1,2-Dimethoxyethane → 4-Methoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

HRID 1623538Notes

Reaction equation

HRID 1623538 reaction equation
Br[C:2]1[C:3]([O:13][CH3:14])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](=[O:12])[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>[CH3:14][O:13][C:3]1[C:2]([C:17]2[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][C:6](=[O:12])[N:7]2[CH3:11]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 667888735-Bromo-4-methoxy-1-methyl-1,3-dihydro-indol-2-one

Product 1

HCID 667882514-Methoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To 5-bromo-4-methoxy-1-methyl-1,3-dihydro-indol-2-one (105 mg, 0.410 mmol) was added 3-pyridineboronic acid (CAS#1692-25-7, 60.5 mg, 0.492 mmol), 1,2-dimethoxyethane (3 mL) and 2 M aqueous sodium carbonate (0.513 ml, 1.025 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), 0.11 mmol/g loading, (186 mg, 0.021 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 120° C. for 2.25 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 (ethyl acetate-dichloromethane, 20 to 100%) to afford 4-methoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 255.1136 (M+H)4; 1H NMR (400 MHz, CO2Cl2) δ ppm 3.20 (s, 3H), 3.66 (s, 2H), 3.72 (s, 3H), 6.68 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.38 (dd, J=7.9, 4.9 Hz, 1H), 7.79-7.96 (m, 1H), 8.52 (d, J=4.0 Hz, 1H), 8.71 (s, 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 (ethyl acetate-dichloromethane, 20 to 100%)

Sources & evidence

ORD record
ord-041cab8e9f5b4f5489cb81804d0026f1
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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