反应详情

13.487 g (51.228 mmol) of ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate (preparation described for example 20A in WO 00/06569) were initially charged in 300 ml of dioxane, and 6 g (51.228 mmol) of 3-(dimethylamino)-2-fluoroacrylaldehyde (preparation described in Justus Liebigs Annalen der Chemie 1970; 99-107) were added at RT. Subsequently, 4.736 ml (61.473 mmol) of trifluoroacetic acid were added and the mixture was heated to reflux while stirring for 3 days. After cooling, the mixture was concentrated under reduced pressure, and water and ethyl acetate were added to the residue. The phases were separated and the organic phase was washed twice with water. The combined aqueous phases were subsequently extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue (22 g) was subsequently purified by chromatography on silica gel (eluent: dichloromethane). This gave 5.67 g (35% of theory) of the title compound.

1. temperaturethe mixture was heated
2. temperatureto reflux
3. temperatureAfter cooling
4. concentrationthe mixture was concentrated under reduced pressure, and water and ethyl acetate
5. additionwere added to the residue
6. customThe phases were separated
7. washthe organic phase was washed twice with water
8. extractionThe combined aqueous phases were subsequently extracted twice with ethyl acetate
9. dry with materialThe combined organic phases were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue (22 g) was subsequently purified by chromatography on silica gel (eluent: dichloromethane)