Ethyl Acetate → 3-[1-(2-Pyridinyl)-1H-1,2,4-triazol-3-yl]benzonitrile

HRID 2213326Notes

Reaction equation

HRID 2213326 reaction equation
Br[C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:3]=1.[C:13]([C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)#[N:14].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.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>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[N:4]1[CH:5]=[N:6][C:2]([C:19]2[CH:20]=[C:15]([CH:16]=[CH:17][CH:18]=2)[C:13]#[N:14])=[N:3]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 112068762-(3-BROMO-1H-1,2,4-TRIAZOL-1-YL)PYRIDINE

Product 1

HCID 101927803-[1-(2-Pyridinyl)-1H-1,2,4-triazol-3-yl]benzonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

2-(3-Bromo-1H-1,2,4-triazol-1-yl)pyridine (0.25 g, 1.12 mmol) and 3-cyanophenylboronic acid (0.33 g, 2.23 mmol) were dissolved in toluene (20 mL) and methanol (2 mL), then deoxygenated via argon bubbling for 10 min. Potassium carbonate (0.23 g, 1.6 mmol) and tetrakis(triphenylphosphine)palladium (129 mg, 0.11 mmol) were then added to the stirred solution. The reaction flask was fitted with a reflux condenser and the mixture stirred at 90° C. for 16 h, after which time it was cooled to ambient temperature and poured into a separatory funnel containing EtOAc (100 mL). The EtOAc solution was washed with H2O (2×100 mL), then brine (100 mL) and the organic phase was dried (MgSO4), filtered and concentrated in vacuo. The resulting crude residue was chromatographed on silica gel eluting with hexanes:EtOAc (40:60)to afford 3-(1-pyridin-2-yl-1H-1,2,4-triazol-3-yl)benzonitrile as a white solid which was then dissolved in dichloromethane (10 mL) and precipitated as the hydrochloride salt (M.p.=185–188° C.) upon treatment with 1M HCl in diethyl ether (1 mL).

Workup

  1. custommethanol (2 mL), then deoxygenated via argon bubbling for 10 min
  2. customThe reaction flask was fitted with a reflux condenser
  3. temperatureafter which time it was cooled to ambient temperature
  4. additionpoured into a separatory funnel
  5. washThe EtOAc solution was washed with H2O (2×100 mL)
  6. dry with materialbrine (100 mL) and the organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting crude residue was chromatographed on silica gel eluting with hexanes:EtOAc (40:60)to

Sources & evidence

ORD record
ord-84e9cd4dbc3c4093ba08835b4494190c
Source dataset
uspto-grants-2006_09
Patent number
US07105548B2

Reaction notes

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