Novel sulfonamide derivative and pharmaceutical composition comprising same

Abstract

The present invention relates to a novel sulfonamide derivative represented by chemical formula 1, and a pharmaceutical composition comprising same. The compound according to the present invention can be effectively used for preventing or treating fibrotic diseases, cancer, or metabolic diseases. [Chemical formula 1] In chemical formula 1, the descriptions of R1, X1, X2, R3a, R3b, A, L' and R5 R' are the same as those defined in the specification.

Description

Novel sulfonamide derivatives and pharmaceutical compositions containing the same

[0001] The present invention relates to a novel quinazoline derivative useful as an HSP47 inhibitor and a pharmaceutical composition containing the same.

[0002]

[0003] HSP47 (Heat shock protein 47) is a molecule that plays an important role in the assembly and secretion processes of extracellular matrix proteins. This protein is primarily required to ensure the proper folding and stability of collagen, and due to these functions, HSP47 plays an important role in tissue repair and fibrosis processes.

[0004]

[0005] HSP47 plays a major role in the synthesis of collagen types I, II, III, IV, and V within living cells, specifically synthesizing and secreting type I and II collagen, which are highly associated with fibrotic diseases. This protein exerts these effects by binding to collagen within the endoplasmic reticulum lumen; acting as a molecular scavenger involved in the maturation of collagen molecules, HSP47 is essential for the proper folding of procollagen. It is known to influence various collagen-mediated fibrotic diseases and plays a key role in the exacerbation of diseases mediated by collagen and fibroblasts, such as in major human organs like the liver, lungs, kidneys, and heart, as well as in all organs where fibrosis occurs and in the metastasis of cancer.

[0006]

[0007] Furthermore, the HSP47 protein is expressed at high levels in the tissues of patients with various fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), hepatic fibrosis, and keloids. It is known that such high levels of HSP47 expression exacerbate the excessive deposition of collagen in the extracellular matrix of tissues. In various animal studies on fibrotic diseases, the association between HSP47 and fibrotic diseases has been proven through experiments on HSP47 inhibition, confirming that HSP47 can serve as a potential therapeutic agent for these conditions. This demonstrates that the reduction of HSP47 and the inhibition of its role are effective in alleviating the progression of fibrotic diseases.

[0008]

[0009] In particular, HSP47 has been identified as playing a major role in the development of fibrotic diseases caused by EMT (Epithelial-Mesenchymal Transition) and FMT (Fibroblast-Mesenchymal Transition), which are critical key elements in the fibrotic process. EMT refers to the differentiation of epithelial cells into mesenchymal cells, a process important in various biological processes such as development, wound healing, tissue reconstruction, and cancer metastasis. During EMT, cells lose the expression of epithelial marker molecules (such as E-cadherin) and increase the expression of mesenchymal marker molecules (such as N-cadherin and vimentin), ultimately leading to the production of extracellular matrix such as collagen. FMT is the process in which fibroblasts acquire mesenchymal characteristics; similar changes to EMT occur during this process, which also ultimately leads to the production of extracellular matrix such as collagen. This production of collagen, in turn, influences the amplification of upstream signals that induce fibrotic diseases, such as TGF-β, thereby causing surrounding normal cells to fibrose and acting as a positive feedback loop that further intensifies fibrosis.

[0010]

[0011] Furthermore, through the regulation of collagen and the extracellular matrix, HSP47 can influence cell motility and invasiveness; various cancer studies have confirmed that HSP47 is often highly associated with tumor invasiveness and metastasis. These processes are interconnected and have a significant impact on cell behavior and tissue dynamics. HSP47 is a key research topic not only in fibrotic diseases but also in EMT and FMT, particularly in cancer research, tissue engineering, and regenerative medicine.

[0012]

[0013] Therefore, the development of sustained small molecule inhibitors against HSP47 is necessary for the treatment of fibrotic diseases.

[0014]

[0015] Accordingly, the inventors of the present invention, as a result of researching a drug that can be usefully used for the treatment of fibrotic diseases, confirmed that the compound according to the present invention, described below, inhibits collagen synthesis by inhibiting HSP47 and inhibits fibrosis induced by representative lung fibroblasts and hepatic stellate cells. Through this, the inventors confirmed that the HSP47 inhibitor according to the present invention can play a key role in the treatment of fibrotic diseases and thus completed the present invention.

[0016]

[0017] The present invention is intended to provide a novel quinazoline derivative useful as an HSP47 inhibitor and a pharmaceutical composition containing the same.

[0018] To solve the above problem, the present invention provides a compound represented by the following chemical formula 1, or a pharmaceutically acceptable salt thereof:

[0019] [Chemical Formula 1]

[0020]

[0021] In the above chemical formula 1,

[0022] R1 is a 5 to 10-membered monocyclic or polycyclic heterocycloalkyl comprising one or two N atoms substituted with one or more Rs; or -N(C 1-5 Alkyl)(C 1-5 alkyl) and,

[0023] R is a halogen; -LN(R a )(R b ); -N(R c )-CO-(R d ); C 1-5 Alkyl; C 1-5 Alkoxy; C comprising one or more heteroatoms among N, O, and S 2-10 Heterocycloalkyl; or C comprising one or more heteroatoms among N, O, and S 2-10 It is heteroaryl, and

[0024] L is a single bond; -CO-; or C 1-5 It is an alkylene, and

[0025] R a to R d are each independently hydrogen; or C 1-5 It is alkyl, and

[0026] X1 is N or C(R 2a ) and,

[0027] X2 is N or C(R 2b ) and,

[0028] R 2a , R 2b , R 3a and R 3b Each independently consists of hydrogen; halogen; hydroxy; -COO(R e ); -N(R f )(R g ); C 1-5 Alkyl; C 1-5 Alkoxy; or C 3-7 It is cycloalkyl, and

[0029] R e to R g are each independently hydrogen; or C 1-5 It is alkyl, and

[0030] A is represented by any one of the following chemical formulas 2a to 2c, and

[0031]

[0032] In the above chemical formulas 2a to 2c,

[0033] R 4a is hydrogen, or bonded to one or two Rs 4c Forming a benzene ring; a pyrazine ring; or a pyridazine ring, substituted or unsubstituted, and

[0034] R 4b They combine with each other to form one or two Rs 4c Forming a benzene ring; a pyrazine ring; or a pyridazine ring, substituted or unsubstituted, and

[0035] R 4c is a halogen; C 1-5 alkyl; or C 1-5 It is an alkoxy,

[0036] n is an integer from 0 to 2, and

[0037] L' is a single bond; or C 1-5 It is an alkylene, and

[0038] R5 is -N(R h )(R i ); C 1-5 Alkyl; C 3-7 Cycloalkyl; or a substituent represented by the following chemical formula 3, and

[0039] [Chemical Formula 3]

[0040]

[0041] In the above chemical formula 3,

[0042] Y1 is N or C(R 5a ) and,

[0043] Y2 is N or C(R 5b ) and,

[0044] R 5a , R 5b , R 6a , R 6b , and R6c Each independently consists of hydrogen, halogen; hydroxy; -COO(R j ); -N(R k )(R l ); -N(R m )-CO-(R n ); C 1-5 Alkyl; C 1-5 Alkoxy; C 7-15 Aralkill; C 7-15 Aralcocyte; or a monocyclic heteroaryl comprising one or more heteroatoms among N, O, and S, or R 6b and R 6c They combine with each other to form a benzene ring; a pentagonal or hexagonal heteroaromatic ring containing one or more heteroatoms among N, O, and S; or a pentagonal or hexagonal heterocycloalkane ring containing one or more heteroatoms among N, O, and S, and

[0045] R h to R n Each independently hydrogen; or C 1-5 It is alkyl, and

[0046] Here, the alkyl, alkylene, alkoxy, cycloalkyl, heterocycloalkyl, heteroaryl, heteroaromatic ring and heterocycloalkane ring are each independently deuterium; halogen; hydroxy; oxo (=O); C 1-4 alkyl; and C 1-4 It is substituted or unsubstituted with one or more substituents selected from the group consisting of alkoxy, or is substituted or unsubstituted with a substituent in which two or more of the substituents exemplified above are connected.

[0047]

[0048] In the above compound, R1 is bonded to the moiety -NH-A-NH-SO2-L'-R5 at an ortho position and is substituted with one or more Rs. Compounds having such a structure can exhibit excellent inhibitory activity against HSP47 by enhancing salt bridge interaction compared to compounds having a structure in which R1 is bonded to the moiety -NH-A-NH-SO2-L'-R5 at a meta or para position and compounds not substituted with Rs.

[0049]

[0050] In this case, if there are two or more Rs, the two or more Rs may each be the same or different.

[0051]

[0052] Preferably, R1 is a 5 to 10-membered monocyclic or polycyclic heterocycloalkyl comprising one or two N atoms substituted with one or two Rs; or -N(C 1-5 Alkyl)(C 1-5 It can be an alkyl.

[0053]

[0054] Here, -N(C 1-5 Alkyl)(C 1-5 Alkyl) can be -N(methyl)2, -N(ethyl)2, -N(methyl)(ethyl), -N(methyl)(propyl), or -N(ethyl)(propyl).

[0055]

[0056] Preferably, the N atom of R1 can bond with an adjacent six-membered ring.

[0057]

[0058] Preferably, R1 may be pyrrolidinyl; piperidinyl; piperazinyl; hexahydropyrrolo[3,4-c]pyrroleyl; or -N(methyl)(ethyl) substituted with one R.

[0059]

[0060] Preferably, R1 can be represented by any one of the following chemical formulas 4a to 4d:

[0061]

[0062] In the above chemical formulas 4a to 4d,

[0063] R is as defined in Chemical Formula 1 above, and

[0064] Z is N or CH, and

[0065] m is 0 or 1.

[0066]

[0067] Preferably, R is a halogen; -LN(R a )(R b ); -N(R c )-CO-(R d ); C 1-5 Alkyl; C 1-5 Alkoxy; or C 1-4 C comprising one or more heteroatoms among N, O, and S that are alkyl-substituted or unsubstituted 2-10 It can be a heterocycloalkyl.

[0068]

[0069] Preferably, R is -L-NH2; -L-NH(C 1-4 Alkyl); -LN(C 1-4 Alkyl)2; -NH-CO-(C 1-4 Alkyl); C 1-4 Alkyl; C 1-4 Alkoxy; or C 1-4 It may be a 5 to 7-membered monocyclic heterocycloalkyl containing one N atom substituted or unsubstituted with an alkyl group.

[0070]

[0071] Preferably, L can be a single bond, -CO-, methylene, or ethylene.

[0072]

[0073] Preferably, R a to R d Each can independently be hydrogen, methyl, or ethyl.

[0074]

[0075] Preferably, R may be -NH2, -NH(CH3), -N(CH3)2, -CO-NH(CH3), -CO-N(CH3)2, -CH2-N(CH3)2, -NH-CO-CH3, methyl, ethyl, methoxy, or methylpiperazinyl.

[0076]

[0077] Preferably, R e to R g Each can independently be hydrogen, methyl, or ethyl.

[0078]

[0079] Preferably, R 2a and R 2b Each can independently be hydrogen, fluoro, chloro, hydroxy, methyl, or methoxy.

[0080]

[0081] Preferably, X1 can be N, CH, C(F), C(Cl), or C(CH3).

[0082]

[0083] Preferably, X2 can be N, CH, C(F), C(Cl), C(OH), C(CH3), or C(OCH3).

[0084]

[0085] Preferably, R 3a and R 3b Each can independently be hydrogen, fluoro, chloro, bromo, hydroxy, -COO(CH3), -NH2, -N(CH3)2, methyl, methoxy, or cyclopropyl.

[0086]

[0087] Preferably, R 3a It can be hydrogen, fluoro, chloro, bromo, hydroxy, -COO(CH3), -NH2, -N(CH3)2, methyl, methoxy, or cyclopropyl.

[0088]

[0089] Preferably, R 3b It can be hydrogen or methyl.

[0090]

[0091] Preferably, R 4c Each can independently be chloro, bromo, methyl, or methoxy.

[0092]

[0093] Also, n is R 4c It refers to the number of, which is 0, 1, or 2. In this case, when n is 2, there are 2 R 4c They may be identical or different from each other.

[0094]

[0095] Preferably, R in one chemical formula 4c They can be identical to each other.

[0096]

[0097] Meanwhile, A is represented by any one of the above chemical formulas 2a to 2c, where the dotted line (---) in A signifies a bond connected to either of the adjacent N atoms on both sides; thus, the bond indicated by * in the following chemical formulas 2a to 2c can be bonded to either the N atom of the six-membered ring -NH- or the N atom of -NH-SO2-L'-R5:

[0098] .

[0099]

[0100] Preferably, A can be represented as any one selected from the group consisting of:

[0101]

[0102] As mentioned above,

[0103] R' 4c Each is independently hydrogen, chloro, bromo, methyl, or methoxy.

[0104]

[0105] Preferably, L' can be a single bond or methylene.

[0106]

[0107] Preferably, R h and R i Each independently hydrogen; or C substituted or unsubstituted with a halogen 1-5 It can be an alkyl.

[0108]

[0109] Preferably, R 5a , R 5b , R 6a , R 6b , and R 6c Each independently consists of hydrogen; halogen; hydroxy; -COO(R j ); -N(R k )(R l ); -N(R m )-CO-(R n ); C substituted or unsubstituted with halogens 1-5 Alkyl; C substituted or unsubstituted with a halogen 1-5 Alkoxy; C substituted or unsubstituted with halogen 7-15 Aralcoxy; or halogen or C 1-4 It is a monocyclic 5-membered heteroaryl comprising one or more heteroatoms among N, O, and S that are alkyl-substituted or unsubstituted, or R 6b and R 6c It can form a halogen-substituted or unsubstituted benzene ring that combines with each other and fuses with an adjacent ring; a five-membered heteroaromatic ring containing one or more heteroatoms among N, O, and S that are halogen-substituted or unsubstituted; or a five-membered heterocycloalkane ring that is oxo-substituted or unsubstituted.

[0110]

[0111] Preferably, R j to R n Each is independently hydrogen; or C substituted or unsubstituted with a halogen 1-5 It can be an alkyl.

[0112]

[0113] Preferably, R 5a , R 5b , R 6a , R 6b , and R 6c Each is independently hydrogen, fluoro, chloro, hydroxy, -N(CH3)2, -NH-CO-CH3, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethoxy, benzyloxy, pyrazolyl, oxazolyl, or methyloxazolyl, or R 6b and R 6c It can form a benzene ring; a furan ring; an oxo-substituted or unsubstituted oxazolidine ring; an oxo-substituted or unsubstituted thiazolidine ring; or an oxo-substituted or unsubstituted imidazolidine ring that combines with each other and fuses with an adjacent ring.

[0114]

[0115] Preferably, R5 may each independently be a substituent represented by methyl, ethyl, n-propyl, isopropyl, cyclopropyl, or any one of the following chemical formulas 3a to 3h:

[0116]

[0117] In the above chemical formula 3a,

[0118] R' 5a , R' 5b , R' 6a , R' 6b , and R' 6c Each is independently hydrogen, fluoro, chloro, hydroxy, -N(CH3)2, -NH-CO-CH3, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethoxy, benzyloxy, pyrazolyl, or methyloxazoleyl.

[0119]

[0120] Preferably, in the above formula 3a,

[0121] R' 5a , R' 5b , R' 6a , R'6b , and R' 6c At least three of them can be hydrogen.

[0122]

[0123] Preferably, the compound represented by the above chemical formula 1 may be represented by any one of the following chemical formulas 1-1 to 1-3:

[0124] [Chemical Formula 1-1]

[0125]

[0126] [Chemical Formula 1-2]

[0127]

[0128] [Chemical Formula 1-3]

[0129]

[0130] In the above chemical formulas 1-1 to 1-3,

[0131] R1, R 2a , R 2b , R 3a , R 3b , A, L' and R5 are as defined in Chemical Formula 1 above.

[0132]

[0133] Preferably, in the above formula 1-1,

[0134] A can be represented by any one selected from the group consisting of the above-described chemical formulas 2a-1, 2a-2, 2a-3, 2b-1, 2b-2, 2b-3, and 2c-1.

[0135]

[0136] Preferably, in the above formula 1-2,

[0137] A can be represented by the chemical formula 2a-2 described above.

[0138]

[0139] Preferably, in the above formula 1-3,

[0140] A can be represented by the chemical formula 2a-2 described above.

[0141]

[0142] Meanwhile, representative examples of compounds represented by the above chemical formula 1 are as follows:

[0143] 1) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0144] 2)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0145] 3)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0146] 4)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0147] 5)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide,

[0148] 6) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0149] 7) 3-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0150] 8) 2-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0151] 9)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide,

[0152] 10) 2-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0153] 11)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0154] 12)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0155] 13)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide,

[0156] 14)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0157] 15)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0158] 16)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0159] 17)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide,

[0160] 18)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide,

[0161] 19)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)cyclopropanesulfonamide,

[0162] 20)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide,

[0163] 21)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)cyclopropanesulfonamide,

[0164] 22)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide,

[0165] 23)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide,

[0166] 24)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide,

[0167] 25) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0168] 26) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide,

[0169] 27)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methylbenzenesulfonamide,

[0170] 28) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide,

[0171] 29)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methoxybenzenesulfonamide,

[0172] 30)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide,

[0173] 31) 3-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0174] 32)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide,

[0175] 33)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0176] 34)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide,

[0177] 35)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0178] 36)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0179] 37)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0180] 38) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide,

[0181] 39) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0182] 40) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0183] 41) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide,

[0184] 42) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0185] 43) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0186] 44) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide,

[0187] 45) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-methoxybenzenesulfonamide,

[0188] 46)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide,

[0189] 47)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0190] 48)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0191] 49)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide,

[0192] 50)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0193] 51)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0194] 52)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-(trifluoromethyl)benzenesulfonamide,

[0195] 53)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-methoxybenzenesulfonamide,

[0196] 54)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide,

[0197] 55)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide,

[0198] 56)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide,

[0199] 57)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0200] 58)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)naphthalene-2-sulfonamide,

[0201] 59) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0202] 60) 4-methyl-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0203] 61) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0204] 62) 4-methoxy-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0205] 63) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0206] 64)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0207] 65)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0208] 66)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0209] 67)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0210] 68)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0211] 69)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0212] 70)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0213] 71)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0214] 72)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0215] 73)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0216] 74) 4-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0217] 75) 4-methoxy-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0218] 76) 3-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0219] 77) 2-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0220] 78)(S)-4-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0221] 79)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-difluorobenzenesulfonamide,

[0222] 80)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide,

[0223] 81)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-difluorobenzenesulfonamide,

[0224] 82)(S)-3,4-dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0225] 83)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0226] 84)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-difluoroquinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0227] 85)(S)-N-(6,7-dichloro-3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0228] 86)(S)-3,5-dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0229] 87)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0230] 88)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0231] 89)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0232] 90)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0233] 91)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0234] 92)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0235] 93)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0236] 94)(S)-5-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0237] 95)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-5-fluoro-2-methylbenzenesulfonamide,

[0238] 96)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide,

[0239] 97)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0240] 98)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0241] 99)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0242] 100)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0243] 101)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0244] 102)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0245] 103)N-methyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide,

[0246] 104) N,N-dimethyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide,

[0247] 105)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0248] 106)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0249] 107)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0250] 108)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0251] 109)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0252] 110)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0253] 111)(S)-N-(4-(N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide,

[0254] 112)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide,

[0255] 113)(S)-3-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0256] 114)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0257] 115)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0258] 116)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0259] 117)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide,

[0260] 118)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0261] 119)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide,

[0262] 120)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0263] 121) 4-methyl-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0264] 122)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)pyridine-3-sulfonamide,

[0265] 123)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0266] 124)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0267] 125)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0268] 126)(S)-4-(benzyloxy)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0269] 127)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-ethoxybenzenesulfonamide,

[0270] 128)(S)-N-(1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-yl)acetamide,

[0271] 129)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-hydroxybenzenesulfonamide,

[0272] 130)(S)-N-(3-((2-(3-methoxypyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0273] 131)N-(3-((2-(3-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0274] 132)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-hydroxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0275] 133)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-hydroxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0276] 134)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0277] 135)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0278] 136)N-(3-((2-(3-((dimethylamino)methyl)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0279] 137)(S)-N-(3-((4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0280] 138)(S)-N-(3-((4-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0281] 139)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0282] 140)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0283] 141)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0284] 142)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0285] 143)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide,

[0286] 144)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide,

[0287] 145)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0288] 146)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0289] 147)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0290] 148)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide,

[0291] 149)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide,

[0292] 150)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide,

[0293] 151) 4-methoxy-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide,

[0294] 152)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0295] 153)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0296] 154)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide,

[0297] 155)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0298] 156)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide,

[0299] 157)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0300] 158)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0301] 159)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0302] 160)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0303] 161)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0304] 162)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide,

[0305] 163)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide,

[0306] 164) Methyl(S)-3-(3-(dimethylamino)pyrrolidine-1-yl)-4-((3-((4-methoxyphenyl)sulfonamido)quinoxalin-2-yl)amino)benzoate,

[0307] 165)(S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0308] 166)(S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0309] 167)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide,

[0310] 168)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide,

[0311] 169)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0312] 170)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0313] 171)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0314] 172)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0315] 173)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0316] 174)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0317] 175)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0318] 176)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide,

[0319] 177)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide,

[0320] 178)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide,

[0321] 179)(S)-N-(4-(N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide,

[0322] 180)(S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0323] 181)(S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0324] 182)(S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide,

[0325] 183)(S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide,

[0326] 184)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methoxybenzenesulfonamide,

[0327] 185)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-6-yl)-4-methoxybenzenesulfonamide,

[0328] 186)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide,

[0329] 187)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide,

[0330] 188)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide,

[0331] 189)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide,

[0332] 190)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)pyrazino[2,3-b]pyrazine-2-yl)-4-methoxybenzenesulfonamide,

[0333] 191)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methylbenzenesulfonamide,

[0334] 192)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-6-yl)-4-methylbenzenesulfonamide,

[0335] 193)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)pyrazino[2,3-b]pyrazine-2-yl)-4-methylbenzenesulfonamide,

[0336] 194)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(1H-pyrazole-5-yl)benzenesulfonamide,

[0337] 195)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)phthalazine-6-yl)-4-methoxybenzenesulfonamide,

[0338] 196)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)phthalazine-6-yl)-4-methylbenzenesulfonamide,

[0339] 197)(S)-1-(5-fluoro-2-(4-((4-methoxyphenyl)sulfonyl)-3,4-dihydroquinoxalin-1(2H)-yl)phenyl)-N,N-dimethylpyrrolidine-3-amine,

[0340] 198)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide,

[0341] 199)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide,

[0342] 200)(S)-1-(5-chloro-2-(4-((4-methoxyphenyl)sulfonyl)-3,4-dihydroquinoxalin-1(2H)-yl)phenyl)-N,N-dimethylpyrrolidine-3-amine,

[0343] 201)(S)-N-(3-((4-chloro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, and

[0344] 202)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-hydroxybenzenesulfonamide.

[0345]

[0346] Meanwhile, the compound represented by the above chemical formula 1 can be understood as a concept that encompasses stereoisomers, mixtures of stereoisomers, and isotope derivatives of the compound.

[0347]

[0348] Specifically, the "stereoisomer" of the compound may be understood to include diastereomers and enantiomers of all possible structures when the compound contains one or more chiral centers.

[0349]

[0350] Additionally, "isotopic derivatives" of the above compound mean that one or more atoms in the compound are replaced by its naturally occurring or non-naturally occurring isotopes. For example, an isotopic derivative of the above compound includes a compound in which at least one hydrogen in the compound is replaced by deuterium.

[0351]

[0352] Additionally, the compound of the present invention may exist in the form of a salt, particularly a pharmaceutically acceptable salt. As the salt, any salt commonly used in the art, such as an acid addition salt formed by a pharmaceutically acceptable free acid, may be used without limitation. The term "pharmaceutically acceptable salt" in the present invention means any organic or inorganic addition salt of said compound at a concentration having a relatively non-toxic and harmless active effect on the patient, such that the side effects caused by said salt do not impair the beneficial efficacy of the compound represented by Formula 1.

[0353]

[0354] The above free acid may be an organic acid or an inorganic acid. As an inorganic acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. may be used, and as an organic acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carboxylic acid, vanillic acid, hydroiodic acid, etc. may be used, but is not limited thereto. Preferably, the above salt may be a hydrochloride salt.

[0355]

[0356] In addition, pharmaceutically acceptable metal salts can be obtained by conventional methods using a base. For example, a compound represented by Formula 1 above can be dissolved in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, and after filtering the undissolved compound salt, the filtrate can be evaporated and dried to obtain a pharmaceutically acceptable metal salt. In this case, it is particularly preferable to prepare a sodium salt, a potassium salt, or a calcium salt as the metal salt.

[0357]

[0358] Other pharmaceutically unacceptable salts or solvates of the compound represented by Formula 1 may be used as intermediates in the preparation of the compound represented by Formula 1, its pharmaceutically acceptable salts, or solvates.

[0359]

[0360] In addition, the compound represented by Formula 1 according to the present invention includes, without limitation, its pharmaceutically acceptable salts as well as solvates such as possible hydrates that can be prepared therefrom or prodrugs thereof.

[0361]

[0362] The solvate of the compound represented by the above chemical formula 1 can be prepared from the compound represented by the chemical formula 1 using methods known in the art.

[0363]

[0364] Additionally, the term "prodrug" of the above compound may be understood to refer to any derivative capable of providing the compound of the present invention, its stereoisomers, mixtures of its stereoisomers, isotopic derivatives thereof, or pharmaceutically acceptable salts thereof by hydrolysis, oxidation, or otherwise reacting under biological conditions (in vitro or in vivo), unless otherwise indicated.

[0365]

[0366] In addition, the present invention may include not only the stoichiometric hydrate of the compound represented by Formula 1 but also compounds containing various amounts of water. The solvates of the compound represented by Formula 1 according to the present invention include both stoichiometric solvates and non-stoichiometric solvates.

[0367]

[0368] In addition, the compound represented by the above chemical formula 1 can be prepared through the following reaction formula 1.

[0369] [Reaction Equation 1]

[0370]

[0371] In the above reaction scheme 1, X independently represents a halogen, and the remaining substituents are as defined in the above chemical formula 1.

[0372]

[0373] Step 1-1 above is a step of preparing a compound represented by Chemical Formula 1-3 by reacting a compound represented by Chemical Formula 1-1 with a compound represented by Chemical Formula 1-2. It is preferable to perform the reaction as an amine substitution reaction in the presence of a base. Potassium carbonate (K2CO3), sodium carbonate (Na2CO3), cesium carbonate (Cs2CO3), 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), etc., may be used as the base, but are not limited thereto.

[0374]

[0375] Step 1-2 above is a step of preparing a compound represented by Chemical Formula 1-6 by reacting the compound represented by Chemical Formula 1-4 with the compound represented by Chemical Formula 1-5. The reaction also proceeds as an amine substitution reaction and can be carried out in the presence of a base. The bases mentioned in Step 1-1 above may be used.

[0376]

[0377] Step 1-3 above is a step of preparing a compound represented by Chemical Formula 1-7 by converting the nitro group of the compound represented by Chemical Formula 1-6 into an amino group. The reaction is a reduction reaction, and it is preferable to carry out the reaction in the presence of a metal catalyst such as zinc, Raney nickel, and palladium carbon (Pd / C), or in the presence of a non-metal catalyst such as sodium dithionite (Na2S2O4).

[0378]

[0379] Step 1-4 above is a step of preparing a compound represented by Chemical Formula 1 by reacting a compound represented by Chemical Formula 1-3 with a compound represented by Chemical Formula 1-7. The reaction is preferably carried out as an amine substitution reaction in the presence of a palladium catalyst, a ligand, and a base, or under an acid catalyst. As the base, the ones mentioned in Step 1-1 above may be used, and as the acid, aluminum chloride, p-toluenesulfonic acid (PTSA), methanesulfonic acid (MsOH), hydrochloric acid, etc. may be used.

[0380]

[0381] The manufacturing method for each step described above can be further specified in the embodiments to be described later.

[0382]

[0383] In addition, the present invention provides a pharmaceutical composition comprising a compound represented by the above chemical formula 1, or a pharmaceutically acceptable salt thereof, as an active ingredient.

[0384]

[0385] More specifically, the present invention may be understood to provide a pharmaceutical composition comprising as an active ingredient a compound represented by Formula 1, a stereoisomer thereof, a mixture of stereoisomers thereof, an isotopic derivative thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof.

[0386]

[0387] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of fibrotic diseases, cancer, or metabolic diseases, comprising a compound represented by the above formula 1, or a pharmaceutically acceptable salt thereof, as an active ingredient.

[0388]

[0389] More specifically, the present invention may be understood as providing a pharmaceutical composition for the treatment or prevention of fibrotic diseases, cancer, or metabolic diseases through the inhibitory action of HSP47, using a compound represented by Formula 1, a stereoisomer thereof, a mixture of stereoisomers thereof, an isotopic derivative thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof as an active ingredient.

[0390]

[0391] The above fibrotic diseases may include systemic sclerosis, multifocal fibrosclerosis, scleroderma graft-versus-host disease, renal systemic fibrosis, organ-specific fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive giant fibrosis, Crohn's disease, keloid, arthral fibrosis, Peyronie's disease, Dupuytren's contracture, adhesive capsulitis, etc. Additionally, organ-specific fibrosis may include pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, asthma, chronic obstructive pulmonary disease, hepatic fibrosis, renal fibrosis, pancreatic fibrosis, nonalcoholic steatohepatitis (NASH), metabolism dysfunction-associated steatohepatitis (MASH), lymph node fibrosis, corneal fibrosis, fibrous cartilage, endometriosis, etc.

[0392]

[0393] The above cancer may be hematological cancer, extranodal marginal zone B-cell lymphoma, glioblastoma, lymphoplasmocytic lymphoma, acute myeloid leukemia, macroglobulinemia, B-cell lymphoma, chronic lymphocytic leukemia, follicular lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, hairy cell leukemia, mantle cell lymphoma, glioblastoma, bladder cancer, pancreatic cancer, ovarian cancer, colorectal cancer, kidney cancer, gastric cancer, transitional cell carcinoma, carcinoid tumor, breast cancer, non-small cell lung cancer, or multiple myeloma.

[0394]

[0395] Cancer also includes non-solid tumors, e.g., blood cancers, said cancer cells originate from the bone marrow. Blood cancers include leukemia, lymphoma, multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, T-cell malignancies, or B-cell malignancies. In particular, T-cell malignancies include mature T-cell lymphoma not otherwise classified, anaplastic large cell lymphoma, angioimmunoblastic lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia, blastocystic natural killer lymphoma, platelet gamma-delta T-cell lymphoma, and lymphoblastic lymphoma. B-cell malignancies include, but are not limited to, chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, Waldenstrom macroglobulinemia, head and neck tumors, marginal zone B-cell lymphoma, Burkitt lymphoma, primary mediastinal B-cell lymphoma, immune large cell lymphoma, precursor B-lymphocytic lymphoma, pre-lymphocytic leukemia, lymphoplasmocyte lymphoma, nasal peripheral zone lymphoma, plasmacytic myeloma, plasmacytoma, intravascular large B-cell lymphoma, primary exudative lymphoma, or lymphomatous granulomatosis.

[0396]

[0397] In some cases, the above cancer includes recurrent or intractable cancer, which is a solid tumor. Such recurrent or intractable cancer includes adenocarcinoma, squamous cell carcinoma, adenosquamous cell carcinoma, anaplastic carcinoma, large cell carcinoma, small cell carcinoma, biliary tract cancer, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, eye tumor, primary fallopian tube cancer, kidney cancer, liver cancer, lung cancer, medulloblastoma, malignant melanoma, oral cancer, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumor, prostate cancer, rectal cancer, skin cancer, gastric cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, and vulvar cancer.

[0398]

[0399] The above metabolic diseases may include hypertension, arteriosclerosis, hyperlipidemia, non-alcoholic fatty liver disease, hyperinsulinemia, type 2 diabetes, insulin resistance syndrome, etc.

[0400]

[0401] The term "prevention" in this invention refers to any act of suppressing or delaying the occurrence, spread, and recurrence of the said disease through the administration of the composition of this invention, and "treatment" refers to any act of improving or beneficially altering the symptoms of the said disease through the administration of the composition of this invention.

[0402]

[0403] The pharmaceutical composition of the present invention may be formulated into oral or parenteral administration forms in accordance with standard pharmaceutical practices. These formulations may contain, in addition to the active ingredient, pharmaceutically acceptable additives such as carriers, adjuvants, or diluents.

[0404]

[0405] Suitable carriers include, for example, physiological saline, polyethylene glycol, ethanol, vegetable oil, and isopropyl myristate, and diluents include, for example, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine, but are not limited thereto. In addition, the compounds of the present invention may be dissolved in oils, propylene glycol, or other solvents commonly used in the preparation of injectable solutions. Furthermore, the compounds of the present invention may be formulated into ointments or creams for topical action.

[0406]

[0407] The preferred dosage of the compound of the present invention varies depending on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the duration, but can be appropriately selected by those skilled in the art. However, for a desirable effect, it is preferable to administer the compound of the present invention at a dose of 0.0001 to 100 mg / kg (body weight) per day, preferably 0.001 to 100 mg / kg (body weight). Administration may be administered once a day or in divided doses via oral or parenteral routes.

[0408]

[0409] Depending on the method of administration, the pharmaceutical composition may contain 0.001 to 99 weight%, preferably 0.01 to 60 weight%, of the compound of the present invention.

[0410]

[0411] The pharmaceutical composition according to the present invention may be administered to mammals, including rats, mice, livestock, and humans, by various routes. All modes of administration are expected, for example, orally, rectally or intravenously, intramuscularly, subcutaneously, intradurally, or intracerebroventricularly.

[0412]

[0413] Meanwhile, the dotted line (---) used in this specification signifies a bond connected to another substituent.

[0414]

[0415] Additionally, in this specification, the halogen group means fluoro, chloro, bromo, or iodo.

[0416]

[0417] In addition, in this specification, the alkyl group may be a straight chain or a branched chain. According to one embodiment, the number of carbon atoms in the alkyl group is 1 to 5. According to another embodiment, the number of carbon atoms in the alkyl group is 1 to 4. Specific examples of the alkyl group include, butyl, ethyl, propyl, N-propyl, isopropyl, butyl, N-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, N-pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethyl-propyl, or 1,1-dimethylpropyl, etc., but are not limited thereto. In addition, the description regarding the alkyl group may apply except that the alkylene group is a divalent group.

[0418]

[0419] Additionally, in this specification, the alkoxy group refers to an alkyl group single-bonded to oxygen and may be a straight chain or a branched chain. According to one embodiment, the number of carbon atoms of the alkoxy group is 1 to 5. According to another embodiment, the number of carbon atoms of the alkoxy group is 1 to 4. Specific examples of the alkoxy group include, butoxy, n-butoxy, isopropoxy, butoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, 1-methylbutoxy, 1-ethylbutoxy, pentyloxy, n-pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, 1-ethyl-propoxy, or 1,1-dimethylpropoxy, but are not limited thereto.

[0420]

[0421] Additionally, in this specification, the cycloalkyl group is understood to mean a monovalent substituent derived from a saturated or unsaturated hydrocarbon ring compound that contains only carbon as a ring-forming atom and does not have aromaticity. According to one embodiment, the number of carbon atoms in the cycloalkyl group is 3 to 7. According to another embodiment, the number of carbon atoms in the cycloalkyl group is 3 to 6. Specific examples of the cycloalkyl group include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, or cycloheptyl.

[0422]

[0423] Additionally, in this specification, the heterocycloalkyl group is understood to mean a monovalent substituent derived from a saturated or unsaturated heterocycloalkane ring that is not aromatic and further comprises a heteroatom such as N, O, or S in addition to carbon as the ring-forming atom. According to one embodiment, the heterocycloalkyl group is a 5- to 10-membered ring having 5 to 10 ring-forming atoms. According to another embodiment, the heterocycloalkyl group is a 5- to 7-membered ring having 5 to 7 ring-forming atoms. Specific examples of the heterocycloalkyl group include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, hexahydropyrrolo[3,4-c]pyrroleyl, imidazolidinyl, oxazolidinyl, thiazolidinyl, etc.

[0424]

[0425] Additionally, in this specification, an aryl group is understood to mean a monovalent substituent derived from a monocyclic or condensed polycyclic aromatic ring having aromaticity and containing only carbon as a ring-forming atom. According to one embodiment, the number of carbon atoms in the aryl group is 6 to 20. According to another embodiment, the number of carbon atoms in the aryl group is 6 to 12. According to yet another embodiment, the number of carbon atoms in the aryl group is 6 to 10. Specific examples of the monocyclic aryl group include, but are not limited to, phenyl, biphenylyl, or terphenylyl. Additionally, examples of the condensed polycyclic aryl group include, but are not limited to, naphthyl, anthracenyl, phenanthryl, pyrenyl, perylenyl, or chrysenyl groups. Additionally, an aryl-alkyl group means an -alkylene-aryl group, and an aryl-cox group means an -O-alkylene-aryl group. Examples of such an aryl-alkyl group and an aryl-cox group include benzyl and benzyloxy, respectively.

[0426]

[0427] Additionally, in this specification, the heteroaryl group is understood to mean a monovalent substituent derived from a heteroaromatic ring having aromaticity, which further includes a heteroatom such as N, O, or S in addition to carbon as a ring-forming atom. According to one embodiment, the heteroaryl group is a 5- to 10-membered ring having 5 to 10 ring-forming atoms. According to another embodiment, the heteroaryl group is a 5- to 7-membered ring having 5 to 7 ring-forming atoms. According to yet another embodiment, the heteroaryl group is a 5- or 6-membered ring having 5 or 6 ring-forming atoms. According to yet another embodiment, the number of carbon atoms in the heteroaryl group is 2 to 10. According to yet another embodiment, the number of carbon atoms in the heteroaryl group is 2 to 8. Specific examples of the above heteroaryl group include, but are not limited to, furanyl, thiophenyl, imidazole, pyrazol, thiazol, isothiazol, oxazol, isooxazol, thiadiazole, oxadiazole, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, or tetrazinyl.

