Two approaches to a 1-aryl-4-trifluoromethyltriazole are described. Initially, a late-stage trifluoromethylation of the corresponding 1-aryl-4-iodotriazole using methyl fluorosulfonyldifluoroacetate (MDFA) was employed. However, the reaction was fraught with several safety and operational challenges, primarily due to the evolution of ∼33 equiv of gas per equiv of substrate. While some of these challenges were either addressed or mitigated through operations in plug flow, the process remained low yielding and suboptimal. Subsequently, a more convergent, longer-term route involving a Cu-mediated decarboxylative Click reaction was developed.

Propylphosphonic anhydride has been shown to be an effective reagent for the synthesis of substituted [1,2,4]­triazolo­[1,5-a]­pyridines from the corresponding N′-hydroxy-N-formimidamides. The reactions worked under mild conditions and exhibited wide functional group tolerance, delivering the triazolopyridines in good to excellent yields and purities.