Synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyridinedicarboxylate

Two syntheses of 7-trifluoromethylpyrazolo[1,5-a]pyridine dicarboxylate have been described. Approach A utilizes a nucleophilic addition of a trifluoromethyl group to N-p-toluenesulfonyliminopyridinium ylide followed by aromatization and subsequent cycloaddition with diethyl acetylenedicarboxylate to give 1b in modest yield. Approach B involves a selective zincation of pyrazolopyridine dicarboxylate at the C7 position with (TMP)2Zn·2LiCl·2MgCl2 followed by iodination and trifluoromethylation to give 1b in good yield. The process in approach B has been successfully demonstrated on scale.