Cesium carbonate → 7-(2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162897Notes

Reaction equation

HRID 1162897 reaction equation
I[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:71]1[CH2:75][CH2:74][CH2:73][C:72]1=[O:76].[Cl-].[NH4+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:76]=[C:72]1[CH2:73][CH2:74][CH2:75][N:71]1[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 25517Ammonium ChlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 231568037-iodo-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 118536737-(2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 82%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

The 7-iodo-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (20.8 mg, 0.05 mmol) prepared in step D of Example 1-1, tris(dibenzylideneacetone)dipalladium (2.2 mg, 0.0025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (4.2 mg, 0.0075 mmol), cesium carbonate (22.8 mg, 0.07 mmol), and 2-pyrrolidone (4.6 μl) were suspended in 1,4-dixane (0.5 ml), and the suspension was then stirred under heating to reflux overnight. Thereafter, the reaction solution was cooled to a room temperature, and a saturated ammonium chloride aqueous solution was then added thereto, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was then distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate hexane=2:1 to 5:1), so as to obtain 7-(2-oxopyrrolidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (15.3 mg; yield: 82%) in the form of a colorless solid.

Workup

  1. temperatureunder heating
  2. temperatureto reflux overnight
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous sodium sulfate
  5. distillationthe solvent was then distilled away under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate hexane=2:1 to 5:1)

Sources & evidence

ORD record
ord-5e4bd257854b4b4ca93ef7ccfb179943
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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