General procedure for the synthesis of 4-chloro-6-fluoroquinazoline from 6-fluoro-4-hydroxyquinazoline: a mixture of 6-fluoro-4-hydroxyquinazoline (1.64 g, 10 mmol) with phosphoryl chloride (7.5 mL, 50 mmol) and phosphorus pentachloride (6 g, 30 mmol) was heated and refluxed for 2 hours in a water bath. Upon completion of the reaction, the reaction mixture was cooled to room temperature and slowly poured into crushed ice to quench the reaction. The precipitated solid product was collected by filtration, washed well with water to remove residual acid and subsequently dried. The crude product was purified by column chromatography (eluent: hexane/ethyl acetate) to afford the target compound 4-chloro-6-fluoroquinazoline. Yield: 65%; Melting point: 140-142 °C; 1H-NMR (DMSO-d6, 300 MHz) δ 8.12 (s, 1H, ArH), 7.47 (dd, 1H, J = 7.9 Hz and 2.8 Hz, ArH), 7.53 (dd, 1H, J = 8.6 Hz and 5.1 Hz, ArH), 7.62 (s, 1H, ArH ); molecular formula: C8H4ClFN2 (molecular weight: 182); MS (ESI) m/z 183 [M + 1]+.
