was obtained as a yellow solid.

[0686]

[0687] Example 75-4: 7-Bromo-3-chloro-6-methoxy-1-(2-methylpyridin-3-yl)dihydroquinoxalin-2(1H)-one

[0688] The compound obtained in Example 75-3 (500 mg, 1.38 mmol, 1 equivalent), phosphoryl chloride (656.97 mg, 5.52 mmol, 0.4 mL, 4 equivalents), N,N-dimethylformamide (0.05 mL, 3 equivalents) were dissolved in toluene (10 mL) and stirred at 80 o The mixture was stirred for 3 hours at C. The reaction mixture was concentrated to obtain the title compound (320 mg, crude mixture) as a yellow solid, which was used in the next reaction without further purification.

[0689]

[0690] Example 75-5: 3-Amino-7-bromo-6-methoxy-1-(2-methylpyridin-3-yl)quinoxalin-2(1H)-one

[0691] The compound obtained in Example 75-4 (320 mg, 840.73 μmol, 1 equivalent) was dissolved in tetrahydrofuran (4 mL), and aqueous ammonia solution (1.96 g, 16.81 mmol, 2.16 mL, 30% purity, 20 equivalents) was added. The reaction mixture was stirred at 25°C for 12 hours. The m / z ([M + H]) of the title compound was determined by LCMS. + =362.9) was observed, the reaction mixture was concentrated under reduced pressure and filtered. The filter cake was concentrated and purified by chromatography (stationary phase: silica, mobile phase: di-petroleum ether: ethyl acetate = 4 / 1 to 1 / 2) to obtain the title compound (270 mg, 747.52 μmol, 88.9% yield) as a yellow solid.

[0692] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.73 - 8.58 (m, 1H), 7.92 - 7.78 (m, 1H), 7.54 - 7.51 (m, 3H), 7.06 (s, 1H), 6.36 (s, 1H), 3.87 (s, 3H), , 2.27 - 2.16 (s, 3H).

[0693]

[0694] Example 75-6: 7-Bromo-8-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0695]

[0696] The compound obtained in Example 75-5 (300 mg, 830.58 mmol, 1 equivalent) and 2-chloroacetaldehyde (814.98 mg, 4.15 mmol, 668.02 μL, 40% purity, 5 equivalent) were added to ethanol (5 mL). The reaction mixture was stirred at 80 o The mixture was stirred for 12 hours at C. The desired m / z ([M + H]+ = 385.2) was detected by LCMS. The reaction mixture was concentrated under reduced pressure and recrystallized using ethanol to obtain the title compound (118 mg, 292.54 μmol, 35.2% yield, 97.5% purity) as a yellow solid.

[0697] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.83 (s, 1H), 8.72 - 8.71 (m, 1H), 7.96 (s, 1H), 7.93-7.91 (s, 1H), 7.73 (s, 1H), 7.60 - 7.56 (m, 1H), 6.62 (s, 1H), 4.01 (s, 3H), 2.25 (s, 3H).

[0698]

[0699] Example 76: 7-Bromo-5-(2-methylpyridin-3-yl)-8-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0700]

[0701] The title compound was synthesized in the same manner as in Example 75, except that the starting material was changed to 1-bromo-5-fluoro-4-nitro-2-(trifluoromethyl)benzene.

[0702] 1H NMR (400 MHz, CDCl3, ppm): δ 8.79 (d, J = 3.4 Hz, 1H), 8.06 (s, 1H), 7.99 (d, J = 1.3 Hz, 1H), 7.79 (d, J = 1.3 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.49 - 7.43 (m, 1H), 6.90 (s, 1H), 2.38 (s, 3H).

[0703]

[0704] Example 77: 7-Bromo-8-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0705]

[0706] The title compound was synthesized in the same manner as in Example 75, except that the starting material was changed to 1-bromo-2,5-difluoro-4-nitrobenzene.

[0707] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.84 - 8.68 (m, 1H), 7.86 (d, J = 1.3 Hz, 1H), 7.76 (d, J = 1.3 Hz, 1H), 7.67 - 7.55 (m, 2H), 7.45 (dd, J = 8.0, 4.7 Hz, 1H), 6.76 (d, J = 6.0 Hz, 1H), 2.37 (s, 3H).

[0708]

[0709] Example 78: 7-Bromo-8-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0710]

[0711] The title compound was synthesized in the same manner as in Example 75, except that the starting material was changed to 1-bromo-5-fluoro-2-methyl-4-nitrobenzene.

[0712] 1H NMR (400 MHz, CDCl3, ppm): δ 8.75 (dd, J = 4.9, 1.6 Hz, 1H), 7.92 (d, J = 1.3 Hz, 1H), 7.73 (d, J = 1.2 Hz, 1H), 7.64 (s, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.43 (dd, J = 8.0, 4.8 Hz, 1H), 6.74 (s, 1H), 2.51 (s, 3H), 2.36 (s, 3H).

[0713]

[0714] Example 79: 7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0715]

[0716] The title compound was synthesized in the same manner as in Example 75, except that the starting material was changed to 1-bromo-2-chloro-5-fluoro-4-nitrobenzene.

[0717] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.83 - 8.71 (m, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.63 - 7.54 (m, 1H), 7.45 (dd, J = 8.0, 4.9 Hz, 1H), 6.82 (s, 1H), 2.37 (s, 3H).

[0718]

[0719] Example 80: (Ra)-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0720]

[0721] The compound of Example 79 was separated using DAICEL CHIRALCEL OD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 4.58 minutes) (ee% = 99.5%) to obtain the title compound as a white solid.

[0722] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.83 - 8.71 (m, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.63 - 7.54 (m, 1H), 7.45 (dd, J = 8.0, 4.9 Hz, 1H), 6.82 (s, 1H), 2.37 (s, 3H).

[0723]

[0724] Example 81: (Sa)-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0725]

[0726] The compound of Example 79 was separated using DAICEL CHIRALCEL OD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 5.60 minutes) (ee% = 99.1%) to obtain the title compound as a white solid.

[0727] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.83 - 8.71 (m, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.63 - 7.54 (m, 1H), 7.45 (dd, J = 8.0, 4.9 Hz, 1H), 6.82 (s, 1H), 2.37 (s, 3H).

[0728]

[0729] Example 82: 7-Bromo-8-(difluoromethyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0730]

[0731] The title compound was synthesized in the same manner as in Example 75, except that the starting material was changed to 1-bromo-2-(difluoromethyl)-5-fluoro-4-nitrobenzene.

[0732] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.89 (s, 1H), 8.71 - 8.70 (m, 1H), 8.59 (s, 1H), 7.88 - 7.86 (m, 1H), 7.73 (s, 1H), 7.56 - 7.53 (m, 1H), 7.21 (t, J = 54 Hz, 1H), 6.68 (s, 1H), 2.27 (s, 3H).

[0733]

[0734] Example 83: 7-Bromo-8-chloro-5-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0735]

[0736] In Example 75-1, 2-methylpyridin-3-amine was changed to 1-methyl-1H-pyrazol-5-amine, and the title compound was synthesized in the same manner as in Example 79.

[0737] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.88 (d, J = 1.4 Hz, 1H), 7.85 (s, 1H), 7.77 - 7.74 (m, 2H), 7.07 (s, 1H), 6.40 (d, J = 2.1 Hz, 1H), 3.71 (s, 3H).

[0738]

[0739] Example 84: 7-Bromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0740]

[0741] In Example 75-6, the title compound was synthesized in the same manner as in Example 78 by changing 2-chloroacetaldehyde to 2-chloropropanal.

[0742] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.79 - 8.68 (m, 1H), 8.00 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.47 - 7.37 (m, 3H), 6.74 (s, 1H), 2.90 (s, 3H), 2.50 (s, 3H), 2.35 (s, 3H).

[0743]

[0744] Example 85: 7,9-Dibromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0745]

[0746] To a solution of the compound of Example 84 (60 mg, 156.58 μmol, 1 equivalent) dissolved in dimethylformamide (2 mL), a solution of N-bromosuccinimide (31 mg, 172.23 μmol, 1.1 equivalent) dissolved in dimethylformamide (2 mL) was slowly added dropwise. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was terminated by the addition of water, the mixture was extracted with dichloromethane (50 mL × 3). The organic layer was washed with a saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by column chromatography (stationary phase: silica, mobile phase: dichloromethane: methanol = 1 / 0 to 10 / 1) to obtain the title compound (30 mg, 64.91 μmol, 41.5% yield, 94.5% purity) as a yellow solid.

[0747] 1H NMR (400 MHz, CDCl3, ppm): δ 8.81 - 8.69 (m, 1H), 7.99 (s, 1H), 7.56 (d, J = 7.4 Hz, 1H), 7.43 (dd, J = 7.9, 4.9 Hz, 1H), 6.75 (s, 1H), 2.91 (s, 3H), 2.51 (s, 3H), 2.34 (s, 3H).

[0748]

[0749] Example 86: 7-Bromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0750]

[0751] In Example 75-6, the title compound was synthesized in the same manner as in Example 79 by changing 2-chloroacetaldehyde to 2-chloropropanal.

[0752] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.76 (d, J = 4.6 Hz, 1H), 8.22 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.49 - 7.40 (m, 2H), 6.82 (s, 1H), 2.90 (s, 3H), 2.36 (s, 3H).

[0753]

[0754] Example 87: 7-Bromo-8-chloro-5-(2-cyclopropylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0755]

[0756] The title compound was synthesized in the same manner as in Example 79, except that 2-methylpyridin-3-amine in Example 75-1 was changed to 2-cyclopropylpyridin-3-amine.

[0757] 1H NMR (400 MHz, CDCl3, ppm): δ 9.25 (s, 1H), 8.77 (d, J = 4.9 Hz, 1H), 7.68 (s, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 7.9, 4.8 Hz, 1H), 6.83 (s, 1H), 2.36 (s, 3H).

[0758]

[0759] Example 88: 1,7-Dibromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0760]

[0761] The title compound was synthesized in the same manner as in Example 85 using the compound obtained in Example 79 as a starting material.

[0762] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.68 (d, J = 4.8 Hz, 1H), 7.89 (s, 1H), 7.87 (s, 1H), 7.75 (s, 1H), 7.54 (d, J = 7.4 Hz, 1H), 7.32 (dd, J = 8.0, 4.7 Hz, 1H), 6.92 (s, 1H), 1.69 - 1.59 (m, 1H), 1.31 - 1.19 (m, 1H), 1.17 - 1.03 (m, 1H), 0.96 - 0.87 (m, 1H), 0.84 - 0.75 (m, 1H).

[0763]

[0764] Example 89: 7-Bromo-1,8-dichloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0765]

[0766] In Example 83, the title compound was synthesized in the same manner as in Example 88, except that N-chlorosuccinimide was used instead of N-bromosuccinimide.

[0767] 1 H NMR (400 MHz, CDCl3, ppm): δ 9.03 (s, 1H), 8.77 (d, J = 4.9 Hz, 1H), 7.63 (s, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.49 - 7.40 (m, 1H), 6.83 (s, 1H), 2.37 (s, 3H).

[0768]

[0769] Example 90: 7-Bromo-5-(2-hydroxypyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one

[0770] Example 90 Reaction scheme for the preparation of compound:

[0771]

[0772] Example 90-1: N-(5-Bromo-4-methyl-2-nitrophenyl)-2-methoxypyridin-3-amine

[0773] The starting materials of Example 75-1 were changed to 1-bromo-5-fluoro-2-methyl-4-nitrobenzene and 2-methoxypyridin-3-amine, and the title compound was synthesized in the same manner as in Example 75-1.

[0774] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.17 (s, 1H), 8.11 (s, 1H), 8.02 (dd,J= 1.2, 4.8 Hz, 1H), 7.80 - 7.71 (m, 1H), 7.16 (s, 1H), 7.07 (dd,J= 4.8 Hz, 1H), 3.90 (s, 3H), 2.30 (s, 3H).

[0775]

[0776] Example 90-2: 5-Bromo-N 1 -(2-methoxypyridin-3-yl)-4-methylbenzene-1,2-diamine

[0777] The title compound was synthesized in the same manner as in Example 75-2 using the compound of Example 90-1 as a starting material.

[0778] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 7.50 (dd, J = 1.6, 4.8 Hz, 1H), 7.07 (s, 1H), 6.79 - 6.70 (m, 3H), 6.58 (dd, J = 1.6, 7.6 Hz, 1H), 4.88 (s, 2H), 3.93 (s, 3H), 2.21 (s, 3H).

[0779]

[0780] Example 90-3: Ethyl 2-((4-bromo-2-((2-methoxypyridin-3-yl)amino)-5-methylphenyl)amino)-2-oxoacetate

[0781] To a mixture of the compound of Example 90-2 (1.2 g, 3.89 mmol, 1 equiv) and sodium carbonate (453.98 mg, 4.28 mmol, 1.1 equiv) dissolved in dichloromethane (12 mL) and water (3 mL) was added ethyl 2-chloro-2-oxoacetate (637.98 mg, 4.67 mmol, 522.08 μL, 1.2 equiv). After purging with nitrogen, the mixture was stirred at room temperature for 2 hours. The reaction was quenched with aqueous ammonium chloride solution (60 mL) and extracted with ethyl acetate (40 × 3 mL). The organic layer was washed with saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Petroleum ether (30 mL) was added to the concentrate, and solidification was carried out at room temperature for 30 minutes. The filter cake produced after filtration was dried under reduced pressure to obtain the title compound (1.5 g, 2.99 mmol, 76.9% yield) as a white solid.

