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

HRID 51100Notes

Reaction equation

HRID 51100 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 liters), 4-hydroxy-6-iodo-7-fluoro-quinazoline (36 grams, 124 mmoles), and dimethylformamide (6 ml) were combined in a one liter 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 liter) and toluene (0.1 liter). The mixture was concentrated to dryness. This procedure was repeated two additional times. To the resulting solid was added 0.5 liters 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 liter) and toluene (0.1 liter)
  7. concentrationThe mixture was concentrated to dryness
  8. additionTo the resulting solid was added 0.5 liters 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-30dfb982b5e5413f82eb5f87770ef0e1
Source dataset
uspto-grants-2004_03
Patent number
US06713485B2

Reaction notes

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