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

HRID 2101834ノート

反応式

HRID 2101834 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
95 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c069fd78f36145c186d765fc77df6ae4
出典データセット
uspto-grants-2009_08
特許番号
US07572820B2

反応ノート

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