反应详情

温度

115 °C

To a round bottom flask were added N-(4-bromo-2,5-difluorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (1.80 g, 4.04 mmol) and potassium carbonate (1.955 g, 14.15 mmol) and water (200 mL). The resulting suspension was refluxed for 16 h at 115° C. The pH of the solution was lowered to ˜6 with 1N aq HCl and then partitioned with 150 mL of ethyl acetate. The aqueous phase was extracted with ethyl acetate (3×) and the combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, then 0-25% isopropanol/ethyl acetate), and the desired fractions were combined and concentrated in vacuo to afford the title product as an off-white solid (400 mg, 31%). MS(ES)+ m/e 426.9, 428.8 M+H]+.

1. custompartitioned with 150 mL of ethyl acetate
2. extractionThe aqueous phase was extracted with ethyl acetate (3×)
3. washthe combined organic layer was washed with brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes
7. concentrationconcentrated in vacuo