[0428]

[0429] In addition, in this specification, the pentagonal or hexagonal heteroaromatic ring is understood to mean a substituent derived from a monocyclic compound having aromaticity, wherein, in addition to carbon as a ring-forming atom, it further comprises one to three heteroatoms selected from O, N, and S. In addition, specific examples of the pentagonal or hexagonal heterocyclic ring include, but are not limited to, furan, thiophene, imidazole, pyrazol, thiazole, isothiazol, oxazole, isooxazole, thiadiazole, oxadiazole, pyridine, pyrimidine, pyridazine, pyrazine, triazine, or tetrazine rings.

[0430]

[0431] Additionally, in this specification, the alkyl, alkylene, alkoxy, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, benzene ring, heteroaromatic ring and heterocycloalkane ring are each independently deuterium; halogen; hydroxy; C 1-4 alkyl; and C 1-4 The alkyl, alkylene, alkoxy, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, benzene ring, heteroaromatic ring, and heterocycloalkane ring are each independently substituted or unsubstituted with one or more substituents selected from the group consisting of deuterium; fluoro; chloro; bromo; hydroxy; methyl; ethyl; propyl; butyl; methoxy; and ethoxy, or are substituted or unsubstituted with substituents in which two or more substituents among the substituents exemplified above are connected.

[0432]

[0433] A compound represented by Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof may be usefully used for the prevention or treatment of fibrotic diseases, cancer, or metabolic diseases.

[0434] The present invention will be explained in more detail below through the following examples. However, the following examples are merely illustrative of the present invention, and the scope of the present invention is not limited thereto.

[0435]

[0436] Example 1: Preparation of 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0437]

[0438] (Step 1)

[0439] 2,3-dichloroquinoxalin (100 g, 1.0 eq), 4-methylbenzenesulfonamide (86 g, 1.0 eq), and potassium carbonate (139 g, 2.0 eq) were dissolved in dimethyl sulfoxide (500 mL), and the temperature was raised to 110 °C and stirred for 12 hours. When the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate = 4:1) to obtain N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide (yield 92.7%, 156 g).

[0440] 1 H NMR (500 MHz, DMSO-d6) δ 8.08 (d, J = 8.0 Hz, 2H), 7.89 (t, J = 7.8 Hz, 2H), 7.83 - 7.75 (m, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H), 2.37 (s, 3H). MS (ES, m / z): 334.21 [M+H] +

[0441] (Step 2)

[0442] 1-fluoro-2-nitrobenzene (3.0 g, 1.0 eq) was dissolved in tetrahydrofuran (30 mL), and then methylpiperazine (2.1 g, 1.0 eq) and potassium carbonate (8.8 g, 3.0 eq) were added. The temperature of the reaction mixture was raised to 66 °C, and after 12 hours of reaction, when the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (ethyl acetate alone) to obtain 1-methyl-4-(2-nitrophenyl)piperazine (yield 85.0 %, 4 g).

[0443] 1H NMR (500 MHz, DMSO-d6) δ 7.79 (dd, J = 8.1, 1.6 Hz, 1H), 7.58 (ddd, J = 8.6, 7.3, 1.7 Hz, 1H), 7.32 (dd, J = 8.3, 1.2 Hz, 1H), 7.15 - 7.08 (m, 1H), 3.02 - 2.94 (m, 4H), 2.42 (t, J = 4.8 Hz, 4H), 2.22 (s, 3H). MS (ES, m / z): 222.10 [M+H] +

[0444] (Step 3)

[0445] The product of step 2 (4.0 g, 1.0 eq) was dissolved in 1,4-dioxane (180 mL), and then Zn (9.5 g, 8.0 eq) and ammonium chloride (7.7 g, 8.0 eq) were added. Water (36 mL) was slowly added while stirring at room temperature. After 12 hours of reaction, the reaction was terminated and filtered through Celite. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain 2-(4-methylpiperazine-1-yl)aniline (yield 88.7%, 3 g).

[0446] 1 H NMR (500 MHz, DMSO-d6) δ 6.89 (d, J = 7.8 Hz, 1H), 6.82 (t, J = 7.7 Hz, 1H), 6.68 (d, J = 7.7 Hz, 1H), 6.55 (t, J = 7.5 Hz, 1H), 4.74 (s, 2H), 2.86 (s, 4H), 2.73 (s, 4H), 2.41 (s, 3H). MS (ES, m / z): 192.21 [M+H] +

[0447] (Step 4)

[0448] The product of Step 1 (1.0 g, 1.0 eq) and the product of Step 3 (573 mg, 1.0 eq) were dissolved in N,N-dimethylformamide (20 mL), and then aluminum chloride (680 mg, 1.5 eq) was slowly added. The temperature of the reaction mixture was raised to 80 °C, and after 12 hours of reaction, when the reaction was complete, an aqueous solution of NaHCO3 was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 35.5%, 520 mg).

[0449] 1 H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.99 - 9.26 (m, 1H), 8.90 (dd, J = 8.0, 1.5 Hz, 1H), 7.98 (d, J = 8.2 Hz, 2H), 7.49 - 7.43 (m, 1H), 7.34 (s, 1H), 7.22 (t, J = 8.6 Hz, 4H), 7.19 - 7.13 (m, 2H), 6.97 (td, J = 7.6, 1.6 Hz, 1H), 3.75 - 3.56 (m, 4H), 3.23 - 3.06 (m, 4H), 2.99 (s, 3H), 2.30 (s, 3H). MS (ES, m / z): 489.47 [M+H] +

[0450]

[0451] Example 2: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0452]

[0453] (Step 1)

[0454] In Step 2 of Example 1, instead of methylpiperazine, N 1 ,N 1 ,N 2Except for using trimethylethane-1,2-diamine, N in the same manner as in Example 1 1 ,N 1 ,N 2 -trimethyl-N 2 -(2-nitrophenyl)ethane-1,2-diamine (4.5 g, yield: 94.8%) was obtained.

[0455] 1 H NMR (500 MHz, DMSO-d6) δ 7.71 (dd, J = 8.1, 1.7 Hz, 1H), 7.49 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 7.28 - 7.22 (m, 1H), 6.95 - 6.88 (m, 1H), 3.19 (q, J = 6.1 Hz, 2H), 2.79 (s, 3H), 2.40 (t, J = 7.0 Hz, 2H), 2.12 (s, 6H). MS (ES, m / z): 224.20 [M+H] +

[0456] (Step 2)

[0457] N in the same way as Step 3 of Example 1 1 -(2-(dimethylamino)ethyl)-N 1 methylbenzene-1,2-diamine (2.1 g, yield: 53.9%) was obtained.

[0458] 1 H NMR (500 MHz, DMSO-d6) δ 6.93 (dd, J = 7.8, 1.4 Hz, 1H), 6.77 (td, J = 7.5, 1.4 Hz, 1H), 6.63 (dd, J = 7.8, 1.6 Hz, 1H), 6.51 (td, J = 7.5, 1.6 Hz, 1H), 4.93 (s, 2H), 2.81 (t, J = 6.6 Hz, 2H), 2.59 (s, 3H), 2.34 (t, J = 6.6 Hz, 2H), 2.16 (s, 6H). MS (ES, m / z): 193.89 [M+H] +

[0459] (Step 3)

[0460] The product compound of Step 1 of Example 1 (200 mg, 1.0 eq), the product compound of Step 2 (116 mg, 1.0 eq), Pd2(dba)3 (55 mg, 0.1 eq), xantphos (104 mg, 0.3 eq), and Cs2CO3 (390 mg, 2.0 eq) were dissolved in 1,4-dioxane (2 mL) and then filled with nitrogen. The temperature of the reaction mixture was raised to 80 °C, and after reacting for 12 hours and the reaction was terminated, an aqueous NH4Cl solution was added after filtering with a Celite filter. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 6.5%, 19 mg).

[0461] 1 H NMR (500 MHz, MeOD) δ 8.94 (dd, J = 8.2, 1.5 Hz, 1H), 8.03 - 7.99 (m, 2H), 7.57 (dd, J = 7.6, 2.0 Hz, 1H), 7.51 (dd, J = 7.6, 2.0 Hz, 1H), 7.35 (dd, J = 7.9, 1.5 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.27 - 7.23 (m, 3H), 7.05 (td, J = 7.7, 1.5 Hz, 1H), 3.42 - 3.38 (m, 2H), 3.32 - 3.29 (m, 2H), 2.93 (s, 6H), 2.81 (s, 3H), 2.38 (s, 3H). MS (ES, m / z): 491.44 [M+H] +

[0462]

[0463] Example 3: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0464]

[0465] (Step 1)

[0466] 1-ethyl-4-(2-nitrophenyl)piperazine (4.5 g, yield: 90.0%) was obtained in the same manner as in Example 1, except that ethylpiperazine was used instead of methylpiperazine in Step 2 of Example 1.

[0467] 1 H NMR (500 MHz, DMSO-d6) δ 7.79 (dd, J = 8.1, 1.6 Hz, 1H), 7.58 (ddd, J = 8.7, 7.3, 1.7 Hz, 1H), 7.31 (dd, J = 8.4, 1.2 Hz, 1H), 7.15 - 7.08 (m, 1H), 2.98 (t, J = 4.9 Hz, 4H), 2.47 (t, J = 4.9 Hz, 4H), 2.37 (q, J = 7.2 Hz, 2H), 1.02 (t, J = 7.2 Hz, 3H). MS (ES, m / z): 236.22 [M+H] +

[0468] (Step 2)

[0469] 2-(4-ethylpiperazine-1-yl)aniline (2.2 g, yield: 56.0%) was obtained by the same method as in Step 3 of Example 1.

[0470] 1 H NMR (500 MHz, DMSO-d6) δ 6.89 (d, J = 7.9 Hz, 1H), 6.80 (t, J = 7.6 Hz, 1H), 6.67 (d, J = 7.9 Hz, 1H), 6.54 (t, J = 7.5 Hz, 1H), 4.68 (s, 2H), 2.80 (s, 4H), 2.59 - 2.47 (m, 4H), 2.38 (q, J = 7.1 Hz, 2H), 1.04 (t, J = 7.2 Hz, 3H). MS (ESI, m / z): 206.2 [M+H] +

[0471] (Step 3)

[0472] N in step 3 of Example 2 1 -(2-(dimethylamino)ethyl)-N 1The title compound (13 mg, yield: 4.3%) was obtained in the same manner as in Example 2, except that 2-(4-ethylpiperazine-1-yl)aniline was used instead of methylbenzene-1,2-diamine.

[0473] 1 H NMR (500 MHz, DMSO-d6) δ 10.18 (s, 1H), 9.90 - 9.22 (m, 1H), 8.92 (d, J = 8.1 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.6 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.26 - 7.12 (m, 6H), 6.98 (t, J = 7.6 Hz, 1H), 3.78 - 3.57 (m, 4H), 3.23 (s, 4H), 3.11 (s, 2H), 2.30 (s, 3H), 1.35 (t, J = 7.3 Hz, 3H). MS (ES, m / z): 503.46 [M+H] +

[0474]

[0475] Example 4: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0476]

[0477] (Step 1)

[0478] (S)-N,N-dimethyl-1-(2-nitrophenyl)pyrrolidine-3-amine (33.0 g, yield: 98.9%) was obtained in the same manner as in Example 1, except that (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine in Step 2 of Example 1.

[0479] 1H NMR (500 MHz, DMSO-d6) δ 7.72 (dd, J = 8.2, 1.7 Hz, 1H), 7.45 (ddd, J = 8.7, 6.9, 1.6 Hz, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.77 (t, J = 7.4 Hz, 1H), 3.33 (td, J = 10.2, 6.4 Hz, 1H), 3.11 (q, J = 8.2 Hz, 3H), 2.75 - 2.66 (m, 1H), 2.17 (s, 6H), 2.12 (dtd, J = 11.9, 6.2, 2.0 Hz, 1H), 1.81 - 1.70 (m, 1H). MS (ESI, m / z): 236.2 [M+H] +

[0480] (Step 2)

[0481] (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine (28.5 g, yield: 99.0%) was obtained by the same method as in Step 3 of Example 1.

[0482] 1 H NMR (500 MHz, DMSO-d6) δ 6.87 (dt, J = 7.8, 1.7 Hz, 1H), 6.78 - 6.71 (m, 1H), 6.65 (dd, J = 8.2, 1.6 Hz, 1H), 6.52 (td, J = 7.4, 1.6 Hz, 1H), 4.58 (s, 2H), 3.20 - 3.10 (m, 1H), 3.08 (ddd, J = 8.8, 6.8, 1.8 Hz, 1H), 2.91 - 2.83 (m, 2H), 2.83 - 2.74 (m, 1H), 2.16 (d, J = 1.9 Hz, 6H), 2.06 - 1.96 (m, 1H), 1.79 - 1.68 (m, 1H). MS (ES, m / z): 206.27 [M+H] +

[0483] (Step 3)

[0484] The product compound of Step 1 of Example 1 (46 g, 1.0 eq), the product compound of Step 2 (28.3 g, 1.0 eq), and PTSA H2O (34.1 g, 1.3 eq) were dissolved in 1-methylpyrrolidin-2-one (230 mL). The reaction mixture was then heated to 130 °C and reacted for 12 hours. Once the reaction was complete, an aqueous solution of NaHCO3 was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 50.5%, 35.0 g).

[0485] 1 H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 8.92 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 7.5 Hz, 1H), 7.33 - 7.28 (m, 1H), 7.21 (t, J = 8.0 Hz, 3H), 7.16 (q, J = 7.6 Hz, 2H), 6.97 (t, J = 7.6 Hz, 1H), 4.23 (s, 1H), 3.59 (s, 2H), 3.51 - 3.45 (m, 2H), 2.99 (s, 6H), 2.72 (d, J = 8.7 Hz, 1H), 2.40 (d, J = 24.1 Hz, 1H), 2.30 (s, 3H). MS (ES, m / z): 503.46 [M+H] +

[0486]

[0487] Example 5: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide

[0488]

[0489] (Step 1)

[0490] N-(3-chloroquinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide (450 mg, yield: 62.4%) was obtained in the same manner as in Example 1, except that 4-(trifluoromethyl)benzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[0491] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(d, J = 8.1 Hz, 2H), 7.81 (d, J = 8.1 Hz, 2H), 7.67 - 7.62 (m, 1H), 7.51 (dd, J = 7.2, 1.8 Hz, 2H), 7.32 (ddd, J = 8.3, 6.2, 2.2 Hz, 1H). MS (ES, m / z): 388.26 [M+H] +

[0492] (Step 2)

[0493] The title compound (40.0 mg, yield: 28.6%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0494] 1 H NMR (500 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.93 - 9.31 (m, 1H), 8.93 - 8.85 (m, 1H), 8.29 (d, J = 7.9 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 7.51 - 7.44 (m, 1H), 7.37 - 7.31 (m, 1H), 7.23 (dd, J = 11.0, 7.8 Hz, 2H), 7.18 (dt, J = 7.6, 4.2 Hz, 2H), 6.98 (td, J = 7.6, 1.4 Hz, 1H), 3.73 - 3.64 (m, 4H), 3.28 - 3.10 (m, 4H), 3.02 (s, 3H). MS (ES, m / z): 543.43 [M+H]+

[0495]

[0496] Example 6: Preparation of 4-Methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0497]

[0498] (Step 1)

[0499] N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide (158 g, yield: 89.9%) was obtained in the same manner as in Example 1, except that 4-methoxybenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[0500] 1 H NMR (500 MHz, DMSO-d6) δ 8.15 (d, J = 8.6 Hz, 2H), 7.89 (t, J = 8.7 Hz, 2H), 7.78 (t, J = 7.7 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H). MS (ES, m / z): 350.33 [M+H] +

[0501] (Step 2)

[0502] The title compound (44.0 mg, yield: 30.5%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0503] 1H NMR (500 MHz, DMSO-d6) δ 10.23 (s, 1H), 10.05 - 9.31 (m, 1H), 8.90 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 7.7 Hz, 1H), 7.38 (s, 1H), 7.22 (t, J = 8.1 Hz, 2H), 7.16 (q, J = 8.1 Hz, 2H), 6.96 (dd, J = 17.1, 8.2 Hz, 3H), 3.76 (s, 3H), 3.70 - 3.50 (m, 4H), 3.45 - 3.24 (m, 4H), 2.96 (s, 3H). MS (ES, m / z): 505.49 [M+H] +

[0504]

[0505] Example 7: Preparation of 3-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0506]

[0507] (Step 1)

[0508] 2,3-dichloroquinoxaline (2.0 g, 1.0 eq), 3-methylbenzenesulfonamide (1.7 g, 1.0 eq), and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (4.6 g, 3.0 eq) were dissolved in acetonitrile (10 mL), and the temperature was raised to 80 °C and stirred for 12 hours. When the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate = 4:1) to obtain N-(3-chloroquinoxaline-2-yl)-3-methylbenzenesulfonamide (yield 49.6%, 1.7 g).

[0509] 1H NMR (500 MHz, DMSO-d6) δ 8.04 - 7.96 (m, 2H), 7.88 (dd, J = 13.9, 8.0 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.56 - 7.46 (m, 2H), 2.43 (s, 3H). MS (ES, m / z): 334.28 [M+H] +

[0510] (Step 2)

[0511] The title compound (64.0 mg, yield: 43.7%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0512] 1 H NMR (500 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.96 - 9.12 (m, 1H), 8.89 (d, J = 8.3 Hz, 1H), 7.97 (s, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.47 (d, J) = 7.7 Hz, 1H), 7.34 (s, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 8.1 Hz, 3H), 7.17 (p, J = 7.0 Hz, 2H), 6.98 (t, J = 7.6 Hz, 1H), 3.74 - 3.57 (m, 4H), 3.23 - 3.06 (m, 4H), 2.99 (s, 3H), 2.36 (s, 3H). MS (ES, m / z): 489.47 [M+H] +

[0513]

[0514] Example 8: Preparation of 2-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0515]

[0516] (Step 1)

[0517] 2,3-dichloroquinoxalin (2.0 g, 1.0 eq), 2-methylbenzenesulfonamide (1.7 g, 1.0 eq), and potassium carbonate (4.2 g, 3.0 eq) were dissolved in N,N-dimethylformamide (20 mL), and the temperature was raised to 90 °C and stirred for 12 hours. When the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate = 4:1) to obtain N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide (yield 48.3%, 1.6 g).

[0518] 1 H NMR (500 MHz, DMSO-d6) δ 8.32 - 8.12 (m, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.80 - 7.69 (m, 2H), 7.62 (s, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 2.70 (s, 3H). MS (ES, m / z): 334.21 [M+H] +

[0519] (Step 2)

[0520] The title compound (46.0 mg, yield: 31.4%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0521] 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.96 (d, J = 8.0 Hz, 1H), 8.18 - 8.13 (m, 1H), 7.96 (s, 1H), 7.52 - 7.43 (m, 1H), 7.37 (d, J = 7.3 Hz, 1H), 7.32 - 7.27 (m, 2H), 7.27 - 7.20 (m, 2H), 7.14 (t, J = 10.4 Hz, 3H), 6.99 (t, J = 7.6 Hz, 1H), 3.71 - 3.55 (m, 4H), 3.24 - 3.08 (m, 4H), 2.94 (s, 3H), 2.63 (s, 3H). MS (ES, m / z): 489.47 [M+H] +

[0522]

[0523] Example 9: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide

[0524]

[0525] (Step 1)

[0526] N-(3-chloroquinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide (2.0 g, yield: 51.3%) was obtained in the same manner as in Example 1, except that 2-(trifluoromethyl)benzenesulfonamide was used instead of 2-methylbenzenesulfonamide in Step 1 of Example 8.

[0527] 1 H NMR (500 MHz, DMSO-d6) δ 8.47 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.92 (t, J = 7.7 Hz, 1H), 7.86 (dt, J = 10.6, 5.6 Hz, 2H), 7.72 (q, J = 11.7 Hz, 2H), 7.61 (t, J = 8.1 Hz, 1H). MS (ES, m / z): 388.26 [M+H] +

[0528] (Step 2)

[0529] The title compound (27.0 mg, yield: 19.3%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0530] 1 H NMR (500 MHz, MeOD) δ 9.01 (dd, J = 8.1, 1.4 Hz, 1H), 8.64 (d, J = 8.0 Hz, 1H), 7.87 - 7.77 (m, 2H), 7.70 (d, J = 7.7 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.31 - 7.17 (m, 4H), 7.02 (t, J = 7.3 Hz, 1H), 3.61 - 3.39 (m, 4H), 3.26 - 3.11 (m, 4H), 2.91 (s, 3H). MS (ES, m / z): 543.50 [M+H] +

[0531]

[0532] Example 10: Preparation of 2-Methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0533]

[0534] (Step 1)

[0535] N-(3-chloroquinoxalin-2-yl)-2-methoxybenzenesulfonamide (2.2 g, yield: 39.7%) was obtained in the same manner as in Example 1, except that 2-methoxybenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[0536] 1H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.72 (t, J = 7.3 Hz, 2H), 7.67 - 7.56 (m, 2H), 7.17 (dd, J = 8.3, 6.2 Hz, 2H), 3.76 (s, 3H). MS (ES, m / z): 350.23 [M+H] +

[0537] (Step 2)

[0538] The title compound (4.0 mg, yield: 2.8%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-2-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0539] 1 H NMR (500 MHz, MeOD) δ 8.97 (d, J = 8.1 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.62 (t, J = 7.5 Hz, 2H), 7.44 (dt, J = 21.0, 7.3 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 7.20 - 7.14 (m, 2H), 7.08 (dt, J = 15.0, 7.7 Hz, 1H), 3.62 (d, J = 4.2 Hz, 3H), 2.94 - 2.79 (m, 4H), 2.72 - 2.45 (m, 4H), 2.39 (s, 3H). MS (ES, m / z): 505.42 [M+H] +

[0540]

[0541] Example 11: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[0542]

[0543] (Step 1)

[0544] N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide (5.6 g, yield: 99.7%) was obtained in the same manner as in Example 1, except that naphthalene-2-sulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[0545] 1 H NMR (500 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.30 (d, J = 7.6 Hz, 1H), 8.18 (d, J = 8.9 Hz, 1H), 8.13 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.72 (t, J = 8.0 Hz, 1H), 7.70 - 7.64 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H). MS (ES, m / z): 370.26 [M+H] +

[0546] (Step 2)

[0547] The title compound (49.0 mg, yield: 34.5%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0548] 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 9.68 (s, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.73 (s, 1H), 8.16 - 8.09 (m, 2H), 7.92 (q, J = 5.8 Hz, 2H), 7.61 - 7.55 (m, 2H), 7.44 (d, J = 7.4 Hz, 1H), 7.33 (s, 1H), 7.27 - 7.19 (m, 2H), 7.13 (t, J = 7.4 Hz, 2H), 6.98 (t, J = 7.7 Hz, 1H), 3.84 - 3.62 (m, 4H), 3.29 - 3.10 (m, 4H), 3.05 (s, 3H). MS (ES, m / z): 525.52 [M+H] +

[0549]

[0550] Example 12: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0551]

[0552] (Step 1)

[0553] The title compound (4.2 g, yield: 19.1%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[0554] 1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.92 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 7.5 Hz, 1H), 7.37 - 7.33 (m, 3H), 7.22 (d, J = 7.9 Hz, 1H), 7.17 (t, J = 7.8 Hz, 3H), 6.96 (dd, J = 19.6, 8.5 Hz, 2H), 4.21 (s, 1H), 3.76 (s, 3H), 3.66 - 3.55 (m, 1H), 3.51 - 3.44 (m, 2H), 2.99 (s, 6H), 2.73 (q, J = 8.3 Hz, 1H), 2.40 (d, J = 20.4 Hz, 2H). MS (ES, m / z): 519.50 [M+H] +

[0555]

[0556] Example 13: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide

[0557]

[0558] (Step 1)

[0559] The title compound (15.0 mg, yield: 5.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0560] 1H NMR (500 MHz, MeOD) δ 8.93 (dd, J = 8.1, 1.5 Hz, 1H), 8.62 (d, J = 7.9 Hz, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.7 Hz, 1H), 7.65 (t, J) = 7.7 Hz, 1H), 7.54 (dd, J = 8.0, 1.5 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.27 - 7.20 (m, 3H), 7.19 - 7.13 (m, 1H), 7.02 (td, J = 7.6, 1.5 Hz, 1H), 4.07 (s, 1H), 3.60 - 3.55 (m, 1H), 3.51 (q, J = 7.1 Hz, 1H), 3.39 (dd, J = 11.3, 7.2 Hz, 1H), 3.03 (s, 6H), 2.96 (td, J = 9.0, 7.0 Hz, 1H), 2.52 (s, 1H), 2.42 (s, 1H). MS (ES, m / z): 557.48 [M+H] +

[0561]

[0562] Example 14: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0563]

[0564] (Step 1)

[0565] The title compound (24.0 mg, yield: 8.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0566] 1H NMR (500 MHz, MeOD) δ 8.86 (dd, J = 8.2, 1.5 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.36 (dd, J = 15.4, 7.8 Hz, 2H), 7.29 - 7.22 (m, 3H), 7.21 - 7.15 (m, 1H), 7.06 - 6.99 (m, 1H), 4.62 (s, 1H), 4.06 - 3.79 (m, 1H), 3.51 (q, J = 7.0 Hz, 1H), 3.38 (dd, J = 11.0, 7.3 Hz, 2H), 2.99 (q, J = 7.9 Hz, 2H), 2.93 (s, 6H), 2.42 (s, 3H). MS (ES, m / z): 503.52 [M+H] +

[0567]

[0568] Example 15: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0569]

[0570] (Step 1)

[0571] The title compound (49.0 mg, yield: 16.3%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0572] 1H NMR (500 MHz, MeOD) δ 8.89 (d, J = 8.2 Hz, 1H), 8.21 (d, J = 7.8 Hz, 1H), 7.58 (s, 1H), 7.42 (s, 2H), 7.35 (s, 1H), 7.29 (s, 3H), 7.22 (dt, J = 15.4, 7.9 Hz, 2H), 7.03 (t, J = 7.6 Hz, 1H), 4.62 (s, 1H), 3.75 (s, 1H), 3.49 (d, J = 21.9 Hz, 1H), 3.38 (s, 2H), 3.07 - 2.97 (m, 2H), 2.86 (d, J = 18.1 Hz, 6H), 2.70 (d, J = 16.1 Hz, 3H). MS (ES, m / z): 503.52 [M+H] +

[0573]

[0574] Example 16: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[0575]

[0576] (Step 1)

[0577] The title compound (7.0 mg, yield: 4.8%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0578] 1H NMR (500 MHz, MeOD) δ 8.87 (dd, J = 8.2, 1.5 Hz, 1H), 8.72 (d, J = 1.8 Hz, 1H), 8.10 (dd, J = 8.7, 1.9 Hz, 1H), 8.07 - 8.02 (m, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.94 - 7.89 (m, 1H), 7.63 - 7.57 (m, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.28 - 7.21 (m, 3H), 7.21 - 7.16 (m, 1H), 7.02 (td, J = 7.6, 1.5 Hz, 1H), 3.85 (s, 1H), 3.51 (q, J = 7.0 Hz, 1H), 3.38 (dd, J = 11.0, 7.2 Hz, 2H), 2.97 (q, J = 8.3 Hz, 1H), 2.90 (s, 6H), 2.35 (s, 2H). MS (ES, m / z): 539.50 [M+H] +

[0579]

[0580] Example 17: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide

[0581]

[0582] (Step 1)

[0583] 2,3-dichloroquinoxaline (500 mg, 1.0 eq), ethanesulfonamide (274 mg, 1.0 eq), and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (1.1 g, 3.0 eq) were dissolved in N,N-dimethylformamide (5 mL), and the temperature was raised to 80 °C and stirred for 12 hours. When the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate = 4:1) to obtain N-(3-chloroquinoxaline-2-yl)ethanesulfonamide (yield 60.2%, 411 mg).

[0584] 1 H NMR (500 MHz, DMSO-d6) δ 7.95 (dd, J = 8.5, 3.7 Hz, 2H), 7.82 (t, J = 7.7 Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 3.79 - 3.60 (m, 2H), 1.33 (t, J) = 7.4 Hz, 3H). MS (ES, m / z): 272.15 [M+H] +

[0585] (Step 2)

[0586] The title compound (15.0 mg, yield: 13.5%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-ethanesulfonamide in Step 4 of Example 1.

[0587] 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 9.61 (s, 1H), 8.92 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 7.4 Hz, 1H), 7.40 (s, 1H), 7.27 - 7.14 (m, 4H), 6.98 (t, J = 7.6 Hz, 1H), 3.52 (s, 4H), 3.40 (s, 2H), 3.10 (s, 4H), 2.89 (s, 3H), 1.19 (q, J = 6.2 Hz, 3H). MS (ES, m / z): 427.36 [M+H] +

[0588]

[0589] Example 18: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide

[0590]

[0591] (Step 1)

[0592] N-(3-chloroquinoxalin-2-yl)methanesulfonamide (451 mg, yield: 69.7%) was obtained in the same manner as in Example 1, except that methanesulfonamide was used instead of ethanesulfonamide in Step 1 of Example 17.

[0593] 1 H NMR (500 MHz, DMSO-d6) δ 8.01 - 7.94 (m, 2H), 7.83 (t, J = 7.7 Hz, 1H), 7.74 (t, J = 7.7 Hz, 1H), 3.51 (s, 3H). MS (ES, m / z): 258.09 [M+H] +

[0594] (Step 2)

[0595] The title compound (7.0 mg, yield: 6.5%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)methanesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0596] 1 H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.57 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.40 (s, 1H), 7.28 - 7.15 (m, 4H), 6.98 (d, J = 7.6 Hz, 1H), 3.57 (s, 4H), 3.21 - 3.01 (m, 7H), 2.92 (s, 3H). MS (ES, m / z): 413.37 [M+H] +

[0597]

[0598] Example 19: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)cyclopropanesulfonamide

[0599]

[0600] (Step 1)

[0601] N-(3-chloroquinoxalin-2-yl)cyclopropanesulfonamide (506 mg, yield: 71.0%) was obtained in the same manner as in Example 1, except that cyclopropanesulfonamide was used instead of ethanesulfonamide in Step 1 of Example 17.

[0602] 1 H NMR (500 MHz, DMSO-d6) δ 8.01 - 7.93 (m, 2H), 7.83 (t, J = 7.7 Hz, 1H), 7.73 (dd, J = 11.2, 6.3 Hz, 1H), 1.26 (d, J = 5.3 Hz, 2H), 1.14 (dq, J = 8.0, 4.9 Hz, 2H). MS (ES, m / z): 284.10 [M+H] +

[0603] (Step 2)

[0604] The title compound (35.0 mg, yield: 30.5%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)cyclopropanesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0605] 1 H NMR (500 MHz, DMSO-d6) δ 10.22 (s, 1H), 9.57 (s, 1H), 8.95 - 8.89 (m, 1H), 7.52 (d, J = 6.9 Hz, 1H), 7.41 (s, 1H), 7.27 - 7.14 (m, 4H), 6.99 (d, J = 7.7 Hz, 1H), 3.51 (s, 4H), 3.31 - 3.20 (m, 1H), 3.09 (s, 4H), 2.86 (s, 3H), 1.00 (s, 2H), 0.82 (s, 2H). MS (ES, m / z): 439.37 [M+H] +

[0606]

[0607] Example 20: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide

[0608]

[0609] (Step 1)

[0610] N-(3-chloroquinoxalin-2-yl)propane-2-sulfonamide (476 mg, yield: 66.3%) was obtained in the same manner as in Example 1, except that propane-2-sulfonamide was used instead of ethanesulfonamide in Step 1 of Example 17.

[0611] 1H NMR (500 MHz, DMSO-d6) δ 7.96 (d, J = 8.4 Hz, 2H), 7.81 (s, 1H), 7.74 (d, J = 9.4 Hz, 1H), 4.38 - 4.10 (m, 1H), 1.39 (d, J = 6.8 Hz, 6H). MS (ES, m / z): 286.14 [M+H] +

[0612] (Step 2)

[0613] The title compound (13.0 mg, yield: 11.3%) was obtained in the same manner as in Example 1, except that N-(3-chloroquinoxalin-2-yl)propane-2-sulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 1.

[0614] 1 H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.93 - 9.20 (m, 1H), 8.94 - 8.88 (m, 1H), 7.51 (dd, J = 6.8, 2.6 Hz, 1H), 7.43 (s, 1H), 7.22 (ddt, J = 15.8, 11.6, 5.5 Hz, 4H), 6.99 (t, J = 7.6 Hz, 1H), 4.12 - 3.91 (m, 1H), 3.63 - 3.39 (m, 4H), 3.08 (s, 4H), 2.84 (s, 3H), 1.31 - 1.20 (m, 6H). MS (ES, m / z): 441.41 [M+H] +

[0615]

[0616] Example 21: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)cyclopropanesulfonamide

[0617]

[0618] (Step 1)

[0619] The title compound (12.0 mg, yield: 10.9%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0620] 1 H NMR (500 MHz, DMSO-d6) δ 9.74 - 9.41 (m, 2H), 8.95 (s, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.39 (s, 1H), 7.24 - 7.15 (m, 4H), 6.98 (d, J = 8.0 Hz, 1H), 4.16 (s, 1H), 3.60 (s, 1H), 3.51 (s, 1H), 3.44 (t, J = 9.1 Hz, 1H), 2.89 (s, 6H), 2.43 - 2.29 (m, 2H), 1.76 (s, 1H), 1.48 (s, 1H), 0.97 (s, 2H), 0.81 (s, 2H). MS (ES, m / z): 453.43 [M+H] +

[0621]

[0622] Example 22: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide

[0623]

[0624] (Step 1)

[0625] The title compound (9.0 mg, yield: 8.1%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0626] 1 H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 2H), 8.96 (s, 1H), 7.49 (s, 1H), 7.35 (s, 1H), 7.19 (t, J = 10.5 Hz, 4H), 6.97 (s, 1H), 4.17 (s, 1H), 3.54 (s, 3H), 2.92 (s, 6H), 1.24 (s, 4H), 1.22 (s, 6H). MS (ES, m / z): 455.46 [M+H] +

[0627]

[0628] Example 23: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide

[0629]

[0630] (Step 1)

[0631] The title compound (3.0 mg, yield: 2.8%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0632] 1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.59 (s, 1H), 8.95 (d, J = 8.0 Hz, 1H), 7.49 (dd, J = 7.5, 2.0 Hz, 1H), 7.36 (s, 1H), 7.19 (dt, J = 12.0, 7.9 Hz, 4H), 6.97 (t, J = 7.5 Hz, 1H), 4.11 (s, 1H), 3.50 (s, 1H), 3.41 (p, J = 7.9 Hz, 2H), 3.28 (d, J = 10.9 Hz, 1H), 2.87 (s, 6H), 2.41 - 2.29 (m, 2H), 1.24 (s, 2H), 1.16 (t, J = 7.5 Hz, 3H). MS (ES, m / z): 441.41 [M+H] +

[0633]

[0634] Example 24: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide

[0635]

[0636] (Step 1)

[0637] The title compound (3.0 mg, yield: 2.9%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0638] 1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 9.56 (s, 1H), 8.96 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.40 (d, J = 7.1 Hz, 1H), 7.20 (dt, J = 14.9, 7.6 Hz, 4H), 6.98 (d, J = 8.0 Hz, 1H), 4.20 (s, 1H), 3.60 - 3.47 (m, 1H), 3.46 - 3.35 (m, 1H), 3.30 (s, 1H), 3.14 (s, 3H), 2.92 (s, 6H), 2.81 (s, 1H), 2.38 (s, 2H). MS (ES, m / z): 427.36 [M+H] +

[0639]

[0640] Example 25: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0641]

[0642] (Step 1)

[0643] (R)-N,N-dimethyl-1-(2-nitrophenyl)pyrrolidine-3-amine (158 mg, yield: 3.2%) was obtained in the same manner as in Example 1, except that (R)-N,N-dimethylpyrrolidine-3-amine was used instead of (S)-N,N-dimethylpyrrolidine-3-amine in Step 2 of Example 1.

[0644] 1H NMR (500 MHz, DMSO-d6) δ 7.73 (dd, J = 8.2, 1.5 Hz, 1H), 7.46 (dt, J = 6.9, 4.4 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.78 (t, J = 7.6 Hz, 1H), 3.35 (dd, J = 12.0, 8.1 Hz, 1H), 3.16 - 3.06 (m, 3H), 2.78 - 2.68 (m, 1H), 2.18 (s, 6H), 2.13 (dq, J = 10.3, 3.1 Hz, 1H), 1.82 - 1.70 (m, 1H). MS (ES, m / z): 236.22 [M+H] +

[0645] (Step 2)

[0646] (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine (120 mg, yield: 87.0%) was obtained by the same method as in Step 3 of Example 1.

[0647] 1 H NMR (500 MHz, DMSO-d6) δ 6.86 (dd, J = 7.8, 1.4 Hz, 1H), 6.79 - 6.67 (m, 1H), 6.65 (dd, J = 7.7, 1.6 Hz, 1H), 6.52 (td, J = 7.6, 1.6 Hz, 1H), 4.58 (s, 2H), 3.16 (dt, J = 8.9, 6.8 Hz, 1H), 3.08 (dd, J = 9.0, 6.8 Hz, 1H), 2.86 (td, J = 8.7, 5.9 Hz, 2H), 2.80 (q, J = 7.2 Hz, 1H), 2.16 (s, 6H), 2.02 (dtd, J = 12.9, 7.7, 5.2 Hz, 1H), 1.78 - 1.68 (m, 1H). MS (ES, m / z): 206.27 [M+H] +

[0648] (Step 3)

[0649] The title compound (12 mg, yield: 4.0%) was obtained in the same manner as in Example 1, except that (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in Step 4 of Example 1.

[0650] 1 H NMR (500 MHz, CDCl3) δ 9.41 (s, 1H), 8.82 (dd, J = 8.2, 1.5 Hz, 1H), 7.91 (d, J = 8.0 Hz, 2H), 7.73 (dd, J = 8.0, 1.4 Hz, 1H), 7.46 - 7.36 (m, 1H), 7.39 - 7.33 (m, 3H), 7.25 - 7.16 (m, 2H), 7.09 (td, J = 7.7, 1.5 Hz, 1H), 3.40 - 3.36 (m, 2H), 3.27 - 2.97 (m, 3H), 3.56 - 2.47 (m, 2H), 2.45 (s, 6H), 2.06 (d, J = 9.8 Hz, 3H). MS (ES, m / z): 503.46 [M+H] +

[0651]

[0652] Example 26: Preparation of 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide

[0653]

[0654] (Step 1)

[0655] N-(3-chloropyrazine-2-yl)-4-methylbenzenesulfonamide (17.8 g, yield: 93.3%) was obtained in the same manner as in Example 1, except that 2,3-dichloropyrazine was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1.

[0656] 1H NMR (500 MHz, DMSO-d6) δ 8.24 (d, J = 2.6 Hz, 1H), 8.13 (d, J = 2.6 Hz, 1H), 7.91 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H). MS (ES, m / z): 284.10 [M+H] +

[0657] (Step 2)

[0658] The product compound from Step 1 (500 mg, 1.0 eq) and 2-(4-methylpiperazine-1-yl)aniline (337 mg, 1.0 eq) were dissolved in isopropyl alcohol (5 mL), and then methanesulfonyl chloride (254 mg, 1.5 eq) was slowly added. The temperature of the reaction mixture was raised to 80 °C, and after 12 hours of reaction, when the reaction was complete, an aqueous solution of NaHCO3 was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 17.5%, 135 mg).

[0659] 1 H NMR (500 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.70 (s, 1H), 8.56 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 7.8 Hz, 2H), 7.23 (t, J = 6.5 Hz, 3H), 7.20 - 7.09 (m, 3H), 6.90 (t, J = 7.3 Hz, 1H), 3.54 - 3.37 (m, 4H), 3.06 (s, 4H), 2.81 (s, 3H), 2.32 (s, 3H). MS (ESI, m / z): 439.3 [M+H] +

[0660]

[0661] Example 27: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methylbenzenesulfonamide

[0662]

[0663] (Step 1)

[0664] The title compound (150 mg, yield: 3.1%) was obtained in the same manner as in Example 26, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 2 of Example 26.

[0665] 1 H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.16 (s, 1H), 8.57 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 7.8 Hz, 2H), 7.19 (dt, J = 12.8, 5.7 Hz, 4H), 7.14 (d, J = 3.3 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 6.88 (t, J = 7.7 Hz, 1H), 4.16 - 3.99 (m, 1H), 3.51 (s, 1H), 3.40 (h, J = 7.1 Hz, 2H), 2.90 (s, 6H), 2.74 (d, J = 8.2 Hz, 1H), 2.45 - 2.36 (m, 2H), 2.32 (d, J = 5.4 Hz, 3H). MS (ESI, m / z): 453.3 [M+H] +

[0666]

[0667] Example 28: Preparation of 4-Methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide

[0668]

[0669] (Step 1)

[0670] N-(3-chloropyrazine-2-yl)-4-methoxybenzenesulfonamide (35.8 g, yield: 89.0%) was obtained in the same manner as in Example 1, except that 2,3-dichloropyrazine was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1 and 4-methoxybenzenesulfonamide was used instead of 4-methylbenzenesulfonamide.

[0671] 1 H NMR (500 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.45 (s, 1H), 7.89 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 2.82 (d, J = 4.8 Hz, 3H). MS (ES, m / z): 300.14 [M+H] +

[0672] (Step 2)

[0673] The title compound (152 mg, yield: 5.0%) was obtained in the same manner as in Example 26, except that N-(3-chloropyrazine-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloropyrazine-2-yl)-4-methylbenzenesulfonamide in Step 2 of Example 26.

[0674] 1 H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 9.68 (s, 1H), 8.56 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 3.5 Hz, 1H), 7.22 - 7.14 (m, 2H), 7.12 (t, J = 7.8 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 6.90 (t, J = 7.3 Hz, 1H), 3.78 (s, 3H), 3.04 (s, 4H), 2.90 (s, 3H), 2.78 (s, 4H). MS (ESI, m / z): 455.3 [M+H] +

[0675]

[0676] Example 29: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methoxybenzenesulfonamide

[0677]

[0678] (Step 1)

[0679] The title compound (14 mg, yield: 0.4%) was obtained in the same manner as in Example 26, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in step 2 of Example 26, and N-(3-chloropyrazine-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloropyrazine-2-yl)-4-methylbenzenesulfonamide.

[0680] 1 H NMR (500 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.56 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.7 Hz, 2H), 7.21 (dd, J = 6.7, 2.7 Hz, 1H), 7.22 - 7.13 (m, 2H), 7.07 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 8.6 Hz, 2H), 6.89 (t, J = 7.8 Hz, 1H), 4.13 - 3.99 (m, 1H), 3.78 (s, 3H), 3.40 (p, J = 7.7) Hz, 2H), 2.90 (s, 6H), 2.74 (d, J = 7.7 Hz, 2H), 2.40 - 2.29 (m, 2H). MS (ESI, m / z): 469.3 [M+H] +

[0681]

[0682] Example 30: Preparation of N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide

[0683]

[0684] (Step 1)

[0685] N-(3-chloroquinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide (928 mg, yield: 47.6%) was obtained in the same manner as in Example 1, except that 3-(trifluoromethyl)benzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[0686] 1 H NMR (500 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.83 - 7.76 (m, 2H), 7.66 (dt, J = 14.5, 8.2 Hz, 2H), 7.52 (t, J = 7.2 Hz, 1H). MS (ES, m / z): 388.26 [M+H] +

[0687] (Step 2)

[0688] The product compound from Step 1 (200 mg, 1.0 eq) and 2-(4-methylpiperazine-1-yl)aniline (99 mg, 1.0 eq) were dissolved in butanol (2 mL), and 4 M HCl in 1,4-dioxane (0.13 ml, 1.5 eq) was slowly added. The temperature of the reaction mixture was raised to 110 °C, and after 12 hours of reaction, when the reaction was complete, an aqueous solution of NaHCO3 was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 24.3%, 68 mg).

[0689] 1H NMR (500 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.89 - 9.34 (m, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.65 (s, 1H), 8.26 (d, J = 7.9 Hz, 1H), 7.79 (d, J) = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.7 Hz, 1H), 7.20 (dq, J = 25.8, 7.2 Hz, 4H), 6.96 (dt, J) = 11.8, 6.7 Hz, 1H), 3.65 - 3.53 (m, 4H), 3.20 - 3.09 (m, 4H), 2.96 (s, 3H). MS (ESI, m / z): 543.3 [M+H] +

[0690]

[0691] Example 31: Preparation of 3-Methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0692]

[0693] (Step 1)

[0694] N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide (1.8 g, yield: 51.8%) was obtained in the same manner as in Example 1, except that 3-methoxybenzenesulfonamide was used instead of 2-methylbenzenesulfonamide in Step 1 of Example 8.

[0695] 1H NMR (500 MHz, DMSO-d6) δ 7.63 (dd, J = 2.6, 1.5 Hz, 1H), 7.59 (dd, J = 8.2, 1.5 Hz, 1H), 7.53 (dt, J = 7.7, 1.3 Hz, 1H), 7.47 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.41 (dd, J = 8.4, 1.5 Hz, 1H), 7.30 (t, J = 7.9 Hz, 1H), 7.25 (ddd, J = 8.3, 6.9, 1.5 Hz, 1H), 6.97 - 6.91 (m, 1H), 3.80 (s, 3H). MS (ES, m / z): 350.30 [M+H] +

[0696] (Step 2)

[0697] The title compound (130 mg, yield: 45.1%) was obtained in the same manner as in Example 30, except that N-(3-chloroquinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide in Step 2 of Example 30.

[0698] 1 H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 9.87 - 9.52 (m, 1H), 8.93 - 8.88 (m, 1H), 7.83 (s, 1H), 7.60 (d, J = 7.7 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.36 - 7.28 (m, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.18 (dt, J = 15.1, 7.4 Hz, 2H), 6.97 (t, J = 7.0 Hz, 2H), 3.83 (s, 3H), 3.74 - 3.59 (m, 4H), 3.25 - 3.07 (m, 4H), 3.01 (s, 3H). MS (ESI, m / z): 505.3 [M+H] +

[0699]

[0700] Example 32: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide

[0701]

[0702] (Step 1)

[0703] In step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N-(4-methylpiperazine-1-yl)aniline instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (3 mg, yield: 0.7%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0704] 1 H NMR (500 MHz, DMSO-d6) δ 9.58 (s, 1H), 9.43 - 9.18 (m, 1H), 9.06 (dd, J = 13.2, 8.1 Hz, 1H), 8.26 (t, J = 6.5 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H), 7.49 - 7.44 (m, 1H), 7.37 - 7.25 (m, 2H), 7.24 - 7.14 (m, 3H), 7.00 (q, J = 6.3 Hz, 1H), 3.40 (t, J = 6.8 Hz, 2H), 3.14 (s, 2H), 2.92 (s, 6H), 2.78 (d, J = 3.2 Hz, 3H). MS (ESI, m / z): 545.4 [M+H] +

[0705]

[0706] Example 33: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0707]

[0708] (Step 1)

[0709] In Step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (3 mg, yield: 0.8%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0710] 1 H NMR (500 MHz, DMSO-d6) δ 9.59 (s, 1H), 9.08 (d, J = 8.0 Hz, 1H), 7.93 (s, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.48 - 7.41 (m, 1H), 7.35 - 7.30 (m, 1H), 7.28 (t, J = 7.3 Hz, 2H), 7.23 - 7.19 (m, 2H), 7.15 (dt, J = 14.4, 6.5 Hz, 3H), 6.99 (t, J = 7.6 Hz, 1H), 3.65 - 3.56 (m, 2H), 3.09 - 3.00 (m, 2H), 2.78 (s, 6H), 2.65 (s, 3H), 2.36 (s, 3H). MS (ESI, m / z): 491.4 [M+H] +

[0711]

[0712] Example 34: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide

[0713]

[0714] (Step 1)

[0715] In step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N-(4-methylpiperazine-1-yl)aniline instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (5 mg, yield: 1.1%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0716] 1 H NMR (500 MHz, DMSO-d6) δ 9.57 (s, 1H), 9.06 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.9 Hz, 2H), 7.46 (t, J = 6.2 Hz, 2H), 7.33 (d, J = 7.9 Hz, 1H), 7.29 - 7.25 (m, 2H), 7.17 (t, J = 7.0 Hz, 2H), 7.00 (t, J = 7.3 Hz, 1H), 3.39 (t, J = 6.7 Hz, 2H), 3.09 - 3.05 (m, 2H), 2.77 (s, 6H), 2.65 (s, 3H). MS (ESI, m / z): 545.3 [M+H] +

[0717]

[0718] Example 35: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[0719]

[0720] (Step 1)

[0721] In step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1The title compound (16 mg, yield: 3.7%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0722] 1 H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 9.23 (s, 1H), 9.05 (d, J = 8.2 Hz, 1H), 7.77 (s, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.47 (d, J = 7.5 Hz, 1H), 7.32 (dd, J = 11.1, 7.8 Hz, 3H), 7.18 (dt, J = 13.5, 7.6 Hz, 3H), 6.99 (q, J = 7.0 Hz, 2H), 3.82 (s, 3H), 3.40 - 3.37 (m, 2H), 3.14 (t, J = 7.3 Hz, 2H), 2.94 (s, 6H), 2.77 (s, 3H). MS (ESI, m / z): 507.4 [M+H] +

[0723]

[0724] Example 36: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0725]

[0726] (Step 1)

[0727] In step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (17 mg, yield: 3.9%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0728] 1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.21 (s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 8.15 - 8.10 (m, 1H), 7.43 (s, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.28 (s, 2H), 7.21 (t, J = 7.7 Hz, 1H), 7.15 (s, 2H), 7.11 (s, 2H), 7.00 (t, J = 7.8 Hz, 1H), 3.46 - 3.38 (m, 2H), 3.18 (s, 2H), 2.94 (s, 6H), 2.75 (s, 3H), 2.64 (s, 3H). MS (ESI, m / z): 491.4 [M+H] +

[0729]

[0730] Example 37: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0731]

[0732] (Step 1)

[0733] In step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N instead of 2-(4-methylpiperazine-1-yl)aniline 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (21 mg, yield: 4.8%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0734] 1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 9.42 - 9.14 (m, 1H), 9.04 (d, J = 8.1 Hz, 1H), 8.02 (dd, J = 8.5, 5.1 Hz, 2H), 7.46 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.16 (dd, J = 17.5, 8.5 Hz, 3H), 6.99 (t, J = 7.7 Hz, 1H), 6.94 (d, J = 8.3 Hz, 2H), 3.77 (s, 3H), 3.39 - 3.35 (m, 2H), 3.13 (t, J = 7.3 Hz, 2H), 2.93 (s, 6H), 2.77 (s, 3H). MS (ESI, m / z): 507.4 [M+H] +

[0735]

[0736] Example 38: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide

[0737]

[0738] (Step 1)

[0739] The title compound (103 mg, yield: 14.4%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0740] 1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.57 (s, 1H), 8.92 (d, J = 7.8 Hz, 1H), 8.25 (d, J = 8.0 Hz, 2H), 7.80 (dd, J = 14.9, 8.0 Hz, 2H), 7.47 (d, J = 6.6 Hz, 1H), 7.37 - 7.27 (m, 2H), 7.24 (d, J = 8.0 Hz, 1H), 7.18 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 4.23 (s, 1H), 3.59 (s, 1H), 3.51 (dd, J = 11.3, 7.4 Hz, 1H), 2.99 (d, J = 15.3 Hz, 6H), 2.75 - 2.68 (m, 2H), 2.55 (s, 2H). MS (ESI, m / z): 557.3 [M+H] +

[0741]

[0742] Example 39: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0743]

[0744] (Step 1)

[0745] The title compound (105 mg, yield: 14.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0746] 1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.62 (s, 1H), 8.92 (d, J = 7.9 Hz, 1H), 8.00 (dd, J = 8.7, 3.8 Hz, 2H), 7.45 (d, J = 7.3 Hz, 1H), 7.34 (s, 1H), 7.25 - 7.20 (m, 1H), 7.17 (dd, J = 10.1, 5.5 Hz, 3H), 7.01 - 6.91 (m, 3H), 4.22 (s, 1H), 4.08 - 4.00 (m, 1H), 3.76 (d, J = 3.9 Hz, 3H), 3.60 (d, J = 17.9 Hz, 1H), 3.48 (dt, J = 11.2, 5.3 Hz, 1H), 2.99 (s, 6H), 2.73 (dd, J = 11.4, 6.0 Hz, 1H), 2.45 - 2.34 (m, 1H). MS (ESI, m / z): 519.3 [M+H] +

[0747]

[0748] Example 40: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0749]

[0750] (Step 1)

[0751] The title compound (185 mg, yield: 24.6%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0752] 1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.61 (s, 1H), 8.92 (d, J = 8.1 Hz, 1H), 7.93 (s, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.46 (d, J = 7.5) Hz, 1H), 7.35 - 7.26 (m, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.17 (t, J = 7.7 Hz, 3H), 6.98 (t, J = 7.7 Hz, 1H), 4.21 (s, 1H), 3.57 (s, 1H), 3.49 (dd, J = 11.2, 7.2 Hz, 1H), 2.99 (s, 6H), 2.77 - 2.68 (m, 2H), 2.40 (s, 2H), 2.36 (s, 3H). MS (ESI, m / z): 503.3 [M+H] +

[0753]

[0754] Example 41: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide

[0755]

[0756] (Step 1)

[0757] The title compound (129 mg, yield: 18.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0758] 1H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 9.48 (s, 1H), 8.85 (d, J = 8.1 Hz, 1H), 8.55 (s, 1H), 8.26 (dd, J = 13.5, 7.9 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.67 (dd, J = 17.2, 8.4 Hz, 1H), 7.58 - 7.49 (m, 1H), 7.25 (d, J = 7.9 Hz, 3H), 7.18 (t, J = 7.8 Hz, 1H), 7.02 (t, J = 7.7 Hz, 1H), 4.15 (s, 1H), 3.49 (dd, J = 11.2, 7.3 Hz, 1H), 3.42 - 3.28 (m, 2H), 2.96 (d, J = 12.8 Hz, 6H), 2.73 (q, J = 8.2 Hz, 1H), 2.42 - 2.24 (m, 2H). MS (ESI, m / z): 557.3 [M+H] +

[0759]

[0760] Example 42: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[0761]

[0762] (Step 1)

[0763] The title compound (30 mg, yield: 4.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0764] 1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.62 (s, 1H), 8.93 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.51 - 7.41 (m, 1H), 7.39 - 7.26 (m, 2H), 7.23 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 7.2 Hz, 3H), 6.98 (t, J = 7.3 Hz, 2H), 4.22 (s, 1H), 3.82 (s, 3H), 3.59 (s, 1H), 3.49 (dd, J = 11.2, 7.2 Hz, 1H), 3.39 (dd, J = 14.8, 7.9 Hz, 1H), 2.99 (s, 6H), 2.71 (d, J = 8.4 Hz, 1H), 2.37 (s, 2H). MS (ESI, m / z): 519.3 [M+H] +

[0765]

[0766] Example 43: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0767]

[0768] (Step 1)

[0769] The title compound (47 mg, yield: 6.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0770] 1H NMR (500 MHz, DMSO-d6) δ 9.89 - 9.45 (m, 2H), 8.98 (d, J = 8.1 Hz, 1H), 8.29 - 8.02 (m, 1H), 7.43 (d, J = 5.3 Hz, 1H), 7.28 (s, 2H), 7.24 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.15 - 7.04 (m, 4H), 6.98 (t, J = 7.6 Hz, 1H), 4.20 (s, 1H), 3.61 (s, 2H), 3.50 (s, 1H), 2.97 (s, 6H), 2.77 - 2.69 (m, 1H), 2.60 (s, 3H), 2.37 (s, 2H). MS (ESI, m / z): 503.3 [M+H] +

[0771]

[0772] Example 44: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide

[0773]

[0774] (Step 1)

[0775] The title compound (93 mg, yield: 13.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0776] 1H NMR (500 MHz, DMSO-d6) δ 9.63 (d, J = 17.0 Hz, 1H), 8.99 (d, J = 8.1 Hz, 1H), 8.59 (dd, J = 8.3, 3.5 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.10 (h, J = 6.2 Hz, 4H), 7.02 - 6.95 (m, 1H), 4.22 (s, 1H), 3.62 (s, 1H), 3.52 (dd, J = 11.3, 7.3 Hz, 1H), 2.97 (s, 6H), 2.70 (d, J = 8.4 Hz, 1H), 2.63 (d, J = 13.3 Hz, 1H), 2.40 (d, J = 22.1 Hz, 2H). MS (ESI, m / z): 557.3 [M+H] +

[0777]

[0778] Example 45: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide

[0779]

[0780] (Step 1)

[0781] The title compound (18 mg, yield: 2.4%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0782] 1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 2H), 8.91 (s, 1H), 8.06 (d, J = 7.8 Hz, 1H), 7.47 (s, 1H), 7.41 (s, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.20 - 7.09 (m, 2H), 7.00 (dt, J = 15.3, 7.8 Hz, 3H), 4.30 - 3.96 (m, 1H), 3.65 (s, 3H), 3.47 - 3.43 (m, 2H), 2.90 (s, 6H), 2.76 - 2.69 (m, 1H), 2.39 - 2.29 (m, 1H), 1.97 (t, J = 8.9 Hz, 2H). MS (ESI, m / z): 519.3 [M+H] +

[0783]

[0784] Example 46: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide

[0785]

[0786] (Step 1)

[0787] The title compound (258 mg, yield: 35.9%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0788] 1H NMR (500 MHz, DMSO-d6) δ 10.05 (s, 1H), 9.48 (s, 1H), 8.90 (d, J = 8.0 Hz, 1H), 8.30 (d, J = 8.1 Hz, 2H), 8.24 (d, J = 8.1 Hz, 1H), 7.85 (dd, J = 16.6, 7.9 Hz, 2H), 7.57 - 7.51 (m, 2H), 7.26 (t, J = 9.2 Hz, 3H), 7.04 (t, J = 7.7 Hz, 1H), 3.72 (d, J = 11.7 Hz, 4H), 3.27 (d, J = 13.4 Hz, 4H), 3.17 - 3.06 (m, 2H), 1.34 (t, J = 7.3 Hz, 3H). MS (ES, m / z): 557.00 [M+H] +

[0789]

[0790] Example 47: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0791]

[0792] (Step 1)

[0793] The title compound (157 mg, yield: 21.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0794] 1H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 9.43 (s, 1H), 8.90 (d, J = 8.1 Hz, 1H), 8.04 (d, J = 8.5 Hz, 2H), 7.51 (s, 2H), 7.24 (t, J = 8.7) Hz, 4H), 6.95 (s, 3H), 3.78 (s, 3H), 3.71 (s, 4H), 3.24 (s, 4H), 3.16 - 3.00 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H). MS (ES, m / z): 518.99 [M+H] +

[0795]

[0796] Example 48: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0797]

[0798] (Step 1)

[0799] The title compound (254 mg, yield: 33.7%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0800] 1H NMR (500 MHz, DMSO-d6) δ 9.99 (s, 1H), 9.71 - 9.20 (m, 1H), 8.88 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 17.4 Hz, 2H), 7.88 (t, J = 9.4 Hz, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.62 - 7.58 (m, 2H), 7.37 (t, J = 7.6 Hz, 1H), 7.30 (dd, J = 13.3, 7.7 Hz, 3H), 7.06 (t, J = 7.4 Hz, 1H), 3.67 (s, 4H), 3.24 (d, J = 11.8 Hz, 4H), 3.08 (s, 2H), 2.39 (s, 3H), 1.32 (t, J = 7.3 Hz, 3H). MS (ESI, m / z): 503.05 [M+H] +

[0801]

[0802] Example 49: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide

[0803]

[0804] (Step 1)

[0805] The title compound (310 mg, yield: 43.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0806] 1H NMR (500 MHz, DMSO-d6) δ 9.99 (s, 1H), 9.50 (s, 1H), 8.88 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 14.2, 7.7 Hz, 2H), 7.62 (t, J = 7.7 Hz, 1H), 7.56 (d, J = 8.6 Hz, 2H), 7.44 (t, J = 7.5 Hz, 1H), 7.33 - 7.24 (m, 3H), 7.06 (t, J = 7.7 Hz, 1H), 3.71 (d, J = 11.8 Hz, 4H), 3.26 (d, J = 14.0 Hz, 4H), 3.09 (t, J = 12.3 Hz, 2H), 1.34 (t, J = 7.3 Hz, 3H). MS (ES, m / z): 557.00 [M+H] +

[0807]

[0808] Example 50: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[0809]

[0810] (Step 1)

[0811] The title compound (39 mg, yield: 5.3%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0812] 1H NMR (500 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.41 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.48 (d, J = 7.6) Hz, 1H), 7.32 (q, J = 7.9 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.17 (dt, J = 15.6, 8.2 Hz, 2H), 6.97 (q, J = 7.2 Hz, 2H), 3.82 (s, 3H), 3.71 (s, 4H), 3.25 (s, 4H), 3.11 (s, 2H), 1.36 (s, 3H). MS (ESI, m / z): 519.4 [M+H] +

[0813]

[0814] Example 51: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0815]

[0816] (Step 1)

[0817] The title compound (165 mg, yield: 21.9%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0818] 1H NMR (500 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.45 (s, 1H), 9.00 (d, J = 8.0 Hz, 1H), 8.20 - 8.13 (m, 1H), 7.47 - 7.42 (m, 1H), 7.30 - 7.28 (m, 2H), 7.27 - 7.21 (m, 2H), 7.17 - 7.06 (m, 4H), 6.99 (t, J = 7.6 Hz, 1H), 3.69 (s, 4H), 3.29 (s, 4H), 3.13 (s, 2H), 2.62 (s, 3H), 1.33 (s, 3H). MS (ESI, m / z): 503.4 [M+H] +

[0819]

[0820] Example 52: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide

[0821]

[0822] (Step 1)

[0823] The title compound (244 mg, yield: 34.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0824] 1H NMR (500 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.43 (s, 1H), 9.01 (d, J = 8.0 Hz, 1H), 8.66 (d, J = 8.0 Hz, 1H), 7.79 (t, J = 7.8 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.50 - 7.45 (m, 1H), 7.29 - 7.21 (m, 2H), 7.14 (dt, J = 7.3, 4.1 Hz, 3H), 6.99 (t, J = 7.7 Hz, 1H), 3.69 (s, 4H), 3.34 - 3.25 (m, 4H), 3.15 (d, J = 11.5 Hz, 2H), 1.34 (t, J = 7.3 Hz, 3H). MS (ESI, m / z): 557.3 [M+H] +

[0825]

[0826] Example 53: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide

[0827]

[0828] (Step 1)

[0829] The title compound (98 mg, yield: 13.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-2-methoxybenzenesulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0830] 1H NMR (500 MHz, DMSO-d6) δ 10.21 (s, 1H), 8.94 (d, J = 8.1 Hz, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.52 (s, 1H), 7.44 (s, 1H), 7.30 - 7.17 (m, 3H), 7.03 (dq, J = 16.1, 7.7 Hz, 3H), 3.65 (s, 8H), 3.05 (s, 4H), 2.90 (s, 2H), 2.61 (s, 2H), 1.22 (s, 3H). MS (ESI, m / z): 519.3 [M+H] +

[0831]

[0832] Example 54: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide

[0833]

[0834] (Step 1)

[0835] The title compound (140 mg, yield: 19.5%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0836] 1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.58 (s, 1H), 8.93 (d, J = 8.1 Hz, 1H), 8.25 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 7.50 - 7.44 (m, 1H), 7.32 (s, 1H), 7.26 - 7.22 (m, 1H), 7.21 - 7.11 (m, 3H), 6.98 (t, J = 7.6 Hz, 1H), 4.25 (s, 1H), 3.61 (d, J = 11.4 Hz, 2H), 3.51 (dd, J = 11.2, 7.3 Hz, 1H), 3.00 (s, 6H), 2.73 (q, J = 8.1 Hz, 1H), 2.46 - 2.36 (m, 2H). MS (ESI, m / z): 557.3 [M+H] +

[0837]

[0838] Example 55: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide

[0839]

[0840] (Step 1)

[0841] The title compound (85 mg, yield: 11.8%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0842] 1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.55 (s, 1H), 8.91 (d, J = 8.0 Hz, 1H), 8.58 (s, 1H), 8.23 ​​(d, J = 8.0 Hz, 1H), 7.80 (s, 1H), 7.66 (t, J = 8.1 Hz, 1H), 7.47 (d, J = 7.5 Hz, 1H), 7.30 (s, 2H), 7.24 (d, J = 7.9 Hz, 1H), 7.18 (q, J = 7.9 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 4.25 (s, 1H), 3.63 (s, 1H), 3.58 (s, 1H), 3.51 (dd, J = 11.2, 7.3 Hz, 1H), 3.01 (d, J = 12.6 Hz, 6H), 2.71 (q, J = 8.4 Hz, 1H), 2.48 - 2.33 (m, 2H). MS (ESI, m / z): 557.4 [M+H] +

[0843]

[0844] Example 56: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide

[0845]

[0846] (Step 1)

[0847] The title compound (68 mg, yield: 9.2%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0848] 1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.92 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 7.2 Hz, 1H), 7.45 - 7.37 (m, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.19 - 7.12 (m, 3H), 6.99 (tt, J = 19.3, 7.5 Hz, 3H), 4.04 (q, J = 7.3 Hz, 1H), 3.64 (s, 3H), 3.50 - 3.42 (m, 2H), 3.17 - 3.09 (m, 1H), 2.88 (d, J = 14.7 Hz, 6H), 2.72 (dd, J = 16.7, 6.1 Hz, 1H), 2.41 - 2.16 (m, 2H). MS (ESI, m / z): 519.3 [M+H] +

[0849]

[0850] Example 57: Preparation of N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[0851]

[0852] (Step 1)

[0853] In Step 4 of Example 1, use N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and N-(4-methylpiperazine-1-yl)aniline instead of N 1 -(2-(dimethylamino)ethyl)-N 1 The title compound (83 mg, yield: 11.7%) was obtained in the same manner as in Example 1, except that methylbenzene-1,2-diamine was used.

[0854] 1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 9.44 - 9.20 (m, 1H), 9.04 (s, 1H), 8.71 (s, 1H), 8.12 (d, J = 8.8 Hz, 2H), 7.93 (s, 2H), 7.58 (s, 2H), 7.44 (s, 1H), 7.32 (d, J = 7.9 Hz, 1H), 7.28 (s, 1H), 7.19 (t, J = 7.7 Hz, 1H), 7.13 (s, 2H), 7.00 (s, 1H), 3.88 - 3.74 (m, 2H), 3.20 - 3.11 (m, 2H), 2.98 (s, 6H), 2.79 (s, 3H). MS (ESI, m / z): 527.4 [M+H] +

[0855]

[0856] Example 58: Preparation of N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[0857]

[0858] (Step 1)

[0859] The title compound (265 mg, yield: 36.4%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-naphthalene-2-sulfonamide and 2-(4-ethylpiperazine-1-yl)aniline was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0860] 1H NMR (500 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.47 (s, 1H), 8.91 (d, J = 8.0 Hz, 1H), 8.72 (s, 1H), 8.11 (td, J = 8.7, 2.9 Hz, 2H), 7.92 (s, 2H), 7.60 - 7.55 (m, 2H), 7.44 (s, 1H), 7.32 (s, 1H), 7.27 - 7.19 (m, 2H), 7.13 (s, 2H), 7.00 (d, J = 7.6 Hz, 1H), 3.87 - 3.66 (m, 4H), 3.35 - 3.26 (m, 4H), 3.13 (s, 2H), 1.47 - 1.32 (m, 3H). MS (ESI, m / z): 539.3 [M+H] +

[0861]

[0862] Example 59: Preparation of (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[0863]

[0864] (Step 1)

[0865] The title compound (132 mg, yield: 18.1%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide and (R)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0866] 1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.64 (s, 1H), 8.91 (s, 1H), 8.71 (s, 1H), 8.16 - 8.10 (m, 1H), 8.06 (dd, J = 8.6, 1.8 Hz, 1H), 7.93 (s, 2H), 7.58 (d, J = 7.2 Hz, 2H), 7.44 (s, 1H), 7.30 (s, 1H), 7.24 (dd, J = 7.9, 1.4 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 7.13 (s, 2H), 6.98 (t, J = 7.6 Hz, 1H), 4.26 (s, 1H), 3.63 (s, 1H), 3.51 (s, 2H), 3.03 (s, 6H), 2.75 (q, J = 8.1 Hz, 1H), 2.48 - 2.32 (m, 2H). MS (ESI, m / z): 539.3 [M+H] +

[0867]

[0868] Example 60: Preparation of 4-methyl-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide

[0869]

[0870] (Step 1)

[0871] The title compound (34 mg, yield: 9.3%) was obtained in the same manner as in Example 1, except that 4-(4-methylpiperazine-1-yl)pyridine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in step 4 of Example 1.

[0872] 1H NMR (500 MHz, DMSO-d6) δ 8.58 (dd, J = 7.0, 1.9 Hz, 1H), 8.35 (d, J = 1.9 Hz, 1H), 7.90 (d, J = 7.9 Hz, 2H), 7.70 (d, J = 8.1 Hz, 1H), 7.63 - 7.56 (m, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.35 (t, J = 7.3 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 3.57 - 3.52 (m, 4H), 2.56 (t, J = 4.9 Hz, 4H), 2.29 (s, 3H), 2.27 (s, 3H). MS (ESI, m / z): 490.3 [M+H] +

[0873]

[0874] Example 61: Preparation of 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide

[0875]

[0876] (Step 1)

[0877] The title compound (54 mg, yield: 14.7%) was obtained in the same manner as in Example 1, except that 2-(4-methylpiperazine-1-yl)pyridine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in step 4 of Example 1.

[0878] 1 H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 2H), 9.14 (d, J = 8.1 Hz, 1H), 7.97 (dd, J = 13.6, 6.4 Hz, 3H), 7.49 (d, J = 7.8 Hz, 1H), 7.35 (s, 1H), 7.28 - 7.12 (m, 6H), 3.66 (s, 4H), 3.46 (s, 2H), 3.18 (s, 2H), 2.97 (s, 3H), 2.31 (s, 3H). MS (ES, m / z): 490.09 [M+H] +

[0879]

[0880] Example 62: Preparation of 4-Methoxy-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide

[0881]

[0882] (Step 1)

[0883] The title compound (9 mg, yield: 2.5%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide and 4-(4-methylpiperazine-1-yl)pyridine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0884] 1 H NMR (500 MHz, DMSO-d6) δ 8.58 (dd, J = 7.0, 1.9 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H), 7.98 - 7.93 (m, 2H), 7.71 (d, J = 8.2 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.35 (t, J = 7.5 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 3.76 (s, 3H), 3.54 (t, J = 5.0 Hz, 4H), 2.56 (t, J = 4.9 Hz, 4H), 2.27 (s, 3H). MS (ESI, m / z): 506.3 [M+H] +

[0885]

[0886] Example 63: Preparation of 4-Methoxy-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide

[0887]

[0888] (Step 1)

[0889] The title compound (36 mg, yield: 10.0%) was obtained in the same manner as in Example 1, except that in step 4 of Example 1, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide and 2-(4-methylpiperazine-1-yl)pyridine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline.

[0890] 1 H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 2H), 9.13 (dd, J = 8.0, 1.7 Hz, 1H), 8.03 (d, J = 8.6 Hz, 2H), 7.99 - 7.92 (m, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.38 (s, 1H), 7.25 - 7.14 (m, 3H), 6.94 (d, J = 8.5 Hz, 2H), 3.76 (s, 3H), 3.64 (s, 4H), 3.48 - 3.38 (m, 4H), 2.96 (s, 3H). MS (ESI, m / z): 506.3 [M+H] +

[0891]

[0892] Example 64: Preparation of N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0893]

[0894] (Step 1)

[0895] N,N-dimethyl-1-(2-nitrophenyl)piperidine-4-amine (16.9 g, yield: 95.4%) was obtained in the same manner as in Example 1, except that N,N-dimethylpiperidine-4-amine was used instead of methylpiperazine in Step 2 of Example 1.

[0896] 1H NMR (500 MHz, DMSO-d6) δ 7.79 (d, J = 8.1 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 3.21 (d, J = 11.9 Hz, 2H), 2.80 (t, J = 11.8 Hz, 2H), 2.25 - 2.21 (m, 1H), 2.19 (s, 6H), 1.81 (d, J = 12.4 Hz, 2H), 1.48 (qd, J = 11.9, 3.7 Hz, 2H). MS (ESI, m / z): 250.2 [M+H] +

[0897] (Step 2)

[0898] 1-(2-aminophenyl)-N,N-dimethylpiperidine-4-amine (10.2 g, yield: 68.8%) was obtained in the same manner as step 3 of Example 1.

[0899] 1 H NMR (500 MHz, DMSO-d6) δ 6.87 (d, J = 7.9 Hz, 1H), 6.78 (t, J = 7.5 Hz, 1H), 6.66 (d, J = 7.8 Hz, 1H), 6.52 (t, J = 7.5 Hz, 1H), 4.69 (s, 2H), 3.08 (d, J = 11.5 Hz, 2H), 2.51 - 2.45 (m, 1H), 2.21 (s, 6H), 2.16 (ddd, J = 14.7, 7.4, 3.7 Hz, 2H), 1.82 (d, J = 12.4 Hz, 2H), 1.56 (tt, J = 12.0, 5.8 Hz, 2H). MS (ESI, m / z): 220.2 [M+H] +

[0900] (Step 3)

[0901] The title compound (84.0 mg, yield: 27.2%) was obtained in the same manner as in Example 4, except that 1-(2-aminophenyl)-N,N-dimethylpiperidine-4-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in step 3 of Example 4.

[0902] 1 H NMR (500 MHz, DMSO-d6) δ 12.18 (s, 1H), 9.82 (s, 1H), 9.64 (s, 1H), 9.00 (s, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.27 (t, J = 63.0 Hz, 7H), 3.48 - 3.38 (m, 2H), 3.23 - 3.18 (m, 2H), 2.91 (s, 6H), 2.78 (t, J = 11.9 Hz, 2H), 2.31 (s, 3H), 2.08 (d, J = 11.3 Hz, 1H). MS (ES, m / z): 516.89 [M+H] +

[0903]

[0904] Example 65: Preparation of N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[0905]

[0906] (Step 1)

[0907] N,N-dimethyl-1-(1-(2-nitrophenyl)piperidin-4-yl)methaneamine (9.0 g, yield: 96.4%) was obtained in the same manner as in Example 1, except that N,N-dimethyl-1-(piperidin-4-yl)methaneamine was used instead of methylpiperazine in Step 2 of Example 1.

[0908] 1H NMR (500 MHz, DMSO-d6) δ 7.78 (dd, J = 8.1, 1.6 Hz, 1H), 7.61 - 7.52 (m, 1H), 7.29 (d, J = 8.3 Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 3.16 (dd, J) = 9.7, 6.3 Hz, 2H), 2.79 (td, J = 12.1, 2.4 Hz, 2H), 2.12 (s, 6H), 2.09 (d, J = 7.3 Hz, 2H), 1.78 - 1.72 (m, 2H), 1.60 (th, J = 11.1, 3.7 Hz, 1H), 1.19 (qd, J = 12.0, 3.9 Hz, 2H). MS (ESI, m / z): 264.2 [M+H] +

[0909] (Step 2)

[0910] 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline (4.0 g, yield: 49.6%) was obtained by the same method as in Step 3 of Example 1.

[0911] 1 H NMR (500 MHz, DMSO-d6) δ 6.88 (d, J = 7.9 Hz, 1H), 6.78 (t, J = 7.6 Hz, 1H), 6.66 (d, J = 7.9 Hz, 1H), 6.53 (t, J = 7.6 Hz, 1H), 4.66 (s, 2H), 3.02 (d, J = 11.3 Hz, 2H), 2.57 - 2.44 (m, 2H), 2.14 (s, 6H), 2.11 (d, J = 7.2 Hz, 2H), 1.77 (d, J = 12.8 Hz, 2H), 1.60 - 1.52 (m, 1H), 1.28 (t, J = 11.5 Hz, 2H). MS (ESI, m / z): 234.3 [M+H] +

[0912] (Step 3)

[0913] The title compound (80.0 mg, yield: 25.2%) was obtained in the same manner as in Example 4, except that 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in step 3 of Example 4.

