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【结 构 式】 
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【分子编号】28931 【品名】tert-butyl (1R)-2-[(2S)-2-([[1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-hydroxy-3-piperidinyl]amino]carbonyl)pyrrolidinyl]-1-benzyl-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C33H44N6O7 【 分 子 量 】636.7486 【元素组成】C 62.25% H 6.96% N 13.2% O 17.59% |
合成路线1
该中间体在本合成路线中的序号：(VI)N2-tert-Butoxycarbonyl-N6-benzyloxycarbonyl-L-arginine (I) is converted by treatment with isobutyl oxycarbonyl chloride (A) and N-methylmorpholine (B) to the lactam (II), and the tert-butoxycarbonyl group is cleaved off to give the aminolactam (III), which is coupled with N-tert-butoxycarbonyl-D-phenylalanyl-L-proline (IV) to the tripeptide (V) using the mixed anhydride method as in the first step. The lactam carbonyl is reduced with LiAlH4 to an aldehyde group present as the cyclic a aminoalcohol (VI). Removal of the benzyloxycarbonyl blocking group provides GYKI-14451. In solution the aldehyde group is either in the cyclic alpha-aminoalcohol form or is hydrated.
| 【1】 Voutilainen, S.; Valkonen, V.P.; Venho, B.; et al.; Magy Kem Lapja 1982, 27, 2, 358-365. |
| 【2】 Bajusz, S.; Szell, E.; Barabas, E.; Bagdy, D. (Gedeon Richter Ltd.); D-Phenylalanyl-L-prolyl-L-arginine aldehyde sulfate and process for the preparation thereof. DE 3200812; FR 2497799; GB 2091270; JP 57181046; US 4399065; US 4478745 . |
| 【3】 Nogradi, M.; GYKI-14451. Drugs Fut 1985, 10, 1, 23. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
| (B) | 28928 | 4-methylmorpholine | 109-02-4 | C5H11NO | 详情 | 详情 |
| (I) | 28927 | tert-butyl 3-[(amino[[(benzyloxy)carbonyl]imino]methyl)amino]propylcarbamate | C17H26N4O4 | 详情 | 详情 | |
| (II) | 28933 | tert-butyl 1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinylcarbamate | C19H26N4O5 | 详情 | 详情 | |
| (III) | 28929 | benzyl (E)-amino(3-amino-2-oxo-1-piperidinyl)methylidenecarbamate | C14H18N4O3 | 详情 | 详情 | |
| (IV) | 28932 | (2S)-1-[(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl]-2-pyrrolidinecarboxylic acid | C19H26N2O5 | 详情 | 详情 | |
| (V) | 28930 | tert-butyl (1R)-2-[(2S)-2-([[1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinyl]amino]carbonyl)pyrrolidinyl]-1-benzyl-2-oxoethylcarbamate | C33H42N6O7 | 详情 | 详情 | |
| (VI) | 28931 | tert-butyl (1R)-2-[(2S)-2-([[1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-hydroxy-3-piperidinyl]amino]carbonyl)pyrrolidinyl]-1-benzyl-2-oxoethylcarbamate | C33H44N6O7 | 详情 | 详情 |