Nipecotic Acid → 1-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

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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 piperidine-3-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 18 mg 1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.16 (2H, dd, J=8.35, 1.98 Hz), 7.83 (2H, dd, J=7.91, 1.54 Hz), 7.56-7.75 (5H, m), 5.13-5.39 (1H, m), 4.11-4.31 (2H, m), 3.21-3.41 (3H, m), 2.96-3.05 (2H, m), 2.70-2.85 (1H, m), 1.75-2.14 (4H, m), 1.62-1.77 (2H, m), 1.36-1.56 (1H, m), 0.98 (3H, t, J=7.36 Hz). MS (m+1)=503. HPLC Peak RT=3.35 minutes (Analytical Method A). Purity=90%.

Provenance & Evidence