N-bromobutanimide → 5-Bromo-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridin-6(7H)-one
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:13]2[NH:14][C:15](=[O:23])[C:16](C(OCC)=O)=[CH:17][C:12]=2[CH:11]=[N:10]1.O.[OH-].[Li+].C1C(=O)N([Br:34])C(=O)C1.C([O-])(O)=O.[Na+]>O.CC#N>[Br:34][C:16]1[C:15](=[O:23])[NH:14][C:13]2[N:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[N:10]=[CH:11][C:12]=2[CH:17]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
Ethyl 1-(2,6-difluorophenyl)-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (9.40 g, 29 mmol) was treated with 80 mL CH3CN and 80 mL water and lithium hydroxide monohydrate (3.10 g, 74 mmol). The resulting suspension was then heated to 90° C. for 1 h. The solution was allowed to cool to 35° C. and treated with N-bromosuccimide (5.20 g, 29 mmol) in one portion. It was allowed to stir for 1 h at RT then treated with another equiv. of N-bromosuccimide (5.20 g, 29 mmol) in one portion. After stirring for an additional 1 h at RT, it was treated with a saturated solution of NaHCO3 and extracted with 2×150 mL EtOAc. The combined organic solution was washed with brine, dried over MgSO4, filtered and concentrated to afford the title compound (8.31 g) as an orange foam in ca. 90% purity. No further purification was carried out prior to use in the next step. MS (ESI, pos.ion) m/z: 326.0/327.9 (M+1). For a related reference, see: Chowdhury, S.; Roy, S. J. Org. Chem. 1997, 62, 199-200.
Workup
- temperatureto cool to 35° C.
- stirringAfter stirring for an additional 1 h at RT
- extractionextracted with 2×150 mL EtOAc
- washThe combined organic solution was washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-3ee62720eb7e4e4c88c0318296195006
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08435987B2
Reaction notes
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