[0782]

[0783] Example 90-4: 7-Bromo-1-(2-methoxypyridin-3-yl)-6-methyl-1,4-dihydroquinoxaline-2,3-dione

[0784] The compound of Example 90-3 (1.5 g, 3.67 mmol, 1 equivalent) was dissolved in tetrahydrofuran (30 mL), and sodium hydride (293.91 mg, 7.35 mmol, 60% purity, 2 equivalents) was added at 0°C, followed by a nitrogen purge. The resulting mixture was stirred at room temperature under nitrogen for 12 hours. The reaction was quenched with an aqueous ammonium chloride solution (60 mL), and extracted with ethyl acetate (40 × 3 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Ethyl acetate (30 mL) was added to the concentrate, and solidification was carried out at room temperature for 30 minutes. The filter cake produced after filtration was dried under reduced pressure to obtain the title compound (640 mg, 1.68 mmol, 45.8% yield, 95.3% purity) as a brown solid.

[0785] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.41 (d,J= 4.4 Hz, 1H), 7.88 (d,J= 7.2 Hz, 1H), 7.30-7.27 (m, 1H), 7.20 (s, 1H), 6.46 (s, 1H), 3.84 (s, 3H), 2.31 (s, 3H).

[0786]

[0787] Example 90-5: 7-Bromo-3-chloro-1-(2-hydroxypyridin-3-yl)-6-methylquinoxalin-2(1H)one

[0788] The title compound was synthesized in the same manner as in Example 75-4 using the compound of Example 90-4 as a starting material.

[0789] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 7.86 (s,1H), 7.80 (dd,J= 2.0 Hz, 1H), 7.71 (dd,J= 2.0 Hz, 1H), 7.04 (s,1H), 7.48-7.45 (m,1H), 2.42 (s, 3H).

[0790]

[0791] Example 90-6: 3-Amino-7-bromo-1-(2-hydroxypyridin-3-yl)-6-methylquinoxalin-2(1H)-one

[0792] The title compound was synthesized in the same manner as in Example 75-5 using the compound of Example 90-5 as a starting material.

[0793]

[0794] Example 90-7: 7-Bromo-5-(2-hydroxypyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one

[0795]

[0796] The title compound was synthesized in the same manner as in Example 75-6 using the compound of Example 90-6 as a starting material.

[0797] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.60 (s,1H), 8.30 (s, 1H), 8.37 (s,1H), 7.80-7.79 (m, 1H), 7.68-7.67 (m, 2H), 6.96 (s, 1H), 6.47-6.44 (t, 1H), 2.44 (s, 3H).

[0798]

[0799] Example 91: 7-Bromo-5-(2-chloropyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one

[0800]

[0801] The compound of Example 90 (130 mg, 350.23 μmol, 1 equivalent) and phosphoryl chloride (3 mL, 32.99 equivalent) and N,N-diisopropylethylamine (135.79 mg, 1.05 mmol, 183.01 μL, 3 equivalent) were added to 110 oC for 24 h. Saturated aqueous sodium bicarbonate solution (15 mL) was slowly added to the reaction mixture, and extracted with ethyl acetate (20 mL X 3). The organic layer was washed with saturated aqueous sodium chloride solution (50 mL X 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150*40mm* 10μm; mobile phase: [water (10 mM ammonium bicarbonate)-acetonitrile]; B%: 22%-52%, 15 min) to obtain the title compound (32 mg, 80.73 μmol, 23.1% yield, 98.3% purity) as a brown solid.

[0802] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.69 - 8.67 (m, 2H), 8.37 (s, 1H), 8.21 (dd, J = 2.0 Hz, 1H), 7.79-7.85 (m, 1H), 7.74 (d, J = 0.8 Hz, 1H), 6.72 (s, 1H), 2.45 (s, 3H).

[0803]

[0804] Example 92: 2,7-Dibromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0805]

[0806] The title compound was synthesized in the same manner as in Example 85 using the compound of Example 86 as a starting material.

[0807] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.76 (dd, J = 4.7, 1.5 Hz, 1H), 8.22 (s, 1H), 7.62 - 7.53 (m, 1H), 7.45 (dd, J = 8.0, 4.8 Hz, 1H), 6.83 (s, 1H), 2.91 (s, 3H), 2.34 (s, 3H).

[0808]

[0809] Example 93: 8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0810] Example 93 Reaction scheme for the preparation of compound:

[0811]

[0812] Example 93-1: 2-Methyl-N-(4-methyl-2-nitro-5-(trifluoromethyl)phenyl)pyridin-3-amine

[0813] 4-Methyl-2-nitro-5-(trifluoromethyl)aniline (5 g, 22.71 mmol, 1 equiv) and 3-bromo-2-methylpyridine (4.30 g, 24.98 mmol, 1.1 equiv), Expos (2.17 g, 4.54 mmol, 0.2 equiv), sodium tert-butoxide (3.06 g, 31.80 mmol, 1.4 equiv), and tris(dibenzylideneacetone)dipalladium(0) (2.08 g, 2.27 mmol, 0.1 equiv) were dissolved in toluene (45 mL) and then purged with nitrogen. The resulting mixture was stirred at 90 o Stirred for 12 hours at C. Starting material disappeared and the desired m / z ([M + H]) was determined by LC-MS. + = 312.1) was detected, 20 mL of ammonium chloride aqueous solution was added, and then extracted with ethyl acetate (30 mL X 2). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the resulting concentrate was purified by column chromatography (stationary phase: silica, mobile phase: petroleum ether: ethyl acetate = 1 / 0 to 3 / 1) to obtain the title compound (3.9 g, 12.53 mmol, 55.2% yield, 89.2% purity) as a yellow solid.

[0814] 1H NMR (400 MHz, DMSO-d6, ppm): δ 9.32 (s, 1H), 8.41 (d, J = 4.0 Hz, 1H), 8.20 (s, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 7.6, 4.0 Hz, 1H), 6.83 (s, 1H), 2.38 (s, 3H), 2.37 (s, 3H).

[0815]

[0816] Example 93-2: 4-Methyl-N 1 -(2-methylpyridin-3-yl)-5-(trifluoromethyl)benzene-1,2-diamine

[0817] The title compound was obtained under the same conditions as in Example 75-2 using the compound obtained in Example 93-1 as a starting material. The following reaction was carried out without further purification.

[0818]

[0819] Example 93-3: Ethyl 2-((5-methyl-2-((2-methylpyridin-3-yl)amino)-4-(trifluoromethyl)phenyl)amino)-2-oxoacetate

[0820] The title compound was obtained under the same conditions as in Example 90-3 using the compound obtained in Example 91-2 as a starting material. The following reaction was carried out without further purification.

[0821]

[0822] Example 93-4: 6-Methyl-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxaline-2,3-dione

[0823] The title compound was obtained under the same conditions as in Example 90-4 using the compound obtained in Example 93-3 as a starting material.

[0824] 1H NMR (400 MHz, DMSO-d6, ppm): δ 12.44 (s, 1H), 8.67 (d, J = 3.6 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.52 (dd, J = 4.8, 7.6 Hz, 1H), 7.23 (s, 1H), 6.34 (s, 1H), 2.40 (s, 3H), 2.45 (s, 3H).

[0825]

[0826] Example 93-5: 3-Chloro-6-methyl-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[0827] The title compound was obtained under the same conditions as in Example 90-5 using the compound obtained in Example 93-4 as a starting material. The following reaction was carried out without further purification.

[0828]

[0829] Example 93-6: 3-Amino-6-methyl-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[0830] The title compound was obtained under the same conditions as in Example 90-6 using the compound obtained in Example 93-5 as a starting material.

[0831]

[0832] Example 93-7: 8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0833]

[0834] The title compound was obtained under the same conditions as in Example 90-7 using the compound obtained in Example 93-6 as a starting material.

[0835] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.78 - 8.61 (m, 2H), 8.43 (s, 1H), 7.95 - 7.84 (m, 1H), 7.74 (s, 1H), 7.60 - 7.47 (m, 1H), 6.58 (s, 1H), 2.54 (s, 3H), 2.24 (s, 3H).

[0836]

[0837] Example 94: (Ra)-8-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0838]

[0839] The compound of Example 93 was separated using DAICEL CHIRALCEL OD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 1.45 min) (ee%>99.9%) to obtain the title compound as a white solid.

[0840] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.78 - 8.61 (m, 2H), 8.43 (s, 1H), 7.95 - 7.84 (m, 1H), 7.74 (s, 1H), 7.60 - 7.47 (m, 1H), 6.58 (s, 1H), 2.54 (s, 3H), 2.24 (s, 3H).

[0841]

[0842] Example 95: (Sa)-8-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0843]

[0844] The compound of Example 93 was separated using DAICEL CHIRALCEL OD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 1.62 min) (ee%=99.8%) to obtain the title compound as a white solid.

[0845] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.78 - 8.61 (m, 2H), 8.43 (s, 1H), 7.95 - 7.84 (m, 1H), 7.74 (s, 1H), 7.60 - 7.47 (m, 1H), 6.58 (s, 1H), 2.54 (s, 3H), 2.24 (s, 3H).

[0846]

[0847] Example 96: 8-Chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0848]

[0849] The title compound was obtained in the same manner as in Example 93-1, using 4-chloro-2-nitro-5-(trifluoromethyl)aniline instead of 4-chloro-2-nitro-5-(trifluoromethyl)aniline as the starting material.

[0850] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.81-8.80 (m, 2H), 8.72 (dd,J= 1.6, 4.8 Hz, 1H), 7.89 (dd,J= 1.6, 7.8 Hz, 1H), 7.78 (d,J= 1.2 Hz, 1H), 7.56 (dd,J= 4.6, 7.8 Hz, 1H), 6.68 (s, 1H), 2.28 (s, 3H).

[0851]

[0852] Example 97: (Ra)-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0853]

[0854] The compound of Example 96 was separated using DAICEL CHIRALPAK AD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 40%, isocratic transfer conditions (retention time: 1.46 min) (ee% = 97.5%) to obtain the title compound as a white solid.

[0855] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.81-8.80 (m, 2H), 8.72 (dd,J= 1.6, 4.8 Hz, 1H), 7.89 (dd,J= 1.6, 7.8 Hz, 1H), 7.78 (d,J= 1.2 Hz, 1H), 7.56 (dd,J= 4.6, 7.8 Hz, 1H), 6.68 (s, 1H), 2.28 (s, 3H).

[0856]

[0857] Example 98: (Sa)-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0858]

[0859] The compound of Example 96 was separated using DAICEL CHIRALPAK AD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 40%, isocratic transfer conditions (retention time: 2.14 minutes) (ee% = 96.6%) to obtain the title compound as a white solid.

[0860] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.81-8.80 (m, 2H), 8.71 (dd,J= 1.6, 4.8 Hz, 1H), 7.88 (dd,J= 1.6, 8.0 Hz, 1H), 7.77 (d,J= 1.2 Hz, 1H), 7.55 (dd,J= 4.8, 8.0 Hz, 1H), 6.67 (s, 1H), 2.27 (s, 3H).

[0861]

[0862] Example 99: 8-Chloro-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0863] Example 99 Reaction scheme for the preparation of compound:

[0864]

[0865] Example 99-1: 3,6-Dichloro-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[0866] To 6-chloro-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxaline-2,3-dione (5.3 g, 14.90 mmol, 1 equivalent), a synthetic intermediate of Example 96, thionyl chloride (50 mL) was added, dimethylformamide (108.91 mg, 1.49 mmol, 114.64 μL, 0.1 equivalent) was added, and the mixture was stirred at 80 °C for 3 hours after a nitrogen purge. The reaction mixture was dried under reduced pressure to obtain the title compound (1.37 g, crude mixture) as a white solid.

[0867]

[0868] Example 99-2: 6-Chloro-3-((2,2-dimethoxypropyl)amino)-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[0869] The compound obtained in Example 99-2 (1.0 g, 2.67 mmol, 1 equiv) was dissolved in dimethylformamide (10 mL), and 2,2-dimethoxypropan-1-amine (1.59 g, 13.36 mmol, 5 equiv) and triethylamine (811.36 mg, 8.02 mmol, 1.12 mL, 3 equiv) were added. After purging with nitrogen, the mixture was stirred at 25 °C for 2 hours. After confirming that the desired reaction had occurred through LC-MS, the reaction was terminated by adding ice water (20 mL). The pH of the reaction mixture was adjusted to 3 by adding 1 M aqueous hydrochloric acid solution, and then extracted with ethyl acetate (20 mL × 3). The organic layer was washed with a saturated aqueous sodium chloride solution (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 0% to 60%) to obtain the title compound (1.05 g, 2.18 mmol, 82% yield, 95% purity) as a white solid.

[0870] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.71 (dd, J = 1.6, 4.8 Hz, 1H), 7.93 (dd, J = 1.6, 7.9 Hz, 1H), 7.80 (t, J = 6.4 Hz, 1H), 7.73 (s, 1H), 7.55 (dd, J = 4.8, 8.0 Hz, 1H), 6.52 (s, 1H), 3.74 (dd, J = 6.8, 13.8 Hz, 1H), 3.67 - 3.52 (m, 1H), 3.21 (d, J = 1.9 Hz, 6H), 2.21 (s, 3H), 1.29 (s, 3H).

