新产品编号:1506573
Chemical Name: 1-[3-[1-[2-(4-Iodophenyl)ethyl]piperidin-4-yl]propyl]-2-(phenoxymethyl)-4-[3-(1-piperidinyl)propoxy]-1H-benzimidazole
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator)
合成路线:The cyclization of 3-hydroxy-1,2-phenylenediamine (I) with 2-phenoxyacetonitrile (II) by means of sodium methoxide in methanol gives the benzimidazole (III),which is acylated with 4-(3-bromopropyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH and KI in hot DMF yielding the N-alkylated benzimidazole (V).The alkylation of the hydroxy group of (V) with 1-(3-bromopropyl)piperidine (VI) by means of NaH and KI as before affords the dialkylated benzimidazole (VII),which is deprotected with TFA in dichloromethane affording the free piperidine (VIII).Finally,the piperidine group of (VIII) is alkylated with 2-(4-iodophenyl)ethyl bromide (IX) by means of NaHCO3 in hot DMF.
📌 参考资料/链接：
参考文献标题:Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists
文献作者:Zarrinmayeh,H.; Zimmerman,D.M.; Cantrell,B.E.; Schober,D.A.; Bruns,R.F.; Gackenheimer,S.L.; Ornstein,P.L.; Hipskind,P.A.; Britton,T.C.; Gehlert,D.R.
参考来源:Bioorg Med Chem Lett 1999,9(5),647
📄 详细内容
合成路线:The cyclization of 3-hydroxy-1,2-phenylenediamine (I) with 2-phenoxyacetonitrile (II) by means of sodium methoxide in methanol gives the benzimidazole (III),which is acylated with 4-(3-bromopropyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH and KI in hot DMF yielding the N-alkylated benzimidazole (V).The alkylation of the hydroxy group of (V) with 1-(3-bromopropyl)piperidine (VI) by means of NaH and KI as before affords the dialkylated benzimidazole (VII),which is deprotected with TFA in dichloromethane affording the free piperidine (VIII).Finally,the piperidine group of (VIII) is alkylated with 2-(4-iodophenyl)ethyl bromide (IX) by means of NaHCO3 in hot DMF.
参考文献标题:Synthesis and evaluation of a series of novel 2-[(4-chlorophenoxy)methyl]benzimidazoles as selective neuropeptide Y Y1 receptor antagonists
文献作者:Zarrinmayeh,H.; Nunes,A.M.; Ornstein,P.L.; Zimmerman,D.M.; Arnold,M.B.; Schober,D.A.; Gackenheimer,S.L.; Bruns,R.F.; Hipskind,P.A.; Britton,T.C.; Cantrell,B.E.; Gehlert,D.R.
参考来源:J Med Chem 1998,41(15),2709