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

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)+.

1. temperatureat reflux overnight
2. temperatureThe reaction was then cooled
3. concentrationconcentrated
4. temperatureThe brown syrup was cooled in an ice bath
5. additionice was added to the reaction mixture
6. additionThe brown sludge was added to 100 mL of 10 M NaOH (aq.) and ice
7. stirringstirred for 20 min
8. filtrationThe mixture was filtered
9. washthe brown solid was washed with water
10. filtrationfiltered
11. customThe filtrate was collected
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-7982dc88b9384c049c7517b66509507d

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2