Anirolac, RS-37326

阿尼罗酸Chemical Name: (?-5-(4-Methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid; (?-2,3-Dihydro-5-(4-methoxybenzoyl)-1H-pyrrolizine-1-carboxylic acid; (?-5-p-Anisoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid
CAS No. 66635-85-6
项目整合开发状态: Phase II
项目研究机构: Roche Bioscience (Originator)
合成路线:This compound can be obtained in the following way:1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III),which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV).The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI),which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII).The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII),which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.

合成路线:By condensation of 3-(chloromethyl)pyridine (I) with 2-mercaptopyrimidine (II) in ethanol-water at room temperature.
📌 参考资料/链接:
参考文献标题:Imidazoyl-substd.thiomethylpyridine derivs.,method of administration thereof and medicaments containing them
文献作者:Engler,H.; Schickaneder,H.; Szelenyi,I.(Heumann Pharma GmbH & Co.)
参考来源:DE 3216843; EP 0093252; US 4810715

📄 详细内容


合成路线:This compound can be obtained in the following way:1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III),which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV).The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI),which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII).The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII),which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.

参考文献标题:Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein
文献作者:Muchowski,J.M.; Greenhouse,R.(Roche Bioscience)
参考来源:US 4347186


合成路线:This compound can be obtained in the following way:1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III),which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV).The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI),which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII).The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII),which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.

参考文献标题:Anirolac
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1986,11(6),449


合成路线:This compound can be obtained in the following way:1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III),which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV).The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI),which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII).The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII),which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.
参考文献标题:Novel syntheses of 5-aroyl-1,2-dihydro-3H-pyrrole-1-carboxilic acids
文献作者:Greenhouse,R.; Franco,F.
参考来源:J Org Chem 1982,471682


产品链接: CAS No. 66635-85-6››