反应详情

To a refluxing mixture of 2-chloro-4-fluoro-5-(pyridin-2-yl)benzoic acid (Preparation 22A, 9.2 g, 36.6 mmol), ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (8.45 g, 36.6 mmol), N,N-diisopropylethylamine (19.2 mL, 110 mmol) and 2-methyltetrahydrofuran (320 mL), was added propylphosphonic anhydride solution (255 mL, 429 mmol, >50% by weight in EtOAc) dropwise under argon, and the reaction maintained at reflux for 5 hours. After cooling to room temperature, the reaction was filtered and the filtrate concentrated in vacuo. The residue was dissolved in ethyl acetate (350 mL) and washed with saturated aqueous sodium hydrogen carbonate solution (300 mL). The organic layer was filtered under vacuum and the solids washed with EtOAc (20 mL) and TBME (200 mL) to give the title compound (51 g, 78%).

1. temperaturethe reaction maintained
2. temperatureat reflux for 5 hours
3. filtrationthe reaction was filtered
4. concentrationthe filtrate concentrated in vacuo
5. dissolutionThe residue was dissolved in ethyl acetate (350 mL)
6. washwashed with saturated aqueous sodium hydrogen carbonate solution (300 mL)
7. filtrationThe organic layer was filtered under vacuum
8. washthe solids washed with EtOAc (20 mL) and TBME (200 mL)