Solid-Phase Synthesis of Pyrazoledicarboxylic Acid Derivatives

Significance

The solid-phase synthesis of a small library of 1,5-disubstituted pyrazole-3,4-dicarboxylic acid derivatives is described. A mono amide of oxalic acid 1 was anchored onto Wang resin to give 2 (Step I). The amide functional group of intermediate 2 was then dehydrated to afford resin-bound cyanoformate 3 (Step II). Subsequent functionalization of 3 was accomplished using an excess of dicarbonyl compounds in the presence of zinc acetylacetonate to give 4a-d (Step III). The solid-supported enamino keto diesters 4a-d reacted with hydrazines (Step IV) to give pyrazoles 5a-n from which the pyrazoledicarboxylic acid derivatives 6a-n were readily released via acidic cleavage (Step V).