[0871]

[0872] Example 99-3: 8-Chloro-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0873]

[0874] To the compound of Example 99-2 (900 mg, 1.97 mmol, 1 equivalent) was added sulfuric acid (4.82 g, 49.10 mmol, 2.62 mL, 24.92 equivalent), and the mixture was stirred at 105°C for 1 hour under nitrogen. After confirming that the desired reaction had occurred through LC-MS, ice water (10 mL) was added, and the mixture was stirred for 10 minutes. The pH of the reaction mixture was adjusted to 8 by adding a saturated aqueous sodium bicarbonate solution. The precipitated solid was filtered, and the filtrate was extracted with ethyl acetate (20 mL × 3). The organic layer was washed with a saturated aqueous sodium chloride solution (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by column chromatography (stationary phase: silica, petroleum ether / ethyl acetate = 0% to 100%) to obtain the title compound (770 mg, 1.94 mmol, 98.5% yield, 99% purity) as a white solid.

[0875] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.72 (dd, J = 1.6, 4.8 Hz, 1H), 8.40 (s, 1H), 7.90 (dd, J = 1.5, 8.0 Hz, 1H), 7.57 (dd, J = 4.8, 8.0 Hz, 1H), 7.52 (s, 1H), 6.71 (s, 1H), 2.93 (s, 3H), 2.26 (s, 3H).

[0876]

[0877] Example 100: 8-Chloro-2-(dimethylamino)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0878] Example 100 Reaction scheme for the preparation of compound:

[0879]

[0880] Example 100-1: 2-Bromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0881] Using the compound of Example 99 as a starting material, the title compound (440 mg, 913.29 μmol, 62.9% yield, 97.9% purity) as a white solid was synthesized in the same manner as in Example 85.

[0882] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.73 (dd, J = 1.2, 4.8 Hz, 1H), 8.42 (s, 1H), 7.87 (dd, J = 1.2, 7.6 Hz, 1H), 7.57 (dd, J = 4.8, 8.0 Hz, 1H), 6.73 (s, 1H), 2.93 (s, 3H), 2.26 (s, 3H).

[0883]

[0884] Example 100-2: 8-Chloro-2-(dimethylamino)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0885]

[0886] Example 100-1 Compound (23.54 mg, 49.91 μmol, 1 equiv), dimethylamine (2 M, 499.08 μL, 20 equiv), cuprous iodide (9.50 mg, 49.91 μmol, 1 equiv), L-proline (6.90 mg, 59.89 μmol, 1.2 equiv), potassium triphosphate (31.78 mg, 149.72 μmol, 3 equiv) were dissolved in dimethyl sulfoxide (1 mL), and after nitrogen purging, the reaction mixture was stirred at 100 °C for 12 hours under nitrogen. Water (3 mL) was added to the reaction mixture, and then extracted with ethyl acetate (3 mL X 2). The organic layer was washed with saturated aqueous sodium chloride solution (5 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5μm; mobile phase: [water(ammonium bicarbonate)-acetonitrile]; B%: 38%-68%, 9 min) to obtain the title compound as a white solid (3 mg, 6.88 μmol, 13.8% yield).

[0887] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.78 (dd, J = 1.6, 4.8 Hz, 1H), 8.29 (s, 1H), 7.56 (dd, J = 1.2, 8.0 Hz, 1H), 7.45 (dd, J = 5.2, 8.0 Hz, 1H), 6.87 (s, 1H), 2.94 (s, 6H), 2.88 (s, 3H), 2.36 (s, 3H).

[0888]

[0889] Example 101: 7-Chloro-9-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0890]

[0891] The title compound was synthesized in the same manner as in Example 90, changing the starting material to 5-chloro-1,3-difluoro-2-nitrobenzene.

[0892] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.81 - 8.59 (m, 1H), 8.40 (dd, J = 1.4, 2.8 Hz, 1H), 7.91 - 7.82 (m, 1H), 7.74 (d, J = 1.4 Hz, 1H), 7.68 (dd, J = 2.4, 12.0 Hz, 1H), 7.59 - 7.48 (m, 1H), 6.29 (s, 1H), 2.27 (s, 3H).

[0893]

[0894] Example 102: 7-Chloro-9-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0895] Example 102 Reaction scheme for the preparation of compound:

[0896]

[0897] Example 102-1: N-(5-chloro-3-fluoro-2-nitrophenyl)-2-methylpyridin-3-amine

[0898] The title compound was synthesized in the same manner as in Example 90-1 using 5-chloro-1,3-difluoro-2-nitrobenzene as the starting material.

[0899] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.59 (br s, 1H), 8.50 (dd, J = 1.2, 4.8 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.30 - 7.26 (m, 1H), 6.64 (dd, J = 2.0, 10.8 Hz, 1H), 6.49 (t, J = 1.8 Hz, 1H), 2.53 (s, 3H).

[0900]

[0901] Example 102-2: N-(5-chloro-3-methoxy-2-nitrophenyl)-2-methylpyridin-3-amine

[0902] The compound of Example 102-1 (5 g, 17.75 mmol, 1 equiv) was dissolved in methanol (50 mL), and sodium methoxide (6.39 g, 35.50 mmol, 30% purity, 2 equiv) was added. After nitrogen purging three times, the mixture was stirred at 25 °C under nitrogen for 2 hours. When the starting material disappeared and the desired m / z was detected through LC-MS, water (100 mL) was added to terminate the reaction, and then extracted with ethyl acetate (50 mL X 3). The organic layer was washed with a saturated aqueous sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (5.2 g, crude mixture) as a white solid, which was used in the next reaction without further purification.

[0903] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.42 (dd, J = 1.4, 4.8 Hz, 1H), 7.72 (s, 1H), 7.55 (dd, J = 1.1, 7.9 Hz, 1H), 7.22 (dd, J = 4.8, 8.0 Hz, 1H), 6.45 (d, J = 2.0 Hz, 1H), 6.36 (d, J = 2.0 Hz, 1H), 3.94 (s, 3H), 2.51 (s, 3H).

[0904]

[0905] Example 102-3: 5-Chloro-3-methoxy-N 1 -(2-methylpyridin-3-yl)benzene-1,2-diamine

[0906] The title compound was synthesized in the same manner as in Example 90-2 using the compound of Example 102-2 as a starting material.

[0907] 1H NMR (400 MHz, CDCl3, ppm): δ 8.07 (dd, J = 1.2, 4.6 Hz, 1H), 7.02 (dd, J = 4.8, 8.2 Hz, 1H), 6.91 (dd, J = 1.2, 8.0 Hz, 1H), 6.67 (q, J = 2.0) Hz, 2H), 5.07 (s, 1H), 3.89 (s, 3H), 3.77 (br s, 2H), 2.54 (s, 3H).

[0908]

[0909] Example 102-4: Ethyl 2-((4-chloro-2-methoxy-6-((2-methylpyridin-3-yl)amino)phenyl)amino)-2-oxoacetate

[0910] The title compound was synthesized in the same manner as in Example 90-3 using the compound of Example 102-3 as a starting material.

[0911] 1 H NMR (400 MHz, CDCl3, ppm): δ 9.10 (s, 1H), 8.21 (dd, J = 1.4, 4.6 Hz, 1H), 7.37 (dd, J = 1.2, 8.0 Hz, 1H), 7.08 (dd, J = 4.8, 8.0 Hz, 1H), 6.83 (s, 1H), 6.59 (d, J = 1.8 Hz, 1H), 6.54 (d, J = 2.0 Hz, 1H), 4.46 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 2.52 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H).

[0912]

[0913] Example 102-5: 7-Chloro-5-methoxy-1-(2-methylpyridin-3-yl)-1,4-dihydroquinoxaline-2,3-dione

[0914] The title compound was synthesized in the same manner as in Example 90-4 using the compound of Example 102-4 as a starting material.

[0915] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.60 (d, J = 3.8 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.46 (dd, J = 4.8, 7.8 Hz, 1H), 6.65 (d, J = 1.8 Hz, 1H), 5.62 (d, J = 2.0 Hz, 1H), 4.40 (br s, 1H), 3.80 (s, 3H), 3.36 (s, 3H).

[0916]

[0917] Example 102-6: 3,7-Dichloro-5-methoxy-1-(2-methylpyridin-3-yl)quinoxalin-2(1H)-one

[0918] The title compound was synthesized in the same manner as in Example 90-5 using the compound of Example 102-5 as a starting material.

[0919]

[0920] Example 102-7: 3-Amino-7-chloro-5-methoxy-1-(2-methylpyridin-3-yl)quinoxalin-2(1H)-one

[0921] The title compound was synthesized in the same manner as in Example 90-6 using the compound of Example 102-6 as a starting material.

[0922] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.67 (dd, J = 1.6, 4.8 Hz, 1H), 7.85 (dd, J = 1.4, 7.8 Hz, 1H), 7.52 (dd, J = 4.8, 8.0 Hz, 1H), 6.91 (d, J = 2.0) Hz, 1H), 5.82 (d, J = 2.0 Hz, 1H), 3.88 (s, 3H), 2.16 (s, 3H).

[0923]

[0924] Example 102-8: 7-Chloro-9-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0925]

[0926] The title compound was synthesized in the same manner as in Example 90-7 using the compound of Example 102-7 as a starting material.

[0927] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.76 (d, J = 1.0 Hz, 1H), 8.69 (dd, J = 1.6, 4.8 Hz, 1H), 7.86 (dd, J = 1.6, 7.8 Hz, 1H), 7.66 (d, J = 1.4 Hz, 1H), 7.54 (dd, J = 4.8, 7.8 Hz, 1H), 7.26 (d, J = 2.2 Hz, 1H), 6.02 (d, J = 2.2 Hz, 1H), 4.13 (s, 3H), 2.23 (s, 3H).

[0928]

[0929] Example 103: 7-Chloro-9-(cyclopropylmethoxy)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0930] Example 103 Reaction scheme for the preparation of compound:

[0931]

[0932] Example 103-1: 7-Chloro-9-hydroxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0933] The compound of Example 102 (500 mg, 1.47 mmol, 1 equiv) was dissolved in dichloroethane (10 mL), and boron tribromide (3.68 g, 14.67 mmol, 10 equiv) was added, and the mixture was stirred at 110 °C for 5 hours. When the starting material disappeared and the desired m / z was detected through LC-MS, ice water (20 mL) was added to stop the reaction, and the mixture was neutralized with a saturated aqueous sodium bicarbonate solution (30 mL). The mixture was extracted with dichloromethane (50 mL X 3). The organic layer was washed with a saturated aqueous sodium chloride solution (100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain the title compound (450 mg, crude mixture) as a yellow solid, which was used in the next reaction without further purification.

[0934] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.13 (s, 1H), 8.67 (dd, J = 1.6, 4.8 Hz, 1H), 7.85 (dd, J = 1.4, 7.8 Hz, 1H), 7.60 (d, J = 1.0 Hz, 1H), 7.53 (dd, J = 4.8, 7.8 Hz, 1H), 6.82 (d, J = 2.2 Hz, 1H), 5.59 (d, J = 1.8 Hz, 1H), 2.23 (s, 3H).

[0935]

[0936] Example 103-2: 7-Chloro-9-(cyclopropylmethoxy)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0937]

[0938] Example 103-1 Compound (500 mg, 1.53 mmol, 1 equiv), bromomethylcyclopropane (413.18 mg, 3.06 mmol, 292.21 μL, 2 equiv), potassium carbonate (634.48 mg, 4.59 mmol, 3 equiv) were added to dimethylformamide (5 mL), and after nitrogen purging three times, the reaction mixture was stirred at 25 °C under nitrogen for 5 hours. When the starting material disappeared and the desired m / z was detected through LC-MS, ice water (10 mL) was added to terminate the reaction, and after stirring for 10 minutes, the mixture was neutralized to pH = 8 with saturated aqueous sodium bicarbonate solution (30 mL). The precipitated solid in the aqueous layer was filtered and extracted with ethyl acetate (20 mL X 3). The organic layer was washed with saturated aqueous sodium chloride solution (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150*40mm*10 μm; mobile phase [water (0.1% ammonium bicarbonate)-acetonitrile]; B%: 28%-58%, 15 min) to obtain the title compound as a white solid (112 mg, 291.16 μmol, 19.0% yield, 99% purity).

[0939] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.85 (d, J = 1.0 Hz, 1H), 8.70 (dd, J = 1.6, 4.8 Hz, 1H), 7.87 (dd, J = 1.4, 7.8 Hz, 1H), 7.71 (d, J = 1.0 Hz, 1H), 7.54 (dd, J = 4.8, 7.8 Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H), 6.01 (d, J = 2.0 Hz, 1H), 4.41 - 3.93 (m, 2H), 2.24 (s, 3H), 1.58 - 1.34 (m, 1H), 0.79 - 0.63 (m, 2H), 0.52 - 0.32 (m, 2H).

[0940]

[0941] Example 104: 7-Chloro-5-(2-methylpyridin-3-yl)-9-(pyrrolidin-1-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0942]

[0943] The compound of Example 101 (70 mg, 212.94 μmol, 1 equiv), pyrrolidine (75.72 mg, 1.06 mmol, 88.88 μL, 5 equiv), and diisopropylethylamine (82.56 mg, 638.83 μmol, 111.27 μL, 3 equiv) were dissolved in dimethylacetamide (1 mL), and after nitrogen purging three times, the reaction mixture was stirred at 100 °C for 2 hours under nitrogen. When the starting material disappeared and the desired m / z was detected through LC-MS, the reaction was terminated by adding water (5 mL), and then extracted with ethyl acetate (5 mL X 2). The organic layer was washed with a saturated aqueous sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5μm; mobile phase: [water (0.1% ammonium bicarbonate)-acetonitrile]; B% 35%-65% 9 min) to obtain the title compound as a white solid (18 mg, 47.34 μmol, 22.23% yield, 99.9% purity).

