A new series of α-pyridinyl-substituted indeno[2,1-c]quinoline derivatives was prepared with good yields according to a two-step synthesis. The first and key step involves the formation of the ring via three-component imino Diels-Alder cycloaddition between an aniline, pyridine-2-carbaldehyde, and indene using boron trifluoride-diethyl ether complex as a catalyst to produce the corresponding 5,6,6a,11b-tetrahydroindeno[2,1-c]quinolines. The second step consisted of their oxidation with powdered sulfur to obtain the corresponding indeno[2,1-c]quinolines, analogues of DNA topoisomerase inhibitor TAS-103.