Cesium carbonate → 2-[5-Cyano-4-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indol-1-yl]acetamide

HRID 1188616Notes

Reaction equation

HRID 1188616 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[CH2:29][C:30]([NH2:32])=[O:31]>C(#N)C>[C:12]([C:11]1[C:3]([C:2]([F:1])([F:20])[F:21])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:29][C:30]([NH2:32])=[O:31])[C:6]([CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:5]2)#[N:13]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 578002104-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indole-5-carbonitrile

Product 1

HCID 578000942-[5-Cyano-4-(trifluoromethyl)-2-(3,3,3-trifluoropropyl)-1H-indol-1-yl]acetamideYield 51%

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 (50 mL) was added Cs2CO3 (0.851 g, 0.2.612 mmol) and 2-bromoacetamide (0.300 g, 1.37 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 (0.121 g, 51% yield): MS (ES) m/z 363 (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-87b5ef98ec9447e8bf944415f12a504a
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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