A mixture of 2-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole (Example 3) (150 mg, 0.280 mmol), 8-oxa-3-azoniabicyclo[3.2.1]octane hydrochloride (209 mg, 1.40 mmol), and DIPEA (0.49 mL, 2.80 mmol) in 1,4-dioxane was stirred at room temperature for 2.5 days. Additional 8-oxa-3-azoniabicyclo[3.2.1]octane hydrochloride (84 mg, 0.561 mmol) was added and the mixture refluxed for 1 hr. The solvent was removed under vacuum, and the residue was diluted with water. The resulting precipitate was dissolved in CH2Cl2 and dried (Na2SO4). The solvent was removed under vacuum. Chromatography on silica eluting with CH2Cl2/MeOH (98:2), followed by recrystallization from CH2Cl2/hexanes gave 3-[2-({4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperazinyl}sulfonyl)ethyl]-8-oxa-3-azabicyclo[3.2.1]octane (118 mg, 87%): mp 219-221° C.; 1H NMR (CDCl3) δ7.85 (dd, J=8.4, 0.5 Hz, 1H), 7.43 (t, JHF=53.5 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 4.26 (m, 2H), 4.05 (s, 3H), 4.01 (br s, 4H), 3.88 (br s, 4H), 3.79 (m, 4H), 3.38 (t, J=5.0 Hz, 4H), 3.07 (dd, J=8.1, 6.3 Hz, 2H), 2.79 (dd, J=8.1, 6.3 Hz, 2H), 2.55 (d, J=10.6 Hz, 2H), 2.38 (dd, J=10.9, 2.0 Hz, 2H), 1.83 (m, 4H); Anal. Calcd. for C28H37F2N9O5S: C, 51.8; H, 5.7; N, 19.4. Found: C, 51.8; H, 5.9; N, 19.3%.
