Dimethylformamide → 6-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

HRID 1677715Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1677715
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12](Br)[CH:13]=1)=[O:4].[CH3:22][N:23](C=O)C>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-]#N.[Zn+2].[C-]#N.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].[Zn]>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12]([C:22]#[N:23])[CH:13]=1)=[O:4]

Komponenten

7

Edukt 2

HCID 6228DimethylformamideHCID 581387736-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Produkt 1

HCID 581388956-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A sealed tube was charged with 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester (1.5 g, 4.3 mmol), Pd2(dba)3 (0.4 g, 0.4 mmol), zinc cyanide (0.6 g, 5 mmol), dppf (0.3 g, 0.4 mmol) and zinc powder (0.2 g, 3 mmol) and DMF (20 mL). The reaction solution was degassed with argon for 15 minutes and warmed at 120° C. for 3 hours. The reaction was cooled to room temperature, diluted with saturated aqueous ammonium chloride (10 mL) and ethyl acetate (50 mL). The organic layer was separated and washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 0-20% ethyl acetate in hexanes to afford 6-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester.

Aufarbeitung

  1. customThe reaction solution was degassed with argon for 15 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with saturated aqueous ammonium chloride (10 mL) and ethyl acetate (50 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a gradient of 0-20% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-d3dac8f4498a43479bcca06d446b17aa
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08008327B2

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