反应详情

温度

50 °C

Hydrazine monohydrate (0.53 mL, 10.8 mmol) is added to a solution of 2-((5-chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methyl)isoindoline-1,3-dione (1.27 g, 3.60 mmol, Step-4) in methanol (50 mL) and stirred for 20 hours at 50° C. After removal of the solvent, the residue is poured into 2 M aqueous sodium hydroxide solution (10 mL) and extracted with DCM (30 mL×3). The organic layer is dried over sodium sulfate. After filtration, the organic layer is concentrated in vacuo. The residue is dissolved in EtOAc (10 mL), 4 M hydrogen chloride in EtOAc (5 mL) is added and stirred for 1 hour. After removal of the solvent, the residue is crystallized from EtOAc/n-hexane to give 0.85 g (91% yield) of the title compound as white solid.

1. customAfter removal of the solvent
2. additionthe residue is poured into 2 M aqueous sodium hydroxide solution (10 mL)
3. extractionextracted with DCM (30 mL×3)
4. dry with materialThe organic layer is dried over sodium sulfate
5. filtrationAfter filtration
6. concentrationthe organic layer is concentrated in vacuo
7. dissolutionThe residue is dissolved in EtOAc (10 mL)
8. addition4 M hydrogen chloride in EtOAc (5 mL) is added
9. stirringstirred for 1 hour
10. customAfter removal of the solvent
11. customthe residue is crystallized from EtOAc/n-hexane