反应详情

Potassium thiocyanate (2.02 g, 20.8 mmol) was suspended in acetic acid (40 mL), and the mixture was stirred at room temperature for 10 min. A solution of N-{5-[(5-aminopyridin-2-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (2.0 g, 5.20 mmol) in acetic acid (40 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 10 min. A solution of bromine (914 mg, 5.72 mmol) in acetic acid (28 mL) was slowly added dropwise to the obtained solution. After the completion of the dropwise addition, the mixture was stirred at room temperature for 4 hr. The yielded yellow insoluble material was filtered off, and washed with acetic acid. The filtrate and washing solution were combined, and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (300 mL), and the suspension was washed with 5% aqueous sodium hydrogen carbonate solution (300 mL), water (300 mL) and saturated brine (300 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (2.20 g, 95%) as a colorless amorphous substance.

1. stirringthe mixture was further stirred at room temperature for 10 min
2. additionAfter the completion of the dropwise addition
3. stirringthe mixture was stirred at room temperature for 4 hr
4. filtrationThe yielded yellow insoluble material was filtered off
5. washwashed with acetic acid
6. washThe filtrate and washing solution
7. concentrationconcentrated under reduced pressure
8. washthe suspension was washed with 5% aqueous sodium hydrogen carbonate solution (300 mL), water (300 mL) and saturated brine (300 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationThe insoluble material was filtered off
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100)
13. concentrationthe obtained solution was concentrated under reduced pressure