新产品编号:408665
Chemical Name: 4-[2-(Benzylamino)ethoxy]-2-trifluoromethyl-1H-benzimidazole
CAS No. 212062-12-9, 212062-13-0 (mono HCl salt)
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Alkylation of 2-amino-3-nitrophenol (I) with 1,2-dichloroethane in 2-butanone afforded the chloroethyl ether (II),which was further condensed with benzylamine (III) to give amine (IV) (1,2).Acylation of (IV) with trifluoroacetic anhydride provided trifluoroacetamide (V).The nitro group of (V) was then reduced by transfer hydrogenation using hydrazine and Pd/C.Cyclization of the resulting phenylenediamine (VI) in refluxing TFA gave rise to benzimidazole (VII).The trifluoroacetamido group of (VII) was finally removed by treatment with K2CO3 in boiling MeOH (1).In a more direct procedure,nitroaniline (IV) was reduced to diamine (VIII) and then cyclized to the title benzimidazole by treatment with TFA.
📌 参考资料/链接：
参考文献标题:4-Aminoalkoxy-1H-benzimidazole derivs.,their preparation and their use as dopamine autoreceptor (D2) agonists
文献作者:Nelson,J.A.; Mewshaw,R.E.(American Home Products Corp.)
参考来源:EP 0973749; WO 9835945
📄 详细内容
合成路线:Alkylation of 2-amino-3-nitrophenol (I) with 1,2-dichloroethane in 2-butanone afforded the chloroethyl ether (II),which was further condensed with benzylamine (III) to give amine (IV) (1,2).Acylation of (IV) with trifluoroacetic anhydride provided trifluoroacetamide (V).The nitro group of (V) was then reduced by transfer hydrogenation using hydrazine and Pd/C.Cyclization of the resulting phenylenediamine (VI) in refluxing TFA gave rise to benzimidazole (VII).The trifluoroacetamido group of (VII) was finally removed by treatment with K2CO3 in boiling MeOH (1).In a more direct procedure,nitroaniline (IV) was reduced to diamine (VIII) and then cyclized to the title benzimidazole by treatment with TFA.
参考文献标题:New generation dopaminergic agents 7.heterocyclic bioisosteres that exploit the 3-OH-phenoxyethylamine D2 template
文献作者:Mewshaw,R.E.; Nelson,J.A.; Shah,U.S.; Shi,X.; Mazandarani,H.; Coupet,J.; Marquis,K.; Brennan,J.A.; Andree,T.H.
参考来源:Bioorg Med Chem Lett 1999,9(17),2593