Water → HCID 49819882, compound

HRID 1623496Notes

Reaction equation

HRID 1623496 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[N:6][CH:7]=1.O.C(=O)([O-])[O-].[Na+].[Na+].Br[C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([CH3:28])[C:23](=[O:29])[CH2:22]2>COCCOC.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.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[N:24]([CH3:28])[C:23](=[O:29])[CH2:22]3)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 24326665-Bromo-1-methyl-2-oxoindolineHCID 44717403(5-Fluoropyridin-3-yl)boronic acid

Product 1

HCID 49819882HCID 49819882, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-fluoropyridine-3-boronic acid (CAS#872041-86-6, 80 mg, 0.57 mmol) in 1,2-dimethoxyethane (0.7 mL) was added water (0.3 mL) and ethanol (0.2 mL. The solution was then charged with sodium carbonate (60 mg, 0.57 mmol), 5-bromo-1-methyl-1,3-dihydro-indol-2-one (CAS#20870-90-0, 132 mg, 0.57 mmol), and dichlorobis(triphenylphosphine)palladium (II) (CAS#13965-03-2, 20.3 mg, 0.029 mmol). The reaction vessel was sealed and is heated by microwave irradiation at 150° C. for 10 minutes. The reaction mixture was cooled to room temperature, filtered and concentrated. The resulting residue was partially purified by semi-preparative reverse phase HPLC (20 to 90% acetonitrile/water vii 0.1% TEA). Final purification was accomplished via silica gel flash chromatography (methanol-dichloromethane, 0 to 7%) to afford 5-(5-fluoro-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one, MS: (ES+) m/z 243 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.18 (s, 3H), 3.64 (s, 2H), 7.13 (d, J=7.8 Hz, 1H), 7.73-7.77 (m, 2H), 8.03 (d, J=9.7 Hz, 1H), 8.53 (d, J=2.7 Hz, 1H), 8.79 (s, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was partially purified by semi-preparative reverse phase HPLC (20 to 90% acetonitrile/water vii 0.1% TEA)
  6. customFinal purification

Sources & evidence

ORD record
ord-688f140adad94a7da47cfc84f6ee3912
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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