Another process for the preparation of Bosentan is reported in U.S. Pat. No. 6,136,971 (hereinafter referred to as the '971 patent) which is multi-step process as illustrated in Path B of Scheme-1. 5-(2-methoxyphenoxy)-2-(2-pyrimidin-2-yl)-4,6(1H,5H)-pyrimidinedione is reacted with phosphorous oxychloride in toluene to obtain 4,6-dichloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidine, which is further condensed with 4-tert-butylbenzenesulfonamide in the presence of anhydrous potassium carbonate and a phase transfer catalyst (e.g., benzyltriethylammonium chloride) in toluene to obtain p-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide potassium salt. The p-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzenesulfonamide potassium salt is then reacted with ethylene glycol mono-tert-butyl ether in toluene in the presence of granular sodium hydroxide to produce p-tert-butyl-N-[6-(2-tert-butyl-ethoxy)-5-(2-methoxyphenoxy)-[2,2′-bipyrimidin]-4-yl]benzenesulfonamide (Bosentan tert-butyl ether). The Bosentan tert-butyl ether obtained is then reacted with formic acid followed by treatment with absolute ethanol to obtain Bosentan formate monoethanolate. The Bosentan formate monoethanolate is further treated with sodium hydroxide in absolute ethanol and water followed by acidic hydrolysis by treating with hydrochloric acid and then the resulting precipitate is suction-filtered; washed with ethanol-water mixture (1:1) to give crude Bosentan. The crude Bosentan obtained is then purified with mixture of ethanol and water and the resulting precipitate is suction-filtered to give pure Bosentan.
