反应详情

To a solution of 1-methyl-1H-pyrazole-3-carboxylic acid (115 mg, 0.92 mmol) in tetrahydrofuran (4.0 mL) were added N,N-dimethylformamide (20 μL, 0.26 mmol) and oxalyl chloride (80 μL, 0.92 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol) in N,N-dimethylacetamide (4.0 mL), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure and ethanol (10 mL) was added to the residue. The mixture was stirred with heating at 75° C. and cooled to room temperature, and the precipitate was collected by filtration to give the title compound (144 mg, 54%) as a white powder.

1. stirringthe mixture was stirred at room temperature for 2 hr
2. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
3. washwashed with saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltrated
6. customThe solvent was evaporated under reduced pressure and ethanol (10 mL)
7. additionwas added to the residue
8. stirringThe mixture was stirred
9. temperaturewith heating at 75° C.
10. temperaturecooled to room temperature
11. filtrationthe precipitate was collected by filtration