[0944] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.86 (d, J = 0.8 Hz, 1H), 8.79 - 8.69 (m, 1H), 7.67 (d, J = 0.8 Hz, 1H), 7.64 (br d, J = 7.2 Hz, 1H), 7.48 (dd, J = 4.8, 8.0 Hz, 1H), 7.15 (d, J = 2.0 Hz, 1H), 6.24 (d, J = 2.0 Hz, 1H), 3.53 - 3.24 (m, 2H), 3.04 - 2.70 (m, 2H), 2.41 (s, 3H), 2.15 - 2.05 (m, 4H).

[0945]

[0946] Example 105: 7-Chloro-9-(methylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0947]

[0948] In Example 104, the reactant pyrrolidine was changed to methylamine, and the temperature was raised to 100 0 120 in C o The title compound was synthesized using the same method, changing to C.

[0949] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.77 (d, J = 1.2 Hz, 1H), 8.69 (dd, J = 1.6, 4.8 Hz, 1H), 7.86 (dd, J = 1.6, 8.9 Hz, 1H), 7.69 (d, J = 1.2 Hz, 1H), 7.54 (dd, J = 4.8, 8.0 Hz, 1H), 6.80 (d, J = 2.0 Hz, 1H), 6.10 (br d, J = 4.4 Hz, 1H), 5.76 (d, J = 2.0 Hz, 1H), 2.87 (d, J = 4.8 Hz, 3H), 2.22 (s, 3H).

[0950]

[0951] Example 106: 7-chloro-9-(dimethylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0952]

[0953] In Example 104, the reactant pyrrolidine was changed to dimethylamine, and the temperature was set to 100 0 120 in C o The title compound was synthesized using the same method, changing to C.

[0954] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.04 (d, J = 1.2 Hz, 1H), 8.69 (dd, J = 1.6, 4.8 Hz, 1H), 7.84 (dd, J = 1.6, 8.0 Hz, 1H), 7.66 (d, J = 1.2 Hz, 1H), 7.53 (dd, J = 4.8, 8.0 Hz, 1H), 7.30 (d, J = 2.4 Hz, 1H), 6.13 (d, J = 2.0 Hz, 1H), 2.75 (d, J = 4.8 Hz, 6H), 2.24 (s, 3H).

[0955]

[0956] Example 107: 7-Bromo-8-chloro-5-(2-methoxypyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0957] Example 107 Reaction scheme for the preparation of compound:

[0958]

[0959] Example 107-1: N-(5-bromo-4-chloro-2-nitrophenyl)-2-methoxypyridin-3-amine

[0960] 2-Methoxypyridin-3-amine (1.76 g, 14.15 mmol, 1.2 equiv) was dissolved in tetrahydrofuran (30 mL), and sodium hydride (707.37 mg, 17.69 mmol, 60% purity, 1.5 equiv) was added under nitrogen at 0 °C. After stirring at 0 °C for 1 h, 1-bromo-2-chloro-5-fluoro-4-nitrobenzene (3 g, 11.79 mmol, 1 equiv) was added, the temperature was raised to 25 °C, and the mixture was stirred for 11 h. When the starting material disappeared and the desired m / z was detected through LC-MS, the reaction was terminated by adding aqueous ammonium chloride solution (50 mL), and then extracted with ethyl acetate (30 mL X 3). The organic layer was washed with a saturated aqueous sodium chloride solution (30 mL X 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrate was purified by silica column chromatography (mobile phase: ethyl acetate / petroleum ether; B%: 0-60%) to obtain the title compound (2.5 g, 5.58 mmol, 47.31% yield, 80% purity) as a yellow solid.

[0961]

[0962] Example 107-2: 5-Bromo-4-chloro-N 1 -(2-methoxypyridin-3-yl)benzene-1,2-diamine

[0963] The title compound was synthesized in the same manner as in Example 75-2 using the compound of Example 107-1 as a starting material.

[0964]

[0965] Example 107-3: Ethyl 2-((4-bromo-5-chloro-2-((2-methoxypyridin-3-yl)amino)phenyl)amino)-2-oxoacetate

[0966] The title compound was synthesized in the same manner as in Example 90-3 using the compound of Example 107-2 as a starting material.

[0967]

[0968] Example 107-4: 7-Bromo-6-chloro-1-(2-methoxypyridin-3-yl)-1,4-dihydroquinoxaline-2,3-dione

[0969] The title compound was synthesized in the same manner as in Example 90-4 using the compound of Example 107-3 as a starting material.

[0970]

[0971] Example 107-5: 7-Bromo-3,6-dichloro-1-(2-methoxypyridin-3-yl)quinoxalin-2(1H)-one

[0972] The title compound was synthesized in the same manner as in Example 90-4 using the compound of Example 107-4 as a starting material.

[0973]

[0974] Example 107-6: 3-Amino-7-bromo-6-chloro-1-(2-methoxypyridin-3-yl)quinoxalin-2(1H)-one

[0975] The compound of Example 107-5 (2.07 g, 5.17 mmol, 1 equivalent) was dissolved in 2,2-dimethoxyethaneamine (10 mL). The reaction mixture was stirred at 25 °C for 1 hour. When the starting material disappeared and the desired m / z was detected by LC-MS, water (30 mL) was added to terminate the reaction, and the mixture was extracted with ethyl acetate (20 mL X 2). The organic layer was washed with a saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (2.2 g, crude mixture) as a yellow solid, which was used in the next reaction without further purification.

[0976]

[0977] Example 107-7: 7-Bromo-6-chloro-3-((2,2-dimethoxyethyl)amino)-1-(2-methoxypyridin-3-yl)quinoxalin-2(1H)-one

[0978] The title compound was synthesized in the same manner as in Example 99-2, using the compound of Example 107-6 as a starting material and using 2,2-dimethoxyethane-1-amine as a reactant instead of 2,2-dimethoxypropan-1-amine, the reactant of Example 99-2.

[0979]

[0980] Example 107-8: 7-Bromo-8-chloro-5-(2-methoxypyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0981]

[0982] The title compound was synthesized in the same manner as in Example 99-3 using the compound of Example 107-7 as a starting material.

[0983] 1 H NMR (400 MHz, DMSO-d6, ppm): 8.71 (d, J=14.8 Hz, 2 H), 8.44 (br d, J = 4.0 Hz, 1 H), 7.93 (br d, J = 7.2 Hz, 1 H), 7.30 (dd, J = 7.2, 5.2 Hz, 1 H), 7.72 (s, 1 H), 6.86 (s, 1 H), δ 3.83 (s, 3 H).

[0984]

[0985] Example 108: 5-(Benzo[d]thiazol-7-yl)-7-bromo-8-chloroimidazo[1,2-a]quinoxalin-4(5H)-one

[0986]

[0987] The title compound was synthesized in the same manner as in Example 79 using benzo[d]thiazol-7-amine instead of 2-methylpyridin-3-amine in Example 5-1.

[0988] 1H NMR (400 MHz, DMSO-d6, ppm): δ 9.48 (s, 1H), 8.81 - 8.70 (m, 2H), 8.37 (dd, J = 0.8, 8.0 Hz, 1H), 7.85 (s, 1H), 7.75 (d, J = 1.2 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 6.69 (s, 1H).

[0989]

[0990] Example 109: 7-Bromo-8-chloro-5-(1H-indol-4-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[0991] Example 109 Reaction scheme for the preparation of compound:

[0992]

[0993] Example 109-1: N-(5-Bromo-4-chloro-2-nitrophenyl)-1-tosyl-1H-indole-4-amine

[0994] The title compound was synthesized in the same manner as in Example 107-1, using 1-tosyl-1H-indole-4-amine instead of 2-methoxypyridin-3-amine, the starting material of Example 107-1.

[0995] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 9.59 - 9.52 (m, 1H), 8.33 - 8.25 (m, 1H), 7.92 - 7.78 (m, 4H), 7.46 - 7.34 (m, 3H), 7.27 - 7.19 (m, 1H), 6.99 - 6.94 (m, 1H), 6.74 - 6.65 (m, 1H), 2.36 - 2.27 (m, 3H).

[0996]

[0997] Example 109-2: 5-Bromo-4-chloro-N 1 -(1-Tosyl-1H-indol-4-yl)benzene-1,2-diamine

[0998] The title compound was synthesized in the same manner as in Example 107-2 using the compound of Example 109-1 as a starting material.

[0999]

[1000] Example 109-3: Ethyl 2-((4-bromo-5-chloro-2-((1-tosyl-1H-indol-4-yl)amino)phenyl)amino)-2-oxoacetate

[1001] The title compound was synthesized in the same manner as in Example 107-3 using the compound of Example 109-2 as a starting material.

[1002]

[1003] Example 109-4: 7-Bromo-6-chloro-1-(1-tosyl-1H-indol-4-yl)-1,4-dihydroquinoxaline-2,3-dione

[1004] The title compound was synthesized in the same manner as in Example 107-4 using the compound of Example 109-3 as a starting material.

[1005]

[1006] Example 109-5: 7-Bromo-3,6-dichloro-1-(1-tosyl-1H-indol-4-yl)quinoxalin-2(1H)-one

[1007] The title compound was synthesized in the same manner as in Example 75-4 using the compound of Example 109-4 as a starting material.

[1008]

[1009] Example 109-6: 3-Amino-7-bromo-6-chloro-1-(1-tosyl-1H-indol-4-yl)quinoxalin-2(1H)-one

[1010] The title compound was synthesized in the same manner as in Example 75-5 using the compound of Example 109-5 as a starting material.

[1011] 1H NMR (400 MHz, CDCl3, ppm): δ 8.27 - 8.14 (m, 1H), 7.90 - 7.79 (m, 2H), 7.67 - 7.60 (m, 2H), 7.58 - 7.50 (m, 1H), 7.36 - 7.29 (m, 2H), 7.22 - 7.17 (m, 1H), 6.67 - 6.58 (m, 1H), 6.29 - 6.20 (m, 1H), 6.15 - 5.65 (m, 2H), 1.91 - 1.61 (m, 3H).

[1012]

[1013] Example 109-7: 7-Bromo-8-chloro-5-(1-tosyl-1H-indol-4-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1014] The title compound was synthesized in the same manner as in Example 75-6 using the compound of Example 109-6 as a starting material.

[1015]

[1016] Example 109-8: 7-Bromo-8-chloro-5-(1H-indol-4-yl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1017]

[1018] The compound of Example 109-7 (136 mg, 191.60 μmol, 1 equivalent) was dissolved in methanol (1.5 mL), and sodium hydroxide (23.45 mg, 586.31 μmol, 3.06 equivalent) was added at 25 °C. The reaction mixture was stirred at 65 °C for 4 hours. When the starting material disappeared and the desired m / z was detected by LC-MS, the reaction mixture was concentrated under reduced pressure. The resulting concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5μm; mobile phase: [water (0.1% ammonium bicarbonate)-acetonitrile]; B%: 35%-65%, 9 min) to obtain the title compound as a white solid (42.76 mg, 103.10 μmol, 48.5% yield, 99.7% purity).

[1019] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 11.55 - 11.47 (m, 1H), 8.75 - 8.70 (m, 1H), 8.69 - 8.65 (m, 1H), 7.72 - 7.69 (m, 1H), 7.66 - 7.60 (m, 1H), 7.43 - 7.39 (m, 1H), 7.36 - 7.29 (m, 1H), 7.11 - 7.07 (m, 1H), 6.63 - 6.59 (m, 1H), 6.27 - 6.20 (m, 1H).

[1020]

[1021] Example 110: 8-Chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1022] Reaction scheme for the preparation of Example 110:

[1023]

[1024] Example 110-1: N-(4-chloro-3-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide

[1025] 4-Chloro-3-(trifluoromethyl)aniline (5 g, 25.57 mmol, 1 equiv) was added to dichloromethane (16.5 mL), and pyridine (10.11 g, 127.83 mmol, 10.32 mL, 5 equiv) and (CF3CO)2O (5.91 g, 28.12 mmol, 3.91 mL, 1.1 equiv) were added dropwise at 0 °C. The reaction mixture was stirred at 25 °C for 2 h. The reaction was observed to be complete by TLC. The reaction mixture was washed with saturated aqueous ammonium chloride solution (40 mL X 3), dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (7 g, 24.01 mmol, 93.9% yield) as an orange solid without further purification.

[1026] 1H NMR (400 MHz, CDCl3, ppm): δ 8.12 - 7.95 (m, 1H), 7.94 - 7.88 (m, 1H), 7.87 - 7.76 (m, 1H), 7.62 - 7.52 (m, 1H).

[1027]

[1028] Example 110-2: N-(4-chloro-2-nitro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide

[1029] CF3SO3H (10.09 g, 67.22 mmol, 5.95 mL, 2.8 equiv) was dissolved in dichloromethane (37 mL), and nitric acid (2.68 g, 41.68 mmol, 1.91 mL, 98% purity, 1.74 equiv) was added at 0 °C. The resulting reaction mixture was stirred at 0 °C for 1 hour, and then a solution of the mixture obtained in Example 110-1 (7 g, 24.01 mmol, 1 equiv) dissolved in dichloromethane (37 mL) was added dropwise at 0 °C, and the mixture was stirred at 25 °C for 12 hours. After confirming the completion of the reaction on TLC, the reaction was terminated by adding a saturated aqueous sodium bicarbonate solution (50 mL), and extracted with dichloromethane (20 mL X 2). The organic layer was washed with a saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0–12%) to obtain the title compound (6.56 g, 19.50 mmol, 81.2% yield) as a yellow solid.

