Here, we demonstrate that the protecting-group-free mechanochemical amide coupling of hydroxycarboxylic acids can be achieved with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as an optimal coupling reagent. The synthetic value of the chemoselective amide-coupling methodology is illustrated by the two-step mechanochemical synthesis of imatinib (2), also known as Gleevec ® (Scheme 1), an anti-cancer drug included in the World Health Organization's List of Essential Medicines. The newly developed route to this API from 4-(hydroxymethyl)benzoic acid (1) exhibits an enhanced safety and sustainability profile in comparison with the previously reported solution-based methodologies.