Bromide ion → 5-(4-amino-2,6-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1591849Notes

Reaction equation

HRID 1591849 reaction equation
Br[C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:10].[CH3:11][N:12]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]1B(O)O.[F-].[K+].[Br-]>C1COCC1.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].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[NH2:6][C:5]1[CH:7]=[C:8]([F:9])[C:2]([C:13]2[N:12]([CH3:11])[C:16]([C:17]#[N:18])=[CH:15][CH:14]=2)=[C:3]([F:10])[CH:4]=1

Participants

8

Reactant 4

HCID 259Bromide ionHCID 522689Potassium FluorideHCID 27362604-Bromo-3,5-difluoroanilineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 160505305-(4-amino-2,6-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrileYield 200.8%

Reagents, catalysts & solvents 3

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-bromo-3,5-difluoroaniline (0.782 g, 3.78 mmol), tris(dibenzylidene-acetone)dipalladium (0.096 g, 0.105 mmol), N-methyl-5-cyanopyrroleboronic acid (1.12 g, 7.46 mmol), and potassium fluoride (0.789 g, 13.6 mmol) in THF (10 mL) was stirred under nitrogen. Tri-tert-butylphosphine (10% solution in hexane, 0.621 mL, 0.210 mmol) was added to the mixture and allowed to stir until the starting bromide was consumed. The mixture was then diluted with 1/1 hexane/tetrahydrofuran, filtered through a plug of silica gel, the solvent evaporated and the residue purified by silica gel column chromatography (hexane/ethylacetate, 70/30) to afford the title compound (1.77 g, 92%).

Workup

  1. customwas consumed
  2. additionThe mixture was then diluted with 1/1 hexane/tetrahydrofuran
  3. filtrationfiltered through a plug of silica gel
  4. customthe solvent evaporated
  5. customthe residue purified by silica gel column chromatography (hexane/ethylacetate, 70/30)

Sources & evidence

ORD record
ord-0f7630364d1741efb9b58342638fcf62
Source dataset
uspto-grants-2007_11
Patent number
US07291643B2

Reaction notes

Loading…