[1030] 1 H NMR (400 MHz, CDCl3, ppm): δ 11.42 - 11.09 (m, 1H), 9.28 - 9.13 (m, 1H), 8.57 - 8.40 (m, 1H).

[1031]

[1032] Example 110-3: 4-Chloro-2-nitro-5-(trifluoromethyl)aniline

[1033] The compound obtained in Example 110-2 (6.56 g, 19.50 mmol, 1 equiv) and potassium carbonate (3.23 g, 23.40 mmol, 1.2 equiv) were added to methanol (35 mL) and purified water (35 mL), and nitrogen purging was performed three times. The reaction mixture was stirred at 25 °C under nitrogen for 2 hours. After confirming the completion of the reaction by TLC, the mixture was concentrated under reduced pressure to remove methanol, and extracted with ethyl acetate (60 mL X 2). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0-16%) to obtain the title compound (4.48 g, 18.63 mmol, 95.5% yield) as a yellow liquid.

[1034] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.19 - 8.06 (m, 1H), 7.90 - 7.71 (m, 2H), 7.65 - 7.52 (m, 1H).

[1035]

[1036] Example 110-4: N-(4-chloro-2-nitro-5-(trifluoromethyl)phenyl)-2-ethylpyridin-3-amine

[1037] The compound obtained in Example 110-3 (4 g, 16.63 mmol, 1 equiv.), 3-bromo-2-ethyl-pyridine (3.40 g, 18.29 mmol, 1.1 equiv.), xantphos (1.92 g, 3.33 mmol, 0.2 equiv.), cesium carbonate (16.25 g, 49.88 mmol, 3 equiv.), tris(dibenzylideneacetone)dipalladium(0) (1.52 g, 1.66 mmol, 0.1 equiv.) were added to dioxane (80 mL), and nitrogen purging was performed three times. The resulting reaction mixture was stirred at 100 °C under nitrogen for 12 hours. After confirming the completion of the reaction by TLC, the reaction mixture was filtered, and the filtrate was concentrated. The concentrate was purified by chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0-16%) to give the title compound (3.9 g, 11.28 mmol, 67.8% yield) as a yellow solid.

[1038] 1 H NMR (400 MHz, CDCl3, ppm): δ 9.47 - 9.23 (m, 1H), 8.65 - 8.52 (m, 1H), 8.44 - 8.31 (m, 1H), 7.67 - 7.53 (m, 1H), 7.36 - 7.22 (m, 1H), 7.21 - 7.09 (m, 1H), 2.94 - 2.75 (m, 2H), 1.31 - 1.25 (m, 3H).

[1039]

[1040] Example 110-5: 4-Chloro-N 1 -(2-ethylpyridin-3-yl)-5-(trifluoromethyl)benzene-1,2-diamine

[1041] The title compound was synthesized in the same manner as in Example 75-2 using the compound of Example 110-4 as a starting material.

[1042] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.03 - 7.96 (m, 1H), 7.11 - 7.07 (m, 1H), 7.06 - 6.99 (m, 1H), 6.94 - 6.87 (m, 2H), 6.75 - 6.67 (m, 1H), 5.83 - 5.74 (m, 2H), 2.85 - 2.68 (m, 2H), 1.32 - 1.16 (m, 3H).

[1043]

[1044] Example 110-6: 6-Chloro-1-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxaline-2,3-dione

[1045] The compound obtained in Example 110-5 (3.14 g, 9.95 mmol, 1 eq.) and triethylamine (2.22 g, 21.89 mmol, 3.05 mL, 2.2 eq.) were added to dichloromethane (95 mL), and ethyl 2-chloro-2-oxoacetate (2.72 g, 19.90 mmol, 2.22 mL, 2 eq.) was added at 0 °C. The reaction mixture was stirred at 25 °C for 2 hours. When the reaction was completed by LC-MS, the reaction mixture was filtered, and the filtrate was concentrated. Tetrahydrofuran (50 mL) was added to the concentrate, and an aqueous sodium hydroxide solution (10%) (25 mL) was added, and the mixture was stirred at 25 °C for 30 minutes. After adding purified water (75 mL) to the reaction mixture, the mixture was extracted with ethyl acetate (100 mL X 3). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0-51%) to obtain the title compound (1.3 g, 3.52 mmol, 35.3% yield) as a yellow solid.

[1046] 1H NMR (400 MHz, DMSO-d6, ppm): δ 12.62 - 12.46 (m, 1H), 8.82 - 8.71 (m, 1H), 7.85 - 7.76 (m, 1H), 7.57 - 7.49 (m, 1H), 7.47 - 7.43 (m, 1H), 6.43 - 6.39 (m, 1H), 2.59 - 2.52 (m, 2H), 1.11 - 1.06 (m, 3H).

[1047]

[1048] Example 110-7: 3,6-Dichloro-1-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[1049] The title compound was synthesized in the same manner as in Example 33-4 using the compound of Example 110-6 as a starting material.

[1050] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.94 - 8.91 (m, 1H), 8.27 - 8.14 (m, 1H), 7.94 - 7.80 (m, 1H), 7.58 - 7.50 (m, 1H), 6.76 - 6.63 (m, 1H), 2.81 - 2.68 (m, 2H), 1.16 - 1.11 (m, 3H).

[1051]

[1052] Example 110-8: 6-Chloro-3-((2,2-dimethoxyethyl)amino)-1-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[1053] The title compound was synthesized in the same manner as in Example 107-7 using the compound of Example 110-7 as a starting material.

[1054] 1H NMR (400 MHz, CDCl3, ppm): δ 8.86 - 8.78 (m, 1H), 7.73 - 7.67 (m, 1H), 7.56 - 7.47 (m, 1H), 7.46 - 7.38 (m, 1H), 6.86 - 6.75 (m, 1H), 6.68 - 6.58 (m, 1H), 4.67 - 4.58 (m, 1H), 3.88 - 3.64 (m, 2H), 3.52 - 3.40 (m, 6H), 2.61 - 2.39 (m, 2H), 1.19 (t,J= 7.4 Hz, 3H).

[1055]

[1056] Example 110-9: 8-Chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1057]

[1058] The title compound was synthesized in the same manner as in Example 99-3 using the compound of Example 110-8 as a starting material.

[1059] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.85 - 8.76 (m, 3H), 7.91 - 7.85 (m, 1H), 7.79 - 7.74 (m, 1H), 7.61 - 7.53 (m, 1H), 6.68 - 6.62 (m, 1H), 2.58 - 2.52 (m, 2H), 1.16 - 1.04 (m, 3H).

[1060]

[1061] Example 111: (Ra)-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1062]

[1063] The compound of Example 110 was separated using DAICEL CHIRALPAK AD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 1.42 min) (ee% = 99.4%) to obtain the title compound as a white solid.

[1064] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.87 - 8.73 (m, 3H), 7.90 - 7.83 (m, 1H), 7.80 - 7.74 (m, 1H), 7.59 - 7.52 (m, 1H), 6.68 - 6.62 (m, 1H), 2.58 - 2.52 (m, 2H), 1.14 - 1.04 (m, 3H).

[1065]

[1066] Example 112: (Sa)-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1067]

[1068] The compound of Example 110 was separated using DAICEL CHIRALPAK AD (250 mm*30 mm, 10 μm); mobile phase: [carbon dioxide-ethanol (0.1% ammonia water)]; B%: 35%, isocratic transfer conditions (retention time: 2.08 min) (ee% = 98.1%) to obtain the title compound as a white solid.

[1069] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.83 - 8.76 (m, 3H), 7.91 - 7.85 (m, 1H), 7.76 (d,J= 1.2 Hz, 1H), 7.60 - 7.52 (m, 1H), 6.68 - 6.63 (m, 1H), 2.59 - 2.52 (m, 2H), 1.13 - 1.05 (m, 3H).

[1070]

[1071] Example 113: 9-Methoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1072] Reaction scheme for the preparation of Example 113:

[1073]

[1074] Example 113-1: 2-Chloro-6-fluoro-4-(trifluoromethyl)aniline

[1075] 2-Fluoro-4-(trifluoromethyl)aniline was dissolved in acetonitrile (20 mL) and N-chlorosuccinimide (1.64 g, 12.28 mmol, 1.1 equivalents) was added. The reaction mixture was stirred at 85 °C for 3 h. LC-MS showed that all the starting material was consumed and the MS ([M+H]) of the desired compound + = 214.2) was observed, the reaction mixture was concentrated under reduced pressure. Petroleum ether (20 mL) was added to the reaction mixture and 25 o After softening at C for 30 minutes, the solid was filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (2 g, 9.37 mmol, 83.9% yield) in the form of a yellow oil. The next reaction was carried out immediately without any additional purification.

[1076] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.40 - 7.31 (m, 1H), 7.24 - 7.12 (m, 1H), 4.57 - 4.26 (m, 2H).

[1077]

[1078] Example 113-2: 1-Chloro-3-fluoro-2-nitro-5-(trifluoromethyl)benzene

[1079] Sodium perborate tetrahydrate (16.21 g, 105.36 mmol, 20.26 mL, 15 equivalents) was dissolved in acetic acid (67.5 mL) and heated to 50°C. Then, a solution of the compound obtained in Example 113-1 (1.5 g, 7.02 mmol, 1 equivalent) dissolved in acetic acid (30 mL) was slowly added. The reaction mixture was stirred at 50 o C and stirred for 24 hours. After confirming that the reaction had proceeded completely on TLC, purified water (150 mL) was added and extracted with ethyl acetate (150 mL X 3). The organic layer was washed with aqueous Na2CO3 solution (pH=7-8), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0-40%) to obtain the title compound (624 mg, 2.56 mmol, 36.5% yield) as a yellow oil.

[1080] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.72 - 7.59 (m, 1H), 7.55 - 7.42 (m, 1H).

[1081]

[1082] Example 113-3: 1-Chloro-3-methoxy-2-nitro-5-(trifluoromethyl)benzene

[1083] Lithium bis(trimethylsilyl)amide (1 M, 12.32 mL, 1.5 equiv) was dissolved in tetrahydrofuran (20 mL), and methanol (315.76 mg, 9.85 mmol, 398.78 μL, 1.2 equiv) was added. The reaction mixture was stirred at 0 °C for 45 min, and a solution of the compound obtained in Example 113-2 (2 g, 8.21 mmol, 1 equiv) in tetrahydrofuran (10 mL) was added at 0 °C, followed by stirring at 25 °C under nitrogen for 12 h. After confirming the progress of the reaction by TLC, the reaction was terminated by adding a saturated aqueous ammonium chloride solution (100 mL) at 0 °C, and then extracted with ethyl acetate (100 mL X 3). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (2 g, crude mixture) as a yellow oil.

[1084] 1 H NMR (400 MHz, CDCl3, ppm): δ 7.39 - 7.34 (m, 1H), 7.21 - 7.16 (m, 1H), 4.02 - 3.95 (m, 3H).

[1085]

[1086] Example 113-4: N-(3-methoxy-2-methyl-5-(trifluoromethyl)phenyl)-2-methylpyridin-3-amine

[1087] The compound obtained in Example 113-3 (1.75 g, 6.85 mmol, 1 equiv), 2-methylpyridin-3-amine (888.56 mg, 8.22 mmol, 1.2 equiv), Pd2(dba)3 (313.51 mg, 342.36 μmol, 0.05 equiv), BINAP (285.66 mg, 458.76 μmol, 0.067 equiv), and cesium carbonate (2.23 g, 6.85 mmol, 1 equiv) were dissolved in toluene (20 mL), degassed, purged with nitrogen three times, and stirred at 110 °C for 12 hours. After confirming the progress of the reaction through LC-MS, the reaction mixture was concentrated under reduced pressure. The concentrate was purified by chromatography (stationary phase: silica, ethyl acetate / petroleum ether 0-25%) to obtain the title compound (1.90 g, 5.81 mmol, 84.9% yield) as a yellow solid.

[1088] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.36 - 8.31 (m, 1H), 8.28 - 8.23 ​​(m, 1H), 7.55 - 7.48 (m, 1H), 7.29 - 7.21 (m, 1H), 6.98 - 6.93 (m, 1H), 6.40 (s, 1H), 3.99 - 3.89 (m, 3H), 2.32 (s, 3H).

[1089]

[1090] Example 113-5: 3-Methoxy-N 1 -(2-methylpyridin-3-yl)-5-(trifluoromethyl)benzene-1,2-diamine

[1091] The title compound was obtained in the same manner as in Example 75-2 using the compound of Example 113-4 as a starting material.

[1092] 1H NMR (400 MHz, DMSO-d6, ppm): δ 7.91 - 7.87 (m, 1H), 7.04 - 6.97 (m, 1H), 6.94 - 6.90 (m, 1H), 6.90 - 6.86 (m, 1H), 6.84 - 6.79 (m, 1H), 6.67 - 6.60 (m, 1H), 5.02 (brs, 2H), 3.87 (s, 3H), 2.44 (s, 3H).

[1093]

[1094] Example 113-6: Ethyl 2-((2-methoxy-6-((2-methylpyridin-3-yl)amino)-4-(trifluoromethyl)phenyl)amino)-2-oxoacetate

[1095] The title compound was synthesized in the same manner as in Example 48-3 using the compound of Example 113-5 as a starting material.

