5-bromo-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide → 5-cyano-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide

HRID 2381791Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2381791
Br[C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:8])=[C:4]([CH3:17])[CH:3]=1.[Cu](C#N)[C:19]#[N:20]>CN(C)C=O>[C:19]([C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:8])=[C:4]([CH3:17])[CH:3]=1)#[N:20]

Komponenten

4

Edukt 2

HCID 684940365-bromo-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamideHCID 178418260HCID 178418260, Verbindung

Produkt 1

HCID 684907745-cyano-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamideAusbeute 45,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 5-bromo-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide (1.92 g, 6.17 mmol) and copper cyanide (2.21 g, 24.68 mmol) in anhydrous N,N-dimethylformamide (25 mL) was stirred under nitrogen atmosphere at 150° C. for 18 h. The reaction mixture was allowed to cool to ambient temperature, and partitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide solution (200 mL). The aqueous layer was extracted with ethyl acetate (100 mL), and combined organic layer was washed with water (2×100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 7% methanol in dichloromethane to afford the title compound as an off-white solid (0.72 g, 45%): 1H NMR (300 MHz, CDCl3) δ 8.60 (s, 1H), 8.57 (s, 1H), 7.71 (dd, J=7.8, 7.8 Hz, 1H), 7.39 (s, 1H), 7.30 (m, 1H), 6.31 (br s, 1H), 4.63 (d, J=5.9 Hz, 2H), 2.50 (s, 3H); MS (ES+) m/z 258.2 (M+1).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. custompartitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide solution (200 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (100 mL)
  4. washwas washed with water (2×100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with 7% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-ec5bda5a2cb842b8b3413d884e9146d5
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258160B2

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