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

HRID 907102Notes

Reaction equation

HRID 907102 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.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=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 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 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) was added to a sealable tube and alternatively evacuated and flushed with N2. To the tube was then added DMF (4 mL) and Et3N (0.25 mL, 1.84 mmol) and the reaction was heated at 80° C. for 20 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 (3×) and saturated NaCl and then dried over MgSO4 and concentrated. The crude reaction mix was 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. additionwas added to a sealable tube
  3. customalternatively evacuated
  4. customflushed with N2
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic phases were washed with H2O (3×) and saturated NaCl
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude reaction
  10. additionmix
  11. customwas absorbed on silica gel (0.6 g)
  12. customchromatographed over silica gel

Sources & evidence

ORD record
ord-26a27ea4d81540999c5a969bf7e0344a
Source dataset
uspto-grants-2011_09
Patent number
US08013006B2

Reaction notes

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