Cesium fluoride → 1-(2-Methyl-3-(phenylamino)quinoxalin-5-yl)ethanone

HRID 1056003Notes

Reaction equation

HRID 1056003 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([CH3:19])=[N:7]2.C([Sn](CCCC)(CCCC)[C:25]([O:27]CC)=[CH2:26])CCC.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[F-].[Cs+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[CH3:19][C:8]1[C:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:10][C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[C:25](=[O:27])[CH3:26])[N:7]=1

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897820828-bromo-3-methyl-N-phenylquinoxalin-2-amine

Product 1

HCID 897822031-(2-Methyl-3-(phenylamino)quinoxalin-5-yl)ethanoneYield 21%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 8-bromo-3-methyl-N-phenylquinoxalin-2-amine (0.64 g, 2.037 mmol), tributyl(1-ethoxyvinyl)stannane (1.032 ml, 3.06 mmol; Aldrich), Pd2(dba)3 (0.187 g, 0.204 mmol), XPhos (Strem, Newburyport, Mass.; 0.097 g, 0.204 mmol), CuI (0.078 g, 0.407 mmol), and cesium fluoride (0.928 g, 6.11 mmol) in dioxane (10.19 ml) was heated in a microwave reactor (Biotage Initiator) for 20 min at 160° C. The mixture was diluted with EtOAc (200 ml), added to a separatory funnel, and washed with saturated aq. NH4Cl (3×150 ml) before the organic layer was separated, dried over Na2SO4, and concentrated. Purification by silica gel (100% hexanes to 30% EtOAc/hexanes) provided 1-(2-methyl-3-(phenylamino)quinoxalin-5-yl)ethanone (183b, 21% yield) as a brown, amorphous solid. MS (ESI, pos. ion) m/z: 278.2 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NH4Cl (3×150 ml) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by silica gel (100% hexanes to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3572b5810df54f828147ad5f13cf4d39
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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