Water → 6,7-Dimethoxyquinazoline

HRID 2213856Notes

Reaction equation

HRID 2213856 reaction equation
IC1C=CC(N[C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=CC=1.C(OCC)(=O)C=C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.O>C(N(CC)CC)C.C(#N)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH3:20])[N:10]=[CH:9][N:8]=[CH:7]2

Participants

9

Reactant 4

HCID 962WaterHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 1474856HCID 1474856, compound

Product 1

HCID 30316616,7-DimethoxyquinazolineYield 169.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Palladium (II) acetate (303 mg, 1.35 mmol) was added to a solution of 4-(4-iodoanilino)-6,7-dimethoxyquinazoline (see example 1c) (6.00 g, 13.5 mmol), ethyl acrylate (1.35 g, 13.5 mmol) and tri(o-tolyl)phosphine (821 mg, 2.70 mmol) in a mixture of triethylamine (60 ml) and acetonitrile (200 ml) and the reaction heated at reflux for 20 hours under an inert atmosphere. The reaction was cooled to ambient temperature, poured into water (600 ml), diluted with ethyl acetate (200 ml) and filtered through celite. The organic layer was separated, the aqueous was extracted with ethyl acetate (2×200 ml) and the combined organic layers were dried over magnesium sulphate before solvent evaporation in vacuo. Purification by flash chromatography on silica gel, eluting with ethyl acetate, yielded 4-(4-(2-carboethoxy)ethenyl)anilino)-6,7-dimethoxyquinazoline (4.36 g, 85% yield) as a yellow solid:

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 20 hours under an inert atmosphere
  3. filtrationfiltered through celite
  4. customThe organic layer was separated
  5. extractionthe aqueous was extracted with ethyl acetate (2×200 ml)
  6. dry with materialthe combined organic layers were dried over magnesium sulphate before solvent evaporation in vacuo
  7. customPurification by flash chromatography on silica gel
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-a766322d2fb3416a9006e5e6944253b6
Source dataset
uspto-grants-2006_09
Patent number
US07105669B1

Reaction notes

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