反应详情

温度

140 °C

A mixture of 4-bromo-1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine (340 mg, 1.2 mmol), Et3N (320 μL, 2.3 mmol), 3-trifluoromethylbenzylamine (250 μL, 1.7 mmol), Pd[PhCN]2Cl2 (10 mg, 0.03 mmol), and 1,1-bis(diphenylphosphino)ferrocene (dppf) (0.04 g, 0.07 mmol) in toluene (15 mL) was sealed in a bomb with stifling, placed under 15 bars of carbon monoxide and warmed at 140° C. After 3 hours, the mixture was cooled to room temperature, returned to atmospheric pressure and opened. The reaction was monitored by HPLC-MS indicating the desired mass M+=415.43. The reaction was diluted with saturated aqueous ammonium chloride (50 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous ammonium chloride (3×20 mL), brine (20 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was dissolved in dichloromethane and purified by silica gel chromatography using a gradient of 0-30% EtOAc in dichloromethane to afford partially purified material. The material from the column was triturated with ether-hexanes to afford an off-white solid. This material was dissolved in dichloromethane and passed through a pad of silica gel (15 mL funnel) eluting with a gradient of 0-40% dichloromethane in EtOAc. The material from the pad was triturated with ether to afford the title compound, mp 172-173° C.

1. customwas sealed in a bomb with stifling
2. temperaturethe mixture was cooled to room temperature
3. extractionextracted with EtOAc (3×20 mL)
4. washThe combined organic layers were washed with saturated aqueous ammonium chloride (3×20 mL), brine (20 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe crude material was dissolved in dichloromethane
9. custompurified by silica gel chromatography
10. customto afford partially purified material
11. customThe material from the column was triturated with ether-hexanes
12. customto afford an off-white solid
13. washeluting with a gradient of 0-40% dichloromethane in EtOAc
14. customThe material from the pad was triturated with ether