反应详情

Triethylamine (208 μl, 1.89 mmol) and thionyl chloride (138 μl, 1.89 mmol) were added to a solution of (3,6-dichloropyridin-2-yl) (pyridin-4-yl)methanol (161 mg, 0.631 mmol) in methylene chloride (10 ml). After stirring at room temperature for 4 hours, the reaction mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue thus obtained. The resulting mixture was washed successively with a saturated aqueous solution of sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue thus obtained was dissolved in acetonitrile (10 ml), followed by the addition of 4-chlorobenzenethiol (137 mg, 0.947 mmol) and potassium carbonate (131 mg, 0.947 mmol). Under nitrogen atmosphere, the reaction mixture was stirred at room temperature for 2 days and then at 60° C. for 4 days. The reaction mixture was cooled to room temperature and then, concentrated under reduced pressure. Ethyl acetate was added to the residue thus obtained. The mixture was washed successively with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash chromatography. A fraction obtained from the eluate with 40% ethyl acetate/hexane was concentrated under reduced pressure. The residue thus obtained was dissolved in methanol (10 ml) and to the resulting solution, were added a 30% aqueous hydrogen peroxide solution and hexaammonium heptamolybdate tetrahydrate (73 mg). The reaction mixture was stirred at room temperature for 5 hours. Methanol was distilled off under reduced pressure. A saturated aqueous solution of sodium bicarbonate was added to the concentrated solution thus obtained, followed by extraction with methylene chloride. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash chromatography. A fraction obtained from the eluate with methanol:methylene chloride (=1:80) was concentrated under reduced pressure, whereby the title compound (49 mg, 0.118 mmol, 19%) was obtained as a white solid.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. additionEthyl acetate was added to the residue
3. customthus obtained
4. washThe resulting mixture was washed successively with a saturated aqueous solution of sodium bicarbonate and brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationAfter filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe residue thus obtained
9. stirringUnder nitrogen atmosphere, the reaction mixture was stirred at room temperature for 2 days
10. waitat 60° C. for 4 days
11. temperatureThe reaction mixture was cooled to room temperature
12. concentrationconcentrated under reduced pressure
13. additionEthyl acetate was added to the residue
14. customthus obtained
15. washThe mixture was washed successively with water and brine
16. dry with materialdried over anhydrous sodium sulfate
17. filtrationfiltered
18. concentrationThe filtrate was concentrated under reduced pressure
19. customThe residue thus obtained
20. concentrationwas concentrated under reduced pressure
21. customThe residue thus obtained
22. stirringThe reaction mixture was stirred at room temperature for 5 hours
23. distillationMethanol was distilled off under reduced pressure
24. additionA saturated aqueous solution of sodium bicarbonate was added to the concentrated solution
25. customthus obtained
26. extractionfollowed by extraction with methylene chloride
27. dry with materialThe organic layer was dried over anhydrous sodium sulfate
28. filtrationfiltered
29. concentrationThe filtrate was concentrated under reduced pressure
30. customThe residue thus obtained