Cesium carbonate → Ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylate

HRID 1027698Notes

Reaction equation

HRID 1027698 reaction equation
[OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.Cl[C:18]1[N:19]=[CH:20][C:21]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[N:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:27][N:26]([CH3:28])[C:24]([C:21]1[N:22]=[CH:23][C:18]([O:1][C:2]2[C:7]3[CH:8]=[C:9]([CH3:11])[O:10][C:6]=3[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=2)=[N:19][CH:20]=1)=[O:25]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11514065Ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylateHCID 590004705-chloro-N,N-dimethylpyrazine-2-carboxamide

Product 1

HCID 59483311Ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The flask was charged with ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate (I-1c: 6.07 g, 27.6 mmol), 5-chloro-N,N-dimethylpyrazine-2-carboxamide (SM-1: 5.06 g, 27.3 mmol), cesium carbonate (9.78 g, 30 mmol). The solids were dissolved in dimethylformamide (60 mL). The reaction was heated to 90° C. for 3 hours. After the reaction was cooled down to ambient temperature, dimethylformamide was removed in vacuo. The crude reaction mixture was partitioned between ethyl acetate (100 ml) and water (30 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with water, brine, dried over sodium sulfate, and concentrated. The crude product was purified by column chromatography (silica gel, 30 to 80% gradient of ethyl acetate in heptane) to give desired ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylate (I-1d) as a light brown solid (8.3 g, 95%).

Workup

  1. temperatureAfter the reaction was cooled down to ambient temperature
  2. customdimethylformamide was removed in vacuo
  3. customThe crude reaction mixture
  4. customwas partitioned between ethyl acetate (100 ml) and water (30 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  6. washThe combined organic layer was washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (silica gel, 30 to 80% gradient of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-bc7169dba9354f8c87a42e014826b687
Source dataset
uspto-grants-2014_05
Patent number
US08735396B2

Reaction notes

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