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【结 构 式】 
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【分子编号】51592 【品名】Carbonochloridic acid, cyclohexyl ester; Cyclohexyl chloroformate 【CA登记号】13248-54-9 |
【 分 子 式 】C7H11ClO2 【 分 子 量 】162.61584 【元素组成】C 51.7% H 6.82% Cl 21.8% O 19.68% |
合成路线1
该中间体在本合成路线中的序号：(X)(R)-Piperazine-2-carboxylic acid, obtained by resolution of the racemic piperazine (VIII) with (-)-camphorsulfonic acid, was regioselectively protected with Boc-ON at the 4-N atom, yielding the tert-butyl carbamate (IX). Subsequent treatment with cyclohexyl chloroformate (X) produced the bis-carbamate (XI), which was further subjected to selective Boc group cleavage under acidic conditions. The resultant piperazine (XII) was condensed with the tricyclic alkyl chloride (XIII), producing a diastereomeric mixture of N-alkylated adducts from which the required isomer (XIV) was isolated by flash chromatography. Finally, coupling of acid (XIV) with the intermediate amine (VII) by means of EDC and HOBt gave rise to the title compound.
| 【1】 Guzi, T.; Taveras, A.G.; Ferreira, J.A.; Desai, J.A.; Wang, J.J.S.; Lalwani, T.; Alvarez, C.; Afonso, A.; Girijavallabhan, V.M.; Mallams, A.K.; Doll, R.J.; Weinstein, J.; Cooper, A.B.; Chao, J.; Rane, D.F.; Aki, C.J.; Kelly, J.M. (Schering Corp.); Tricyclic farnesyl protein transferase inhibitors. EP 1140902; WO 0037459 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 51590 | N-benzyl-3-(4-methyl-1H-imidazol-1-yl)-1-propanamine; N-benzyl-N-[3-(4-methyl-1H-imidazol-1-yl)propyl]amine | C14H19N3 | 详情 | 详情 | |
| (VIII) | 25933 | 2-piperazinecarboxylic acid; Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
| (IX) | 51591 | (2R)-4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C10H18N2O4 | 详情 | 详情 | |
| (X) | 51592 | Carbonochloridic acid, cyclohexyl ester; Cyclohexyl chloroformate | 13248-54-9 | C7H11ClO2 | 详情 | 详情 |
| (XI) | 51593 | (2R)-4-(tert-butoxycarbonyl)-1-[(cyclohexyloxy)carbonyl]-2-piperazinecarboxylic acid | C17H28N2O6 | 详情 | 详情 | |
| (XII) | 51594 | (2R)-1-[(cyclohexyloxy)carbonyl]-2-piperazinecarboxylic acid | C12H20N2O4 | 详情 | 详情 | |
| (XIII) | 17936 | 8,11-dichloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C14H11Cl2N | 详情 | 详情 | |
| (XIV) | 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 |