【结 构 式】 |
【分子编号】58430 【品名】(3R)-3-[(4-methyl-1H-imidazol-1-yl)methyl]piperidine 【CA登记号】 |
【 分 子 式 】C10H17N3 【 分 子 量 】179.2652 【元素组成】C 67% H 9.56% N 23.44% |
合成路线1
该中间体在本合成路线中的序号:(XIII)Reduction of (R)-ethyl nipecotate (VII) with LiAlH4 yields 3-piperidinemethanol (VIII), which is further protected as the N-Boc derivative (IX) by using Boc2O. Treatment of the piperidine alcohol (IX) with p-toluenesulfonyl chloride and pyridine leads to tosylate (X). Condensation of the sodium derivative of 4-methylimidazole (XI) with tosylate (X) gives rise to a mixture of regioisomeric N-alkylated imidazoles, which are chromatographically separated after derivatization with trityl chloride. The desired isomer (XII) is then deprotected under acidic conditions, giving piperidine (XIII). Finally, EDC-mediated coupling between piperidine (XIII) and the piperazinecarboxylic acid (VI) furnishes the title amide.
【1】 Cooper, A.B.; Girijavallabhan, V.M.; Mallams, A.K.; Doll, R.J.; Kelly, J.M.; Rane, D.F.; Taveras, A.G.; Guzi, T.; Strickland, C.; Chao, J. (Schering Corp.); Farnesyl protein transferase inhibitors. EP 1140904; JP 2002533335; WO 0037458 . |
【2】 Cooper, A.B.; Girijavallabhan, V.M.; Mallams, A.K.; Doll, R.J.; Kelly, J.M.; Rane, D.F.; Taveras, A.G.; Guzi, T.; Strickland, C.; Chao, J. (Schering Corp.); Farnesyl protein transferase inhibitors. US 6362188 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 51595 | (2R)-4-[(11S)-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-[(cyclohexyloxy)carbonyl]-2-piperazinecarboxylic acid | C26H30ClN3O4 | 详情 | 详情 | |
(VII) | 12453 | ethyl (3R)hexahydro-3-pyridinecarboxylate | C8H15NO2 | 详情 | 详情 | |
(VIII) | 57427 | (1S)-2,2-dimethylcyclopropanecarbonyl chloride | C6H9ClO | 详情 | 详情 | |
(IX) | 35221 | tert-butyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate | C11H21NO3 | 详情 | 详情 | |
(X) | 57428 | ethyl 3-ethyl-2-pentenoate | C9H16O2 | 详情 | 详情 | |
(XI) | 51586 | 4-Methylimidazole; 4-Methyl-1H-imidazole; 4-Methyl Imidazole | 822-36-6 | C4H6N2 | 详情 | 详情 |
(XII) | 58429 | tert-butyl (3S)-3-[(4-methyl-1H-imidazol-1-yl)methyl]-1-piperidinecarboxylate | C15H25N3O2 | 详情 | 详情 | |
(XIII) | 58430 | (3R)-3-[(4-methyl-1H-imidazol-1-yl)methyl]piperidine | C10H17N3 | 详情 | 详情 |