Comprehensive Update on Synthetic Aspects of Bosentan Derivatives.

Abstract

Bosentan and its analogues were first reported as endothelin (ET) receptor antagonists in US patent No. 5, 292,740 in 1994. Bosentan synthesis has been reported by employing different methods from the reaction between (4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine and 4- (tert-butyl) benzenesulfonamide and 4-(tert-butyl)-N-(6-chloro-5-(2-methoxyphenoxy)-[2,2'- bipyrimidin]-4-yl) benzenesulfonamide in the form of different salts like potassium salt, ammonium salt, sodium salt, and free, on its reaction with ethylene glycol. Several changes have been observed in the chemistry of the involved intermediate synthesis, particularly coupling chemistry, to produce bosentan derivatives with high purity and yield.