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【结 构 式】 
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【分子编号】68253 【品名】(2S,4R)-tert-butyl 4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidine-1-carboxylate 【CA登记号】 |
【 分 子 式 】C29H35ClN4O8S 【 分 子 量 】635.138 【元素组成】C 54.84% H 5.55% Cl 5.58% N 8.82% O 20.15% S 5.05% |
合成路线1
该中间体在本合成路线中的序号：(XXV)Alternatively, condensation of 1,7-dichloro-4-methoxyisoquinoline (XXI) with 1-(tert-butoxycarbonyl)-4(R)-hydroxy-L-proline (XVI) in the presence of t-BuOK in DMSO gives 1-(tert-butoxycarbonyl)-4(R)-[(7-chloro-4-methoxyisoquinolin-1-yl)oxy]-L-proline (XXIV), which is then coupled with 1(R)-amino-2(S)-vinylcyclopropanecarboxamide (XI) by means of EDC, HOBt and DIEA , or HATU and DIEA in CH2Cl2 , to yield the corresponding dipeptide derivative (XXV). NBoc cleavage by means of HCl in i-PrOH (1) or refluxing MeOH provides amine hydrochloride (XXVI), which is finally condensed with N-(tert-butoxycarbonyl)-3-methyl-L-valine (XIX) using HATU and DIEA in .
| 【1】 Perrone, R.K., Wang, C., Ying, W., Song, A.I. (Bristol-Myers Squibb Co.).Crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-cholor-4-methoxy-1-isoquino linyl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide. CN 101903371, EP 2231639, JP 2011507869, KR 2010099703, WO 2009085659. |
| 【2】 Sun, L.Q., Wang, A.X., Chen, J. et al. Design and optimization of a series of potent and novel HCV NS3 protease inhibitors leading to the discovery of BMS-650032. 241st ACS Natl Meet (March 27-30, Anaheim) 2011, Abst MEDI 73. |
| 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 |
| (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 |
| (XXI) | 68249 | 1,7-dichloro-4-methoxyisoquinoline | C10H7Cl2NO | 详情 | 详情 | |
| (XXIV) | 68254 | 1-(tert-butoxycarbonyl)-4(R)-[(7-chloro-4-methoxyisoquinolin-1-yl)oxy]-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)pyrrolidine-2-carboxylic acid | C20H23ClN2O6 | 详情 | 详情 | |
| (XXV) | 68253 | (2S,4R)-tert-butyl 4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidine-1-carboxylate | C29H35ClN4O8S | 详情 | 详情 | |
| (XXVI) | 68252 | (2S,4R)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-N-((1S,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide hydrochloride | C24H27ClN4O6S.HCl | 详情 | 详情 |