N,N'-Dimethylethylenediamine → 2-(5-Bromo-4-methylpyridin-3-yl)-5-methylisoindolin-1-one

HRID 661828Notes

Reaction equation

HRID 661828 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH3:8].C[C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][NH:16][C:17]2=[O:20])=[CH:13][CH:12]=1.[C:21](=O)([O-])[O-].[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[Br:9][C:6]1[C:7]([CH3:8])=[C:2]([N:16]2[CH2:15][C:14]3[C:18](=[CH:19][CH:11]=[C:12]([CH3:21])[CH:13]=3)[C:17]2=[O:20])[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 8193383,5-Dibromo-4-methylpyridineHCID 124964736-Methyl-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 593751432-(5-Bromo-4-methylpyridin-3-yl)-5-methylisoindolin-1-oneYield 30.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Step 2 A mixture of 3,5-dibromo-4-methylpyridine (2.00 g, 7.97 mmol), 6-methylisoindolin-1-one (1.173 g, 7.97 mmol), copper (I) iodide (0.076 g, 0.399 mmol), potassium carbonate (2.203 g, 15.94 mmol) and N1,N2-dimethylethane-1,2-diamine (0.070 g, 0.797 mmol) in 1,4-dioxane (20 mL) was heated at 100° C. for 15 h. The mixture was cooled to rt, filtered through Celite and washed with DCM. The filtrate was diluted with DCM (100 mL) and washed with water (10 mL) and brine (10 mL), then was dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 80:20 hexane-EtOAc to EtOAc) to give 2-(5-bromo-4-methylpyridin-3-yl)-5-methylisoindolin-1-one (760 mg, 30%). 1H NMR (400 MHz, chloroform-d) δ 8.68 (1H, s), 8.42 (1H, s), 7.84 (1H, d, J=7.77 Hz), 7.37 (1H, d, J=7.77 Hz), 7.34 (1H, s), 4.73 (2H, s), 2.50 (3H, s), 2.35 (3H, s). Mass spectrum m/z 317, 319 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered through Celite
  3. washwashed with DCM
  4. additionThe filtrate was diluted with DCM (100 mL)
  5. washwashed with water (10 mL) and brine (10 mL)
  6. customwas dried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (
  9. washeluting with a gradient from 80:20 hexane-EtOAc to EtOAc)

Sources & evidence

ORD record
ord-a2c4ad030fb54265af157e0a01be2f39
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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