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【结 构 式】 
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【分子编号】68433 【品名】methyl 8-bromo-4-(((3S,5R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1S,2R)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl)oxy)-7-methoxyquinoline-2-carboxylate 【CA登记号】 |
【 分 子 式 】C36H45BrN4O10 【 分 子 量 】773.678 【元素组成】C 55.89% H 5.86% Br 10.33% N 7.24% O 20.68% |
合成路线1
该中间体在本合成路线中的序号：(XI)Alcohol (VIII) is converted to the corresponding brosylate (IX) by treatment with p-bromobenzenesulfonyl chloride in the presence of DMAP and Et3N in CH2Cl2 . Subsequent displacement of the sulfonate group of compound (IX) with the quinolinol (X) in the presence of Cs2CO3 in NMP affords the ether adduct (XI) . Selective hydrolysis of diester (XI) by means of NaOH in THF/H2O generates the sodium salt (XII), which, after conversion to a mixed anhydride with i-BuOCOCl and Et3N in THF, is treated in situ with CH2N2 to give the diazoketone (XIII). Finally, reaction of diazoketone (XIII) with concentrated HBr in THF yields the α-bromoketone (I) .
| 【1】 Llinas-Brunet, M., Bailey, M.D., Goudreau, N. et al. Discovery of a potent and selective noncovalent linear inhibitor of the hepatitis C virus NS3 protease (BI 201335). J Med Chem 2010, 53(17): 6466-76. |
| 【2】 Llinas-Brunet, M., Bailey, M., Bhardwaj, P. et al. (Boehringer Ingelheim International GmbH & Co. KG). Hepatitis C inhibitor compounds. US 7585845. |
| 【3】 Bhardwaj, P., Forgione, P., Goudreau, N. et al. (Boehringer Ingelheim International GmbH). Hepatitis C inhibitor compounds. EP 1654261, JP 2006528937, JP 2010043129, US 2005020503, US 2011177030, US 8067438, WO 2004103996. |
| 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) | 68425 | (1S,2R)-methyl 1-((2R,4S)-4-((8-bromo-2-(2-bromoacetyl)-7-methoxyquinolin-4-yl)oxy)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate | C36H44Br2N4O9 | 详情 | 详情 | |
| (VIII) | 68436 | (1S,2R)-methyl 1-((2R,4R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate | C24H37N3O7 | 详情 | 详情 | |
| (IX) | 68435 | (1S,2R)-methyl 1-((2R,4R)-4-(((4-bromophenyl)sulfonyl)oxy)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate | C30H40BrN3O9S | 详情 | 详情 | |
| (X) | 68434 | methyl 8-bromo-4-hydroxy-7-methoxyquinoline-2-carboxylate | C12H10BrNO4 | 详情 | 详情 | |
| (XI) | 68433 | methyl 8-bromo-4-(((3S,5R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1S,2R)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl)oxy)-7-methoxyquinoline-2-carboxylate | C36H45BrN4O10 | 详情 | 详情 | |
| (XII) | 68432 | sodium 8-bromo-4-(((3S,5R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1S,2R)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl)oxy)-7-methoxyquinoline-2-carboxylate | C35H42BrN4NaO10 | 详情 | 详情 | |
| (XIII) | 68431 | (1S,2R)-methyl 1-((2R,4S)-4-((8-bromo-2-(2-diazoacetyl)-7-methoxyquinolin-4-yl)oxy)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate | C36H43BrN6O9 | 详情 | 详情 |