3-Hydroxypiperidine → HCID 89907350, compound

Participants

Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Example 35, 1 g, 2.53 mmol), 3-hydroxypiperidine (307 mg, 3.03 mmol) and DIPEA (883 μL, 5.06 mmol) in iPrOH (2528 μL) were added to a MW vial and subjected to MW irradiation at 140° C. for 60 min. The vial was cooled to RT and the RM was evaporated to dryness under reduced pressure, treated with 0.5 M HCl (25 mL) and extracted with EtOAc. The combined extracts were washed with HCl 0.5 M, brine, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (Silica gel column, 24 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1)), from 15% to 60% EtOAc-EtOH+0.1% NH4OH (9:1)) to afford the title compound as a white foam. UPLC-MS (condition 1) tR=2.89 min, m/z=460.0-462.0 [M+H]+, m/z=458.0-460.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.27-1.45 (m, 1H) 1.46-1.66 (m, 1H) 1.73-1.87 (m, 1H) 1.89-2.01 (m, 1H) 2.74 (dd, J=12.23, 9.29 Hz, 1H) 2.92 (t, J=10.64 Hz, 1H) 3.56-3.70 (m, 1H) 3.70-3.81 (m, 1H) 3.91 (dd, J=12.10, 3.30 Hz, 1H) 4.87 (d, J=4.40 Hz, 1H) 7.36 (d, J=8.56 Hz, 2H) 7.85 (d, J=9.05 Hz, 2H) 8.42 (d, J=1.96 Hz, 1H) 8.76 (d, J=1.96 Hz, 1H) 10.37 (s, 1H).

Provenance & Evidence