反应详情

Diethyl {1-[(1-ethyl-1H-pyrazol-5-yl)amino]propylidene}propanedioate (1.00 g, 3.23 mmol, e.g. which can be as prepared in Intermediate 2B) was dissolved in toluene (8 ml). To the resulting dark orange solution, 1,8-diazabicyclo[5.4.0]undec-7-ene (“DBU”, 0.97 ml, 0.98 g, 6.46 mmol, 2.0 equivalents) was added, and the reaction mixture was heated at reflux for 17 hours. Further toluene (8 ml) was added to the reaction mixture, after a reduction in volume after heating had been noted. The reaction mixture was allowed to cool, and washed with water (8 ml). The two layers were separated, and the organic layer was discarded after HPLC analysis suggested that the majority of the product was in the aqueous layer. The aqueous layer, whose pH was 12, was acidified to pH 1 using concentrated aqueous hydrochloric acid (0.6 ml), whereupon gas was seen to evolve and solid precipitated spontaneously from solution. This solid was filtered and washed with water. The resulting beige solid (0.55 g) was dried in a vacuum oven at 60° C. overnight. The title compound was obtained as a beige solid (0.46 g, about 54% theory yield). HPLC (5 min generic solvent gradient): TRET about 2.33. Mass Spectrum: Found: MH+ 264.1, (M-H)− 262.1.

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 17 hours
3. temperatureafter a reduction in volume after heating
4. temperatureto cool
5. washwashed with water (8 ml)
6. customThe two layers were separated
7. customsolid precipitated spontaneously from solution
8. filtrationThis solid was filtered
9. washwashed with water
10. dry with materialThe resulting beige solid (0.55 g) was dried in a vacuum oven at 60° C. overnight