Dimethylacetamide → HCID 66795102, compound

HRID 2403217Notes

Reaction equation

HRID 2403217 reaction equation
O=[C:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][C:4]#[N:5].C[C:13]([N:15](C)C)=O.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.Cl.[CH:36]1([NH:42]N)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.C([O-])(=O)C.[Na+]>C1(C)C=CC=CC=1.CN(C=O)C>[CH:36]1([N:42]2[C:2]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)=[C:3]([C:13]#[N:15])[CH:4]=[N:5]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

8

Reactant 5

HCID 31374DimethylacetamideHCID 64799BenzoylacetonitrileHCID 207836Cyclohexylhydrazine hydrochlorideHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 517045Sodium Acetate

Product 1

HCID 66795102HCID 66795102, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-oxo-3-phenylpropanenitrile (Avocado; 2.2 g; 15 mmol) in toluene (100 mL) was added DMF.DMA (2.7 mL; 20 mmol) and PPTS (375 mg). The mixture was heated to 90° C. for 4 hours. The solvent was removed in vacuo and DCM (100 mL) and water (100 mL) were added and the mixture passed through a hydrophobic frit. The solvent was removed in vacuo and the residue redissolved in ethanol (95 mL) and water (9.5 mL). This solution was added to a mixture of cyclohexylhydrazine hydrochloride (Fluorochem; 2.26 g; 15 mmol), and sodium acetate (2.46 g; 30 mmol). The mixture was heated to reflux for 24 hours and the ethanol removed in vacuo. DCM (100 mL) and water (50 mL) were added and the mixture was filtered through a hydrophobic frit and the solvent removed in vacuo. The residue was purified by flash chromatography on a Biotage 40+M column, eluting with petrol containing increasing amounts of EtOAc. The residue was triturated with diethyl ether to give the title compound as an off-white solid. 1H NMR: (CDCl3, 400 MHz) δ 7.85 (1H, s), 7.58-7.50 (3H, m), 7.46-7.37 (2H, m), 4.14-4.04 (1H, m), 2.07-1.95 (2H, m), 1.95-1.78 (4H, m), 1.74-1.59 (1H, m), 1.72-0.81 (3H, m). LC/MS: 252 (M+H)+. HPLC (Method B) Rt 4.30 min (Purity: 96.3%).

Workup

  1. customThe solvent was removed in vacuo and DCM (100 mL) and water (100 mL)
  2. additionwere added
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue redissolved in ethanol (95 mL)
  5. temperatureThe mixture was heated
  6. temperatureto reflux for 24 hours
  7. customthe ethanol removed in vacuo
  8. additionDCM (100 mL) and water (50 mL) were added
  9. filtrationthe mixture was filtered through a hydrophobic frit
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by flash chromatography on a Biotage 40+M column
  12. washeluting with petrol containing
  13. temperatureincreasing amounts of EtOAc
  14. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-7a907195d464442c9772b8e586b69ae9
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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