反应详情

温度

10 °C

5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 107, 78 g, 166 mmol) was sonicated in DMF (300 mL) with N,N-diisopropylethylamine (58 mL, 332 mmol) to give a clear solution, which was cooled to 10° C. TPTU (74 g, 249 mmol) was added portionwise and the mixture stirred at 10° C. for 20 minutes. A solution of 1-amino-2-methylpropan-2-ol (22.1 g, 249 mmol) in DMF (50 mL) was added dropwise at 10° C. and the mixture then allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was partitioned between EtOAc (600 mL) and water (600 mL). The aqueous layer was separated and extracted with additional EtOAc (3×200 mL). The combined organic layers were washed with saturated aqueous ammonium chloride solution (300 mL), water (5×200 mL), dried (magnesium sulphate) and concentrated in vacuo to give an orange oil. The oil was treated with acetonitrile (300 mL) and the resulting solid collected by filtration, washed with acetonitrile and dried under vacuum to afford the title compound as a colourless solid (60 g, 66%).

1. customto give a clear solution, which
2. temperatureto warm to room temperature
3. stirringstirred for 16 hours
4. customThe reaction mixture was partitioned between EtOAc (600 mL) and water (600 mL)
5. customThe aqueous layer was separated
6. extractionextracted with additional EtOAc (3×200 mL)
7. washThe combined organic layers were washed with saturated aqueous ammonium chloride solution (300 mL), water (5×200 mL)
8. dry with materialdried (magnesium sulphate)
9. concentrationconcentrated in vacuo
10. customto give an orange oil
11. filtrationthe resulting solid collected by filtration
12. washwashed with acetonitrile
13. customdried under vacuum