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, 0.452 mmol) in pyridine (4.0 mL) was added cyclopropanecarbonyl chloride (90 μL, 0.994 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methanol (2.0 mL)/tetrahydrofuran (2.0 mL)/water (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 neutralized with 1N hydrochloric acid, diluted with ethyl acetate (100 mL), washed with water (50 mL) and saturated brine (50 mL), successively, 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 silica gel column chromatography (hexane/ethyl acetate=70/30→0/100), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether to give the title compound (129 mg, 56%) as a colorless amorphous substance.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in methanol (2.0 mL)/tetrahydrofuran (2.0 mL)/water (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. additiondiluted with ethyl acetate (100 mL)
6. washwashed with water (50 mL) and saturated brine (50 mL)
7. dry with materialsuccessively, and dried over anhydrous sodium sulfate
8. filtrationThe insoluble material was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30→0/100)
11. concentrationthe obtained solution was concentrated under reduced pressure
12. customThe residue was triturated with ethyl acetate/diisopropyl ether