Raney Nickel-Catalyzed Deuterium Labeling of Nitrogen Containing Heterocycles and Pharmaceuticals under Continuous Flow Conditions

Abstract

Deuterium-labeled compounds play a pivotal role in physical organic chemistry, life sciences, and materials science. This has resulted in a surge of interest in deuterium-labeled active pharmaceutical ingredients in recent years. In this study, we present a continuous flow Raney nickel-catalyzed hydrogen isotope exchange process that boasts compatibility with a wide spectrum of nitrogen-containing heterocycles and pharmaceutical compounds. The broad applicability of the developed method was demonstrated through successful labeling of various purine bases, imidazoles, pyridines, and active pharmaceutical ingredients, including complex structures like abacavir and remdesivir. Control experiments revealed Raney nickel‘s crucial role in the exchange process, showcasing the superiority of the continuous flow approach over batch reactions. Furthermore, a scaled-up experiment demonstrated the robustness of the catalyst.