Phosphorus oxychloride → 4-Chloro-6-iodoquinazoline

HRID 240572Notes

Reaction equation

HRID 240572 reaction equation
[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]2O.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:24]>ClC(Cl)C>[Cl:24][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=2)[N:8]=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 178518013HCID 178518013, compound

Product 1

HCID 111738094-Chloro-6-iodoquinazolineYield 71.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a cooled (0° C.) suspension of 6-iodoquinazolin-4-ol (107.6 g, 396 mmol) and DIEA (138 mL, 791 mmol) in dichloroethane (600 mL) was added POCl3 (44.25 mL, 475 mmol). After heating to 90° C. for 16 hours, the reaction mixture was cooled to room temperature and the crystals (73.8 g) collected by filtration. The filtrate was concentrated under reduced pressure and azeotroped twice with toluene. The solids (8.3 g) were triturated with isopropanol (450 mL) and cooled in an ice bath before collecting by filtration and drying under high vacuum. The two solids were combined to provide the product (82.1 g, 71%) as white solid.

Workup

  1. temperatureTo a cooled
  2. temperaturethe reaction mixture was cooled to room temperature
  3. filtrationthe crystals (73.8 g) collected by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customazeotroped twice with toluene
  6. customThe solids (8.3 g) were triturated with isopropanol (450 mL)
  7. temperaturecooled in an ice bath
  8. filtrationbefore collecting by filtration
  9. customdrying under high vacuum

Sources & evidence

ORD record
ord-ad219e877a854a068d6759347dc4aff7
Source dataset
uspto-grants-2014_02
Patent number
US08648087B2

Reaction notes

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