An Alternate Synthesis of Bosentan Monohydrate, an Endothelin Receptor Antagonist

An alternate synthesis of an endothelin receptor antagonist bosentan monohydrate is reported. This new synthetic route involves the coupling of p - tert -butyl- N -[6-chloro-5-(2-methoxy-phenoxy)(2,2′-bipyrimidin)-4-yl]benzene sulfonamide with commercially available raw material (2,2-dimethyl-1,3-dioxolan-4-yl)methanol as the key step. Attractive features of this approach are its versatileness, commercial availability of raw materials, usage of eco-friendly reagents, and it efficiently provides the desired bosentan monohydrate free from reported impurities such as dimer, N-alkylated, and pyrimidinone impurities.