反应详情

To 0.186 g (1.96 mmol) of 5-aminopyrimidine in THF (4 mL) was added 1.1 mL of NaHMDS (2 M solution in THF) at 0° C. and the mixture was stirred for 15 min. A solution of 0.238 g (0.65 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (5 mL) was added and the resulting mixture WAS stirred for 1 hr at room temperature. The resulting mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed with water, and aq. NH3, and dried. Removal of the solvent, followed by chromatography on alumina, eluting with CH2Cl2/EtOAc (1:9), then CH2Cl2/EtOAc (1:3), gave an off-white powder. Recrystallization from ethanol gave 0.123 g (47% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(5-pyrimidinyl)-1,3,5-triazin-2-amine: mp 290-292° C.; 1H NMR (CDCl3) δ9.07 (s, 2H), 9.02 (s, 1H), 8.37 (d, J=7.2 Hz, 1H), 7.89 (dd, J=7.7, 1.5 Hz, 1H), 7.57 (t, JHF=53.7 Hz, 1H), 7.47-7.40 (m, 2H), 7.11 (s, 1H), 3.95-3.92 (m, 4H), 3.83 (br s, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.0; N, 29.6. Found: C, 53.4; H, 4.2; N, 29.4%.

1. stirringthe resulting mixture WAS stirred for 1 hr at room temperature
2. extractionextracted with EtOAc
3. washThe organic layer was washed with water, and aq. NH3
4. customdried
5. customRemoval of the solvent
6. washeluting with CH2Cl2/EtOAc (1:9)
7. customCH2Cl2/EtOAc (1:3), gave an off-white powder
8. customRecrystallization from ethanol