Study On Synthesis Technology Of Anti - Gout Drug Febuxostat

Febuxostat, a new non-purine selective xanthine oxidase inhibitor, which was discovered by Teijin Pharma Limited (Teijin Pharma) of Tokyo, was available by prescription in pharmacies for the chronic management of hyperuricemia in patients with gout.The relationship between xanthine oxidase inhibitor and gout was introduced, and the development of xanthine oxidase inhibitors was reviewed in this thesis. The aim of the paper is to study the synthesis process of febuxostat. Starting from 4-hydroxybenzonitrile, the target compounds were synthesized via thioformylation, cyclization, formylation, oximation, cyanidation, and further hydrolysis. The total yield was 29.3%.In the paper, the synthesis process of febuxostat was investigated overall, and particularly, two key steps including thioformylation and formylation were studied. the 4-hydroxybenzothioamide was prepared smoothly without handling of gaseous hydrogen sulfide and the product of formylation was obtained with higher yield by Duff reaction. In brief, most of the reactions involved are mild and easily put in practice.This process has an economic advantage in view of the application for large-scale synthesis.The related structure of the target molecule and some intermediates were identified by IR, ’H-NMR and MS.