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【结 构 式】 
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【分子编号】50442 【品名】benzyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-[(2R)-2-([(2S)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl]carbonyl)pyrrolidinyl]-4-oxobutanoate 【CA登记号】 |
【 分 子 式 】C38H47N5O6 【 分 子 量 】669.82128 【元素组成】C 68.14% H 7.07% N 10.46% O 14.33% |
合成路线1
该中间体在本合成路线中的序号：(XX)Pyrrolidine (XV) was coupled with N-Boc-D-proline (XVI) using EDC to provide amide (XVII). After acid cleavage of the Boc protecting group of (XVII), the resultant amine (XVIII) was further coupled with N-Boc-L-aspartic acid alpha-benzyl ester (XIX) to yield peptide (XX). Pinner reaction of nitrile (XX) with EtOH and HCl, with concomitant transesterification and Boc group cleavage, furnished imidate (XXI). Subsequent treatment of the imidate (XXI) with methanolic ammonia produced the corresponding amidine ester (XXII) along with some amide analogue (XXIII). Finally, basic hydrolysis of this mixture yielded the desired amidino acid.
| 【1】 Koo, B.A.; Min, J.K.; Hong, W.S.; Ryu, E.J.; Nam, W.H.; Kim, J.M. (C & C Research Laboratories); Aromatic amidine derivs. useful as selective thrombin inhibitors. EP 0918768; JP 2000504030; US 6201006; WO 9745424 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 50438 | 1-ethyl-2-[2-[(2S)pyrrolidinyl]ethyl]-1H-indole-6-carbonitrile | C17H21N3 | 详情 | 详情 | |
| (XVI) | 19061 | (2R)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid; (2R)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-D-proline | C10H17NO4 | 详情 | 详情 | |
| (XVII) | 50439 | tert-butyl (2R)-2-([(2S)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl]carbonyl)-1-pyrrolidinecarboxylate | C27H36N4O3 | 详情 | 详情 | |
| (XVIII) | 50440 | 1-ethyl-2-(2-[(2S)-1-[(2R)pyrrolidinylcarbonyl]pyrrolidinyl]ethyl)-1H-indole-6-carbonitrile | C22H28N4O | 详情 | 详情 | |
| (XIX) | 50441 | (3S)-4-(benzyloxy)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid | C16H21NO6 | 详情 | 详情 | |
| (XX) | 50442 | benzyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-[(2R)-2-([(2S)-2-[2-(6-cyano-1-ethyl-1H-indol-2-yl)ethyl]pyrrolidinyl]carbonyl)pyrrolidinyl]-4-oxobutanoate | C38H47N5O6 | 详情 | 详情 | |
| (XXI) | 50445 | ethyl (2S)-2-amino-4-((2R)-2-[[(2S)-2-(2-[6-[ethoxy(imino)methyl]-1-ethyl-1H-indol-2-yl]ethyl)pyrrolidinyl]carbonyl]pyrrolidinyl)-4-oxobutanoate | C30H43N5O5 | 详情 | 详情 | |
| (XXII) | 50443 | ethyl (2S)-2-amino-4-((2R)-2-[[(2S)-2-(2-[6-[amino(imino)methyl]-1-ethyl-1H-indol-2-yl]ethyl)pyrrolidinyl]carbonyl]pyrrolidinyl)-4-oxobutanoate | C28H40N6O4 | 详情 | 详情 | |
| (XXIII) | 50444 | (2S)-2-amino-4-((2R)-2-[[(2S)-2-(2-[6-[amino(imino)methyl]-1-ethyl-1H-indol-2-yl]ethyl)pyrrolidinyl]carbonyl]pyrrolidinyl)-4-oxobutanamide | C26H37N7O3 | 详情 | 详情 |