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

HRID 907097Notes

Reaction equation

HRID 907097 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) was added to a flask and alternatively evacuated and flushed with N2. The reaction was then heated at reflux for 24 h and then cooled to room temperature. The reaction mixture was diluted with H2O and extracted with EtOAc (2×). The combined organic phases were washed with H2O and saturated NaCl and then dried over MgSO4 and concentrated. The crude reaction mix purified by flash chromatographt 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. additionwas added to a flask
  2. customalternatively evacuated
  3. customflushed with N2
  4. temperatureThe reaction was then heated
  5. temperatureat reflux for 24 h
  6. additionThe reaction mixture was diluted with H2O
  7. extractionextracted with EtOAc (2×)
  8. washThe combined organic phases were washed with H2O and saturated NaCl
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe crude reaction
  12. additionmix
  13. custompurified by flash chromatographt on silica gel

Sources & evidence

ORD record
ord-28902c0a165743709751bf81d80f44d6
Source dataset
uspto-grants-2011_09
Patent number
US08013006B2

Reaction notes

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