IMPROVED SYNTHESIS OF THROMBOXANE A(2) RECEPTOR ANTAGONISTS WITH A DIBENZOXEPIN RING-SYSTEM

Two derivatives of sodium (E)-11-[2-(1 -benzimidazolyl)ethylidene]-11-oxo-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate, novel nonprostanoid thromboxane A(2) (TXA(2)) 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.