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为了提高抗肿瘤药物vismodegib合成反应的产率并控制反应成本,制备了合成目标化合物所需的中间体,并对Negishi偶联反应条件进行了考察.通过单因素分析法,研究了不同的摩尔比、催化剂用量和回流时间对反应的影响.结果表明,在反应混合物2-溴吡啶、2-氯-N-(4-氯-3-碘苯基)-4-(甲磺酰)苯甲酰胺、氯化锌、正丁基锂和四(三苯基膦)钯的摩尔比为1.0∶0.5∶1.5∶1.1∶0.05及回流时间为24 h的条件下,反应收率提高到了72%.该反应条件明显提高了合成效率,避免了原料/催化剂的过多消耗,同时避免了过长的反应时间.反应体系配比和反应时间的优化在合成vismodegib的过程中对提高效率和经济性有重要作用.
In order to increase the yield of the synthetic antitumor drug vismodegib and control the cost of the reaction, the intermediates needed for the synthesis of the target compound were prepared and the Negishi coupling reaction conditions were investigated.Under the single factor analysis method, different molar ratios , The amount of catalyst and the reflux time on the reaction.The results showed that in the reaction mixture 2-bromopyridine, 2-chloro-N- (4-chloro-3- iodophenyl) -4- (methylsulfonyl) benzamide , Zinc chloride, n-butyllithium and tetrakis (triphenylphosphine) palladium was 1.0: 0.5: 1.5: 1.1: 0.05 and the reflux time was 24 h, the reaction yield increased to 72% The reaction conditions significantly increase the efficiency of the synthesis and avoid excessive consumption of feedstock / catalyst while avoiding excessive reaction time Optimization of the reaction mixture and reaction time is important in improving the efficiency and economy in the synthesis of vismodegib effect.