反应详情

A stirred suspension of 4-bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluorobenzenesulfonamide (3.4 g, 7.2 mmol) in 1,2-dimethoxyethane (80 ml) was treated with a solution of sodium carbonate (3.8 g, 36 mmol) in water (20 ml). (5-Methyl-2-furanyl)boronic acid (1.4 g, 10.8 mmol) and bis(triphenylphosphine)palladium(II) chloride (10 mg, 0.2 mol %) were added with some water and the mixture was stirred at reflux for 3 hours. Additional (5-methyl-2-furanyl)boronic acid (420 mg, 3.3 mmol) was added and the mixture was heated at reflux for a further 30 minutes. After cooling to room temperature, ethyl acetate (50 ml), water (50 ml) and charcoal (3 g) were added and the mixture was stirred at room temperature for 30 minutes. The mixture was filtered through celite, the ethyl acetate layer separated and the aqueous layer was further extracted with ethyl acetate. The ethyl acetate extracts were combined washed with water and brine dried over anhydrous sodium sulfate and evaporated. The residue was purified by chromatography on a 100 g column eluting with 1:40 to 1:10 2M ammonia in methanol: dichloromethane. Residue was then triturated in ether, dissolved in ether/pentane and evaporated. Residue was then triturated in pentane, washed in pentane, air dried and then dried at 50° C. under argon and high vacuum to give the title compound (E248). MS (ES+) m/e 474 [M+H]+.

1. temperatureat reflux for 3 hours
2. temperaturethe mixture was heated
3. temperatureat reflux for a further 30 minutes
4. stirringthe mixture was stirred at room temperature for 30 minutes
5. filtrationThe mixture was filtered through celite
6. customthe ethyl acetate layer separated
7. extractionthe aqueous layer was further extracted with ethyl acetate
8. washThe ethyl acetate extracts were combined washed with water and brine
9. dry with materialdried over anhydrous sodium sulfate
10. customevaporated
11. customThe residue was purified by chromatography on a 100 g column
12. washeluting with 1:40 to 1:10 2M ammonia in methanol
13. customResidue was then triturated in ether
14. dissolutiondissolved in ether/pentane
15. customevaporated
16. customResidue was then triturated in pentane
17. washwashed in pentane
18. customair dried
19. customdried at 50° C. under argon