3-{1-[6-(2,4-Difluorophenyl)pyridin-2-yl]-2-oxobut-3-yn-1-yl}-4-fluorobenzonitrile → 3-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-4-fluorobenzonitrile

HRID 1360683Notes

Reaction equation

HRID 1360683 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=2[F:28])[C:23]#[N:24])[C:16](=[O:19])[C:17]#[CH:18])[CH:12]=[CH:11][CH:10]=1>CN1C(=O)CCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]2[C:13]([CH:12]=[CH:11][CH:10]=1)=[C:15]([C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[F:28])[C:23]#[N:24])[C:16](=[O:19])[CH:17]=[CH:18]2

Participants

3

Reactant 1

HCID 577003623-{1-[6-(2,4-Difluorophenyl)pyridin-2-yl]-2-oxobut-3-yn-1-yl}-4-fluorobenzonitrile

Product 1

HCID 160647573-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-4-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-{1-[6-(2,4-difluorophenyl)pyridin-2-yl]-2-oxobut-3-yn-1-yl}-4-fluorobenzonitrile (From Step E above, 24 g, 63.8 mmol) in NMP was heated to 90° C. for ½ hour. LCMS analysis revealed the reaction was complete and the reaction was poured into ice water (4 L). After stirring for 12 h, the solid precipitate was collected by filtration. The solid was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH). The aqueous filtrate was extracted with EtOAc. The organic layer was washed with H2O (4×), brine (2×), dried over MgSO4, and condensed in vacuo. The crude residue was purified using silica gel chromatography (CH2Cl2/EtOAc/MeOH). A combined 7.8 g of the title compound was collected.

Workup

  1. filtrationthe solid precipitate was collected by filtration
  2. customThe solid was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH)
  3. extractionThe aqueous filtrate was extracted with EtOAc
  4. washThe organic layer was washed with H2O (4×), brine (2×)
  5. dry with materialdried over MgSO4, and condensed in vacuo
  6. customThe crude residue was purified
  7. customA combined 7.8 g of the title compound was collected

Sources & evidence

ORD record
ord-2f9454ceb9c44dd1a50b5bbe4b0c3db0
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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