反应详情

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide (200 mg, 0.453 mmol) produced in Example C29(iv) in pyridine (4.0 mL) was added 2-chloro-2-oxoethyl acetate (73 μL, 0.68 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with methanol (2.0 mL). 1N Aqueous sodium hydroxide solution (2.0 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added to neutralize the residue, and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with water (100 mL) and 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→80/20), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/tetrahydrofuran/hexane to give the title compound (104 mg, 46%) as a colorless powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionthe residue was diluted with methanol (2.0 mL)
3. addition1N Aqueous sodium hydroxide solution (2.0 mL) was added
4. stirringthe mixture was stirred at room temperature for 1 hr
5. concentrationThe reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid
6. additionwas added
7. extractionthe mixture was extracted with ethyl acetate (100 mL)
8. washThe organic layer was washed with water (100 mL) and saturated brine (100 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 (ethyl acetate/methanol=100/0→80/20)
13. concentrationthe obtained solution was concentrated under reduced pressure
14. customThe residue was crystallized from ethyl acetate/tetrahydrofuran/hexane