Acrylonitrile → (2E)-3-(4-amino-3-bromothieno[3,2-c]pyridin-7-yl)acrylonitrile

HRID 2390694Notes

Reaction equation

HRID 2390694 reaction equation
[Br:1][C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](I)[C:5]=2[S:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[C:38](#[N:41])[CH:39]=[CH2:40]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:7]1[C:6]2[C:2]([Br:1])=[CH:3][S:4][C:5]=2[C:10](/[CH:40]=[CH:39]/[C:38]#[N:41])=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 7855AcrylonitrileHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 184507913-Bromo-7-iodothieno[3,2-C]pyridin-4-amine

Product 1

HCID 18450639(2E)-3-(4-amino-3-bromothieno[3,2-c]pyridin-7-yl)acrylonitrileYield 88.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
77 °C

Procedure

To a solution of 3-bromo-7-iodothieno[3,2-c]pyridin-4-ylamine (430 mg, 1.21 mmol), triphenylphosphine (128 mg, 0.48 mmol) and sodium carbonate (257 mg, 2.42 mmol) in N,N-dimethylformamide (6 ml) was added acrylonitrile (0.32 ml, 4.84 mmol) followed by palladium(II) acetate (56 mg, 0.24 mmol). The reaction was heated at 77° C. for 18 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under reduced pressure. The residue was purified by flash chromatography on silica gel using ethyl acetate as the mobile phase to give the title compound (300 mg, 88%) as an off-white solid used directly in the following Suzuki coupling step. LCMS (Conditions g); 2.28; MS: MH+ 280.

Workup

  1. temperatureto cool to ambient temperature
  2. customsolvents were removed under reduced pressure
  3. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5a286ebbce364b0da818ee7b78dd9d92
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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