Regioselective Synthesis of 1,4-Disubstituted-1,2,3-Triazole Hybrids Containing Isatin and 1,4-Dihydropyridines mediated by Ionic Liquid/Water/Cu(I) System

In the present work, we report the sustainable regioselective synthesis of a novel series of 1,2,3-triazole-based hybrid molecules containing isatins and 1,4-dihydropyridines by Copper(I)-catalyzed Azide-Alkyne 1,3-dipolar Cycloaddition (CuAAC). We designed and realized these hybrid molecules with the idea to produce multitarget agents with poten-tially improved bioactivity, enhanced pharmacokinetic properties and a reduced risk of drug resistance. Our synthetic strategy provides mild reaction conditions, high reaction yields, a simple recover procedure and a reusable catalytic system based on an environ-mentally benign solvent mixture of ionic liquid/water. The latter was recovered together with the Cu(I) catalyst generated in situ and Na-ascorbate and reused until six times, maintaining high efficacy in terms of regioselectivity and reaction yields. Finally, a mech-anism of the reaction was proposed, involving the key role of IL.