ORGN 181

Fused 1,2,4-triazoles exhibit a diverse range of biological activities and have been evaluated as anti-inflammatory agents, PDE IV inhibitors, MAP kinase inhibitors particularly, P38 kinase inhibitors, and GPIIb/IIIA fibrinogen receptor antagonists. Traditionally, these compounds are prepared by condensation of an alkoxy imine with an acyl hydrazide to produce an intermediate N-acyl amidrazone that undergoes cyclodehydration to afford the target, fused 1,2,4-triazole.  We have developed an efficient, one-pot synthesis of fused [5,5]-, [5,6]-, and [5,7]-3-[2-aryl(heteroaryl)vinyl]-1,2,4-triazoles employing diethoxyphosphinyl acetic acid hydrazide (DAAH) to construct the key intermediate N-acyl amidrazones directly from aldehydes and alkoxy imines.

There are no isolated intermediates in this three-step process, which affords the fused [5,5]-, [5,6]-, and [5,7]-1,2,4-triazoles in moderate to excellent overall yield from readily available starting materials.