Reaction Steps
To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(methylamino)piperidin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (100 mg, 0.18 mmol) in DMF (4 mL) was added DIEA (46 mg, 0.36 mmol), 4-(bromomethyl)-2,5-dihydrofuran-2-one (63 mg, 0.36 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 (40.0% up to 48.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 40.0% in 2 min); Detector, UV 254/220 nm. This resulted in 15.5 mg (13%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(4-[methyl[(5-oxo-2,5-dihydrofuran-3-yl)methyl]amino]piperidin-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 20) [M+H]+=655.2, RT=1.91 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=1.6, 7.2 Hz), 8.69-8.68 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.8, 8.8 Hz), 7.55 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=9.2 Hz), 7.28 (dd, 1H, J=4.4, 7.2 Hz), 7.09 (t, 1H, J=73.2 Hz), 6.04 (s, 1H), 5.24-5.22 (m, 2H), 4.86 (d, 2H, J=1.2 Hz), 4.39-3.37 (m, 1H), 4.01-3.93 (m, 1H), 3.47 (s, 2H), 3.10-3.01 (m, 1H), 2.67-2.62 (m, 2H), 2.20 (s, 3H), 1.76-1.73 (m, 2H), 1.56-1.42 (m, 1H), 1.40-1.29 (m, 1H).
