Dimethylformamide → 3-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])[C:5]2([C:14]1[C:15]([O:20][CH2:21][CH3:22])=[N:16][CH:17]=[CH:18][CH:19]=1)[OH:13].[CH3:23][N:24](C)C=O>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[CH2:21]([O:20][C:15]1[C:14]([C:5]2([OH:13])[C:4]3[C:8](=[CH:9][C:10]([F:11])=[C:2]([C:23]#[N:24])[CH:3]=3)[NH:7][C:6]2=[O:12])=[CH:19][CH:18]=[CH:17][N:16]=1)[CH3:22]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 150 °C
Procedure
161 mg (0.14 mmol) of tetrakis(triphenylphosphine)palladium (0) were added to a solution of 1.7 g (4.63 mmol) of 5-bromo-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-1,3-dihydroindol-2-one from example a.1 and 544 mg (4.63 mmol) of zinc cyanide in 18 ml of dimethylformamide (DMF), and the mixture was agitated in a Biotage microwave apparatus at 150° C. for 1 h. The reaction solution was worked up by diluting with 300 ml of water, extracting with ethyl acetate (3×) and washing with saturated sodium chloride solution (1×). The combined organic phases were dried over magnesium sulfate and filtered, and the solvent was removed in vacuo. 1.67 g of 3-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile were obtained.
Workup
- extractionextracting with ethyl acetate (3×)
- washwashing with saturated sodium chloride solution (1×)
- dry with materialThe combined organic phases were dried over magnesium sulfate
- filtrationfiltered
- customthe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-a512612913aa48d497144ffc2801fd6e
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434713B2
Reaction notes
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