2‐Aminopyrazine catalyzed three‐component and one‐pot construction of 2‐amino‐4H‐chromene‐3‐carbonitrile by mortar‐pestle grinding and molecular docking studies

Abstract

A highly efficient and environmentally friendly method for the synthesis of 2‐amino‐4H‐chromene‐3‐carbonitrile (ACC) derivatives has been successfully established. This innovative, solvent‐free approach involves a tandem three‐component and one‐pot reaction utilizing arylaldehyde, dicyanomethane, and dimedone/cyclohexane‐1,3‐dione, catalyzed by 2‐aminopyrazine under the mortar‐pestle grinding technique. Key attributes of this synthetic strategy include its simplicity, high efficiency, cost‐effectiveness, absence of column chromatography, shorter reaction times (18–40 min), and consistently high yields (89%–96%). Furthermore, computational studies have been conducted against the 4RHT protein using the synthesized compounds.