BAY-57-1293
普瑞利韦Chemical Name: N-[5-(Aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-(4-pyridin-2-ylphenyl)acetamide
CAS No. 348086-71-5
项目整合开发状态: Preclinical
项目研究机构: Bayer (Originator)
合成路线:The condensation of 2-(4-bromophenyl)acetic acid methyl ester (I) with 2-(trimethylstannyl)pyridine (II) by means of Pd(PPh3)4 in refluxing toluene gives 2-[4-(2-pyridyl)phenyl]acetic acid methyl ester (III),which is hydrolyzed with KOH in THF/water to yield the corresponding acetic acid (IV).Finally,this compound is condensed with 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) by means of HOBt and DEC in DMF to afford the target phenylacetamide.The intermediate 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) is obtained as follows: the reaction of 1-chloroacetone (VI) with KSCN in water gives the corresponding thiocyanato (VII),which is cyclized by means of dry HCl in dichloromethane to yield 2-chloro-4-methylthiazole (VIII).The reaction of (VIII) with Cl-SO3H and SOCl2 affords the sulfonyl chloride (IX),which is treated with ammonia in THF/water to provide 2-chloro-4-methylthiazole-5-sulfonamide (X).Finally,this compound is treated with methylamine in acetonitrile to obtain the target sulfonamide intermediate (V).
📌 参考资料/链接：
参考文献标题:Thiazolyl amide derivs.
文献作者:Fischer,R.; Bender,W.; Henninger,K.; Eckenberg,P.; Handke,G.; Keldenich,J.; Weber,O.; Kleymann,G.; Betz,U.; Hendrix,M.; Schneider,U.; Jensen,A.; Baumeister,J.(Bayer AG)
参考来源:DE 19962532; WO 0147904
📄 详细内容
合成路线:The condensation of 2-(4-bromophenyl)acetic acid methyl ester (I) with 2-(trimethylstannyl)pyridine (II) by means of Pd(PPh3)4 in refluxing toluene gives 2-[4-(2-pyridyl)phenyl]acetic acid methyl ester (III),which is hydrolyzed with KOH in THF/water to yield the corresponding acetic acid (IV).Finally,this compound is condensed with 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) by means of HOBt and DEC in DMF to afford the target phenylacetamide.The intermediate 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) is obtained as follows: the reaction of 1-chloroacetone (VI) with KSCN in water gives the corresponding thiocyanato (VII),which is cyclized by means of dry HCl in dichloromethane to yield 2-chloro-4-methylthiazole (VIII).The reaction of (VIII) with Cl-SO3H and SOCl2 affords the sulfonyl chloride (IX),which is treated with ammonia in THF/water to provide 2-chloro-4-methylthiazole-5-sulfonamide (X).Finally,this compound is treated with methylamine in acetonitrile to obtain the target sulfonamide intermediate (V).
参考文献标题:Incompetitive inhibitors of helicase primase
文献作者:Fischer,R.; Bender,W.; Henninger,K.; Eckenberg,P.; Handke,G.; Keldenich,J.; Weber,O.; Kleymann,G.; Betz,U.; Hendrix,M.; Schneider,U.; Jensen,A.; Baumeister,J.; Hewlett,G.; Pevzner,V.(Bayer AG)
参考来源:DE 10044353; WO 0220014
产品链接: CAS No. 348086-71-5››