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【结 构 式】 
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【药物名称】 【化学名称】N-[1-[2(S)-Amino-4-methylpentyl]piperidin-4-yl]-N-(4-benzyloxyphenyl)-N-(3-methyl-2-butenyl)amine 【CA登记号】 【 分 子 式 】C29H43N3O 【 分 子 量 】449.68556 |
【开发单位】Pfizer (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Calcium Channel Blockers |
合成路线1
The reaction of N-(tert-butoxycarbonyl)-L-leucine (I) with N,O-dimethylhydroxylamine and HBTU in DMF gives the corresponding methoxyamide (II), which is reduced with LiAlH4 in ethyl ether yielding the aldehyde (III). The reductocondensation of (III) with the piperidine (IV) by means of sodium triacetoxyborohydride in dichloromethane affords the protected adduct (V), which is finally deprotected with TFA in dichloromethane. The intermediate piperidine (IV) has been obtained as follows: The reductocondensation of the piperidinone (VI) with 4-(benzyloxy)aniline (VII) by means of sodium triacetoxyborohydride in dichloromethane gives the secondary amine (VIII), which is alkylated with 3-methyl-2-butenyl bromide (IX) and DIPEA in THF yielding the protected piperidine (IX). Finally, this compound is deprotected with TFA in dichloromethane to afford the target intermediate (IV).
| 【1】 Siebers, K.M.; Hu, L.-Y.; Rafferty, M.F.; et al.; Neuronal N-type calcium channel blocker: Structure-activity relationship of a series of (S)-2-amino-1(4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl)-4-methyl-pentan-1-one analogs. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 259. |
| 【2】 Rafferty, M.F.; Ryder, T.R.; Hu, L.-Y. (Pfizer Inc.); Aniline derivs. as calcium channel blockers. WO 9907689 . |
| 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) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (II) | 40395 | tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-methylbutylcarbamate | C13H26N2O4 | 详情 | 详情 | |
| (III) | 27058 | tert-butyl (1S)-1-formyl-3-methylbutylcarbamate | C11H21NO3 | 详情 | 详情 | |
| (IV) | 38232 | N-[4-(benzyloxy)phenyl]-N-(3-methyl-2-butenyl)-N-(4-piperidinyl)amine; N-[4-(benzyloxy)phenyl]-N-(3-methyl-2-butenyl)-4-piperidinamine | C23H30N2O | 详情 | 详情 | |
| (V) | 40394 | tert-butyl (1S)-1-([4-[4-(benzyloxy)(3-methyl-2-butenyl)anilino]-1-piperidinyl]methyl)-3-methylbutylcarbamate | C34H51N3O3 | 详情 | 详情 | |
| (VI) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (VII) | 22460 | 4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (VIII) | 38230 | tert-butyl 4-[4-(benzyloxy)anilino]-1-piperidinecarboxylate | C23H30N2O3 | 详情 | 详情 | |
| (IX) | 12989 | 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene | 870-63-3 | C5H9Br | 详情 | 详情 |
| (X) | 38231 | tert-butyl 4-[4-(benzyloxy)(3-methyl-2-butenyl)anilino]-1-piperidinecarboxylate | C28H38N2O3 | 详情 | 详情 |