Dimethylformamide → HCID 68716147, compound

HRID 1913192Notes

Reaction equation

HRID 1913192 reaction equation
[ClH:1].Br[C:3]1[CH:4]=[C:5]([C:9]2[C:10](=[O:21])[N:11]([C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=3)[NH:12][CH:13]=2)[CH:6]=[N:7][CH:8]=1.[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[CH3:20][C:18]1[CH:17]=[CH:16][N:15]=[C:14]([N:11]2[C:10](=[O:21])[C:9]([C:5]3[CH:4]=[C:3]([C:22]#[N:23])[CH:8]=[N:7][CH:6]=3)=[CH:13][NH:12]2)[CH:19]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68715751HCID 68715751, compound

Product 1

HCID 68716147HCID 68716147, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

200 mg (0.5 mmol) of the compound from Example 7, 47 mg (0.4 mmol) of zinc cyanide and 19 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) are reacted in 3 ml of DMF at 220° C. in a single-mode microwave oven (Emrys Optimizer) for 50 min. The reaction mixture is then concentrated under reduced pressure, the residue is taken up in 2 ml of ethanol and the mixture is adjusted with 1 N aqueous sodium hydroxide solution to pH 10. The mixture is extracted with ethyl acetate, the organic phase is dried over sodium sulfate and concentrated under reduced pressure and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with 0.1% formic acid added to the water). The product-containing fractions are concentrated under reduced pressure, the residue is dissolved in 1 ml of ethanol and 0.5 ml of a 4 N solution of hydrogen chloride in dioxane is added. The mixture is stirred at RT for min and then concentrated under reduced pressure, and the residue is dried under high vacuum.

Workup

  1. concentrationThe reaction mixture is then concentrated under reduced pressure
  2. extractionThe mixture is extracted with ethyl acetate
  3. dry with materialthe organic phase is dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe residue is purified by preparative HPLC (RP18 column
  6. additionmobile phase: acetonitrile/water gradient with 0.1% formic acid added to the water)
  7. concentrationThe product-containing fractions are concentrated under reduced pressure
  8. dissolutionthe residue is dissolved in 1 ml of ethanol
  9. addition0.5 ml of a 4 N solution of hydrogen chloride in dioxane is added
  10. concentrationconcentrated under reduced pressure
  11. customthe residue is dried under high vacuum

Sources & evidence

ORD record
ord-c4d71bdc47bd495da3e191f3946a0733
Source dataset
uspto-grants-2013_12
Patent number
US08609698B2

Reaction notes

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