CAJ | 학술논문

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．
위료제고항종류약물 vismodegib 합성반응적산솔병공제반응성본，제비료합성목표화합물소수적중간체，병대 Negishi 우련반응조건진행료고찰．통과단인소분석법，연구료불동적마이비、최화제용량화회류시간대반응적영향．결과표명，재반응혼합물2-추필정、2-록-N-（4-록-3-전분기）-4-（갑광선）분갑선알、록화자、정정기리화사（삼분기련）파적마이비위1．0∶0．5∶1．5∶1．1∶0．05급회류시간위24 h 적조건하，반응수솔제고도료72％．해반응조건명현제고료합성효솔，피면료원료/최화제적과다소모，동시피면료과장적반응시간．반응체계배비화반응시간적우화재합성 vismodegib 적과정중대제고효솔화경제성유중요작용．
In order to improve the yield and reduce the cost in the synthesis of antitumor drug vismodegib the key intermediates are prepared and the Negishi reaction step is examined.The effects of different molar ratios of reactants dosages of catalyst and time for refluxing are investigated by using single factor tests.The results demonstrate that when the molar ratios of 2-bromopyridine 2-chloro-N-4-chloro-3-iodophenyl -4-methylsulfonyl benzamide zinc chloride n-butyllithium and tetrakis triphenyl phosphine palladium are changed to 1.0∶0.5∶1.5∶1.1∶0.05 and the mixture is refluxed for 24 h the production yield is improved to 72%.This reaction condition significantly enhances the synthetic efficiency avoids consuming excessive raw materials/catalysts and meanwhile prevents a prolonged reaction time.The optimization of the proportion of reactants and the heating time is proved to be important for the efficiency and economy in cross-coupling reaction to synthesize vismodegib.