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

HRID 2101834노트

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HRID 2101834 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
95 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c069fd78f36145c186d765fc77df6ae4
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572820B2

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