反应详情

To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridazin-3-ylamine (1.0 g, 3.5 mmol) in THF (15 ml) was added triethylamine (0.59 mL, 4.3 mmol). The mixture was cooled in an ice bath and a solution of 4-chlorobutyryl chloride (0.48 mL, 4.3 mmol) in THF (5 mL) was added dropwise. After stirring for 1 h at room temperature the precipitate was filtered and the organic phase was evaporated. The residue was dissolved in methanol (20 mL), sodium bicarbonate (1 spatula) was added and the mixture was stirred at room temperature for 1 h. The solvent was evaporated and the residue was extracted (dichloromethane/water). Then the organic phase was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane/ethyl acetate=100:0 to 60:40) afforded the title compound (740 mg, 54%) (as the least polar component of two formed in the reaction) which was obtained as a white solid. MS: m/e=387.3 [M+H]+.

1. temperatureThe mixture was cooled in an ice bath
2. filtrationwas filtered
3. customthe organic phase was evaporated
4. dissolutionThe residue was dissolved in methanol (20 mL)
5. additionsodium bicarbonate (1 spatula) was added
6. stirringthe mixture was stirred at room temperature for 1 h
7. customThe solvent was evaporated
8. extractionthe residue was extracted (dichloromethane/water)
9. dry with materialThen the organic phase was dried over sodium sulfate
10. concentrationconcentrated
11. customPurification by chromatography (SiO2, heptane/ethyl acetate=100:0 to 60:40)