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【结 构 式】

【分子编号】19654

【品名】1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride

【CA登记号】

【 分 子 式 】C10H7ClF3NO3S

【 分 子 量 】313.6844296

【元素组成】C 38.29% H 2.25% Cl 11.3% F 18.17% N 4.47% O 15.3% S 10.22%
与该中间体有关的原料药合成路线共 3 条
合成路线1合成路线2合成路线3

合成路线1

该中间体在本合成路线中的序号：(VII)

The bromination of styrene (II) with N-bromosuccinimide in the presence of cyanamide (I) provided 2-bromo-1-phenylethylcyanamide (III). Further addition of MeOH to (III) in the presence of HCl, followed by Na2CO3-promoted cyclization, produced the methoxyimidazoline (IV). Acylation of indoline (V) with trifluoroacetic anhydride and pyridine gave amide (VI) and subsequent chlorosulfonation yielded sulfonyl cloride (VII). This acid chloride was coupled to imidazoline (IV) in the presence of NaHCO3 in aqueous acetone to furnish a mixture of sulfonyl imidazolines (VIII) and (IX). The major isomer (IX) was isolated by column chromatography, and then, hydrolysis with HCl in MeOH at r.t. provided imidazolidinone (X). The trifluoroacetamide group of (X) was further hydrolyzed by treatment with NaOH in aqueous MeOH to give (XI). Subsequent condensation of (XI) with 4-nitrobenzoyl chloride (XII) in the presence of pyridine yielded 4-nitrobenzamide (XIII), which was finally reduced to the aminobenzamide by hydrogenation using Raney-nickel as the catalyst.

参考文献 中间体
合成目标
【1】 Jung, S.-H.; Lee, H.S.; Song, J.S.; Kim, H.M.; Han, S.B.; Lee, C.W.; Lee, M.; Choi, D.R.; Lee, J.A.; Chung, Y.H.; Yoon, S.J.; Moon, E.Y.; Hwang, H.S.; Seong, S.K.; Lee, D.K.; Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones. Bioorg Med Chem Lett 1998, 8, 12, 1547.
【2】 Yoon, S.J.; Chung, Y.H.; Lee, M.S.; Choi, D.R.; Lee, J.A.; Lee, H.S.; Yun, H.R.; Lee, D.K.; Moon, E.Y.; Hwang, H.S.; Choi, C.H.; Jung, S.H. (Dong-Wha Pharmaceuticals Industry Co. Ltd); Arylsulfonylimidazolone derivs. as an antitumor agent. EP 1021437; JP 2000505096; US 5929103; WO 9807719 .
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) 19648 Cyanamide 420-04-2 CH2N2 详情 详情
(II) 19649 1-vinylbenzene 100-42-5 C8H8 详情 详情
(III) 19650 2-bromo-1-phenylethylcyanamide C9H9BrN2 详情 详情
(IV) 19651 methyl 5-phenyl-4,5-dihydro-1H-imidazol-2-yl ether; 2-methoxy-5-phenyl-4,5-dihydro-1H-imidazole C10H12N2O 详情 详情
(V) 19652 indoline 496-15-1 C8H9N 详情 详情
(VI) 19653 1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone C10H8F3NO 详情 详情
(VII) 19654 1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride C10H7ClF3NO3S 详情 详情
(VIII) 19655 2,2,2-trifluoro-1-[5-[(2-methoxy-5-phenyl-4,5-dihydro-1H-imidazol-1-yl)sulfonyl]-2,3-dihydro-1H-indol-1-yl]-1-ethanone C20H18F3N3O4S 详情 详情
(IX) 19656 2,2,2-trifluoro-1-[5-[(2-methoxy-4-phenyl-4,5-dihydro-1H-imidazol-1-yl)sulfonyl]-2,3-dihydro-1H-indol-1-yl]-1-ethanone C20H18F3N3O4S 详情 详情
(X) 19657 4-phenyl-1-[[1-(2,2,2-trifluoroacetyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-2-imidazolidinone C19H16F3N3O4S 详情 详情
(XI) 19658 1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone C17H17N3O3S 详情 详情
(XII) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(XIII) 19660 1-[[1-(4-nitrobenzoyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-phenyl-2-imidazolidinone C24H20N4O6S 详情 详情

合成路线2

该中间体在本合成路线中的序号：(VII)

A synthesis of the (S)-enantiomer of the target compound has also been reported, starting from (S)-1-phenylethanolamine (XIV). Treatment with phenyl chloroformate (XV) and NaHCO3 yielded carbamate (XVI). Subsequent reaction of (XVI) with methanesulfonyl chloride and Et3N provided mesylate (XVII). The sulfonamide (XVIII) was prepared from sulfonyl chloride (VII) by treatment with ammonia gas in CH2Cl2. Condensation of this sulfonamide with mesylate (XVII) in the presence of NaH produced the chiral imidazolidinone (XIX). Finally, the target compound was obtained by condensation with 4-nitrobenzoyl chloride (XII), followed by reduction with H2 in the presence of Raney-Ni.

