Dimethyl Sulfoxide → 2-(3-Bromo-2-methyl-phenyl)-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-one

HRID 2069753Notes

Reaction equation

HRID 2069753 reaction equation
[CH3:1][N:2]([CH3:14])[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][CH2:7][CH2:6]2.C(=O)([O-])[O-].[K+].[K+].CS(C)=O.[Br:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](Br)[C:27]=1[CH3:33]>ClCCl>[Br:25][C:26]1[C:27]([CH3:33])=[C:28]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([N:2]([CH3:14])[CH3:1])[CH:4]=3)[C:9]2=[O:13])[CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 346812,6-DibromotolueneHCID 574241216-(Dimethylamino)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 592164782-(3-Bromo-2-methyl-phenyl)-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-oneYield 63.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (150 mg, 0.789 mmol), cuprous iodide (30 mg, 0.16 mmol) and potassium carbonate (109 mg, 0.789 mmol) were deposited in a sealed vessel. 3 mL DMSO and 2,6-dibromotoluene (395 mg, 1.58 mmol) were added. Argon was bubbled through the mixture for 2 minutes and the lid was tightly closed. This was heated at 150° C. for 24 hours. Cuprous iodide (30 mg, 0.16 mmol) was added and the mixture was heated at 150° C. for an additional 24 hours. This was diluted with dichoromethane and filtered through a pad of celite. The filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide. The dichloromethane layer was washed with brine. The combined aqueous layers were washed with dichloromethane. The combined dichloromethane layers were dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes) to yield 2-(3-Bromo-2-methyl-phenyl)-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (181 mg, 0.504 mmol). MS (ESI) 361.1 (M+H)+.

Workup

  1. customArgon was bubbled through the mixture for 2 minutes
  2. customthe lid was tightly closed
  3. temperaturethe mixture was heated at 150° C. for an additional 24 hours
  4. filtrationfiltered through a pad of celite
  5. customThe filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide
  6. washThe dichloromethane layer was washed with brine
  7. washThe combined aqueous layers were washed with dichloromethane
  8. dry with materialThe combined dichloromethane layers were dried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. custompurified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ccdd0878348f4612972d1a0ade3650d2
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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