阿法替尼合成工艺研究

Synthesis of Afatimib

目的对阿法替尼的合成工艺进行研究。方法以6-氨基-7-羟基-3,4-二氢喹唑啉-4-酮和乙酰氯分别作为起始原料,经过乙酰化反应、氯代反应、水解反应、Mitsunobu反应、酰化反应,缩合得到最终目标产物。结果试验总收率为46.6%。结论该制备方法原料易得,工艺简洁,经济环保,有利于该药品的工业化生产。

Objective To study the synthetic technology of afatimib.Methods 6-amino-7-hydroxy,4-dihydro-quinazolin-4-one and acetyl chloride were used as the starting materials,and the target compound was obtained after a series of chemical reactions including acetylation reaction,chlorination reaction,hydrolysisreaction,Mitsunobu reaction,and acetylation reaction.Results The overall yield was 46.6%.Conclusion This improved process could lower the cost of preparation,simplify the operating conditions,increase the yield,and is more suitable for industrial purposes.