反应详情

To a solution of N-{5-[(2-amino-7-cyano-1,3-benzothiazol-6-yl)oxy]-2-fluorophenyl}-2,2,2-trifluoroacetamide (1.0 g, 2.52 mmol) in tetrahydrofuran (10 mL) were added pyridine (1.0 mL, 12.5 mmol) and cyclopropanecarbonyl chloride (395 μL, 4.35 mmol), and the mixture was stirred at room temperature for 10% hr. Pyridine (4.0 mL, 50 mmol) and cyclopropanecarbonyl chloride (100 μL, 1.10 mmol) were added, and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed successively with 1N hydrochloric acid (20 mL×2), 5% aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (410 mg, 38%) as a white powder.

1. stirringthe mixture was further stirred at room temperature for 1 hr
2. washwashed successively with 1N hydrochloric acid (20 mL×2), 5% aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationInsoluble material was filtered off
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20)
7. concentrationthe obtained solution was concentrated under reduced pressure
8. customThe residue was crystallized from ethyl acetate/n-hexane