反应详情

Potassium thiocyanate (7.00 g, 72 mmol) was suspended in acetic acid (120 mL) and the mixture was stirred at room temperature for 10 min. To the obtained solution was added a solution of N-[5-(4-aminophenoxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide (6.90 g, 18 mmol) in acetic acid (120 mL), and the mixture was further stirred at room temperature for 30 min. To the obtained solution was added dropwise slowly a solution of bromine (3.60 g, 22.5 mmol) in acetic acid (80 mL) and, after the completion of the dropwise addition, the mixture was further stirred at room temperature for 12 hr. The resulting yellow insoluble material was filtered off and washed with acetic acid. The filtrate and the washing were combined and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (400 mL), washed with 5% aqueous sodium hydrogencarbonate solution (200 mL×2) and saturated brine (200 mL), successively, 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=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (6.27 g, 79%) as a pale-yellow amorphous substance.

1. stirringthe mixture was further stirred at room temperature for 30 min
2. additionafter the completion of the dropwise addition
3. stirringthe mixture was further stirred at room temperature for 12 hr
4. filtrationThe resulting yellow insoluble material was filtered off
5. washwashed with acetic acid
6. concentrationconcentrated under reduced pressure
7. washwashed with 5% aqueous sodium hydrogencarbonate solution (200 mL×2) and saturated brine (200 mL)
8. dry with materialsuccessively, and dried over anhydrous sodium 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=50/50→0/100)
12. concentrationthe obtained solution was concentrated under reduced pressure