In this research, microwave‐assisted “one‐pot” multicomponent reactions have been employed for the synthesis of new chromeno[2,3‐d]pyrimidines containing fluorine atoms. The biological significance of the obtained compounds was highlighted by evaluating in vitro for cytotoxic activity against four human cancer cell lines (HepG2, hepatoma carcinoma; MCF7, breast cancer; A549, non‐small lung cancer; KB, epidermoid carcinoma). Interestingly, two compounds revealed significant inhibitory activity against A549 cell line, and showed low toxicity to human embryonic kidney (Hek‐293) cell line. The synthetic efficacy and cytotoxic potency have offered an opportunity to further development of chromeno[2,3‐d]pyrimidines containing fluorine atoms as potential anticancer agents.

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