The free‐solvent multicomponent reaction under microwave irradiation of 6‐aminopyrimidin‐4(3H)‐ones (1) with dimedone (2) and N,N‐dimethylformamide dimethylacetal yields the pyrimido[4,5‐c]isoquinolinones (5a‐j). In this process, the intermediate of cyclization was isolated. The structure of the synthesized compounds was determined on the basis of nmr measurements, especially by 1H,1H‐,1H,13C COSY, and DEPT. These compounds showed antifungal in vitro activity particularly against dermatophytes.