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

HRID 380385

Reaction equation

HRID 380385 reaction equation
[Cl: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-]>[Cl: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 640654(3H)-Quinazolinone, 3-(2-chlorophenyl)-6-fluoro-2-methyl-HCID 27631912-Methyl-1,3-thiazole-4-carbaldehyde

Product 1

HCID 536551213-(2-chloro-phenyl)-6-fluoro-2-[2-(2-methyl-thiazol-4-yl)-vinyl]-3H-quinazolin-4-one

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 962WaterSolvent

Procedure

Anhydrous zinc chloride (0.133 g, 0.98 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, then dioxane (7 mL) was added. To this mixture was added 3-(2-chloro-phenyl)-6-fluoro-2-methyl-3H-quinazolin-4-one (0.14 g, 0.49 mmol), acetic anhydride (0.138 mL, 1.46 mmol), and 2-methylthiazole-4-carboxaldehyde (0.185 g, 1.46 mmol in 4 mL of dioxane). The reaction was refluxed 4 hours, cooled to ambient temperature, and diluted with water. 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 was triturated with ether, filtered and dried to afford 0.16 9 (57%) of 3-(2-chloro-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
  3. additiondioxane (7 mL) was added
  4. temperatureThe reaction was refluxed 4 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. customThis residue was triturated with ether
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-d8542aa3a8dc49a6b451ae7af259e18b
Source dataset
uspto-grants-2001_10
Patent number
US06303615B1

Linked notes

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