反应详情

To 0.282 g (2.25 mmol) of 4-amino-6-methoxypyrimidine in THF (4 mL) was added 1.30 mL of NaHMDS (2 M solution in THF) and the mixture was stirred for 10 min. A solution of 0.297 g (0.75 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) in THF (5 mL) was added. The resulting mixture was stirred at room temperature for 1 hr. After neutralization with acetic acid, the mixture was diluted with water, and extracted with EtOAc. The organic layer was washed successively with water and aqueous NH3, and dried. Removal of the solvent, followed by chromatography on silica eluting with CH2Cl2/EtOAc (1:1) gave a white powder. Recrystallization from ethanol/CH2Cl2 gave 0.103 g (30% yield) of 4-(2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl)-N-(6-methoxypyrimidin-4-yl)-6-morpholino-1,3,5-triazin-2-amine: mp 256-259° C.; 1H NMR (CDCl3) δ8.52 (s, 1H), 7.96-7.94 (m, 2H), 7.59 (s, 1H), 7.49 (t, JHF=53.5 Hz, 1H), 7.36 (d, J=8.4 Hz, 1H), 6.84 (d, J=8.1 Hz, 1H), 4.06 (s, 3H), 4.00 (s, 3H), 3.99-3.96 (m, 4H), 3.84 (s, 4H); HRMS (FAB MH+) Calcd for C21H22F2N9O3: m/z 486.1808. Found: m/z 486.1808.

1. stirringThe resulting mixture was stirred at room temperature for 1 hr
2. extractionextracted with EtOAc
3. washThe organic layer was washed successively with water and aqueous NH3
4. customdried
5. customRemoval of the solvent
6. customgave a white powder
7. customRecrystallization from ethanol/CH2Cl2