Cesium fluoride → 2-(4-aminophenyl)-1-ethyl-6-methoxy-1H-indole-3-carbonitrile

HRID 502115Notes

Reaction equation

HRID 502115 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]#[N:15])=[C:4]1I)[CH3:2].[F-].[Cs+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:3][C:11]1[CH:6]=[CH:7][C:8]([C:4]2[N:3]([CH2:1][CH3:2])[C:11]3[C:6]([C:5]=2[C:14]#[N:15])=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=3)=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 25953Cesium fluorideHCID 594256441-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile

Product 1

HCID 116017362-(4-aminophenyl)-1-ethyl-6-methoxy-1H-indole-3-carbonitrileYield 137.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 1-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile (1.25 g, 3.83 mmol), 4-(4,4,5,5-tetramethyl)-1,3-2-dioxaboralanyl-2-yl-aniline (0.96 g, 4.90 mmol), CsF (1.46 g, 9.58 mmol) and Pd(PPh3)2Cl2 (110 mg, 0.15 mmol) in DME (20 mL) is added to a flask and alternatively evacuated and flushed with N2. The reaction is then heated at reflux for 24 h and then cooled to room temperature. The reaction mixture is diluted with H2O and extracted with EtOAc (2×). The combined organic phases are washed with H2O and saturated NaCl and then dried over MgSO4 and concentrated. The crude reaction mix is purified by flash chromatography on silica gel using EtOAc/CH2Cl2 (5/95) as eluent to afford 765 mg (69%) of 2-(4-aminophenyl)-1-ethyl-6-methoxy-1H-indole-3-carbonitrile as a yellow solid.

Workup

  1. additionis added to a flask
  2. customalternatively evacuated
  3. customflushed with N2
  4. temperatureThe reaction is then heated
  5. temperatureat reflux for 24 h
  6. additionThe reaction mixture is diluted with H2O
  7. extractionextracted with EtOAc (2×)
  8. washThe combined organic phases are washed with H2O and saturated NaCl
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe crude reaction
  12. additionmix
  13. customis purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-35531b83094e4bb2a30ce3ca12ad5254
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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