AbstractA practical and mild three‐component reaction of indoles, quinoxalin‐2(1H)‐ones, and CF3SO2Na is disclosed for the facile access of various 3‐[2‐(trifluoromethyl)1H‐indol‐3‐yl]quinoxalin‐2(1H)‐ones using low‐cost and catalytic amount of CuF2 as the catalyst. This strategy exhibits high site‐selectivity, step economy, and broad substrates scope. Synthetic utility was demonstrated by the one‐pot two‐step synthesis of N‐alkyl triazoles compounds via a click chemistry. To evaluate the antiproliferative activity of these compounds, A549 s (human lung adenocarcinoma cells) and HUVECs, as a model of toxicity, were used in MTT assay. The outcomes disclosed for 6‐CO2Me and a N‐alkyl triazole derivatives were of potent antiproliferative effect against A549 s (IC50 = 4.7 and 14.9 μM, respectively) with slight cytotoxicity in HUVECs. Morphological study was conducted by AO/EB dual staining, indicated hydrochloride 6‐CO2Me derivative was capable of inducing apoptosis of A549 cells.