Efficient One-pot HATU Mediated Coupling of Dicarboxylic Acid and Amines for the Synthesis of Diamide at Ambient Temperature

Background: Amide bond is prevalent in peptides. Moreover, at least 25% pharmaceutical products also contain amide bond. A wide ranging strategy including Ugi reaction and related multicomponent reactions is available for the synthesis of amide. While HATU mediated direct one-pot diamide synthesis is scarcely investigated in the literature. Objective: The objective of this work is to achieve a one pot synthesis of diamide using various coupling reagents. Method: Straightforward one-pot coupling of dicarboxylic acid with corresponding amine was accomplished in the presence of HATU under ambient condition using 2-Me THF as an industrial green solvent. Results: A range of (hetero)aromatic and aliphatic dicarboxylic acids were coupled with aromatic and aliphatic amines to give 55-89% yield of the products at ambient temperature. Conclusion: Among various coupling reagents scrutinized, HATU was proven to be ‘gold standard’ to accomplish one-pot synthesis of diamides. Keywords: Coupling reagents, diamide, HATU, one-pot, peptides, rt.