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
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.