反应详情

To a solution of 0.186 g (1.96 mmol) of 5-aminopyrimidine in THF (4 mL) at 0° C. was added 1.1 mL of NaHMDS (2 M solution in THF), 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 RT. After neutralization with acetic acid, the mixture was diluted with water and extracted with EtOAc. The organic layer was washed sequentially with water and aq. NH3, dried and concentrated. Chromatography on alumina, eluting first with CH2Cl2/EtOAc (1:9) and then with CH2Cl2/EtOAc (1:3) to CH2Cl2/EtOAc (7:3) 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, J=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, 4.1; N, 29.6. Found: C, 53.4; H, 4.2; N, 29.4%.

1. stirringthe resulting mixture was stirred for 1 hr at RT
2. extractionextracted with EtOAc
3. washThe organic layer was washed sequentially with water and aq. NH3
4. customdried
5. concentrationconcentrated
6. washChromatography on alumina, eluting first with CH2Cl2/EtOAc (1:9)
7. customwith CH2Cl2/EtOAc (1:3) to CH2Cl2/EtOAc (7:3) gave an off-white powder
8. customRecrystallization from ethanol