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【结 构 式】 
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【分子编号】22027 【品名】benzyl 4-(dimethylamino)-4-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C24H31N3O3 【 分 子 量 】409.52856 【元素组成】C 70.39% H 7.63% N 10.26% O 11.72% |
合成路线1
该中间体在本合成路线中的序号：(IX)The hydrolysis of 1-benzyl-4-(methylamino)piperidine-4-carboxamide (I) with refluxing concentrated aqueous HCl gives the corresponding free acid (II), which is debenzylated with H2 over Pd/C in basic medium yielding 4-(methylamino)piperidine-4-carboxylic acid sodium salt (III). The protection of (III) with benzyl chloroformate (IV) in basic THF - water affords 1-(benzyloxycarbonyl)-4-(methylamino)piperidine 4 carboxylic acid (V), which by cyclization with phosgene in dioxane is converted to benzyl 1-methyl-2,4-dioxo 3-oxa-1,8-diazaspiro[4.5]decane-8 carboxylate (VI). The reaction of (VI) with 2,6-dimethylaniline (II) by heating at 160 C gives benzyl 4-(2,6-dimethylphenylaminocarbonyl)-4-(methylamino)piperidine-1-carboxylate (VIII), which is methylated with refluxing methyl iodide to the corresponding dimethylamino compound (IX). The deprotection of (IX) with H2 over Pd/C in methanol yields 4-(dimethylamino)-N-(2,6-dimethylphenyl)piperidine-4-carboxamide (X), which is finally condensed with 1,2-epoxycyclohexane (XI) in refluxing ethanol.
| 【1】 De Bruyn, M.F.L.; Van Daele, G.H.P.; Verdonck, M.G.C. (Janssen Pharmaceutica NV); N-Aryl-alpha-aminocarboxamide derivs.. EP 0121972; ES 8506615 . |
| 【2】 Castaner, J.; Prous, J.; Transcainidine. Drugs Fut 1988, 13, 3, 239. |
| 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) | 22019 | 1-benzyl-4-(methylamino)-4-piperidinecarboxamide | 1024-11-9 | C14H21N3O | 详情 | 详情 |
| (II) | 22020 | 1-benzyl-4-(methylamino)-4-piperidinecarboxylic acid | C14H20N2O2 | 详情 | 详情 | |
| (III) | 22021 | sodium 4-(methylamino)-4-piperidinecarboxylate | C7H13N2NaO2 | 详情 | 详情 | |
| (IV) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (V) | 22023 | 1-[(benzyloxy)carbonyl]-4-(methylamino)-4-piperidinecarboxylic acid | C15H20N2O4 | 详情 | 详情 | |
| (VI) | 22024 | benzyl 1-methyl-2,4-dioxo-3-oxa-1,8-diazaspiro[4.5]decane-8-carboxylate | C16H18N2O5 | 详情 | 详情 | |
| (VII) | 17527 | 2,6-Xylidine; 2,6-Dimethylaniline; 2,6-Dimethylphenylamine | 87-62-7 | C8H11N | 详情 | 详情 |
| (VIII) | 22026 | benzyl 4-[(2,6-dimethylanilino)carbonyl]-4-(methylamino)-1-piperidinecarboxylate | C23H29N3O3 | 详情 | 详情 | |
| (IX) | 22027 | benzyl 4-(dimethylamino)-4-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate | C24H31N3O3 | 详情 | 详情 | |
| (X) | 22028 | 4-(dimethylamino)-N-(2,6-dimethylphenyl)-4-piperidinecarboxamide | C16H25N3O | 详情 | 详情 | |
| (XI) | 17986 | 7-oxabicyclo[4.1.0]heptane; cyclohexene oxide | 286-20-4 | C6H10O | 详情 | 详情 |