论文部分内容阅读
以5-溴-2-氟吡啶为原料,经取代、成环、偶联反应,合成了医药中间体6-苯基-[1,2,4]三唑[4,3-a]吡啶-3-胺(Ⅳ),利用1HNMR、13CNMR和高分辨质谱对其结构进行了表征。对中间体6-溴-[1,2,4]三唑[4,3-a]吡啶-3-胺(Ⅲ)的合成方法和反应机理进行了探讨,考察了反应时间、反应温度、反应物配比、溶剂配比、催化剂用量等对目标产物收率的影响,结果表明:化合物Ⅲ的最佳合成工艺条件为:反应温度40℃,反应时间15 min;化合物Ⅳ的最佳合成工艺条件为:溶剂配比V(水)∶V(1,4-二氧六环)=1.0∶2.0,n(Ⅲ)∶n(苯硼酸)=1.0∶1.2,n(Ⅲ)∶n[Pd(pph3)2Cl2]=1.0∶0.1,反应温度80℃。经三步反应得到化合物Ⅳ的总收率为60%。
In order to synthesize the intermediate 6-phenyl- [1,2,4] triazolo [4,3-a] pyridine- The structure of 3-amine (Ⅳ) was characterized by 1HNMR, 13CNMR and high resolution mass spectrometry. The synthesis and reaction mechanism of 6-bromo- [1,2,4] triazolo [4,3-a] pyridin-3-amine were investigated. The effects of reaction time, reaction temperature, The results showed that the optimum synthesis conditions of compound Ⅲ were: reaction temperature 40 ℃, reaction time 15 min; the optimum synthesis conditions of compound Ⅳ Is: solvent ratio V (water): V (1,4-dioxane) = 1.0: 2.0, n pph3) 2Cl2] = 1.0: 0.1, the reaction temperature is 80 ° C. The total yield of compound IV obtained in three steps was 60%.