1,2-Dimethoxyethane → HCID 66959245, compound

HRID 1360569Notes

Reaction equation

HRID 1360569 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].COCCOC.Br[C:25]1[C:26]([C:39]#[N:40])=[N:27][N:28]([CH2:35][CH2:36][O:37][CH3:38])[C:29]=1[CH2:30][CH2:31][CH2:32][CH2:33][Cl:34]>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.O>[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:25]1[C:26]([C:39]#[N:40])=[N:27][N:28]([CH2:35][CH2:36][O:37][CH3:38])[C:29]=1[CH2:30][CH2:31][CH2:32][CH2:33][Cl:34]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 164270902-Aminophenylboronic acid hydrochloride2×HCID 66958818HCID 66958818, compound

Product 1

HCID 66959245HCID 66959245, compoundYield 57.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

2-Aminophenylboronic acid hydrochloride (16.2 g, 93.5 mmol), potassium carbonate (42.5 g, 308 mmol), DME (333 mL), water (166 mL), and 4-bromo-5-(4-chlorobutyl)-1-(2-methoxyethyl)-1H-pyrazole-3-carbonitrile (30 g, 93.5 mmol) were combined in a flask, which was then evacuated three times and filled with nitrogen. Dichlorobis(triphenylphosphine)palladium(II) (0.65 g, 0.94 mmol) was then added, and the reaction was heated at 110° C. for one hour. An analysis by HPLC indicated the presence of starting material, and additional 2-aminophenylboronic acid hydrochloride (16.2 g, 93.5 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.65 g, 0.94 mmol) were added. The reaction was then heated at reflux overnight and allowed to cool to ambient temperature. Water (30 mL) was added, and the mixture was extracted with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered through a layer of CELITE filter agent, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting sequentially with 25% ethyl acetate in hexanes and 75% ethyl acetate in hexanes) to provide 18 g of 4-(2-aminophenyl)-5-(4-chlorobutyl)-1-(2-methoxyethyl)-1H-pyrazole-3-carbonitrile as a maroon oil.

Workup

  1. customwhich was then evacuated three times
  2. additionfilled with nitrogen
  3. additionwere added
  4. temperatureThe reaction was then heated
  5. temperatureat reflux overnight
  6. temperatureto cool to ambient temperature
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe combined extracts were dried over sodium sulfate
  9. filtrationfiltered through a layer of CELITE filter agent
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography on silica gel (
  12. washeluting sequentially with 25% ethyl acetate in hexanes and 75% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bc636587a85a491ab99dbbe330e1d007
Source dataset
uspto-grants-2011_02
Patent number
US07879849B2

Reaction notes

Loading…