Potassium Fluoride → 5-(4-Amino-2,5-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1591825Notes

Reaction equation

HRID 1591825 reaction equation
Br[C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[CH3:11][N:12]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]1B(O)O.[F-].[K+]>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]>[NH2:6][C:5]1[C:4]([F:10])=[CH:3][C:2]([C:13]2[N:12]([CH3:11])[C:16]([C:17]#[N:18])=[CH:15][CH:14]=2)=[C:8]([F:9])[CH:7]=1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 27732854-Bromo-2,5-difluoroanilineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 160504335-(4-Amino-2,5-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrileYield 77%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
25 °C

Procedure

4-Bromo-2,5-difluoroaniline (0.1 g, 4.85 mmol), 1-methyl-5-cyano-2-pyrrole-boronic acid (1.3 g, 8.7 mmol), KF (0.93 g, 16 mmol), and Pd2(dba)3 (117 mg, 0.12 mmol) were added to a 50 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (12.1 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes) (0.72 mL, 0.24 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 16 hours. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane) afforded 5-(4-amino-2,5-difluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile as a white solid (0.87 g, 77%).

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 minutes
  3. additionTHF (12.1 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 minutes
  5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (0.72 mL, 0.24 mmol) was added via syringe
  6. additionThe mixture was diluted with 250 mL of EtOAc
  7. filtrationfiltered through a plug of silica gel
  8. washwashed with 200 mL of EtOAc
  9. concentrationconcentrated
  10. customto give a crude brown/black semi-solid
  11. customPurification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-843b3fad7be5403da56aad780ca5d97d
Source dataset
uspto-grants-2007_11
Patent number
US07291643B2

Reaction notes

Loading…