Vanoxerine hydrochloride, I-893, GBR-12909
伐诺司林Chemical Name: 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
CAS No. 67469-69-6 (free base)
项目整合开发状态: Phase I
项目研究机构: Yamanouchi (Originator), National Institute on Drug Abuse (Licensee)
合成路线:Condensation of bis(4-fluorophenyl)methyl 2-chloroethyl ether (I) with piperazine (II) in refluxing toluene afforded the monosubstituted piperazine (III).This was then alkylated with (3-bromopropyl)benzene (IV) in boiling EtOH to furnish the title compound.
📌 参考资料/链接：
参考文献标题:Piperazine derivs.,process for their preparation and their use
文献作者:Gootjes,J.(Gist-Brocades NV)
参考来源:DE 2755752; US 4202896
📄 详细内容
合成路线:Condensation of bis(4-fluorophenyl)methyl 2-chloroethyl ether (I) with piperazine (II) in refluxing toluene afforded the monosubstituted piperazine (III).This was then alkylated with (3-bromopropyl)benzene (IV) in boiling EtOH to furnish the title compound.
参考文献标题:Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake
文献作者:Van der Zee,P.; et al.
参考来源:Eur J Med Chem 1980,15(4),363
合成路线:1-(3-Phenylpropyl)piperazine (III) has been obtained by condensation of 3-phenylpropyl bromide (I) with piperazine (II) in refluxing acetonitrile.The condensation of bis(4-fluorophenyl)methanol (IV) with 2-chloroethanol (V) by means of sulfuric acid gives the 2-chloroethyl bis(4-fluorophenyl)methyl ether (VI),which si treated with NaI to yield the corresponding iodo derivative (VII).Finally this compound is condensed with the intermediate piperazine (III) by means of aq.Na2CO3 to afford the target disubstituted piperazine.
参考文献标题:Scale-up synthesis of the dopamine uptake inhibitor GBR-12909
文献作者:Zhang,J.; Ironside,M.D.; Sugathapala,P.M.; Robertson,J.; Darey,M.C.P.
参考来源:Org Process Res Dev 2002,6(5),621
产品链接: CAS No. 67469-69-6››