新产品编号:1900491
Chemical Name: (-)-trans-N,N'-(1,8-Octanediyl)bis[4-(4-chlorophenyl)-1-methylpiperidine-3-carboxamide]
项目整合开发状态: Biological Testing
项目研究机构: Georgetown University (Originator), UT Medical Branch at Galveston (Originator)
合成路线:Addition of 4-chlorophenylmagnesium bromide (II) to arecoline (I) in Et2O at -10 C afforded the corresponding 4-arylpiperidine-3-carboxylate as a mixture of trans (III) and cis (IV) isomers.After chromatographic isolation of the racemic cis isomer (IV),resolution employing dibenzoyl-D-tartaric acid furnished the dextro enantiomer (cis)(+)-(IV).Its epimerization in the presence of NaOMe produced a 1:5.6 mixture of cis/trans isomers,from which the major compound (-)-(trans)(III) was isolated by flash chromatography.Acid hydrolysis of its methyl ester group provided carboxylic acid (V),that was further converted to acid chloride (VI) using oxalyl chloride (1,2).Finally,coupling of (VI) with 1,8-octanediamine (VII) gave the title diamide.
📌 参考资料/链接：
参考文献标题:Monomeric and dimeric heterocycles,and therapeutic uses thereof
文献作者:Tamiz,A.P.; Araldi,G.L.; Kozikowski,A.P.(Georgetown University)
参考来源:WO 0020390
📄 详细内容
合成路线:Addition of 4-chlorophenylmagnesium bromide (II) to arecoline (I) in Et2O at -10 C afforded the corresponding 4-arylpiperidine-3-carboxylate as a mixture of trans (III) and cis (IV) isomers.After chromatographic isolation of the racemic cis isomer (IV),resolution employing dibenzoyl-D-tartaric acid furnished the dextro enantiomer (cis)(+)-(IV).Its epimerization in the presence of NaOMe produced a 1:5.6 mixture of cis/trans isomers,from which the major compound (-)-(trans)(III) was isolated by flash chromatography.Acid hydrolysis of its methyl ester group provided carboxylic acid (V),that was further converted to acid chloride (VI) using oxalyl chloride (1,2).Finally,coupling of (VI) with 1,8-octanediamine (VII) gave the title diamide.
参考文献标题:Application of the bivalent ligand approach to the design of novel dimeric serotonin reuptake inhibitors
文献作者:Tamiz,A.P.; Johnson,K.M.; Wang,C.Z.; Kozikowski,A.P.; Zhang,J.; Zhang,M.
参考来源:J Am Chem Soc 2000,122(22),5393