反应详情

N-[3-Cyano-4-(4-hydroxypiperidin-1-yl)phenyl]benzo[b]thiophene-2-carboxamide (2.0 g) obtained in Example 12, tertiary butyldimethylsilyl chloride (0.9 g) and imidazole (0.4 g) were added to dimethylformamide (20 ml) and the mixture was stirred at room temperature for 12 hr. Then the reaction mixture was treated with water and the organic layer was extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogencarbonate solution and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in dimethylformamide. Under ice-cooling, sodium hydride (60% contained, 0.2 g) (was added and the mixture was stirred for 1 hr and methyl iodide (0.6 g) was added. The mixture was further stirred for 1 hr. The reaction mixture was treated with water and the organic layer was extracted with toluene. The extract was washed with water and the solvent was evaporated under reduced pressure. To the residue were added tetrabutylammonium fluoride (0.93 g) and tetrahydrofuran(15 ml) and the mixture was stirred at 60° C. for 4.5 hr. Then the solvent was evaporated and the residue was separated and purified by silica gel column chromatography (mobile phase: chloroform) to give the title compound (0.8 g). melting point: 211-212° C.

1. extractionthe organic layer was extracted with ethyl acetate
2. washThe extract was washed with aqueous sodium hydrogencarbonate solution
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionthe obtained residue was dissolved in dimethylformamide
6. temperatureUnder ice-cooling
7. additionsodium hydride (60% contained, 0.2 g) (was added
8. stirringthe mixture was stirred for 1 hr
9. additionmethyl iodide (0.6 g) was added
10. stirringThe mixture was further stirred for 1 hr
11. additionThe reaction mixture was treated with water
12. extractionthe organic layer was extracted with toluene
13. washThe extract was washed with water
14. customthe solvent was evaporated under reduced pressure
15. additionTo the residue were added tetrabutylammonium fluoride (0.93 g) and tetrahydrofuran(15 ml)
16. stirringthe mixture was stirred at 60° C. for 4.5 hr
17. customThen the solvent was evaporated
18. customthe residue was separated
19. custompurified by silica gel column chromatography (mobile phase: chloroform)