Potassium Carbonate → 3-fluoro-2-(5-methyl-1-oxo-6-(4-(1H-pyrazol-1-yl)benzyl)-1,3-dihydro-2H-isoindol-2-yl)benzonitrile

HRID 629346Notes

Reaction equation

[N:1]1([C:6]2[CH:23]=[CH:22][C:9]([CH2:10][C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][NH:16][C:17]4=[O:20])=[CH:13][C:12]=3[CH3:21])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].F[C:31]1[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:32]=1[C:33]#[N:34]>CN(C=O)C.O.C(OCC)(=O)C>[F:39][C:38]1[C:31]([N:16]2[CH2:15][C:14]3[C:18](=[CH:19][C:11]([CH2:10][C:9]4[CH:22]=[CH:23][C:6]([N:1]5[CH:5]=[CH:4][CH:3]=[N:2]5)=[CH:7][CH:8]=4)=[C:12]([CH3:21])[CH:13]=3)[C:17]2=[O:20])=[C:32]([CH:35]=[CH:36][CH:37]=1)[C:33]#[N:34]

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 6-(4-(1H-pyrazol-1-yl)benzyl)-5-methylisoindolin-1-one (0.05 g) in DMF (1.00 mL) were added potassium carbonate (0.07 g) and 2,3-difluorobenzonitrile (0.05 g), and the mixture was stirred overnight at 150° C. under argon atmosphere. The reaction mixture was diluted with water and ethyl acetate, and the mixture was partitioned. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and then HPLC (water/methanol) to give the title compound (7.80 mg).

Workup

customthe mixture was partitioned
washThe organic layer was washed with water and saturated brine
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record: ord-1d21878b54024110ad5a2784f63fdb89
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315458B2

Reaction notes

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