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

Participants

Reaction Steps

To a solution of 0.159 g (1.67 mmol) of 3-aminopyridazine in THF (3 mL) at 0° C. was added 0.93 mL of NaHMDS (2 M solution in THF), and the mixture was stirred for 15 min. A solution of 0.317 g (0.84 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (6 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 hexane-EtOAc (8:2) then with CH2Cl2/EtOAc (2:1) to CH2Cl2/EtOAc (1:1) gave a white powder. Recrystallization from ethanol/CH2Cl2 gave 0.065 g (18% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(3-pyridazinyl)-1,3,5-triazin-2-amine: mp 271-273° C.; 1H NMR (DMSO-d6) δ 11.16 (br s, 1H), 8.98 (dd, J=4.7, 1.4 Hz, 1H), 8.67 (d, J=8.0 Hz, 1H), 8.61 (d, JHF=8.4 Hz, 1H), 8.08 (t, JHF=52.8 Hz, 1H), 7.86 (dd, J=7.7, 0.7 Hz, 1H), 7.73 (dd, J=9.1, 4.7 Hz, 1H), 7.53-7.43 (m, 2H), 3.86 (s, 4H), 3.75 (s, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.1; N, 29.6. Found: C, 53.7; H, 4.2; N, 29.5%.

Provenance & Evidence