1,2-Dimethoxyethane → HCID 66788747, compound

HRID 1623524Notes

Reaction equation

HRID 1623524 reaction equation
Br[C:2]1[C:3]([Cl:13])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](=[O:12])[CH2:5]2.[N:14]1[CH:19]=[CH:18][CH:17]=[C:16](B(O)O)[CH:15]=1.COCCOC>ClCCl.C(=O)([O-])[O-].[Na+].[Na+].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>[Cl:13][C:3]1[C:2]([C:16]2[CH:15]=[N:14][CH:19]=[CH:18][CH:17]=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 3

HCID 80711,2-DimethoxyethaneHCID 27343783-Pyridinylboronic acidHCID 66788022HCID 66788022, compound

Product 1

HCID 66788747HCID 66788747, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent2×

Conditions

Temperature
100 °C

Procedure

To 5-bromo-4-chloro-1-methyl-1,3-dihydro-indol-2-one (78 mg, 0.3 mmol) was added 3-pyridine boronic acid (CAS#1692-25-7, 50.2 mg, 0.41 mmol), 1,2-dimethoxyethane (2.5 mL) and 2 M aqueous sodium carbonate (0.410 mL, 0.82 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, (167 mg, 0.015 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 100° C. for 75 minutes. The reaction mixture was cooled to room temperature, diluted with dichloromethane and saturated aqueous sodium carbonate, 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-heptane, 40 to 100%) to afford 4-chloro-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 259.0636 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 3.27 (s, 3H), 3.62 (s, 2H), 6.85 (d, J=8.1 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 7.38-7.48 (m, 1H), 7.85 (d, J=7.8 Hz, 1H), 8.64 (dd, J=4.9, 1.6 Hz, 1H), 8.69 (d, J=2.3 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. customthe layers were separated
  6. extractionThe aqueous layer was extracted two times with dichloromethane
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane, 40 to 100%)

Sources & evidence

ORD record
ord-9a407166242546298e2f51adab25be6c
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

Loading…