Hydrochloric Acid → 2-[(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]ethyl)(pyridin-3-ylmethyl)amino]acetic acid

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A mixture of ethyl 2-[(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]ethyl)(pyridin-3-ylmethyl)amino]acetate (180 mg, 0.29 mmol), ethanol (10 mL) and 1 N sodium hydroxide (2 mL) was stirred at room temperature for 30 min. The mixture was acidified with 1 HCl to pH 5. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18 silica gel; mobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=24:40 within 12 min; Detector, UV 254 nm. 8.6 mg product was obtained. This resulted in 8.6 mg (5%) of 2-[(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]ethyl)(pyridin-3-ylmethyl)amino]acetic acid formate as a white solid. LCMS (Method 20) [M+H]+=597.2, RT=2.72 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.72 (s, 1H), 9.34 (d, 1H, J=7.2 Hz), 8.69-8.68 (m, 2H), 8.39-8.37 (m, 3H), 7.63-7.60 (m, 2H), 7.51 (d, 1H, J=2.1 Hz), 7.43 (d, 1H, J=9.0 Hz), 7.32-7.22 (m, 2H), 6.99 (t, 1H, J=73.2 Hz), 4.33-4.22 (m, 2H), 3.83 (s, 2H), 3.334 (s, 2H), 3.15-3.07 (m, 2H).

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