반응 #531818

ord-cc9345925d1249abb23c8341bead0fc5

반응 방정식

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

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도The reaction mixture was heated
  2. 2
    온도at reflux for 4.5 hours
  3. 3
    기타Thin layer chromatography on silica gel confirmed completion of the reaction
  4. 4
    여과filtered through Celite®
  5. 5
    세척by washing three times with 10% aqueous sodium bicarbonate solution
  6. 6
    추출The organic extract
  7. 7
    건조was dried (MgSO4)
  8. 8
    농축concentrated under reduced pressure
  9. 9
    기타the residual solid was purified by chromatography on silica gel

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08475819B2uspto-grants-2013_07