Acetic Acid → 4-Piperidinecarboxylic acid

Participants

Reaction Steps

Sodium cyanoborohydride (17.3 mg; 0.275 mmol) was added to a solution of 4-(5-(1-cyclohexyl-5-(tetrahydrofuran-2-yl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (99 mg; 0.25 mmol), obtained from step 2, and isonipecotic acid (64.6 mg; 0.50 mmol) in methanol (3 mL) and acetic acid (45 μL; 0.75 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the crude material purified by reverse phase preparative HPLC to give Example 125 as a white solid. 1H NMR: (DMSO-d6, 400 MHz) δ 8.20 (1 H, s), 8.04 (2 H, d, J=8.0 Hz), 7.54 (2 H, d, J=8.0 Hz), 5.72 (1 H, dd, J=9.5, 6.9 Hz), 4.47 (1 H, d, J=8.2 Hz), 4.16 (1 H, q, J=7.5 Hz), 3.97 (1 H, q, J=7.5 Hz), 3.57 (2 H, s), 2.79 (2 H, d, J=10.9 Hz), 2.55-2.50 (1 H, m), 2.26-2.13 (3 H, m), 2.11-1.78 (11 H, m), 1.72 (1 H, d, J=12.5 Hz), 1.65-1.52 (2 H, m), 1.50-1.35 (2 H, m), 1.35 (1 H, m). LC/MS: 506 (M+H)+. HPLC (Method B) Rt 2.77 min (Purity: 99.2%).

Provenance & Evidence