Chlorosuccinimide → 3-chloro-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1188411Notes

Reaction equation

HRID 1188411 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.C1C(=O)N([Cl:23])C(=O)C1>CN(C=O)C>[Cl:23][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:11]([C:12]#[N:13])[C:3]=2[C:2]([F:14])([F:1])[F:15])[NH:7][CH:6]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 674054494-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 578003853-chloro-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To an ice-cold solution of 4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.015 g, 0.071 mmol) in DMF (2 mL), under N2, was added a solution of NCS (0.011 g, 0.079 mmol) in DMF (0.5 mL). The mixture was stirred at rt for 1 h and then heated at 75° C. for 40 min. Upon cooling, the mixture was partitioned between Et2O and 0.1N HCl. The organic phase was washed with water and sat'd brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by radial chromatography (50-100% CH2Cl2 hexanes gradient, followed by 1-5% MeOH—CH2Cl2 gradient) to afford the title compound (0.014 g, 82% yield): MS (ES) m/z 245 (M+1).

Workup

  1. temperatureheated at 75° C. for 40 min
  2. temperatureUpon cooling
  3. customthe mixture was partitioned between Et2O and 0.1N HCl
  4. washThe organic phase was washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by radial chromatography (50-100% CH2Cl2 hexanes gradient, followed by 1-5% MeOH—CH2Cl2 gradient)

Sources & evidence

ORD record
ord-4946111f18e142c6b6726c4e0b06bd86
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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