1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 50923276, compound

Participants

Reaction Conditions

Reaction Steps

To (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (45.4 mg, 0.198 mmol) was added TFA/DCM (1:1). The mixture was stirred for 1 hour and solvent was removed solvent in vacuo, followed by chasing once with DCM. The resulting mixture was dried in vacuo. This crude residue was dissolved in DMSO (2 mL) and DBU (0.060 mL, 0.396 mmol) was added. After 5 minutes, 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) was added. 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); 20-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 6 mg of (3R)-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, MeOH-d3) δ ppm 8.21 (2H, d, J=7.91 Hz), 7.71 (2H, dd, J=8.02, 1.65 Hz), 7.47-7.56 (5H, m), 4.46 (1H, br. s.), 4.10 (2H, d, J=6.37 Hz), 3.25-3.61 (2H, m), 2.92-3.03 (3H, m), 2.91 (2H, br. s.), 2.01-2.27 (1H, m), 1.81-2.00 (3H, m), 1.60-1.76 (2H, m, J=7.61, 7.61, 7.61, 7.61, 7.36 Hz), 1.20-1.59 (1H, m), 0.95 (3H, t, J=7.36 Hz). MS (m+1)=503. HPLC Peak RT=3.32 minutes (Analytical Method A). Purity=96%.

Provenance & Evidence