Cesium carbonate → 1-{[5-(5-Bromo-3-pyridinyl)-1,2,4-oxadiazol-3-yl]methyl}-4-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indole-5-carbonitrile

HRID 2102125Notes

Reaction equation

HRID 2102125 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])[NH:7]2.C([O-])([O-])=O.[Cs+].[Cs+].[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[C:33]([C:35]2[O:39][N:38]=[C:37]([CH2:40]Cl)[N:36]=2)[CH:34]=1>C(#N)C>[Br:28][C:29]1[CH:34]=[C:33]([C:35]2[O:39][N:38]=[C:37]([CH2:40][N:7]3[C:8]4[C:4](=[C:3]([C:2]([F:1])([F:20])[F:21])[C:11]([C:12]#[N:13])=[CH:10][CH:9]=4)[CH:5]=[C:6]3[CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:36]=2)[CH:32]=[N:31][CH:30]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 289795273-Bromo-5-[3-(chloromethyl)-1,2,4-oxadiazol-5-YL]pyridineHCID 578002104-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indole-5-carbonitrile

Product 1

HCID 578002641-{[5-(5-Bromo-3-pyridinyl)-1,2,4-oxadiazol-3-yl]methyl}-4-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indole-5-carbonitrileYield 23%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indole-5-carbonitrile (Example 302A) (0.200 g, 0.653 mmol) in anhydrous acetonitrile (25 mL) was added Cs2CO3 (0.851 g, 0.2.612 mmol) and 3-bromo-5-[3-(chloromethyl)-1,2,4-oxadiazol-5-yl]pyridine (0.269 g, 0.979 mmol). The mixture was heated under N2, for 2 h. Upon cooling, the mixture was partitioned between EtOAc and water. The organic phase was separated, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient) to afford a pure product (0.081 g, 23% yield): MS (ES) m/z 544 (M+1).

Workup

  1. temperatureThe mixture was heated under N2, for 2 h
  2. temperatureUpon cooling
  3. customthe mixture was partitioned between EtOAc and water
  4. customThe organic phase was separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-a5dcd07bd83144f39baf6184b751d9f7
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Reaction notes

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