反应详情

To a solution of N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.451 mmol) produced in Example C33(iv) in pyridine (4.0 mL) was added 2-chloro-2-oxoethyl acetate (78 μL, 0.722 mmol), and the mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL) was added, and the mixture was washed with water (50 mL), 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 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 dissolved in methanol (4.0 mL), 1N aqueous sodium hydroxide solution (4.0 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, neutralized with 1N hydrochloric acid, and extracted with ethyl acetate (100 ml×2). 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 (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/hexane to give the title compound (112 mg, 50%) as a colorless solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL)
2. additionwas added
3. washthe mixture was washed with water (50 mL), 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 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. dissolutionThe obtained residue was dissolved in methanol (4.0 mL)
8. addition1N aqueous sodium hydroxide solution (4.0 mL) was added
9. stirringthe mixture was stirred at room temperature for 1 hr
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. extractionextracted with ethyl acetate (100 ml×2)
12. washThe organic layer was washed with water (100 mL) and saturated brine (100 mL)
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationThe insoluble material was filtered off
15. concentrationthe filtrate was concentrated under reduced pressure
16. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
17. concentrationthe obtained solution was concentrated under reduced pressure
18. customThe residue was triturated with ethyl acetate/hexane