1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)pyrrolidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol, Preparation 1C (30 mg, 0.066 mmol) and pyrrolidine-3-carboxylic acid (22.81 mg, 0.198 mmol) in DMSO (2 mL) was added DBU (0.030 mL, 0.198 mmol). The reaction mixture was heated at 80° C. for 2 hours. The crude material was purified via preparative LC/MS with the following conditions: Column. Waters XBridge C18, 19×100 mm, 5-μm particles; Guard Column: none; Mobile Phase A: 5:95 acetonitrile:water with 0.05% TFA; Mobile Phase B: 95:5, acetonitrile:water with 0.05% TFA; Gradient: 25-100% B over 10 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the product were combined and dried via centrifugal evaporation. The yield of 1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl) pyrrolidine-3-carboxylic acid was 16.3 mg, and its purity was 96%. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.21 (2H, d, J=8.35 Hz), 7.81 (2H, dd, J=8.02, 1.65 Hz), 7.69 (2H, d, J=8.35 Hz), 7.54-7.66 (3H, m), 5.10-5.22 (1H, m), 3.39-3.54 (4H, m), 3.24-3.27 (3H, m), 3.00-3.10 (2H, m), 2.23-2.57 (2H, m), 1.70-1.83 (2H, m), 1.05 (3H, t, J=7.36 Hz). MS (m+1)=489. HPLC Peak RT=2.08 minutes. (Analytical Method C). Purity=96%.

Provenance & Evidence