Expeditious solid-phase synthesis of pyrazoledicarboxylic acid derivatives by functionalization of resin-bound cyanoformate

Esterification of the Wang resin 5 with the monoamide of oxalic acid (oxamic acid, 7) followed by dehydration of the amide function furnishes the resin-bound cyanoformate 9, which can be elaborated by zinc-catalyzed reaction with beta-keto esters. The obtained enamino keto diesters 10a-d react with hydrazines affording, after removal from the solid support, fully substituted pyrazoledicarboxylic acids 12a-n, Optimization of the above sequence and the solid-phase synthesis of a small test-library of 1,5-disubstituted pyrazole-3,4-dicarboxylic acid derivatives are described. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).