Dimethylformamide → N-[3-[5-chloro-2-(difluoromethoxy)pyridin-3-yl]-1-[(5-oxooxolan-2-yl)methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

Participants

Reaction Steps

A 8-mL microwave tube was charged with N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (150 mg, 0.37 mmol), 5-(chloromethyl)oxolan-2-one (74.6 mg, 0.55 mmol), Cs2CO3 (242 mg, 0.74 mmol) in DMF (2 mL). The vessel was evacuated under vacuum and refilled with nitrogen 3 times. The final reaction mixture was irradiated with microwave radiation at 120° C. for 30 min. The resulting mixture was concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with ethyl acetate. 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 (39.0% up to 53.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 39.0% in 2 min); Detector, UV 254/220 nm. This resulted in 35.8 mg (19%) of N-[3-[5-chloro-2-(difluoromethoxy)pyridin-3-yl]-1-[(5-oxooxolan-2-yl)methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 20) [M+H]+=503.1, RT=1.65 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=1.5, 6.9 Hz), 8.68-8.66 (m, 2H), 8.38 (s, 1H), 7.63 (dd, 1H, J=2.7, 8.7 Hz), 7.61 (d, 1H, J=2.7 Hz), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.2, 6.9 Hz), 7.00 (t, 1H, J=73.2 Hz), 4.98-4.94 (m, 1H), 4.48 (d, 2H, J=5.1 Hz), 2.46-2.23 (m, 3H), 2.07-1.98 (m, 1H).

Provenance & Evidence