1,2-Dimethoxyethane → 1-methyl-2-oxo-5-pyridin-3-yl-2,3-dihydro-1H-indole-6-carbonitrile

HRID 1623545Notes

Reaction equation

HRID 1623545 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[C:11]#[N:12])[N:7]([CH3:13])[C:6](=[O:14])[CH2:5]2.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:17]3[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=3)=[C:10]([C:11]#[N:12])[CH:9]=2)[CH2:5][C:6]1=[O:14]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 667939935-bromo-1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile

Product 1

HCID 667938971-methyl-2-oxo-5-pyridin-3-yl-2,3-dihydro-1H-indole-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To 5-bromo-1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile (58 mg, 0.23 mmol) was added 3-pyridine boronic acid (CAS#1692-25-7, 28 mg, 0.23 mmol), 1,2-dimethoxyethane (2.0 mL) and 2 M aqueous sodium carbonate (0.230 mL, 0.46 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.09 mmol/g loading, (105 mg, 0.009 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 100° C. for 1.75 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 6%) to afford 1-methyl-2-oxo-5-pyridin-3-yl-2,3-dihydro-1H-indole-6-carbonitrile; HRMS: (ESI) m/z 248.0838 (M−H)−; 1H NMR (400 MHz, CDCl3) δ ppm 3.30 (s, 2H), 3.68 (s, 2H), 7.19 (s, 1H), 7.42 (s, 1H), 7.49-7.58 (m, 1H), 8.02 (d, J=7.6 Hz, 1H), 8.72 (dd, J=4.8, 1.1 Hz, 1H), 8.77 (d, J=1.8 Hz, 1H).

Workup

  1. customThe reaction mixture was degassed
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered through glass wool
  6. additionThe filtrate was further diluted with saturated aqueous sodium bicarbonate
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted two times with dichloromethane
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 6%)

Sources & evidence

ORD record
ord-1a8c544601564a61ae5db29fa432a0d9
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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