反应详情

温度

40 °C

A solution of 13-bromo-4-iodo-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (10.0 g, 24.4 mmol) and acetamidine hydrochloride (2.63 g, 26.9 mmol) in triethylamine (6.90 mL, 49.4 mmol) and N,N-dimethylformamide (32.0 mL) was thoroughly degassed with N2. Palladium acetate (276 mg, 1.22 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.40 g, 2.44 mmol) were added and the solution was degassed with CO for 1 minute. A CO balloon was attached to the flask and the reaction was heated to 40° C. for 2 h. After being cooled to room temperature, the mixture was further treated with isopropylhydrazine hydrochloride (4.05 g, 36.6 mmol) and acetic acid (15 mL). The resulting mixture was heated again to 80° C. for 1 h. After cooling to room temperature, the mixture was diluted with H2O (400 mL). The resulting solid was collected by filtration and purified by silica gel chromatography using 15-50% EtOAc in petroleum ether as eluant to give the title compound (4.9 g, 50% yield). LCMS m/z [M+H]+ 406.0.

1. customthe solution was degassed with CO for 1 minute
2. temperatureAfter being cooled to room temperature
3. temperatureThe resulting mixture was heated again to 80° C. for 1 h
4. temperatureAfter cooling to room temperature
5. filtrationThe resulting solid was collected by filtration
6. custompurified by silica gel chromatography