[0914] 1 H NMR (500 MHz, DMSO-d6) δ 10.10 (s, 1H), 9.26 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 7.6 Hz, 2H), 7.45 (s, 1H), 7.36 - 7.04 (m, 5H), 6.96 (s, 1H), 3.25 - 3.12 (m, 2H), 3.08 - 2.96 (m, 2H), 2.85 (s, 6H), 2.75 (d, J = 11.2 Hz, 2H), 2.31 (s, 3H), 2.05 - 1.90 (m, 3H), 1.85 (s, 2H). MS (ES, m / z): 530.94 [M+H] +

[0915]

[0916] Example 66: Preparation of N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0917]

[0918] (Step 1)

[0919] The title compound (119 mg, yield: 39.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpiperidin-4-amine and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0920] 1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.96 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 7.8 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.17 - 7.06 (m, 5H), 6.92 (dd, J = 13.2, 7.9 Hz, 3H), 3.75 (s, 3H), 3.10 (d, J = 11.2 Hz, 2H), 2.65 (t, J = 11.3 Hz, 2H), 2.32 (s, 6H), 2.08 (qd, J = 11.9, 3.7 Hz, 2H), 1.81 (d, J = 11.8 Hz, 1H), 1.76 (d, J = 10.9 Hz, 2H). MS (ES, m / z): 532.97 [M+H] +

[0921]

[0922] Example 67: Preparation of N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[0923]

[0924] (Step 1)

[0925] The title compound (83.0 mg, yield: 26.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0926] 1H NMR (500 MHz, DMSO-d6) δ 10.11 (s, 1H), 9.17 (s, 1H), 8.94 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.44 (s, 1H), 7.30 (s, 1H), 7.15 (t, J = 8.3 Hz, 4H), 6.94 (s, 3H), 3.76 (s, 3H), 3.18 (s, 2H), 3.03 (d, J = 11.1 Hz, 2H), 2.85 (s, 6H), 2.74 (t, J = 11.3 Hz, 2H), 2.11 - 1.93 (m, 3H), 1.85 (s, 2H). MS (ES, m / z): 546.95 [M+H] +

[0927]

[0928] Example 68: Preparation of N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0929]

[0930] (Step 1)

[0931] The title compound (118 mg, yield: 38.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpiperidin-4-amine and N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0932] 1H NMR (500 MHz, DMSO-d6) δ 12.21 (s, 1H), 10.38 (s, 1H), 9.80 (s, 1H), 8.95 - 8.90 (m, 1H), 8.02 (s, 1H), 7.92 (s, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.64 (s, 1H), 7.47 (s, 2H), 7.27 - 7.21 (m, 3H), 7.08 (s, 1H), 3.41 - 3.32 (m, 2H), 3.16 (d, J = 11.3 Hz, 2H), 2.79 (t, J = 11.6 Hz, 7H), 2.39 (s, 3H), 2.09 (d, J = 11.3 Hz, 2H), 1.93 (d, J = 12.8 Hz, 2H). MS (ES, m / z): 516.96 [M+H] +

[0933]

[0934] Example 69: Preparation of N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[0935]

[0936] (Step 1)

[0937] The title compound (133 mg, yield: 41.8%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0938] 1H NMR (500 MHz, DMSO-d6) δ 10.08 (s, 1H), 9.27 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H), 7.36 - 7.23 (m, 2H), 7.23 - 7.04 (m, 4H), 6.96 (s, 1H), 3.17 (s, 2H), 3.02 (s, 2H), 2.85 (s, 6H), 2.73 (dd, J = 19.3, 8.7 Hz, 2H), 2.36 (s, 3H), 1.97 - 1.79 (m, 5H). MS (ES, m / z): 531.01 [M+H] +

[0939]

[0940] Example 70: Preparation of N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[0941]

[0942] (Step 1)

[0943] The title compound (165 mg, yield: 54.3%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpiperidin-4-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[0944] 1H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.67 (s, 1H), 9.03 (s, 1H), 7.76 (s, 1H), 7.57 (s, 1H), 7.46 (s, 1H), 7.30 (s, 2H), 7.17 (s, 4H), 6.96 (s, 2H), 3.82 (s, 3H), 3.46 - 3.37 (m, 2H), 3.22 (s, 2H), 2.93 (s, 6H), 2.79 (t, J = 11.9 Hz, 2H), 2.09 (d, J = 11.5 Hz, 2H), 1.94 (d, J = 14.6 Hz, 1H). MS (ESI, m / z): 533.4 [M+H] +

[0945]

[0946] Example 71: Preparation of N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[0947]

[0948] (Step 1)

[0949] The title compound (107 mg, yield: 34.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0950] 1H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 9.25 (s, 1H), 8.94 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.30 (s, 2H), 7.16 (s, 4H), 6.95 (s, 2H), 3.82 (s, 3H), 3.39 (q, J = 7.0 Hz, 1H), 3.18 (s, 2H), 3.02 (s, 2H), 2.85 (s, 6H), 2.74 (t, J = 11.4 Hz, 2H), 2.10 - 1.93 (m, 2H), 1.86 (s, 2H). MS (ESI, m / z): 547.4 [M+H] +

[0951]

[0952] Example 72: Preparation of N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0953]

[0954] (Step 1)

[0955] The title compound (54.0 mg, yield: 17.5%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpiperidin-4-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0956] 1H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 2H), 9.10 (s, 1H), 8.21 - 8.16 (m, 1H), 7.51 - 6.89 (m, 10H), 3.58 - 3.50 (m, 1H), 3.46 - 3.38 (m, 1H), 3.27 - 3.17 (m, 2H), 2.87 (s, 6H), 2.81 (t, J = 11.8 Hz, 2H), 2.66 - 2.61 (m, 3H), 2.10 (d, J = 11.7 Hz, 2H), 2.04 - 1.90 (m, 1H). MS (ESI, m / z): 517.4 [M+H] +

[0957]

[0958] Example 73: Preparation of N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[0959]

[0960] (Step 1)

[0961] The title compound (161 mg, yield: 50.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-((dimethylamino)methyl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0962] 1H NMR (500 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.23 (s, 1H), 9.01 (s, 1H), 8.19 - 8.14 (m, 1H), 7.59 - 6.87 (m, 10H), 3.22 - 2.97 (m, 4H), 2.83 (s, 6H), 2.76 (s, 2H), 2.63 (s, 2H), 1.90 (d, J = 56.8 Hz, 3H). MS (ESI, m / z): 531.4 [M+H] +

[0963]

[0964] Example 74: Preparation of 4-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0965]

[0966] (Step 1)

[0967] 1-methyl-4-(1-(2-nitrophenyl)piperidin-4-yl)piperazine (17.2 g, yield: 79.8%) was obtained in the same manner as in Example 1, except that 1-methyl-4-(piperidin-4-yl)piperazine was used instead of methylpiperazine in Step 2 of Example 1.

[0968] 1 H NMR (500 MHz, DMSO-d6) δ 7.79 (d, J = 8.1 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.08 (t, J = 7.8 Hz, 1H), 3.21 (d, J = 11.8 Hz, 2H), 2.80 (t, J = 11.9 Hz, 2H), 2.49 (s, 4H), 2.31 (m, 5H), 2.14 (s, 3H), 1.82 (d, J = 12.3 Hz, 2H), 1.56 - 1.44 (m, 2H). MS (ESI, m / z): 305.3 [M+H] +

[0969] (Step 2)

[0970] 2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)aniline (2.6 g, yield: 17.0%) was obtained by the same method as in Step 3 of Example 1.

[0971] 1 H NMR (500 MHz, CDCl3) δ 7.00 - 6.95 (m, 1H), 6.95 - 6.88 (m, 1H), 6.72 (ddd, J = 7.5, 4.4, 2.9 Hz, 2H), 3.98 (s, 2H), 3.20 (dd, J = 12.6, 3.8 Hz, 2H), 2.69 (s, 4H), 2.62 (td, J = 11.9, 2.1 Hz, 2H), 2.54 (s, 4H), 2.38 (tt, J = 11.4, 3.9 Hz, 1H), 2.32 (s, 3H), 1.98 (dt, J = 12.7, 3.0 Hz, 2H), 1.67 (qd, J = 12.0, 3.9 Hz, 2H). MS (ESI, m / z): 275.3 [M+H] +

[0972] (Step 3)

[0973] The title compound (157 mg, yield: 45.8%) was obtained in the same manner as in Example 4, except that 2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in step 3 of Example 4.

[0974] 1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.43 (s, 1H), 8.96 (d, J = 8.1 Hz, 1H), 7.92 (s, 1H), 7.83 (d, J = 7.7 Hz, 1H), 7.48 (s, 1H), 7.30 (s, 2H), 7.16 (dd, J = 14.5, 8.1 Hz, 3H), 6.98 (d, J = 8.4 Hz, 1H), 3.20 - 2.93 (m, 6H), 2.79 (s, 3H), 2.74 - 2.55 (m, 6H), 2.36 (s, 3H), 2.30 - 2.03 (m, 3H), 1.79 (s, 2H). MS (ESI, m / z): 572.4 [M+H] +

[0975]

[0976] Example 75: Preparation of 4-Methoxy-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0977]

[0978] (Step 1)

[0979] The title compound (58.0 mg, yield: 17.3%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-(4-methylpiperazine-1-yl)piperidin-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[0980] 1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.30 (s, 1H), 8.98 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 7.5 Hz, 1H), 7.33 (s, 1H), 7.14 (dd, J = 13.4, 7.6 Hz, 4H), 6.93 (d, J = 8.9 Hz, 3H), 3.75 (s, 3H), 3.21 - 2.95 (m, 8H), 2.84 - 2.62 (m, 6H), 2.28 - 2.05 (m, 4H), 1.81 (s, 2H). MS (ESI, m / z): 588.4 [M+H] +

[0981]

[0982] Example 76: Preparation of 3-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0983]

[0984] (Step 1)

[0985] The title compound (74.0 mg, yield: 21.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-(4-methylpiperazine-1-yl)piperidin-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0986] 1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.32 (s, 1H), 8.98 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 7.8 Hz, 2H), 7.44 (d, J = 7.4 Hz, 1H), 7.31 (s, 2H), 7.20 (d, J = 7.8 Hz, 2H), 7.14 (t, J = 6.6 Hz, 3H), 6.95 (t, J = 7.6 Hz, 1H), 3.23 - 2.92 (m, 8H), 2.87 - 2.60 (m, 8H), 2.29 (s, 3H), 2.24 - 2.03 (m, 2H), 1.89 - 1.70 (m, 2H). MS (ESI, m / z): 572.4 [M+H] +

[0987]

[0988] Example 77: Preparation of 2-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0989]

[0990] (Step 1)

[0991] The title compound (184 mg, yield: 53.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, 2-(4-(4-methylpiperazine-1-yl)piperidin-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[0992] 1H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.41 - 9.19 (m, 1H), 9.09 (d, J = 8.1 Hz, 1H), 8.17 (d, J = 7.0 Hz, 1H), 7.42 (t, J = 4.4 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.20 - 7.09 (m, 3H), 7.09 (s, 3H), 6.94 (t, J = 7.7 Hz, 1H), 3.24 - 2.94 (m, 8H), 2.82 - 2.68 (m, 6H), 2.61 (s, 3H), 2.39 - 2.10 (m, 4H), 1.93 - 1.71 (m, 2H). MS (ESI, m / z): 572.4 [M+H] +

[0993]

[0994] Example 78: Preparation of (S)-4-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[0995]

[0996] The title compound (7.8 mg, yield: 9%) was obtained in the same manner as in Example 4, except that 4-chloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[0997] 1H NMR (500 MHz, CDCl3) δ 9.37 (s, 1H), 8.81 (d,J= 8.1 Hz, 1H), 8.00 (d,J= 8.3 Hz, 2H), 7.73 (d,J= 8.1 Hz, 1H), 7.52 (d,J= 8.4 Hz, 2H), 7.43 (t,J= 9.0 Hz, 1H), 7.36 (t,J= 7.5 Hz, 1H), 7.30 (d,J= 17.5 Hz, 2H), 7.24 - 7.16 (m, 2H), 7.08 (t,J= 7.6 Hz, 1H), 3.29 (dd,J= 9.2, 6.7 Hz, 1H), 3.17 - 3.05 (m, 3H), 3.01 (s, 1H), 2.41 (s, 6H), 2.04-1.90 (m, 2H).

[0998]

[0999] Example 79: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-difluorobenzenesulfonamide

[1000]

[1001] (Step 1)

[1002] N-(3-chloroquinoxalin-2-yl)-3,5-difluorobenzenesulfonamide (475 mg, yield: 85%) was obtained in the same manner as in Example 1, except that 3,5-difluorobenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1003] 1 H NMR (500 MHz, DMSO-d6) δ 7.89 (dd, J = 8.3, 1.4 Hz, 1H), 7.87 - 7.81 (m, 3H), 7.78 (ddd, J = 8.4, 7.0, 1.4 Hz, 1H), 7.70 - 7.60 (m, 2H). MS (ESI, m / z): 355.1 [M+H] +

[1004] (Step 2)

[1005] The title compound (26 mg, yield: 58%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3,5-difluorobenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1006] 1 H NMR (500 MHz, DMSO-d6) δ 9.79 - 9.69 (m, 1H), 9.53 (s, 1H), 8.93 (d, J = 8.0 Hz, 1H), 7.76 - 7.68 (m, 2H), 7.53 - 7.46 (m, 1H), 7.38 - 7.30 (m, 2H), 7.26 - 7.14 (m, 4H), 6.98 (td, J = 7.6, 1.5 Hz, 1H), 4.24 - 4.19 (m, 1H), 3.57 (t, J = 5.4 Hz, 1H), 3.50 (dd, J = 11.2, 7.2 Hz, 1H), 3.43 - 3.36 (m, 1H), 3.34 - 3.27 (m, 1H), 3.00 - 2.96 (m, 6H), 2.72 (q, J = 8.2 Hz, 1H), 2.41 (d, J = 10.0 Hz, 1H). MS (ESI, m / z): 525.3 [M+H] +

[1007]

[1008] Example 80: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide

[1009]

[1010] The title compound (38 mg, yield: 47%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1011] 1H NMR (500 MHz, CDCl3) δ 9.39 (s, 1H), 8.83 (d,J= 10.0 Hz, 1H), 8.12 (d,J= 8.4 Hz, 2H), 7.70 (d,J= 8.1 Hz, 1H), 7.42 - 7.29 (m, 5H), 7.22 - 7.14 (m, 2H), 7.07 (t,J= 7.7 Hz, 1H), 3.21 (t,J= 10.0 Hz, 1H), 3.17-3.13 (m, 1H), 3.05-3.02 (m, 2H), 2.85 (t,J= 10.0 Hz, 1H), 2.31 (s, 6H), 2.03-1.96 (m, 1H), 1.90-1.82 (m, 1H).

[1012]

[1013] Example 81: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-difluorobenzenesulfonamide

[1014]

[1015] (Step 1)

[1016] N-(3-chloroquinoxalin-2-yl)-3,4-difluorobenzenesulfonamide (476 mg, yield: 85%) was obtained in the same manner as in Example 1, except that 3,4-difluorobenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1017] 1 H NMR (500 MHz, DMSO-d6) δ 8.21 (ddd,J= 9.9, 7.4, 2.3 Hz, 1H), 8.06 (d,J= 9.3 Hz, 1H), 7.89 (d,J= 8.4 Hz, 2H), 7.78 (ddd,J= 8.5, 7.0, 1.4 Hz, 1H), 7.75 - 7.70 (m, 1H), 7.70 - 7.65 (m, 1H). MS (ESI, m / z): 355.1 [M+H] +

[1018] (Step 2)

[1019] The title compound (30 mg, yield: 63%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3,4-difluorobenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1020] 1 H NMR (500 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.83 (d, J = 8.0 Hz, 1H), 8.17 (d, J = 2.4 Hz, 1H), 7.91 (dd, J = 8.5, 2.2 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 8.3 Hz, 1H), 7.46 - 7.39 (m, 1H), 7.35 (t, J = 5.3 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.08 (t, J = 7.8 Hz, 1H), 3.21 (dq, J = 15.3, 7.8 Hz, 2H), 3.08 (m, 2H), 2.90 (m, 1H), 2.37 (s, 6H), 2.04 (m, 1H), 1.92 (s, 1H) MS (ESI, m / z): 525.3 [M+H] +

[1021]

[1022] Example 82: Preparation of (S)-3,4-Dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1023]

[1024] (Step 1)

[1025] 3,4-dichloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide (276 mg, yield: 85%) was obtained in the same manner as in Example 1, except that 3,4-dichlorobenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1026] 1 H NMR (500 MHz, DMSO-d6) δ 8.36 (d,J= 2.1 Hz, 1H), 8.11 (dd,J= 8.5, 2.1 Hz, 1H), 7.90 (t,J= 8.7 Hz, 1H), 7.85 (d,J= 8.3 Hz, 1H), 7.79 (ddd,J= 8.4, 7.1, 1.4 Hz, 1H), 7.67 (t,J= 7.6 Hz, 1H). MS (ESI, m / z): 355.1 [M+H] +

[1027] (Step 2)

[1028] The title compound (29 mg, yield: 58%) was obtained in the same manner as in Example 4, except that 3,4-dichloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1029] 1 H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.49 (s, 1H), 8.92 (dd, J = 8.1, 1.5 Hz, 1H), 8.06 (d, J = 2.1 Hz, 2H), 7.68 (t, J = 2.0 Hz, 1H), 7.49 (dd, J = 7.4, 2.0 Hz, 1H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 7.25 - 7.15 (m, 4H), 6.98 (td, J = 7.6, 1.5 Hz, 1H), 4.22 (dq, J = 8.8, 4.3 Hz, 1H), 3.55 (td, J = 8.8, 3.1 Hz, 1H), 3.50 (dd, J = 11.3, 7.3 Hz, 1H), 3.35 - 3.26 (m, 1H), 2.99 (s, 6H), 2.75 - 2.68 (m, 1H), 2.50 - 2.36 (m, 2H). MS (ESI, m / z): 557.3 [M+H] +

[1030]

[1031] Example 83: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1032]

[1033] The title compound (32 mg, yield: 30%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1034] 1 H NMR (500 MHz, CDCl3) δ 9.42 (s, 1H), 8.82 (d,J= 8.1 Hz, 1H), 8.06 (d,J= 7.7 Hz, 2H), 7.72 (d,J= 8.1 Hz, 1H), 7.62 (t,J= 7.5 Hz, 1H), 7.56 (t,J= 7.7 Hz, 2H), 7.41 (t,J= 6.5 Hz, 1H), 7.34 (t,J= 6.5 Hz, 1H), 7.30 (s, 1H), 7.18 (d,J= 8.4 Hz, 2H), 7.08 (t,J= 7.7 Hz, 1H), 3.30 (t,J= 7.7 Hz, 1H), 3.15-3.10 (m, 1H), 3.07-2.92 (m, 3H), 2.99 - 2.94 (m, 1H), 2.35 (s, 6H), 2.01-1.93 (m, 1H), 1.90-1.82 (m, 1H).

[1035]

[1036] Example 84: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-difluoroquinoxalin-2-yl)-4-methylbenzenesulfonamide

[1037]

[1038] The title compound (27 mg, yield: 27%) was obtained in the same manner as in Example 1, except that 2,3-dichloro-6,7-difluoroquinoxaline was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1 and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1039] 1 H NMR (500 MHz, CDCl3) δ 9.51 (s, 1H), 8.76 (d,J= 8.0 Hz, 1H), 7.95 (d,J= 8.0 Hz, 2H), 7.45 (d,J= 9.0 Hz, 1H), 7.31-7.28 (m, 2H), 7.22-7.13 (m, 3H), 7.44 (t,J= 7.5 Hz, 1H), 3.37 (s, 1H), 3.25-3.10 (m, 4H), 2.60 (s, 6H), 2.42 (s, 3H), 2.18 (s, 1H), 2.06 (s, 1H).

[1040]

[1041] Example 85: Preparation of (S)-N-(6,7-dichloro-3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1042]

[1043] The title compound (42 mg, yield: 42%) was obtained in the same manner as in Example 1, except that 2,3,6,7-tetrachloroquinoxaline was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1 and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1044] 1H NMR (500 MHz, CDCl3) δ 9.59 (s, 1H), 8.79 (d,J= 8.0 Hz, 1H), 7.95 (d,J= 8.0 Hz, 2H), 7.74 (s, 1H), 7.47 (s, 1H), 7.31-7.28 (m, 2H), 7.20 (t,J= 7.5 Hz, 1H), 7.12 (t,J= 8.0 Hz, 1H), 7.05 (t,J= 7.5 Hz, 1H), 3.41 (s, 2H), 3.31 (s, 1H), 3.23 (s, 1H), 3.13-3.08 (m, 2H), 2.65 (s, 6H), 2.42 (s, 3H), 2.21 (s, 1H), 2.10 (s, 1H).

[1045]

[1046] Example 86: Preparation of (S)-3,5-Dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1047]

[1048] (Step 1)

[1049] 3,5-dichloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide (269 mg, yield: 82%) was obtained in the same manner as in Example 1, except that 3,5-dichlorobenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1050] 1 H NMR (500 MHz, DMSO-d6) δ 8.13 (d, J = 1.9 Hz, 2H), 7.95 (t, J = 1.9 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.84 - 7.76 (m, 2H), 7.67 (td, J = 7.2, 2.2 Hz, 1H). MS (ESI, m / z): 388.2 [M+H] +

[1051] (Step 2)

[1052] The title compound (34 mg, yield: 60%) was obtained in the same manner as in Example 4, except that 3,5-dichloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1053] 1 H NMR (500 MHz, CDCl3) δ 9.40 (s, 1H), 8.83 (d, J = 8.1 Hz, 1H), 7.96 (ddd, J = 9.6, 7.2, 2.4 Hz, 1H), 7.89 - 7.83 (m, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.46 - 7.39 (m, 1H), 7.39 - 7.30 (m, 3H), 7.19 (d, J = 8.0 Hz, 2H), 7.11 - 7.05 (m, 1H), 3.40 (t, J = 7.2 Hz, 1H), 3.21 (h, J) = 7.0 Hz, 2H), 3.07 (dt, J = 14.8, 10.3 Hz, 2H), 2.89 (d, J = 9.0 Hz, 1H), 2.43 - 2.37 (m, 1H), 2.36 (s, 6H), 2.11 - 1.99 (m, 2H), 1.91 (dq, J = 13.3, 7.2 Hz, 1H). MS (ESI, m / z): 557.3 [M+H] +

[1054]

[1055] Example 87: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1056]

[1057] (Step 1)

[1058] (S)-N,N-dimethyl-1-(3-methyl-2-nitrophenyl)pyrrolidine-3-amine (4.7 g, yield: 97.5%) was obtained in the same manner as in Example 1, except that (S)-N,N-dimethyl-1-(3-methyl-2-nitrophenyl)pyrrolidine-3-amine was used instead of methylpiperazine and 1-fluoro-3-methyl-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1.

[1059] 1 H NMR (500 MHz, DMSO-d6) δ 7.54 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 3.23 - 3.07 (m, 4H), 2.99 (t, J = 7.9) Hz, 1H), 2.78 (p, J = 7.5 Hz, 1H), 2.31 (s, 3H), 2.14 (s, 6H), 2.07 (dtd, J = 10.1, 6.9, 3.0 Hz, 1H), 1.76 (dq, J = 11.7, 8.8 Hz, 1H). MS (ESI, m / z): 250.2 [M+H] +

[1060] (Step 2)

[1061] (S)-1-(2-amino-3-methylphenyl)-N,N-dimethylpyrrolidine-3-amine (1.0 g, yield: 24.4%) was obtained by the same method as in Step 3 of Example 1.

[1062] 1H NMR (500 MHz, DMSO-d6) δ 6.73 (t, J = 7.6 Hz, 1H), 6.48 (d, J = 7.9 Hz, 1H), 6.32 (d, J = 7.4 Hz, 1H), 4.85 (s, 2H), 3.14 (q, J = 7.9 Hz, 3H), 3.01 (t, J = 7.6 Hz, 1H), 2.78 (p, J = 6.9 Hz, 1H), 2.17 (s, 6H), 2.15 (s, 3H), 2.08 - 2.01 (m, 1H), 1.88 (dq, J = 12.1, 8.2 Hz, 1H). MS (ESI, m / z): 220.2 [M+H] +

[1063] (Step 3)

[1064] The title compound (15.0 mg, yield: 6.5%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1065] 1 H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.70 (s, 1H), 8.84 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 7.9 Hz, 2H), 7.48 - 7.43 (m, 1H), 7.33 (s, 1H), 7.22 (d, J = 7.9 Hz, 2H), 7.16 (q, J = 6.3 Hz, 3H), 6.78 (d, J = 7.7 Hz, 1H), 3.63 - 3.55 (m, 1H), 3.49 - 3.39 (m, 2H), 3.30 - 3.20 (m, 2H), 2.97 (s, 6H), 2.50 - 2.42 (m, 2H), 2.33 (s, 3H), 2.30 (s, 3H). MS (ESI, m / z): 517.3 [M+H] +

[1066]

[1067] Example 88: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1068]

[1069] (Step 1)

[1070] The title compound (8.0 mg, yield: 3.5%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4, and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1071] 1 H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 1H), 8.84 (d, J = 8.2 Hz, 1H), 8.03 - 7.97 (m, 2H), 7.42 - 7.32 (m, 2H), 7.34 (s, 1H), 7.16 (q, J = 7.4 Hz, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 7.6 Hz, 1H), 3.76 (s, 3H), 3.60 (d, J = 12.4 Hz, 1H), 3.50 - 3.24 (m, 4H), 2.97 (s, 6H), 2.33 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1072]

[1073] Example 89: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[1074]

[1075] (Step 1)

[1076] The title compound (13.0 mg, yield: 5.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide.

[1077] 1 H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.72 (s, 1H), 8.84 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 7.6) Hz, 1H), 7.33 - 7.26 (m, 2H), 7.22 (d, J = 7.5 Hz, 1H), 7.16 (t, J = 7.7 Hz, 3H), 6.78 (d, J = 7.6 Hz, 1H), 3.60 (t, J = 10.7 Hz, 1H), 3.50 - 3.25 (m, 4H), 2.97 (s, 6H), 2.62 - 2.44 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1078]

[1079] Example 90: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1080]

[1081] (Step 1)

[1082] The title compound (12.0 mg, yield: 5.3%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[1083] 1 H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.71 (s, 1H), 8.85 (d, J = 8.1 Hz, 1H), 7.75 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.47 (d, J = 7.6) Hz, 1H), 7.32 (t, J = 8.0 Hz, 2H), 7.17 (q, J = 9.1 Hz, 3H), 6.98 (d, J = 7.9 Hz, 1H), 6.78 (d, J = 7.5 Hz, 1H), 4.03 (q, J = 7.2 Hz, 1H), 3.81 (s, 3H), 3.60 (t, J = 8.6 Hz, 1H), 3.51 - 3.24 (m, 5H), 2.97 (s, 6H), 2.33 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1084]

[1085] Example 91: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1086]

[1087] (Step 1)

[1088] The title compound (33.0 mg, yield: 14.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1089] 1 H NMR (500 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.76 (s, 1H), 8.87 (d, J = 8.0 Hz, 1H), 8.19 - 8.14 (m, 1H), 7.45 - 7.41 (m, 1H), 7.29 (s, 2H), 7.20 - 7.06 (m, 5H), 6.79 (d, J = 7.6 Hz, 1H), 3.59 (s, 1H), 3.32 - 3.27 (m, 2H), 2.94 (s, 6H), 2.33 (s, 3H), 2.18 (t, J = 8.1 Hz, 2H), 2.01 - 1.85 (m, 2H). MS (ESI, m / z): 517.4 [M+H] +

[1090]

[1091] Example 92: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[1092]

[1093] (Step 1)

[1094] The title compound (18.0 mg, yield: 8.0%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide.

[1095] 1 H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.84 (d, J = 8.0 Hz, 1H), 8.69 (s, 1H), 8.14 - 8.09 (m, 1H), 8.06 (dd, J = 8.6, 1.9 Hz, 1H), 7.90 (d, J = 8.5 Hz, 2H), 7.57 (dd, J = 6.3, 3.1 Hz, 2H), 7.44 - 7.38 (m, 1H), 7.26 (s, 1H), 7.15 (t, J = 7.9 Hz, 1H), 7.10 (s, 3H), 6.78 (d, J = 7.5 Hz, 1H), 3.64 (s, 1H), 3.32 - 3.27 (m, 2H), 3.00 (s, 6H), 2.34 (s, 3H), 2.18 (t, J = 8.2 Hz, 2H), 1.95 - 1.86 (m, 2H). MS (ESI, m / z): 553.4 [M+H] +

[1096]

[1097] Example 93: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1098]

[1099] (Step 1)

[1100] The title compound (136 mg, yield: 18.3%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1101] 1 H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.63 (s, 1H), 8.93 (d, J = 7.6 Hz, 1H), 7.75 (s, 1H), 7.56 (d, J = 7.5 Hz, 1H), 7.46 (d, J = 7.4 Hz, 1H), 7.30 (s, 2H), 7.22 (d, J = 7.8 Hz, 1H), 7.17 (t, J = 8.0 Hz, 3H), 6.97 (d, J = 10.4 Hz, 2H), 4.23 (s, 1H), 3.81 (d, J = 2.5 Hz, 3H), 3.60 (s, 1H), 3.48 (t, J = 9.0 Hz, 1H), 3.42 - 3.37 (m, 0H), 2.99 (s, 7H), 2.70 (s, 2H), 2.42 (s, 1H). MS (ESI, m / z): 519.3 [M+H] +

[1102]

[1103] Example 94: Preparation of (S)-5-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1104]

[1105] (Step 1)

[1106] 5-chloro-N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide (331 mg, yield: 93%) was obtained in the same manner as in Example 1, except that 5-chloro-2-methylbenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1107] 1 H NMR (500 MHz, DMSO-d6) δ 8.19 (d, J = 2.5 Hz, 1H), 7.86 (d, J = 8.2 Hz, 1H), 7.80 - 7.70 (m, 2H), 7.66 - 7.57 (m, 2H), 7.43 (d, J = 8.2 Hz, 1H), 2.68 (s, 3H). MS (ESI, m / z): 368.1 [M+H] +

[1108] (Step 2)

[1109] The title compound (45 mg, yield: 47%) was obtained in the same manner as in Example 4, except that 5-chloro-N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1110] 1 H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 9.61 (s, 1H), 8.96 (dd, J = 8.0, 1.5 Hz, 1H), 8.20 (d, J = 2.4 Hz, 1H), 7.47 - 7.42 (m, 1H), 7.35 (dd, J = 8.2, 2.5 Hz, 1H), 7.24 (dd, J = 8.0, 1.5 Hz, 1H), 7.22 - 7.07 (m, 5H), 6.98 (td, J = 7.6, 1.5 Hz, 1H), 4.20 (s, 1H), 3.60 (s, 1H), 3.51 (dd, J = 11.3, 7.3 Hz, 1H), 3.40 - 3.36 (m, 3H), 2.98 (s, 7H), 2.69 (q, J = 8.1 Hz, 1H), 2.54 (s, 3H), 2.44 - 2.34 (m, 1H). MS (ESI, m / z): 537.2 [M+H] +

[1111]

[1112] Example 95: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-5-fluoro-2-methylbenzenesulfonamide

[1113]

[1114] (Step 1)

[1115] N-(3-chloroquinoxalin-2-yl)-5-fluoro-2-methylbenzenesulfonamide (326 mg, yield: 91%) was obtained in the same manner as in Example 1, except that 5-fluoro-2-methylbenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1116] 1 H NMR (500 MHz, DMSO-d6) δ 7.96 (dd,J= 9.0, 2.6 Hz, 1H), 7.86 (d,J= 8.2 Hz, 1H), 7.74 (t,J= 7.6 Hz, 1H), 7.62 (t,J= 7.7 Hz, 1H), 7.48 - 7.40 (m, 2H), 7.15 - 7.05 (m, 1H). 2.66 (s, 3H). MS (ESI, m / z): 352.1 [M+H] +

[1117] (Step 2)

[1118] The title compound (52 mg, yield: 61%) was obtained in the same manner as in Example 4, except that 5-fluoro-N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1119] 1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.63 (s, 1H), 8.97 (d, J = 8.0 Hz, 1H), 7.91 (dd, J = 9.5, 2.7 Hz, 1H), 7.44 (dd, J = 6.5, 3.3 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.22 - 7.04 (m, 6H), 6.98 (t, J = 7.6 Hz, 1H), 4.20 (s, 1H), 3.68 - 3.54 (m, 1H), 3.51 (dd, J = 11.3, 7.2 Hz, 1H), 3.38 (d, J = 2.9 Hz, 1H), 2.98 (s, 6H), 2.69 (dd, J = 10.1, 6.9 Hz, 1H), 2.54 (s, 3H), 2.50 - 2.48 (m, 1H), 2.45 - 2.30 (m, 1H). MS (ESI, m / z): 521.4 [M+H] +

[1120]

[1121] Example 96: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide

[1122]

[1123] (Step 1)

[1124] N-(3-chloroquinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide (326 mg, yield: 91%) was obtained in the same manner as in Example 1, except that 3,5-dimethylbenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1125] 1H NMR (500 MHz, DMSO-d6) δ 7.89 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.83 - 7.75 (m, 3H), 7.68 (t, J = 7.8 Hz, 1H), 7.29 (s, 1H).MS (ESI, m / z): 348.2 [M+H] +

[1126]

[1127] (Step 2)

[1128] The title compound (42 mg, yield: 45%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1129] 1 H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.59 (s, 1H), 8.91 (d, J = 8.0 Hz, 1H), 7.69 (s, 2H), 7.46 (d, J = 7.7 Hz, 1H), 7.32 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.17 (t, J = 7.8 Hz, 2H), 7.04 (s, 1H), 6.97 (t, J = 7.7 Hz, 1H), 4.21 (s, 1H), 3.60 - 3.54 (m, 1H), 3.48 (dd, J = 11.1, 7.2 Hz, 1H), 2.97 (s, 6H), 2.74 (q, J = 8.2 Hz, 1H), 2.56 - 2.53 (m, 1H), 2.45 - 2.34 (m, 1H), 2.31 (s, 6H), 2.33 - 2.29 (m, 1H) MS (ESI, m / z): 517.2 [M+H] +

[1130]

[1131] Example 97: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1132]

[1133] (Step 1)

[1134] (S)-N,N-dimethyl-1-(4-methyl-2-nitrophenyl)pyrrolidine-3-amine (4.7 g, yield: 97.5%) was obtained in the same manner as in Example 1, except that (S)-N,N-dimethyl-1-(4-methyl-2-nitrophenyl)pyrrolidine-3-amine was used instead of methylpiperazine and 1-fluoro-4-methyl-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1.

[1135] 1 H NMR (500 MHz, DMSO-d6) δ 7.64 (d, J = 8.4 Hz, 1H), 6.87 (s, 1H), 6.60 (d, J = 8.4 Hz, 1H), 3.38 - 3.29 (m, 1H), 3.16 - 3.04 (m, 3H), 2.71 (ddd, J = 15.1, 9.1, 6.5 Hz, 1H), 2.32 (s, 3H), 2.18 (s, 6H), 2.12 (dtd, J = 12.2, 6.3, 2.0 Hz, 1H), 1.80 - 1.69 (m, 1H). MS (ESI, m / z): 250.2 [M+H] +

[1136] (Step 2)

[1137] (S)-1-(2-amino-4-methylphenyl)-N,N-dimethylpyrrolidine-3-amine (4.0 g, yield: 96.7%) was obtained by the same method as in Step 3 of Example 1.

[1138] 1H NMR (500 MHz, DMSO-d6-d6) δ 6.87 (s, 1H), 6.60 (d, J = 8.4 Hz, 1H), 6.54 (s, 1H), 4.35 (s, 2H), 3.38 - 3.29 (m, 1H), 3.13 - 3.05 (m, 3H), 2.89 - 2.82 (m, 1H), 2.32 (s, 3H), 2.17 (s, 6H), 2.05 - 1.95 (m, 1H), 1.80 - 1.66 (m, 1H). MS (ESI, m / z): 220.2 [M+H] +

[1139] (Step 3)

[1140] The title compound (50.0 mg, yield: 16.1%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1141] 1 H NMR (500 MHz, DMSO-d6-d6) δ 9.69 (s, 1H), 9.49 (s, 1H), 8.76 (d, J = 8.1 Hz, 1H), 7.93 (d, J = 7.9 Hz, 2H), 7.42 (d, J = 7.3 Hz, 1H), 7.27 (d, J = 7.9 Hz, 1H), 7.20 (d, J = 8.1 Hz, 2H), 7.14 (s, 2H), 7.03 (s, 1H), 6.97 (d, J = 8.1 Hz, 1H), 4.19 (s, 1H), 3.54 (s, 1H), 3.45 (dd, J = 11.2, 7.2 Hz, 1H), 2.97 (s, 6H), 2.72 (d, J = 8.8 Hz, 2H), 2.36 (s, 1H), 2.32 (d, J = 9.7 Hz, 1H), 2.29 (d, J = 2.6 Hz, 6H). MS (ESI, m / z): 517.4 [M+H] +

[1142]

[1143] Example 98: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1144]

[1145] (Step 1)

[1146] The title compound (78.0 mg, yield: 25.5%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1147] 1 H NMR (500 MHz, DMSO-d6) δ 9.49 (s, 1H), 8.76 (d, J = 8.2 Hz, 1H), 8.09 (t, J = 9.6 Hz, 1H), 7.99 (d, J = 8.6 Hz, 2H), 7.54 (s, 1H), 7.42 (d, J = 7.7 Hz, 1H), 7.31 (s, 1H), 7.13 (d, J = 8.7 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 6.95 (dt, J = 17.2, 8.7 Hz, 3H), 4.19 (s, 1H), 3.81 (s, 1H), 3.77 (s, 1H), 3.75 (s, 3H), 3.55 (s, 1H), 3.45 (dd, J = 11.2, 7.3 Hz, 1H), 2.97 (s, 6H), 2.72 (d, J = 11.4 Hz, 2H), 2.29 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1148]

[1149] Example 99: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[1150]

[1151] (Step 1)

[1152] The title compound (71.0 mg, yield: 23.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide.

