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【结 构 式】

【分子编号】68440

【品名】(4S)-tert-butyl 4-hydroxy-2-(((1R,2S)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidine-1-carboxylate

【CA登记号】 

【 分 子 式 】C17H26N2O6

【 分 子 量 】354.403

【元素组成】C 57.61% H 7.39% N 7.90% O 27.09%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XV)

Tripeptide derivative (VIII) is obtained by coupling of N-Boc-4(R)-hydroxy-L-proline (XIV) with methyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate (Vb) by means of TBTU and DIEA in DMF to afford amide (XV). Subsequent Mitsunobu condensation of alcohol (XV) with p-nitrobenzoic acid (PNBA) in the presence of PPh3 and DEAD in THF gives the fully protected dipeptide (XVI), from which the N-Boc group is removed by treatment with HCl in dioxane, yielding the corresponding amine (XVII) . Coupling of dipeptide ester (XVII) with N-(cyclopentyloxycarbonyl)-3-methyl-L-valine (XVIII) [prepared by condensation of cyclopentyl succinimidyl carbonate (XX) with 3-methyl-L-valine (XIX) by means of Et3N in THF/H2O in the presence of TBTU and DIEA in CH2Cl2 provides tripeptide derivative (XXI), which by selective hydrolysis of the PNB ester (XXI) by means of LiOH in H2O/THF produces the tripeptide derivative (VIII) .

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.
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.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(Vb) 68460 (1R,2R)-methyl 1-amino-2-vinylcyclopropanecarboxylate   C7H11NO2 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
(XIV) 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
(XV) 68440 (4S)-tert-butyl 4-hydroxy-2-(((1R,2S)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidine-1-carboxylate   C17H26N2O6 详情 详情
(XVI) 68441 (2S,4R)-tert-butyl 2-(((1R,2S)-1-(methoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)-4-((4-nitrobenzyl)oxy)pyrrolidine-1-carboxylate   C24H31N3O8 详情 详情
(XVII) 68439 (1R,2S)-methyl 1-((2R,4R)-4-((4-nitrobenzyl)oxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride   C19H23N3O6.HCl 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
(XIX) 28445 (2S)-2-amino-3,3-dimethylbutyric acid C6H13NO2 详情 详情
(XX) 68443 cyclopentyl succinimidyl carbonate;N-(Cyclopentyloxycarbonyloxy)succinimide;1-[[(cyclopentyloxy)carbonyl]oxy]-2,5-Pyrrolidinedione 128595-07-3 C10H13NO5 详情 详情
(XXI) 68437 (1R,2S)-methyl 1-((2S,4R)-1-(2-(((cyclopentyloxy)carbonyl)amino)-3,3-dimethylbutanoyl)-4-((4-nitrobenzyl)oxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate   C31H42N4O9 详情 详情
Extended Information