Triethylamine → 6-Bromo-4-chloro-quinazoline

HRID 1187272Notes

Reaction equation

HRID 1187272 reaction equation
[Br: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.C(N(CC)CC)C.P(Cl)(Cl)([Cl:22])=O>O1CCOCC1>[Br: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:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 1354449056-bromoquinazolin-4-ol

Product 1

HCID 167703106-Bromo-4-chloro-quinazoline

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 6-Bromo-3H-quinazolin-4-one (1.5 g, 6.65 mmole) in 1,4-dioxane (30 ml) under nitrogen was added triethylamine (2.8 ml, 19.9 mmole). The resulting suspension was rapidly stirred while phosphorous oxychloride (1.85 ml, 19.9 mmole) was added over 5 minutes. The reaction was stirred at room temperature for 5 minutes, then heated at 80° C. for 30 minutes, when no starting material was detectable by LC/MS. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The resulting residue was partitioned between ethyl acetate and water. The insoluble material was collected by filtration and washed with water. The layers of the filtrate where separated and the organic layer was washed twice with water and once with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting solid was combined with the collected precipitate and the mixture was recrystallized from ethyl acetate/hexanes to give 760 mg after drying in vacuo. The resulting compound was characterized as follows: masspectrometry: M/Z=244; HPLC: method A, Rt 1.51 minutes.

Workup

  1. additionwas added over 5 minutes
  2. temperatureheated at 80° C. for 30 minutes
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customThe resulting residue was partitioned between ethyl acetate and water
  6. filtrationThe insoluble material was collected by filtration
  7. washwashed with water
  8. customThe layers of the filtrate where separated
  9. washthe organic layer was washed twice with water and once with brine
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe mixture was recrystallized from ethyl acetate/hexanes
  14. customto give 760 mg
  15. customafter drying in vacuo

Sources & evidence

ORD record
ord-5e45e977b32046e988c888e0badce87b
Source dataset
uspto-grants-2014_03
Patent number
US08673929B2

Reaction notes

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