Icopezil maleate, CP-118954-11, CP-118954
艾考哌齐 Chemical Name: 3-[2-(1-Benzylpiperidin-4-yl)ethyl]-6,7-dihydro-5H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one maleate salt (1:1)
CAS No. 145815-98-1, 145508-78-7 (free base)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:The Friedel Crafts condensation of 6-methoxyindolin-2-one (I) with acetyl chloride and AlCl3 gives the 5-acetyl-6-methoxyindolin-2-one (II),which is treated with hydroxylamine and acetic anhydride to yield the O-acetyloxime (III).The cyclization of (III) affords the 3-methyl-6,7-dihydro-5H-isoxazolo[4,5-f]indol-6-one (IV),which is condensed with 4-(iodomethyl)piperidine-1-carboxylic acid tert-butyl ester (V) to provide the adduct (VI).Finally this compound is deprotected with TFA and benzylated with benzyl bromide (VII) to furnish the target compound.
📌 参考资料/链接：
参考文献标题:5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxaxol-6-one: A potent and centrally-selective inhibitor of acetylcholinesterase with an improved margin of safety
文献作者:Villalobos,A.; Butler,T.W.; Chapin,D.S.; Chen,Y.L.; DeMattos,S.B.; Ives,J.L.; Jones,S.B.; Liston,D.R.; Nagel,A.A.; Nason,D.M.; et al.
参考来源:J Med Chem 1995,38(15),2802
📄 详细内容
合成路线:Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II),which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene,Na in benzene or Na in ether/benzene.
合成路线:The Friedel Crafts condensation of 6-methoxyindolin-2-one (I) with acetyl chloride and AlCl3 gives the 5-acetyl-6-methoxyindolin-2-one (II),which is treated with hydroxylamine and acetic anhydride to yield the O-acetyloxime (III).The cyclization of (III) affords the 3-methyl-6,7-dihydro-5H-isoxazolo[4,5-f]indol-6-one (IV),which is condensed with 4-(iodomethyl)piperidine-1-carboxylic acid tert-butyl ester (V) to provide the adduct (VI).Finally this compound is deprotected with TFA and benzylated with benzyl bromide (VII) to furnish the target compound.
参考文献标题:New acetylcholinesterease inhibitors
文献作者:Maggi,A.; Brufani,M.; Lappa,S.; Filocamo,L.
参考来源:Drugs Fut 1997,22(4),397
产品链接: CAS No. 145815-98-1›› 产品链接: CAS No.145508-78-7››