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

HRID 1913085Notes

Reaction equation

HRID 1913085 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)([O-])[O-].[Na+].[Na+].C([O-])(=O)C>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.O.C(O)C>[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 175AcetateHCID 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 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 ethyle 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-(cyclopropylmethyl)-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-(cyclopropylmethyl)-2-(4-fluoro-2-methylphenyl)pyrido[2,3-b]pyrazin-3(4H)-one as a white solid

Sources & evidence

ORD record
ord-006a332060884f35957a26b882b5f493
Source dataset
uspto-grants-2013_12
Patent number
US08609689B2

Reaction notes

Loading…