N,N-Dimethylpropargylamine → 5-(3-Dimethylamino-prop-1-ynyl)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427535Notes

Reaction equation

HRID 2427535 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.[CH3:25][N:26]([CH3:30])[CH2:27][C:28]#[CH:29]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[CH3:25][N:26]([CH3:30])[CH2:27][C:28]#[C:29][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:23])([F:24])[F:22])=[CH:16][CH:15]=1)[CH2:5]2

Participants

5

Reactant 2

HCID 81643N,N-DimethylpropargylamineHCID 11560384HCID 11560384, compound

Product 1

HCID 116970215-(3-Dimethylamino-prop-1-ynyl)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 6%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

5-Bromo-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (50 mg, 0.125 mmol), 1-dimethylamino-2-propyne (194 μL, 0.14 mmol), trimethylacteylene (20 μL, 0.14 mmol), Pd(PPh3)2Cl2 (1.9 mg, 0.003 mmol) and copper iodide (1.0 mg, 0.006 mmol) were stirred together at 120° C. for 30 minutes. The reaction was cooled and partitioned between aqueous NaHCO3 and EtOAc, and the organic was washed with 1N HCl and then basified with 1N NaOH, extracting with EtOAc. The solvent was removed under reduced pressure and purified on silica (2% ammonia in MeOH/EtOAc) to afford 2.8 mg (6%) of a yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.34 (d, 2H), 7.29 (d, 2H), 7.20 (d, 2H), 4.78 (s, 2H), 4.22 (s, 2H), 3.49 (s, 2H), 2.74 (s, 3H), 2.38 (s, 6H).

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between aqueous NaHCO3 and EtOAc
  3. washthe organic was washed with 1N HCl
  4. extractionextracting with EtOAc
  5. customThe solvent was removed under reduced pressure
  6. custompurified on silica (2% ammonia in MeOH/EtOAc)

Sources & evidence

ORD record
ord-318dfceb266f45448b9a7c1a47839cb1
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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