Lintitript, SR-27897
SR 27897(Lintitript),竞争性非肽CCK 1受体拮抗剂Chemical Name: 1-(Carboxymethyl)-N-[4-(2-chlorophenyl)thiazol-2-yl]indole-2-carboxamide; 2-[[N-[4-(2-Chlorophenyl)-2-thiazolyl]amino]carbonyl]-1H-indole-1-acetic acid
CAS No. 136381-85-6
项目整合开发状态: Discontinued
项目研究机构: Sanofi-Aventis (Originator)
合成路线:The esterification of indole-2-carboxylic acid (I) with benzyl alcohol and CDI gives the corresponding benzyl ester (II),which is alkylated with methyl bromoacetate (III) by means of NaH in DMF yielding 1-(methoxycarbonylmethyl)-1H-indole-2-carboxylic acid benzyl ester (IV).The debenzylation of (IV) with H2 over Pd/C in ethanol/DMF affords the free acid (V),which is condensed with 4-(2-chlorophenyl)thiazol-2-amine (VI) by means of benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) in DMF to give the carboxamide (VII).Finally,the ester group of (VII) is hydrolyzed with NaOH or KOH in methanol/water.
📌 参考资料/链接：
参考文献标题:Heterocyclic derivs.of acylaminothiazole,their preparation and pharmaceutical compsns.containing them
文献作者:Bras,J.-P.; Frehel,D.; Gully,D.; Valette,G.(Sanofi-Synthabo )
参考来源:EP 0432040; FR 2655344; FR 2661677; JP 1991279374; JP 1998130147; US 5189049
📄 详细内容
合成路线:The esterification of indole-2-carboxylic acid (I) with benzyl alcohol and CDI gives the corresponding benzyl ester (II),which is alkylated with methyl bromoacetate (III) by means of NaH in DMF yielding 1-(methoxycarbonylmethyl)-1H-indole-2-carboxylic acid benzyl ester (IV).The debenzylation of (IV) with H2 over Pd/C in ethanol/DMF affords the free acid (V),which is condensed with 4-(2-chlorophenyl)thiazol-2-amine (VI) by means of benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) in DMF to give the carboxamide (VII).Finally,the ester group of (VII) is hydrolyzed with NaOH or KOH in methanol/water.
参考文献标题:Method for preparing lintitript potassium salt
文献作者:Radisson,J.(Sanofi-Synthabo )
参考来源:FR 2781227; WO 0005233
产品链接: CAS No. 136381-85-6››