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

HRID 506206Notes

Reaction equation

HRID 506206 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.[O:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1B(O)O.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>[O:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:13]=1[NH:12][C:4]1[C:5]([CH3:11])=[C:6]2[C:10](=[C:2]([Cl:1])[CH:3]=1)[NH:9][CH:8]=[CH:7]2)[C:19]#[N:20]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 2776266Benzo[b]furan-2-boronic acidHCID 684470354-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrile

Product 1

HCID 684660545-(1-benzofuran-2-yl)-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrileYield 15%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrile (122 mg, 0.3 mmol) in DMF (4 mL) was added 2-benzofuranboronic acid (162 mg, 0.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (34 mg, 0.03 mmol) under nitrogen atmosphere and the reaction mixture was heated at 60° C. overnight. After the solution was cooled to room temperature, ethyl acetate was added, and the organic phase was washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography (ethyl acetate/hexane) to give 5-(1-benzofuran-2-yl)-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile (18 mg, 15%). HPLC retention time: 13.4 min.(g); MS: 399.3 (M+H); and HRMS: 399.1009.

Workup

  1. temperatureAfter the solution was cooled to room temperature
  2. washthe organic phase was washed with water and 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-a400cda3dee84b2e9d3b4ed14eb58167
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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