Phosphorus oxychloride → 8-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one

Participants

Reaction Steps

A mixture of 8-bromo-3-cyclopropylquinazoline-2,4(1H,3H)-dione (723b; 5.00 g, 17.79 mmol), POCl3 (8.29 mL, 89.0 mmol) and DIPEA (12.38 mL, 71.1 mmol) was stirred at reflux overnight. The reaction was then cooled and concentrated. The brown syrup was cooled in an ice bath and then ice was added to the reaction mixture. The brown sludge was added to 100 mL of 10 M NaOH (aq.) and ice and stirred for 20 min. The mixture was filtered and the brown solid was washed with water and then put into solution with CH2Cl2 and filtered. The filtrate was collected and dried over Na2SO4, filtered and concentrated to afford 8-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one (723) (4.54 g, 15.16 mmol, 85% yield) as a brown solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.17 (dd, J=8.02, 1.56 Hz, 1H), 7.99 (dd, J=7.82, 1.56 Hz, 1H), 7.32 (t, J=7.92 Hz, 1H), 3.02 (tt, J=7.12, 4.03 Hz, 1H), 1.33-1.43 (m, 2H), 0.94-1.04 (m, 2H). m/z (ES, +ve) 298.9, 301.0 (M+H)+.

Provenance & Evidence