Réaction #531815

ord-d46e7aa5a3e14a82b05e5ef83b855d65

Équation de réaction

N#[C][Cu]
copper(I) cyanide
Cc1cc(I)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one
Cc1cc(I)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
benzoxazinone
Cc1cc(I)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one
N#[C][Cu]
copper(I) cyanide
Cc1cc(C#N)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
title compound
Cc1cc(C#N)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazin-4-one

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    TempératureAfter heating the reaction mixture
  2. 2
    Températureat reflux overnight
  3. 3
    AutreThe reaction mixture turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction
  4. 4
    Filtrationfiltered through Celite®
  5. 5
    Lavageby washing three times with 10% aqueous sodium bicarbonate solution
  6. 6
    ExtractionThe organic extract
  7. 7
    Séchagewas dried (MgSO4)
  8. 8
    Concentrationconcentrated under reduced pressure

Mode opératoire

To a solution of 2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one (i.e. the benzoxazinone product of Step D) (500 mg, 0.94 mmol) in tetrahydrofuran (10 mL) was added copper(I) iodide (180 mg, 0.094 mmol), tetrakis(triphenyphosphine)palladium(0) (5.4 mg, 0.047 mmol) and copper(I) cyanide (420 mg, 4.7 mmol) sequentially at room temperature. After heating the reaction mixture at reflux overnight, additional copper(I) cyanide (420 mg, 4.7 mmol), copper(I) iodide (107 mg, 0.56 mmol) and tetrakis(triphenylphosphine)palladium(0) (325 mg, 0.28 mmol) were added and the reflux was continued for 1 hour. The reaction mixture turned black in color, at which point 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 to afford 410 mg of the title compound as a crude yellow solid.

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US08475819B2uspto-grants-2013_07