新产品编号:645965
Chemical Name: 2-(Benzyloxycarboxamido)-3-[4-[2-[3-methoxy-4-[3-(2-methylphenyl)ureido]phenyl]acetamidomethyl]piperidin-1-yl]propionic acid
CAS No. 247254-24-6
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator)
合成路线:Selective protection of the secondary amino group of 4-(aminomethyl)piperidine (I) was achieved via conversion to imine (III) upon condensation with benzaldehyde (II),followed by treatment with di-tert-butyl dicarbonate to afford carbamate (IV).Subsequent acid hydrolysis of the imine function of (IV) furnished the mono-protected diamine (V).Coupling of amine (V) with 3-methoxy-4-(3-o-tolylureido)phenylacetic acid (VI) using HATU furnished amide (VII).Acidic cleavage of the N-Boc protecting group of (VII) gave piperidine (VIII).Aziridine (X) was prepared from ethyl 2,3-dibromopropionate (IX) by treatment with ammonia in acetonitrile.Condensation of (X) with N-(benzyloxycarbonyloxy)succinimide produced the benzyl carbamate (XI).Regioselective ring opening of the aziridine (XI) with piperidine (VIII) yielded adduct (XII).The ethyl ester group of (XII) was finally hydrolyzed to the target carboxylic acid under basic conditions.
📌 参考资料/链接：
参考文献标题:Substd.diamines and their use as cell adhesion inhibitors
文献作者:McCarthy,C.; Morley,A.D.; Harris,N.V.(Rh鬾e-Poulenc Rorer Ltd.)
参考来源:WO 9954321
📄 详细内容
合成路线:Selective protection of the secondary amino group of 4-(aminomethyl)piperidine (I) was achieved via conversion to imine (III) upon condensation with benzaldehyde (II),followed by treatment with di-tert-butyl dicarbonate to afford carbamate (IV).Subsequent acid hydrolysis of the imine function of (IV) furnished the mono-protected diamine (V).Coupling of amine (V) with 3-methoxy-4-(3-o-tolylureido)phenylacetic acid (VI) using HATU furnished amide (VII).Acidic cleavage of the N-Boc protecting group of (VII) gave piperidine (VIII).Aziridine (X) was prepared from ethyl 2,3-dibromopropionate (IX) by treatment with ammonia in acetonitrile.Condensation of (X) with N-(benzyloxycarbonyloxy)succinimide produced the benzyl carbamate (XI).Regioselective ring opening of the aziridine (XI) with piperidine (VIII) yielded adduct (XII).The ethyl ester group of (XII) was finally hydrolyzed to the target carboxylic acid under basic conditions.
参考文献标题:Diamine containing VLA-4 antagonists
文献作者:Astles,P.C.; Harris,N.V.; Morley,A.D.
参考来源:Bioorg Med Chem 2001,9(8),2195