Dimethylformamide → 4-Chloro-6-iodoquinazoline

HRID 414997Notes

Reaction equation

HRID 414997 reaction equation
CN(C)C=O.[C:6]([Cl:11])(=O)[C:7](Cl)=O.[I:12][C:13]1[CH:14]=C2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][N:17]=C2O>ClCCCl>[Cl:11][C:6]1[C:7]2[C:20](=[CH:21][CH:22]=[C:13]([I:12])[CH:14]=2)[N:19]=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 178518013HCID 178518013, compound

Product 1

HCID 111738094-Chloro-6-iodoquinazolineYield 99.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a stirred solution of anhydrous dimethyl foramide (DMF) (3.20 ml) in 1,2-dichloroethane (DCE) (10 ml), cooled in an ice-water bath, is added dropwise under nitrogen a solution of oxalyl chloride (5.2 ml, 60 mmol) in DCE (25 ml). A white precipitate forms during the addition. After the end of addition the cold bath is removed and the reaction mixture is stirred at room temperature for 5 minutes. 6-Iodo-quinazolin-4-ol (5.0 g, 18 mmol) is added in portions via scoopula under nitrogen flow and the mixture is heated immediately to reflux. Heating is continued for 4.5 hours, followed by cooling to room temperature. The reaction mixture is poured into excess ice-water mixture (approximately 300 ml) and extracted with DCM (approximately 500 ml). The aqueous layer is further extracted with DCM (2×50 ml). The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure to yield 5.2 g (99%) of desired product as a tan solid.

Workup

  1. additionA white precipitate forms during the addition
  2. additionAfter the end of addition the cold bath
  3. customis removed
  4. temperaturethe mixture is heated immediately
  5. temperatureto reflux
  6. temperatureHeating
  7. waitis continued for 4.5 hours
  8. temperatureby cooling to room temperature
  9. extractionextracted with DCM (approximately 500 ml)
  10. extractionThe aqueous layer is further extracted with DCM (2×50 ml)
  11. dry with materialThe combined organic extracts are dried (Na2SO4)
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86f9ec1d543847198a353932f109587c
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Reaction notes

Loading…