反应详情

温度

190 °C

To a solution of 0.39 g (0.85 mmol) 6-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one in 2.5 mL DMF was added 0.13 g (1.4 mmol) copper(I) cyanide and the mixture heated in a sealed tube at 190° C. for 2 hours. After cooling to room temperature, the reaction mixture was diluted with 125 mL ether, washed 2×100 mL water and 1×100 mL brine, dried over dried over MgSO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (40 g silica gel cartridge, linear gradient 5-75% EtOAc/hexanes) followed by preperative chiral chromatography (5×50 mm Chiralcel OD, 100% MeOH) provided the first peak (−) 6-chloro-4-cyclopropyl-4-(4-cyanophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. Optical rotation −83° (c=0.00175 g/mL in CH2Cl2, Na lamp,) 1H NMR (CDCl3, 400 MHz) δ 8.18 (s, NH); 7.64 (br d, 2H, J=7.88 Hz); 7.39 (br d, 2H, J=6.22 Hz); 7.26 (obscured, 1H); 6.85 (br m, 1H); 6.74 (d, 1H, J=8.24 Hz); 4.34 (m, 1H); 4.23 (br m, 1H); 1.62 (m, 1H); 0.82 (m, 2H); 0.20 (m, 1H); 0.097 (m, 1H); MS (Electrospray): exact mass calculated for C20H15ClF3N3O+H 406.0925 found 406.0935 Collect 0.1 g second peak Optical rotation +100° (c=0.002 g/mL in CH2Cl2, Na lamp,).

1. temperatureAfter cooling to room temperature
2. washwashed 2×100 mL water and 1×100 mL brine
3. customdried
4. dry with materialover dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification by normal phase chromatography (40 g silica gel cartridge, linear gradient 5-75% EtOAc/hexanes)