Improved synthesis of thromboxane A2 receptor antagonists with a dibenzoxepin ring system

Article abstract of DOI:10.1055/s-1995-4088

Two derivatives of sodium (E)-11-[2-(1-benzimidazolyl)ethylidene]11-oxo-6,11-dihydrodibenz[b,e]o xepin-2-carboxylate, novel nonprostanoid thromboxane A₂ (TXA₂) receptor antagonists, were synthesized from methyl 11-oxo-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate. The carbonyl group at C11 was converted into a formylmethylene, then into a 1-azadiene moiety by reaction with a 2-aminoformanilide derivative. Stereo- and regioselective elaboration of the unsymmetrical imidazoles was achieved through a sequence of the transformation of E,Z-1-azadiene intermediates to E isomers under acidic conditions followed by cyclization to imidazoles.