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

HRID 913689Notes

Reaction equation

HRID 913689 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-013457d40415448581080ba24a596c07
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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