[1153] 1 H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.48 (s, 1H), 8.75 (d, J = 8.2 Hz, 1H), 7.93 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 7.4 Hz, 1H), 7.32 - 7.27 (m, 2H), 7.21 (d, J = 7.5 Hz, 1H), 7.17 - 7.12 (m, 2H), 7.03 (s, 1H), 6.97 (d, J = 8.2 Hz, 1H), 4.19 (s, 1H), 3.54 (s, 2H), 3.46 (dd, J = 11.1, 7.2 Hz, 1H), 2.97 (s, 6H), 2.73 (q, J = 8.6 Hz, 1H), 2.42 - 2.38 (m, 2H), 2.35 (s, 3H), 2.29 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1154]

[1155] Example 100: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1156]

[1157] (Step 1)

[1158] The title compound (75.0 mg, yield: 24.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[1159] 1 H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.49 (s, 1H), 8.77 (d, J = 8.2 Hz, 1H), 7.75 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 7.4 Hz, 1H), 7.31 (t, J = 8.0 Hz, 2H), 7.16 (d, J = 6.3 Hz, 2H), 7.03 (s, 1H), 6.97 (d, J = 8.3 Hz, 2H), 4.19 (s, 1H), 3.83 (s, 1H), 3.81 (s, 3H), 3.55 (s, 1H), 3.46 (dd, J = 11.2, 7.2 Hz, 1H), 3.39 - 3.33 (m, 1H), 2.97 (s, 6H), 2.71 (d, J = 8.7 Hz, 1H), 2.44 - 2.36 (m, 1H), 2.29 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1160]

[1161] Example 101: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1162]

[1163] (Step 1)

[1164] The title compound (77.0 mg, yield: 24.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1165] 1 H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.55 (s, 1H), 8.81 (s, 1H), 8.16 - 8.11 (m, 1H), 7.41 (s, 1H), 7.28 (s, 2H), 7.15 (s, 1H), 7.12 - 7.07 (m, 3H), 7.05 (s, 1H), 6.98 (d, J = 8.3 Hz, 1H), 4.18 (s, 1H), 3.58 (s, 1H), 3.47 (t, J = 9.1 Hz, 1H), 2.96 (s, 6H), 2.73 (s, 2H), 2.63 (d, J = 10.5 Hz, 1H), 2.59 (s, 3H), 2.47 - 2.34 (m, 1H), 2.30 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1166]

[1167] Example 102: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[1168]

[1169] (Step 1)

[1170] The title compound (123 mg, yield: 41.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide.

[1171] 1 H NMR (500 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.84 (s, 1H), 8.75 (d, J = 8.2 Hz, 1H), 8.70 (s, 1H), 8.11 (dd, J = 9.9, 4.5 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.91 (d, J = 7.9 Hz, 2H), 7.67 (q, J = 7.3 Hz, 1H), 7.57 (p, J = 5.3 Hz, 2H), 7.41 (d, J = 7.0 Hz, 1H), 7.34 - 7.25 (m, 2H), 7.18 (q, J = 7.8 Hz, 1H), 7.11 (dq, J = 9.4, 5.1 Hz, 2H), 6.97 (d, J = 8.2 Hz, 1H), 4.20 (s, 1H), 3.56 (s, 1H), 3.48 (dd, J = 11.2, 7.2 Hz, 1H), 3.36 (s, 1H), 3.00 (s, 6H), 2.75 (q, J = 8.1 Hz, 1H), 2.44 - 2.35 (m, 2H), 2.29 (s, 3H). MS (ESI, m / z): 553.4 [M+H] +

[1172]

[1173] Example 103: Preparation of N-methyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide

[1174]

[1175] The title compound (46 mg, yield: 42%) was obtained in the same manner as in Example 1, except that N-methylpyrrolidine-3-carboxamide was used instead of 1-methylpiperazine in Step 2 of Example 1 and 1-(2-aminophenyl)-N-methylpyrrolidine-3-carboxamide was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1176] 1 H NMR (500 MHz, CDCl3) δ 11.83 (s, 1H), 9.46 (s, 1H), 8.79 (d,J= 8.1 Hz, 1H), 7.90 (d,J= 8.0 Hz, 2H), 7.73 (d,J= 8.0 Hz, 1H), 7.42 (t,J= 6.5 Hz, 1H), 7.36-7.33 (m, 3H), 7.33 - 7.28 (m, 1H), 7.20-7.18 (m, 2H), 7.12 - 7.05 (m, 1H), 7.09 (t,J= 7.8 Hz, 1H), 6.44 (s, 1H), 3.60 (t,J= 8.2 Hz, 1H), 3.37-3.32 (m, 1H), 3.25 - 3.17 (m, 1H), 3.13-3.08 (m, 1H), 2.90 - 2.88 (m, 1H), 2.85 (d,J= 4.5 Hz, 3H), 2.44 (s, 3H), 2.32 - 2.25 (m, 1H), 2.16 - 2.09 (m, 1H).

[1177]

[1178] Example 104: Preparation of N,N-dimethyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide

[1179]

[1180] The title compound (34 mg, yield: 31%) was obtained in the same manner as in Example 1, except that pyrrolidine-3-carboxylic acid dimethylamide was used instead of methylpiperazine in Step 2 of Example 1 and 1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-carboxamide was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1181] 1 H NMR (500 MHz, CDCl3) δ 11.78 (s, 1H), 9.66 (s, 1H), 8.82 (d,J= 8.1 Hz, 1H), 7.91 (d,J= 8.0 Hz, 2H), 7.72 (d,J= 8.0 Hz, 1H), 7.40 (t,J= 7.5 Hz, 1H), 7.35 - 7.17 (m, 6H), 7.08 (t,J= 7.5 Hz, 1H), 3.50-3.40 (m, 2H), 3.22 (t,J= 9.2 Hz, 1H), 3.13-3.04 (m, 2H), 3.10 (s, 3H), 3.00 (s, 3H), 2.43 (s, 3H), 2.26-2.20 (m, 1H), 2.14-2.08 (m, 1H).

[1182]

[1183] Example 105: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1184]

[1185] (Step 1)

[1186] (S)-N,N-dimethyl-1-(5-methyl-2-nitrophenyl)pyrrolidine-3-amine (4.7 g, yield: 97.5%) was obtained in the same manner as in Example 1, except that (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine and 2-fluoro-4-methyl-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1.

[1187] 1H NMR (500 MHz, DMSO-d6) δ 7.55 (s, 1H), 7.30 (d, J = 8.6 Hz, 1H), 6.97 (d, J = 8.7 Hz, 1H), 3.36 - 3.27 (m, 1H), 3.08 (dd, J = 10.1, 5.4 Hz, 3H), 2.71 (p, J = 7.1 Hz, 1H), 2.25 (s, 3H), 2.17 (s, 6H), 2.12 (dt, J = 11.6, 6.1 Hz, 1H), 1.80 - 1.69 (m, 1H). MS (ESI, m / z): 250.2 [M+H] +

[1188] (Step 2)

[1189] (S)-1-(2-amino-5-methylphenyl)-N,N-dimethylpyrrolidine-3-amine (4.0 g, yield: 96.7%) was obtained by the same method as in Step 3 of Example 1.

[1190] 1 H NMR (500 MHz, DMSO-d6) δ 6.76 (d, J = 7.9 Hz, 1H), 6.46 (d, J = 2.0 Hz, 1H), 6.32 (dd, J = 7.9, 2.0 Hz, 1H), 4.52 (s, 2H), 3.10 (dt, J = 9.1, 7.1 Hz, 1H), 3.02 (h, J = 4.0 Hz, 1H), 2.80 (dtd, J = 16.9, 8.4, 6.0 Hz, 3H), 2.15 (s, 6H), 2.12 (s, 3H), 2.00 (ddd, J = 15.0, 7.6, 4.1 Hz, 1H), 1.71 (ddt, J = 12.2, 8.4, 6.3 Hz, 1H). MS (ESI, m / z): 220.2 [M+H] +

[1191] (Step 3)

[1192] The title compound (94.0 mg, yield: 30.4%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1193] 1 H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.77 (s, 1H), 7.94 (d, J = 7.9 Hz, 2H), 7.51 - 7.44 (m, 1H), 7.34 (s, 1H), 7.22 (d, J = 8.4 Hz, 3H), 7.16 (d, J = 6.6 Hz, 2H), 7.11 (d, J = 8.1 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 4.17 (s, 1H), 3.49 (s, 2H), 3.43 (dd, J = 11.1, 7.3) Hz, 1H), 3.33 - 3.27 (m, 1H), 2.97 (s, 6H), 2.71 (dq, J = 16.5, 8.2 Hz, 1H), 2.36 (s, 1H), 2.34 (s, 3H), 2.30 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1194]

[1195] Example 106: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1196]

[1197] (Step 1)

[1198] The title compound (89.0 mg, yield: 29.3%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1199] 1 H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 9.58 (s, 1H), 8.76 (s, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.50 - 7.45 (m, 1H), 7.40 - 7.36 (m, 1H), 7.18 (s, 2H), 7.11 (d, J = 8.0 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 7.9 Hz, 1H), 4.16 (s, 1H), 3.77 (s, 3H), 3.53 - 3.39 (m, 2H), 3.32 - 3.26 (m, 1H), 2.96 (s, 6H), 2.70 (q, J = 8.3 Hz, 1H), 2.38 - 2.35 (m, 2H), 2.34 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1200]

[1201] Example 107: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[1202]

[1203] (Step 1)

[1204] The title compound (89.0 mg, yield: 28.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide.

[1205] 1 H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.78 (s, 1H), 7.93 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 6.5 Hz, 1H), 7.29 (s, 3H), 7.22 (s, 1H), 7.16 (s, 2H), 7.11 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 4.21 (s, 1H), 3.65 - 3.62 (m, 1H), 3.52 (s, 2H), 3.43 (dd, J = 11.1, 7.2 Hz, 1H), 3.30 - 3.25 (m, 1H), 2.98 (s, 6H), 2.70 (q, J = 8.1 Hz, 1H), 2.36 (s, 3H), 2.34 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1206]

[1207] Example 108: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1208]

[1209] (Step 1)

[1210] The title compound (143 mg, yield: 47.0%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[1211] 1 H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.79 (s, 1H), 7.74 (s, 1H), 7.56 (d, J = 7.3 Hz, 1H), 7.47 (s, 1H), 7.32 (s, 2H), 7.17 (s, 3H), 7.10 (d, J = 7.1 Hz, 1H), 6.97 (s, 1H), 6.78 (s, 1H), 4.19 (s, 1H), 3.81 (d, J = 5.1 Hz, 3H), 3.51 (s, 1H), 3.44 (d, J = 10.8) Hz, 1H), 2.97 (s, 6H), 2.67 (s, 1H), 2.34 (d, J = 5.3 Hz, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1212]

[1213] Example 109: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1214]

[1215] (Step 1)

[1216] The title compound (113 mg, yield: 36.4%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1217] 1 H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.82 (s, 1H), 8.17 - 8.11 (m, 1H), 7.44 (s, 1H), 7.28 (s, 2H), 7.16 - 7.07 (m, 4H), 6.78 (d, J = 7.9 Hz, 1H), 4.16 (s, 1H), 3.52 (s, 1H), 3.45 (d, J = 10.2 Hz, 1H), 2.95 (s, 6H), 2.74 - 2.66 (m, 1H), 2.59 (d, J = 4.4 Hz, 3H), 2.48 - 2.39 (m, 3H), 2.34 (s, 3H). MS (ESI, m / z): 557.4 [M+H] +

[1218]

[1219] Example 110: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[1220]

[1221] (Step 1)

[1222] The title compound (56.0 mg, yield: 18.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide.

[1223] 1 H NMR (500 MHz, DMSO-d6) δ 9.87 (s, 1H), 9.63 (s, 1H), 8.77 (s, 1H), 8.70 (s, 1H), 8.15 - 7.99 (m, 2H), 7.91 (d, J = 7.8 Hz, 2H), 7.68 (t, J = 7.2 Hz, 1H), 7.60 - 7.54 (m, 2H), 7.46 - 7.41 (m, 1H), 7.36 - 7.25 (m, 1H), 7.22 - 7.08 (m, 2H), 6.78 (d, J = 7.4 Hz, 1H), 4.21 (s, 1H), 3.53 (s, 1H), 3.46 (dd, J = 11.5, 6.4 Hz, 1H), 3.00 (s, 6H), 2.72 (q, J = 7.4 Hz, 1H), 2.46 - 2.37 (m, 3H), 2.33 (s, 3H). MS (ESI, m / z): 553.4 [M+H] +

[1224]

[1225] Example 111: Preparation of (S)-N-(4-(N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

[1226]

[1227] (Step 1)

[1228] N-(4-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)acetamide (130 mg, yield: 70%) was obtained in the same manner as in Example 1, except that N-(4-sulfamoylphenyl)acetamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1229] 1 H NMR (500 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.12 (d,J= 8.4 Hz, 2H), 7.90 (dd,J= 11.1, 8.3 Hz, 2H), 7.79 (d,J= 8.9 Hz, 3H), 7.68 (t,J= 7.7 Hz, 1H), 2.07 (s, 3H). MS (ESI, m / z): 377.2 [M+H] +

[1230] (Step 2)

[1231] The title compound (42 mg, yield: 45%) was obtained in the same manner as in Example 4, except that N-(4-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)acetamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1232] 1 H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 9.56 (s, 1H), 8.87 (s, 1H), 7.99 (d, J = 8.3 Hz, 2H), 7.65 (s, 1H), 7.49 (d, J = 7.8 Hz, 0H), 7.37 - 7.08 (m, 2H), 7.00 (s, 1H), 4.28 - 4.15 (m, 1H), 3.53 (s, 1H), 3.46 (dd, J = 11.2, 7.3 Hz, 1H), 3.37 - 3.33 (m, 1H), 2.93 (s, 6H), 2.71 (q, J = 8.2 Hz, 1H), 2.60 - 2.53 (m, 1H), 2.40 (s, 1H), 2.05 (s, 3H). MS (ESI, m / z): 546.4 [M+H]+

[1233]

[1234] Example 112: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide

[1235]

[1236] (Step 1)

[1237] N-(3-chloroquinoxalin-2-yl)benzofuran-6-sulfonamide (152 mg, yield: 85%) was obtained in the same manner as in Example 1, except that benzofuran-6-sulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1238] 1 H NMR (500 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.26 (d, J = 2.1 Hz, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.88 - 7.84 (m, 2H), 7.76 (t, J = 7.7 Hz, 1H), 7.66 (t, J = 7.7 Hz, 1H), 7.15 - 7.06 (m, 2H). MS (ESI, m / z): 360.19 [M+H] +

[1239] (Step 2)

[1240] The title compound (110 mg, yield: 70%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)benzofuran-6-sulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1241] 1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.61 (s, 1H), 8.90 (s, 1H), 8.36 (s, 1H), 8.11 (s, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.68 (s, 1H), 7.46 (s, 1H), 7.30 (s, 1H), 7.23 (d, J = 7.9 Hz, 2H), 7.17 (t, J = 7.7 Hz, 2H), 6.99 (d, J = 8.2 Hz, 2H), 4.23 (s, 1H), 3.58 (s, 1H), 3.49 (t, J = 9.3 Hz, 1H), 3.41 - 3.24 (m, 1H), 2.73 (q, J = 8.2 Hz, 1H), 2.66 - 2.55 (m, 1H), 2.48 - 2.30 (m, 1H). MS (ESI, m / z): 529.42 [M+H] +

[1242]

[1243] Example 113: Preparation of (S)-3-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1244]

[1245] (Step 1)

[1246] N-(3-chloroquinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide (148 mg, yield: 82%) was obtained in the same manner as in Example 1, except that 3-(dimethylamino)benzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1247] 1H NMR (500 MHz, DMSO-d6) δ 7.33 (t, J = 8.0 Hz, 1H), 7.21 (s, 2H), 7.13 (t, J = 2.2 Hz, 1H), 7.10 - 7.05 (m, 1H), 6.90 (dd, J = 8.4, 2.6 Hz, 1H), 2.95 (s, 6H). MS (ESI, m / z): 363.2 [M+H] +

[1248] (Step 2)

[1249] The title compound (103 mg, yield: 65%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1250] 1 H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.64 (s, 1H), 8.92 (s, 1H), 7.62 (s, 1H), 7.47 (s, 1H), 7.35 - 7.30 (s, 1H), 7.26 (d, J = 7.4 Hz, 2H), 7.24 - 7.04 (m, 4H), 6.98 (s, 1H), 6.75 (s, 1H), 4.15 (d, J = 50.2 Hz, 1H), 3.62 - 3.54 (m, 1H), 3.47 (dd, J = 11.2, 7.2 Hz, 1H), 3.41 - 3.26 (m, 1H), 3.24 (d, J = 16.5 Hz, 1H), 2.96 (s, 6H), 2.93 (s, 6H), 2.70 (s, 1H), 2.45 - 2.31 (m, 1H). MS (ESI, m / z): 532.43 [M+H] +

[1251]

[1252] Example 114: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1253]

[1254] (Step 1)

[1255] (S)-N,N-dimethyl-1-(2-methyl-6-nitrophenyl)pyrrolidine-3-amine (4.7 g, yield: 97.5%) was obtained in the same manner as in Example 1, except that (S)-N,N-dimethyl-1-(2-methyl-6-nitrophenyl)pyrrolidine-3-amine was used instead of methylpiperazine and 2-fluoro-1-methyl-3-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1.

[1256] 1 H NMR (500 MHz, DMSO-d6) δ 7.26 (t, J = 7.9 Hz, 1H), 6.81 (d, J = 8.5 Hz, 1H), 6.68 (d, J = 7.3 Hz, 1H), 3.24 (dtd, J = 26.6, 9.9, 6.7 Hz, 3H), 3.04 (t, J = 8.6 Hz, 1H), 2.77 - 2.67 (m, 1H), 2.19 (s, 3H), 2.16 (s, 6H), 2.09 (ddt, J = 12.4, 6.5, 3.3 Hz, 1H), 1.80 - 1.68 (m, 1H). MS (ESI, m / z): 250.2 [M+H] +

[1257] (Step 2)

[1258] (S)-1-(2-amino-6-methylphenyl)-N,N-dimethylpyrrolidine-3-amine (4.0 g, yield: 96.7%) was obtained by the same method as in Step 3 of Example 1.

[1259] 1H NMR (500 MHz, DMSO-d6) δ 6.85 - 6.78 (m, 1H), 6.68 (t, J = 7.8 Hz, 1H), 6.48 (t, J = 7.6 Hz, 1H), 4.35 (s, 2H), 3.25 - 3.21 (m, 1H), 3.09 - 3.02 (m, 1H), 2.84 (dtd, J = 16.8, 8.6, 6.0 Hz, 3H), 2.16 (s, 6H), 2.08 (s, 3H), 2.08 - 1.97 (m, 1H), 1.79 - 1.68 (m, 1H). MS (ESI, m / z): 220.2 [M+H] +

[1260] (Step 3)

[1261] The title compound (32.0 mg, yield: 10.3%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1262] 1 H NMR (500 MHz, DMSO-d6) δ 7.98 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.9 Hz, 1H), 7.24 - 7.16 (m, 4H), 7.16 - 7.10 (m, 1H), 7.09 (q, J = 5.6 Hz, 2H), 7.03 (s, 1H), 6.87 (d, J = 18.6 Hz, 2H), 4.21 (s, 1H), 3.53 (s, 1H), 3.46 (dd, J = 11.5, 6.4 Hz, 1H), 3.16 (s, 1H), 2.93 - 2.83 (m, 1H), 2.73 (s, 6H), 2.37 - 2.34 (m, 2H), 2.32 (s, 3H), 2.16 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1263]

[1264] Example 115: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1265]

[1266] (Step 1)

[1267] The title compound (21.0 mg, yield: 6.9%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1268] 1 H NMR (500 MHz, DMSO-d6) δ 8.03 (d, J = 8.5 Hz, 2H), 7.29 (s, 1H), 7.19 (s, 1H), 7.14 - 7.05 (m, 2H), 7.03 (s, 1H), 6.95 (d, J = 8.9 Hz, 2H), 6.89 - 6.81 (m, 2H), 4.21 (s, 1H), 3.77 (s, 3H), 3.53 (s, 1H), 3.46 (dd, J = 11.5, 6.4 Hz, 1H), 3.20 - 2.83 (m, 1H), 2.93 - 2.83 (m, 1H), 2.73 (s, 6H), 2.96 - 2.67 (m, 2H), 2.16 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1269]

[1270] Example 116: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[1271]

[1272] (Step 1)

[1273] The title compound (70.0 mg, yield: 22.5%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide.

[1274] 1 H NMR (500 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.96 (s, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.31 (s, 2H), 7.26 - 7.16 (m, 3H), 7.13 - 7.00 (m, 1H), 6.87 (dd, J = 19.3, 7.5 Hz, 2H), 4.21 (s, 1H), 3.96 - 3.74 (m, 2H), 3.23 - 3.13 (m, 2H), 2.88 (s, 2H), 2.74 (s, 6H), 2.38 (s, 3H), 2.16 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1275]

[1276] Example 117: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1277]

[1278] (Step 1)

[1279] The title compound (55.0 mg, yield: 18.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[1280] 1 H NMR (500 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.77 (s, 1H), 7.61 (d, J = 7.7 Hz, 1H), 7.39 - 7.28 (m, 2H), 7.21 (d, J = 8.4 Hz, 1H), 7.14 - 7.06 (m, 2H), 7.03 - 6.96 (m, 1H), 6.87 (dd, J = 19.8, 7.8 Hz, 2H), 4.21 (s, 1H), 3.96 - 3.89 (m, 2H), 3.83 (s, 3H), 3.17 (d, J = 10.2 Hz, 2H), 2.89 (s, 2H), 2.73 (s, 6H), 2.16 (s, 3H). MS (ESI, m / z): 533.4 [M+H] +

[1281]

[1282] Example 118: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1283]

[1284] (Step 1)

[1285] The title compound (36.0 mg, yield: 11.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1286] 1 H NMR (500 MHz, DMSO-d6) δ 8.13 (d, J = 7.8 Hz, 1H), 7.38 - 7.27 (m, 2H), 7.26 - 7.14 (m, 3H), 7.13 - 6.98 (m, 4H), 6.86 (dd, J = 14.6, 7.9 Hz, 2H), 4.21 (s, 1H), 3.96 - 3.74 (m, 2H), 3.27 - 3.18 (m, 2H), 3.03 (d, J = 8.5 Hz, 1H), 2.70 (s, 6H), 2.65 (s, 3H), 2.17 (s, 1H), 2.13 (s, 3H). MS (ESI, m / z): 517.4 [M+H] +

[1287]

[1288] Example 119: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide

[1289]

[1290] (Step 1)

[1291] The title compound (36.0 mg, yield: 12.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)naphthalene-2-sulfonamide.

[1292] 1 H NMR (500 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.69 (s, 1H), 8.19 - 8.10 (m, 2H), 8.08 - 8.01 (m, 2H), 7.93 (dd, J = 9.0, 5.4 Hz, 2H), 7.71 - 7.64 (m, 1H), 7.63 - 7.54 (m, 2H), 7.53 - 7.46 (m, 1H), 7.28 (s, 1H), 7.24 (s, 1H), 7.12 (t, J = 7.9 Hz, 1H), 6.82 (dd, J = 23.8, 7.9 Hz, 2H), 3.74 (s, 2H), 3.25 - 3.17 (m, 2H), 2.97 (d, J = 8.8 Hz, 2H), 2.65 - 2.61 (m, 6H), 2.11 (s, 1H), 2.08 (s, 3H). MS (ESI, m / z): 553.4 [M+H] +

[1293]

[1294] Example 120: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1295]

[1296] The title compound (45 mg, yield: 32%) was obtained in the same manner as in Example 4, except that (3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine was used instead of (S)-N,N-dimethylpyrrolidine-3-amine in Step 1 of Example 4, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of tert-butyl(S)-(1-(2-aminophenyl)pyrrolidine-3-yl)carbamate was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in Step 3.

[1297] 1 H NMR (500 MHz, CDCl3) δ 9.48 (s, 1H), 8.82 (d,J= 8.2 Hz, 1H), 7.89 - 7.84 (m, 2H), 7.65 (d,J= 7.8 Hz, 1H), 7.32 (d,J= 8.5 Hz, 1H), 7.23 (s, 1H), 7.16 (s, 1H), 7.14-7.12 (m, 2H), 6.96 (s, 1H), 6.89 (s, 1H), 3.79 (s, 1H), 3.13 (s, 1H), 2.91 - 2.87 (m, 1H), 2.61 (s, 1H), 2.37 (s, 1H), 2.20 (s, 1H), 2.06 (s, 1H).

[1298]

[1299] Example 121: Preparation of 4-methyl-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1300]

[1301] The title compound (57 mg, yield: 54%) was obtained in the same manner as in Example 4, except that cis-2-methyl-octahydropyrrolo[3,4-c]pyrrolo was used instead of (S)-N,N-dimethylpyrrolodin-3-amine in Step 1 of Example 4, and 2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrolo-2(1H)-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolodin-3-amine in Step 3.

[1302] 1 H NMR (500 MHz, CDCl3) δ 9.26 (s, 1H), 8.85 (d,J= 8.1 Hz, 1H), 7.90 (d,J= 8.0 Hz, 2H), 7.72 (d,J= 8.5 Hz, 1H), 7.39 (t,J= 7.0 Hz, 1H), 7.36 - 7.28 (m, 4H), 7.26 - 7.12 (m, 2H), 7.07 (t,J= 7.0 Hz, 1H), 3.15-3.11 (m, 2H), 2.99 - 2.91 (m, 8H), 2.65 (s, 3H), 2.43 (s, 3H).

[1303]

[1304] Example 122: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)pyridine-3-sulfonamide

[1305]

[1306] (Step 1)

[1307] N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (149 mg, yield: 93%) was obtained in the same manner as in Example 1, except that pyridine-3-sulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1308] 1H NMR (500 MHz, DMSO-d6) δ 8.90 - 8.85 (m, 2H), 8.11 (d, J = 5.1 Hz, 2H), 7.83 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.69 (t, J = 7.8) Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H). MS (ESI, m / z): 321.1 [M+H] +

[1309] (Step 2)

[1310] The title compound (92 mg, yield: 63%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1311] 1 H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H), 9.56 (s, 1H), 9.16 (d, J = 2.2 Hz, 1H), 8.92 (dd, J = 8.2, 1.4 Hz, 1H), 8.58 (dd, J = 4.8, 1.7 Hz, 1H), 8.42 (dt, J = 8.0, 2.0 Hz, 1H), 7.50 - 7.44 (m, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.23 (dd, J = 7.9, 1.4 Hz, 1H), 7.22 - 7.12 (m, 3H), 6.98 (td, J = 7.7, 1.5 Hz, 1H), 4.26 - 4.18 (m, 1H), 3.64 - 3.54 (m, 1H), 3.50 (dd, J = 11.2, 7.2 Hz, 1H), 3.41 - 3.24 (m, 1H), 3.00 (s, 6H), 2.72 (q, J = 8.2 Hz, 1H), 2.56 - 2.52 (m, 1H), 2.43 - 2.36 (m, 1H). MS (ESI, m / z): 490.3 [M+H] +

[1312]

[1313] Example 123: Preparation of (S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1314]

[1315] (Step 1)

[1316] N-(3-chloroquinoxalin-2-yl)-4-(dimethylamino)benzenesulfonamide (1.5 g, yield: 83.9%) was obtained in the same manner as in Example 1, except that 4-(dimethylamino)benzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1317] 1 H NMR (500 MHz, DMSO-d6) δ 7.91 - 7.86 (m, 2H), 7.69 (d, J = 8.2 Hz, 1H), 7.60 (dt, J = 15.1, 8.2 Hz, 2H), 7.40 (d, J = 7.8 Hz, 1H), 6.72 - 6.66 (m, 2H), 2.93 (s, 6H). MS (ESI, m / z): 363.1 [M+H] +

[1318] (Step 2)

[1319] The title compound (7.0 mg, yield: 2.5%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-(dimethylamino)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1320] 1H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.83 (s, 1H), 7.87 (d, J = 8.6 Hz, 2H), 7.46 (s, 1H), 7.25 - 7.05 (m, 4H), 6.78 (d, J = 12.4 Hz, 1H), 6.67 (s, 2H), 3.63 - 3.51 (m, 2H), 2.95 (d, J = 27.9 Hz, 12H), 2.70 (s, 1H), 2.64 (s, 1H),2.57 - 2.53 (m, 2H), 2.39 - 2.33 (m, 1H), 2.32 (s, 3H). MS (ESI, m / z): 546.4 [M+H] +

[1321]

[1322] Example 124: Preparation of (S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1323]

[1324] (Step 1)

[1325] The title compound (11.0 mg, yield: 3.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-(dimethylamino)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1326] 1H NMR (500 MHz, DMSO-d6) δ 9.49 (s, 1H), 8.73 (s, 1H), 7.86 (d, J = 8.7 Hz, 2H), 7.43 (s, 1H), 7.33 (s, 1H), 7.23 - 7.09 (m, 3H), 7.02 (s, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.66 (d, J = 8.7 Hz, 2H), 4.17 (s, 1H), 3.57 - 3.37 (m, 2H), 2.95 (d, J = 28.7 Hz, 12H), 2.80 - 2.70 (m, 2H), 2.43 - 2.32 (m, 2H), 2.29 (s, 3H). MS (ESI, m / z): 546.4 [M+H] +

[1327]

[1328] Example 125: Preparation of (S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1329]

[1330] (Step 1)

[1331] The title compound (11.0 mg, yield: 3.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-(dimethylamino)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1332] 1H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.75 (s, 1H), 7.87 (d, J = 8.6 Hz, 2H), 7.47 (s, 1H), 7.43 - 7.28 (m, 2H), 7.18 (s, 2H), 7.10 (d, J = 8.1 Hz, 1H), 6.77 (dd, J = 13.6, 8.4 Hz, 1H), 6.67 (d, J = 8.6 Hz, 2H), 4.14 (s, 1H), 3.43 - 3.36 (m, 2H), 2.95 (d, J = 27.6 Hz, 12H), 2.75 - 2.68 (m, 2H), 2.42 - 2.35 (m, 1H), 2.34 (s, 3H), 2.01 - 1.89 (m, 1H). MS (ESI, m / z): 546.4 [M+H] +

[1333]

[1334] Example 126: Preparation of (S)-4-(benzyloxy)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1335]

[1336] The title compound (57 mg, yield: 58%) was obtained in the same manner as in Example 4, except that 4-(benzyloxy)-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1337] 1H NMR (500 MHz, CDCl3) δ 9.40 (s, 1H), 8.82 (d,J= 7.5 Hz, 1H), 7.98 (d,J= 9.0 Hz, 2H), 7.71 (d,J= 7.5 Hz, 1H), 7.42-7.28 (m, 7H), 7.17 (d,J= 8.0 Hz, 1H), 7.08 (d,J= 8.5 Hz, 1H), 5.14 (s, 2H), 3.31 (s, 1H), 3.13 (s, 1H), 3.05-3.02 (m, 3H), 2.35 (s, 6H), 1.99 (s, 1H), 1.88 (s, 1H).

[1338]

[1339] Example 127: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-ethoxybenzenesulfonamide

[1340]

[1341] The title compound (80 mg, yield: 78%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-4-ethoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 3 of Example 4.

[1342] 1 H NMR (500 MHz, CDCl3) δ 9.39 (s, 1H), 8.82 (d,J= 8.0 Hz, 1H), 7.93 (d,J= 8.5 Hz, 2H), 7.72 (d,J= 8.0 Hz, 1H), 7.41 (s, 1H), 7.35 (s, 1H), 7.19 (dd,J= 8.5, 10.5 Hz, 2H), 7.08 (t,J= 7.0 Hz, 1H), 6.99 (d,J= 9.0 Hz, 1H), 4.11-4.09 (m, 2H), 3.37 (s, 1H), 3.18-3.06 (m, 4H), 2.50 (s, 6H), 2.06 (s, 2H), 1.45 (s, 3H).

[1343]

[1344] Example 128: Preparation of (S)-N-(1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-yl)acetamide

[1345]

[1346] The compound of Example 120 (15 mg, 1.0 eq) was dissolved in dichloromethane (2 mL), acetyl chloride (3 mL, 1.5 eq) and triethylamine (13 mL, 3 eq) were added, and the reaction was carried out at room temperature for 3 hours. After the reaction was completed, the residue obtained by vacuum concentration was purified by column chromatography (methylene chloride: methanol = 20:1) to obtain the title compound (6 mg, yield 35%).

[1347] 1 H NMR (500 MHz, CDCl3) δ 11.66 (s, 1H), 9.97 (s, 1H), 8.76 (d,J= 7.0 Hz, 1H), 7.88 (d,J= 8.0 Hz, 1H), 7.73 (d,J= 7.5 Hz, 1H), 7.43 (t,J= 7.5 Hz, 1H), 7.37-7.19 (m, 5H), 7.10 (t,J= 7.5 Hz, 1H), 6.71 (s, 1H), 4.75 (s, 1H), 3.31 (s, 1H), 3.23-3.15 (m, 2H), 2.84-2.82 (m, 1H), 2.44 (s, 3H), 2.07 (s, 3H), 1.60 (s, 3H), 1.77-1.15 (m, 1H), 0.90-0.86 (m, 1H).

[1348]

[1349] Example 129: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-hydroxybenzenesulfonamide

[1350]

[1351] The compound of Example 126 (35 mg, 1.0 eq) was dissolved in methanol (2 mL), Pd / C (3.5 mg, 10 wt.%) was added, and the reaction was carried out at room temperature for 6 hours. After the reaction was finished, the mixture was filtered through a celite pad and then concentrated under reduced pressure. The residue obtained from the reduced pressure concentration was purified by column chromatography (methylene chloride: methanol = 20:1) to obtain the title compound (23 mg, yield 78%).

[1352] 1 H NMR (500 MHz, CDCl3) δ 9.23 (s, 1H), 8.83 (d,J= 7.6 Hz, 1H), 7.85 (d,J= 7.8 Hz, 2H), 7.71 (d,J= 7.9 Hz, 1H), 7.41 (t,J= 7.5 Hz, 1H), 7.35 (t,J= 7.5 Hz, 1H), 7.30 (s, 1H), 7.23-7.20 (m, 1H), 7.13-7.11 (m, 1H), 7.09 - 7.02 (m, 3H), 3.45 (s, 1H), 3.36 (s, 1H), 3.17 (s, 2H), 2.88 (d,J= 8.7 Hz, 1H), 2.59 (s, 6H), 2.04 (s, 2H).

[1353]

[1354] Example 130: Preparation of (S)-N-(3-((2-(3-methoxypyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1355]

[1356] The title compound (11 mg, yield: 11%) was obtained in the same manner as in Example 4, except that (S)-2-(3-methoxypyrrolidin-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1357] 1H NMR (500 MHz, CDCl3) δ 11.82 (s, 1H), 9.20 (s, 1H), 8.53 (s, 1H), 8.00 - 7.97 (m, 2H), 7.64 (d,J= 7.9 Hz, 1H), 7.42 - 7.30 (m, 5H), 7.26-7.23 (m, 1H), 7.17 - 7.14 (m, 1H), 3.98 (s, 1H), 3.64 (s, 1H), 3.35 (s, 3H), 3.29 - 3.22 (m, 2H), 3.06 (d,J= 11.1 Hz, 1H), 2.44 (s, 3H), 2.16 (s, 1H), 2.03 (s, 1H), 0.09 (s, 1H).

[1358]

[1359] Example 131: Preparation of N-(3-((2-(3-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1360]

[1361] The title compound (57 mg, yield: 53%) was obtained in the same manner as in Example 4, except that N,N-dimethylpiperidine-3-amine was used instead of (S)-N,N-dimethylpyrrolidine-3-amine in Step 1 of Example 4 and 1-(2-aminophenyl)-N,N-dimethylpiperidine-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in Step 3.

[1362] 1H NMR (500 MHz, CDCl3) δ 9.76 (s, 1H), 8.94 (d,J= 8.2 Hz, 1H), 7.93 (d,J= 8.0 Hz, 2H), 7.76 (d,J= 6.9 Hz, 1H), 7.42 (t,J= 7.6 Hz, 1H), 7.39 - 7.33 (m, 3H), 7.30 (s, 1H), 7.24 (t,J= 7.7 Hz, 1H), 7.17 (d,J= 7.7 Hz, 1H), 7.07 (t,J= 7.6 Hz, 1H), 3.26 (d,J= 10.8 Hz, 1H), 2.94-2.80 (m, 2H), 2.72-2.62 (m, 2H), 2.52 (s, 6H), 2.45 (s, 3H), 2.09 (d,J= 11.4 Hz, 1H), 1.82 (s, 1H), 1.61 - 1.45 (m, 2H).

[1363]

[1364] Example 132: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-hydroxyphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1365]

[1366] (Step 1)

[1367] (S)-3-(3-(dimethylamino)pyrrolidine-1-yl)-4-nitrophenol (3.0 g, yield: 93.8%) was obtained in the same manner as in Example 1, except that 3-fluoro-4-nitrophenol was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine.

[1368] 1H NMR (500 MHz, DMSO-d6) δ 10.37 (s, 1H), 7.69 (d, J = 9.0 Hz, 1H), 6.30 (d, J = 2.9 Hz, 1H), 6.22 (dd, J = 8.7, 2.9 Hz, 1H), 4.03 (dd, J = 8.7, 2.9 Hz, 1H) 6.9, 3.5 Hz, 1H), 3.07 (t, J = 11.0 Hz, 2H), 3.04 - 2.97 (m, 1H), 2.70 (s, 1H), 2.17 (d, J = 3.5 Hz, 6H), 2.10 (d, J = 12.1 Hz, 1H), 1.74 (t, J = 10.2 Hz, 1H). MS (ESI, m / z): 252.1 [M+H] +

[1369] (Step 2)

[1370] (S)-4-amino-3-(3-(dimethylamino)pyrrolidin-1-yl)phenol (2.5 g, yield: 94.6%) was obtained by the same method as in Step 3 of Example 1.

