Dimethylformamide → HCID 86723037, compound

HRID 522324Notes

Reaction equation

HRID 522324 reaction equation
[Cl:1][C:2]1[C:3](I)=[N:4][N:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:17]=3[CH:18]([CH3:20])[CH3:19])[C:9]2=[O:28])[C:6]=1[CH3:7].[CH3:30][N:31](C=O)C>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:1][C:2]1[C:3]([C:30]#[N:31])=[N:4][N:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:17]=3[CH:18]([CH3:20])[CH3:19])[C:9]2=[O:28])[C:6]=1[CH3:7]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86723038HCID 86723038, compound

Product 1

HCID 86723037HCID 86723037, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(4-chloro-3-iodo-5-methylpyrazol-1-yl)-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one (0.057 g, 0.11 mmol), Zn(CN)2 (0.025 g, 0.21 mmol), Pd2(dba)3 (0.010 g, 0.011 mmol) and dppf (0.009 g, 0.016 mmol) in DMF (2 mL) was heated at 85° C. for 1 h under a N2 atmosphere. The mixture was then cooled to room temperature, quenched with sat. NaHCO3 (30 mL,) and extracted with EtOAc (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo and purified by flash chromatography (SiO2, 0˜100% EtOAc/CH2Cl2 gradient elution) to give 4-chloro-1-[1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]-2-oxo-pyrrolidin-3-yl]-5-methylpyrazole-3-carbonitrile (0.042 g, 92%).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customquenched with sat. NaHCO3 (30 mL,)
  3. extractionextracted with EtOAc (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (SiO2, 0˜100% EtOAc/CH2Cl2 gradient elution)

Sources & evidence

ORD record
ord-49c63220027e4337877f290e7c1245de
Source dataset
uspto-grants-2016_05
Patent number
US09328116B2

Reaction notes

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