N-arylation of 3-alkoxypyrazoles, the case of the pyridines

In the course of a research program focused on the preparation of libraries of new chemical entities derived from 3-alkoxypyrazoles, we studied their N-pyridylation using 2, 3 or 4-bromopyridines. This was achieved using Cristau and Taillefer copper-catalyzed arylation method and mostly led to the 3-alkoxy-1H-pyrazol-1-yl pyridine isomer along with lesser amount of the alternative 5-alkoxy-1H-pyrazol-1-yl pyridine. The structures of these isomers were often established via their chemical transformations and sometimes recourse to unambiguous synthetic routes for comparison purposes. The alternative use of 2-fluoropyridine-based arylation was also investigated and lifted some of the limitations encountered in the course of this study.