新产品编号:935471
Chemical Name: N-[3-[2-Amino-3-cyano-6-(2-hydroxyphenyl)pyridin-4-yl]phenyl]-3-(1-piperidinyl)propionamide hydrochloride
CAS No. 433958-84-0, 433957-88-1 (free base), 433958-92-0 (trifluoroacetate)
项目整合开发状态: Preclinical
项目研究机构: Bayer (Originator)
合成路线:2'-Hydroxyacetophenone (I) is protected as the silyl ether (II) employing t-butyldimethylsilyl chloride and imidazole.Condensation of acetophenone (II) with 3-nitrobenzaldehyde (III) and malononitrile in the presence of ammonium acetate gives rise to the cyanopyridine (IV).The nitro group of (IV) is then reduced to the corresponding amine (V) by catalytic hydrogenation over Pd/C.3-Piperidinylpropionic acid (VI) is then activated as the acid chloride (VII) upon treatment with oxalyl chloride.Subsequent coupling of acid chloride (VII) with amine (V) furnishes amide (VIII).Finally,desilylation of (VIII) by means of either tetrabutylammonium fluoride or HCl in dioxane leads to the title compound.(1,2)
📌 参考资料/链接：
参考文献标题:4-Aryl pyridine derivs.
文献作者:Yoshida,N.; Masuda,T.; Sakakibara,S.; Murata,T.; Yoshino,T.; Umeda,M.; Shimada,M.; Lowinger,T.B.; Komura,H.; Shintani,T.; Ziegelbauer,K.B.; Fuchikami,K.; Ikegami,Y.; Shimazaki,M.(Bayer AG)
参考来源:EP 1339687; JP 2002193938; WO 0244153
📄 详细内容
合成路线:2'-Hydroxyacetophenone (I) is protected as the silyl ether (II) employing t-butyldimethylsilyl chloride and imidazole.Condensation of acetophenone (II) with 3-nitrobenzaldehyde (III) and malononitrile in the presence of ammonium acetate gives rise to the cyanopyridine (IV).The nitro group of (IV) is then reduced to the corresponding amine (V) by catalytic hydrogenation over Pd/C.3-Piperidinylpropionic acid (VI) is then activated as the acid chloride (VII) upon treatment with oxalyl chloride.Subsequent coupling of acid chloride (VII) with amine (V) furnishes amide (VIII).Finally,desilylation of (VIII) by means of either tetrabutylammonium fluoride or HCl in dioxane leads to the title compound.(1,2)
参考文献标题:Discovery of novel and selective IKK-beta serine-threonine protein kinase inhibitors.Part 1
文献作者:Murata,T.; Shimada,M.; Sakakibara,S.; Yoshino,T.; Kadono,H.; Masuda,T.; Shimazaki,M.; Shintani,T.; Fuchikami,K.; Sakai,K.; Inbe,H.; Takeshita,K.; Niki,T.; Umeda,M.; Bacon,K.B.; Ziegelbauer,K.B.; Lowinger,T.B.
参考来源:Bioorg Med Chem Lett 2003,13(5),913