Hydrazine hydrate (1:1) → (5-Chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methanamine hydrochloride
Reaction equation
O.NN.[Cl:4][C:5]1[CH:6]=[C:7]([CH2:16][N:17]2C(=O)C3C(=CC=CC=3)C2=O)[CH:8]=[N:9][C:10]=1[O:11][CH2:12][CH:13]([F:15])[F:14]>CO>[ClH:4].[Cl:4][C:5]1[CH:6]=[C:7]([CH2:16][NH2:17])[CH:8]=[N:9][C:10]=1[O:11][CH2:12][CH:13]([F:14])[F:15]Participants
4
Conditions
- Temperature
- 50 °C
Procedure
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.
Workup
- customAfter removal of the solvent
- additionthe residue is poured into 2 M aqueous sodium hydroxide solution (10 mL)
- extractionextracted with DCM (30 mL×3)
- dry with materialThe organic layer is dried over sodium sulfate
- filtrationAfter filtration
- concentrationthe organic layer is concentrated in vacuo
- dissolutionThe residue is dissolved in EtOAc (10 mL)
- addition4 M hydrogen chloride in EtOAc (5 mL) is added
- stirringstirred for 1 hour
- customAfter removal of the solvent
- customthe residue is crystallized from EtOAc/n-hexane
Sources & evidence
- ORD record
- ord-677724ad5f9343b1801f9ec3a00434de
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09187475B2
Reaction notes
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