Deuteration of pharmaceutical drugs decreases the metabolism of the drug, retains the biochemical potency, and enhances the overall therapeutic profile. Strategies for direct deuteration of pharmaceutical drugs are of increasing interest in medicinal research since development of such drugs can address unmet medical needs. In our studies, deuterium oxide (D<sub>2</sub>O) and an NHC-Amidate Pd(II) catalyst are used to achieve direct deuteration of pharmaceutical drugs at the N-Methyl and O-Methyl sites. This is of paramount importance since metabolic sites of such compounds are commonly known to be at the N-Methyl and O-Methyl positions. Up to 75% hydrogen-deterium exchange has been detected using our catalytic methods and further development of conditions for higher H/D exchange will be presented. Metabolism studies by liver enzymes will also be reported to demonstrate kinetic isotope effects between deuterated and unaltered pharmaceutical drugs.

Direct H/D exchange of pharmaceuticals using an NHC-amidate Pd(II) catalyst in D<sub>2</sub>O

251st National Meeting (2016)

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Direct H/D exchange of pharmaceuticals using an NHC-amidate Pd(II) catalyst in D2O

Direct H/D exchange of pharmaceuticals using an NHC-amidate Pd(II) catalyst in D₂O