反应详情

温度

105 °C

1-(Azetidin-3-yl)-4-methylpiperazine (95 mg, 0.609 mmol), tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamate (300 mg, 0.609 mmol), cesium carbonate (397 mg, 1,218 mmol), Pd2(dba)3 (27.9 mg, 0.030 mmol) and BINAP (56.9 mg, 0.091 mmol) were suspended in toluene (6088 μl) at room temperature. The reaction was degassed under vacuum and backfilled with N2 (4 times), and then heated to 105° C. for 4 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through celite and concentrated. Column chromatography (24 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution) afforded tert-butyl (2-chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)(4-methoxybenzyl)carbamate (213.1 mg).

1. customThe reaction was degassed under vacuum
2. temperatureAfter cooling to room temperature
3. additionthe reaction mixture was diluted with EtOAc
4. filtrationfiltered through celite and
5. concentrationconcentrated
6. washColumn chromatography (24 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution)