Bromide ion → [4-(5-Cyano-1-methyl-1H-pyrrol-2-yl)-2-fluorophenyl]cyanamide

HRID 1993966Notes

Reaction equation

HRID 1993966 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]#[N:10])=[C:4]([F:11])[CH:3]=1.[CH3:12][N:13]1[C:17]([C:18]#[N:19])=[CH:16][CH:15]=[C:14]1B(O)O.C(=O)([O-])[O-].[K+].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Br-]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1COCC1>[F:11][C:4]1[CH:3]=[C:2]([C:14]2[N:13]([CH3:12])[C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH:7]=[CH:6][C:5]=1[NH:8][C:9]#[N:10]

Participants

8

Reactant 5

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acidHCID 62483485(4-Bromo-2-fluorophenyl)cyanamide

Product 1

HCID 16037644[4-(5-Cyano-1-methyl-1H-pyrrol-2-yl)-2-fluorophenyl]cyanamideYield 12.5%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-bromo-2-fluorophenylcyanamide (0.106 g, 0.5 mmol), tris(dibenzylideneacetone) dipalladium (11.6 mg, 0.0126 mmol), N-methyl-5-cyanopyrroleboronic acid (0.150 g, 1 mmol), and potassium carbonate (0.276 g, 2 mmol) were placed in a 40 mL vial fitted with a septa. The vial was then filled with a continuous flow of nitrogen and THF (2 mL) was added with stirring. Tri-tert-butylphosphine (10 wt % in hexane) (0.0486 mL, 0.0252 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/ethylacetate, filtered through a plug of silica gel, the solvent evaporated and the residue was flash chromatographed on silica gel using 4/1 Hexane/THF to give [2-fluoro-4-(5-cyano-1-methyl-1H-pyrrol-2-yl)phenyl]cyanamide (0.015 g, 12%).

Workup

  1. customvial fitted with a septa
  2. additionwas added
  3. customwas consumed
  4. additionThe mixture was then diluted with 1/1 hexane/ethylacetate
  5. filtrationfiltered through a plug of silica gel
  6. customthe solvent evaporated
  7. customchromatographed on silica gel using 4/1 Hexane/THF

Sources & evidence

ORD record
ord-a8f13faf5a334ad0817a8ed1ecfde632
Source dataset
uspto-grants-2010_01
Patent number
US07652062B2

Reaction notes

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