Cesium carbonate → HCID 50923705, compound

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) and 5-hydroxypiperidine-3-carboxylic acid (21.81 mg, 0.150 mmol) in 2-propanol (2 mL) and DMSO (2.000 mL) was added cesium carbonate (122 mg, 0.376 mmol). The reaction mixture was heated at 80° C. Next, 5-hydroxypiperidine-3-carboxylic acid (21.81 mg, 0.150 mmol) was added and the reaction was checked after 4 hr. Product peak was observed but starting material remained. The reaction mixture was heated 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 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% 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 desired product was 5.6 mg, and its purity was 99%. 1H NMR (400 MHz, MeOD) δ ppm 8.21 (2H, d, J=7.78 Hz), 7.69 (4H, d, J=6.78 Hz), 7.53-7.65 (3H, m), 5.19 (1H, dt, J=10.10, 3.61 Hz), 4.16 (1H, br. s.), 3.08-3.26 (5H, m), 2.86-3.06 (2H, m), 1.87-2.06 (3H, m). MS (m+1)=545.

Provenance & Evidence