5-iodo-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile → 5-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile

HRID 506193Notes

Reaction equation

HRID 506193 reaction equation
I[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:9]=1[NH:10][C:11]1[C:12]([CH3:20])=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2)[C:7]#[N:8].C([Sn](CCCC)(CCCC)[C:26]1[O:27][C:28]2[CH:34]=[CH:33][C:32]([CH:35]=[O:36])=[CH:31][C:29]=2[CH:30]=1)CCC>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:35]([C:32]1[CH:33]=[CH:34][C:28]2[O:27][C:26]([C:2]3[CH:3]=[N:4][CH:5]=[C:6]([C:9]=3[NH:10][C:11]3[C:12]([CH3:20])=[C:13]4[C:17](=[CH:18][CH:19]=3)[NH:16][CH:15]=[CH:14]4)[C:7]#[N:8])=[CH:30][C:29]=2[CH:31]=1)=[O:36]

Participants

5

Reactant 2

HCID 684438315-iodo-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrileHCID 86616834HCID 86616834, compound

Product 1

HCID 866168355-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrileYield 76.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-iodo-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile (2.5 g, 6.7 mmol), 2-(tributylstannyl)-1-benzofuran-5-carbaldehyde (4.35 g, 10 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.34 mmol) in DMF (25 mL) was heated at 120° C. for 1 h. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water, resulting in a suspension. The insoluble material was removed by filtration and the residue was washed thoroughly with ethyl acetate. The organic layer (from filtrate) was washed with water twice and brine, dried over sodium sulfate, and concentrated and the residue was purified by column chromatography (ethyl acetate/hexane, 1:1) to give 2.0 g (76%) of 5-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile as a yellow solid. HPLC retention time: 10.7 min.(h); MS: 393.2 (M+H); melting point: 235-237° C.; and HRMS: 393.13484.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. customresulting in a suspension
  4. customThe insoluble material was removed by filtration
  5. washthe residue was washed thoroughly with ethyl acetate
  6. washThe organic layer (from filtrate) was washed with water twice
  7. dry with materialbrine, dried over sodium sulfate
  8. concentrationconcentrated
  9. customthe residue was purified by column chromatography (ethyl acetate/hexane, 1:1)

Sources & evidence

ORD record
ord-3835316e2c3741ae8981c9e2bfb8ef04
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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