Dimethylformamide → 1-ethyl-2-(4-fluorophenylethynyl)-6-methoxy-1H-indole-3-carbonitrile

HRID 502120Notes

Reaction equation

HRID 502120 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:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]#[CH:25])=[CH:20][CH:19]=1.CN(C=O)C.CCN(CC)CC>O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[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]1[C:25]#[C:24][C:21]1[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=1)[CH3:2]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 5226271-Ethynyl-4-fluorobenzeneHCID 594256441-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile

Product 1

HCID 116597201-ethyl-2-(4-fluorophenylethynyl)-6-methoxy-1H-indole-3-carbonitrileYield 82%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 1-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile (150 mg, 0.46 mmol), prepared as described in example 1Ga, step A, 4-fluorophenylacetylene (80 mg, 0.0.69 mmol), bis(triphenylphosphine)palladium (II) dichloride (6 mg, 0.009 mmol) and CuI (4 mg, 0.018 mmol) is added to a sealable tube and alternatively evacuated and flushed with N2. To the tube is then added DMF (4 mL) and Et3N (0.25 mL, 1.84 mmol) and the reaction is heated at 80° C. for 20 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 (3×) and saturated NaCl and then dried over MgSO4 and concentrated. The crude reaction mix is absorbed on silica gel (0.6 g) and chromatographed over silica gel using EtOAc/hexanes (10-20%) as eluent to afford 120 mg (82%) of 1-ethyl-2-(4-fluorophenylethynyl)-6-methoxy-1H-indole-3-carbonitrile as a yellow solid.

Workup

  1. customprepared
  2. additionis added to a sealable tube
  3. customalternatively evacuated
  4. customflushed with N2
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic phases are washed with H2O (3×) and saturated NaCl
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude reaction
  10. additionmix
  11. customis absorbed on silica gel (0.6 g)
  12. customchromatographed over silica gel

Sources & evidence

ORD record
ord-e845eea873594d7bb489674c0dfa7e0c
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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