4-Chloro-6-methoxy-2-methylquinazoline

Synthesis

51413-71-9

60395-90-6

6-Methoxy-2-methylquinazolin-4-ol (233 mg, 1.23 mmol) was used as starting material and suspended in phosphoryl chloride (POCl3, 10 mL, 108 mmol). The reaction mixture was stirred under reflux conditions for 2.5 days and a gradual transformation of the suspension into a reddish brown solution was observed. Upon completion of the reaction, the mixture was cooled to room temperature and the excess phosphoryl chloride was subsequently removed by evaporation under reduced pressure. The residue was partitioned between 5% aqueous sodium bicarbonate solution (NaHCO3, 100 mL) and ethyl acetate (100 mL) for extraction. The organic layer was washed sequentially with 5% aqueous sodium bicarbonate solution (100 mL) and pure water (100 mL). The washed organic layer was dried with anhydrous sodium sulfate (Na2SO4) and subsequently concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using cyclohexane/ethyl acetate as eluent. The final target product, 4-chloro-6-methoxy-2-methylquinazoline, was obtained as a white solid (142 mg, 0.681 mmol) in 56% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6) and UPLC-MS (ESI): 1H NMR δ 7.92 (d, J = 9.1 Hz, 1H), 7.70 (dd, J = 9.1, 2.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 3.96 (s, 3H), 2.71 (s, 3H); UPLC-MS (ESI) RT 3.88 min, m/z 209 [M + H]+ (purity >95%).

References