An efficient MW-assisted synthesis of eight new 6-nitrilemethyl-pyrrolo[3,4-b]pyridin-5-ones via a domino process: aza Diels-Alder / N-acylation / aromatization (dehydration-decarboxylation) from their corresponding 2-aminonitrile-oxazoles and maleic anhydride is described. The use of MW as heat source and scandium (III) triflate as catalyst to promote the cycloaddition process was crucial to construct these polyfunctionalized products in very good yields (51–79%) considering both, their molecular complexity, and that only one domino-type experimental procedure was required for their synthesis. It is worthy to note that all herein reported products have not been synthesized nor isolated anywhere. However, they can be of high interest for synthetic and medicinal chemistry community because the pyrrolo[3,4-b]pyridin-5-one is the structural core of various bioactive compounds. In the same context, it can be considered as a privileged aza-analogue of the isoindolin-1-one, which in turn is the core of numerous anticancer agents.