反应详情

温度

40 °C

A 1.0 M solution of zinc chloride in Et2O (18.5 mL, 18.5 mmol) was added to a solution of 2,6-dichloro-5-trifluoromethylpyrimidine (2.81 g, 13.0 mmol) in t-BuOH/DCE (1:1, 50 mL) at 0° C. over a period of 20 minutes then the resulting mixture was stirred for 1 hour. A solution of 5-amino-2-trifluoromethylpyrimidine (2.00 g, 12.3 mmol) and DIPEA (3.22 mL, 18.5 mmol) in t-BuOH/DCE (1:1, 30 mL) was added over 20 minutes then the resulting mixture was stirred at room temperature for 4 days, before heating to 40° C. and stirred for a further 24 hours. The volatiles were removed under reduced pressure to give a solid residue. Water (100 mL) was added and the suspension sonicated for 30 minutes. The resulting mixture was extracted with EtOAc (3×100 mL) and CHCl3 (100 mL). The organic extracts were combined, passed through a phase separation cartridge and the volatiles were evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage Isolera, 2×40 g SiO2, 0-25% EtOAc in petroleum benzine 40-60° C.) to give the title compound A16 as a white solid (1.78 g, 42%); 1H NMR (400 MHz, d6-DMSO) δ 11.21 (s, 1H), 9.02 (d, J=2.5 Hz, 1H), 8.96-8.89 (m, 1H), 8.40 (dd, J=8.6, 2.2 Hz, 1H), 7.92 (d, J=8.6 Hz, 1H). LCMS-A: rt 5.931 min; m/z 343 [M+H]+.

1. stirringthe resulting mixture was stirred at room temperature for 4 days
2. stirringstirred for a further 24 hours
3. customThe volatiles were removed under reduced pressure
4. customto give a solid residue
5. customthe suspension sonicated for 30 minutes
6. extractionThe resulting mixture was extracted with EtOAc (3×100 mL) and CHCl3 (100 mL)
7. custompassed through a phase separation cartridge
8. customthe volatiles were evaporated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (Biotage Isolera, 2×40 g SiO2, 0-25% EtOAc in petroleum benzine 40-60° C.)