Acetic Acid → HCID 66854377, compound

Participants

Reaction Steps

To 0.225 g (2.37 mmol) of 4-aminopyrimidine in THF (3 mL) was added 1.30 mL of NaHMDS (2 M solution in THF) and the mixture was stirred for 10 min. A solution of 0.320 g (0.81 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole in THF (5 mL) was added and the resulting mixture was stirred for 1 hr. The reaction 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 silica, eluting first with hexanes-EtOAc (1:1), then CH2Cl2/EtOAc (1:1) to CH2Cl2/EtOAc (1:3) gave a white powder. Recrystallization from EtOH/CH2Cl2 gave 0.058 g (16% yield) of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(4-pyrimidinyl)-1,3,5-triazin-2-amine: mp 234-236° C.; 1H NMR (CDCl3) δ8.91 (d, J=1.0 Hz, 1H), 8.65 (d, J=5.8 Hz, 1H), 8.23 (dd, J=5.8, 1.3 Hz, 1H), 7.99 (s, 1H), 7.93 (dd, J=8.3, 0.5 Hz, 1H), 7.47 (t, JHF=53.4 Hz, 1H), 7.38 (t, J=8.2 Hz, 1H), 6.85 (d, J=7.8 Hz, 1H), 4.06 (s, 3H), 3.97-3.96 (m, 4H), 3.86-3.84 (m, 4H); Anal. Calcd. for C20H19F2N9O20.31H2O: C, 52.1; H, 4.3; N, 27.3. Found: C, 51.7; H, 4.15; N, 27.3%.

Provenance & Evidence