Tilomisole, NSC-310633, Wy-18251
噻氯咪索Chemical Name: 3-(4-Chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid
CAS No. 58433-11-7
项目整合开发状态: Phase II
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:This compound can be obtained in two different ways,both starting from 2-mercaptobenzimidazole (I):1) The cyclization of (I) with 3-bromo-3-(p-chlorobenzoyl)propionic acid (II) in acetic acid at 100 C gives 3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo[3,2-a]benzimidazole-2-acetic acid (III),which is dehydrated by means of HCl in refluxing dioxane.2) The condensation of (I) with ethyl 3-bromo-3-(p-chlorobenzoyl)propionate (IV) in refluxing ethanol gives 3-(benzimidazol-2-ylthio)-3-(p-chlorobenzoyl)propionic acid ethyl ester (V),which is cyclized by treatment with water yielding 3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo[3,2-a]benzimidazole-2-acetic acid ethyl ester (VI).This compound is then hydrolyzed by treatment with NaOH in hot water to afford (III).
📌 参考资料/链接：
参考文献标题:WY-18,251
文献作者:Castar,J.
参考来源:Drugs Fut 1981,6(8),500
📄 详细内容
合成路线:This compound can be obtained in two different ways,both starting from 2-mercaptobenzimidazole (I):1) The cyclization of (I) with 3-bromo-3-(p-chlorobenzoyl)propionic acid (II) in acetic acid at 100 C gives 3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo[3,2-a]benzimidazole-2-acetic acid (III),which is dehydrated by means of HCl in refluxing dioxane.2) The condensation of (I) with ethyl 3-bromo-3-(p-chlorobenzoyl)propionate (IV) in refluxing ethanol gives 3-(benzimidazol-2-ylthio)-3-(p-chlorobenzoyl)propionic acid ethyl ester (V),which is cyclized by treatment with water yielding 3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo[3,2-a]benzimidazole-2-acetic acid ethyl ester (VI).This compound is then hydrolyzed by treatment with NaOH in hot water to afford (III).
参考文献标题:Syntheses of heterocyclic fused thiazole acetic acids
文献作者:Bell,S.C.; Wei,P.H.
参考来源:J Med Chem 1976,19(4),524-530
产品链接: CAS No. 58433-11-7››