Cesium carbonate → [1-(3,5-Difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamino]-acetonitrile

HRID 1158839Notes

Reaction equation

HRID 1158839 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:9]=[C:10]([CH:32]=[C:33]([F:35])[CH:34]=1)[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([NH2:21])[CH:19]=2)[C:14]([S:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N+:29]([O-:31])=[O:30])=[CH:13]1.Br[CH2:37][C:38]#[N:39]>CN(C)C=O>[F:7][C:8]1[CH:9]=[C:10]([CH:32]=[C:33]([F:35])[CH:34]=1)[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([NH:21][CH2:37][C:38]#[N:39])[CH:19]=2)[C:14]([S:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N+:29]([O-:31])=[O:30])=[CH:13]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11534BromoacetonitrileHCID 594638551-(3,5-Difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamine

Product 1

HCID 11518048[1-(3,5-Difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamino]-acetonitrileYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (3.8 g, 11.7 mmol) was added to an ice-cooled solution of 1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamine (Example 15a; 3.2 g, 7.79 mmol) in dry dimethyl formamide (15 ml). After 15 min. stirring, bromoacetonitrile (7.4 g, 62.3 mmol) was added and the reaction mixture was heated at 80° C. for 2 h. The mixture was quenched with water and the product was extracted into ethyl acetate. The combined organic phases were washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (toluene/acetone 95:5) and crystallization from acetonitrile afforded the title compound (0.42 g). 1H-NMR (CDCl3) δ 8.27 (dd, 1H, J=8.4 and 1.6 Hz), 7.37 (d, 1H, J=8.6 Hz), 7.32 (s, 1H), 7.31 (ddd, 1H, J=8.4, 7.4 and 1.6 Hz), 7.19 (ddd, 1H, J=8.4, 7.4 and 1.6 Hz), 6.99 (dd, 1H, J=8.4 and 1.6 Hz), 6.76 (tt, 1H, J=8.6 and 2.0 Hz), 6.67 (m, 2H), 6.64 (dd, 1H, J=8.6 and 2.0 Hz), 6.54 (d, 1H, J=2.0 Hz), 5.32 (s, 2H), 4.13 (d, 2H, J=6.6 Hz), 4.04 (t, 1H, J=6.6 Hz).

Workup

  1. customThe mixture was quenched with water
  2. extractionthe product was extracted into ethyl acetate
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customColumn chromatography (toluene/acetone 95:5) and crystallization from acetonitrile

Sources & evidence

ORD record
ord-d8ce3226560e49fcae28dbeddd95337f
Source dataset
uspto-grants-2010_10
Patent number
US07812036B2

Reaction notes

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