反应详情

温度

85 °C

Isopropyl alcohol (1 mL), 2-fluoro-3-pyridineboronic acid (49.8 mg), a 1 N sodium carbonate solution (354 μL) and bis(tri-tert-butylphosphine)palladium (0) (3.61 mg) were added to a solution of benzyl (±)-[(4aR*,8aS)-8a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[d][1,3]thiazin-2-yl]carbamate (35 mg) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 85° C. for 9.5 hours. The reaction solution was cooled to room temperature, and the solvent was evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography to obtain an intermediate. The resulting intermediate was dissolved in chloroform (2 mL). Iodotrimethylsilane (30 μL) was added, followed by stirring for 14 hours. The reaction solution was returned to room temperature, and a sodium bicarbonate solution was added to the reaction mixture. The mixture was diluted with ethyl acetate and sodium thiosulfate was added, followed by stirring for 30 minutes. The reaction mixture was extracted with ethyl acetate when it became transparent. The organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was sequentially purified by NH-pTLC and pTLC to obtain the title compound (2.0 mg).

1. temperatureThe reaction solution was cooled to room temperature
2. customthe solvent was evaporated under reduced pressure
3. customThe residue was purified by NH-silica gel column chromatography
4. customto obtain an intermediate
5. stirringby stirring for 14 hours
6. customwas returned to room temperature
7. additionwas added
8. stirringby stirring for 30 minutes
9. extractionThe reaction mixture was extracted with ethyl acetate when it
10. washThe organic layer was washed with brine
11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
12. customthe solvent was evaporated under reduced pressure
13. customThe residue was sequentially purified by NH-pTLC