瑞巴匹特羧乙酯的合成

Synthesis of diethyl ribamipide carboxylate

以N-乙酰乙酰苯胺为原料,经溴化、环合制得4-溴甲基喹啉-2-酮(Ⅲ);由盐酸氨基丙二酸二乙酯经酰化制得4-氯苯甲酰胺基丙二酸二乙酯(Ⅳ);最后用4-溴甲基喹啉-2-酮(Ⅲ)和4-氯苯甲酰胺基丙二酸二乙酯(Ⅳ)经烃化反应合成瑞巴匹特羧乙酯(Ⅰ).结果表明:在n(Ⅳ)∶n(Ⅲ)∶n(乙醇钠)=1∶1∶1.2,回流反应2 h时,合成总收率63.81%(以N-乙酰乙酰苯胺计).

The diethyl-2-（ 4-chlorobenzoylamino ）-2-（ 1, 2-dihydro-2-oxo-4-quinolyl ） malonate, an intermediate of ribamipide was synthesized from N-Acetoacetanilide as material. Firstly, 4- （bromomethyl）-quinolin-2（1H）-one was obtained by the bromination and cyclization. Then, diethyl-2- （4-chlorobenzamido）malonate was obtained by the acylation of diethyl aminomalonate hydroehloride. Finally, diethyl-2-（4-chlorobenzoylamino）-2- （1,2-dihydro-2-oxo-4-quinoiyl） malonate was prepared by alkylation of 4-（ bromomethyl）-qui-nolin-2 （ 1H ）-one with diethyl-2-（4-chlorobenzamido） malonate, under the conditions which were as follows： the molar ratio of Ⅳ to Ⅲto sodium alcoholate was 1 ： 1：1.2 ,the refluxed time was 2 h. The total yield was 63.81% （with N-Acetoacetanilide as the material）.