A convenient method has been proposed for the preparation of new derivatives of adamantine-based drugs, such as memantine and rimantadine. The synthesis was performed by functionalization of amino-group of memantine and rimantadine by ipso-substitution of cyano-group at C5 position of 1,2,4-triazine scaffold with the corresponding aminoadamantane moieties with subsequent aza-Diels–Alder transformation of 1,2,4-triazine cycle into pyridine one in some cases. © 2023, Pleiades Publishing, Ltd.