反应详情

A mixture of (R/S) tert-butyl N-[2-([[3-iodo-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl](methyl)amino)ethyl]carbamate (200 mg, 0.43 mmol, 1.00 equiv), K3PO4.3H2O (439 mg, 1.65 mmol, 3.83 equiv), 1-(tert-butoxycarbonyl)-1H-indazol-5-ylboronic acid (300 mg, 1.14 mmol, 2.66 equiv) and Pd(dppf)Cl2.CH2Cl2 (135 mg) in ethylene glycol dimethyl ether (20 mL) and water (1 mL) was stirred under nitrogen at 85° C. for 3 h. The resulting mixture was cooled to room temperature and concentrated under vacuum. The residue was dissolved in 5 mL of methanol and 5 mL of DMSO and then purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to give 50 mg (21%) of (R/S) tert-butyl 5-(4-(((2-(tert-butoxycarbonylamino)ethyl)amino)methyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)-1H-indazole-1-carboxylate as a colorless oil. LCMS (method A, ESI): RT=1.34 min, m/z=555.1 [M+H].

1. concentrationconcentrated under vacuum
2. dissolutionThe residue was dissolved in 5 mL of methanol
3. custom5 mL of DMSO and then purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters))
4. waitdown to 18% in 2 min)