[1096]

[1097] Example 113-7: 5-Methoxy-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-1,4-dihydroquinoxaline-2,3-dione

[1098] The compound obtained in Example 113-6 (2.21 g, 5.56 mmol, 1 equiv) was dissolved in dichloromethane (25 mL), and triethylamine (2.25 g, 22.25 mmol, 3.10 mL, 4 equiv) was added. The reaction mixture was stirred at 25 °C for 12 hours. After confirming the completion of the reaction by LC-MS, the reaction mixture was concentrated under reduced pressure. Acetonitrile was added to the concentrate, and solidification was carried out at 25 °C for 30 minutes to obtain the title compound (1.95 g, crude mixture) as a white solid.

[1099] 1H NMR (400 MHz, DMSO-d6, ppm): δ 12.05 - 11.49 (m, 1H), 8.72 - 8.62 (m, 1H), 7.90 - 7.75 (m, 1H), 7.59 - 7.43 (m, 1H), 7.32 - 7.16 (m, 1H), 6.01 (s, 1H), 4.00 - 3.97 (m, 3H), 2.24 (s, 3H).

[1100]

[1101] Example 113-8: 3-Chloro-5-methoxy-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[1102] The compound obtained in Example 113-7 (1.95 g, 5.55 mmol, 1 equivalent) was dissolved in phosphoryl chloride (9.75 mL), and after nitrogen purging three times, the reaction mixture was stirred at 110 °C for 16 hours under nitrogen. After confirming that the reaction had proceeded completely by LC-MS, the reaction mixture was concentrated under reduced pressure to obtain the title compound (2.05 g, crude mixture) as a black oil, which was used in the next reaction without further purification.

[1103]

[1104] Example 113-9: 3-Amino-5-methoxy-1-(2-methylpyridin-3-yl)-7-(trifluoromethyl)quinoxalin-2(1H)-one

[1105] The title compound in the form of a yellow solid was synthesized in the same manner as in Example 33-5 using the compound obtained in Example 113-8 as a starting material.

[1106] 1 H NMR (400 MHz, CDCl3, ppm): δ 8.83 - 8.71 (m, 1H), 7.63 - 7.51 (m, 1H), 7.51 - 7.39 (m, 1H), 7.08 - 6.98 (m, 1H), 6.42 - 5.90 (m, 3H), 4.10 - 4.06 (m, 3H), 2.35 - 2.27 (m, 3H).

[1107]

[1108] Example 113-10: 9-Methoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1109]

[1110] The title compound in the form of a yellow solid was obtained in the same manner as in Example 33-6 using the compound obtained in Example 113-9 as a starting material.

[1111] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.88 - 8.82 (m, 1H), 8.76 - 8.67 (m, 1H), 7.94 - 7.85 (m, 1H), 7.74 - 7.68 (m, 1H), 7.61 - 7.51 (m, 1H), 7.48 - 7.42 (m, 1H), 6.29 - 6.20 (m, 1H), 4.26 - 4.17 (m, 3H), 2.27 - 2.21 (m, 3H).

[1112]

[1113] Example 115: 9-(Difluoromethoxy)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1114] Reaction scheme for the preparation of Example 115:

[1115]

[1116] Example 115-1: 9-Hydroxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1117] The title compound of Example 113 (250 mg, 667.88 μmol, 1 equiv) was added to pyridine hydrochloric acid (3.00 g, 25.96 mmol, 38.87 equiv), and the reaction mixture was stirred at 210 °C for 1 hour. After the reaction was observed to proceed completely by LC-MS, the reaction mixture was cooled to 25 °C, pH adjusted to 5-6 with aqueous sodium bicarbonate solution, and extracted with dichloromethane / isopropyl alcohol (100 mL X 6). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography (stationary phase: silica, petroleum ether / ethyl acetate 0-100%) to obtain the title compound (480 mg, 1.33 mmol, 97.78% yield) as a yellow solid.

[1118] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 12.26 (br s, 1H), 8.95 - 8.86 (m, 1H), 8.78 - 8.62 (m, 1H), 7.91 - 7.85 (m, 1H), 7.70 - 7.66 (m, 1H), 7.58 - 7.51 (m, 1H), 7.22 - 7.17 (m, 1H), 6.09 - 6.03 (m, 1H), 2.34 - 2.17 (m, 3H).

[1119]

[1120] Example 115-2: 9-(Difluoromethoxy)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1121]

[1122] The compound obtained in Example 115-1 (120 mg, 333.07 μmol, 1 equivalent) was dissolved in dimethylformamide (2.4 mL), and cesium carbonate (217.04 mg, 666.13 μmol, 2 equivalents) and sodium chloride difluoroacetate (126.95 mg, 832.66 μmol, 2.5 equivalents) were added. The reaction mixture was stirred at 100 °C for 2 hours. After confirming the completion of the reaction by LC-MS, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5um; mobile phase: [water (10 mM ammonium bicarbonate)-acetonitrile, B%: 30%-60%, 9 min) to obtain the title compound (77.05 mg, 185.24 μmol, 51.36% yield, 98.6% purity) as a white solid.

[1123] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.75 - 8.69 (m, 1H), 8.64 - 8.59 (m, 1H), 7.91 - 7.90 (m, 1H), 7.90 - 7.87 (m, 1H), 7.79 - 7.75 (m, 1H), 7.72 - 7.69 (m, 1H), 7.67 - 7.64 (m, 1H), 7.58 - 7.54 (m, 1H), 7.53 - 7.51 (m, 1H), 6.53 - 6.49 (m, 1H), 2.36 - 2.16 (m, 3H).

[1124]

[1125] Example 117: 5-(2-Methylpyridin-3-yl)-9-(2,2,2-trifluoroethoxy)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1126]

[1127] The compound obtained in Example 115-1 (120 mg, 333.07 μmol, 1 equivalent) was dissolved in dimethylformamide (2.4 mL), and cesium carbonate (217.04 mg, 666.13 μmol, 2 equivalents) and TfOCH2CF3 (85.04 mg, 366.37 μmol, 50.65 μL, 1.1 equivalents) were added. The reaction mixture was stirred at 25 °C for 2 hours. After confirming the completion of the reaction by LC-MS, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5um; mobile phase: [water (10 mM ammonium bicarbonate)-acetonitrile, B%: 34%-64%, 15 min) to obtain the title compound (97.6 mg, 219.56 μmol, 60.87% yield, 99.5% purity) as a white solid.

[1128] 1 H NMR (400 MHz, DMSO-d6, ppm): δ 8.79 - 8.67 (m, 1H), 8.62 - 8.50 (m, 1H), 7.95 - 7.86 (m, 1H), 7.82 - 7.75 (m, 1H), 7.67 - 7.62 (m, 1H), 7.61 - 7.53 (m, 1H), 6.38 - 6.30 (m, 1H), 5.46 - 5.26 (m, 2H), 2.33 - 2.18 (m, 3H).

[1129]

[1130] Example 118: 9-Ethoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one

[1131]

[1132] The compound obtained in Example 115-1 (120 mg, 333.07 μmol, 1 equivalent) was dissolved in dimethylformamide (2.4 mL), and cesium carbonate (217.04 mg, 666.13 μmol, 2 equivalents) and bromoethane (97.99 mg, 899.28 μmol, 67.12 μL, 2.7 equivalents) were added. The reaction mixture was stirred at 25 °C for 2 hours. After confirming the completion of the reaction by LC-MS, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by prep-HPLC (column: Waters Xbridge 150*25mm* 5um; mobile phase: [water (10 mM ammonium bicarbonate)-acetonitrile, B%: 30%-60%, 9 min) to obtain the title compound (79.79 mg, 202.89 μmol, 56.25% yield, 98.7% purity) as a white solid.

[1133] 1H NMR (400 MHz, DMSO-d6, ppm): δ 8.85 - 8.78 (m, 1H), 8.75 - 8.67 (m, 1H), 7.93 - 7.84 (m, 1H), 7.74 - 7.69 (m, 1H), 7.59 - 7.50 (m, 1H), 7.47 - 7.39 (m, 1H), 6.26 - 6.19 (m, 1H), 4.56 - 4.41 (m, 2H), 2.31 - 2.19 (m, 3H), 1.62 - 1.52 (m, 3H)

[1134]

[1135] Experimental Example 1: Evaluation of MAT2A activity inhibition ability

[1136] In vitro assay: Methionine and adenosine triphosphate (ATP) are converted to S-adenosylmethionine (SAM) and inorganic phosphate (pi) by the catalytic action of methionine adenosyltransferase 2A (MAT2A). The pi produced in this process is detected by the colorimetric assay PiColorLock™ Phosphate Detection Reagent, allowing the activity of MAT2A to be evaluated based on the amount of pi produced by the enzymatic reaction. Each compound was evaluated under the following test conditions 1 or 2.

[1137] [Test Condition 1]

[1138] MAT2A inhibitor concentration: maximum concentration 50 μM, 5-fold dilution (7 groups in total)

[1139] MAT2A concentration: 12 ng / μL

[1140] ATP and Met concentrations: 100 μM, 80 μM

[1141] [Test Condition 2]

[1142] MAT2A inhibitor concentration: maximum concentration 1 μM, 3-fold dilution (7 groups in total)

[1143] MAT2A concentration: 4 ng / μL

[1144] ATP and Met concentrations: 300 μM, 150 μM

[1145] Reagents: Methionine (Catalog No. M5308) and ATP (Catalog No. A2383) were purchased from Sigma Aldrich (USA). MAT2A (Catalog No. 71401) was purchased from BPS Bioscience (USA), and PiColorLock™ Phosphate Detection Reagent (Catalog No. 303-0030) was purchased from Novus (USA).

[1146] Buffer solution (assay buffer) composition: 50 mM Tris-HCl pH 8.0, 50 mM KCl, 15 mM MgCl2, 0.3 mM EDTA, 0.005% (w / v) BSA

[1147] Experimental procedure: Each compound was diluted 5-fold or 3-fold based on the highest concentration (5 mM or 1 mM or 0.1 mM) using DMSO. The diluted compounds were each diluted 20-fold using a buffer solution, and then mixed with MAT2A (30 ng / μL or 10 ng / μL) diluted in a buffer solution at a volume ratio of 1:2 and treated at room temperature for 30 minutes. The negative control group is a group that was not treated with the MAT2A enzyme or the compound according to an example of the present application, and the positive control group is a group that was treated with only the MAT2A enzyme and was not treated with the compound according to an example of the present application.

[1148] In each well of a 384-well plate, 30 μL of the mixed solution, 20 μL of a 1:1 mixed solution of ATP (0.5 mM or 1.5 mM), and Met (0.4 mM or 0.75 mM) were mixed, and the mixture was treated at room temperature for 1 hour. After the enzyme reaction, PiColorLock TM, Accelerator (Accelerator) was treated with 13 μL of a 100:1 mixed solution to each well, and reacted for 5 minutes at room temperature. After treating 5 μL of stabilizer to each well, reacted for 25 minutes at room temperature, and the absorbance at 630 nm was measured using SpectraMax M4 (Molecular Devices, USA) to determine the IC of the compound. 50 The value was calculated.

[1149] Analysis method: The enzyme activity (%) of each experimental group was calculated as {(average OD of compound treatment group - average OD of negative control group) / (average OD of positive control group - average OD of negative control group)} * 100. A dose-response curve (4-parameter) was created using the enzyme activity according to the concentration of each compound treatment in GraphPad Prism 9, and then the 50% enzyme inhibition value (IC) was calculated through nonlinear regression analysis. 50 ) was calculated. IC for the MAT2A activity inhibition ability of a compound according to an example of the present application 50 The measurement results are shown in Table 2 (+++: greater than 1 to 100 nM, ++: greater than 100 to 1,000 nM, +: greater than 1,000 to 10,000 nM, -: greater than 10,000 nM).

[1150] Example MAT2A enzyme IC 501++2++3++4++5++6++7++8+9-10+++11++12-13++14++15+16++17++18+19+20-21+++22+++23+++24++25+++26+++27++28-29-30-31-32+++33+++34+++35++36++37++38++39++40++41+42-43-44+++45+++46++47-48++49++50+51-52++53-54+++55+++56++57++58++59+60++61- 62++63-64++65+++71+72+73++74++75++76-77+++78+++79+++80-81+++82-83+84++85++86++87+++88++89++90-91+++92++93+++94-95+++96+++97-98+++99+++100++101+++102+++103+++104-105+++106-107+++108+++109+++110+++111-112+++113+++115++117+++118+++

[1151] As shown in Table 2, the compound according to one example of the present application had a high inhibitory ability against MAT2A activity.

[1152]

[1153] Experimental Example 2: Evaluation of the Proliferation Inhibition of MTAP-Deficient Cancer Cells Induced by MAT2A Inhibition

[1154] The compound according to an example of the present application was treated as a MAT2A inhibitor to the HCT116 (MTAPdel) cell line, a colon cancer cell line with a deletion of the MTAP gene, and the change in cell number was measured using the WST-1 assay reagent after 120 hours of culture. The WST-1 assay is an analytical method that measures cell number by measuring the production of a chromogenic substance called formazan from tetrazolium salts by intracellular mitochondrial dehydrogenase. In addition, the wild-type colon cancer HCT116 (MTAPWT) cell line containing the MTAP gene was used as a control and the experiment was performed in the same manner as the experimental group.

