1,2-Dimethoxyethane → HCID 49765789, compound

HRID 1623534Notes

Reaction equation

HRID 1623534 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:20])[C:7](B3OC(C)(C)C(C)(C)O3)=[CH:8][CH:9]=2)[CH2:4][C:3]1=[O:21].[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27](Br)[CH:28]=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>[Br:22][C:23]1[CH:28]=[C:27]([C:7]2[C:6]([CH3:20])=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:2]([CH3:1])[C:3](=[O:21])[CH2:4]3)[CH:26]=[N:25][CH:24]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 693693,5-DibromopyridineHCID 66793850HCID 66793850, compound

Product 1

HCID 49765789HCID 49765789, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To 1,4-dimethyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-indol-2-one, prepared as described in Example 34a (90 mg, 0.31 mmol) was added 3,5-dibromopyridine (CAS#625-92-3, 223 mg, 0.940 mmol), 1,2-dimethoxyethane (3.0 mL), and 2 M aqueous sodium carbonate (0.376 mL, 0.75 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, (171 mg, 0.019 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 120° C. for 2 hours. The reaction mixture was then 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, 0 to 65%) to furnish 5-(5-bromo-pyridin-3-yl)-1,4-dimethyl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 317.0289 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 210 (s, 3H), 3.26 (s, 3H), 3.50 (s, 2H), 6.78 (d, J=8.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.82 (t, J=2.0 Hz, 1H), 8.50 (d, J=1.8 Hz, 1H), 8.68 (d, J=2.1 Hz, 1H).

Workup

  1. customThe reaction mixture was degassed
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was then 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, 0 to 65%)

Sources & evidence

ORD record
ord-8f941891d8b743dfaf1a91ca909ffada
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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