反应详情

To a mixture of 3-(imidazo[1,2-b]pyridazin-6-yloxy)benzoic acid (128 mg, 0.50 mmol), aniline (56 mg, 0.60 mmol), 1-hydroxybenzotriazole hydrate (92 mg, 0.60 mmol) and N,N-dimethylformamide (5 mL) were added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (192 mg, 1.00 mmol) and triethylamine (0.209 mL, 1.50 mmol), and the mixture was stirred at room temperature for 18 hr. 1N Aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→75/25) and precipitated from ethyl acetate to give the title compound (122 mg, 0.37 mmol, yield 74%) as a white solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated brine
3. concentrationconcentrated under reduced pressure
4. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→75/25)
5. customprecipitated from ethyl acetate