Cesium carbonate → 4-{4-[5-(benzyloxy)pyridin-3-yl]-9H-carbazol-9-yl}-2-fluorobenzonitrile

HRID 1877478

Reaction equation

HRID 1877478 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:10])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:59]([O:66][C:67]1[CH:68]=[C:69]([C:73]2[C:85]3[C:84]4[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=4)[NH:78][C:77]=3[CH:76]=[CH:75][CH:74]=2)[CH:70]=[N:71][CH:72]=1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:59]([O:66][C:67]1[CH:68]=[C:69]([C:73]2[C:85]3[C:84]4[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=4)[N:78]([C:2]4[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:10])[CH:3]=4)[C:77]=3[CH:76]=[CH:75][CH:74]=2)[CH:70]=[N:71][CH:72]=1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7360294-Bromo-2-fluorobenzonitrileHCID 673086444-[5-(benzyloxy)pyridin-3-yl]-9H-carbazole

Product 1

HCID 673091964-{4-[5-(benzyloxy)pyridin-3-yl]-9H-carbazol-9-yl}-2-fluorobenzonitrileYield 64.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

1.08 g of 4-bromo-2-fluorobenzonitrile, 4.48 g of caesium carbonate, 0.25 g of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and 0.08 g of palladium acetate are successively added, under argon, to a solution of 1.27 g of 4-[5-(benzyloxy)pyridin-3-yl]-9H-carbazole in 100 ml of dioxane. The reaction mixture is refluxed for 2 and a half hours, cooled to ambient temperature, filtered through celite and concentrated under reduced pressure. The residue is purified by silica gel chromatography, elution being carried out with a mixture of cyclohexane and ethyl acetate (80/20 by volume), so as to give 1.1 g of 4-{4-[5-(benzyloxy)pyridin-3-yl]-9H-carbazol-9-yl}-2-fluorobenzonitrile in the form of a colourless oil, the characteristics of which are the following:

Workup

  1. temperatureThe reaction mixture is refluxed for 2 and a half hours
  2. filtrationfiltered through celite and
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by silica gel chromatography, elution
  5. additionbeing carried out with a mixture of cyclohexane and ethyl acetate (80/20 by volume)

Sources & evidence

ORD record
ord-79273cafb8e84b1fa9699b19c630ebad
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Linked notes

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