Zomepirac sodium, McN-2783-21-98, Zomax
1H-吡咯-2-醋酸,5-(4-氯苯甲基)-1,4-二甲基-,钠盐,水合物(1:1:2) 佐美酸钠盐 佐美酸Chemical Name: 5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetic acid sodium salt dihydrate
CAS No. 64092-49-5, 64092-48-4 (anhydrous), 33369-31-2 (free base, anhydrous)
项目整合开发状态: Withdrawn
项目研究机构: Cilag (Originator)
合成路线:The hydrolysis of ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) with refluxing aqueous NaOH gives 3-carboxy-1,4-dimethylpyrrole-2-acetic acid (II),which is partially esterified with refluxing ethanol - dry HCl yielding ethyl 3-carboxy-1,4-dimethylpyrrole-2-acetate (III).The decarboxylation of (III) by heating at 190-210 C affords ethyl 1,4-dimethylpyrrole-2-acetate (IV),which by a Vilsmeier aroylation with p-chloro-N,N-dimethylbenzamide (A) and POCl3 in refluxing dichloroethane is converted into ethyl 5-p-chlorobenzoyl-1,4-dimethylpyrrole-2-acetate (V).Finally,this product is hydrolyzed with refluxing aqueous 1N NaOH.
📌 参考资料/链接：
参考文献标题:5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents.2.The 4-methyl compounds
文献作者:Carson,J.R.; Wong,S.
参考来源:J Med Chem 1973,16(2),172-174
📄 详细内容
合成路线:The hydrolysis of ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) with refluxing aqueous NaOH gives 3-carboxy-1,4-dimethylpyrrole-2-acetic acid (II),which is partially esterified with refluxing ethanol - dry HCl yielding ethyl 3-carboxy-1,4-dimethylpyrrole-2-acetate (III).The decarboxylation of (III) by heating at 190-210 C affords ethyl 1,4-dimethylpyrrole-2-acetate (IV),which by a Vilsmeier aroylation with p-chloro-N,N-dimethylbenzamide (A) and POCl3 in refluxing dichloroethane is converted into ethyl 5-p-chlorobenzoyl-1,4-dimethylpyrrole-2-acetate (V).Finally,this product is hydrolyzed with refluxing aqueous 1N NaOH.
合成路线:The starting product ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) can be obtained by condensation of diethyl acetonedicarboxylate (X) with chloroacetone (IX) by means of methylamine in water,the compound (XI) being formed as an intermediate which is not isolated.The Friedel-Crafts aroylation of (I) with p-chlorobenzoyl chloride (B) and AlCl3 in refluxing dichloroethane gives ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (VI),which by hydrolysis with aqueous 1N NaOH yields 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetic acid (VII).The partial esterification of (VII) with ethanol and HCl produces ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetate (VIII),which by decarboxylation at 210-30 C is converted into the ester (V) already obtained.
参考文献标题:Zomepirac
文献作者:Hillier,K.; Castar,J.
参考来源:Drugs Fut 1977,2(10),698
合成路线:The starting product ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) can be obtained by condensation of diethyl acetonedicarboxylate (X) with chloroacetone (IX) by means of methylamine in water,the compound (XI) being formed as an intermediate which is not isolated.The Friedel-Crafts aroylation of (I) with p-chlorobenzoyl chloride (B) and AlCl3 in refluxing dichloroethane gives ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (VI),which by hydrolysis with aqueous 1N NaOH yields 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetic acid (VII).The partial esterification of (VII) with ethanol and HCl produces ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetate (VIII),which by decarboxylation at 210-30 C is converted into the ester (V) already obtained.
参考文献标题:Aroyl-substituted pyrroles
文献作者:Carson,J.R.
参考来源:DE 2102746; FR 2081455; GB 1327308; JP 55033401; JP 55033402; US 3752826; US 3865840; US 4070368