P-Anisidine → 5-[(4-Fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarbonitrile

HRID 2364549Notes

Reaction equation

HRID 2364549 reaction equation
Br[C:2]1[C:3]([C:16]#[N:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:24][O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[F:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][C:6]2[CH:7]=[C:2]([NH:30][C:29]3[CH:31]=[CH:32][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[C:3]([C:16]#[N:17])=[N:4][CH:5]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 7732P-AnisidineHCID 10796Cesium carbonateHCID 59799017HCID 59799017, compound

Product 1

HCID 694824515-[(4-Fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarbonitrileYield 83%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

A dry 50 mL flask was charged with 3-bromo-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrile (55.3 mg, 0.190 mmol), cesium carbonate (87 mg, 0.266 mmol), palladium acetate (2.1 mg, 0.0095 mmol), rac-BINAP (8.9 mg, 0.0143 mmol), 4-(methyloxy)aniline (28 mg, 0.228 mmol) and toluene (5 mL). The mixture was refluxed for 5 hours, cooled to ambient temperature, filtered through Celite eluting with dichloromethane, and concentrated under reduced pressure. Purification by silica gel chromatography (0-100% ethyl acetate/hexanes gradient elution) gave 5-[(4-fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarbonitrile (52.2 mg, 83% yield) as a white solid. 1H NMR (CDCl3) δ 7.88 (s, 1 H), 7.07-7.02 (m, 4 H), 6.98-6.88 (m, 5 H), 6.21 (br s, 1 H), 3.82 (s, 2 H); MS m/z 334 (M+1).

Workup

  1. temperatureThe mixture was refluxed for 5 hours
  2. filtrationfiltered through Celite
  3. washeluting with dichloromethane
  4. concentrationconcentrated under reduced pressure
  5. customPurification
  6. washby silica gel chromatography (0-100% ethyl acetate/hexanes gradient elution)

Sources & evidence

ORD record
ord-13ddff4dd9cd478a84c707b96cc9cd49
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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