Water → 1-(Cyclopropylmethyl)-2-ethyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 2101969Notes

Reaction equation

HRID 2101969 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[C:11]([C:14]([F:17])([F:16])[F:15])[C:10]([C:18]#[N:19])=[CH:9][CH:8]=2)[CH3:4].Br[CH2:21][CH:22]1[CH2:24][CH2:23]1.O>CN(C=O)C.CCOCC>[CH:22]1([CH2:21][N:6]2[C:7]3[C:12](=[C:11]([C:14]([F:17])([F:15])[F:16])[C:10]([C:18]#[N:19])=[CH:9][CH:8]=3)[CH:13]=[C:5]2[CH2:3][CH3:4])[CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 674038192-ethyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 674048981-(Cyclopropylmethyl)-2-ethyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 64.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a slurry of hexanes-washed NaH (0.0112 g, 0.279 mmol) in DMF (1 mL) at 0° C. was added a solution of 2-ethyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.0332 g, 0.139 mmol) in DMF (1 mL), dropwise over 3 min. The mixture was stirred 30 min and bromomethylcyclopropane (0.030 mL, 0.28 mmol) was added via syringe. The mixture was stirred 5 h at rt, diluted with Et2O, poured into water, and the layers were separated. The aqueous layer was extracted with Et2O (×2), combined organics were washed (H2O, brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by RP-HPLC(C18 column, MeCN/H2O with 0.1% TFA), affording 0.0261 g of the title compound as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.55-7.47 (m, 2H), 6.59 (s, 1H), 4.07 (d, J=6.4 Hz, 2H), 2.84 (q, J=7.4 Hz, 2H), 1.44 (t, J=7.5 Hz, 3H), 1.24-1.01 (m, 1H), 0.66-0.57 (m, 2H), 0.41-0.32 (m, 2H).

Workup

  1. stirringThe mixture was stirred 5 h at rt
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with Et2O (×2)
  4. washcombined organics were washed (H2O, brine)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by RP-HPLC(C18 column, MeCN/H2O with 0.1% TFA),

Sources & evidence

ORD record
ord-86bfd4ffb23e4199932da8522d6b7dfd
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Reaction notes

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