Thionyl Chloride → 2-cyclopropyl-N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide

To a solution of cyclopropylacetic acid (441 mg, 4.4 mmol) in tetrahydrofuran (8.0 mL) were added N,N-dimethylformamide (1 drop) and thionyl chloride (0.32 mL, 4.4 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and dissolved in N,N-dimethylacetamide (2.0 mL). To a solution of 6-iodoimidazo[1,2-b]pyridazin-2-amine (1.04 g, 4.0 mmol) in N,N-dimethylacetamide (6.0 mL) was added dropwise the above-mentioned solution under ice-cooling. The mixture was stirred at room temperature for 2 hr. Under ice-cooling, aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=80/20→100/0), and recrystallized from ethyl acetate to give the title compound (982 mg, 72%) as pale-green crystals.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutiondissolved in N,N-dimethylacetamide (2.0 mL)
3. temperaturecooling
4. stirringThe mixture was stirred at room temperature for 2 hr
5. temperatureUnder ice-cooling
6. extractionthe mixture was extracted with ethyl acetate
7. washThe extract was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltrated
10. customThe solvent was evaporated under reduced pressure
11. customthe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=80/20→100/0)
12. customrecrystallized from ethyl acetate

ORDレコード

ord-95b6a0e82bfa4e108a85bfb32ab231e1

出典データセット

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08044049B2