[1371] 1 H NMR (500 MHz, DMSO-d6) δ 8.35 (s, 1H), 6.48 (d, J = 8.3 Hz, 1H), 6.33 (s, 1H), 6.19 (d, J = 8.4 Hz, 1H), 4.08 - 3.93 (m, 1H), 3.13 (q, J = 8.0 Hz, 1H), 3.05 (t, J = 8.1 Hz, 1H), 2.86 (t, J = 7.9 Hz, 2H), 2.17 (s, 6H), 2.00 (d, J = 9.6 Hz, 1H), 1.76 - 1.69 (m, 1H). MS (ESI, m / z): 222.2 [M+H] +

[1372] (Step 3)

[1373] The step 2 product (2.5 g, 1.0 eq) was dissolved in EA (60 mL) and stirred at rt for 30 minutes. After slowly stirring 1 M HCl in EA (14.7 mL, 1.3 eq) and stirring at rt for 2 hours, the mixture was filtered with EA to obtain (S)-4-amino-3-(3-(dimethylamino)pyrrolidin-1-yl)phenol hydrochloride (yield 97.3%, 2.8 g).

[1374] 1 H NMR (500 MHz, DMSO-d6) δ 8.56 (s, 1H), 6.53 (d, J = 8.4 Hz, 1H), 6.37 (s, 1H), 6.27 (d, J = 8.4 Hz, 1H), 3.82 (s, 1H), 3.26 - 3.14 (m, 2H), 3.06 (t, J = 9.0 Hz, 1H), 2.83 (q, J = 8.2 Hz, 1H), 2.74 (s, 6H), 2.24 (q, J = 8.7 Hz, 1H), 2.12 (dq, J = 13.8, 7.1 Hz, 1H).

[1375] (Step 4)

[1376] The title compound (59.0 mg, yield: 7.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-4-amino-3-(3-(dimethylamino)pyrrolidin-1-yl)phenol hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1377] 1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 9.35 - 8.97 (m, 2H), 8.68 - 8.45 (m, 1H), 8.00 (d, J = 8.3 Hz, 2H), 7.47 - 7.34 (m, 1H), 7.33 - 7.22 (m, 1H), 7.22 - 7.06 (m, 2H), 7.04 - 6.85 (m, 2H), 6.61 (d, J = 2.6 Hz, 1H), 6.56 (dd, J = 8.7, 2.5 Hz, 1H), 4.16 (s, 1H), 3.77 (s, 3H), 3.42 - 3.34 (m, 2H), 2.93 (s, 6H), 2.81 - 2.69 (m, 2H), 1.91 (s, 2H). MS (ESI, m / z): 535.3 [M+H] +

[1378]

[1379] Example 133: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-hydroxyphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1380]

[1381] (Step 1)

[1382] (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)-3-nitrophenol (2.2 g, yield: 78.1%) was obtained in the same manner as in Example 1, except that 4-fluoro-3-nitrophenol was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1383] 1H NMR (500 MHz, DMSO-d6) δ 7.10 (s, 1H), 6.97 (q, J = 9.3 Hz, 2H), 3.17 - 2.89 (m, 4H), 2.69 (t, J = 8.1 Hz, 1H), 2.16 (d, J = 4.4 Hz, 6H), 2.09 (dt, J = 12.1, 6.2 Hz, 1H), 1.73 (q, J = 10.2 Hz, 1H). MS (ESI, m / z): 252.2 [M+H] +

[1384] (Step 2)

[1385] (S)-3-amino-4-(3-(dimethylamino)pyrrolidin-1-yl)phenol (2.0 g, yield: 90.8%) was obtained by the same method as in Step 3 of Example 1.

[1386] 1 H NMR (500 MHz, DMSO-d6) δ 8.60 (s, 1H), 6.72 (d, J = 8.4 Hz, 1H), 6.64 - 6.55 (m, 1H), 5.93 (d, J = 8.4 Hz, 1H), 4.60 (s, 2H), 3.01 - 2.91 (m, 2H), 2.80 - 2.71 (m, 3H), 2.15 (s, 6H), 1.98 (s, 1H), 1.71 (s, 1H). MS (ESI, m / z): 222.2 [M+H] +

[1387] (Step 3)

[1388] (S)-3-amino-4-(3-(dimethylamino)pyrrolidin-1-yl)phenol hydrochloride (2.2 g, yield: 93.1%) was obtained by the same method as step 3 of Example 132.

[1389] 1H NMR (500 MHz, DMSO-d6) δ 10.53 (s, 1H), 9.34 (s, 1H), 7.03 (d, J = 8.5 Hz, 1H), 6.50 (s, 1H), 6.39 (s, 1H), 3.85 (s, 1H), 3.35 - 3.28 (m, 2H), 3.15 (q, J = 6.6 Hz, 1H), 3.09 (dd, J = 11.1, 6.8 Hz, 1H), 2.80 (s, 6H), 2.28 (t, J = 7.0 Hz, 1H), 2.14 (dd, J = 13.7, 7.7 Hz, 1H).

[1390] (Step 4)

[1391] The title compound (38.0 mg, yield: 5.0%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-3-amino-4-(3-(dimethylamino)pyrrolidin-1-yl)phenol hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1392] 1 H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 9.81 - 9.61 (m, 2H), 9.20 (s, 1H), 8.49 (s, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.48 - 7.44 (m, 1H), 7.37 - 7.24 (m, 1H), 7.22 - 7.11 (m, 2H), 7.05 (d, J = 8.3 Hz, 1H), 6.99 - 6.87 (m, 1H), 6.38 - 6.34 (m, 1H), 4.17 (s, 1H), 3.76 (s, 3H), 3.50 - 3.19 (m, 3H), 2.97 (s, 6H), 2.73 - 2.60 (m, 1H), 2.60 - 2.42 (m, 2H). MS (ESI, m / z): 535.3 [M+H] +

[1393]

[1394] Example 134: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1395]

[1396] (Step 1)

[1397] (S)-1-(5-chloro-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (150 g, yield: 97.6%) was obtained in the same manner as in Example 1, except that 4-chloro-2-fluoro-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1398] 1 H NMR (500 MHz, DMSO-d6) δ 7.76 (d, J = 8.8 Hz, 1H), 7.10 (s, 1H), 6.79 (d, J = 8.8 Hz, 1H), 3.13 (p, J = 9.9 Hz, 4H), 2.73 (t, J = 8.0 Hz, 1H), 2.17 (s, 6H), 2.15 - 2.08 (m, 1H), 1.76 (q, J = 10.1 Hz, 1H). MS (ESI, m / z): 270.2 [M+H] +

[1399] (Step 2)

[1400] The product of Step 1 (150 g, 1.0 eq) was dissolved in MeOH (1.5 L) and Water (1.5 L) and stirred at rt. After adding Na2S2O4 (581 g, 6.0 eq), the mixture was stirred at 55°C for 2 hours. After the reaction was complete, the solvent was removed by reducing pressure concentration, and the organic layer was separated using water and ethyl acetate. The mixture was then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain (S)-1-(2-amino-5-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine (88.0 g, yield: 66.0%).

[1401] 1 H NMR (500 MHz, DMSO-d6) δ 6.81 (d, J = 2.4 Hz, 1H), 6.75 (dd, J = 8.4, 2.3 Hz, 1H), 6.63 (dd, J = 8.4, 2.2 Hz, 1H), 4.74 (s, 2H), 3.13 (dt, J) = 23.5, 9.0 Hz, 2H), 2.93 (p, J = 7.1 Hz, 3H), 2.24 (s, 6H), 2.05 (dq, J = 13.0, 6.6 Hz, 1H), 1.77 (dq, J = 14.4, 7.2 Hz, 1H). MS (ESI, m / z): 240.2 [M+H] +

[1402] (Step 3)

[1403] (S)-1-(2-amino-5-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine hydrochloride (98.8 g, yield: 94.3%) was obtained in the same manner as step 3 of Example 132.

[1404] 1H NMR (500 MHz, DMSO-d6) δ 10.93 (s, 1H), 7.14 (d, J = 8.5 Hz, 1H), 7.10 (s, 1H), 7.06 - 7.00 (m, 1H), 3.89 (s, 1H), 3.59 - 3.49 (m, 1H), 3.37 (td, J = 8.5, 3.8 Hz, 1H), 3.31 (dd, J = 10.8, 6.8 Hz, 1H), 3.01 (q, J = 8.2 Hz, 1H), 2.80 (s, 6H), 2.39 - 2.27 (m, 1H), 2.21 (dq, J = 13.9, 7.0 Hz, 1H).

[1405] (Step 4)

[1406] N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide (60.0 g, 1.0 eq) and (S)-1-(2-amino-5-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine hydrochloride (47.4 g, 1.0 eq) were dissolved in acetonitrile (600 mL). The reaction mixture was then heated to 82 °C and reacted for 12 hours. Once the reaction was complete, an aqueous solution of NaHCO3 was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (dichloromethane:methanol = 9:1) to obtain the title compound (yield 80.0 %, 63.2 g).

[1407] 1H NMR (500 MHz, CDCl3) δ 9.15 (s, 1H), 8.72 (d, J = 8.7 Hz, 1H), 7.97 - 7.91 (m, 2H), 7.68 (dd, J = 8.0, 1.5 Hz, 1H), 7.40 (td, J = 7.6, 1.6) Hz, 1H), 7.34 (td, J = 7.6, 1.5 Hz, 1H), 7.29 (dd, J = 8.7, 2.0 Hz, 1H), 7.13 (dd, J = 8.7, 2.4 Hz, 1H), 7.10 (d, J = 2.4 Hz, 1H), 7.04 - 6.97 (m, 2H), 3.87 (s, 3H), 3.36 (dd, J = 9.2, 6.6 Hz, 1H), 3.33 - 3.27 (m, 1H), 3.18 (ddt, J = 15.3, 9.0, 4.5 Hz, 2H), 3.04 (dt, J = 9.4, 7.0 Hz, 1H), 2.52 (s, 6H), 2.07 (dh, J = 12.9, 6.5 Hz, 2H). MS (ESI, m / z): 553.3 [M+H] +

[1408]

[1409] Example 135: Preparation of (S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1410]

[1411] (Step 1)

[1412] (S)-1-(4-chloro-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (3.0 g, yield: 97.6%) was obtained in the same manner as in Example 1, except that 4-chloro-1-fluoro-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1413] 1H NMR (500 MHz, DMSO-d6) δ 7.81 (d, J = 2.9 Hz, 1H), 7.50 (dd, J = 9.0, 2.8 Hz, 1H), 7.09 (d, J = 8.9 Hz, 1H), 3.12 (q, J = 8.1 Hz, 4H), 2.74 (q, J = 7.7 Hz, 1H), 2.50 (d, J = 4.9 Hz, 3H), 2.17 (d, J = 2.9 Hz, 6H), 2.12 (dd, J = 11.9, 6.3 Hz, 1H), 1.76 (p, J = 10.0 Hz, 1H). MS (ESI, m / z): 270.1 [M+H] +

[1414] (Step 2)

[1415] (S)-1-(2-amino-4-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine (2.5 g, yield: 93.8%) was obtained by the same method as in Step 3 of Example 1.

[1416] 1 H NMR (500 MHz, DMSO-d6) δ 6.84 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 2.5 Hz, 1H), 6.50 (dd, J = 8.3, 2.4 Hz, 1H), 4.95 (s, 2H), 3.07 (q, J = 8.1) Hz, 2H), 3.01 (s, 1H), 2.91 (q, J = 8.0 Hz, 2H), 2.29 (s, 6H), 2.06 (dq, J = 13.4, 6.9 Hz, 1H), 1.79 (dq, J = 13.9, 7.1 Hz, 1H). MS (ESI, m / z): 240.2 [M+H] +

[1417] (Step 3)

[1418] (S)-1-(2-amino-4-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine hydrochloride (2.6 g, yield: 91.6%) was obtained by the same method as step 3 of Example 132.

[1419] 1H NMR (500 MHz, DMSO-d6) δ 10.88 (s, 1H), 7.02 (d, J = 8.5 Hz, 1H), 6.98 (s, 1H), 6.86 (d, J = 8.4 Hz, 1H), 3.87 (s, 1H), 3.44 (dd, J = 10.9, 3.8 Hz, 1H), 3.29 (td, J = 8.8, 4.0 Hz, 1H), 3.19 (dd, J = 10.9, 7.0 Hz, 1H), 2.88 (q, J = 8.0 Hz, 1H), 2.79 (dd, J = 9.9, 4.2 Hz, 6H), 2.29 (q, J = 8.3 Hz, 1H), 2.18 (dq, J = 13.8, 7.2 Hz, 1H).

[1420] (Step 4)

[1421] The title compound (90.0 mg, yield: 11.4%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1422] 1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 9.89 - 9.56 (m, 2H), 9.01 (s, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.52 - 7.42 (m, 1H), 7.39 - 7.29 (m, 1H), 7.27 - 7.11 (m, 2H), 7.06 - 6.99 (m, 1H), 6.98 - 6.85 (m, 2H), 4.22 (s, 1H), 3.76 (s, 3H), 3.64 - 3.53 (m, 1H), 3.48 (dd, J = 11.1, 7.1 Hz, 1H), 3.37 - 3.25 (m, 1H), 2.98 (s, 6H), 2.75 - 2.68 (m, 1H), 2.45 - 2.38 (m, 2H). MS (ESI, m / z): 553.3 [M+H] +

[1423]

[1424] Example 136: Preparation of N-(3-((2-(3-((dimethylamino)methyl)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1425]

[1426] The title compound (23 mg, yield: 21%) was obtained in the same manner as in Example 4, except that N,N-dimethyl-1-(pyrrolidin-3-yl)methaneamine was used instead of (S)-N,N-dimethylpyrrolidin-3-amine in Step 1 of Example 4, and 2-(3-((dimethylamino)methyl)pyrrolidin-1-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in Step 3.

[1427] 1H NMR (500 MHz, CDCl3) δ 9.47 (s, 1H), 8.80 (d,J= 8.5 Hz, 1H), 7.89 (d,J= 8.0 Hz, 2H), 7.70 (d,J= 8.0 Hz, 1H), 7.41 (t,J= 7.5 Hz, 1H), 7.35-7.32 (m, 3H), 7.28 (t,J= 8.0 Hz, 1H), 7.18-7.08 (m, 2H), 7.05 (t,J= 7.5 Hz, 1H), 3.21 (dd,J= 7.5, 9.0 Hz, 1H), 3.08-3.04 (m, 2H), 2.95 (dd,J= 5.0, 9.5 Hz, 1H), 2.72-2.64 (m, 3H), 2.48 (s, 6H), 2.43 (s, 3H), 2.15-2.13 (m, 1H), 2.03 (s, 2H), 1.70-1.61 (m, 1H).

[1428]

[1429] Example 137: Preparation of (S)-N-(3-((4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1430]

[1431] (Step 1)

[1432] (S)-N,N-dimethyl-1-(3-nitropyridine-4-yl)pyrrolidine-3-amine (20.0 g, yield: 89.5%) was obtained in the same manner as in Example 1, except that 4-fluoro-3-nitropyridine was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine.

[1433] 1H NMR (500 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.25 (d, J = 6.1 Hz, 1H), 6.97 (d, J = 6.1 Hz, 1H), 3.37 (dt, J = 10.6, 5.2 Hz, 1H), 3.26 (dq, J = 18.0, 8.3 Hz, 2H), 3.15 (t, J = 9.3 Hz, 1H), 2.76 (ddd, J = 15.1, 8.7, 6.3 Hz, 1H), 2.18 (s, 6H), 2.13 (dq, J = 8.2, 2.9 Hz, 1H), 1.84 - 1.71 (m, 1H). MS (ESI, m / z): 237.2 [M+H] +

[1434] (Step 2)

[1435] (S)-4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-amine (3.8 g, yield: 21.5%) was obtained by the same method as in Step 3 of Example 1.

[1436] 1 H NMR (500 MHz, DMSO-d6) δ 7.79 (s, 1H), 7.65 (d, J = 5.3 Hz, 1H), 6.54 (d, J = 5.3 Hz, 1H), 4.48 (s, 2H), 3.43 - 3.31 (m, 2H), 3.21 - 3.10 (m, 2H), 2.70 (p, J = 7.6 Hz, 1H), 2.17 (s, 6H), 2.05 (dtd, J = 10.7, 6.8, 3.4 Hz, 1H), 1.71 (dq, J = 12.2, 8.7 Hz, 1H). MS (ESI, m / z): 207.21 [M+H] +

[1437] (Step 3)

[1438] (S)-4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-amine hydrochloride (4.3 g, yield: 97.4%) was obtained by the same method as in step 3 of Example 132.

[1439] 1H NMR (500 MHz, DMSO-d6) δ 7.94 - 7.89 (m, 1H), 7.83 (s, 1H), 6.80 (d, J = 6.6 Hz, 1H), 5.40 (s, 2H), 3.96 - 3.88 (m, 3H), 3.82 (dp, J = 14.5, 7.1 Hz, 1H), 3.61 (dt, J = 10.3, 7.7 Hz, 1H), 2.74 (s, 6H), 2.35 (dtd, J = 13.8, 7.0, 3.6 Hz, 1H), 2.25 (dq, J = 12.7, 8.5 Hz, 1H).

[1440] (Step 4)

[1441] The title compound (151 mg, yield: 20.3%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)pyridine-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1442] 1 H NMR (500 MHz, DMSO-d6) δ 8.52 (d, J = 7.3 Hz, 1H), 8.19 (s, 1H), 7.95 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 8.2 Hz, 1H), 7.60 - 7.48 (m, 2H), 7.32 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 7.5 Hz, 1H), 4.16 - 4.04 (m, 1H), 4.04 - 3.96 (m, 1H), 3.93 - 3.83 (m, 1H), 3.75 (s, 3H), 2.83 (s, 1H), 2.27 (s, 6H), 1.87 (s, 3H). MS (ES, m / z): 520.40 [M+H] +

[1443]

[1444] Example 138: Preparation of (S)-N-(3-((4-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1445]

[1446] (Step 1)

[1447] The title compound (135 mg, yield: 3.0%) was obtained in the same manner as in Example 4, except that (S)-4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-amine hydrochloride was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in step 3 of Example 4.

[1448] 1 H NMR (500 MHz, DMSO-d6) δ 8.51 (d, J = 7.1 Hz, 1H), 8.17 (s, 1H), 7.89 (d, J = 7.8 Hz, 2H), 7.68 (d, J = 8.3 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.50 (d, J = 8.9 Hz, 1H), 7.32 (t, J = 7.9 Hz, 1H), 7.18 (d, J = 7.9 Hz, 2H), 6.87 (d, J = 7.4 Hz, 1H), 4.07 (s, 1H), 4.00 (s, 1H), 3.86 (d, J = 9.5 Hz, 1H), 3.71 (t, J = 9.5 Hz, 1H), 2.79 (s, 1H), 2.29 (s, 3H), 2.24 (s, 6H), 2.19 - 2.16 (m, 1H), 1.82 (t, J = 10.2 Hz, 1H). MS (ESI, m / z): 504.3 [M+H] +

[1449]

[1450] Example 139: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1451]

[1452] (Step 1)

[1453] (S)-N,N-dimethyl-1-(3-nitropyridine-2-yl)pyrrolidine-3-amine (20.0 g, yield: 89.5%) was obtained in the same manner as in Example 1, except that 2-fluoro-3-nitropyridine was used instead of 1-fluoro-2-nitrobenzene and (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine in Step 2 of Example 1.

[1454] 1 H NMR (500 MHz, CDCl3) δ 8.36 - 8.31 (m, 1H), 8.08 (dd, J = 8.0, 1.8 Hz, 1H), 6.67 (dd, J = 8.1, 4.5 Hz, 1H), 3.62 (td, J = 11.1, 6.6 Hz, 1H), 3.49 - 3.31 (m, 3H), 2.77 (ddt, J = 11.2, 8.5, 4.2 Hz, 1H), 2.30 (s, 6H), 2.20 (dt, J = 12.8, 6.3 Hz, 1H), 1.93 - 1.82 (m, 1H). MS (ESI, m / z): 237.2 [M+H] +

[1455] (Step 2)

[1456] The product of Step 1 (1.08 g, 1.0 eq), Na2S2O4 (3.2 g, 4 eq), and K2CO3 (1.27 g, 2 eq) were dissolved in MeOH (9.0 mL) and H2O (9.0 mL), and the reaction mixture was heated to 55 °C and stirred for 4 hours. When the reaction was complete, the organic layer was separated using water and ethyl acetate, and the title compound obtained by drying on anhydrous magnesium sulfate was dissolved in ethyl acetate (5 mL), and then 1 N HCl ethyl acetate solution (1 eq) was added while stirring. The resulting solid was filtered to obtain (S)-2-(3-(dimethylamino)pyrrolidin-1-yl)pyridine-3-amine hydrochloride (0.55 g, yield: 50%).

[1457] 1 H NMR (500 MHz, DMSO-d6) δ 11.29 (s, 1H), 7.52 (dd, J = 5.0, 1.6 Hz, 1H), 7.04 (d, J = 7.7 Hz, 1H), 6.81 (dd, J = 7.7, 5.0 Hz, 1H), 3.89 (p, J = 6.6 Hz, 1H), 3.70 (dd, J = 11.6, 5.2 Hz, 1H), 3.64 - 3.56 (m, 2H), 3.23 (q, J = 8.4 Hz, 1H), 2.78 (s, 6H), 2.35 - 2.16 (m, 2H). MS (ESI, m / z): 207.21 [M+H] +

[1458] (Step 3)

[1459] The title compound (84 mg, yield: 33%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidin-1-yl)pyridine-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1460] 1 H NMR (500 MHz, DMSO-d6) δ 10.20 (s, 1H), 9.14 (s, 1H), 8.79 (s, 1H), 8.01 (d, J = 8.6 Hz, 2H), 7.96 (d, J = 4.9 Hz, 1H), 7.45 (dd, J = 7.5, 1.9 Hz, 1H), 7.23 (d, J = 8.2 Hz, 2H), 7.17 - 7.03 (m, 2H), 7.00 (d, J = 8.3 Hz, 2H), 4.01 (s, 1H), 3.78 (s, 3H), 3.77 - 3.72 (m, 1H), 3.63 (d, J = 8.8 Hz, 1H), 3.58 (dd, J = 11.8, 4.9 Hz, 1H), 3.10 (q, J = 8.6 Hz, 1H), 2.87 (s, 6H), 2.54 (d, J = 3.5 Hz, 1H), 2.37 (s, 1H). MS (ESI, m / z): 520.3 [M+H] +

[1461]

[1462] Example 140: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1463]

[1464] (Step 1)

[1465] The title compound (74 mg, yield: 30%) was obtained in the same manner as in Example 134, except that N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide in step 3 of Example 134.

[1466] 1H NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.99 (s, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.90 (d, J = 8.2 Hz, 1H), 7.44 (t, J = 8.5 Hz, 1H), 7.36 (t, J = 8.2 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.26 - 7.12 (m, 5H), 7.11 (s, 1H), 4.11 (s, 1H), 3.78 - 3.70 (m, 2H), 3.57 (d, J = 13.6) Hz, 1H), 3.27 (s, 1H), 2.93 (s, 6H), 2.54 - 2.50 (m, 1H), 2.37 (dd, J = 4.0, 2.1 Hz, 1H), 2.30 (d, J = 3.1 Hz, 3H). MS (ESI, m / z): 503.6 [M+H] +

[1467]

[1468] Example 141: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1469]

[1470] (Step 1)

[1471] 2-chloro-5-methyl-3-nitropyridine (0.86 g, 1.0 eq) was dissolved in acetonitrile (25 mL), and then (S)-N,N-dimethylpyrrolidin-3-amine (0.6 g, 1.05 eq) and potassium carbonate (1.0 g, 1.5 eq) were added. The reaction mixture was heated to 50 °C and reacted overnight. When the reaction was complete, the organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain (S)-N,N-dimethyl-1-(5-methyl-3-nitropyridine-2-yl)pyrrolidin-3-amine (1.15 g, yield: 92%).

[1472] 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J = 2.1 Hz, 1H), 7.92 (d, J = 2.2 Hz, 1H), 3.61 (td, J = 11.1, 6.6 Hz, 1H), 3.44 (dd, J = 10.9, 8.8 Hz, 1H), 3.38 (dd, J = 10.9, 6.8 Hz, 1H), 3.32 (ddd, J = 10.8, 8.4, 1.8 Hz, 1H), 2.77 (tt, J = 9.4, 6.3 Hz, 1H), 2.30 (s, 6H), 2.28 (s, 3H), 2.19 (dt, J = 12.1, 6.7 Hz, 1H), 1.87 (qd, J = 10.9, 8.3 Hz, 1H). MS (ESI, m / z): 221.2 [M+H] +

[1473] (Step 2)

[1474] The product of Step 1 (1.15 g, 1.0 eq), Na2S2O4 (3.2 g, 4 eq), and K2CO3 (1.27 g, 2 eq) were dissolved in MeOH (11.5 mL) and H2O (11.5 mL), and the reaction mixture was stirred for 4 hours at 55 °C. When the reaction was complete, the organic layer was separated using water and ethyl acetate and dried over anhydrous magnesium sulfate to obtain (S)-2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylpyridine-3-amine (0.40 g, yield: 40%).

[1475] 1H NMR (500 MHz, DMSO-d6) δ 7.31 (d, J = 2.0 Hz, 1H), 6.71 (d, J = 2.1 Hz, 1H), 4.57 (s, 2H), 4.03 (q, J = 7.1 Hz, 1H), 3.46 - 3.37 (m, 1H), 3.39 - 3.30 (m, 2H), 3.19 - 3.14 (m, 1H), 2.70 (p, J = 7.7 Hz, 1H), 2.17 (s, 7H), 2.08 (s, 3H), 2.04 - 1.98 (m, 2H), 1.68 (dq, J = 11.9, 8.4 Hz, 1H). MS (ESI, m / z): 221.2 [M+H] +

[1476] (Step 3)

[1477] The product of Step 2 (0.40 g, 1.0 eq) was dissolved in ethyl acetate (5 mL), and then 1 N HCl ethyl acetate solution (1 eq) was added while stirring. The obtained solid was filtered to obtain (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine hydrochloride (0.47 g, yield: 99%).

[1478] 1 H NMR (500 MHz, DMSO-d6) δ 11.50 (s, 1H), 7.38 (s, 1H), 7.23 (s, 1H), 4.05 - 3.95 (m, 0H), 3.97 - 3.85 (m, 1H), 3.57 (q,J= 8.1 Hz, 1H), 2.81 (d,J= 3.9 Hz, 6H), 2.44 - 2.28 (m, 1H), 2.20 (s, 3H). MS (ESI, m / z): 221.2 [M+H] +

[1479] (Step 4)

[1480] The title compound (26 mg, yield: 37%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine HCl.

[1481] 1 H NMR (500 MHz, CDCl3) δ 8.66 (s, 1H), 8.64 (s, 1H), 7.98 (d, J = 8.5 Hz, 2H), 7.87 (s, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.38 (dt, J = 20.7, 7.3 Hz, 2H), 7.30 (d, J = 8.0 Hz, 1H), 7.03 (d, J = 8.5 Hz, 2H), 3.89 (s, 3H), 3.53 (t, J = 8.9 Hz, 1H), 3.37 - 3.26 (m, 3H), 2.95 (s, 1H), 2.36 (s, 6H), 2.34 (s, 3H), 2.04 - 1.95 (m, 1H), 1.84 (p, J = 8.8 Hz, 1H). MS (ESI, m / z): 532.4 [M+H] +

[1482]

[1483] Example 142: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1484]

[1485]

[1486] (Step 1)

[1487] The title compound (26 mg, yield: 37%) was obtained in the same manner as in Example 4, except that (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine HCl was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine in step 3 of Example 4.

[1488] 1 H NMR (500 MHz, CDCl3) δ 8.72 (s, 1H), 8.68 (s, 1H), 7.92 (d, J = 7.9 Hz, 2H), 7.87 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.45 - 7.33 (m, 4H), 7.31 (d, J = 7.2 Hz, 1H), 3.59 (t, J = 8.9 Hz, 1H), 3.39 (t, J = 8.7 Hz, 1H), 3.33 - 3.31 (m, 1H), 3.25 (q, J = 8.4 Hz, 1H), 3.16 (s, 1H), 2.46 (s, 9H), 2.35 (s, 3H), 2.04 (s, 1H), 1.94 - 1.92 (m, 1H). MS (ESI, m / z): 518.3 [M+H] +

[1489]

[1490] Example 143: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide

[1491]

[1492] (Step 1)

[1493] N-(3-chloroquinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide (158 mg, yield: 90%) was obtained in the same manner as in Example 1, except that 3,4-dimethoxybenzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1494] 1H NMR (500 MHz, DMSO-d6) δ 7.90 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.79 (t, J = 7.2 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.6 Hz, 1H), 3.87 (s, 3H), 3.83 (s, 3H). MS (ESI, m / z): 380.2 [M+H] +

[1495] (Step 2)

[1496] The title compound (91 mg, yield: 59%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1497] 1 H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.91 (d,J= 8.0 Hz, 1H), 7.83 (s, 1H), 7.56 (dd,J= 8.4, 2.1 Hz, 1H), 7.50 - 7.44 (m, 1H), 7.41 (s, 1H), 7.24 - 7.12 (m, 4H), 6.97 (t,J= 7.8 Hz, 2H), 4.18 (s, 1H), 3.84 (s, 3H), 3.75 (s, 3H), 3.70 - 3.54 (m, 1H), 3.47 (dd,J= 11.2, 7.2 Hz, 1H), 2.97 (s, 6H), 2.71 (q,J= 8.1 Hz, 1H), 2.60 - 2.52 (m, 1H), 2.38 (s, 1H). MS (ESI, m / z): 549.3 [M+H] +

[1498]

[1499] Example 144: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide

[1500]

[1501] (Step 1)

[1502] N-(3-chloroquinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide (152 mg, yield: 85%) was obtained in the same manner as in Example 1, except that 4-(2-methyloxazole-4-yl)benzenesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1503] 1 H NMR (500 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.22 (d, J = 8.2 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H), 7.89 (dt, J = 8.1, 1.7 Hz, 2H), 7.77 (t, J = 7.7) Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H), 2.47 (s, 3H). MS (ESI, m / z): 401.2 [M+H] +

[1504] (Step 2)

[1505] The title compound (97 mg, yield: 59%) was obtained in the same manner as in Example 4, except that N-(3-chloroquinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 3 of Example 4.

[1506] 1H NMR (500 MHz, DMSO-d6) δ 9.97 (s, 1H), 9.57 (s, 1H), 8.90 (d, J = 8.2 Hz, 1H), 8.52 (s, 1H), 8.10 (d, J = 8.1 Hz, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.19 (dt, J = 20.1, 8.0 Hz, 5H), 7.15 - 7.07 (m, 1H), 6.98 (t, J = 7.6 Hz, 1H), 4.17 (s, 1H), 3.64 - 3.44 (m, 2zH), 3.35 - 3.08 (m, 1H), 2.96 (s, 6H), 2.75 (q, J = 8.1 Hz, 1H), 2.55 - 2.52 (m, 1H), 2.45 (s, 3H), 2.42 - 2.24 (m, 1H). MS (ESI, m / z): 570.46 [M+H] +

[1507]

[1508] Example 145: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1509]

[1510] (Step 1)

[1511] (S)-1-(5-methoxy-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (7.5 g, yield: 96.8%) was obtained in the same manner as in Example 1, except that 2-fluoro-4-methoxy-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1512] 1H NMR (500 MHz, DMSO-d6) δ 7.76 (dd, J = 8.7, 2.8 Hz, 1H), 6.41 (d, J = 2.8 Hz, 1H), 6.38 (dd, J = 9.3, 2.5 Hz, 1H), 3.84 (d, J = 2.7 Hz, 3H), 3.41 - 3.34 (m, 1H), 3.19 - 3.04 (m, 3H), 2.72 (d, J = 8.3 Hz, 1H), 2.18 (t, J = 2.4 Hz, 6H), 2.15 - 2.08 (m, 1H), 1.75 (p, J = 10.1 Hz, 1H). MS (ESI, m / z): 266.2 [M+H] +

[1513] (Step 2)

[1514] (S)-1-(2-amino-5-methoxyphenyl)-N,N-dimethylpyrrolidine-3-amine (3.8 g, yield: 57.1%) was obtained by the same method as in Step 3 of Example 1.

[1515] 1 H NMR (500 MHz, DMSO-d6) δ 6.57 (dd, J = 8.5, 2.5 Hz, 1H), 6.44 (d, J = 2.7 Hz, 1H), 6.35 (dd, J = 8.4, 2.8 Hz, 1H), 4.14 (s, 2H), 3.63 (d, J = 8.4, 2.8 Hz, 1H) 2.4 Hz, 3H), 3.22 - 3.13 (m, 1H), 3.12 - 3.06 (m, 1H), 2.89 (q, J = 7.6 Hz, 2H), 2.77 (p, J = 7.2 Hz, 1H), 2.16 (d, J = 2.7 Hz, 6H), 2.06 - 1.95 (m, 1H), 1.71 (h, J = 7.1 Hz, 1H). MS (ESI, m / z): 236.2 [M+H] +

[1516] (Step 3)

[1517] (S)-1-(2-amino-5-methoxyphenyl)-N,N-dimethylpyrrolidine-3-amine hydrochloride (4.0 g, yield: 92.1%) was obtained by the same method as in step 3 of Example 132.

[1518] 1 H NMR (500 MHz, DMSO-d6) δ 9.58 (s, 1H), 7.23 (d, J = 8.6 Hz, 1H), 6.72 (d, J = 2.8 Hz, 1H), 6.68 (d, J = 8.7 Hz, 1H), 3.89 (s, 1H), 3.75 (s, 3H), 3.56 (dd, J = 10.9, 3.7 Hz, 1H), 3.38 - 3.26 (m, 2H), 2.99 (q, J = 8.1 Hz, 1H), 2.81 (s, 6H), 2.32 (ddt, J = 12.9, 8.8, 4.6 Hz, 1H), 2.23 (dq, J = 13.5, 6.9 Hz, 1H).

[1519] (Step 4)

[1520] The title compound (704 mg, yield: 22.1%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride was used instead of (S)-1-(2-amino-5-methoxyphenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1521] 1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 9.16 (s, 1H), 8.60 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.53 - 7.48 (m, 1H), 7.47 - 7.44 (m, 1H), 7.33 - 7.28 (m, 2H), 7.23 (d, J = 7.9 Hz, 2H), 6.80 - 6.72 (m, 2H), 4.03 (s, 1H), 3.76 (s, 3H), 3.45 (dd, J = 11.0, 7.3 Hz, 1H), 2.89 (s, 6H), 2.80 (q, J = 8.3 Hz, 1H), 2.36 (s, 1H), 2.34 (s, 3H), 2.30 (s, 2H), 2.25 (s, 1H). MS (ESI, m / z): 533.3 [M+H] +

[1522]

[1523] Example 146: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1524]

[1525] (Step 1)

[1526] The title compound (1.0 g, yield: 31.9%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-amino-5-methoxyphenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1527] 1H NMR (500 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.60 (s, 1H), 8.01 (d, J = 8.5 Hz, 2H), 7.55 - 7.48 (m, 1H), 7.48 - 7.43 (m, 1H), 7.35 - 7.28 (m, 1H), 7.25 - 7.19 (m, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.4 Hz, 1H), 6.77 - 6.72 (m, 1H), 4.03 (q, J = 7.1 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.45 (dd, J = 11.1, 7.2 Hz, 1H), 3.41 - 3.27 (m, 6H), 2.85 - 2.80 (m, 1H), 2.25 (s, 2H), 2.18 (t, J = 8.1 Hz, 1H), 1.90 (p, J = 7.6 Hz, 1H). MS (ESI, m / z): 549.3 [M+H] +

[1528]

[1529] Example 147: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1530]

[1531] (Step 1)

[1532] (S)-1-(4-methoxy-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (7.5 g, yield: 96.8%) was obtained in the same manner as in Example 1, except that 1-fluoro-4-methoxy-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1533] 1H NMR (500 MHz, DMSO-d6) δ 7.29 (q, J = 2.8 Hz, 1H), 7.17 (dt, J = 9.4, 2.9 Hz, 1H), 7.08 - 7.02 (m, 1H), 3.74 (d, J = 2.6 Hz, 3H), 3.30 (td, J = 8.4, 5.5 Hz, 1H), 3.12 - 2.98 (m, 3H), 2.71 (q, J = 7.7 Hz, 1H), 2.17 (d, J = 2.8 Hz, 6H), 2.10 (dp, J = 9.2, 3.1 Hz, 1H), 1.74 (p, J = 10.1 Hz, 1H). MS (ESI, m / z): 266.2 [M+H] +

[1534] (Step 2)

[1535] (S)-1-(2-amino-4-methoxyphenyl)-N,N-dimethylpyrrolidine-3-amine (4.8 g, yield: 71.1%) was obtained by the same method as in Step 3 of Example 1.

[1536] 1 H NMR (500 MHz, DMSO-d6) δ 6.82 (dt, J = 8.6, 2.2 Hz, 1H), 6.25 (t, J = 2.5 Hz, 1H), 6.08 (dd, J = 8.5, 2.6 Hz, 1H), 4.70 (s, 2H), 3.62 (t, J) = 2.1 Hz, 3H), 3.04 (q, J = 7.7 Hz, 1H), 2.98 (p, J = 5.5 Hz, 1H), 2.83 - 2.73 (m, 3H), 2.14 (t, J = 2.3 Hz, 6H), 2.03 - 1.93 (m, 1H), 1.76 - 1.66 (m, 1H). MS (ESI, m / z): 236.2 [M+H] +

[1537] (Step 3)

[1538] (S)-1-(2-amino-4-methoxyphenyl)-N,N-dimethylpyrrolidine-3-amine hydrochloride (5.1 g, yield: 92.0%) was obtained by the same method as in step 3 of Example 132.

