Ethyl Acetate → 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-(5-formyl-1-benzofuran-2-yl)nicotinonitrile

HRID 506202Notes

Reaction equation

HRID 506202 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[C:18]([C:19]#[N:20])=[CH:17][N:16]=[CH:15][C:14]=2I)[C:5]([CH3:11])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C([Sn](CCCC)(CCCC)[C:27]1[O:28][C:29]2[CH:35]=[CH:34][C:33]([CH:36]=[O:37])=[CH:32][C:30]=2[CH:31]=1)CCC.C(OCC)(=O)C>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>[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[C:18]([C:19]#[N:20])=[CH:17][N:16]=[CH:15][C:14]=2[C:27]2[O:28][C:29]3[CH:35]=[CH:34][C:33]([CH:36]=[O:37])=[CH:32][C:30]=3[CH:31]=2)[C:5]([CH3:11])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 684470354-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrileHCID 86616834HCID 86616834, compound

Product 1

HCID 866168374-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-(5-formyl-1-benzofuran-2-yl)nicotinonitrileYield 82.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrile (405 mg, 1 mmol) in DMF (7 mL) was added 2-(tributylstannyl)-1-benzofuran-5-carbaldehyde (609 mg, 1.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (110 mg, 0.1 mmol) under nitrogen atmosphere, the reaction mixture was heated at 110° C. for 1.5 h and cooled to room temperature and ethyl acetate was added to the resulting mixture. The organic phase was washed with water, saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated and the residue was purified by flash column chromatography (ethyl acetate/hexane) to give 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-(5-formyl-1-benzofuran-2-yl)nicotinonitrile as a yellow solid (351 mg, 82%). HPLC retention time: 12.4 min.(g); and MS: 427.3 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic phase was washed with water, saturated aqueous sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customthe residue was purified by flash column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-899b3b2a063f428192d3cee8ff19b537
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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