反应详情

温度

0 °C

Zinc(II) chloride (1.0 M in Et2O; 2.00 mL, 2.00 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.399 g, 1.84 mmol) in 1:1 DCE/t-BuOH (15 mL) at 0° C. under a nitrogen atmosphere. The resulting mixture was stirred for 1 hour at 0° C. and then tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate (A21) (0.510 g, 1.67 mmol) in 1:1 DCE/tBuOH (15 mL) was added. A solution of Et3N (0.256 mL, 1.84 mmol) in 1:1 DCE/t-BuOH (15 mL) was added dropwise at 0° C. and the resulting mixture was vigorously stirred for a further 30 minutes at 0° C. then at room temperature for 16 hours. The volatiles were removed in vacuo to afford a brown residue which was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to yield a pale yellow solid. The solid was suspended in MeOH (15 mL) and water (15 mL) and the resulting suspension filtered to give the title compound A22 as a white solid (0.561 g, 69%); 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.64 (s, 1H), 7.45 (d, J=8.6 Hz, 2H), 3.87-3.30 (m, 8H), 1.47 (s, 9H). LCMS-A: rt 6.206 min; m/z 484.1 [M−H]−.

1. stirringthe resulting mixture was vigorously stirred for a further 30 minutes at 0° C.
2. waitat room temperature for 16 hours
3. customThe volatiles were removed in vacuo
4. customto afford a brown residue which
5. customwas purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
6. customto yield a pale yellow solid
7. filtrationwater (15 mL) and the resulting suspension filtered