Acetic Anhydride → 3-(2-bromo-phenyl)-6-fluoro-2-[2-(2-methyl-thiazol-4-yl)-vinyl]-3H-quinazolin-4-one

HRID 381271

Reaction equation

HRID 381271 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH3:20].C(OC(=O)C)(=O)C.[CH3:28][C:29]1[S:30][CH:31]=[C:32]([CH:34]=O)[N:33]=1>O.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH:20]=[CH:34][C:32]1[N:33]=[C:29]([CH3:28])[S:30][CH:31]=1

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 27631912-Methyl-1,3-thiazole-4-carbaldehydeHCID 183629723-(2-bromo-phenyl)-6-fluoro-2-methyl-3H-quinazolin-4-one

Product 1

HCID 545587883-(2-bromo-phenyl)-6-fluoro-2-[2-(2-methyl-thiazol-4-yl)-vinyl]-3H-quinazolin-4-oneYield 52%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 962WaterSolvent

Procedure

Anhydrous zinc chloride (0.150 g, 1.1 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 (5 mL) was then added. To this mixture was added 3-(2-bromo-phenyl)-6-fluoro-2-methyl-3H-quinazolin-4-one (0.182 g, 0.55 mmol), acetic anhydride (0.156 mL, 1.65 mmol), and 2-methylthiazole-4-carboxaldehyde (0.209 g, 1.65 mmol in 3 mL of dioxane). The reaction was refluxed 3 hours, and was then cooled to ambient temperature. Once the reaction had cooled to ambient temperature it was diluted with water. The resulting mixture was repeatedly extracted with chloroform. The combined chloroform layers were washed with water and brine, then dried over magnesium sulfate and then concentrated to yield a dark residue. This residue was triturated with ether, filtered and dried to afford 0.116 g (52% of 3-(2-bromo-phenyl)-6-fluoro-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 (5 mL)
  3. additionwas then added
  4. temperatureThe reaction was refluxed 3 hours
  5. temperatureOnce the reaction had cooled to ambient temperature it
  6. extractionThe resulting mixture was repeatedly extracted with chloroform
  7. washThe combined chloroform layers were washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customto yield a dark residue
  11. customThis residue was triturated with ether
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-94c0797a413549b18d356abe3b76d66b
Source dataset
uspto-grants-2001_10
Patent number
US06306864B1

Linked notes

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