Hydrochloric Acid → HCID 118208537, compound

Participants

Reaction Conditions

Reaction Steps

Potassium cyanate (55.6 mg, 0.69 mmol), water (2.4 mL) and hydrochloric acid (2.0 M in water, 0.3 mL, 0.60 mmol) were added to a solution of racemic 4-((4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl)piperidin-4-ol (49 mg, 0.11 mmol) in THF (0.8 mL). The mixture was stirred at 55° C. for 3.5 hours. Additional hydrochloric acid standard solution (2.0 M in water, 0.15 mL, 0.30 mmol) and potassium cyanate (20.0 mg, 0.25 mmol) were added. The mixture was heated for another 2 hours then saturated sodium bicarbonate and EtOAc were added. The organic phase was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on reverse phase HPLC (ACN/water with 0.1% TFA modifier) to afford 4-hydroxy-4-((4-(3-methyl-5((4-(trifluoromethyl) pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)methyl) piperidine-1-carboxamide. MS ESI calc'd for C22H25F3N7O2 [M+H]+476. found 476. 1H NMR (500 MHz, CD3OD) δ 8.68 (d, J=4.9, 1H), 7.96 (s, 1H), 7.84 (s, 1H), 7.82 (s, 1H), 7.37 (s, 1H), 7.10 (s, 1H), 7.09 (d, J=4.9, 1H), 4.16 (s, 2H), 3.78 (d, J=13.2, 2H), 3.20 (t, J=11.3, 2H), 2.35 (s, 3H), 1.71-1.56 (m, 2H), 1.48 (d, J=13.1, 2H).

Provenance & Evidence