1-(2-Bromo-5-fluorophenyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one → 4-Fluoro-2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)benzonitrile

HRID 1664187Notes

Reaction equation

HRID 1664187 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[N:12]([CH3:15])[CH:11]=[N:10]1.[C:16]([Cu])#[N:17]>CN1C(=O)CCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:16]#[N:17])=[C:3]([N:9]2[C:13](=[O:14])[N:12]([CH3:15])[CH:11]=[N:10]2)[CH:4]=1

Participants

4

Reactant 2

HCID 588778431-(2-Bromo-5-fluorophenyl)-4-methyl-1H-1,2,4-triazol-5(4H)-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 588779024-Fluoro-2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)benzonitrileYield 79%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 1-(2-bromo-5-fluorophenyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one (0.484 g, 1.78 mmol), CuCN (0.319 g, 3.56 mmol), and 8 mL of NMP was subjected to microwave irradiation at 120° C. for 3 h. The brown mixture was filtered over Celite® and washed with DMF. This solution was treated with 10% aqueous NH4OH (28-30% solution) and extracted with EtOAc. The combined organic fractions were successively washed with 10% aqueous NH4OH (28-30% solution), saturated aqueous NH4Cl, water, brine and dried over Na2SO4. The resulting mixture was concentrated in vacuo and the residue was purified with a Biotage column chromatography system on silica gel with hexanes:ethyl acetate (3:7 to 2:8) gradient as the eluent to afford the title compound as a pink solid (0.305 g, 79% yield): 1H NMR (400 MHz, CDCl3) δ 7.76 (1H, dd, J=8.8, 5.8 Hz), 7.72 (1H, dd, J=9.6, 2.5 Hz), 7.64 (1H, s), 7.10 (1H, ddd, J=8.7, 7.4, 2.7 Hz), 3.40 (3H, s); LCMS (+ESI, M+H+) m/z 219.

Workup

  1. customirradiation at 120° C. for 3 h
  2. filtrationThe brown mixture was filtered over Celite®
  3. washwashed with DMF
  4. additionThis solution was treated with 10% aqueous NH4OH (28-30% solution)
  5. extractionextracted with EtOAc
  6. washThe combined organic fractions were successively washed with 10% aqueous NH4OH (28-30% solution), saturated aqueous NH4Cl, water, brine
  7. dry with materialdried over Na2SO4
  8. concentrationThe resulting mixture was concentrated in vacuo
  9. customthe residue was purified with a Biotage column chromatography system on silica gel with hexanes:ethyl acetate (3:7 to 2:8) gradient as the eluent

Sources & evidence

ORD record
ord-20c4779918bd4b6b9f4ad5610fea3b65
Source dataset
uspto-grants-2011_10
Patent number
US08039458B2

Reaction notes

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