Hydrochloric Acid → HCID 118522316, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)-4-methylpiperidine-4-carboxylate (500 mg, 0.83 mmol) in methanol (10 mL) was added a solution of potassium carbonate (700 mg, 5.06 mmol) in water (5 mL). The resulting solution was stirred at 60° C. overnight and acidified with 1 N HCl to pH 2. The solids were collected by filtration. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% FA and MeCN (30.0% MeCN up to 35.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 30.0% in 2 min); Detector, UV 254/220 nm. This resulted in 26.6 mg of 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)-4-methylpiperidine-4-carboxylic acid as a white solid. LCMS (Method 20) [M+H]+=588.2, RT=2.79 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 12.5 (br, 1H), 9.76 (s, 1H), 9.34 (d, 1H, J=6.8 Hz), 8.69-8.68 (m, 2H), 8.32 (s, 1H), 7.63 (dd, 1H, J=2.8, 8.8 Hz), 7.56 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.29 (dd, 1H, J=4.4, 7.2 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.28-5.18 (m, 2H), 3.96-3.93 (m, 1H), 3.74-3.70 (m, 1H), 3.26-3.23 (m, 1H), 3.01-2.95 (m, 1H), 1.98-1.93 (m, 2H), 1.46-1.30 (m, 2H), 1.18 (s, 3H).

Provenance & Evidence