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【结 构 式】

【分子编号】25222

【品名】(3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl methanesulfonate

【CA登记号】

【 分 子 式 】C27H37N3O6S

【 分 子 量 】531.6734

【元素组成】C 61% H 7.01% N 7.9% O 18.06% S 6.03%

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:(V)

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
Extended Information