新产品编号:1020899
Chemical Name: 3-[3-(tert-Butylthio)-1-(4-chlorobenzyl)-5-(2-pyridylmethoxy)indol-2-yl]-2,2-dimethylpropionic acid
项目整合开发状态: Preclinical
项目研究机构: Merck Frosst (Originator)
合成路线:The cyclization of substituted phenylhydrazine (I) with 5-(tert-butylsulfanyl)-2,2-dimethyl-4-oxopentanoic acid methyl ester (II) by means of AcOH/AcONa in toluene gives the indolylpropionic ester (III),which is demethylated with AlCl3 and ethanethiol in dichloromethane and reesterified with diazomethane yielding the hydroxy derivative (IV).The reaction of (IV) with 2-(bromomethyl)pyridine (V) by means of K2CO3 in DMF affords the ether (VI),which is finally hydrolyzed with LiOH to give the target propionic acid.
📌 参考资料/链接：
参考文献标题:Substituted thiopyrano[2,3,4-c,d]indoles as potent,selective,and orally active inhibitors of 5-lipoxygenase.Synthesis and biological evaluation of L-691,816
文献作者:Hutchinson,J.H.; Riendeau,D.; Brideau,C.; Chan,C.C.; Delorme,D.; Denis,D.; Falgueyret,J.P.; Fortin,R.; Guay,J.; Hamel,P.; et al.
参考来源:J Med Chem 1993,36(19),2771
📄 详细内容
合成路线:The cyclization of substituted phenylhydrazine (I) with 5-(tert-butylsulfanyl)-2,2-dimethyl-4-oxopentanoic acid methyl ester (II) by means of AcOH/AcONa in toluene gives the indolylpropionic ester (III),which is demethylated with AlCl3 and ethanethiol in dichloromethane and reesterified with diazomethane yielding the hydroxy derivative (IV).The reaction of (IV) with 2-(bromomethyl)pyridine (V) by means of K2CO3 in DMF affords the ether (VI),which is finally hydrolyzed with LiOH to give the target propionic acid.
参考文献标题:Substituted indoles as potent and orally active 5-lipoxygenase activating protein (FLAP) inhibitors
文献作者:Frenette,R.; Hutchinson,J.H.; L間er,S.; Therien,M.; Brideau,C.; Chan,C.C.; Charleson,S.; Ethier,D.; Guay,J.; Jones,T.R.; McAuliffe,M.; Piechuta,H.; Riendeau,D.; Tagari,P.; Girard,Y.
参考来源:Bioorg Med Chem Lett 1999,9(16),2391