Sodium Cyanide → 6-(4-Chloro-3-methoxy-phenyl)-2,2-dimethyl-3,6-dioxo-5-pyridin-4-yl-hexanenitrile

HRID 2223097Notes

Reaction equation

HRID 2223097 reaction equation
[CH3:1][C:2]([CH3:15])([C:5](=[O:14])[CH:6]=[CH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)[C:3]#[N:4].[C-]#N.[Na+].[Cl:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][C:21]=1[O:28][CH3:29].C(=O)([O-])O.[Na+]>CN(C=O)C.O>[Cl:19][C:20]1[CH:27]=[CH:26][C:23]([C:24](=[O:25])[CH:7]([C:8]2[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=2)[CH2:6][C:5](=[O:14])[C:2]([CH3:15])([CH3:1])[C:3]#[N:4])=[CH:22][C:21]=1[O:28][CH3:29]

Participants

7

Reactant 4

HCID 8929Sodium CyanideHCID 516892Sodium BicarbonateHCID 129097254-Chloro-3-methoxybenzaldehydeHCID 691376492,2-Dimethyl-3-oxo-5-pyridin-4-yl-pent-4-enenitrile

Product 1

HCID 691376796-(4-Chloro-3-methoxy-phenyl)-2,2-dimethyl-3,6-dioxo-5-pyridin-4-yl-hexanenitrileYield 222.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of the product of Example 1 Step 1 (4.0 g, 20.0 mmol) in DMF (7 ml) was added to a solution of sodium cyanide (300 mg, 6.12 mmol) in DMF (7 ml) over 15 minutes at room temperature. After stirring for a further 15 minutes, a solution of 4-chloro-3-methoxy-benzaldehyde (F. Claudi et al., J. Med. Chem., 1992, 35, 4408) (640 mg, 3.75 mmol) in DMF (6 ml) was added dropwise. The mixture was stirred at room temperature for 18 hours and then diluted with water and the pH of the solution adjusted to 9 with aqueous sodium hydrogen carbonate solution. The mixture was extracted with chloroform and the organic phase washed with water and brine, dried and concentrated in vacuo. The residue was chromatographed on silica gel eluting with chloroform/ethanol/0.880 ammonia solution (90:9:1) to give the title compound (3.1 g, 42%); MS (ES+) m/e 371, 373 [M+H]+.

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. extractionThe mixture was extracted with chloroform
  3. washthe organic phase washed with water and brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel eluting with chloroform/ethanol/0.880 ammonia solution (90:9:1)

Sources & evidence

ORD record
ord-b8606eb0ae104e2294f4aee316cf6d52
Source dataset
uspto-grants-2008_05
Patent number
US07375105B2

Reaction notes

Loading…