Solid-phase library synthesis of triazolopyridazines via [4+2] cycloadditions

The solid-phase library synthesis of triazolopyridazines was accomplished using a [4+2] cycloaddition strategy. The Homer-Wadsworth-Emmons (HWE) reagent diethylphosphonoacetic acid was attached to the N-terminus of amino acids on Rink amide solid-phase peptide synthesis support. The HWE reaction with a variety of alpha,beta-unsaturated aldehydes gave high conversion to diene amides. Subsequent [4+2] cycloaddition with ii-substituted urazines gave triazolopyridazines upon cleavage from resin. An alternate [4+2] cycloaddition method with urazine followed by a Mitsunobu reaction also provided triazolopyridazines. (C) 1999 Elsevier Science Ltd. All rights reserved.