反应详情

温度

70 °C

A solution of N-(4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-5-amine (0.67 g), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.067 mL) and methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxoheptanoate (0.8 g) in diethylaniline (5 mL) was stirred at 180° C. for 5 hr. The mixture was allowed to cool, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crudely purified by silica gel column chromatography. This was dissolved in tetrahydrofuran (4 mL). Tetrabutylammonium fluoride (2.5 mL) was added, and the mixture was stirred at 70° C. for 2 hr. The mixture was allowed to cool, ethyl acetate and saturated aqueous ammonium chloride solution were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. This was dissolved in acetonitrile (6 mL), 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one (1.0 g) was added, and the mixture was stirred for 3 hr. Ethyl acetate, water and sodium thiosulfate were added to the reaction mixture, and the mixture was stirred for 30 min. After stirring, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in ethanol (3 mL)-tetrahydrofuran (3 mL), and sodium borohydride (0.045 g) was added at 0° C. After stirring at 0° C. for 2 hr, ethyl acetate and then saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.48 g, 44%).

1. temperatureto cool
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with water and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated
6. customThe residue was crudely purified by silica gel column chromatography
7. dissolutionThis was dissolved in tetrahydrofuran (4 mL)
8. additionTetrabutylammonium fluoride (2.5 mL) was added
9. temperatureto cool
10. additionethyl acetate and saturated aqueous ammonium chloride solution were added
11. extractionthe mixture was extracted with ethyl acetate
12. washThe organic layer was washed with water and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated
15. dissolutionThis was dissolved in acetonitrile (6 mL)
16. addition1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one (1.0 g) was added
17. stirringthe mixture was stirred for 3 hr
18. additionEthyl acetate, water and sodium thiosulfate were added to the reaction mixture
19. stirringthe mixture was stirred for 30 min
20. stirringAfter stirring
21. extractionthe mixture was extracted with ethyl acetate
22. washThe organic layer was washed with saturated brine
23. dry with materialdried over anhydrous magnesium sulfate
24. customthe solvent was evaporated
25. dissolutionThe residue was dissolved in ethanol (3 mL)-tetrahydrofuran (3 mL), and sodium borohydride (0.045 g)
26. additionwas added at 0° C
27. stirringAfter stirring at 0° C. for 2 hr
28. additionethyl acetate and then saturated aqueous ammonium chloride solution were added
29. extractionThe mixture was extracted with ethyl acetate
30. washthe organic layer was washed with saturated brine
31. dry with materialdried over anhydrous magnesium sulfate
32. concentrationconcentrated
33. customThe residue was purified by silica gel column chromatography