Ethanol → 4-(cyclopropylmethyl)-2-(4-fluoro-2-methylphenyl)pyrido[2,3-b]pyrazin-3(4H)-one

HRID 238128Notes

Reaction equation

HRID 238128 reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][CH:10]2[CH2:12][CH2:11]2)[C:5]2[N:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[C:20]([CH3:27])[CH:19]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C(OCC)(=O)C.O>[CH:10]1([CH2:9][N:6]2[C:7](=[O:8])[C:2]([C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][C:20]=3[CH3:27])=[N:3][C:4]3[CH:16]=[CH:15][CH:14]=[N:13][C:5]2=3)[CH2:12][CH2:11]1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 2734665(4-Fluoro-2-methylphenyl)boronic acidHCID 581031982-bromo-4-(cyclopropylmethyl)pyrido[2,3-b]pyrazin-3(4H)-one

Product 1

HCID 442187314-(cyclopropylmethyl)-2-(4-fluoro-2-methylphenyl)pyrido[2,3-b]pyrazin-3(4H)-oneYield 45.3%

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 200 mg (0.71 mM) of 2-bromo-4-(cyclopropylmethyl)pyrido[2,3-b]pyrazin-3(4H)-one and 25.3 mg (0.036 mM) of bis(triphenylphosphine) palladium(II)chloride in 1 ml of dimethylformamide were added 142.9 mg (0.93 mM) of (4-fluoro-2-methylphenyl)boronic acid, 0.1 ml of ethanol and 715 μl of a 2M aqueous solution of sodium carbonate. The reaction mixture was then refluxed for 20 h under stirring. Water and ethyl acetate were added. The organic layer was separated, washed with water, dried on anhydrous sodium sulfate and the solvent was removed under vacuum. The compound was further purified by silica gel column chromatography, using dichloromethane as eluant, to give, after evaporation, 100 mg of 4-(cyclopropyl methyl)-2-(4-fluoro-2-methylphenyl)pyrido[2,3-b]pyrazin-3(4H)-one as a white solid. (Yield: 45.3%)

Workup

  1. temperatureThe reaction mixture was then refluxed for 20 h
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materialdried on anhydrous sodium sulfate
  5. customthe solvent was removed under vacuum
  6. customThe compound was further purified by silica gel column chromatography
  7. customto give
  8. customafter evaporation, 100 mg of 4-(cyclopropyl methyl)-2-(4-fluoro-2-methylphenyl)pyrido[2,3-b]pyrazin-3(4H)-one as a white solid

Sources & evidence

ORD record
ord-097d87da5f6542c9b4fcd8b73d3afb78
Source dataset
uspto-grants-2014_02
Patent number
US08642617B2

Reaction notes

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