反应详情

温度

80 °C

To a mixture of (S)-piperidine-3-carboxylic acid, HCl (29.5 mg, 0.178 mmol) in NMP (2 mL) was added cesium carbonate (97 mg, 0.297 mmol). The reaction mixture was stirred for 30 minutes. Next, 3-(4-(2-bromoethyl)phenyl)-5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazole (26 mg, 0.059 mmol) and sodium iodide (2 mg, 0.013 mmol) were added. The reaction mixture was heated at 80° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 20 mL/min. The resulting material was 4mg of (S)-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenethyl)piperidine-3-carboxylic acid as a TFA salt. MS (m+1)=487. HPLC Peak RT=3.67 minutes (Analytical Method A). 1H NMR (400 MHz, MeOH-d3) δ ppm 8.03 (2H, m), 7.71 (2H, dd, J=7.91, 1.54 Hz), 7.46-7.56 (3H, m), 7.39 (2H, m, J=8.57 Hz), 4.26-4.49 (2H, m), 3.27 (1H, dd, J=12.96, 3.95 Hz), 3.05-3.15 (3H, m), 2.86-3.04 (5H, m), 2.65-2.81 (1H, m), 1.89-2.03 (1H, m), 1.57-1.77 (5H, m), 0.95 (3H, t, J=7.36 Hz).

1. filtrationThe reaction mixture was filtered
2. custompurified by HPLC
3. custom25 minute