Sodium methanethiolate → 2-methyl-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1851105Notes

Reaction equation

HRID 1851105 reaction equation
CS(O[CH2:6][CH:7]([N:9]1[C:17]2[C:12](=[C:13]([C:20]([F:23])([F:22])[F:21])[C:14]([C:18]#[N:19])=[CH:15][CH:16]=2)[CH:11]=[C:10]1[CH3:24])[CH3:8])(=O)=O.[CH3:25][S-:26].[Na+]>CN(C=O)C.O>[CH3:24][C:10]1[N:9]([CH:7]([CH3:8])[CH2:6][S:26][CH3:25])[C:17]2[C:12]([CH:11]=1)=[C:13]([C:20]([F:21])([F:23])[F:22])[C:14]([C:18]#[N:19])=[CH:15][CH:16]=2

Participants

5

Reactant 2

HCID 4378561Sodium methanethiolate2×HCID 867091612-(5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl)propyl methanesulfonate

Product 1

HCID 867091622-methyl-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 74.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl)propyl methanesulfonate (0.145 g, 0.402 mmol) in DMF (3 mL) was added sodium thiomethoxide (0.056 g, 0.805 mmol) in one portion. After 90 min, additional sodium thiomethoxide (2 eq) was added, and the mixture stirred for another 1 h. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (30 mL). The organic phase was washed with 0.1N HCl (1×20 mL) and brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel using a 0-30% EtOAc-hexane gradient to give 2-methyl-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.094 g, 71% yield) as a colorless oil: MS (ESI): m/z 313 (MH+).

Workup

  1. extractionextracted with EtOAc (30 mL)
  2. washThe organic phase was washed with 0.1N HCl (1×20 mL) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed over silica gel using a 0-30% EtOAc-hexane gradient

Sources & evidence

ORD record
ord-c3b6a31b6153474383f2f50ca8006228
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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