Thionyl Chloride → 4-Chloro-6-iodo-7-fluoro-quinazoline Hydrochloride

HRID 585608Notes

Reaction equation

HRID 585608 reaction equation
S(Cl)([Cl:3])=O.O[C:6]1[C:15]2[C:10](=[CH:11][C:12]([F:17])=[C:13]([I:16])[CH:14]=2)[N:9]=[CH:8][N:7]=1>CN(C)C=O>[ClH:3].[Cl:3][C:6]1[C:15]2[C:10](=[CH:11][C:12]([F:17])=[C:13]([I:16])[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 178419030HCID 178419030, compound

Product 1

HCID 219520054-Chloro-6-iodo-7-fluoro-quinazoline HydrochlorideYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Thionyl chloride (0.6 litres), 4-hydroxy-6iodo-7-fluoro-quinazoline (36 grams, 124 mmoles), and dimethylformamide (6 ml) were combined in a one litre one-neck flask fitted with a magnetic stir bar. The mixture was placed under anhydrous nitrogen and heated to a gentle reflux for 24 hours. The mixture was allowed to cool, followed by concentrating the reaction mixture to a thick yellowish residue. To this residue was added dichloromethane (0.1 litre) and toluene (0.1 litre). The mixture was concentrated to dryness. This procedure was repeated two additional times. To the resulting solid was added 0.5 litres of dry dichloromethane and the mixture was stirred for one hour. The mixture was filtered and the remaining solids were washed with minimal dichloromethane. The dichoromethane filtrates were combined, concentrated to a solid, and dried under vacuum at room temperature to yield 28.6 grams (67%) of the title compound. 1H NMR (400 MHz, CDCl3-d1) δ: 9.03(s, 1H), 8.76(d, 1H), 7.69(d, 1H). ESI-MS m/z 309(M+1).

Workup

  1. customfitted with a magnetic stir bar
  2. temperatureheated to
  3. temperaturea gentle reflux for 24 hours
  4. temperatureto cool
  5. concentrationby concentrating the reaction mixture to a thick yellowish residue
  6. additionTo this residue was added dichloromethane (0.1 litre) and toluene (0.1 litre)
  7. concentrationThe mixture was concentrated to dryness
  8. additionTo the resulting solid was added 0.5 litres of dry dichloromethane
  9. filtrationThe mixture was filtered
  10. washthe remaining solids were washed with minimal dichloromethane
  11. concentrationconcentrated to a solid
  12. customdried under vacuum at room temperature

Sources & evidence

ORD record
ord-53e4e81d356a4a5a9cc28621c2641f40
Source dataset
uspto-grants-2005_08
Patent number
US06933299B1

Reaction notes

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