Bromide ion → 5-(4-Amino-2-cyanophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1591846Notes

Reaction equation

HRID 1591846 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5](Cl)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:11][N:12]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]1B(O)O.[F-].[K+].[Br-]>O1CCCC1.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>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:13]2[N:12]([CH3:11])[C:16]([C:17]#[N:18])=[CH:15][CH:14]=2)=[C:6]([C:7]#[N:8])[CH:9]=1

Participants

8

Reactant 4

HCID 259Bromide ionHCID 522689Potassium FluorideHCID 109972345-Amino-2-chlorobenzonitrileHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 160505295-(4-Amino-2-cyanophenyl)-1-methyl-1H-pyrrole-2-carbonitrileYield 92.8%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 5-amino-2-chlorobenzonitrile (1.3 g, 8.58 mmol), tris(dibenzylideneacetone)dipalladium (0.192 g, 0.209 mmol), N-methyl-5-cyanopyrroleboronic acid (2.55 g, 17.16 mmol), and potassium fluoride (1.81 g, 31.25 mmol) in tetrahydrofuran (20 mL) was stirred under nitrogen. Tri-tert-butylphosphine (10% solution in hexane, 1.23 mL, 0.414 mmol) was added to the mixture and allowed to stir 3 hours at 50° C. until the starting bromide was consumed. The mixture was then diluted with 1/1 hexane/tetrahydrofuran and filtered through a plug of silica gel. The solvent was evaporated and the residue was purified by silica gel column chromatography (hexane/ethylacetate, 90/10 to 50/50) 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 was evaporated
  5. customthe residue was purified by silica gel column chromatography (hexane/ethylacetate, 90/10 to 50/50)

Sources & evidence

ORD record
ord-b0b53fbfd39649368c6adaa2d00ee86d
Source dataset
uspto-grants-2007_11
Patent number
US07291643B2

Reaction notes

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