反应详情

To a suspension of calcium chloride (135 mg, 1.1 mmol) in tetrahydrofuran/ethanol (2/1, 1 mL) was added a solution of sodium borohydride (92 mg, 2.2 mmol) and methyl 2-({[6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]amino}carbonyl)cyclopropanecarboxylate (180 mg, 0.37 mmol) in tetrahydrofuran/ethanol (2/1, 1 mL), and the mixture was stirred at room temperature for 18 hr. Saturated aqueous ammonium chloride solution and ethyl acetate were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (×3). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0, and then methanol/ethyl acetate=0/100→5/95) to give the title compound (35 mg, 20%) as a white solid.

1. extractionthe aqueous layer was extracted with ethyl acetate (×3)
2. washCombined organic layer was washed with saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltrated
5. concentrationThe filtrate was concentrated under reduced pressure
6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0