【结 构 式】 |
【分子编号】25220 【品名】benzyl (3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutanoate 【CA登记号】 |
【 分 子 式 】C33H39N3O5 【 分 子 量 】557.68988 【元素组成】C 71.07% H 7.05% N 7.53% O 14.34% |
合成路线1
该中间体在本合成路线中的序号:(III)Condensation of N-Boc-L-aspartic acid gamma-benzyl ester (I) with N-benzhydryl piperazine (II) using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBT) as the condensig agents gave amide (III). Reduction of the ester group of (III) with NaBH4 in refluxing EtOH provided alcohol (IV), which was treated with methanesulfonyl chloride to afford mesylate (V). Subsequent reaction of (V) with sodium azide in N,N'-dimethylimidazolidinone gave azide (VI), and further cycloaddition of this azide with methyl propiolate (VII) in refluxing dichloroethane furnished triazole (VIII). The tert-butoxycarbonyl protecting group of (VIII) was then removed by treatment with trifluoroacetic acid at room temperature to yield amine (IX), which was condensed with indole-2-carboxylic acid (X) in the presence of EDC and HOBT to give amide (XI). Finally, hydrolysis of (XI) with LiOH provided the target carboxylic acid.
【1】 Ogawa, M.; Morita, T.; Matsuda, K.; Iibuchi, N.; Kidokoro, S. (Tobishi Pharmaceutical Co.); Amino acid deriv. having anti-CKK activity. EP 0710661; JP 1996119940; JP 1996176144; US 5716958 . |
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) | 25219 | (2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid | 7536-58-5 | C16H21NO6 | 详情 | 详情 |
(II) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |
(III) | 25220 | benzyl (3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutanoate | C33H39N3O5 | 详情 | 详情 | |
(IV) | 25221 | tert-butyl (1S)-1-[(4-benzhydryl-1-piperazinyl)carbonyl]-3-hydroxypropylcarbamate | C26H35N3O4 | 详情 | 详情 | |
(V) | 25222 | (3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl methanesulfonate | C27H37N3O6S | 详情 | 详情 | |
(V) | 25223 | tert-butyl (1S)-3-azido-1-[(4-benzhydryl-1-piperazinyl)carbonyl]propylcarbamate | C26H34N6O3 | 详情 | 详情 | |
(VII) | 19588 | methyl propiolate | 922-67-8 | C4H4O2 | 详情 | 详情 |
(VIII) | 25224 | methyl 1-[(3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C30H38N6O5 | 详情 | 详情 | |
(IX) | 25225 | methyl 1-[(3S)-3-amino-4-(4-benzhydryl-1-piperazinyl)-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C25H30N6O3 | 详情 | 详情 | |
(X) | 25226 | 1H-Indole-2-carboxylic acid; Indole-2-carboxylic acid | 1477-50-5 | C9H7NO2 | 详情 | 详情 |
(XI) | 25227 | methyl 1-[(3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(1H-indol-2-ylcarbonyl)amino]-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C34H35N7O4 | 详情 | 详情 |