反应详情

温度

80 °C

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 piperidine-2-carboxylic acid (25.6 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 reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 19 mg of 1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-2-carboxylic acid as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.10 (2H, dd, J=8.35, 2.20 Hz), 7.77 (2H, dd, J=7.91, 1.54 Hz), 7.52-7.64 (5H, m), 5.20 (1H, d, J=18.24 Hz), 3.67 (2H, br. s.), 2.87-3.01 (2H, m), 1.99-2.21 (2H, m), 1.69-1.88 (4H, m), 1.64 (2H, dq, J=15.24, 7.59 Hz), 1.39-1.56 (3H, m), 0.92 (3H, t, J=7.36 Hz). MS (m+1)=503. HPLC Peak RT=3.47 minutes (Analytical Method A). Purity=88%.

1. filtrationThe reaction mixture was filtered
2. custompurified by HPLC
3. custom25 minute
4. customIsolated fractions with correct mass were freeze-dried overnight