Diisopropylethylamine → HCID 118522407, compound

Participants

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, 0.43 mmol) in DMF (10 mL) was added 4-(piperazin-1-yl)oxolan-2-one hydrochloride (250 mg, 1.21 mmol), HATU (247 mg, 0.65 mmol), DIEA (167 mg, 1.29 mmol). The resulting solution was stirred at room temperature overnight. Water (50 mL) was added. The resulting solution was extracted with DCM (×3) and the organic layers combined. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 8% MeOH in DCM. The crude product (80 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters)): Column, XSelect CSH Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 0.05% FA and MeCN (32.0% MeCN up to 60.0% in 10 min); Detector, 254/220. 37 mg product was obtained. This resulted in 36.7 mg (14%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(5-oxooxolan-3-yl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 28) [M+H]+=615.0, RT=0.99 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (d, 1H, J=6.9 Hz), 8.69-8.67 (m, 2H), 8.30 (s, 1H), 7.62 (dd, 1H, J=2.4, 9.0 Hz), 7.56 (s, 1H), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.2, 6.9 Hz), 7.02 (t, 1H, J=73.2 Hz), 5.24 (s, 2H), 4.44-4.38 (m, 1H), 4.26-4.18 (m, 1H), 3.49 (t, 4H, J=5.1 Hz), 3.40-3.37 (m, 1H), 2.78-2.68 (m, 1H), 2.60-2.55 (m, 1H), 2.47-2.35 (m, 4H).

Provenance & Evidence