Dimethylacetamide → HCID 67110399, compound

HRID 706226Notes

Reaction equation

HRID 706226 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Cl)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[CH:29]=[CH:28][C:23]3[N:24]=[C:25]([CH3:27])[S:26][C:22]=3[CH:21]=1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].C[C:32]([N:34](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:5][C:6]([C:8]1[N:9]=[C:10]([C:32]#[N:34])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[CH:29]=[CH:28][C:23]3[N:24]=[C:25]([CH3:27])[S:26][C:22]=3[CH:21]=1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 86617083HCID 86617083, compound

Product 1

HCID 67110399HCID 67110399, 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 1-chloro-4-hydroxy-6-(2-methyl-benzothiazol-6-yloxy)-isoquinoline-3-carboxylic acid butyl ester (369 mg, 0.84 mmol), tris(dibenzylideneacetone)dipalladium(0) (38 mg, 0.04 mmol), 1,1′-bis(diphenylphosphino)ferrocene (46 mg, 0.08 mmol), zinc cyanide (59 mg, 0.50 mmol), zinc (6 mg, 0.10 mmol) and dimethylacetamide (2 mL) was stirred at 120° C. for two hours and twenty minutes before it was cooled to room temperature, partitioned between ethyl acetate and water, and filtered. The filtrate was washed with water and 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 ethyl acetate and dichloromethane to give the title compound as a white solid (245 mg): MS: (+) m/z 434.30 (M+1).

Workup

  1. temperaturewas cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. filtrationfiltered
  4. washThe filtrate was washed with water and 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 ethyl acetate and dichloromethane

Sources & evidence

ORD record
ord-0fb518e9905949c78fd3aee0e3239153
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

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