Convenient and Reliable Routes Towards 2-Aminothiazoles: Palladium-Catalyzed versus Copper-Catalyzed Aminations of Halothiazoles

Two efficient methods for the amination of 2-halothiazoles are presented here. A first protocol requires a Pd/L system. Several 2-aminothiazoles were synthesized under optimized conditions and isolated in good yields. The first palladium-catalyzed CN coupling reactions between 2-halothiazoles and primary alkylamines are presented. In a second part, ligand-free copper-catalyzed aminations of 2-halothiazoles by alkylamines and aniline in a green solvent have been developed. The protocol is very effective for primary and secondary amines and perfectly tolerates the presence of another halide moiety on the 2-halothiazole. The reaction occurs under the assistance of microwave irradiation, which drastically decreases the reaction time. The reaction leads to the formation of 2-aminothiazoles, key molecules in pharmaceutical research.