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.With 2-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 7 were then subjected to cyclization and cyanation reactions to give topiroxostat(1)with an overall of 52.3％(based on 2-chloroisonicotinic acid)and a purity of 99.95％(HPLC).The structure of the target product was confirmed by 1H-NMR,13C-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.
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