Dimethylacetamide → HCID 67110404, compound

HRID 706244Notes

Reaction equation

HRID 706244 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:34]=[CH:33][C:23]3[N:24]=[C:25]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[S:26][C:22]=3[CH:21]=1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].C[C:37]([N:39](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:37]#[N:39])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[CH:34]=[CH:33][C:23]3[N:24]=[C:25]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[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 86617086HCID 86617086, compound

Product 1

HCID 67110404HCID 67110404, 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-morpholin-4-yl-benzothiazol-6-yloxy)-isoquinoline-3-carboxylic acid butyl ester (200 mg, 0.39 mmol), tris(dibenzylideneacetone)-dipalladium(0) (18 mg, 0.02 mmol), 1,1′-bis(diphenylphosphino)ferrocene (22 mg, 0.04 mmol), zinc cyanide (27 mg, 0.23 mmol), zinc (3 mg, 0.05 mmol) and dimethylacetamide (0.93 mL) was stirred at 120° C. for two hours before it was cooled to room temperature, partitioned between ethyl acetate and water, 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 (137 mg): MS: (+) m/z 505.31 (M+1); (−) m/z 503.31 (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-0266018321c7470d8250cae080a0e967
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

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