Dimethylformamide → HCID 67396653, compound

HRID 1426698Notes

Reaction equation

HRID 1426698 reaction equation
Cl[C:2]1[C:7]([C:8]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:9]=2[F:32])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:33][N:34](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:33]([C:2]1[C:7]([C:8]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:9]=2[F:32])=[CH:6][CH:5]=[CH:4][N:3]=1)#[N:34]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86623991HCID 86623991, compound2×

Product 1

HCID 67396653HCID 67396653, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A suspension of tert-butyl {[5-(2-chloropyridin-3-yl)-4-fluoro-1-(phenylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (7.24 g), zinc cyanide (3.55 g) and tetrakis(triphenylphosphine)palladium (0) (3.56 g) in N,N-dimethylformamide (80 mL) was stirred at 120° C. for 20 hr. The reaction mixture was cooled to room temperature, and insoluble materials were filtered off. Water was added to the filtrate, and the mixture was extracted with ethyl acetate. The extract washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=2:1) to give a mixture of tert-butyl {[5-(2-chloropyridin-3-yl)-4-fluoro-1-(phenylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate and the title compound. A suspension of the obtained mixture, zinc cyanide (3.56 g) and tetrakis(triphenylphosphine)palladium (0) (3.38 g) in N,N-dimethylformamide (80 mL) was stirred at 120° C. for 12 hr. The reaction mixture was cooled to room temperature, and insoluble materials were filtered off. Water was added to the filtrate, and the mixture was extracted with ethyl acetate. The extract washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=2:1) to give the title compound as a yellow oil (yield 5.84 g, 82%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationinsoluble materials were filtered off
  3. additionWater was added to the filtrate
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=2:1)
  9. customto give

Sources & evidence

ORD record
ord-d857a242f74545a89e82a54289963233
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

Loading…