[1539] 1 H NMR (500 MHz, DMSO-d6) δ 11.02 (s, 1H), 6.99 (d, J = 8.7 Hz, 1H), 6.47 (d, J = 2.9 Hz, 1H), 6.35 (dd, J = 8.8, 2.8 Hz, 1H), 3.85 (dp, J = 8.7, 4.4 Hz, 1H), 3.67 (s, 3H), 3.36 (dd, J = 11.0, 3.7 Hz, 1H), 3.18 (td, J = 8.6, 4.0 Hz, 1H), 3.08 (dd, J = 11.0, 6.8 Hz, 1H), 2.84 - 2.78 (m, 1H), 2.77 (s, 6H), 2.26 (dtd, J = 12.6, 8.1, 4.0 Hz, 1H), 2.16 (tt, J = 10.8, 5.3 Hz, 1H).

[1540] (Step 4)

[1541] The title compound (344 mg, yield: 10.8%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride was used instead of (S)-1-(2-amino-4-methoxyphenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1542] 1H NMR (500 MHz, DMSO-d6) δ 9.91 - 9.58 (m, 1H), 8.67 (d, J = 3.0 Hz, 1H), 7.93 (d, J = 7.8 Hz, 2H), 7.46 (d, J = 7.3 Hz, 1H), 7.43 - 7.36 (m, 1H), 7.22 (d, J = 8.2 Hz, 2H), 7.20 - 7.13 (m, 3H), 6.56 - 6.50 (m, 1H), 4.15 (s, 1H), 3.79 (s, 2H), 3.47 - 3.36 (m, 2H), 3.32 - 3.25 (m, 3H), 2.96 (s, 6H), 2.45 - 2.41 (m, 1H), 2.36 (s, 1H), 2.30 (s, 3H). MS (ESI, m / z): 533.3 [M+H] +

[1543]

[1544] Example 148: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide

[1545]

[1546] (Step 1)

[1547] The title compound (642 mg, yield: 16.4%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1548] 1H NMR (500 MHz, DMSO-d6) δ 9.84 - 9.61 (m, 2H), 8.67 (s, 1H), 7.99 (d, J = 8.3 Hz, 2H), 7.48 - 7.44 (m, 1H), 7.39 - 7.28 (m, 1H), 7.24 - 7.10 (m, 3H), 6.95 (s, 2H), 6.56 - 6.51 (m, 1H), 4.17 (s, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.48 - 3.45 (m, 1H), 3.43 - 3.36 (m, 2H), 3.32 - 3.26 (m, 2H), 2.97 (s, 6H), 2.69 (q, J = 8.3 Hz, 1H). MS (ESI, m / z): 549.3 [M+H] +

[1549]

[1550] Example 149: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide

[1551]

[1552] (Step 1)

[1553] The title compound (39 mg, yield: 24%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine HCl.

[1554] 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J = 8.4 Hz, 2H), 7.87 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.65 (s, 1H), 7.42 - 7.35 (m, 2H), 7.31-7.28 (m, 2H), 7.23 (s, 1H), 3.53 - 3.49 (m, 1H), 3.38 - 3.27 (m, 3H), 2.86 (s, 1H), 2.41 (s, 6H), 2.34 (s, 3H), 2.31 (s, 6H), 1.96 - 1.95 (m, 1H), 1.80 (td, J = 8.6 Hz, 1H) MS (ESI, m / z): 532.4 [M+H] +

[1555]

[1556] Example 150: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide

[1557]

[1558] (Step 1)

[1559] The title compound (86 mg, yield: 32%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidin-1-yl)pyridine-3-amine.

[1560] 1H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.23 (s, 1H), 9.00 (s, 1H), 7.94 (d, J = 4.8 Hz, 1H), 7.69 (s, 2H), 7.44 (dd, J = 7.9, 1.6 Hz, 1H), 7.34 (s, 2H), 7.26 - 6.94 (m, 4H), 4.10 (s, 1H), 3.75 (dd, J = 11.8, 7.2 Hz, 2H), 3.57 (dd, J = 11.9, 4.2 Hz, 1H), 3.08 (d, J = 8.9 Hz, 1H), 2.93 (s, 6H), 2.55 - 2.53 (m, J = 15.6 Hz, 1H), 2.45 - 2.33 (m, 1H), 2.31 (s, 6H). MS (ESI, m / z): 518.2 [M+H] +

[1561]

[1562] Example 151: Preparation of 4-methoxy-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide

[1563]

[1564] The title compound (50 mg, yield: 47%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, cis-2-methyl-octahydropyrrolo[3,4-c]pyrrolo was used instead of (S)-N,N-dimethylpyrrolidin-3-amine, and in Step 3, 2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrolo-2(1H)-yl)aniline was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine, and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1565] 1H NMR (500 MHz, CDCl3) δ 9.21 (s, 1H), 8.85 (d,J= 8.1 Hz, 1H), 7.93 (d,J= 8.5 Hz, 2H), 7.71 (d,J= 8.0 Hz, 1H), 7.40 (t,J= 7.6 Hz, 1H), 7.37 - 7.26 (m, 2H), 7.21 (d,J= 8.1 Hz, 2H), 7.08 (t,J= 7.6 Hz, 1H), 6.98 (d,J= 8.5 Hz, 2H), 5.45 (s, 1H), 3.87 (s, 3H), 3.13 (s, 2H), 3.05 - 3.01 (m, 4H), 2.97 (d,J= 9.4 Hz, 2H), 2.70 (s, 3H), 2.04 (s, 2H).

[1566]

[1567] Example 152: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1568]

[1569] The title compound (30 mg, yield: 21%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, tert-butyl(S)-pyrrolidin-3-yl carbamate was used instead of (S)-N,N-dimethylpyrrolidin-3-amine, and in Step 3, tert-butyl(S)-(1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-yl)carbamate was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine, and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1570] 1H NMR (500 MHz, DMSO-d6-d6) δ 9.73 (s, 1H), 8.93 (s, 1H), 8.14 (s, 3H), 8.03 (d, J= 8.3 Hz, 2H), 7.49 - 7.44 (m, 1H), 7.33 (s, 1H), 7.26 (d,J= 7.9 Hz, 1H), 7.19-7.15 (m, 3H), 6.96 (s, 3H), 4.01 (s, 1H), 3.77 (s, 3H), 3.42 (d,J= 10.6 Hz, 1H), 3.29 (s, 2H), 3.19 - 3.11 (m, 1H), 3.07 (s, 1H), 2.03 (s, 1H).

[1571]

[1572] Example 153: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1573]

[1574] (Step 1)

[1575] The title compound (163 mg, yield: 20.3%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride was used instead of (S)-1-(2-amino-5-chlorophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1576] 1H NMR (500 MHz, DMSO-d6) δ 9.99 - 9.68 (m, 1H), 9.55 (s, 1H), 8.92 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 7.7 Hz, 1H), 7.35 - 7.27 (m, 2H), 7.26 - 7.12 (m, 5H), 4.20 (s, 1H), 3.60 (s, 1H), 3.51 (dd, J = 11.1, 7.2 Hz, 1H), 3.41 - 3.24 (m, 1H), 2.97 (s, 6H), 2.77 (q, J = 8.3 Hz, 1H), 2.59 - 2.52 (m, 1H), 2.45 - 2.39 (m, 1H), 2.29 (s, 3H). MS (ESI, m / z): 537.3 [M+H] +

[1577]

[1578] Example 154: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide

[1579]

[1580] (Step 1)

[1581] The title compound (265 mg, yield: 32.9%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methylbenzenesulfonamide.

[1582] 1H NMR (500 MHz, DMSO-d6) δ 10.14 - 9.65 (m, 1H), 9.55 (s, 1H), 8.92 (d, J = 8.7 Hz, 1H), 7.92 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.45 (d, J) = 7.9 Hz, 1H), 7.33 - 7.26 (m, 2H), 7.25 - 7.11 (m, 5H), 4.21 (s, 1H), 3.62 - 3.58 (m, 1H), 3.52 (dd, J = 11.3, 7.2 Hz, 1H), 3.40 - 3.24 (m, 2H), 2.98 (s, 6H), 2.78 (q, J = 8.3 Hz, 1H), 2.45 - 2.39 (m, 1H), 2.35 (s, 3H). MS (ESI, m / z): 537.3 [M+H] +

[1583]

[1584] Example 155: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide

[1585]

[1586] (Step 1)

[1587] The title compound (226 mg, yield: 28.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3-methoxybenzenesulfonamide.

[1588] 1H NMR (500 MHz, DMSO-d6) δ 10.01 - 9.65 (m, 1H), 9.55 (s, 1H), 8.93 (d, J = 8.7 Hz, 1H), 7.75 (s, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.46 (d, J) = 7.7 Hz, 1H), 7.31 (t, J = 8.1 Hz, 2H), 7.26 - 7.12 (m, 4H), 6.96 (d, J = 8.2 Hz, 1H), 4.21 (s, 1H), 3.81 (s, 3H), 3.62 - 3.59 (m, 1H), 3.52 (dd, J = 11.3, 7.2 Hz, 2H), 3.41 - 3.23 (m, 1H), 2.97 (s, 6H), 2.80 - 2.68 (m, 1H), 2.47 - 2.38 (m, 1H). MS (ESI, m / z): 553.3 [M+H] +

[1589]

[1590] Example 156: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide

[1591]

[1592] (Step 1)

[1593] The title compound (316 mg, yield: 39.9%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-2-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1594] 1H NMR (500 MHz, DMSO-d6) δ 10.13 - 9.71 (m, 1H), 9.61 (s, 1H), 8.97 (d, J = 8.7 Hz, 1H), 8.16 - 8.11 (m, 1H), 7.42 (d, J = 6.4 Hz, 1H), 7.30 - 7.24 (m, 3H), 7.22 (dd, J = 8.7, 2.4 Hz, 1H), 7.19 - 7.01 (m, 4H), 4.17 (s, 1H), 3.68 - 3.56 (m, 1H), 3.53 (t, J = 9.3 Hz, 1H), 3.43 - 3.20 (m, 2H), 2.95 (s, 6H), 2.78 (d, J = 8.9 Hz, 1H), 2.59 (s, 3H), 2.42 - 2.33 (m, 1H). MS (ESI, m / z): 537.3 [M+H] +

[1595]

[1596] Example 157: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide

[1597]

[1598] The title compound (3 mg, yield: 3%) was obtained in the same manner as in Example 1, except that 2,3-dichloro-6,7-dimethoxyquinoxaline was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1 and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1599] 1H NMR (500 MHz, CDCl3) δ 9.26 (s, 1H), 8.76 (d,J= 8.1 Hz, 1H), 7.89 (d,J= 7.9 Hz, 2H), 7.34 (d,J= 8.0 Hz, 2H), 7.20 (m, 3H), 7.07 (t,J= 7.7 Hz, 1H), 6.77 (s, 1H), 4.02 (s, 3H), 4.00 (s, 3H), 3.41 (s, 1H), 3.20-3.13 (m, 2H), 3.03 (s, 1H), 2.54 (s, 6H), 2.44 (s, 3H), 2.07 (s, 1H), 1.74 (s, 1H), 1.52 (s, 1H).

[1600]

[1601] Example 158: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1602]

[1603] The title compound (40 mg, yield: 39%) was obtained in the same manner as in Example 1, except that 2,3-dichloro-6,7-dimethylquinoxaline was used instead of 2,3-dichloroquinoxaline and 4-methoxybenzene-sulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1, and (S)-1-(2-amino-4-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1604] 1H NMR (500 MHz, CDCl3) δ 9.32 (s, 1H), 8.81 (d,J= 8.0 Hz, 1H), 7.96 (dd,J= 8.9, 1.9 Hz, 2H), 7.50 (s, 1H), 7.16 (d,J= 8.1 Hz, 2H), 7.05 (s, 2H), 7.00 (d,J= 7.8 Hz, 2H), 5.32 (d,J= 1.8 Hz, 1H), 3.87 (s, 3H), 3.32 (s, 1H), 3.15-3.00 (m, 4H), 2.37 (s, 12H), 2.08 - 1.97 (m, 1H), 1.93-1.88 (m, 1H).

[1605]

[1606] Example 159: Preparation of (S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1607]

[1608] The title compound (10 mg, yield: 9.3%) was obtained in the same manner as in Example 4, except that 4-chloro-1-fluoro-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 1 of Example 4 and N-(3-chloro-6,7-dimethylquinoxaline-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxaline-2-yl)-4-methylbenzenesulfonamide in Step 3.

[1609] 1H NMR (500 MHz, MeOD) δ 8.95 (s, 1H), 8.02 (d,J= 8.5 Hz, 2H), 7.37 (s, 1H), 7.31 (s, 1H), 7.16-7.14 (m, 1H), 7.02 (d,J= 8.5 Hz, 2H), 6.96 - 6.92 (m, 1H), 4.13-4.09 (m, 1H), 3.83 (s, 3H), 3.75-3.67 (m, 1H), 3.42-3.35 (m, 2H), 2.96-2.91 (m, 1H), 2.81 (s, 6H), 2.33 (d,J= 4.0 Hz, 6H), 2.25-2.21 (m, 1H).

[1610]

[1611] Example 160: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1612]

[1613] (Step 1)

[1614] 2,4-difluoro-1-nitrobenzene (10.0 g, 1.0 eq) was dissolved in tetrahydrofuran (200 mL), followed by the addition of (S)-N,N-dimethylpyrrolidin-3-amine (7.2 g, 1.0 eq) and potassium carbonate (17.4 g, 2.0 eq). The reaction mixture was reacted at rt for 12 hours, and once the reaction was complete, an aqueous NH4Cl solution was added. The organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (ethyl acetate alone) to obtain (S)-1-(5-fluoro-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (yield 94.2%, 15 g).

[1615] 1H NMR (500 MHz, DMSO-d6) δ 7.79 (dd, J = 9.1, 6.2 Hz, 1H), 6.80 (dd, J = 12.5, 2.8 Hz, 1H), 6.59 - 6.51 (m, 1H), 3.62 - 3.56 (m, 1H), 3.32 (td, J = 10.3, 6.5 Hz, 1H), 3.16 - 3.05 (m, 2H), 2.68 (h, J = 6.6 Hz, 1H), 2.21 - 2.11 (m, 6H), 2.14 - 2.06 (m, 1H), 1.80 - 1.69 (m, 1H). MS (ESI, m / z): 254.2 [M+H] +

[1616] (Step 2)

[1617] (S)-1-(2-amino-5-fluorophenyl)-N,N-dimethylpyrrolidine-3-amine (8.7 g, yield: 65.4%) was obtained by the same method as in Step 3 of Example 1.

[1618] 1 H NMR (500 MHz, DMSO-d6) δ 6.68 - 6.57 (m, 2H), 6.53 (td, J = 8.6, 2.8 Hz, 1H), 4.41 (s, 2H), 3.20 (q, J = 7.7 Hz, 1H), 3.11 (t, J = 8.1 Hz, 1H), 2.90 (dt, J = 9.5, 5.0 Hz, 2H), 2.78 (p, J = 7.5 Hz, 1H), 2.16 (s, 6H), 2.08 - 1.97 (m, 1H), 1.72 (dq, J = 14.7, 7.6 Hz, 1H). MS (ESI, m / z): 224.2 [M+H] +

[1619] (Step 3)

[1620] The title compound (1.1 g, yield: 34.4%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1621] 1 H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.41 (s, 1H), 8.86 (s, 1H), 7.93 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.6 Hz, 1H), 7.32 - 7.28 (m, 1H), 7.20 (d, J = 7.8 Hz, 2H), 7.14 (t, J = 8.3 Hz, 2H), 7.08 (dd, J = 10.5, 2.8 Hz, 1H), 7.01 - 6.94 (m, 1H), 4.26 - 4.09 (m, 1H), 3.58 (s, 1H), 3.48 (t, J = 9.3 Hz, 1H), 3.37 (d, J = 11.1 Hz, 1H), 2.95 (s, 6H), 2.78 (d, J = 8.4 Hz, 1H), 2.46 - 2.35 (m, 2H), 2.29 (s, 3H). MS (ESI, m / z): 521.3 [M+H] +

[1622]

[1623] Example 161: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1624]

[1625] (Step 1)

[1626] The title compound (696 mg, yield: 22.7%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1627] 1 H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.41 (s, 1H), 8.86 (s, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 7.7 Hz, 1H), 7.31 (s, 1H), 7.20 - 7.11 (m, 2H), 7.08 (d, J = 10.8 Hz, 1H), 6.98 (t, J = 9.1 Hz, 1H), 6.93 (d, J = 8.3 Hz, 2H), 4.25 - 4.13 (m, 1H), 3.75 (s, 3H), 3.64 - 3.54 (m, 1H), 3.48 (t, J = 9.2 Hz, 1H), 3.39 - 3.34 (m, 1H), 2.96 (s, 6H), 2.84 - 2.73 (m, 1H), 2.46 - 2.34 (m, 2H). MS (ESI, m / z): 537.3 [M+H] +

[1628]

[1629] Example 162: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide

[1630]

[1631] (Step 1)

[1632] The title compound (38 mg, yield: 20%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide, and (S)-2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylpyridine-3-amine HCl was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine.

[1633] 1 H NMR (500 MHz, DMSO-d6) δ 9.28 (s, 1H), 8.92 (s, 1H), 8.50 (s, 1H), 8.09 (d, J = 8.0 Hz, 2H), 7.81 - 7.74 (m, 3H), 7.46 (d, J = 7.7 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.24 - 7.07 (m, 3H), 4.06 (s, 1H), 3.68 (ddd, J = 17.8, 10.8, 6.7 Hz, 1H), 3.51 (dd, J = 11.6, 4.4 Hz, 1H), 3.03 (q, J = 8.4 Hz, 1H), 2.91 (s, 6H), 2.55 (d, J = 9.9 Hz, 1H), 2.45 (s, 3H), 2.39 (q, J = 7.1 Hz, 2H), 2.31 (s, 3H) MS (ESI, m / z): 584.44 [M+H] +

[1634]

[1635] Example 163: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide

[1636]

[1637] (Step 1)

[1638] The title compound (25 mg, yield: 31%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine HCl.

[1639] 1 H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.32 (s, 1H), 8.92 (s, 1H), 7.83 (s, 1H), 7.76 (s, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.37 (s, 1H), 7.26 - 7.05 (m, 3H), 6.96 (d, J = 8.3 Hz, 1H), 4.11 (s, 1H), 3.84 (s, 3H), 3.75 (s, 3H), 3.69 (dd, J = 11.8, 7.2 Hz, 2H), 3.50 (dd, J = 12.1, 3.8 Hz, 1H), 3.40 - 3.25 (m, 1H), 2.94 (s, 6H), 2.55 - 2.52 (m, 1H), 2.46 - 2.35 (m, 1H), 2.31 (s, 3H). MS (ESI, m / z): 564.4 [M+H] +

[1640]

[1641] Example 164: Preparation of Methyl(S)-3-(3-(dimethylamino)pyrrolidine-1-yl)-4-((3-((4-methoxyphenyl)sulfonamido)quinoxalin-2-yl)amino)benzoate

[1642]

[1643] (Step 1)

[1644] Methyl(S)-3-(3-(dimethylamino)pyrrolidin-1-yl)-4-nitrobenzoate (14.0 g, yield: 95.0%) was obtained in the same manner as in Example 1, except that methyl 3-fluoro-4-nitrobenzoate was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1645] 1 H NMR (500 MHz, DMSO-d6) δ 7.82 (dd, J = 8.4, 2.7 Hz, 1H), 7.50 (d, J = 2.8 Hz, 1H), 7.25 (dd, J = 8.4, 2.5 Hz, 1H), 3.88 (d, J = 2.7 Hz, 3H), 3.35 (t, J = 13.3 Hz, 1H), 3.20 (t, J = 9.2 Hz, 1H), 3.13 (p, J = 9.3 Hz, 2H), 2.74 (t, J = 7.8 Hz, 1H), 2.17 (s, 6H), 2.13 (d, J = 6.6) Hz, 1H), 1.78 (p, J = 9.9 Hz, 1H). MS (ESI, m / z): 294.2 [M+H] +

[1646] (Step 2)

[1647] Methyl(S)-4-amino-3-(3-(dimethylamino)pyrrolidine-1-yl)benzoate (9.0 g, yield: 71.6%) was obtained by the same method as in Step 3 of Example 1.

[1648] 1H NMR (500 MHz, DMSO-d6) δ 7.43 (d, J = 9.6 Hz, 1H), 6.67 (d, J = 7.9 Hz, 1H), 5.49 (s, 1H), 4.11 (s, 2H), 3.74 (s, 3H), 3.16 - 3.07 (m, 2H), 2.85 (ddt, J = 24.5, 14.7, 8.1 Hz, 3H), 2.16 (s, 6H), 2.08 - 1.97 (m, 1H), 1.75 (dq, J = 13.9, 7.2 Hz, 1H). MS (ESI, m / z): 264.3 [M+H] +

[1649] (Step 3)

[1650] The title compound (522 mg, yield: 15.8%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, methyl(S)-4-amino-3-(3-(dimethylamino)pyrrolidin-1-yl)benzoate was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1651] 1H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.75 (s, 1H), 9.06 (d, J = 8.2 Hz, 1H), 7.99 (dd, J = 8.5, 3.5 Hz, 2H), 7.85 - 7.79 (m, 1H), 7.77 - 7.72 (m, 1H), 7.54 - 7.48 (m, 1H), 7.35 (s, 1H), 7.22 (q, J = 6.3 Hz, 1H), 7.19 - 7.13 (m, 1H), 6.96 - 6.90 (m, 2H), 4.30 - 4.15 (m, 1H), 3.84 (s, 3H), 3.75 (s, 3H), 3.63 (s, 1H), 3.59 - 3.51 (m, 1H), 3.41 (d, J = 11.1 Hz, 1H), 2.99 (s, 6H), 2.76 (q, J = 8.2 Hz, 1H), 2.60 - 2.56 (m, 1H), 2.47 - 2.39 (m, 1H). MS (ESI, m / z): 577.3 [M+H] +

[1652]

[1653] Example 165: Preparation of (S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1654]

[1655] (Step 1)

[1656] (S)-1-(5-bromo-2-nitrophenyl)-N,N-dimethylpyrrolidine-3-amine (14.0 g, yield: 98.0%) was obtained in the same manner as in Example 1, except that 4-bromo-2-fluoro-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine.

[1657] 1H NMR (500 MHz, DMSO-d6) δ 7.67 (dt, J = 8.9, 2.2 Hz, 1H), 7.22 (d, J = 2.8 Hz, 1H), 6.91 (dd, J = 8.8, 2.3 Hz, 1H), 3.32 (d, J = 8.9 Hz, 1H), 3.11 (q, J = 7.2 Hz, 3H), 2.71 (p, J = 7.7 Hz, 1H), 2.17 (s, 6H), 2.15 - 2.07 (m, 1H), 1.75 (p, J = 10.1 Hz, 1H). MS (ESI, m / z): 314.1 [M+H] +

[1658] (Step 2)

[1659] (S)-1-(2-amino-5-bromophenyl)-N,N-dimethylpyrrolidine-3-amine (8.5 g, yield: 67.2%) was obtained by the same method as in Step 3 of Example 1.

[1660] 1 H NMR (500 MHz, DMSO-d6) δ 6.90 (s, 1H), 6.86 (d, J = 8.4 Hz, 1H), 6.59 (d, J = 8.3 Hz, 1H), 4.74 (s, 2H), 4.11 (s, 1H), 3.18 (s, 3H), 3.09 (t, J = 8.1 Hz, 1H), 2.87 (q, J = 6.9 Hz, 2H), 2.78 (p, J = 7.4 Hz, 1H), 2.16 (s, 6H), 2.01 (dq, J = 13.7, 7.1 Hz, 1H), 1.72 (dq, J) = 14.5, 7.5 Hz, 1H). MS (ESI, m / z): 284.1 [M+H] +

[1661] (Step 3)

[1662] The title compound (877 mg, yield: 25.2%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1663] 1 H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.54 (s, 1H), 8.85 (d, J = 8.4 Hz, 1H), 7.96 - 7.90 (m, 2H), 7.45 (d, J = 7.5 Hz, 1H), 7.36 - 7.31 (m, 3H), 7.24 - 7.11 (m, 4H), 4.20 - 4.13 (m, 1H), 3.59 - 3.56 (m, 1H), 3.51 (t, J = 9.4 Hz, 1H), 3.38 (d, J = 10.9 Hz, 1H), 2.97 (s, 6H), 2.76 (d, J = 8.6 Hz, 1H), 2.67 - 2.57 (m, 1H), 2.40 (s, 1H), 2.29 (s, 3H). MS (ESI, m / z): 581.2 [M+H] +

[1664]

[1665] Example 166: Preparation of (S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1666]

[1667] (Step 1)

[1668] The title compound (891 mg, yield: 26.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1669] 1 H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.56 (s, 1H), 8.87 (d, J = 8.5 Hz, 1H), 7.99 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 7.7 Hz, 1H), 7.36 - 7.30 (m, 3H), 7.21 - 7.10 (m, 2H), 6.92 (d, J = 8.4 Hz, 2H), 4.23 - 4.12 (m, 1H), 3.75 (s, 3H), 3.58 (s, 1H), 3.50 (t, J = 9.4 Hz, 1H), 3.40 - 3.35 (m, 1H), 2.96 (s, 6H), 2.77 (q, J = 8.6 Hz, 1H), 2.45 - 2.34 (m, 1H), 2.09 (s, 1H). MS (ESI, m / z): 597.2 [M+H] +

[1670]

[1671] Example 167: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide

[1672]

[1673] (Step 1)

[1674] The title compound (28 mg, yield: 29%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)benzofuran-6-sulfonamide, and (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of (S)-2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-amine HCl.

[1675] 1 H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.31 (s, 1H), 8.92 (s, 1H), 8.34 (s, 1H), 8.09 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.32 (s, 1H), 7.23 - 7.11 (m, 2H), 6.98 (s, 1H), 4.13 (s, 1H), 3.72 - 3.67 (m, 2H), 3.51 (dd, J = 11.9, 3.8 Hz, 1H), 3.40 - 3.25 (m, 1H), 2.96 (s, 6H), 2.54 - 2.51 (m, 1H), 2.45- 2.33 (m, 1H), 2.31 (s, 3H). MS (ESI, m / z): 544.4 [M+H] +

[1676]

[1677] Example 168: Preparation of (S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide

[1678]

[1679] (Step 1)

[1680] The title compound (75.1 mg, yield: 67%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)benzofuran-6-sulfonamide.

[1681] 1 H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 9.00 (s, 1H), 8.34 (s, 1H), 8.09 (s, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.67 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 7.7 Hz, 1H), 7.32 (s, 1H), 7.24 (d, J = 8.5 Hz, 1H), 7.22 - 7.06 (m, 3H), 7.01 (d, J = 9.9 Hz, 1H), 6.99 (s, 1H), 4.23 (s, 1H), 3.67 - 3.55 (m, 2H), 3.48 (dd, J = 17.5, 9.4 Hz, 2H), 3.32 - 3.26 (m, 1H), 3.00 (s, 6H), 2.72 (q, J = 8.8 Hz, 1H), 2.44 (s, 1H). MS (ESI, m / z): 563.14 [M+H] +

[1682]

[1683] Example 169: Preparation of (S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide

[1684]

[1685] The title compound (4.6 mg, yield: 4%) was obtained in the same manner as in Example 1, except that 2,3-dichloro-6,7-dimethoxyquinoxaline was used instead of 2,3-dichloroquinoxaline in Step 1 of Example 1 and (S)-1-(2-amino-4-chlorophenyl)-N,N-dimethylpyrrolidine-3-amine was used instead of 2-(4-methylpiperazine-1-yl)aniline in Step 4.

[1686] 1 H NMR (500 MHz, MeOD) δ 8.93 (s, 1H), 7.95 (d,J= 7.7 Hz, 2H), 7.31 (d,J= 7.8 Hz, 2H), 7.18 (d,J= 8.4 Hz, 1H), 7.11 (d,J= 11.1 Hz, 2H), 6.96 (d,J= 8.7 Hz, 1H), 3.99 (s, 1H), 3.93 (s, 3H), 3.90 (s, 3H), 3.49-3.44 (m, 2H), 3.39-3.38 (m, 1H), 2.97 (s, 6H), 2.93-2.87 (m, 1H), 2.51-2.42 (m, 1H), 2.38 (s, 3H), 2.06-1.99 (m, 1H).

[1687]

[1688] Example 170: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1689]

[1690] The title compound (10 mg, yield: 7%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, tert-butyl(S)-pyrrolidin-3-yl carbamate was used instead of (S)-N,N-dimethylpyrrolidin-3-amine and 4-chloro-1-fluoro-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene, and in Step 3, tert-butyl(S)-(1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and 4-chloro-1-fluoro-2-nitrobenzene) carbamate were used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide.

[1691] 1 H NMR (500 MHz, DMSO-d6-d6) δ 9.75 (s, 1H), 9.02 (s, 1H), 8.13 (s, 3H), 8.03 (d, J= 8.3 Hz, 2H), 7.47 (s, 1H), 7.35 (s, 1H), 7.27 (d,J= 8.3 Hz, 1H), 7.23-7.14 (m, 2H), 7.00 (s, 1H), 6.95 (s, 2H), 4.02 (s, 1H), 3.76 (s, 3H), 3.42 (s, 1H), 3.29 (s, 2H), 3.14 (s, 1H), 3.07 (s, 1H), 2.03 (s, 1H).

[1692]

[1693] Example 171: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1694]

[1695] The title compound (10 mg, yield: 3%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, tert-butyl(S)-pyrrolidin-3-yl carbamate was used instead of (S)-N,N-dimethylpyrrolidin-3-amine and 4-chloro-2-fluoro-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene, and in Step 3, tert-butyl(S)-(1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and tert-(S)-(1-(2-amino-5-chlorophenyl)pyrrolidin-3-yl)carbamate were used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1696] 1 H NMR (500 MHz, DMSO-d6-d6) δ 9.58 (s, 1H), 8.94 (d,J= 8.7 Hz, 1H), 8.13 (s, 3H), 8.02 (d,J= 5.9 Hz, 2H), 7.46 (d,J= 7.1 Hz, 1H), 7.34 (d,J= 7.8 Hz, 1H), 7.27 (s, 1H), 7.25 - 7.14 (m, 3H), 6.94 (d,J= 8.4 Hz, 2H), 4.03 (s, 1H), 3.76 (s, 3H), 3.47 (d,J= 10.7 Hz, 1H), 3.30 (s, 2H), 3.20-3.08 (m, 2H), 2.07-1.99 (m, 1H).

[1697]

[1698] Example 172: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1699]

[1700] (Step 1)

[1701] (S)-1-(4-fluoro-2-nitrophenyl)-N,N-dimethylpyrrolidine-3-amine (15.0 g, yield: 94.2%) was obtained in the same manner as in Example 160, except that 1,4-difluoro-2-nitrobenzene was used instead of 2,4-difluoro-1-nitrobenzene in Step 1 of Example 160.

[1702] 1 H NMR (500 MHz, DMSO-d6) δ 7.69 - 7.62 (m, 1H), 7.41 (dt, J = 9.7, 5.0 Hz, 1H), 7.08 (dd, J = 9.2, 4.6 Hz, 1H), 3.35 - 3.28 (m, 1H), 3.09 (dt, J = 17.4, 6.1 Hz, 3H), 2.71 (q, J = 7.5 Hz, 1H), 2.17 (d, J = 5.1 Hz, 6H), 2.14 - 2.08 (m, 1H), 1.75 (p, J = 10.2 Hz, 1H). MS (ESI, m / z): 254.2 [M+H] +

[1703] (Step 2)

[1704] (S)-1-(2-amino-4-fluorophenyl)-N,N-dimethylpyrrolidine-3-amine (11.2 g, yield: 84.7%) was obtained by the same method as in Step 3 of Example 1.

[1705] 1 H NMR (500 MHz, DMSO-d6) δ 6.90 - 6.82 (m, 1H), 6.43 (dd, J = 11.2, 3.1 Hz, 1H), 6.25 (dt, J = 11.1, 5.3 Hz, 1H), 4.96 (s, 2H), 3.08 (d, J = 8.0 Hz, 1H), 3.01 (t, J = 6.1 Hz, 1H), 2.86 - 2.76 (m, 3H), 2.15 (t, J = 2.4 Hz, 6H), 2.04 - 1.94 (m, 1H), 1.73 (dq, J = 18.0, 6.0 Hz, 1H). MS (ESI, m / z): 224.2 [M+H] +

[1706] (Step 3)

[1707] The title compound (109 mg, yield: 3.5%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1708] 1 H NMR (500 MHz, DMSO-d6) δ 9.95 - 9.62 (m, 2H), 8.80 (dd, J = 11.6, 3.1 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.33 (s, 1H), 7.26 (dd, J = 8.7, 5.9 Hz, 1H), 7.23 - 7.13 (m, 4H), 6.77 (td, J = 8.6, 3.1 Hz, 1H), 4.28 - 4.15 (m, 1H), 3.53 (s, 1H), 3.46 (dd, J = 11.2, 7.3 Hz, 1H), 3.37 - 3.33 (m, 1H), 2.98 (s, 6H), 2.71 (q, J = 8.2 Hz, 1H), 2.60 - 2.53 (m, 1H), 2.40 (s, 1H), 2.30 (s, 3H). MS (ESI, m / z): 521.3 [M+H] +

[1709]

[1710] Example 173: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1711]

[1712] (Step 1)

[1713] The title compound (257 mg, yield: 8.4%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1714] 1 H NMR (500 MHz, DMSO-d6) δ 10.00 - 9.59 (m, 2H), 8.80 (dd, J = 11.7, 3.0 Hz, 1H), 7.99 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.35 (s, 1H), 7.26 (dd, J = 8.7, 5.8 Hz, 1H), 7.22 - 7.14 (m, 2H), 6.94 (d, J = 8.2 Hz, 2H), 6.78 (d, J = 9.1 Hz, 1H), 4.28 - 4.14 (m, 1H), 3.76 (s, 3H), 3.52 (s, 2H), 3.45 (dd, J = 11.2, 7.2 Hz, 1H), 3.38 - 3.34 (m, 1H), 2.98 (s, 6H), 2.71 (q, J = 8.2 Hz, 1H), 2.40 (s, 1H). MS (ESI, m / z): 537.3 [M+H] +

[1715]

[1716] Example 174: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1717]

[1718] The title compound (12 mg, yield: 4%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, tert-butyl(S)-pyrrolidin-3-yl carbamate was used instead of (S)-N,N-dimethylpyrrolidin-3-amine and 4-chloro-1-fluoro-2-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene, and in Step 3, tert-butyl(S)-(1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine)pyrrolidin-3-yl)carbamate was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine.

[1719] 1 H NMR (500 MHz, DMSO-d6-d6) δ 9.76 (s, 1H), 9.02 (d,J= 2.5 Hz, 1H), 8.13 (s, 3H), 7.97 (d,J= 10 Hz, 2H), 7.48 (d,J= 7.6 Hz, 1H), 7.33 (d,J= 7.7 Hz, 1H), 7.28 (d,J= 8.5 Hz, 1H), 7.23 (s, 1H), 7.24 - 7.14 (m, 3H), 7.00 (d,J= 8.4 Hz, 1H), 4.03 (s, 1H), 3.29 (s, 2H), 3.16-3.11 (m, 1H), 3.08 (dd,J= 10.7, 5.9 Hz, 1H), 2.30 (s, 3H), 2.06-1.99 (m, 1H).

[1720]

[1721] Example 175: Preparation of (S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1722]

[1723] The title compound (7 mg, yield: 2%) was obtained in the same manner as in Example 4, except that in Step 1 of Example 4, tert-butyl(S)-pyrrolidin-3-yl carbamate was used instead of (S)-N,N-dimethylpyrrolidin-3-amine and 4-chloro-2-fluoro-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene, and in Step 3, tert-butyl(S)-(1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine)pyrrolidin-3-yl)carbamate was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine.

[1724] 1 H NMR (500 MHz, DMSO-d6-d6) δ 9.58 (s, 1H), 8.93 (d,J= 8.7 Hz, 1H), 8.13 (s, 3H), 7.97 (d,J= 6.0 Hz, 2H), 7.46 (d,J= 7.6 Hz, 1H), 7.31 (d,J= 7.5 Hz, 1H), 7.27 (d,J= 2.5 Hz, 1H), 7.25 - 7.12 (m, 5H), 4.03 (s, 1H), 3.46 (d,J= 10.7 Hz, 1H), 3.30 (s, 2H), 3.22 - 3.09 (m, 2H), 2.30 (s, 3H), 2.07-1.99 (m, 1H).

[1725]

[1726] Example 176: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide

[1727]

[1728] (Step 1)

[1729] The title compound (82 mg, yield: 75%) was obtained in the same manner as in Example 134, except that N-(3-chloroquinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 134.

[1730] 1 H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 9.53 (s, 1H), 8.90 (d, J = 8.5 Hz, 1H), 7.68 (s, 2H), 7.45 (d, J = 7.8 Hz, 1H), 7.31 (s, 1H), 7.24 (d, J = 2.3 Hz, 1H), 7.21 (dd, J = 8.7, 2.5 Hz, 1H), 7.19 - 7.15 (m, 2H), 7.03 (s, 1H), 4.21 (s, 1H), 3.58 (s, 1H), 3.51 (dd, J = 11.2, 7.3 Hz, 1H), 3.31 (t, J = 7.1 Hz, 1H), 2.97 (s, 3H), 2.79 (q, J = 8.2 Hz, 1H), 2.30 (s, 6H), 2.18 (t, J = 8.1 Hz, 1H), 1.90 (p, J = 7.6 Hz, 1H). MS (ESI, m / z): 551.4 [M+H] +

[1731]

[1732] Example 177: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide

[1733]

[1734] (Step 1)

[1735] The title compound (77.3 mg, yield: 66%) was obtained in the same manner as in Example 134, except that N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide in step 4 of Example 134.

