Toluene → 4-Chloro-6-iodoquinazoline

HRID 1881675Notes

Reaction equation

HRID 1881675 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][NH:6][C:5]2=O.P(Cl)(Cl)([Cl:15])=O.C1(C)C=CC=CC=1.C(N(CC)CC)C>CC(C)=O>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[Cl:15]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 1354016666-Iodoquinazolin-4-one

Product 1

HCID 111738094-Chloro-6-iodoquinazolineYield 89%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

In a 500 mL-volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 50.0 g (184 mmol) of 6-iodoquinazolin-4-one, 33.8 g (221 mmol) of phosphorus oxychloride, and 300 mL of toluene in a nitrogen atmosphere. While the mixture was stirred at room temperature, 22.3 g (221 mmol) of triethylamine was slowly added. The resulting mixture was heated at 60° C. for 30 minutes and then heated at 75° C. for 2 hours, for carrying out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature, and 50 mL of acetone was added. The mixture was then cooled to 0° C. and stirred for 30 minutes. Thus precipitated pale yellow crystalline product of 6-iodo-4-chloroquinazoline was collected by filtration. Subsequently, the crystalline product was placed in 200 mL of water, and 9 mL of aqueous sodium hydroxide (1 mol/L) was added. The aqueous mixture (pH 10-11) was stirred for 30 minutes at room temperature. The crystalline product was collected by filtration, washed successively with 100 mL of acetone, 200 mL of water and 100 mL of acetone, and dried at 60° C. under reduced pressure, to give 47.4 g (isolated yield: 89%, purity 99% in terms of area percentage determined by high performance liquid chromatography) of 6-iodo-4-chloroquinazoline as a yellowish crystalline product.

Workup

  1. customIn a 500 mL-volume glass vessel equipped with a stirrer
  2. temperatureThe resulting mixture was heated at 60° C. for 30 minutes
  3. temperatureheated at 75° C. for 2 hours
  4. customreaction
  5. temperaturethe reaction mixture was cooled to room temperature
  6. temperatureThe mixture was then cooled to 0° C.
  7. stirringstirred for 30 minutes
  8. filtrationThus precipitated pale yellow crystalline product of 6-iodo-4-chloroquinazoline was collected by filtration
  9. addition9 mL of aqueous sodium hydroxide (1 mol/L) was added
  10. stirringThe aqueous mixture (pH 10-11) was stirred for 30 minutes at room temperature
  11. filtrationThe crystalline product was collected by filtration
  12. washwashed successively with 100 mL of acetone, 200 mL of water and 100 mL of acetone
  13. customdried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-5b8fd59d7bd149669424cac3745e7a5b
Source dataset
uspto-grants-2012_11
Patent number
US08318932B2

Reaction notes

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