【结 构 式】 |
【药物名称】 【化学名称】1-[4-[4-[1(S)-[4-(1,3-Benzodioxol-5-ylmethyl)phenyl]ethyl]-3(S)-methylpiperazin-1-yl]piperidin-1-yl]-1-(2,6-dimethylphenyl)methanone 【CA登记号】 【 分 子 式 】C35H43N3O3 【 分 子 量 】553.75126 |
【开发单位】Schering-Plough (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Chemokine CCR5 Antagonists |
合成路线1
The lithium derivative (II), prepared from p-bromo-alpha-methylbenzylamine (I), was added to piperonal (III) to obtain the diaryl carbinol (IV), which was further deoxygenated to (V) using triethylsilane and trifluoroacetic acid. Basic hydrolysis of the trifluoroacetamide function of (V) provided amine (VI). This was then alkylated with the chiral triflate (VII) to afford amino ester (VIII). Subsequent acylation of amine (VIII) with chloroacetyl chloride (IX), followed by cyclization of the resulting chloroacetamide (X) with ammonia, led to the diketopiperazine (XI). Reduction of the carbonyl groups of (XI), followed by reductive amination of the resulting piperazine (XII) with N-Boc-4-piperidinone (XIII), gave the piperidinyl piperazine (XIV). After acidic Boc group cleavage of (XIV), the resulting piperidine (XV) was finally condensed with 2,6-dimethylbenzoic acid (XVI) to yield the target benzamide.
【1】 Tagat, J.R.; et al.; Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine as a key pharmacophore element. Bioorg Med Chem Lett 2001, 11, 16, 2143. |
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) | 50550 | N-[(1S)-1-(4-bromophenyl)ethyl]-2,2,2-trifluoroacetamide | C10H9BrF3NO | 详情 | 详情 | |
(II) | 50551 | C10H8F3Li2NO | 详情 | 详情 | ||
(III) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
(IV) | 50552 | N-((1S)-1-[4-[1,3-benzodioxol-5-yl(hydroxy)methyl]phenyl]ethyl)-2,2,2-trifluoroacetamide | C18H16F3NO4 | 详情 | 详情 | |
(V) | 50553 | N-[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]-2,2,2-trifluoroacetamide | C18H16F3NO3 | 详情 | 详情 | |
(VI) | 50554 | (1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]-1-ethanamine; (1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethylamine | C16H17NO2 | 详情 | 详情 | |
(VII) | 50555 | ethyl (2R)-2-[[(trifluoromethyl)sulfonyl]oxy]propanoate | C6H9F3O5S | 详情 | 详情 | |
(VIII) | 50556 | ethyl (2S)-2-([(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]amino)propanoate | C21H25NO4 | 详情 | 详情 | |
(IX) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
(X) | 50557 | ethyl (2S)-2-[[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl](2-chloroacetyl)amino]propanoate | C23H26ClNO5 | 详情 | 详情 | |
(XI) | 50558 | (6S)-1-[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]-6-methyl-2,5-piperazinedione | C21H22N2O4 | 详情 | 详情 | |
(XII) | 50559 | (2S)-1-[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]-2-methylpiperazine | C21H26N2O2 | 详情 | 详情 | |
(XIII) | 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 |
(XIV) | 50560 | tert-butyl 4-((3S)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]-3-methylpiperazinyl)-1-piperidinecarboxylate | C31H43N3O4 | 详情 | 详情 | |
(XV) | 50561 | (2S)-1-[(1S)-1-[4-(1,3-benzodioxol-5-ylmethyl)phenyl]ethyl]-2-methyl-4-(4-piperidinyl)piperazine | C26H35N3O2 | 详情 | 详情 | |
(XVI) | 50562 | m-Xylylic acid; 2,6-Dimethylbenzoic acid; m-Xylene-2-carboxylic acid | 632-46-2 | C9H10O2 | 详情 | 详情 |