Precise Azine Deuteration in Pharmaceuticals Using In-Situ Generated Nickel Nanocatalysts

The development of site specific deuteration methods is cornerstone for accelerating deuterated drugs discovery in pharmaceutical research. In this context, the precise deuteration of azines at their metabolic target sites is of paramount importance to allow modulation of those active pharmaceutical ingredients metabolism mediated by aldehyde oxidase and therefore give rise to new therapeutic agents. Herein, we describe an easy-to-implement method achieving high isotopic enrichments and regioselectivity in the deuteration of various azines, including pyridine, pyrimidine but also triazole and oxazole substructures within complex pharmaceuticals. This hydrogen isotope exchange reaction relies on the in-situ formation of nickel nanoparticles from air-stable and commercially available Ni(0) precatalysts, using deuterium gas as the isotopic source.