Dimethyl Sulfoxide → acetic acid 2-bromo-6-[6-(ethyl-methyl-amino)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzyl ester

HRID 2245667Notes

Reaction equation

HRID 2245667 reaction equation
[CH2:1]([N:3]([CH3:15])[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH2:8][CH2:7]2)[CH3:2].[Br:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24](Br)[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>C(OCC)(=O)C.O>[Br:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][CH:13]=[C:4]([N:3]([CH2:1][CH3:2])[CH3:15])[CH:5]=3)[C:10]2=[O:14])[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 592163926-(Ethyl-methyl-amino)-3,4-dihydro-2H-isoquinolin-1-oneHCID 592164132,6-Dibromobenzyl acetate

Product 1

HCID 59216502acetic acid 2-bromo-6-[6-(ethyl-methyl-amino)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzyl esterYield 27.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

6-(Ethyl-methyl-amino)-3,4-dihydro-2H-isoquinolin-1-one (2.07 g, 10.1 mmol), acetic acid 2,6-dibromo-benzyl ester (6.25, 20.3 mmol), cuprous iodide (386 mg, 2.03 mmol) and potassium carbonate (1.40, 10.1 mmol) were deposited in a sealed vessel. 30 mL DMSO was added. Argon was bubbled through the mixture for 3 minutes and the lid was tightly closed. This was heated at 150° C. for 24 hours. Cuprous iodide (386 mg, 2.03 mmol) was added and the mixture was heated at 150° C. for an additional 24 hours. This was diluted with 300 mL ethyl acetate and 300 mL water. After stirring for 20 minutes, this was filtered through a pad of celite. The layers were separated. The ethylacetate layer was dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes) to yield acetic acid 2-bromo-6-[6-(ethyl-methyl-amino)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzyl ester (1.21 g, 2.81 mmol). MS (ESI) 433.0 (M+H)+.

Workup

  1. customArgon was bubbled through the mixture for 3 minutes
  2. customthe lid was tightly closed
  3. temperaturethe mixture was heated at 150° C. for an additional 24 hours
  4. filtrationthis was filtered through a pad of celite
  5. customThe layers were separated
  6. dry with materialThe ethylacetate layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-6c6ebaefaee14a4b93484fa3afc9b416
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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