【摘要】 目的 优化托吡司他的合成工艺。方法 以2-氯异烟酸（2）为起始原料，经氯代、醇解、肼解反应得到2-氯异烟肼（5）;以4-氰基吡啶（6）为起始原料，在甲醇钠催化下与甲醇反应生成异烟亚氨酸甲酯（7）;化合物5和7经环合、氰基化反应制得托吡司他。结果与结论目标产物结构经¹H-NMR,¹³C-NMR和ESI-MS谱确证，总收率为52.3%（以2-氯异烟酸计）,纯度为99.95%（HPLC法）。该合成方法原料价廉易得、成本低、操作简便、选择性好、工艺稳定，有利于工业化生产。更多还原

【Abstract】 Topiroxostat is a xanthine oxidase inhibitor widely used in the treatment of gout and hyperuricemia,demonstrating significant clinical efficacy and good tolerability.In this study,we developed a new synthetic route inspired by previous literature methods.With2-chloroisonicotinic acid（2）as the raw material,2-chloroisonicotinohydrazide（5）was synthesized through chlorination,alcoholysis and hydrazinolysis reactions.Meanwhile,4-cyanopyridine（6）was used as the starting material and reacted with methanol under sodium methoxide catalysis to produce methyl isonicotinimidate（7）.Compounds 5 and 7were then subjected to cyclization and cyanation reactions to give topiroxostat（1）with an overall of52.3%（based on2-chloroisonicotinic acid）and a purity of99.95%（HPLC）.The structure of the target produc was confirmed by 1H-NMR,¹³ C-NMR and ESI-MS.This synthesis method offers advantages such as readily available raw materials,lower cost,simpler operation,higher selectivity and stable processes,and is suitable for industrial production.■更多还原