Dimethylamine → HCID 46918202, compound

Participants

Reaction Steps

The above alcohol (305 mg, 0.51 mmol) in CH2Cl2 (15 mL) was treated with Et3N (0.3 mL) and methanesulfonyl chloride (0.2 mL, 2.5 mmol) at 0° C. The reaction mixture was stirred at this temp for 45 min and 40% aqueous solution of dimethylamine (5 mL) was then added. Stirring was continued for 2 days at 20° C., and the CH2Cl2 was evaporated. The residue was diluted with water, and the resulting precipitate was washed with water and dried. Chromatography on neutral alumina, eluting with CH2Cl2/MeOH (98:2), followed by chromatography on silica, eluting with CH2Cl2/MeOH/aq. NH3 (96:3:1) gave N-{1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-piperidinyl}-N-[3-(dimethylamino)propyl]methanesulfonamide (200 mg, 63%). The amine was converted to the hydrochloride salt by combining with 1.25 M HCl in MeOH. Recrystallization from MeOH/isopropanol gave N-{1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-piperidinyl}-N-[3-(dimethylamino)propyl]methanesulfonamide hydrochloride: mp 187-191° C.; 1H NMR (DMSO-d6) δ9.83 (br s, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.70 (t, JHF=52.9 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 6.95 (d, J=7.9 Hz, 1H), 4.84-4.73 (m, 2H), 3.98 (s, 3H), 3.92-3.85 (m, 1H), 3.80 (m, 4H), 3.70 (m, 4H), 3.16 (t, J=7.4 Hz, 2H), 3.11-2.96 (m, 7H), 2.71 (s, 6H), 1.91-1.83 (m, 4H), 1.73-1.68 (m, 2H); Anal. Calcd. for C27H40ClF2N9O4S.H2O: C, 47.8; H, 6.2; N, 18.6; Cl, 5.2. Found: C, 47.9; H, 6.2; N, 18.6; Cl, 5.0%.

Provenance & Evidence