Abstract

An improved and efficient synthetic process developed for an endothelin receptor antagonist, bosentan monohydrate by condensing a key intermediate 4-tert-butyl-N-(6-hydroxy-5-(2-methoxyphenoxy)-2,2’-bipyrimidine-4- yl)benezenesulfonamide 5 with commercially cheaper chloro acetonitrile and α-halo esters. This synthetic approach efficiently provides highly pure bosentan without formation of the major impurity 2 (dimer) and less than 0.15% of Nalkylated impurity 3 and pyrimidinone impurity 5 in the final product. In the present process upon purification of bosentan monohydrate gave overall yield of 62-65%.

Keywords: Pyrimidinone, chloro acetonitrile, α-halo esters, bosentan monohydrate.