1,2-Dimethoxyethane → HCID 66787917, compound

HRID 1623498Notes

Reaction equation

HRID 1623498 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](B3OC(C)(C)C(C)(C)O3)=[CH:8][CH:9]=2)[CH2:4][C:3]1=[O:20].Br[C:22]1[CH:23]=[N:24][CH:25]=[C:26]([C:28]2([CH3:33])[O:32][CH2:31][CH2:30][O:29]2)[CH:27]=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>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:22]3[CH:23]=[N:24][CH:25]=[C:26]([C:28]4([CH3:33])[O:32][CH2:31][CH2:30][O:29]4)[CH:27]=3)=[CH:8][CH:9]=2)[CH2:4][C:3]1=[O:20]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 7099161HCID 7099161, compoundHCID 585476651-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-indol-2-one

Product 1

HCID 66787917HCID 66787917, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
105 °C

Procedure

To 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-indol-2-one (109 mg, 0.4 mmol), prepared as described in Example 3a, was added 3-bromo-5-(2-methyl-1,3-dioxolan-2-yl)pyridine (CAS#59936-01-5, 107 mg, 0.44 mmol), 1,2-dimethoxyethane (3.0 mL), and 2 M aqueous sodium carbonate (0.45 mL, 0.9 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, (182 mg, 0.02 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 105° C. for 3 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-5-[5-(2-methyl-[1,3]-dioxolan-2-yl)-pyridin-3-yl]-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 311.1395 (M+H)+; 1H NMR (400 MHz, CDCl3) δppm 1.73 (s, 3H), 3.28 (s, 3H), 3.62 (s, 2H), 3.82-3.88 (m, 2H), 4.08-4.16 (m, 2H), 6.94 (d, J=7.8 Hz, 1H), 7.49-7.58 (m, 2H), 7.97 (s, 1H), 8.71 (d, J=2.0 Hz, 1H), 8.77 (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. 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-39426584b5b2418ea8c396a2415c62fc
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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