反应详情

To a solution of N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide (300 mg, 0.681 mmol) produced in Example A3(iv) in tetrahydrofuran (8.0 mL) were added a solution of 2-chloro-2-oxoethyl acetate (77 μL, 0.715 mmol) in tetrahydrofuran (2.0 mL) and triethylamine (141 μL, 1.02 mmol), and the mixture was stirred at room temperature for 30 min. To the reaction mixture were added 2-chloro-2-oxoethyl acetate (154 μL, 1.43 mmol) and triethylamine (290 μL, 2.10 mmol), and the mixture was further stirred at room temperature for 1.5 hr. To the reaction mixture was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at room temperature for 30 min and neutralized with 1N hydrochloric acid. The obtained mixture was extracted with ethyl acetate (100 mL×2). The combined organic layer was washed with saturated brine (100 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 (ethyl acetate/methanol=100/0→90/10), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether to give the title compound (220 mg, 65%) as a colorless solid.

1. stirringthe mixture was further stirred at room temperature for 1.5 hr
2. extractionThe obtained mixture was extracted with ethyl acetate (100 mL×2)
3. washThe combined organic layer was washed with saturated brine (100 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationThe insoluble material was filtered off
6. concentrationthe filtrate was concentrated under reduced pressure
7. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10)
8. concentrationthe obtained solution was concentrated under reduced pressure
9. customThe residue was triturated with ethyl acetate/diisopropyl ether