N,N'-Dimethylethylenediamine → 7-(2-oxoazetidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

HRID 1162894Notes

Reaction equation

HRID 1162894 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.[NH:23]1[CH2:26][CH2:25][C:24]1=[O:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC.[Cl-].[NH4+]>O1CCOCC1.[Cu](I)I>[O:27]=[C:24]1[CH2:25][CH2:26][N:23]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

8

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 1367212-AzetidinoneHCID 231568037-iodo-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

Product 1

HCID 118534187-(2-oxoazetidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-oneYield 44.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

The 7-iodo-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (10.0 mg, 0.024 mmol) prepared in step D, copper iodide (I) (0.48 mg, 0.0025 mmol), 2-azetidinone (2.13 mg, 0.03 mmol), and potassium phosphate (11.1 mg, 0.0525 mmol) were suspended in 1,4-dioxane (0.25 ml). Thereafter, N,N′-dimethylethylenediamine (2.6 μl) was added to the suspension, and the obtained mixture was 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=3:1 to 6:1), so as to obtain 7-(2-oxoazetidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (3.8 mg; yield: 44%) 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=3:1 to 6:1)

Sources & evidence

ORD record
ord-d30939ba8c784688878a6042cb015cbc
Source dataset
uspto-grants-2010_10
Patent number
US07820693B2

Reaction notes

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