反应详情

Under cooling with ice, diethyl oxalate (3.10 mL) and 1-[1-(phenylsulfonyl)pyrrol-2-yl]-1-ethanone (2.49 g) were added to sodium ethoxide (1.63 g) in ethanol (20 mL), followed by stirring at room temperature for 5 hours. To the reaction mixture, 5-hydrazino-2-methoxypyridine hydrochloride (2.52 g) obtained from Referential Example 1 and ethanol (20 mL) were added, and the resultant mixture was refluxed under heat for 14.5 hours, and then cooled in air. The reaction solvent was removed under reduced pressure, and the residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate. The aqueous layer was extracted again with ethyl acetate. The organic layers were combined, and then dried over sodium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, the residue was purified through silica gel column chromatography (ethyl acetate-hexane), to thereby give 1-(6-methoxy-3-pyridyl)-5-[1-(phenylsulfonyl)pyrrol-2-yl] pyrazole-3-carboxylic acid ethyl ester as an oily product (3.28 g, 72%). To the thus-obtained ethyl ester (3.28 g) in ethanol (22 mL), aqueous 1N sodium hydroxide (22 mL) was added, followed by stirring at room temperature for 2 days. Aqueous 1N hydrochloric acid was added to the reaction mixture, and the precipitated solid was recovered by filtration, to thereby give the title compound as a solid (1.40 g, 68%).

1. additionwere added
2. temperatureunder heat for 14.5 hours
3. temperaturecooled in air
4. customThe reaction solvent was removed under reduced pressure
5. customthe residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate
6. extractionThe aqueous layer was extracted again with ethyl acetate
7. dry with materialdried over sodium sulfate anhydrate
8. filtrationfollowed by filtration
9. customThe solvent was removed under reduced pressure
10. customthe residue was purified through silica gel column chromatography (ethyl acetate-hexane)
11. additionTo the thus-obtained ethyl ester (3.28 g) in ethanol (22 mL), aqueous 1N sodium hydroxide (22 mL) was added
12. stirringby stirring at room temperature for 2 days
13. additionAqueous 1N hydrochloric acid was added to the reaction mixture
14. filtrationthe precipitated solid was recovered by filtration