Aminopyridazine → 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(3-pyridazinyl)-1,3,5-triazin-2-amine

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Reaction Steps

To 0.215 g (2.26 mmol) of 3-aminopyridazine (Example 23) 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]-6-(4-morpholinyl)-N-(3-pyridazinyl)-1,3,5-triazin-2-amine: mp 261-263° C.; 1H NMR (DMSO-d6) δ11.13 (s, 1H), 8.97 (dd, J=4.7, 1.4 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.05 (t, JHF=52.9 Hz, 1H), 7.73 (dd, J=9.1, 4.7 Hz, 1H), 7.41 (t, J=8.3 Hz, 1H), 6.97 (d, J=7.8 Hz, 1H), 3.98 (s, 3H), 3.85 (s, 4H), 3.75 (s, 4H); Anal. Calcd. for C20H19F2N9O2: C, 52.75; H, 4.2; N, 27.7. Found: C, 52.7; H, 4.25; N, 27.7%.

Provenance & Evidence