新产品编号:876937
Chemical Name: 1-[4-(4-Fluorophenoxy)benzyl]-2-oxoimidazolidine-4(R)-carbohydroxamic acid
CAS No. 352665-40-8
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:The alkylation of 1-(benzyloxycarbonyl)-2-oxoimidazolidine-5(R)-carboxylic acid tert-butyl ester (I) with 4-(4-fluorophenoxy)benzyl bromide (II) by means of K2CO3 in acetone gives 1-(benzyloxycarbonyl)-3-[4-(4-fluorophenoxy)benzyl]-2-oxoimidazolidine-5(R)-carboxylic acid tert-butyl ester (III),which is deprotected by hydrogenation with H2 over Pd/C in ethanol to afford 1-[4-(4-fluorophenoxy)benzyl]-2-oxoimidazolidine-4(R)-carboxylic acid tert-butyl ester (IV).The cleavage of the tert-butyl protecting group of (IV) by means of TFA in dichloromethane affords the free carboxylic acid (V),which is condensed with O-[2-(trimethylsilyl)ethyl]hydroxylamine (VI) by means of HOBt,DIEA and DEC to provide the corresponding amide (VII).Finally,the desilylation of (VII) by means of BF3 ethearate in dichloromethane gives rise to the target hydroxamic acid.
📌 参考资料/链接：
参考文献标题:Imidazolylbenzophenone derivs.
文献作者:Amada,H.; Miyata,N.; Kobayashi,Y.; Ishii,T.; Sato,M.(Taisho Pharmaceutical Co.,Ltd.)
参考来源:WO 0168610
📄 详细内容
合成路线:The alkylation of 1-(benzyloxycarbonyl)-2-oxoimidazolidine-5(R)-carboxylic acid tert-butyl ester (I) with 4-(4-fluorophenoxy)benzyl bromide (II) by means of K2CO3 in acetone gives 1-(benzyloxycarbonyl)-3-[4-(4-fluorophenoxy)benzyl]-2-oxoimidazolidine-5(R)-carboxylic acid tert-butyl ester (III),which is deprotected by hydrogenation with H2 over Pd/C in ethanol to afford 1-[4-(4-fluorophenoxy)benzyl]-2-oxoimidazolidine-4(R)-carboxylic acid tert-butyl ester (IV).The cleavage of the tert-butyl protecting group of (IV) by means of TFA in dichloromethane affords the free carboxylic acid (V),which is condensed with O-[2-(trimethylsilyl)ethyl]hydroxylamine (VI) by means of HOBt,DIEA and DEC to provide the corresponding amide (VII).Finally,the desilylation of (VII) by means of BF3 ethearate in dichloromethane gives rise to the target hydroxamic acid.
参考文献标题:Design and synthesis of 2-oxo-imidazolidine-4-carboxylic acid hydroxymides as potent matrix metalloproteinase-13 inhibitors
文献作者:Robinson,R.P.; Laird,E.R.; Donahue,K.M.; Lopresti-Morrow,L.L.; Mitchell,P.G.; Reese,M.R.; Reeves,L.M.; Rouch,A.I.; Stam,E.J.; Yocum,S.A.
参考来源:Bioorg Med Chem Lett 2001,11(9),1211