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

Sandrine Guillou (1) , Frédéric J. Bonhomme (1) , Di Betina Chahine (1) , Olivier Nesme (1) , Yves Louis Janin (1, 2)

1 Chimie Organique
2 CSVB - Conception, synthèse et vectorisation de biomolécules

n 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.

Sandrine Guillou, Frédéric J. Bonhomme, Di Betina Chahine, Olivier Nesme, Yves Louis Janin. N-arylation of 3-alkoxypyrazoles, the case of the pyridines. Tetrahedron, 2010, 66 (14), pp.2654-2663. ⟨10.1016/j.tet.2010.02.032⟩. ⟨pasteur-00463851⟩