反应详情

温度

60 °C

To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (320 mg, 0.66 mmol) in ethanol (20 mL) was added 50% ethyl 2-oxoacetate hydrate (268 mg, 1.31 mmol), AcOH (0.1 mL, 1.75 mmol) and NaBH3CN (83 mg, 1.32 mmol). The resulting solution was stirred at 60° C. for 12 h and concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 2% MeOH in DCM. The crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=55:75 within 12 min; Detector, UV 254 nm. 25.3 mg product was obtained. This resulted in 25.3 mg (7%) of ethyl 2-(4-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]piperidin-1-yl)acetate as an off-white solid. LCMS (Method 20) [M+H]+=574.2, RT=2.70 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.36 (s, 1H), 8.69-8.67 (m, 2H), 8.36 (s, 1H), 7.63-7.25 (m, 5H), 4.25-4.23 (m, 1H), 4.13-4.10 (m, 2H), 3.28-3.27 (m, 2H), 3.01-2.98 (m, 2H), 2.42-2.40 (m, 2H), 2.12-1.98 (m, 4H), 1.25-1.20 (m, 3H).

1. concentrationconcentrated under vacuum
2. customThe crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
3. waitmobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=55:75 within 12 min