Reaction Steps
To a solution of {3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid (200 mg, 0.35 mmol) in DMF (4 mL) was added 1-methyl-4-(piperidin-4-yl)piperazine hydrochloride (170 mg, 0.77 mmol), DIEA (134.4 mg, 1.04 mmol), HATU (160 mg, 0.42 mmol). The resulting solution was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum. 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 (25.0% up to 34.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 25.0% in 2 min); Detector, UV 254/220 nm. This resulted in 74.3 mg (32%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide formate as a off-white solid. LCMS (Method 20) [M+H]+=628.2, RT=2.20 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.36-9.34 (dd, 1H, J=1.6, 7.2 Hz), 8.69-8.68 (m, 2H), 8.31 (s, 1H), 7.63 (dd, 1H, J=2.4, 8.8 Hz), 7.55 (d, 1H, J=2.4 Hz), 7.46 (d, 1H, J=9.2 Hz), 7.29 (dd, 1H, J=4.0, 6.8 Hz), 7.09 (t, 1H, J=73.2 Hz), 5.25-5.21 (m, 2H), 4.36-4.29 (m, 1H), 3.98-3.79 (m, 1H), 3.10-3.00 (m, 1H), 2.69-2.51 (m, 1H), 2.49-2.32 (m, 8H), 2.18 (s, 3H), 1.91-1.86 (m, 2H), 1.47-1.41 (m, 1H), 1.39-1.25 (m, 1H).
