反应详情

Potassium thiocyanate (2.96 g, 30.5 mmol) was suspended in acetic acid (20 mL), and the suspension was stirred at room temperature for 10 min. To the obtained solution was added N-{5-[(5-aminopyridin-2-yl)(methyl)amino]-2-fluorophenyl}-2,2,2-trifluoroacetamide (2.0 g, 6.96 mmol), and the mixture was further stirred at room temperature for 10 min. To the obtained solution was slowly added dropwise a solution of bromine (1.17 g, 7.30 mmol) in acetic acid (10 mL). After the completion of the dropwise addition, the mixture was stirred at room temperature for 20 hr. The yielded black insoluble material was filtered off, and washed with acetic acid. The filtrate and the washing solution were combined, and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (100 mL), and the suspension was washed with saturated aqueous sodium hydrogen carbonate solution (70 mL) and saturated brine (100 mL), and dried over anhydrous magnesium 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=40/60→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (1.00 g, 43%) as a colorless powder.

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 20 hr
4. filtrationThe yielded black insoluble material was filtered off
5. washwashed with acetic acid
6. concentrationconcentrated under reduced pressure
7. washthe suspension was washed with saturated aqueous sodium hydrogen carbonate solution (70 mL) and saturated brine (100 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationThe insoluble material was filtered off
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→0/100)
12. concentrationthe obtained solution was concentrated under reduced pressure
13. customThe residue was crystallized from ethyl acetate/hexane