唑尼沙胺的化学合成技术研究

A Study of the Synthesis of Zonisamide

目的用两种方法合成唑尼沙胺,选择最佳合成路径。方法以1,2苯-并异噁唑-3-乙酸为起始原料,分别通过1步或3步反应合成1,2苯-并异噁唑-3-甲磺酸钠,然后经氯化和氨解,合成了抗癫痫药唑尼沙胺。结果目标化合物经1H NMR和MS确证,两条路线的总收率分别为31.6%和46.2%。结论路线2工艺简单,条件温和,收率较高,适合工业化生产,故路线2优于路线1。

Objective To study and compare two synthetic methods of zonisamide.Methods Sodium 1,2-benzisoxazole-3-methanesulfonate was prepared from 1,2-Benzisoxazole-3-acetic acid by one-step or three-step reaction respectively.Zonisamide was synthesized from Sodium 1,2-benzisoxazole-3-methanesulfonate via chlorination and amidation.Results The structure of zonisamide was identified by 1H NMR and MS.The overall yield of the two methods was 31.6% and 46.2% respectively.Conclusion Route 2 requires milder in reactive conditions,more simple in procedure and higher in total yield.It is more suitable for industrial production.