Dimethyl Sulfoxide → 2-(3-(2-Hydroxyethyl)piperidin-1-yl)-1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol) in 2-propanol (2 mL) was added 2-(piperidin-3-yl)ethanol (19.41 mg, 0.150 mmol). The reaction mixture was heated to 80° C. DMSO (1 mL) was added to help solubilize. The reaction mixture was stirred overnight. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 MeOH:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 MeOH:water with 10-mM ammonium acetate; Gradient: 45-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the Example 31 was 13.0 mg, and its purity was 100%. 1H NMR (400 MHz, MeOD) δ ppm 8.18 (2H, d, J=8.03 Hz), 7.52-7.75 (7H, m), 5.01 (1H, ddd, J=8.60, 4.20, 4.02 Hz), 3.54-3.72 (2H, m), 3.13 (2H, br. s.), 2.73 (2H, br. s.), 2.32 (1H, br. s.), 2.11 (1H, br. s.), 1.61-1.92 (4H, m), 1.48 (2H, dd, J=13.68, 6.90 Hz), 1.04 (1H, br. s.). MS (m+1)=529.

Provenance & Evidence