8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one → 8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-cyano-4H-3,1-benzoxazin-4-one

HRID 1751768Notes

Reaction equation

HRID 1751768 reaction equation
[Cl:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[N:16]([C:17]4[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][N:18]=4)[N:15]=[C:14]([Cl:24])[CH:13]=3)[O:8][C:7](=[O:25])[C:6]=2[CH:5]=[C:4](I)[CH:3]=1.[Cu][C:28]#[N:29]>O1CCCC1.C(OCC)(=O)C.[Cu]I>[Cl:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[N:16]([C:17]4[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][N:18]=4)[N:15]=[C:14]([Cl:24])[CH:13]=3)[O:8][C:7](=[O:25])[C:6]=2[CH:5]=[C:4]([C:28]#[N:29])[CH:3]=1

Participants

6

Reactant 2

HCID 668577638-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one2×HCID 178418546HCID 178418546, compound

Product 1

HCID 668575628-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-cyano-4H-3,1-benzoxazin-4-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one (i.e. the benzoxazinone product of Step B) (575 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper(I) iodide (840 mg, 0.44 mmol), tetrakis(triphenyphosphine)palladium(0) (255 mg, 0.22 mmol) and copper(I) cyanide (500 mg, 5.5 mmol) sequentially at room temperature. The reaction mixture was then heated at reflux overnight. The reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction. The reaction was 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 375 mg of the title compound as a crude yellow solid.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux overnight
  3. customThe reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction
  4. filtrationfiltered through Celite®
  5. washby washing three times with 10% aqueous sodium bicarbonate solution
  6. extractionThe organic extract
  7. dry with materialwas dried (MgSO4)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a765df1fab2b491fac289dcbe51677c3
Source dataset
uspto-grants-2015_10
Patent number
US09161540B2

Reaction notes

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