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

HRID 1188586Notes

Reaction equation

HRID 1188586 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:26][C:27]1[N:31]=[C:30]([C:32]2[S:33][CH:34]=[CH:35][CH:36]=2)[O:29][N:28]=1>C(#N)C>[CH2:1]([C:4]1[N:5]([CH2:26][C:27]2[N:31]=[C:30]([C:32]3[S:33][CH:34]=[CH:35][CH:36]=3)[O:29][N:28]=2)[C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:15])([F:16])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 594028453-(Bromomethyl)-5-(2-thienyl)-1,2,4-oxadiazoleHCID 674051552-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 578005032-Propyl-1-{[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]methyl}-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 64.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 153A) (0.150 g, 0.595 mmol) in anhydrous acetonitrile (25 mL) was added Cs2CO3 (0.193 g, 0.595 mmol) and 3-(bromomethyl)-5-(2-thienyl)-1,2,4-oxadiazole (0.213 g, 0.893 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 (0.159 g, 64% yield): MS (ES) m/z 416 (M+).

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-5950de4965414567ba6a41773d59d7b6
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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