Ethanesulfonylchloride, 2-chloro- → HCID 66698109, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-piperidinyloxy)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 16) (1.52 g, 3.29 mmol) and DIPEA (2.3 ml, 4 eq.) in CH2Cl2 (30 mL) at 0° C. was added 2-chloroethanesulfonyl chloride (1 mL, excess). The reaction mixture was stirred at 20° C. for 20 hrs and diluted with water (50 mL). The CH2Cl2 layer was separated and the aqueous layer was further extracted with CH2Cl2 (3×20 mL). The combined organic fractions were washed successively with aq. HOAc, aq. K2CO3, and water, and dried (MgSO4). Evaporation of the solvent and chromatography of the residue on silica, eluting with CH2Cl2/EtOAc (9:1) gave 2-(difluoromethyl)-4-methoxy-1-(4-(4-morpholinyl)-6-{[1-(vinylsulfonyl)-4-piperidinyl]oxy}-1,3,5-triazin-2-yl)-1H-benzimidazole (1.17 g, 65% yield): mp (CH2Cl2/MeOH) 266-269° C.; 1H NMR (DMSO-d6) δ 7.95 (d, J=7.9 Hz, 1H), 7.70 (t, JHF=52.8 Hz, 1H), 7.44 (t, J=8.2 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.88 (dd, J=16.5, 10.0 Hz, 1H), 6.19 (d, J=10.0 Hz, 1H), 6.15 (d, J=16.5 Hz, 1H), 5.26-5.20 (m, 1H), 3.98 (s, 3H), 3.84 (m, 4H), 3.74-3.32 (m, 4H), 3.39-3.32 (m, 2H), 3.14-3.08 (m, 2H), 2.14-2.09 (m, 2H), 1.90-1.18 (m, 2H); Anal. Calcd. for C23H27F2N7O5S.0.5CH2Cl2: C, 47.7; H, 4.7; N, 16.5. Found: C, 47.8; H, 4.7; N, 16.8%.

Provenance & Evidence