SB-431542
4-[4-(1,3-苯并二唑-5-基)-5-(2-吡啶基)-1H-咪唑-2-基]-苯酰胺水合物Chemical Name: 4-[4-(1,3-Benzodioxol-5-yl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzamide
CAS No. 301836-41-9
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Reaction of piperonyloyl chloride (I) with N,O-dimethylhydroxylamine gives rise to the Weinreb amide (II).This is then condensed with the lithium anion of 2-picoline (III) to produce ketone (IV).Nitrosation of (IV) with NaNO2/HCl leads to keto oxime (V).Subsequent cyclization of (V) with p-formylbenzonitrile (VI) in the presence of ammonium acetate in AcOH affords the N-hydroxy imidazole (VII),which is further reduced to the triaryl imidazole (VIII) by means of triethyl phosphite in DMF.The cyano group of (VIII) is then hydrolyzed under acidic conditions to provide carboxylic acid (IX).After activation of (IX) as the corresponding acid chloride (X),treatment with ammonium hydroxide in THF yields the target carboxamide (1,2).
📌 参考资料/链接：
参考文献标题:Triarylimidazoles
文献作者:Callahan,J.F.; Burgess,J.L.(GlaxoSmithKline Inc.)
参考来源:EP 1169317; JP 2002541253; US 6465493; WO 0061576
📄 详细内容
合成路线:Reaction of piperonyloyl chloride (I) with N,O-dimethylhydroxylamine gives rise to the Weinreb amide (II).This is then condensed with the lithium anion of 2-picoline (III) to produce ketone (IV).Nitrosation of (IV) with NaNO2/HCl leads to keto oxime (V).Subsequent cyclization of (V) with p-formylbenzonitrile (VI) in the presence of ammonium acetate in AcOH affords the N-hydroxy imidazole (VII),which is further reduced to the triaryl imidazole (VIII) by means of triethyl phosphite in DMF.The cyano group of (VIII) is then hydrolyzed under acidic conditions to provide carboxylic acid (IX).After activation of (IX) as the corresponding acid chloride (X),treatment with ammonium hydroxide in THF yields the target carboxamide (1,2).
参考文献标题:Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5)
文献作者:Callahan,J.F.; Burgess,J.L.; Fornwald,J.A.; Gaster,L.M.; Harling,J.D.; Harrington,F.P.; Heer,J.; Kwon,C.; Lehr,R.; Mathur,A.; Olson,B.A.; Weinstock,J.; Laping,N.J.
参考来源:J Med Chem 2002,45(5),999
产品链接: CAS No. 301836-41-9››