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【结 构 式】 
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【分子编号】68445 【品名】(1R,2S)-methyl 1-((2S,4R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate 【CA登记号】 |
【 分 子 式 】C24H37N3O7 【 分 子 量 】479.5738 【元素组成】C 60.11% H 7.78% N 8.76% O 23.35% |
合成路线1
该中间体在本合成路线中的序号：(XXV)Coupling of 4(R)-hydroxy-L-proline methyl ester hydrochloride (XXII) with N-(cyclopentyloxycarbonyl)-3-methyl-L-valine (XVIII) by means of EDC, HOBt and DIEA in DMF affords the dipeptide derivative (XXIII), which is then subjected to methyl ester hydrolysis with LiOH in H2O/MeOH/THF to yield dipeptide carbamate (XXIV) (isolated as solvate with MTBE). Subsequent condensation of compound (XXIV) with the chloroquinoline (VII) using t-BuOK in DMSO gives rise to the key intermediate (IV) .
Coupling of the dipeptide carbamate (XXIV) with methyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate tosylate salt (Va) by means of EDC, HOBt and DIEA in DMF leads to the tripeptide ester (XXV), which by hydrolysis with LiOH in H2O/MeOH/THF provides the carboxylic acid intermediate (VI) .
| 【1】 Berkenbusch, T., Busacca, C.A., Jaeger, B., Varsolona, R.J. (Boehringer Ingelheim Pharma GmbH & Co. KG). Crystalline forms of a 2-thiazolyl-4-quinolinyl-oxy derivative, a potent HCV inhibitor. CN 102159571, EP 2331538, JP 2012502910, KR 2011059841, US 2010093792, WO 2010033444. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 68428 | methyl 1(R)-amino-2(S)- vinylcyclopropanecarboxylate tosylate salt;(1R,2S)-methyl 1-amino-2-vinylcyclopropanecarboxylate 4-methylbenzenesulfonate | C7H11NO2.C7H8O3S | 详情 | 详情 | |
| (IV) | 68427 | (2R,4S)-4-((8-bromo-2-(2-isobutyramidothiazol-4-yl)-7-methoxyquinolin-4-yl)oxy)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid | C34H42BrN5O8S | 详情 | 详情 | |
| (VI) | 68429 | (1S,2R)-1-((2R,4S)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylic acidtripeptide carbamate | C23H35N3O7 | 详情 | 详情 | |
| (VII) | 68430 | N-(4-(8-bromo-4-chloro-7-methoxyquinolin-2-yl)thiazol-2-yl)isobutyramide | C17H15BrClN3O2S | 详情 | 详情 | |
| (XVIII) | 68442 | 2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoic acid;N-(cyclopentyloxycarbonyl)-3-methyl-L-valine | C12H21NO4 | 详情 | 详情 | |
| (XXII) | 68444 | 4(R)-hydroxy-L-proline methyl ester hydrochloride;(2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride | C6H11NO3.HCl | 详情 | 详情 | |
| (XXIII) | 68447 | (2S,4R)-methyl 1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxylate | C18H30N2O6 | 详情 | 详情 | |
| (XXIV) | 68446 | (2S,4R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxylic acid | C17H28N2O6 | 详情 | 详情 | |
| (XXV) | 68445 | (1R,2S)-methyl 1-((2S,4R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate | C24H37N3O7 | 详情 | 详情 |