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【结 构 式】 
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【药物名称】DW-2282 【化学名称】(+)-(S)-1-[1-(4-Aminobenzoyl)indolin-5-ylsulfonyl]-4-phenylimidazolidin-2-one 【CA登记号】203861-05-6 (monoHCl), 203860-97-3 (racemic monoHCl) 【 分 子 式 】C24H22N4O4S 【 分 子 量 】462.53134 |
【开发单位】Dong-Wha (Originator) 【药理作用】Oncolytic Drugs |
合成路线1
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.
| 【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 |