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

HRID 506207Notes

Reaction equation

HRID 506207 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.[Cl:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(OC(C)C)OC(C)C)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.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:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:14]2[CH:15]=[N:16][CH:17]=[C:18]([C:13]=2[NH:12][C:4]2[C:5]([CH3:11])=[C:6]3[C:10](=[C:2]([Cl:1])[CH:3]=2)[NH:9][CH:8]=[CH:7]3)[C:19]#[N:20])=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 684470354-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrileHCID 68466808Diisopropyl 4-(2-chloroethoxy)phenylboronate

Product 1

HCID 684656455-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrileYield 84.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrile (534 mg, 1.3 mmol) in DME (30 mL) was added diisopropyl 4-(2-chloroethoxy)phenylboronate (754 mg, 2.6 mmol), sodium carbonate solution (2.7 mL of 2M solution, 5.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (150 mg, 0.15 mmol) under nitrogen atmosphere and the reaction mixture was heated at 80° C. for 6 h and cooled to room temperature. Ethyl acetate was added and the organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue was purified by flash column chromatography (ethyl acetate/hexane) to give 5-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile as a yellow solid (482 mg, 84%). HPLC retention time: 10.7 min.(g) and MS: 437.2 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. washthe organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution
  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-39d9238e5e2d45dd8f24f14d31a953a6
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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