1,1'-Carbonyldiimidazole → 3-Benzyloxy-1-(2,4-difluorophenyl)-6,7-difluoro-1H-quinazoline-2,4-dione

HRID 2416864Notes

Reaction equation

HRID 2416864 reaction equation
[CH2:1]([O:8][NH:9][C:10](=[O:28])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[F:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30]>C1COCC1>[CH2:1]([O:8][N:9]1[C:10](=[O:28])[C:11]2[C:12](=[CH:13][C:14]([F:18])=[C:15]([F:17])[CH:16]=2)[N:19]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C:29]1=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 22632987N-Benzyloxy-2-(2,4-difluoroanilino)-4,5-difluoro-benzamide

Product 1

HCID 226329863-Benzyloxy-1-(2,4-difluorophenyl)-6,7-difluoro-1H-quinazoline-2,4-dioneYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-benzyloxy-2-(2,4-difluoroanilino)-4,5-difluoro-benzamide (Example I-4, 5.66 g, 15 mmol) and carbonyldiimidazole (2.83 g, 17 mmol) were combined in 300 mL of THF and heated to reflux for 30 hours. The solution was cooled, concentrated, and redissolved in chloroform. The solution was washed with 1N HCl, saturated NaHCO3, brine, and dried over magnesium sulfate. The solution was concentrated to give 4.25 g of a solid which was purified by column chromatography (silica gel, CHCl3/MeOH, 98:2) to give 2.0 g of the title compound as a solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 30 hours
  3. temperatureThe solution was cooled
  4. concentrationconcentrated
  5. dissolutionredissolved in chloroform
  6. washThe solution was washed with 1N HCl, saturated NaHCO3, brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-b3ea84760f924c9b952e7fd595700612
Source dataset
uspto-grants-2004_11
Patent number
US06825199B2

Reaction notes

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