Acetic Anhydride → HCID 49826222, compound

HRID 380383Notes

Reaction equation

HRID 380383 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[N:6]([C:13]1[C:14]([CH3:19])=[N:15][CH:16]=[CH:17][CH:18]=1)[C:5]2=[O:20].C(OC(=O)C)(=O)C.[CH3:28][C:29]1[S:30][CH:31]=[C:32]([CH:34]=O)[N:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.[Cl-].[Zn+2].[Cl-].CO>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]=[CH:34][C:32]1[N:33]=[C:29]([CH3:28])[S:30][CH:31]=1)[N:6]([C:13]1[C:14]([CH3:19])=[N:15][CH:16]=[CH:17][CH:18]=1)[C:5]2=[O:20]

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 27631912-Methyl-1,3-thiazole-4-carbaldehydeHCID 22347424HCID 22347424, compound

Product 1

HCID 49826222HCID 49826222, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Anhydrous zinc chloride (2.7 g, 20 mmol) was fused with a nitrogen purge in a round bottom flask with an open flame. The reaction vessel was allowed to return to ambient temperature, at which time dioxane (150 mL) was then added. To this mixture was added 6-fluoro-2-methyl-3-(2-methyl-pyridin-3-yl)-3H-quinazolin-4-one (2.6 g, 10 mmol), acetic anhydride (2.8 mL, 30 mmol), and 2-methylthiazole-4-carboxaldehyde (3.7 g, 30 mmol). The reaction was refluxed 2 hours, cooled to ambient temperature, and diluted with water. Sodium carbonate was added until the mixture was basic. The mixture was repeatedly extracted with chloroform. The combined chloroform layer was washed with water and brine and finally dried over sodium sulfate and concentrated to leave a dark residue. This residue treated with methanol and concentrated (effectively azeotroping residual chloroform from the residue) and this process was repeated to leave a brown solid. The solid was triturated with ether (twice), filtered and dried to afford 3.1 g (82%) of 6-fluoro-3-(2-methyl-pyridin-3-yl)-2-[2-(2-methyl-thiazol-4-yl)-vinyl]-3H-quinazolin-4-one as tan solid.

Workup

  1. custompurge in a round bottom flask with an open flame
  2. customto return to ambient temperature, at which time dioxane (150 mL)
  3. additionwas then added
  4. temperatureThe reaction was refluxed 2 hours
  5. extractionThe mixture was repeatedly extracted with chloroform
  6. washThe combined chloroform layer was washed with water and brine
  7. dry with materialfinally dried over sodium sulfate
  8. concentrationconcentrated
  9. customto leave a dark residue
  10. concentrationconcentrated (
  11. customeffectively azeotroping residual chloroform from the residue) and this process
  12. customto leave a brown solid
  13. customThe solid was triturated with ether (twice),
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-d9bfc7c0746c4859865b38fa74c9cf1b
Source dataset
uspto-grants-2001_10
Patent number
US06303615B1

Reaction notes

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