4-Bromo-2-fluoroaniline → 5-(4-amino-3-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1593552Notes

Reaction equation

HRID 1593552 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[CH3:10][N:11]1[C:15]([C:16]#[N:17])=[CH:14][CH:13]=[C:12]1B(O)O.[F-].[K+]>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].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:12]2[N:11]([CH3:10])[C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)=[CH:3][C:4]=1[F:9]

Participants

7

Reactant 3

HCID 1230504-Bromo-2-fluoroanilineHCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 156045005-(4-amino-3-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrileYield 27.6%

Reagents, catalysts & solvents 3

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

4-Bromo-2-fluoroaniline (2.42 g, 12.8 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (2.3 g, 15.3 mmol), KF (2.45 g, 42.2 mmol), and Pd2(dba)3 (147 mg, 0.16 mmol) were added to a 100 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 min. THF (32 mL) was added and the mixture was purged with nitrogen for an additional 5 min. A solution of tri-t-butylphosphine (10 wt % in hexanes) (0.95 mL, 0.32 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 5 h. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed through with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification by flash chromatography (20% acetone/hexane) afforded 5-(4-amino-3-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile (0.76 g) as an off-white solid.

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 min
  3. additionTHF (32 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 min
  5. filtrationfiltered through a plug of silica gel
  6. washwashed through with 200 mL of EtOAc
  7. concentrationconcentrated
  8. customto give a crude brown/black semi-solid
  9. customPurification by flash chromatography (20% acetone/hexane)

Sources & evidence

ORD record
ord-d331768799ba464ea36d50583314e710
Source dataset
uspto-grants-2007_11
Patent number
US07297713B2

Reaction notes

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