反应详情

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide (313 mg, 683 μmol) produced in Example C1(vii) in pyridine (10 mL) were added 2-chloro-2-oxoethyl acetate (254 mg, 1.86 mmol) and N,N-dimethylpyridine-4-amine (85 mg, 696 μmol), and the mixture was stirred at room temperature for 2 hr. Methanol (10 mL) was added to the reaction solution, the mixture was stirred for 1 hr, conc. aqueous ammonia (4 mL) was added, and the mixture was further stirred for 1 hr. The reaction solution was concentrated under reduced pressure, and residue was dissolved in tetrahydrofuran (10 mL) and ethyl acetate (50 mL). The solution was washed with 0.1N hydrochloric acid (50 mL), saturated aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous magnesium 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 recrystallized from a mixture of ethyl acetate and diisopropyl ether to give the title compound (125 mg, 35%) as colorless crystals.

1. stirringthe mixture was stirred for 1 hr
2. stirringthe mixture was further stirred for 1 hr
3. concentrationThe reaction solution was concentrated under reduced pressure, and residue
4. dissolutionwas dissolved in tetrahydrofuran (10 mL)
5. washThe solution was washed with 0.1N hydrochloric acid (50 mL), saturated aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationThe insoluble material was filtered off
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20)
10. customrecrystallized from a mixture of ethyl acetate and diisopropyl ether