异丁司特的合成工艺改进

A Novel Method for the Synthesis of Ibudilast

以硫酸羟胺与发烟硫酸反应得到羟胺-O-磺酸,然后与2-甲基吡啶、氢碘酸合成1-氨基-2-甲基吡啶碘化物,最后与异丁酰氯反应合成异丁司特。优化条件下,总收率47.4%,纯度99.2%。产品结构经质谱、核磁确证。该工艺原料廉价易得,生产成本低,环境污染小,操作简单,适合工业化生产。

Hydroxylamine-O-sulfonic acid,obtained from the reacton between hydroxylamine sulfate and fuming sulfuric acid,reacted with 2-methylpyridine and hydrogen iodide to obtain 1-amino-2-methylpyridine iodide,and Ibudilast was obtained from the reaction between 1-amino-2-methylpyridine iodide and isobutyryl chloride finally.The total yield was 47.4% with a purity of 99.2%.The structure of this product was confirmed using MS and1H NMR.This process has the advantages including cheap and easily available raw materials,lower cost,more environmentally friendly,simple operation,and more conducive to industrial production.