Quinoline, as an advantageous skeleton of drug modification, has important application value in the field of innovational drug research and development, and the methodological studies on its structural modification has also attracted much attention. In view of this, a one-pot method to synthesize a series of novel quinoline polycyclic compounds were constructed with 5-fluorosubstituted-4-chloroquinoline derivatives and binucleophilic reagents as the starting materials. The key step of this method is the reaction of 4-chloro-5-fluoroquinoline-3-carboxylates with ortho-substituted anilines (binucleophilic reagents) in N,N-dimethylformamide, and in the presence of deacid reagents to complete a cascade substitution of chlorine and fluorine under heating conditions, to afford diversified quinoline polycyclic derivatives without separating the mono-substituted intermediates. The method is simple and efficient, does not require any catalysts, and with good tolerance of various functional groups. The structures of the products were confirmed by 1H NMR, 13C NMR and high resolution mass spectrum (HRMS).