Hydrochloric Acid → HCID 118045017, compound

Participants

Reaction Steps

A mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2, 80 mg, 0.166 mmol), piperidin-4-ol (33.5 mg, 0.331 mmol), DIPEA (0.116 mL, 0.662 mmol) and iPrOH (0.331 mL) was added to a vial, which was sealed and subjected to MW irradiation at 140° C. for 1 h. Aq. 37% HCl (202 μL, 2.46 mmol) and MeOH (1 mL) was added and the mixture was stirred at RT. The RM was treated with sat. aq. NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by preparative SFC (Column DEAP, from 21% to 26% in 10 min.) to afford the title product as a white solid. UPLC-MS (Condition 3) tR=0.95 min, m/z=464.1 [M+H]+, m/z=508.0 [M+formic acid-H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.49 (m, 2H) 1.73 (d, J=10.27 Hz, 2H) 2.87 (t, J=10.51 Hz, 2H) 3.50 (d, J=13.08 Hz, 2H) 3.62 (dd, J=8.19, 4.16 Hz, 1H) 4.67 (d, J=4.03 Hz, 1H) 6.54-6.70 (m, 1H) 7.34 (d, J=8.80 Hz, 2H) 7.77 (m, J=1.22 Hz, 2H) 7.88 (d, J=9.05 Hz, 2H) 8.27 (m, J=2.08 Hz, 1H) 8.69-8.78 (m, 1H) 10.31-10.44 (m, 1H) 12.96-13.21 (m, 1H).

Provenance & Evidence