• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】58443

【品名】3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]aniline; 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]phenylamine

【CA登记号】

【 分 子 式 】C10H10ClN3S

【 分 子 量 】239.72832

【元素组成】C 50.1% H 4.2% Cl 14.79% N 17.53% S 13.38%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

Condensation of 3-chloro-4-fluoronitrobenzene (I) with the sodium derivative of 2-mercapto-1-methylimidazole (II) affords the diaryl sulfide (III). Subsequent nitro group reduction in (III) using iron dust and ammonium chloride provides the intermediate aniline (IV).

1 Dutia, M.; Powell, D.W.; Berger, D.M.; et al.; Synthesis and evaluation of 4-anilino substituted 3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 105.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 58441 2-chloro-1-fluoro-4-nitrobenzene; 3-Chloro-4-fluoronitrobenzene; 4-Fluoro-3-chloronitrobenzene 350-30-1 C6H3ClFNO2 详情 详情
(II) 18783 1-methyl-1H-imidazol-2-ylhydrosulfide; 1-methyl-1H-imidazole-2-thiol 60-56-0 C4H6N2S 详情 详情
(III) 58442 2-chloro-4-nitrophenyl 1-methyl-1H-imidazol-2-yl sulfide; 2-[(2-chloro-4-nitrophenyl)sulfanyl]-1-methyl-1H-imidazole C10H8ClN3O2S 详情 详情
(IV) 58443 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]aniline; 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]phenylamine C10H10ClN3S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

Alkylation of vanillic acid methyl ester (V) with 3-chloropropyl tosylate (VI) in the presence of K2CO3 and Aliquat 336 gives the chloropropyl ether (VII). Subsequent electrophilic nitration of (VII) in hot HOAc affords the ortho-nitrobenzoate (VIII), which is further reduced to the amino benzoate analogue (IX) employing Fe/NH4Cl. Condensation of amino ester (IX) with dimethylformamide dimethylacetal provides adduct (X). This is then converted to the key quinoline derivative (XI) upon condensation with acetonitrile in the presence of butyllithium. Chlorination of (XI) with boiling POCl3 leads to the 4-chloroquinoline (XII). This is then coupled with the (imidazolylsulfanyl)aniline (IV) using pyridinium chloride in refluxing ethoxyethanol to furnish the anilino quinoline adduct (XIII). Finally, displacement of the chloride group of (XIII) with morpholine (XIV) in DMF provides the title compound.

1 Dutia, M.; Powell, D.W.; Berger, D.M.; et al.; Synthesis and evaluation of 4-anilino substituted 3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 105.
2 Frost, P.; Floyd, M.B. Jr.; Wissner, A.; Hamann, P.R.; Zhang, N.; Tsou, H.-R.; Berger, D.M.; Salvati, M.E. (Wyeth); Substd. 3-cyanoquinolines as protein tyrosine kinase inhibitors. EP 1117659; JP 2002525369; WO 0018761 .
3 Frost, P.; Floyd, M.B. Jr.; Wissner, A.; Hamann, P.R.; Zhang, N.; Tsou, H.-R.; Berger, D.M.; Salvati, M.E. (Wyeth); Substd. 3-cyanoquinolines. US 6288082 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV) 58443 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]aniline; 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]phenylamine C10H10ClN3S 详情 详情
(V) 29176 methyl 4-hydroxy-3-methoxybenzoate 3943-74-6 C9H10O4 详情 详情
(VI) 55581 3-Chloropropyl-p-toluenesulfonate C10H13ClO3S 详情 详情
(VII) 50008 methyl 4-(3-chloropropoxy)-3-methoxybenzoate C12H15ClO4 详情 详情
(VIII) 50009 methyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate C12H14ClNO6 详情 详情
(IX) 50010 methyl 2-amino-4-(3-chloropropoxy)-5-methoxybenzoate C12H16ClNO4 详情 详情
(X) 50011 methyl 4-(3-chloropropoxy)-2-[[(E)-(dimethylamino)methylidene]amino]-5-methoxybenzoate C15H21ClN2O4 详情 详情
(XI) 50012 7-(3-chloropropoxy)-4-hydroxy-6-methoxy-3-quinolinecarbonitrile C14H13ClN2O3 详情 详情
(XII) 48519 4-chloro-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile C14H12Cl2N2O2 详情 详情
(XIII) 58444 4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile C24H21Cl2N5O2S 详情 详情
(XIV) 10388 Morpholine 110-91-8 C4H9NO 详情 详情
Extended Information