反应详情

The solution of 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (136 mg, 0.20 mmol) in trifluoroacetic acid (1.5 mL) was stirred at 60° C. for 1 h. It was cooled to rt and treated with 5N NaOH solution to pH 9˜10. The resulting mixture was extracted with methylene chloride. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by preparative thin layer chromatography using 8% of 2N ammonium in methanol/methylene chloride as eluent provided the 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one as a white solid. 1H NMR (CDCl3, 500 MHz): δ 1.03 (d, 3H, J=5.7 Hz), 1.08 (d, 3H, J=5.7 Hz), 1.66 (m, 2H), 2.37 (t, 1H, J=8.2 Hz), 2.43 (t, 1H, J=11.9 Hz), 2.56 (brs, 1H), 2.83 (t, 1H, J=9.2 Hz), 2.90 (d, 1H, J=8.7 Hz), 3.14 (s, 1H), 3.54 (m, 2H), 3.64 (t, 1H, J=13.0 Hz), 4.33 (abq, 2H, J=14.2 Hz), 5.12 (s, 1H), 6.24 (s, 1H), 6.84 (s, 1H), 7.08 (t, 1H, J=8.0 Hz), 7.28 (m, 2H), 7.39 (d, 1H, J=8.0 Hz), 7.54 (t, 1H, J=8.0 Hz). MS (API-ES+): 573 (M+H).

1. extractionThe resulting mixture was extracted with methylene chloride
2. washThe organic layer was washed with water and brine
3. dry with materialdried over anhydrous sodium sulfate
4. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography