Transcainide, R-54718
群司卡尼Chemical Name: (?-trans-4-(Dimethylamino)-N-(2,6-dimethylphenyl)-1-(2-hydroxycyclohexyl)-4-piperidinecarboxamide
CAS No. 88296-62-2
项目整合开发状态: Phase II
项目研究机构: Janssen (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:N-Aryl-alpha-aminocarboxamide derivs.
文献作者:De Bruyn,M.F.L.; Van Daele,G.H.P.; Verdonck,M.G.C.(Janssen Pharmaceutica NV)
参考来源:EP 0121972; ES 8506615
📄 详细内容
合成路线: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.
参考文献标题:Transcainidine
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1988,13(3),239
产品链接: CAS No. 88296-62-2››