[1155] Cell lines and reagents: HCT116 (MTAPWT (Catalog No. HD PAR-034), MTAPdel (Catalog No. HD R02-033)) cell lines were purchased from Horizon Discovery (USA). RPMI1640 media (Catalog No. 22400-093), FBS (Fetal Bovine serum, Catalog No. 16000044), and Penicillin / Strptomycin (Catalog No. 15140-122) were purchased from GIBCO (USA). WST-1 (Catalog No. EZ-BULK150) was purchased from Dogen (Korea).

[1156] Experimental procedure: HCT116 (MTAP WT, MTAP del) cell lines were seeded in 96-well plates at a density of 1,000 cells / well in RPMI1640 medium containing 10% FBS and 1% Penicillin / Streptomycin and allowed to attach for 24 hours. Once the cells attached to the plate, the cells were treated with drugs at a 4-fold dilution from a maximum concentration of 10 μM. After 120 hours of drug treatment, 20 μL of WST-1 solution was treated for 2 hours, and the absorbance was measured at 450 nm using a SpectraMax M4 (Molecular device). Data analysis was calculated with the DMSO control value set at 100%. IC 50 The values ​​were calculated as the concentration at which cell proliferation was inhibited by 50% by interpolation using a four-parameter fit of the dose-response curve using the GraphPad Prism 8.4.3 program. The cancer cell proliferation inhibition ability and selectivity of compounds according to an example of the present application in MTAP-deficient cancer cells are shown in Table 3 (+++: 1 to 100 nM, ++: greater than 100 to 1,000 nM, +: greater than 1 to 10 μM, -: greater than 10 μM).

[1157] Example HCT116 MTAP - / -HCT116 WT1++-2+-3++-4++-5+-6+++7+-8--9--10+++++11+++++13++-14++-15++-16++-17++-18+-19+-20--21+++- 22+++-23++-24--25+++++26+++-27++-28--30--32++++33+++34+++++35++-36++-37++-38+++-39++-40++ -45++++46++-49++-52+-54+++++55++++56++++57+++++58+++++60--65++++71--73++-74++-75++-77++++78+++-79++++81++++84+++-85+++-86++-87+++-88++-89++-91+++-92--93+++-95+++-96+++-98+++-99+++- 100++- 101+++-102+++-103+++-105+++-107--108+++109++-110--112--113+++-

[1158] As shown in Table 3, it was confirmed that the compounds according to an example of the present application exhibited high cell proliferation inhibition ability and selectivity against MTAP-deficient cancer cells associated with MAT2A. That is, the compounds according to an example of the present application exhibited superior cell proliferation inhibition ability against the HCT116 (MTAPdel) cell line, which is a colon cancer cell line with a deleted MTAP gene, compared to the wild-type colon cancer HCT116 (MTAPWT) cell line containing the MTAP gene, and thus effectively suppressed the cancer and exhibited excellent selectivity against the cancer with a deleted MTAP gene. Therefore, the compounds according to an example of the present application can act more effectively on the MTAP-deficient cancer patient group.

[1159] Through the above results, it was shown that a compound according to an example of the present application can effectively suppress the growth of MTAP-deficient cancer cells by inhibiting MAT2A, and can be usefully used as a pharmaceutical composition for preventing or treating cancer.

Claims

1. A compound of the following chemical formula 1, an optical isomer, a stereoisomer, a racemate, an isotope variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, A is , , , or And, R 2 is (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 1-6 )alkoxy, (C 1-6 )alkylsulfonyl, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, nitro, amino, acetyl, (C 1-6 )alkylamino, (C 1-6 )alkylcarbonyl, (C 1-6 )alkoxycarbonyl, aminocarbonyl, (C 1-6 )alkylaminocarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )hydroxyalkoxy, (C 1-6 )hydroxyalkylamino, (C 1-6 )alkoxy-(C 1-6 )alkyl, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )alkoxy-(C 1-6 )alkylamino, (C 1-6 )aminoalkyl, (C 1-6 )aminoalkoxy, (C 1-6 )aminoalkylamino, a 3-membered to 10-membered heteroaryl comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heteroaryloxy comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heteroarylamino comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyl comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyloxy comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclylamino comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyloxyalkoxy comprising at least one heteroatom selected from N, O and S, or a 3-membered to 10-membered Heterocyclyloxyalkylamino, wherein said heterocyclyl or said heteroaryl is unsubstituted or R a , R b , and R c is substituted with one or more of the R a , R b , and R c is independently (C 1-6 )alkyl, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy, hydroxy, halo, cyano, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy-(C 1-6 ) alkyl, and (C 1-6 ) is selected from aminoalkyl; R 3 is hydrogen, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 1-6 )alkoxy, halo, halo(C 1-6 )alkyl-(C 1-6 )alkoxy, (C 1-6 )alkylsulfonyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, (C 1-6 )alkyloxy, cyano, amino, (C 1-6 )alkylamino, aminocarbonyl-(C 1-6 )alkylaminocarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )hydroxyalkoxy, (C 1-6 )hydroxyalkylamino, (C 2-6 )alkoxyalkyl, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )alkoxy-(C 1-6 )alkylamino, (C 1-6 )aminoalkyl, (C 1-6 )aminoalkoxy, (C 1-6 )aminoalkylamino, a 3-membered to 10-membered heteroaryl comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heteroaryloxy comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heteroarylamino comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyl comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyloxy comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclylamino comprising at least one heteroatom selected from N, O and S, a 3-membered to 10-membered heterocyclyl-(C 1-6 )alkyloxy, 3- to 10-membered heterocyclyloxy-(C containing one or more heteroatoms selected from N, O and S 1-6 )alkoxy, or a 3- to 10-membered heterocyclyloxy-(C containing one or more heteroatoms selected from N, O and S 1-6 ) alkylamino, and the alkoxy, heterocyclyl or heteroaryl is unsubstituted or R a , R b , and R c is substituted with one or more of the R a , R b , and R c is independently (C 1-6 )alkyl, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy, hydroxy, halo, cyano, (C 1-6 )alkoxycarbonyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy-(C 1-6 ) alkyl, and (C 1-6 ) is selected from aminoalkyl; R 4 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkenyl, (C 1-6 )alkynyl, (C 1-6 )alkoxy, (C 1-6 )alkyl-(C 1-6 )alkoxy, (C 1-6 )alkylthiol, (C 1-6 )alkylsulfonyl, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, amino, (C 1-6 )alkylamino, aminocarbonyl, or (C 1-6 ) is alkylaminocarbonyl; R 1 is a 5- to 20-membered mono- or bicyclic aryl or a 3- to 10-membered mono- or bicyclic heteroaryl containing one or more heteroatoms selected from N, O and S, wherein the aryl or heteroaryl is unsubstituted or has one or more substituents R d is replaced by; R d is halo, oxo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 3-10 )cycloalkyl-(C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 1 -C 6 )hydroxyalkyl, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkylsulfonamide, a 3- to 10-membered heteroaryl containing at least one heteroatom selected from N, O and S, a 3- to 10-membered heterocycloalkyl or phenyl containing at least one heteroatom selected from N, O and S; R 5 and R 6 is independently hydrogen, halo, hydroxy, acetyl, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy(C 1-6 )alkyl, -(C 1-6 )alkyl-amino, aminocarbonyl, (C 1-6 )alkylaminocarbonyl, di(C 1-6 )alkylaminocarbonyl, aminocarbonyl(C 1-6 )alkyl, aminosulfonyl(C 1-6 )alkyl, (C 1-6 )alkoxy, -amino(C 1-6 )-alkyl, -amino-di(C 1-6 )alkyl, (C 1-6 )alkylcarbonyl, or -(C 1-6 )Alkyl-R e And, Above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkylamino, or a 3- to 10-membered mono- or bicyclic heterocycle containing one or more heteroatoms selected from N, O and S, wherein R e is not substituted (C 1-6 )substituted with alkyl or hydroxy, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

2. In paragraph 1, Above R 1 is a 5- to 20-membered mono- or bicyclic aryl, or a 3- to 10-membered mono- or bicyclic heteroaryl containing one or more heteroatoms selected from N, O and S, wherein R 1 has one or more substituents R d Replaced with, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

3. In paragraph 1, Above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) is an alkylcarbonyl; Above R 3 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkoxy, halo(C 1-6 )alkyl(C 1-6 )alkoxy, halo(C 1-6 )alkyl, (C 1-6 )alkylamino, or pyrrolidine; Above R 4 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, or (C 1-6 ) is haloalkyl; Above R 1 is unsubstituted or has 1 to 3 substituents R d is replaced by; Above R d is halo, oxo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, or (C 1 -C 6 ) is an alkylsulfonamide; Above R 5 and R 6 is independently hydrogen, halo, hydroxy, acetyl, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy(C 1-6 )alkyl, amino(C 1-6 )alkyl, di(C 1-6 )alkylaminocarbonyl, (C 1-6 )alkoxy, (C 1-6 )alkylamino, di(C 1-6 )alkylamino, (C 1-6 )Alkylamino(C 1-6 )alkyl, (C 1-6 )Alkylamino(C 1-6 )alkylhydroxy, (C 1-6 )Alkylamino(C 1-6 )alkyl(C 1-6 )alkoxy, or (C 1-6 ) alkyl carbonyl, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

4. In paragraph 1, Above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) is an alkylcarbonyl; Above R 3 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkoxy, halo(C 1-6 )alkyl(C 1-6 )alkoxy, halo(C 1-6 )alkyl, (C 1-6 )alkylamino, or pyrrolidine; Above R 4 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, or (C 1-6 ) is haloalkyl; Above R 1 is 1 to 3 substituents R d is replaced by; Above R d is halo, oxo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, or (C 1 -C 6 ) is an alkylsulfonamide; Above R 5 and R 6 is independently hydrogen, halo, hydroxy, acetyl, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )hydroxyalkyl, (C 1-6 )alkoxy(C 1-6 )alkyl, amino(C 1-6 )alkyl, di(C 1-6 )alkylaminocarbonyl, (C 1-6 )alkoxy, (C 1-6 )alkylamino, di(C 1-6 )alkylamino, (C 1-6 )Alkylamino(C 1-6 )alkyl, (C 1-6 )Alkylamino(C 1-6 )alkylhydroxy, (C 1-6 )Alkylamino(C 1-6 )alkyl(C 1-6 )alkoxy, or (C 1-6 ) alkyl carbonyl, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

5. In paragraph 1, Above R 1 is phenyl, pyrazine, pyrazole, pyridine, indole, dihydrobenzofuran, or benzothiazole, and R 1 is unsubstituted or substituted with halo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, or (C 1 -C 6 ) substituted with alkylsulfonamide, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

6. In paragraph 1, Above R 1 is phenyl, pyrazine, pyrazole, pyridine, indole, dihydrobenzofuran, or benzothiazole, and R 1 Silver halo, cyano, hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 3-10 )cycloalkyl, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, or (C 1 -C 6 ) substituted with alkylsulfonamide, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

7. In paragraph 1, Above R 2 is (C 1-3 )alkyl, (C 1-3 )alkoxy, halo, (C 3-6 )cycloalkyl, cyano, acetyl, (C 1-3 )Dihaloalkyl, (C 1-3 )trihaloalkyl, or (C 1-3 )Trihaloalkoxy, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

8. In paragraph 1, The above A is , , or And, Above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) alkyl carbonyl, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

9. In paragraph 8, Above R 2 is fluoro, chloro, bromo, iodo, methyl, isopropyl, acetyl, cyano, nitro, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, or trifluoroethoxy, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

10. In paragraph 1, The above A is , , or And, Above R 2 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkyl, (C 1-6 )haloalkoxy, (C 3-10 )cycloalkyl, cyano, acetyl, or (C 1-6 ) is an alkyl carbonyl, Above R 3 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, (C 1-6 )haloalkoxy, halo(C 1-6 )alkyl(C 1-6 )alkoxy, halo(C 1-6 )alkyl, (C 1-6 )alkylamino, or pyrrolidine, Above R 4 is (C 1-6 )alkyl, (C 1-6 )alkoxy, halo, or (C 1-6 )haloalkyl, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

11. In paragraph 10, The above A is and Any one selected from the group consisting of, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

12. In paragraph 11, The above A is one selected from the group consisting of: Compounds, optical isomers, stereoisomers, racemates, isotopic variants, solvates, hydrates, or pharmaceutically acceptable salts thereof: and .

