新产品编号:1935295
Chemical Name: 1-[3-[3,3-Bis(4-methylphenyl)-2,5-dioxopyrrolidin-1-yl]propyl]-4-(2-methylphenyl)piperidine-4-carbonitrile
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:The intermediate piperidine (IV) was prepared by bis-alkylation of o-methylphenylacetonitrile (I) with N-Boc-bis(2-chloroethyl)amine (II),followed by deprotection of the resulting N-Boc-piperidine (III) with HCl in EtOAc.
合成路线:Di-tolylacetic acid (V) was converted into the benzyl ester (VI) using benzyl bromide and K2CO3 in DMF.Subsequent alpha-alkylation of ester (VI) with ethyl bromoacetate provided diester (VII).The benzyl ester group of (VII) was then removed by hydrogenolysis over Pd/C.Condensation of the resulting mono-acid (VIII) with 3-bromopropylamine (IX) in the presence of EDC and HOBt furnished the N-(bromopropyl)succinimide (X).This was finally condensed with piperidine (IV) to provide the title compound.
📌 参考资料/链接：
参考文献标题:Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists
文献作者:Bell,M.G.; DiPardo,R.M.; Crowell,T.A.; et al.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 298
📄 详细内容
合成路线:The intermediate piperidine (IV) was prepared by bis-alkylation of o-methylphenylacetonitrile (I) with N-Boc-bis(2-chloroethyl)amine (II),followed by deprotection of the resulting N-Boc-piperidine (III) with HCl in EtOAc.
合成路线:Di-tolylacetic acid (V) was converted into the benzyl ester (VI) using benzyl bromide and K2CO3 in DMF.Subsequent alpha-alkylation of ester (VI) with ethyl bromoacetate provided diester (VII).The benzyl ester group of (VII) was then removed by hydrogenolysis over Pd/C.Condensation of the resulting mono-acid (VIII) with 3-bromopropylamine (IX) in the presence of EDC and HOBt furnished the N-(bromopropyl)succinimide (X).This was finally condensed with piperidine (IV) to provide the title compound.
参考文献标题:Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists
文献作者:DiPardo,R.M.; Patane,M.A.; Newton,R.C.; Price,R.A.; Broten,T.P.; Chang,R.S.L.; Ransom,R.W.; Di Salvo,J.; Freidinger,R.M.; Bock,M.G.
参考来源:Bioorg Med Chem Lett 2001,11(14),1959