Phosphorus oxychloride → 4-Chloro-1-(3,4-dimethoxy-phenyl)-6-oxo-1,6-dihydro-pyridazine-3-carbonitrile

HRID 241809Notes

Reaction equation

HRID 241809 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:11]2[C:16](=[O:17])[CH:15]=[C:14](O)[C:13]([C:19]([NH2:21])=O)=[N:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].P(Cl)(Cl)([Cl:24])=O>CC#N>[Cl:24][C:14]1[C:13]([C:19]#[N:21])=[N:12][N:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:16](=[O:17])[CH:15]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 578862251-(3,4-Dimethoxy-phenyl)-4-hydroxy-6-oxo-1,6-dihydro-pyridazine-3-carboxylic acid amide

Product 1

HCID 578861954-Chloro-1-(3,4-dimethoxy-phenyl)-6-oxo-1,6-dihydro-pyridazine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The starting amide (30) (190 mg) was dissolved in 1 ml of CH3CN, treated with 1 ml of phosphorus oxychloride, and heated to reflux. After 18-20 hours the reaction was complete by HPLC. The reaction mixture was poured into ice and stirred for one hour. The product was extracted with ethyl acetate, the organic phase dried over magnesium sulfate, filtered, and concentrated to dryness. This material was then purified by normal phase column SiO2 chromatography affording 90 mg of desired nitrile chloride (31) as a solid. MS+: m/e=292.0 (M+H), 1H-NMR (500 MHz, MeOH-d4): δ 7.40 (s, 1H), 7.18 (s, 1H), 7.12 (d, 1H), 7.08 (d, 1H), 3.90 (s, 3H), 3.85 (s, 3H), ppm.

Workup

  1. temperatureheated to reflux
  2. additionThe reaction mixture was poured into ice
  3. extractionThe product was extracted with ethyl acetate
  4. dry with materialthe organic phase dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThis material was then purified by normal phase column SiO2 chromatography

Sources & evidence

ORD record
ord-b1a794a12a4d4e28b102cb292a1f6462
Source dataset
uspto-grants-2014_02
Patent number
US08653088B2

Reaction notes

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