Z. Heng
2012
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Journal
Journal of Wuhan Institute of Technology
Abstract
Bosentan is an orally active dual endothelin(ET) receptor antagonist,can improve exercise capacity and survival in patients with pulmonary arterial hypertension.With 5-(2-methoxy-phenyl)-2-(pyrimidin-2-yl)-tetrahydropyr-imidin-4,6-dione as starting material,bosentan(1) was prepared by chlorination,sulfonylation and etherification,.The structures of target molecule and intermediates were confirmed by IR、1H-NMR and MS.Using single factor analysis and the uniform design,the optimal reaction conditions of each reaction were obtained.The total yield was up to 71.5%.The chlorination reaction of this process gets rid of deacid reagent and uses less phosphorus oxychloride;phase transfer catalyst in sulfonylation reaction shortens reaction time and increases reaction yield;etherification reaction introduces hydroxyethoxy group only in one step,decreasing reaction steps.Therefore the process is concise,environmental friendly and economically.