反应详情

To 0.216 g (1.73 mmol) of 6-methoxy-3-pyridazinamine (J. Med. Chem. 2006, 49, 4409-4424) in THF (3 mL) was added 0.97 mL of NaHMDS (2 M solution in THF), and the mixture was stirred for 10 min. A solution of 0.233 g (0.59 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) was added and the resulting mixture was stirred for 10 min. The resulting mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed successively with water and aqueous NH3, dried, and concentrated. Recrystallization from ethanol/CH2Cl2 gave 0.086 g (30% yield) of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-(6-methoxy-3-pyridazinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 256-259° C.; 1H NMR (DMSO-d6) δ 10.85 (s, 1H), 8.24 (d, J=9.2 Hz, 1H), 8.15 (d, J=7.7 Hz, 1H), 7.99 (t, JHF=52.6 Hz, 1H), 7.40 (t, J=8.2 Hz, 1H), 7.29 (d, J=9.5 Hz, 1H), 6.96 (d, J=8.0 Hz, 1H), 4.00 (s, 3H), 3.97 (s, 3H), 3.84-3.79 (m, 4H), 3.72 (s, 4H); Anal. Calcd. For C21H21F2N9O30.5H2O: C, 51.1; H, 4.5; N, 25.5. Found: C, 51.4; H, 4.6; N, 25.0%.

1. stirringthe resulting mixture was stirred for 10 min
2. extractionextracted with EtOAc
3. washThe organic layer was washed successively with water and aqueous NH3
4. customdried
5. concentrationconcentrated
6. customRecrystallization from ethanol/CH2Cl2