Triethylamine → 4-Ethoxy-quinazoline-6-carbaldehyde

HRID 1783625Notes

Reaction equation

HRID 1783625 reaction equation
BrC1C=C2C(=CC=1)[N:8]=[CH:7][N:6]=[C:5]2[O:12][CH2:13][CH3:14].C1([CH:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)CCP)C=CC=CC=1.C(N(CC)CC)C.[C]=[O:39].C([SiH](CCCCCC)CCCCCC)CCCCC>CN(C)C=O.CCCCCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.ClCCl>[CH2:13]([O:12][C:5]1[C:27]2[C:28](=[CH:29][CH:30]=[C:25]([CH:21]=[O:39])[CH:26]=2)[N:8]=[CH:7][N:6]=1)[CH3:14]

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 76231CID 76231HCID 7307686-Bromo-4-ethoxyquinazolineHCID 53436545Diphenylpropyl phosphineHCID 178418416HCID 178418416, compound3×

Product 1

HCID 575906244-Ethoxy-quinazoline-6-carbaldehydeYield 66%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The mixture of 6-bromo-4-ethoxy-quinazoline (example 10a, 506 mg, 2 mmol,), diphenylpropyl phosphine (45.6 mg, 0.2 mmol), palladium acetate (44.8 mg, 0.2 mmol) and triethyl amine (505 mg, 5 mmol) in anhydrous N,N-dimethylformamide (DMF) (25 ml) was charged with carbon monoxide at 75 psi. After the above reaction mixture was stirred at room temperature for 15 min, the carbon monoxide was released, and trihexylsilane (1140 mg, 4 mmol) was added. The resulted reaction mixture was charged with carbon monoxide at 75 psi, and heated at 80° C. for 18 hr. After cooling the reaction to room temperature, dichlormethane was added. The resulted solution was extracted with water for 3 times. Organic layer was collected and concentrated to give a yellow solid. Flash chromatography (Merck silica gel 60, 230-400 mesh, 10%-40% ethyl acetate in hexane for 40 min) gave 4-ethoxy-quinazoline-6-carbaldehyde (256 mg, 66%) as a light yellow solid. LC-MS m/e 203 (MH+).

Workup

  1. customThe resulted reaction mixture
  2. temperatureheated at 80° C. for 18 hr
  3. temperatureAfter cooling
  4. customthe reaction to room temperature
  5. extractionThe resulted solution was extracted with water for 3 times
  6. customOrganic layer was collected
  7. concentrationconcentrated
  8. customto give a yellow solid

Sources & evidence

ORD record
ord-f77a56980c514bce8ba192b20d4f3644
Source dataset
uspto-grants-2009_03
Patent number
US07501428B2

Reaction notes

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