Cesium carbonate → 4-Chloro-2-(difluoromethyl)-1-{[5-(3,5-difluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-1H-indole-5-carbonitrile

HRID 913400Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 913400
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:13]([F:15])[F:14])[NH:6]2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:23][C:24]1[N:28]=[C:27]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=2)[O:26][N:25]=1>CC#N>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:13]([F:14])[F:15])[N:6]2[CH2:23][C:24]1[N:28]=[C:27]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=2)[O:26][N:25]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 249856324-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrileHCID 431202093-(Chloromethyl)-5-(3,5-difluorophenyl)-1,2,4-oxadiazole

Produkt 1

HCID 247644714-Chloro-2-(difluoromethyl)-1-{[5-(3,5-difluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-1H-indole-5-carbonitrileAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of 4-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile (0.23 g, 1.0 mmol) in anhydrous MeCN (5 mL) was added Cs2CO3 (0.38 g, 1.15 mmol) and 3-(chloromethyl)-5-(3,5-difluorophenyl)-1,2,4-oxadiazole (0.27 g, 1.15 mmol). The mixture was heated in a sealed tube at 95° C., under N2, for 1 h. Upon cooling, the mixture was partitioned between EtOAc and water. The organic phase was washed with water and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (2-30% EtOAc-hexanes gradient) and the product was crystallized from CH2Cl2-hexanes to afford the title compound as a white solid (0.32 g, 77% yield): 1H NMR (400 MHz, acetone-d6) δ 7.91 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.70 (m, 2H), 7.45 (t, J=53.4 Hz, 1H), 7.42 (tt, J=9.0, 2.4 Hz, 1H), 7.20 (s, 1H), 5.95 (s, 2H); MS (ES) m/z 421 (M+1).

Aufarbeitung

  1. temperatureUpon cooling
  2. customthe mixture was partitioned between EtOAc and water
  3. washThe organic phase was washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (2-30% EtOAc-hexanes gradient)
  7. customthe product was crystallized from CH2Cl2-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-9fb029a3d0514220b950442c31d89d9e
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026262B2

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