Diisopropylethylamine → HCID 46918066, 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) (200 mg, 0.373 mmol), thiomorpholine 1-oxide trifluoroacetate (U.S. Pat. No. 6,372,773) (242 mg, 1.12 mmol), and DIPEA (0.45 mL, 2.61 mmol) was refluxed in THF (60 mL) for 4 days. The THF was removed under vacuum and the residue was dissolved in dioxane (60 mL). Additional thiomorpholine 1-oxide trifluoroacetate (161 mg, 0.745 mmol) and DIPEA (0.45 mL, 2.61 mmol) were added and the mixture was refluxed for 2 days. The solvent was removed under vacuum and the residue was diluted with water. The resulting precipitate was filtered, washed with water, and dissolved in CH2Cl2. The solution was dried (Na2SO4) and the solvent was removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (95:5), followed by recrystallization from CH2Cl2/hexane gave 138 mg (56% yield) of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(1-oxido-4-thiomorpholinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole: mp (CH2Cl2/hexane) 229-231° C.; 1H NMR (CDCl3) δ7.85 (d, J=8.0 Hz, 1H), 7.43 (t, JHF=53.5 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.9 Hz, 1H), 4.05 (s, 3H), 4.01 (br s, 4H), 3.89 (br s, 4H), 3.79 (m, 4H), 3.38 (t, J=5.0 Hz, 4H), 3.15 (m, 4H), 2.99 (dd, J=8.8, 5.4, 2H), 2.79 (m, 6H); Anal. Calcd. for C26H35F2N9O5S2.0.2H2O: C, 47.4; H, 5.4; N, 19.1. Found: C, 47.3; H, 5.5; N, 18.7.

Provenance & Evidence