反应详情

2,4-dichloro-5-(5-fluoropyridin-2-yl)benzoic acid hydrochloride (Preparation 20, 900 mg, 3.15 mmol), ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (683 mg, 2.95 mmol) and diisopropylethylamine (3.28 mL, 18.88 mmol) were added to EtOAc (30 mL) and heated to reflux under an atmosphere of nitrogen. A 50% solution of propylphosphonic cyclic anhydride in EtOAc (9 g, 14.16 mmol) was added dropwise, and the reaction was kept at reflux for 3 hours. After cooling, the reaction was basified with saturated aqueous sodium hydrogen carbonate solution. The organic layer was collected, dried over magnesium sulphate and concentrated in vacuo. The residue was dissolved in ethanol (30 mL) and solid sodium carbonate (˜2 g) was added with rapid stirring for 1 hour. The mixture was filtered and the filtrate concentrated in vacuo. The residue was stirred with dilute aqueous sodium hydrogen carbonate, filtered, washed with water and dried in vacuo. The resulting solid was triturated with TBME to afford the title compound (822 mg, 52%).

1. temperatureheated
2. temperatureto reflux under an atmosphere of nitrogen
3. temperatureat reflux for 3 hours
4. temperatureAfter cooling
5. customThe organic layer was collected
6. dry with materialdried over magnesium sulphate
7. concentrationconcentrated in vacuo
8. dissolutionThe residue was dissolved in ethanol (30 mL)
9. additionsolid sodium carbonate (˜2 g) was added
10. filtrationThe mixture was filtered
11. concentrationthe filtrate concentrated in vacuo
12. stirringThe residue was stirred with dilute aqueous sodium hydrogen carbonate
13. filtrationfiltered
14. washwashed with water
15. customdried in vacuo
16. customThe resulting solid was triturated with TBME