反应详情

A suspension of 2-chloronicotinic acid (0.15 g), 4-(4-fluorobenzyl)-4-hydroxypiperidine hydrochloride (0.26 g), HATU (0.43 g) and triethylamine (0.66 mL) in DMF (5 mL) was stirred at room temperature for 4 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in DME (5.0 mL), and pyridine-4-boronic acid (0.13 g), sodium carbonate (0.20 g), tetrakis(triphenylphosphine)palladium(0) (0.055 g) and water (1.0 mL) were added thereto, and the mixture was stirred at 140° C. for 1 hr under microwave irradiation. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and then purified by preparative HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)), and the obtained fraction was concentrated under reduced pressure. To the residue was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (0.21 g).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe residue was dissolved in DME (5.0 mL)
6. additionpyridine-4-boronic acid (0.13 g), sodium carbonate (0.20 g), tetrakis(triphenylphosphine)palladium(0) (0.055 g) and water (1.0 mL) were added
7. stirringthe mixture was stirred at 140° C. for 1 hr under microwave irradiation
8. additionThe reaction mixture was diluted with water
9. extractionthe mixture was extracted with ethyl acetate
10. washThe extract was washed with saturated brine
11. dry with materialdried over anhydrous sodium sulfate
12. customThe solvent was evaporated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
14. custompurified by preparative HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA))
15. concentrationthe obtained fraction was concentrated under reduced pressure
16. additionTo the residue was added saturated aqueous sodium hydrogen carbonate solution
17. extractionthe mixture was extracted with ethyl acetate
18. dry with materialThe extract was dried over anhydrous sodium sulfate
19. customthe solvent was evaporated under reduced pressure