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【结 构 式】 
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【分子编号】68246 【品名】tert-butyl (1-((2S,4R)-2-(((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate 【CA登记号】 |
【 分 子 式 】C25H40N4O8S 【 分 子 量 】556.681 【元素组成】C 53.94% H 7.24% N 10.06% O 22.99% S 5.76% |
合成路线1
该中间体在本合成路线中的序号：(XX)Coupling of primary amine (XI) with 1-(tert-butoxycarbonyl)-4(R)-hydroxy-L-proline (XVI) by means of HATU and DIEA in CH2Cl2 gives dipeptide (XVII), which is treated with TFA in CH2Cl2 to provide the deprotected dipeptide (XVIII). Condensation of peptide (XVIII) with N-(tert-butoxycarbonyl)-3-methyl-L-valine (XIX) using HATU and DIEA in CH2Cl2 affords tripeptide (XX), which is finally condensed with 1,7-dichloro-4-methoxyisoquinoline (XXI) in the presence of LaCl3 and t-BuOK in DMF (1).
1,7-Dichloro-4-methoxyisoquinoline (XXI) is obtained by cyclization of 3-(4-chlorophenyl)-3-methoxyacrylic acid (XXII) with (PhO)2PON3 by means of of Et3N in benzene, resulting in 7-chloro-4-methoxyisoquinolin-1(2H)-one (XXIII), which is then chlorinated with POCl3 in refluxing DMF .
| 【1】 Campbell, J.A., Wang, X.A., Sin, N. et al. (Bristol-Myers Squibb Co.). Hepatitis C virus inhibitors. EP 1505963, EP 2340830, JP 2005533028, KR 2010093140, US 200410659, US 6995174, US 2011311482, WO 200309974. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 68243 | tert-butyl ((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamate hydrochloride | C14H22N2O5S.HCl | 详情 | 详情 | |
| (XVI) | 16094 | (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid | 16094 | C10H17NO5 | 详情 | 详情 |
| (XVII) | 68248 | (2S,4R)-tert-butyl 2-(((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidine-1-carboxylate | C19H29N3O7S | 详情 | 详情 | |
| (XVIII) | 68247 | (2S,4R)-N-((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-4-hydroxypyrrolidine-2-carboxamide 2,2,2-trifluoroacetate | C14H21N3O5S.C2HF3O2 | 详情 | 详情 | |
| (XIX) | 22251 | (2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutyric acid;2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoic acid;N-(tert-butoxycarbonyl)-3-methyl-L-valine | 62965-35-9 | C11H21NO4 | 详情 | 详情 |
| (XX) | 68246 | tert-butyl (1-((2S,4R)-2-(((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate | C25H40N4O8S | 详情 | 详情 | |
| (XXI) | 68249 | 1,7-dichloro-4-methoxyisoquinoline | C10H7Cl2NO | 详情 | 详情 | |
| (XXII) | 68250 | 3-(4-chlorophenyl)-3-methoxyacrylic acid | C10H9ClO3 | 详情 | 详情 | |
| (XXIII) | 68251 | 7-chloro-4-methoxyisoquinolin-1(2H)-one | C10H8ClNO2 | 详情 | 详情 |