Thiomorpholine → HCID 67543789, compound

Participants

Reaction Steps

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) (180 mg, 0.335 mmol), thiomorpholine (0.17 mL, 1.68 mmol) in THF (50 mL) was stirred at room temperature for 3 days and then at reflux for 3 hrs. The solvent was removed under vacuum and the residue was dissolved in dioxane (30 mL) and additional thiomorpholine (0.17 mL, 1.68 mmol) was added. The reaction mixture was refluxed for 2 days. The solvent was removed under vacuum and the residue diluted with water. The resulting precipitate was filtered, washed with water and dissolved in CH2Cl2. The solution was dried (Na2SO4) and solvent removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (98:2), followed by recrystallization from CH2Cl2/hexane gave 180 mg (84% yield) of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(4-thiomorpholinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole: mp (CH2Cl2/hexane) 210-212° C.; 1H NMR (CDCl3) δ 7.86 (dd, J=8.3, 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), 4.05 (s, 3H), 4.00 (br s, 4H), 3.89 (br s, 4H), 3.79 (m, 4H), 3.38 (t, J=5.1 Hz, 4H), 3.11 (dd, J=8.3, 6.1 Hz, 2H), 2.87 (dd, J=8.3, 6.1 Hz, 2H), 2.73 (dd, J=6.1, 3.8 Hz, 4H), 2.63 (m, 4H); Anal. Calcd. for C26H35F2N9O4S2.0.5H2O: C, 48.1; H, 5.6; N, 19.4. Found: C, 48.2; H, 5.4; N, 19.3%.

Provenance & Evidence