13. In paragraph 1, Above R 5 is hydrogen, halo, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 1-6 )alkyl-amino-, di(C 1-6 )alkyl-amino-, (C 1-6 )haloalkyl, acetyl, or -CH 2 R e And, Above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkyl-amino-, or a 3- to 10-membered mono- or bicyclic heterocycle containing one or more heteroatoms selected from N, O and S, wherein R e is unsubstituted or (C 1-6 )substituted with alkyl or hydroxy, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

14. In paragraph 13, Above R e is halo, (C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-(C 1-6 )alkoxy, -amino-(C 1-6 )alkyl-hydroxy, (C 1-6 )haloalkoxy, (C 1-6 )alkoxy-(C 1-6 )alkoxy, (C 1-6 )hydroxyalkoxy, (C 1-6 )alkyl-amino-, azetidine, morpholine, piperazine, or heterospirocarbocyclyl, and R e is unsubstituted or (C 1-6 )substituted with alkyl or hydroxy, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

15. In paragraph 13, Above R e is methoxy, methylamine, hydroxyethylamine, methoxyethylamine, azetidine, 3-hydroxyazetidine, methylpiperazine, morpholine, or 2-oxa-7-azaspiro[3.5]nonane, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

16. In paragraph 1, Above R 6 Silver hydrogen, halo, (C 1-6 )alkyl, (C 1-6 )haloalkyl, acetyl, or hydroxyl, A compound, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

17. In paragraph 1, The compound of the above chemical formula 1 is selected from among the following (1) to (120): Compounds, optical isomers, stereoisomers, racemates, isotopic variants, solvates, hydrates, or pharmaceutically acceptable salts thereof: 1) 7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 2) 7-chloro-5-phenylimidazo[1,2-a]quinoxalin-4(5H)-one 3) 7-chloro-5-(2-ethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 4) 7-chloro-5-(2,3-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 5) 7-chloro-5-(2-isopropylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 6) 7-chloro-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 7) 7-chloro-5-(2-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 8) 7-chloro-5-(4-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 9) 7-chloro-5-(5-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 10) 5-(3-fluoro-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 11) 7-chloro-5-(3-chloro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 12) 7-chloro-5-(2-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 13) 7-Cyclopropyl-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 14) 5-(3-fluoro-2-methylphenyl)-7-methoxyimidazo[1,2-a]quinoxalin-4(5H)-one 15) 5-(3-Fluoro-2-methylphenyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one 16) 7-Cyclopropyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 17) 7-Methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 18) 4-Oxo-5-(o-tolyl)-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile 19) 5-(o-tolyl)-7-(trifluoromethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one 20) (R a )-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 21) (S a )-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 22) 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 23) 7-chloro-5-(2-chlorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 24) 7-Acetyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 25) 7-Iodo-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 26) 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 27) 5-(3-Fluoro-2-methylphenyl)-4-oxo-4,5-dihydroimidazo[1,2-a]quinoxaline-7-carbonitrile 28) 5-(o-tolyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one 29) 5-(3-Fluoro-2-methylphenyl)-7-(2,2,2-trifluoroethoxy)imidazo[1,2-a]quinoxalin-4(5H)-one 30) 7-Ethoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 31) 7-Ethoxy-5-(3-fluoro-2-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 32) 7-Bromo-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 33) 7-Chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 34) 7-Chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 35) 7-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 36) 7-Methyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 37) 7-chloro-5-(2-methoxyphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 38) 5-(2-bromophenyl)-7-chloroimidazo[1,2-a]quinoxalin-4(5H)-one 39) 7-Chloro-5-(m-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 40) 7-Chloro-5-(3-fluorophenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 41) 7-Fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 42) 3-Chloro-5-(o-tolyl)imidazo[1,2-a]pyrido[4,3-e]pyrazin-6(5H)-one 43) 2-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)benzonitrile 44)N-(3-(7-chloro-4-oxoimidazo[1,2-a]quinoxalin-5(4H)-yl)phenyl)methanesulfonamide 45) 7-Chloro-2-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 46) 7-(Difluoromethyl)-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 47) 7-Isopropyl-5-(o-tolyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 48) 7-Chloro-5-(3-methylpyrazin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 49) 5-(o-tolyl)-7-(trifluoromethyl)imidazo[1,2-a]pyrido[2,3-e]pyrazin-4(5H)-one 50) 7-chloro-5-(2-(trifluoromethoxy)phenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 51) 7-chloro-5-(2,6-dimethylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 52) 7-Chloro-5-(2-fluoro-6-methylphenyl)imidazo[1,2-a]quinoxalin-4(5H)-one 53) 7-Chloro-5-(3-methylpyridin-2-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 54) 7-Chloro-5-(2-chloropyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 55) 2-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 56) 5-(2-Methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 57) 1-Bromo-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 58) 1-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 59) 1-Acetyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 60) 2-Acetyl-1-hydroxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 61) 7-Chloro-2-((4-methylpiperazin-1-yl)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 62) 7-Chloro-5-(2-methylpyridin-3-yl)-2-(morpholinomethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 63) 2-((2-Oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 64) 7-Chloro-2-(((2-methoxyethyl)amino)methyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 65) 5-(2,3-dihydrobenzofuran-4-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 66) 2-((methylamino)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one 67) 2-(methoxymethyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one 68) 2-(((2-hydroxyethyl)amino)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one 69) 2-(azetidin-1-ylmethyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one 70) 2-((3-hydroxyazetidine-1-yl)methyl)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-3,3a-dihydroimidazo[1,2-a]quinoxalin-4(5H)-one 71) 7-Chloro-9-fluoro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 72) 8-Bromo-7-chloro-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 73) 7-Chloro-8-methyl-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 74) 7-Bromo-8-methoxy-5-(o-tolyl)imidazo[1,2-a]quinoxalin-4(5H)-one 75) 7-Bromo-8-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 76) 7-Bromo-5-(2-methylpyridin-3-yl)-8-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 77) 7-Bromo-8-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 78) 7-Bromo-8-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 79) 7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 80) (R a )-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 81) (S a )-7-Bromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 82) 7-Bromo-8-(difluoromethyl)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 83) 7-Bromo-8-chloro-5-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 84) 7-Bromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 85) 7,9-Dibromo-1,8-dimethyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 86) 7-Bromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 87) 7-Bromo-8-chloro-5-(2-cyclopropylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 88) 1,7-Dibromo-8-chloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 89) 7-Bromo-1,8-dichloro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 90) 7-Bromo-5-(2-hydroxypyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one 91) 7-Bromo-5-(2-chloropyridin-3-yl)-8-methylimidazo[1,2-a]quinoxalin-4(5H)-one 92) 2,7-Dibromo-8-chloro-1-methyl-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 93) 8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 94) (R a )-8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 95) (S a )-8-Methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 96) 8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 97) (R a )-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 98) (S a )-8-chloro-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 99) 8-Chloro-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 100) 8-chloro-2-(dimethylamino)-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 101) 7-chloro-9-fluoro-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 102) 7-chloro-9-methoxy-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 103) 7-chloro-9-(cyclopropylmethoxy)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 104) 7-Chloro-5-(2-methylpyridin-3-yl)-9-(pyrrolidin-1-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 105) 7-chloro-9-(methylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 106) 7-chloro-9-(dimethylamino)-5-(2-methylpyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 107) 7-Bromo-8-chloro-5-(2-methoxypyridin-3-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 108) 5-(Benzo[d]thiazol-7-yl)-7-bromo-8-chloroimidazo[1,2-a]quinoxalin-4(5H)-one 109) 7-Bromo-8-chloro-5-(1H-indol-4-yl)imidazo[1,2-a]quinoxalin-4(5H)-one 110) 8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 111) (R a )-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 112) (S a )-8-chloro-5-(2-ethylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 113) 9-Methoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 114) 9-Methylamino-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 115) 9-(Difluoromethoxy)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 116) 5-(2-Methylpyridin-3-yl)-9-(trifluoromethoxy)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 117) 5-(2-Methylpyridin-3-yl)-9-(2,2,2-trifluoroethoxy)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 118) 9-Ethoxy-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 119) 8-Chloro-1-methyl-2-(methylamino)-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one 120) 8-Chloro-2-methoxy-1-methyl-5-(2-methylpyridin-3-yl)-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4(5H)-one; 18. A pharmaceutical composition comprising a compound according to any one of claims 1 to 17, an optical isomer, a stereoisomer, a racemate, an isotope variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

19. In claim 18, the pharmaceutical composition is a pharmaceutical composition for preventing or treating a disease related to the methionine adenosyltransferase 2A (MAT2A) protein.

20. A pharmaceutical composition according to claim 19, wherein the disease associated with the MAT2A protein is cancer.

21. A pharmaceutical composition according to claim 20, wherein the cancer is a cancer in which the activity or expression of methylthioadenosine phosphorylase (MTAP) is reduced, or a cancer in which all or part of the MTAP gene is deleted.

22. In clause 20, the cancer is acoustic neuroma, adenocarcinoma, adrenal cancer, anal cancer, angiosarcoma, benign monoclonal gammopathy, cholangiocarcinoma, bladder cancer, breast cancer, brain cancer, lymphoma, multiple myeloma, lacrimal gland tumor, bronchial cancer, cervical cancer, craniopharyngioma, colorectal cancer, epithelial carcinoma, ependymoma, endothelial sarcoma, endometrial cancer, esophageal cancer, Barrett's adenocarcinoma, Ewing's sarcoma, eye cancer, gallbladder cancer, stomach cancer, colon cancer, gastrointestinal stromal tumor (GIST), head and neck cancer, oral cancer (OSCC), pharyngeal cancer, hematopoietic system cancer, hemangioblastoma, inflammatory myofibroblastic tumor, immunocytotoxic amyloidosis, kidney cancer, renal cell carcinoma, liver cancer, lung cancer, melanoma, uveal melanoma, acute myeloid A pharmaceutical composition, wherein the compound is at least one selected from the group consisting of leukemia (AML), myelodysplastic syndrome (MDS), mesothelioma, myeloproliferative disorder (MPD), chronic idiopathic myelofibrosis, chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), neuroblastoma, neurofibroma, neuroendocrine cancer, osteosarcoma, ovarian cancer, papillary adenocarcinoma, pancreatic cancer, penile cancer, prostate cancer, rectal cancer, rhabdomyosarcoma, salivary gland cancer, skin cancer, small intestinal cancer, soft tissue sarcoma, thyroid cancer, urethral cancer, vaginal cancer, glioblastoma multiforme (GBM), glioma, peripheral nerve sheath tumor, thymic cancer, adenoid cystic carcinoma (ACC), and vulvar cancer.

23. In paragraph 20, A pharmaceutical composition, wherein the cancer is at least one selected from the group consisting of lung cancer, bladder cancer, stomach cancer, esophageal cancer, head and neck cancer, pancreatic cancer, colon cancer, biliary tract cancer, mesothelioma, peripheral nerve sheath tumor, thymic cancer, and adenoid cystic carcinoma (ACC).

24. In paragraph 22, A pharmaceutical composition, wherein the brain cancer is at least one selected from the group consisting of meningioma, glioma, medulloblastoma, glioblastoma, and brain metastasis.

25. A composition for inhibiting MAT2A protein activity, comprising a compound according to any one of claims 1 to 17, an optical isomer, a stereoisomer, a racemate, an isotope variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof.

26. A pharmaceutical combination for treating and / or preventing cancer in a subject, comprising a compound according to any one of claims 1 to 17, an optical isomer, a stereoisomer, a racemate, an isotopic variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof; and a cytotoxic anticancer agent.

27. A pharmaceutical combination for treating and / or preventing cancer in a subject, comprising a compound according to any one of claims 1 to 17, an optical isomer, a stereoisomer, a racemate, an isotope variant, a solvate, a hydrate, or a pharmaceutically acceptable salt thereof; and a combination of a targeted anticancer agent.

28. A pharmaceutical combination according to claim 26, wherein the cytotoxic anticancer agent comprises at least one selected from the group consisting of an alkylating agent, an antimetabolite, a DNA polymerase inhibitor, and a microtubule inhibitor.

29. A pharmaceutical combination in claim 27, wherein the targeted anticancer agent comprises at least one selected from the group consisting of a monoclonal antibody, a small molecule targeted therapeutic agent, an antibody-drug conjugate, and an immune checkpoint inhibitor.

30. A pharmaceutical combination according to claim 26 or 27, wherein the cancer is a cancer in which the activity or expression of methylthioadenosine phosphorylase (MTAP) is reduced, or a cancer in which all or part of the MTAP gene is deleted.

31. In the 26th or 27th paragraph, the cancer is acoustic neuroma, adenocarcinoma, adrenal cancer, anal cancer, angiosarcoma, benign monoclonal gammopathy, cholangiocarcinoma, bladder cancer, breast cancer, brain cancer, lymphoma, multiple myeloma, lacrimal gland tumor, bronchial cancer, cervical cancer, craniopharyngioma, colorectal cancer, epithelial carcinoma, ependymoma, endothelial sarcoma, endometrial cancer, esophageal cancer, Barrett's adenocarcinoma, Ewing's sarcoma, eye cancer, gallbladder cancer, stomach cancer, colon cancer, gastrointestinal stromal tumor (GIST), head and neck cancer, oral cancer (OSCC), pharyngeal cancer, hematopoietic system cancer, hemangioblastoma, inflammatory myofibroblastic tumor, immunocytotoxic amyloidosis, kidney cancer, renal cell carcinoma, liver cancer, lung cancer, melanoma, uveal melanoma A pharmaceutical combination comprising at least one selected from the group consisting of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), mesothelioma, myeloproliferative disorder (MPD), chronic idiopathic myelofibrosis, chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), neuroblastoma, neurofibroma, neuroendocrine cancer, osteosarcoma, ovarian cancer, papillary adenocarcinoma, pancreatic cancer, penile cancer, prostate cancer, rectal cancer, rhabdomyosarcoma, salivary gland cancer, skin cancer, small intestinal cancer, soft tissue sarcoma, thyroid cancer, urethral cancer, vaginal cancer, glioblastoma multiforme (GBM), glioma, peripheral nerve sheath tumor, thymic cancer, adenoid cystic carcinoma (ACC) and vulvar cancer.

32. In paragraph 26 or 27, A pharmaceutical combination, wherein the cancer is at least one selected from the group consisting of lung cancer, bladder cancer, stomach cancer, esophageal cancer, head and neck cancer, pancreatic cancer, colon cancer, biliary tract cancer, mesothelioma, peripheral nerve sheath tumor, thymic cancer, and adenoid cystic carcinoma (ACC).

33. In paragraph 31, A pharmaceutical combination wherein the brain cancer is at least one selected from the group consisting of meningioma, glioma, medulloblastoma, glioblastoma and brain metastasis.

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