参考文献 中间体
合成目标
【1】 Jung, S.-H.; Lee, H.S.; Song, J.S.; Kim, H.M.; Han, S.B.; Lee, C.W.; Lee, M.; Choi, D.R.; Lee, J.A.; Chung, Y.H.; Yoon, S.J.; Moon, E.Y.; Hwang, H.S.; Seong, S.K.; Lee, D.K.; Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones. Bioorg Med Chem Lett 1998, 8, 12, 1547.
【2】 Yoon, S.J.; Chung, Y.H.; Lee, M.S.; Choi, D.R.; Lee, J.A.; Lee, H.S.; Yun, H.R.; Lee, D.K.; Moon, E.Y.; Hwang, H.S.; Choi, C.H.; Jung, S.H. (Dong-Wha Pharmaceuticals Industry Co. Ltd); Arylsulfonylimidazolone derivs. as an antitumor agent. EP 1021437; JP 2000505096; US 5929103; WO 9807719 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII) 19654 1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride C10H7ClF3NO3S 详情 详情
(XII) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(XIV) 10973 (2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol 20989-17-7 C8H11NO 详情 详情
(XV) 13580 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate 1885-14-9 C7H5ClO2 详情 详情
(XVI) 19663 phenyl (1S)-2-hydroxy-1-phenylethylcarbamate C15H15NO3 详情 详情
(XVII) 19664 (2S)-2-[(phenoxycarbonyl)amino]-2-phenylethyl methanesulfonate C16H17NO5S 详情 详情
(XVIII) 19665 1-(2,2,2-trifluoroacetyl)-5-indolinesulfonamide C10H9F3N2O3S 详情 详情
(XIX) 19666 (4S)-1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone C17H17N3O3S 详情 详情
(XX) 19667 (4S)-1-[[1-(4-nitrobenzoyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-phenyl-2-imidazolidinone C24H20N4O6S 详情 详情

合成路线3

该中间体在本合成路线中的序号：(III)

Protection of indoline (I) using trifluoroacetic anhydride provided N-trifluoroacetylindoline (II), which was sulfonated with chlorosulfonic acid to give sulfonyl chloride (III). Further treatment with ammonia in CH2Cl2 produced sulfonamide (IV). Phenylglycinol (V) was condensed with phenyl chloroformate to afford carbamate (VI). Subsequent reaction of (VI) with metanesulfonyl chloride and triethylamine yielded mesylate (VII). The condensation of sulfonamide (IV) with mesylate (VII), with concomitant cyclization of carbamate group and trifluoroacetyl deprotection, furnished imidazolone (VIII). This was further condensed with 4-nitrobenzoyl chloride (IX), and the resulting 4-nitrobenzamide (X) was finally reduced to the target aminobenzamide by hydrogenation over Raney Nickel.

参考文献 中间体
合成目标
【1】 Yoon, S.J.; Chung, Y.H.; Lee, M.S.; Choi, D.R.; Lee, J.A.; Lee, H.S.; Yun, H.R.; Lee, D.K.; Moon, E.Y.; Hwang, H.S.; Choi, C.H.; Jung, S.H. (Dong-Wha Pharmaceuticals Industry Co. Ltd); Arylsulfonylimidazolone derivs. as an antitumor agent. EP 1021437; JP 2000505096; US 5929103; WO 9807719 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
13580 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate 1885-14-9 C7H5ClO2 详情 详情
(I) 19652 indoline 496-15-1 C8H9N 详情 详情
(II) 19653 1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone C10H8F3NO 详情 详情
(III) 19654 1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride C10H7ClF3NO3S 详情 详情
(IV) 19665 1-(2,2,2-trifluoroacetyl)-5-indolinesulfonamide C10H9F3N2O3S 详情 详情
(V) 10973 (2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol 20989-17-7 C8H11NO 详情 详情
(VI) 19663 phenyl (1S)-2-hydroxy-1-phenylethylcarbamate C15H15NO3 详情 详情
(VII) 19664 (2S)-2-[(phenoxycarbonyl)amino]-2-phenylethyl methanesulfonate C16H17NO5S 详情 详情
(VIII) 19666 (4S)-1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone C17H17N3O3S 详情 详情
(IX) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(X) 19667 (4S)-1-[[1-(4-nitrobenzoyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-phenyl-2-imidazolidinone C24H20N4O6S 详情 详情
Extended Information