Pyridine → 3-(1-cyano-1-methylethyl)-N-(5-{[2-(glycoloylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}-2-methylphenyl)benzamide

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Reaction Steps

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.

Provenance & Evidence