苯甲酸阿格列汀合成工艺的改进

Improved synthesis of alogliptin benzoate

目的改进苯甲酸阿格列汀的合成工艺。方法以6-氯尿嘧啶为起始原料,先与碘甲烷反应合成3-甲基-6-氯尿嘧啶,继而在无机碱的参与下与2-溴甲基苄腈反应得2-(6-氯-3甲基-2,4-二氯代-3,4-二氢-2H-嘧啶-1-基甲基)-苄腈,然后再在无机碱的存在下与(R)-3-氨基哌啶二盐酸发生取代反应,最后与苯甲酸成盐得苯甲酸阿格列汀。结果合成得到苯甲酸阿格列汀,总收率达到57.09%,纯度为99.6%。结论该工艺经过改进,降低了毒害,成本降低,经济环保,适合工业化生产。

Objective To improve synthetic process of alogliptin benzoate. Methods Alogliptin benzoate was synthesized from 6-chlorine uracil and iodomethane to give 3-methyl-6-chlorine uracil,then in the presence of inorganic base with 2-bromine methyl benzonitrile reaction to 2-(6-methyl chloride-3-2,4-dichloro generation-3,4-dihydro-2 h-pyrimidine-1-methyl)-benzonitrile,which was subjected to displacement with(R)-3-aminopiperidine in the presence of inorganic base. And then salified with benzoic acid to obtain alogliptin benzoate. Results Alogliptin benzoate was synthesized. The overall yield was 57. 09%,and its purity was 99. 6%. Conclusion The improvement reduced toxic,and was economic and environmental. It was suitable for industrial production.