Gedatolisib的合成工艺改进

Improved synthesis of gedatolisib

目的研究gedatolisib的合成工艺。方法以三聚氯氰为起始原料,依次经取代、Suzuki偶联、异氰酸酯成脲、水解、缩合等5步反应得到目标化合物。结果与结论该合成路线总收率达43.6%(以三聚氯氰计),各步反应条件温和,操作简便,生产成本降低,为中试放大奠定基础。

Gedatolisib,a PI3K/mTOR dual inhibitor,was developed by Pfizer. An optimal route has been developed based on the literatures in this paper. Taking cyanuric chloride as the starting material,gedatolisib was synthesized through five steps,including substitution,Suzuki coupling,addition,hydrolysis and condensation. Its total yield was 43. 6%（ calculated from cyanuric chloride） which was 10. 4% higher than that reported in literature and its purity was 99. 9%. The structure of gedatolisib was confirmed by MS,~1H-NMR.The improved process has several advantages over these reported procedures,such as mild conditions,lowcost,and high yields. The synthetic route is more suitable for industrial production owing to the simple operation and high yield.