Reaction #531818

ord-cc9345925d1249abb23c8341bead0fc5

Reaction equation

CNC(=O)c1cc(I)cc(C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
1-(3-chloro-2-pyridinyl)-N-[4-iodo-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
CNC(=O)c1cc(I)cc(C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
diamide
CNC(=O)c1cc(I)cc(C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
1-(3-chloro-2-pyridinyl)-N-[4-iodo-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
N#[C][Cu]
copper(I) cyanide
CNC(=O)c1cc(C#N)cc(C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
title compound
CNC(=O)c1cc(C#N)cc(C)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    TemperatureThe reaction mixture was heated
  2. 2
    Temperatureat reflux for 4.5 hours
  3. 3
    OtherThin layer chromatography on silica gel confirmed completion of the reaction
  4. 4
    Filtrationfiltered through Celite®
  5. 5
    Washby washing three times with 10% aqueous sodium bicarbonate solution
  6. 6
    ExtractionThe organic extract
  7. 7
    Dryingwas dried (MgSO4)
  8. 8
    Concentrationconcentrated under reduced pressure
  9. 9
    Otherthe residual solid was purified by chromatography on silica gel

Procedure

To a solution of 1-(3-chloro-2-pyridinyl)-N-[4-iodo-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (i.e. the diamide product of Step A) (410 mg, 0.72 mmol) in tetrahydrofuran (8 mL) was added copper(I) iodide (24 mg, 0.126 mmol), tetrakis(triphenyphosphine)palladium(0) (70 mg, 0.060 mmol) and copper(I) cyanide (640 mg, 7.2 mmol) sequentially at room temperature. The reaction mixture was heated at reflux for 4.5 hours. Thin layer chromatography on silica gel confirmed completion of the reaction. The reaction mixture was then diluted with ethyl acetate (20 mL) and filtered through Celite®, followed by washing three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure and the residual solid was purified by chromatography on silica gel to afford 114 mg of the title compound, a compound of the present invention, as a white solid, melting at 214-216° C.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08475819B2uspto-grants-2013_07