Dimethylacetamide → HCID 68426450, compound

HRID 642368Notes

Reaction equation

HRID 642368 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:11]=[C:10](Br)[C:9]2[N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[S:15][C:8]=2[C:7]=1[OH:23])=[O:5])[CH3:2].C[C:25]([N:27](C)C)=O>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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N.[Zn]>[CH2:1]([O:3][C:4]([C:6]1[N:11]=[C:10]([C:25]#[N:27])[C:9]2[N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[S:15][C:8]=2[C:7]=1[OH:23])=[O:5])[CH3:2]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 86617356HCID 86617356, compound

Product 1

HCID 68426450HCID 68426450, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 4-bromo-2-(4-fluoro-phenyl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester (157 mg, 0.40 mmole), tris(dibenzylideneacetone)-dipalladium(0)(18 mg, 0.02 mmole), 1,1′-bis(diphenylphosphino)ferrocene (22 mg, 0.04 mmole), zinc cyanide (28 mg, 0.24 mmole) and zinc (3 mg, 0.05 mmole) in dimethylacetamide (0.8 ml) was stirred at 120° C. for 4.5 h before it was cooled to room temperature, partitioned between ethyl acetate and water, filtered. The filtrate washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of methanol and dichloromethane to give the title compound as a yellow solid (64 mg). MS: (+) m/z 344.26 (M+1), MS: (−) m/z 342.27 (M−1).

Workup

  1. temperaturewas cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. filtrationfiltered
  4. washThe filtrate washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel with a gradient of methanol and dichloromethane

Sources & evidence

ORD record
ord-3ae07c5d867a40b1ba776417a8d0cea7
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

Loading…