A unique approach in mechanosynthesis, joining solid-state NMR spectroscopy, X-ray crystallography, and theoretical calculations, is employed for the first time to study the mechanism of the formation of the C-N amide bond using EDC·HCl as a coupling reagent. It has been proved that EDC·HCl, which in the crystal lattice exists exclusively in the cyclic form (X-ray data), easily undergoes transformation to a pseudocyclic stable intermediate in reaction with carboxylic acid forming a low-melt phase (differential scanning calorimetry, solid-state NMR). The obtained intermediate is reactive and can be further used for synthesis of amides in reaction with appropriate amines.