E-4031
N-[4-[[1-[2-(6-甲基-2-吡啶基)乙基]-4-哌啶基]羰基]苯基]甲磺酰胺二盐酸盐 N-[4-[1-[2-(6-甲基吡啶-2-基)乙基]哌啶-4-羰基]苯基]甲烷磺酰胺 Chemical Name: N-[4-[1-[2-(6-Methylpyridin-2-yl)ethyl]piperidin-4-ylcarbonyl]phenyl]methanesulfonamide dihydrochloride dihydrate
CAS No. 113559-13-0 (anhydrous), 113558-89-7 (free base, anhydrous)
项目整合开发状态: Phase II
项目研究机构: Eisai (Originator)
合成路线:The mesylation of aniline (I) with methanesulfonyl chloride gives the sulfonamide (II),which is condensed with 1-acetylpiperidine-4-carbonyl chloride (III) by means of AlCl3 in dichloromethane to give N-[4-(1-acetylpiperidin-4-ylcarbonyl)phenyl]methanesulfonamide (IV).Deacetylation of (IV) with HCl in water yields the piperidine (V),which is finally condensed with 2-methyl-6-vinylpyridine by means of sodium acetate in methanol - water.The same procedure has been performed with [14C]-labeled aniline in order to obtain [14C]-labeled E-4031.
📌 参考资料/链接：
参考文献标题:Piperidine deriv.,pharmaceutical compsn.containing the same and use
文献作者:Oinuma,H.; Yamanaka,M.; Miyake,K.; Hoshiko,T.; Minami,N.; Shoji,T.; Daiku,Y.; Sawada,K.; Nomoto,K.(Eisai Co.,Ltd.)
参考来源:EP 0235752; US 4876262; US 4996215; US 5118689; US 5179095
📄 详细内容
合成路线:The mesylation of aniline (I) with methanesulfonyl chloride gives the sulfonamide (II),which is condensed with 1-acetylpiperidine-4-carbonyl chloride (III) by means of AlCl3 in dichloromethane to give N-[4-(1-acetylpiperidin-4-ylcarbonyl)phenyl]methanesulfonamide (IV).Deacetylation of (IV) with HCl in water yields the piperidine (V),which is finally condensed with 2-methyl-6-vinylpyridine by means of sodium acetate in methanol - water.The same procedure has been performed with [14C]-labeled aniline in order to obtain [14C]-labeled E-4031.
参考文献标题:4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent,selective,bioavailable class III antiarrhythmic agents
文献作者:Oinuma,H.; Miyake,K.; Yamanaka,M.; Nomoto,K.-I.; Katoh,H.; Sawada,K.; Shino,M.; Hamano,S.
参考来源:J Med Chem 1990,33(3),903
合成路线:The mesylation of aniline (I) with methanesulfonyl chloride gives the sulfonamide (II),which is condensed with 1-acetylpiperidine-4-carbonyl chloride (III) by means of AlCl3 in dichloromethane to give N-[4-(1-acetylpiperidin-4-ylcarbonyl)phenyl]methanesulfonamide (IV).Deacetylation of (IV) with HCl in water yields the piperidine (V),which is finally condensed with 2-methyl-6-vinylpyridine by means of sodium acetate in methanol - water.The same procedure has been performed with [14C]-labeled aniline in order to obtain [14C]-labeled E-4031.
参考文献标题:E-4031
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1992,17(6),455
合成路线:The mesylation of aniline (I) with methanesulfonyl chloride gives the sulfonamide (II),which is condensed with 1-acetylpiperidine-4-carbonyl chloride (III) by means of AlCl3 in dichloromethane to give N-[4-(1-acetylpiperidin-4-ylcarbonyl)phenyl]methanesulfonamide (IV).Deacetylation of (IV) with HCl in water yields the piperidine (V),which is finally condensed with 2-methyl-6-vinylpyridine by means of sodium acetate in methanol - water.The same procedure has been performed with [14C]-labeled aniline in order to obtain [14C]-labeled E-4031.
参考文献标题:Synthesis of antiarrhythmic [phenyl-14C]4'-[(4-piperidyl)carbonyl]methanesulfonanilides
文献作者:Shino,M.; Oinuma,H.; Hamano,S.; Miyake,K.; Yamanaka,M.
参考来源:J Label Compd Radiopharm 1990,28(8),921
产品链接: CAS No. 113559-13-0›› 产品链接: CAS No.113558-89-7››