[1736] 1H NMR (500 MHz, DMSO-d6) δ 9.55 (s, 1H), 8.92 (d, J = 8.6 Hz, 1H), 7.83 (s, 1H), 7.55 (dd, J = 8.4, 2.0 Hz, 1H), 7.46 (dd, J = 7.9, 1.6 Hz, 1H), 7.37 (s, 1H), 7.23 (d, J = 2.4 Hz, 1H), 7.21 (dd, J = 8.7, 2.4 Hz, 1H), 7.15 (q, J = 6.8 Hz, 1H), 6.95 (d, J = 8.5 Hz, 1H), 4.19 (s, 1H), 3.83 (s, 3H), 3.75 (s, 3H), 3.60 (s, 1H), 3.50 (dd, J = 11.3, 7.3 Hz, 2H), 2.97 (s, 6H), 2.75 (q, J = 8.3 Hz, 1H), 2.60 - 2.55 (m, 1H), 2.45 - 2.41 (m, 1H). MS (ESI, m / z): 583.4 [M+H] +

[1737]

[1738] Example 178: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide

[1739]

[1740] (Step 1)

[1741] The title compound (69 mg, yield: 61%) was obtained in the same manner as in Example 134, except that N-(3-chloroquinoxalin-2-yl)benzofuran-6-sulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in step 4 of Example 134.

[1742] 1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.56 (s, 1H), 8.91 (s, 1H), 8.33 (s, 1H), 8.08 (s, 1H), 7.91 (s, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.30 (s, 1H), 7.25 (d, J = 2.3 Hz, 1H), 7.21 (dd, J = 8.8, 2.3 Hz, 1H), 7.18 - 7.09 (m, 2H), 6.98 (s, 1H), 4.23 (s, 1H), 3.66 - 3.60 (m, 2H), 3.53 (t, J = 9.3 Hz, 2H), 3.30 (d, J = 7.0 Hz, 1H), 3.00 (s, 6H), 2.77 (d, J = 8.6 Hz, 1H). MS (ESI, m / z): 563.14 [M+H] +

[1743]

[1744] Example 179: Preparation of (S)-N-(4-(N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

[1745]

[1746] (Step 1)

[1747] The title compound (59.7 mg, yield: 58%) was obtained in the same manner as in Example 134, except that N-(4-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)acetamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide in Step 4 of Example 134.

[1748] 1H NMR (500 MHz, DMSO-d6) δ 10.07 (s, 1H), 9.54 (s, 1H), 8.91 (d, J = 8.7 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.44 (dd, J = 7.7, 1.8 Hz, 1H), 7.31 (s, 1H), 7.23 (d, J = 2.4 Hz, 1H), 7.20 (dd, J = 8.7, 2.4 Hz, 1H), 7.18 - 7.11 (m, 2H), 4.18 (bs, 1H), 3.58 (bs, 1H), 3.50 (dd, J = 11.1, 7.2 Hz, 2H), 2.96 (s, 6H), 2.77 (dq, J = 13.3, 7.1 Hz, 2H), 2.42 (s, 1H), 2.03 (s, 3H). MS (ESI, m / z): 580.2 [M+H] +

[1749]

[1750] Example 180: Preparation of (S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1751]

[1752] (Step 1)

[1753] (S)-1-(5-(dimethylamino)-2-nitrophenyl)-N,N-dimethylpyrrolidin-3-amine (5.0 g, yield: 56.1%) was obtained in the same manner as in Example 1, except that 3-fluoro-N,N-dimethyl-4-nitroaniline was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidin-3-amine was used instead of methylpiperazine.

[1754] 1H NMR (500 MHz, DMSO-d6) δ 7.74 (d, J = 9.4 Hz, 1H), 6.23 (dd, J = 9.4, 2.5 Hz, 1H), 5.87 (d, J = 2.6 Hz, 1H), 3.40 (td, J = 10.3, 6.4 Hz, 1H), 3.19 (dd, J = 10.1, 8.3 Hz, 1H), 3.11 (ddd, J = 10.3, 7.9, 2.4 Hz, 1H), 3.06 - 3.00 (m, 7H), 2.68 (ddt, J = 10.1, 8.6, 6.1 Hz, 1H), 2.17 (s, 6H), 2.11 (dtd, J = 12.1, 6.2, 2.2 Hz, 1H), 1.74 (dtd, J = 11.7, 10.1, 7.9 Hz, 1H). MS (ESI, m / z): 279.2 [M+H] +

[1755] (Step 2)

[1756] (S)-3-(3-(dimethylamino)pyrrolidine-1-yl)-N1,N1-dimethylbenzene-1,4-diamine (1.9 g, yield: 42.3%) was obtained by the same method as in Step 3 of Example 1.

[1757] 1 H NMR (500 MHz, DMSO-d6) δ 6.54 (d, J = 8.4 Hz, 1H), 6.38 (d, J = 2.7 Hz, 1H), 6.26 (dd, J = 8.4, 2.7 Hz, 1H), 4.01 (s, 2H), 3.16 (dt, J = 9.2, 7.1 Hz, 1H), 3.08 (dd, J = 9.2, 7.0 Hz, 1H), 2.89 (qd, J = 8.2, 4.3 Hz, 2H), 2.83 - 2.73 (m, 1H), 2.71 (s, 6H), 2.16 (s, 6H), 2.05 - 1.95 (m, 1H), 1.77 - 1.67 (m, 1H). MS (ESI, m / z): 249.2 [M+H] +

[1758] (Step 3)

[1759] The title compound (676 mg, yield: 41.3%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1760] 1 H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 9.22 (s, 1H), 8.63 (s, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.38 (s, 1H), 7.32 - 7.17 (m, 3H), 7.12 (s, 2H), 6.61 - 6.53 (m, 2H), 4.15 (s, 1H), 3.57 - 3.42 (m, 4H), 2.97 - 2.93 (m, 6H), 2.88 (s, 6H), 2.76 (q, J = 8.4 Hz, 1H), 2.37 (dd, J = 4.0, 2.2 Hz, 1H), 2.30 (s, 3H). MS (ESI, m / z): 546.3 [M+H] +

[1761]

[1762] Example 181: Preparation of (S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1763]

[1764] (Step 1)

[1765] The title compound (724 mg, yield: 45.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-3-(3-(dimethylamino)pyrrolidin-1-yl)-N1,N1-dimethylbenzene-1,4-diamine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1766] 1 H NMR (500 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.64 (s, 1H), 8.03 - 7.96 (m, 2H), 7.37 (s, 1H), 7.29 (s, 1H), 7.12 (s, 2H), 6.94 (s, 2H), 6.61 - 6.53 (m, 2H), 4.23 - 4.09 (m, 1H), 3.76 (s, 3H), 3.57 - 3.41 (m, 4H), 2.96 (s, 6H), 2.88 (s, 6H), 2.76 (d, J = 7.7 Hz, 1H), 2.37 (p, J = 1.8 Hz, 1H). MS (ESI, m / z): 562.3 [M+H] +

[1767]

[1768] Example 182: Preparation of (S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide

[1769]

[1770] (Step 1)

[1771] (S)-1-(5-cyclopropyl-2-nitrophenyl)-N,N-dimethylpyrrolidine-3-amine (3.0 g, yield: 98.7%) was obtained in the same manner as in Example 1, except that 4-cyclopropyl-2-fluoro-1-nitrobenzene was used instead of 1-fluoro-2-nitrobenzene in Step 2 of Example 1 and (S)-N,N-dimethylpyrrolidine-3-amine was used instead of methylpiperazine.

[1772] 1 H NMR (500 MHz, DMSO-d6) δ 7.63 (d, J = 8.5 Hz, 1H), 6.76 (d, J = 1.8 Hz, 1H), 6.41 (dd, J = 8.6, 1.7 Hz, 1H), 3.39 - 3.30 (m, 2H), 3.17 - 3.03 (m, 3H), 2.70 (ddd, J = 15.1, 8.8, 6.3 Hz, 1H), 2.17 (s, 6H), 2.18 - 2.06 (m, 1H), 1.97 (tt, J = 8.5, 5.0 Hz, 1H), 1.80 - 1.68 (m, 1H), 1.06 - 0.96 (m, 2H), 0.83 - 0.75 (m, 2H). MS (ESI, m / z): 276.2 [M+H] +

[1773] (Step 2)

[1774] (S)-1-(2-amino-5-cyclopropylphenyl)-N,N-dimethylpyrrolidine-3-amine (2.5 g, yield: 95.0%) was obtained by the same method as in Step 3 of Example 1.

[1775] 1H NMR (500 MHz, DMSO-d6) δ 6.64 (d, J = 2.0 Hz, 1H), 6.56 (d, J = 8.0 Hz, 1H), 6.46 (dd, J = 8.1, 2.0 Hz, 1H), 4.36 (s, 2H), 3.15 (dt, J = 8.9, 7.0 Hz, 1H), 3.07 (dd, J = 9.2, 6.9 Hz, 1H), 2.92 - 2.84 (m, 2H), 2.79 (p, J = 7.2 Hz, 1H), 2.17 (s, 6H), 2.00 (qd, J = 7.5, 3.7) Hz, 1H), 1.79 - 1.68 (m, 2H), 0.78 (dt, J = 8.6, 3.1 Hz, 2H), 0.57 - 0.47 (m, 2H). MS (ESI, m / z): 246.2 [M+H] +

[1776] (Step 3)

[1777] The title compound (539 mg, yield: 22.1%) was obtained in the same manner as in Example 4, except that (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine in step 3 of Example 4.

[1778] 1H NMR (500 MHz, DMSO-d6) δ 9.33 (s, 1H), 8.66 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.64 - 7.60 (m, 1H), 7.51 - 7.46 (m, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.27 - 7.19 (m, 3H), 6.96 (s, 1H), 6.86 (d, J = 8.4 Hz, 1H), 4.03 - 3.99 (m, 1H), 3.46 (dd, J = 11.0, 7.3 Hz, 1H), 3.32 - 3.28 (m, 1H), 2.87 (s, 6H), 2.76 (q, J = 8.2 Hz, 1H), 2.36 (s, 1H), 2.34 (s, 3H), 2.31 - 2.15 (m, 2H), 1.90 (tt, J = 8.6, 5.1 Hz, 1H), 1.00 - 0.89 (m, 2H), 0.71 - 0.63 (m, 2H). MS (ESI, m / z): 543.3 [M+H] +

[1779]

[1780] Example 183: Preparation of (S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide

[1781]

[1782] (Step 1)

[1783] The title compound (817 mg, yield: 34.1%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-4-methoxybenzenesulfonamide.

[1784] 1H NMR (500 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.58 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.5 Hz, 2H), 7.90 (s, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.33 (p, J = 7.0 Hz, 2H), 7.12 (t, J = 6.6 Hz, 2H), 6.98 (s, 1H), 6.86 (d, J = 8.6 Hz, 1H), 3.92 - 3.72 (m, 4H), 3.44 (t, J = 9.1 Hz, 1H), 3.30 (s, 1H), 3.19 (s, 1H), 2.89 - 2.73 (m, 7H), 2.11 - 2.07 (m, 2H), 1.94 - 1.82 (m, 1H), 1.00 - 0.88 (m, 2H), 0.72 - 0.60 (m, 2H). MS (ESI, m / z): 559.3 [M+H] +

[1785]

[1786] Example 184: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methoxybenzenesulfonamide

[1787]

[1788] (Step 1)

[1789] (S)-1-(2-amino-5-fluorophenyl)-N,N-dimethylpyrrolidine-3-amine (80 mg, 0.358 mmol), N-(3-iodonaphthalene-2-yl)-4-methoxybenzenesulfonamide (189 mg, 0.430 mmol), Pd-PEPPSI TM-IPent (20 mg, 0.024 mmol) and Cs2CO3 (233 mg, 0.717 mmol) were dissolved in 8 mL of 1,4-dioxane, dressed with nitrogen, and stirred under nitrogen at 100 °C for 18 hours. Once the reaction was complete, the temperature was lowered to room temperature, and the organic layer was separated using water and ethyl acetate. The mixture was then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was first purified by column chromatography (eluting with MeOH / DCM, 0 to 8%) and secondarily purified by prep-HPLC (Column: Gemini 5 μm C18 150 × 21.2 mm, mobile phase: ACN - H2O (0.1% FA), gradient: 30 - 70) to obtain the title compound (yield 5%, 10 mg).

[1790] 1 H NMR (400 MHz, DMSO-d6) δ 7.71-7.63 (m, 2 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.45-7.38 (m, 2 H), 7.23-7.16 (m, 1 H), 7.15-7.07 (m, 1 H), 7.05-6.98 (m, 2 H), 6.89 (s, 1 H), 6.87-6.80 (m, 1 H), 6.71-6.60 (m, 2 H), 6.58-6.50 (m, 1 H), 3.78 (s, 3 H), 3.32-3.23 (m, 2 H), 3.11-3.06 (m, 2 H), 2.71-2.65 (m, 1 H), 2.11 (s, 6 H), 1.93-1.83 (m, 1 H), 1.64-1.52 (m, 1 H). MS (ES, m / z): 535.21 [M+H] +

[1791]

[1792] Example 185: Preparation of (S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-6-yl)-4-methoxybenzenesulfonamide

[1793]

[1794] (Step 1)

[1795] 6-bromo-7-nitroquinoxaline (500 mg, 1.968 mmol), (S)-1-(2-amino-5-fluorophenyl)-N,N-dimethylpyrrolidin-3-amine (439 mg, 1.968 mmol), SPhos (73 mg, 0.179 mmol), SPhos Pd G2 (76 mg, 0.106 mmol), and Na2CO3 (626 mg, 5.905 mmol) were dissolved in 1,4-dioxane (20 mL), dressed with nitrogen, and stirred under nitrogen at 100 °C for 18 hours. When the reaction was complete, the temperature was lowered to room temperature, the organic layer was separated using water and ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by column chromatography (eluting with MeOH / DCM, 0 to 10%) to obtain (S)-N-(2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)-7-nitroquinoxalin-6-amine (yield 22%, 220 mg).

[1796] MS (ES, m / z): 397.17 [M+H] +

[1797] (Step 2)

[1798] The product compound from Step 1 (220 mg, 0.555 mmol) and Pd / C (44 mg, 0.042 mmol, 10% wt) were dissolved in MeOH (30 mL), dressed with hydrogen, and stirred under hydrogen at room temperature for 1 hour. Once the reaction was complete, the solution was filtered with MeOH and then concentrated under reduced pressure to obtain (S)-N 6 -(2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)quinoxalin-6,7-diamine (yield 59%, 200 mg) was obtained.

[1799] MS (ES, m / z): 367.20 [M+H] +

[1800] (Step 3)

[1801] The product compound of Step 2 (120 mg, 0.328 mmol) was dissolved in pyridine (5 mL) by stirring. 4-methoxybenzenesulfonyl chloride (135 mg, 0.655 mmol) was dissolved in pyridine (5 mL) and slowly added dropwise. After stirring at 50 °C for 1 hour to terminate the reaction, the temperature was lowered to room temperature, and the organic layer was separated using water and ethyl acetate. The mixture was then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was first purified by column chromatography (eluting with MeOH / DCM, 0 to 10%) and secondarily purified by prep-HPLC (Column: Xbridge Prep C18 5um OBD, mobile phase: ACN - H2O (0.05% NH3·H2O), gradient: 30 - 45) to obtain the title compound (yield 37%, 68 mg).

[1802] 1 H NMR (400 MHz, DMSO-d6) δ 8.32-8.25 (m, 2 H), 7.94 (s, 1 H), 7.76-7.70 (m, 2 H), 7.35-7.28 (m, 1 H), 7.27 (s, 1 H), 7.00-6.95 (m, 2 H), 6.88-6.82 (m, 1 H), 6.81-6.74 (m, 2 H), 3.76 (s, 3 H), 3.64-3.55 (m, 1 H), 3.40-3.35 (m, 3 H), 3.07-2.99 (m, 1 H), 2.60 (s, 6 H), 2.22-2.11 (m, 1 H), 2.05-1.90 (m, 1 H). MS (ES, m / z): 537.20 [M+H] +

[1803]

[1804] Example 186: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide

[1805]

[1806] (Step 1)

[1807] N-(3-chloroquinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide (475 mg, yield: 24.7%) was obtained in the same manner as in Example 1, except that p-tolylmethanesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1808] 1 H NMR (500 MHz, DMSO-d6) δ 11.27 (s, 1H), 7.84 (dd, J = 17.5, 8.2 Hz, 2H), 7.70 (t, J = 7.7 Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.7 Hz, 2H), 4.78 (s, 2H), 2.26 (s, 3H). MS (ESI, m / z): 348.1 [M+H] +

[1809] (Step 2)

[1810] The title compound (156 mg, yield: 49.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-amino-5-chlorophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide.

[1811] 1H NMR (500 MHz, DMSO-d6) δ 9.60 - 9.33 (m, 2H), 8.91 (s, 1H), 7.56 - 7.47 (m, 2H), 7.30 - 7.15 (m, 4H), 7.12 - 7.07 (m, 2H), 7.02 (d, J = 7.6 Hz, 2H), 4.72 (d, J = 13.3 Hz, 1H), 4.63 (d, J = 13.2 Hz, 1H), 4.07 - 3.99 (m, 1H), 3.41 - 3.35 (m, 1H), 3.32 - 3.20 (m, 2H), 2.68 (s, 6H), 2.57 (s, 1H), 2.20 (s, 3H), 2.15 - 2.07 (m, 2H). MS (ESI, m / z): 551.3 [M+H] +

[1812]

[1813] Example 187: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide

[1814]

[1815] (Step 1)

[1816] The title compound (257 mg, yield: 83.6%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide.

[1817] 1H NMR (500 MHz, DMSO-d6) δ 9.66 - 9.19 (m, 2H), 8.87 (s, 1H), 7.54 - 7.46 (m, 2H), 7.28 - 7.18 (m, 2H), 7.11 - 7.07 (m, 2H), 7.06 - 6.95 (m, 4H), 4.73 (d, J = 13.3 Hz, 1H), 4.63 (d, J = 13.2 Hz, 1H), 4.07 - 3.99 (m, 1H), 3.43 - 3.35 (m, 1H), 3.32 - 3.20 (m, 2H), 2.68 (s, 6H), 2.56 (s, 1H), 2.21 (s, 3H), 2.10 (q, J = 7.0 Hz, 2H). MS (ESI, m / z): 535.3 [M+H] +

[1818]

[1819] Example 188: Preparation of (S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide

[1820]

[1821] (Step 1)

[1822] N-(3-chloroquinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide (510 mg, yield: 27.9%) was obtained in the same manner as in Example 1, except that (4-methoxyphenyl)methanesulfonamide was used instead of 4-methylbenzenesulfonamide in Step 1 of Example 1.

[1823] 1H NMR (500 MHz, DMSO-d6) δ 11.29 (s, 1H), 7.85 (dd, J = 19.3, 8.2 Hz, 2H), 7.70 (q, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.25 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 8.3 Hz, 2H), 4.77 (s, 2H), 3.72 (s, 3H). MS (ESI, m / z): 364.1 [M+H] +

[1824] (Step 2)

[1825] The title compound (200 mg, yield: 64.2%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide.

[1826] 1 H NMR (500 MHz, DMSO-d6) δ 9.62 - 9.34 (m, 2H), 8.92 - 8.89 (m, 1H), 7.58 - 7.49 (m, 2H), 7.32 - 7.16 (m, 4H), 7.15 - 7.10 (m, 2H), 6.81 - 6.76 (m, 2H), 4.70 (d, J = 13.4 Hz, 1H), 4.62 (d, J = 13.3 Hz, 1H), 4.12 - 3.96 (m, 1H), 3.66 (s, 3H), 3.41 - 3.35 (m, 1H), 3.33 - 3.27 (m, 1H), 3.24 (dd, J = 11.1, 3.3 Hz, 1H), 2.69 (s, 6H), 2.61 - 2.57 (m, 1H), 2.12 (td, J = 8.5, 4.0 Hz, 2H). MS (ESI, m / z): 567.3 [M+H] +

[1827]

[1828] Example 189: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide

[1829]

[1830] (Step 1)

[1831] The title compound (236 mg, yield: 77.9%) was obtained in the same manner as in Example 4, except that in step 3 of Example 4, (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine was used instead of (S)-1-(2-aminophenyl)-N,N-dimethylpyrrolidin-3-amine hydrochloride and N-(3-chloroquinoxalin-2-yl)-4-methylbenzenesulfonamide was used instead of N-(3-chloroquinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide.

[1832] 1 H NMR (500 MHz, DMSO-d6) δ 9.67 - 9.15 (m, 2H), 8.86 (s, 1H), 7.51 (dd, J = 7.6, 1.9 Hz, 2H), 7.28 - 7.18 (m, 2H), 7.13 (d, J = 8.2 Hz, 2H), 7.06 - 6.95 (m, 2H), 6.82 - 6.75 (m, 2H), 4.71 (d, J = 13.4 Hz, 1H), 4.61 (d, J = 13.3 Hz, 1H), 4.07 - 3.99 (m, 1H), 3.66 (s, 3H), 3.52 - 3.35 (m, 2H), 3.23 (dd, J = 11.1, 3.5 Hz, 1H), 2.68 (s, 6H), 2.60 - 2.57 (m, 1H), 2.10 (q, J = 7.1 Hz, 2H). MS (ESI, m / z): 551.3 [M+H] +

[1833]

[1834] Example 190: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)pyrazino[2,3-b]pyrazine-2-yl)-4-methoxybenzenesulfonamide

[1835]

[1836] (Step 1)

[1837] Pyrazine-2,3-diamine (1.0 g, 0.009 mol) was dissolved in diethyl oxalate (26 mL), and the temperature was raised to 190 °C and stirred for 4 hours. When the reaction was complete, the temperature was lowered to rt. The mixture was filtered using ethanol and ethyl acetate to obtain pyrazino[2,3-b]pyrazine-2,3-diol (yield 70%, 1.0 g).

[1838] 1 H NMR (400 MHz, DMSO-d6) δ 12.56 (s, 2 H), 8.07 (s, 2 H). MS (ESI, m / z): 165.03 [M+H] +

[1839] (Step 2)

[1840] The product of Step 1 (2.0 g, 0.012 mol) and POCl3 (20 mL) were dissolved in TEA (1 mL), and the temperature was raised to 110 °C and stirred for 2 hours. When the reaction was complete, the temperature was lowered to rt. The organic layer was separated using water and ethyl acetate, dried over aN hydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluting with DCM / PE, 0 to 100%) to obtain 2,3-dichloropyrazino[2,3-b]pyrazine (yield 18%, 500 mg).

[1841] MS (ESI, m / z): 200.97 [M+H] +

[1842] (Step 3)

[1843] 4-methoxybenzenesulfonamide (140 mg, 0.746 mmol) was dissolved in DMF (3 mL), and NaH (50 mg, 1.246 mmol, 60% wt) was added at 0 °C. Then, the second-step product compound (150 mg, 0.746 mmol) was added, and the mixture was stirred at 0 °C for 35 minutes. When the reaction was complete, the mixture was quenched with water. The resulting residue was purified by C18 column chromatography (eluting with ACN - H2O (0.1% FA), gradient: 0 to 17%) to obtain N-(3-chloropyrazino[2,3-b]pyrazine-2-yl)-4-methoxybenzenesulfonamide (yield 30%, 100 mg).

[1844] MS (ESI, m / z): 352.02 [M+H] +

[1845] (Step 4)

[1846] The 3-step product compound (100 mg, 0.284 mmol) and (S)-1-(2-amino-5-fluorophenyl)-N,N-dimethylpyrrolidine-3-amine (63 mg, 0.284 mmol) were dissolved in ACN (10 mL), sealed with nitrogen, and stirred at 100 °C for 18 hours. When the reaction was complete, the temperature was lowered to rt. The resulting residue was purified by column chromatography (eluting with MeOH / DCM, 0 to 13%) to obtain the title compound (yield 22%, 35.8 mg).

[1847] 1H NMR (400 MHz, DMSO-d6) δ 9.82-9.68 (m, 1 H), 9.63 (s, 1 H), 8.87-8.78 (m, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 8.24 (d, J = 2.4 Hz, 1 H), 8.05-7.95 (m, 2 H), 7.13 (dd, J = 10.8, 2.8 Hz, 1 H), 7.07-6.98 (m, 1 H), 6.98-6.88 (m, 2 H), 4.27-4.12 (m, 1 H), 3.76 (s, 3 H), 3.63-3.48 (m, 2 H), 3.43-3.35 (m, 1 H), 2.96 (s, 6 H), 2.86-2.75 (m, 1 H), 2.47-2.37 (m, 1 H). MS (ESI, m / z): 539.19 [M+H] +

[1848]

[1849] Example 191: Preparation of (S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methylbenzenesulfonamide

[1850]

[1851] (Step 1)

[1852] 3-iodonaphthalene-2-amine (250 mg, 0.929 mmol) was dissolved in pyridine (6 mL) by stirring at 0 °C, and 4-methylbenzenesulfonyl chloride (266 mg, 1.394 mmol) was dissolved in pyridine (2 mL) and slowly added dropwise. After stirring at 50 °C for 1 hour, the temperature was lowered to rt when the reaction was complete. The resulting residue was purified by column chromatography (eluting with EtOAc / PE, 0 to 10%) to obtain N-(3-iodonaphthalene-2-yl)-4-methylbenzenesulfonamide (yield 64%, 300 mg).

[1853] MS (ESI, m / z): 423.98 [M+H] +

[1854] (Step 2)

[1855] Step 1 product compound (100 mg, 0.236 mmol) and (S)-1-(2-amino-5-fluorophenyl)-N,N-dimethylpyrrolidine-3-amine (53 mg, 0.236 mmol), Pd-PEPPSI TM -IPent (20 mg, 0.024 mmol) and Cs2CO3 (154 mg, 0.473 mmol) were dissolved in 1,4-dioxane (8 mL), sealed with nitrogen, an...

Claims

A compound represented by the following chemical formula 1, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, R1 is a 5 to 10-membered monocyclic or polycyclic heterocycloalkyl comprising one or two N atoms substituted with one or more Rs; or -N(C 1-5 Alkyl)(C 1-5 alkyl) and, R is a halogen; -LN(R a )(R b ); -N(R c )-CO-(R d ); C 1-5 Alkyl; C 1-5 Alkoxy; C comprising one or more heteroatoms among N, O, and S 2-10 Heterocycloalkyl; or C comprising one or more heteroatoms among N, O, and S 2-10 It is heteroaryl, and L is a single bond; -CO-; or C 1-5 It is an alkylene, and R a to R d are each independently hydrogen; or C 1-5 It is alkyl, and X1 is N or C(R 2a ) and, X2 is N or C(R 2b ) and, R 2a , R 2b , R 3a and R 3b Each independently consists of hydrogen; halogen; hydroxy; -COO(R e ); -N(R f )(R g ); C 1-5 Alkyl; C 1-5 Alkoxy; or C 3-7 It is cycloalkyl, and R e to R g are each independently hydrogen; or C 1-5 It is alkyl, and A is represented by any one of the following chemical formulas 2a to 2c, and In the above chemical formulas 2a to 2c, R 4a is hydrogen, or bonded to one or two Rs 4c Forming a benzene ring; a pyrazine ring; or a pyridazine ring, substituted or unsubstituted, and R 4b They combine with each other to form one or two Rs 4c Forming a benzene ring; a pyrazine ring; or a pyridazine ring, substituted or unsubstituted, and R 4c Each is independently a halogen; C 1-5 alkyl; or C 1-5 It is an alkoxy, n is an integer from 0 to 2, and L' is a single bond; or C 1-5 It is an alkylene, and R5 is -N(R h )(R i ); C 1-5 Alkyl; C 3-7 Cycloalkyl; or a substituent represented by the following chemical formula 3, and [Chemical Formula 3] In the above chemical formula 3, Y1 is N or C(R 5a ) and, Y2 is N or C(R 5b ) and, R 5a , R 5b , R 6a , R 6b , and R 6c Each independently consists of hydrogen; halogen; hydroxy; -COO(R j ); -N(R k )(R l ); -N(R m )-CO-(R n ); C 1-5 Alkyl; C 1-5 Alkoxy; C 7-15 Aralkill; C 7-15 Aralcocyte; or a monocyclic heteroaryl comprising one or more heteroatoms among N, O, and S, or R 6b and R 6c They combine with each other to form a benzene ring; a pentagonal or hexagonal heteroaromatic ring containing one or more heteroatoms among N, O, and S; or a pentagonal or hexagonal heterocycloalkane ring containing one or more heteroatoms among N, O, and S, and R h to R n Each independently hydrogen; or C 1-5 It is alkyl, and Here, the alkyl, alkylene, alkoxy, cycloalkyl, heterocycloalkyl, heteroaryl, heteroaromatic ring and heterocycloalkane ring are each independently deuterium; halogen; hydroxy; oxo (=O); C 1-4 alkyl; and C 1-4 It is substituted or unsubstituted with one or more substituents selected from the group consisting of alkoxy, or is substituted or unsubstituted with a substituent in which two or more of the substituents exemplified above are connected. In paragraph 1, R1 is substituted with 1 R, pyrrolidinyl; piperidinyl; piperazinyl; hexahydropyrrolo[3,4-c]pyrroleyl; or -N(methyl)(ethyl), A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, R1 is represented by any one of the following chemical formulas 4a to 4d, Compound, or pharmaceutically acceptable salt thereof: In the above chemical formulas 4a to 4d, R is as defined in Paragraph 1, and Z is N or CH, and m is 0 or 1. In paragraph 1, R is -NH2, -NH(CH3), -N(CH3)2, -CO-NH(CH3), -CO-N(CH3)2, -CH2-N(CH3)2, -NH-CO-CH3, methyl, ethyl, methoxy, or methylpiperazinyl, A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, X1 is N, CH, C(F), C(Cl), or C(CH3), A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, X2 is N, CH, C(F), C(Cl), C(OH), C(CH3), or C(OCH3), A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, R 3a and R 3b Each is independently hydrogen, fluoro, chloro, bromo, hydroxy, -COO(CH3), -NH2, -N(CH3)2, methyl, methoxy, or cyclopropyl, A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, A is represented as any one selected from the group consisting of the following, Compound, or pharmaceutically acceptable salt thereof: In the above, R' 4c Each is independently hydrogen, chloro, bromo, methyl, or methoxy. In paragraph 1, L' is a single bond or methylene, A compound, or a pharmaceutically acceptable salt thereof. In paragraph 1, R5 is each independently a substituent represented by methyl, ethyl, n-propyl, isopropyl, cyclopropyl, or any one of the following chemical formulas 3a to 3h, Compound, or pharmaceutically acceptable salt thereof: In the above chemical formula 3a, R' 5a , R' 5b , R' 6a , R' 6b , and R' 6c Each is independently hydrogen, fluoro, chloro, hydroxy, -N(CH3)2, -NH-CO-CH3, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethoxy, benzyloxy, pyrazolyl, or methyloxazoleyl. In paragraph 1, The compound represented by the above chemical formula 1 is represented by any one of the following chemical formulas 1-1 to 1-3, Compound, or pharmaceutically acceptable salt thereof: [Chemical Formula 1-1] [Chemical Formula 1-2] [Chemical Formula 1-3] In the above chemical formulas 1-1 to 1-3, R1, R 2a , R 2b , R 3a , R 3b , A, L' and R5 are as defined in Paragraph 1. In paragraph 1, The compound represented by the above chemical formula 1 is, 1) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 2)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 3)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 4)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 5)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide, 6) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 7) 3-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 8) 2-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 9)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide, 10) 2-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 11)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 12)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 13)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide, 14)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 15)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 16)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 17)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide, 18)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide, 19)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)cyclopropanesulfonamide, 20)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide, 21)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)cyclopropanesulfonamide, 22)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)propane-2-sulfonamide, 23)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)ethanesulfonamide, 24)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)methanesulfonamide, 25) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 26) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide, 27)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methylbenzenesulfonamide, 28) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)pyrazine-2-yl)benzenesulfonamide, 29)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)pyrazine-2-yl)-4-methoxybenzenesulfonamide, 30)N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide, 31) 3-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 32)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide, 33)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 34)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide, 35)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 36)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 37)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 38) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide, 39) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 40) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 41) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide, 42) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 43) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 44) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide, 45) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-methoxybenzenesulfonamide, 46)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide, 47)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 48)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 49)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide, 50)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 51)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 52)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-(trifluoromethyl)benzenesulfonamide, 53)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)-2-methoxybenzenesulfonamide, 54)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide, 55)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide, 56)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide, 57)N-(3-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 58)N-(3-((2-(4-ethylpiperazine-1-yl)phenyl)amino)quinoxaline-2-yl)naphthalene-2-sulfonamide, 59) (R)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 60) 4-methyl-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide, 61) 4-methyl-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide, 62) 4-methoxy-N-(3-((4-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide, 63) 4-methoxy-N-(3-((2-(4-methylpiperazine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)benzenesulfonamide, 64)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 65)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 66)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 67)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 68)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 69)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 70)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 71)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 72)N-(3-((2-(4-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 73)N-(3-((2-(4-((dimethylamino)methyl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 74) 4-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 75) 4-methoxy-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 76) 3-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 77) 2-methyl-N-(3-((2-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 78)(S)-4-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 79)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-difluorobenzenesulfonamide, 80)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide, 81)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-difluorobenzenesulfonamide, 82)(S)-3,4-dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 83)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 84)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-difluoroquinoxalin-2-yl)-4-methylbenzenesulfonamide, 85)(S)-N-(6,7-dichloro-3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 86)(S)-3,5-dichloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 87)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 88)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 89)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 90)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 91)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 92)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 93)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 94)(S)-5-chloro-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 95)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-5-fluoro-2-methylbenzenesulfonamide, 96)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, 97)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 98)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 99)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 100)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 101)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 102)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 103)N-methyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide, 104)N,N-dimethyl-1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-carboxamide, 105)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 106)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 107)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 108)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 109)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 110)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 111)(S)-N-(4-(N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide, 112)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide, 113)(S)-3-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 114)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 115)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 116)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 117)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxaline-2-yl)-3-methoxybenzenesulfonamide, 118)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 119)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-3-methylphenyl)amino)quinoxalin-2-yl)naphthalene-2-sulfonamide, 120)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 121) 4-methyl-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 122)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)pyridine-3-sulfonamide, 123)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-6-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 124)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-5-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 125)(S)-4-(dimethylamino)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 126)(S)-4-(benzyloxy)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 127)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-ethoxybenzenesulfonamide, 128)(S)-N-(1-(2-((3-((4-methylphenyl)sulfonamido)quinoxalin-2-yl)amino)phenyl)pyrrolidine-3-yl)acetamide, 129)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-hydroxybenzenesulfonamide, 130)(S)-N-(3-((2-(3-methoxypyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 131)N-(3-((2-(3-(dimethylamino)piperidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 132)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-hydroxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 133)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-hydroxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 134)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 135)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 136)N-(3-((2-(3-((dimethylamino)methyl)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 137)(S)-N-(3-((4-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 138)(S)-N-(3-((4-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 139)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)pyridine-3-yl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 140)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 141)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 142)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 143)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide, 144)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide, 145)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 146)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-methoxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 147)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 148)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methoxyphenyl)amino)quinoxaline-2-yl)-4-methoxybenzenesulfonamide, 149)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, 150)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, 151) 4-methoxy-N-(3-((2-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)phenyl)amino)quinoxalin-2-yl)benzenesulfonamide, 152)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 153)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 154)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methylbenzenesulfonamide, 155)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 156)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-methylbenzenesulfonamide, 157)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide, 158)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide, 159)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethylquinoxalin-2-yl)-4-methoxybenzenesulfonamide, 160)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 161)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 162)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-4-(2-methyloxazole-4-yl)benzenesulfonamide, 163)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide, 164) Methyl(S)-3-(3-(dimethylamino)pyrrolidine-1-yl)-4-((3-((4-methoxyphenyl)sulfonamido)quinoxalin-2-yl)amino)benzoate, 165)(S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 166)(S)-N-(3-((4-bromo-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 167)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-methylpyridine-3-yl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide, 168)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide, 169)(S)-N-(3-((5-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-6,7-dimethoxyquinoxalin-2-yl)-4-methylbenzenesulfonamide, 170)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 171)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 172)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 173)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-5-fluorophenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 174)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-5-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 175)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 176)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,5-dimethylbenzenesulfonamide, 177)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-3,4-dimethoxybenzenesulfonamide, 178)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)benzofuran-6-sulfonamide, 179)(S)-N-(4-(N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide, 180)(S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 181)(S)-N-(3-((4-(dimethylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 182)(S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methylbenzenesulfonamide, 183)(S)-N-(3-((4-cyclopropyl-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, 184)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methoxybenzenesulfonamide, 185)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-6-yl)-4-methoxybenzenesulfonamide, 186)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide, 187)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(p-tolyl)methanesulfonamide, 188)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide, 189)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-2-yl)-1-(4-methoxyphenyl)methanesulfonamide, 190)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)pyrazino[2,3-b]pyrazine-2-yl)-4-methoxybenzenesulfonamide, 191)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)naphthalene-2-yl)-4-methylbenzenesulfonamide, 192)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)quinoxalin-6-yl)-4-methylbenzenesulfonamide, 193)(S)-N-(3-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)pyrazino[2,3-b]pyrazine-2-yl)-4-methylbenzenesulfonamide, 194)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-4-(1H-pyrazole-5-yl)benzenesulfonamide, 195)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)phthalazine-6-yl)-4-methoxybenzenesulfonamide, 196)(S)-N-(7-((2-(3-(dimethylamino)pyrrolidine-1-yl)-4-fluorophenyl)amino)phthalazine-6-yl)-4-methylbenzenesulfonamide, 197)(S)-1-(5-fluoro-2-(4-((4-methoxyphenyl)sulfonyl)-3,4-dihydroquinoxalin-1(2H)-yl)phenyl)-N,N-dimethylpyrrolidin -3-amine, 198)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidine-1-yl)phenyl)amino)quinoxalin-2-yl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide, 199)(S)-N-(3-((2-(3-aminopyrrolidin-1-yl)-4-chlorophenyl)amino)quinoxalin-2-yl)-3-methoxybenzenesulfonamide, 200)(S)-1-(5-chloro-2-(4-((4-methoxyphenyl)sulfonyl)-3,4-dihydroquinoxalin-1(2H)-yl)phenyl)-N,N-dimethylpyrrolidine-3-amine, 201)(S)-N-(3-((4-chloro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide, and 202)(S)-N-(3-((4-chloro-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)quinoxalin-2-yl)-4-hydroxybenzenesulfonamide One of which is selected from the group consisting of A compound, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising, as an active ingredient, a compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition for the prevention or treatment of fibrotic disease, cancer, or metabolic disease, comprising as an active ingredient a compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof.

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