氟马西尼的合成工艺改进

Improved Synthesis of Flumazenil

对氟马西尼的合成工艺进行研究.以2-氨基-5-氟苯甲酸为起始原料,经过缩合、闭环等一系列步骤得到关键桥环中间体6-氟靛红酸酐(3)和7-氟-3,4二氢-4-甲基-2H-1,4苯并二氮杂卓-2,5(1H)-二酮(4),通过3步反应得到氟马西尼.结果:大范围改进现有氟马西尼的制备工艺,工艺总收率为21.6%,纯度大于99.9%.结论:该工艺操作简便,稳定性好,收率高,适用于工业化生产.

The objective is to improve the synthesis of flumazenil.The methods are:starting from 2-Amino-5-Fluor benzoic acid,the key intermediate 6-Fluoroisatoic?anhydride(3)and 7-Fluoro-3,4-dihydro-4-methyl-1 H-1,4-Benzodiazepine-2,5-dione(4)was obtained via such procedures as condensation reaction and ring closure reaction.Through 3-step reaction,flumazenil was prepared.The results show that the existing preparation process of flumazenil was modified greatly and the total yield of the whole process reached21.6%,and its purity was more than 99.9%.The conclusion is that this improved process is simple,stable,productive and suitable for the industrial production.