Sodium hydride → 7-Benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazoline

HRID 577384Notes

Reaction equation

HRID 577384 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:10]=[C:9]([F:11])[C:7]([NH2:8])=[C:6]([F:12])[CH:5]=1.[CH2:13]([O:20][C:21]1[CH:30]=[C:29]2[C:24]([C:25](Cl)=[N:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[O:32][CH3:33])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C=O)C>[CH2:13]([O:20][C:21]1[CH:30]=[C:29]2[C:24]([C:25]([NH:8][C:7]3[C:9]([F:11])=[CH:10][C:4]([Br:3])=[CH:5][C:6]=3[F:12])=[N:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[O:32][CH3:33])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6101914-Bromo-2,6-difluoroanilineHCID 106619987-(Benzyloxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 107906057-Benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazolineYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 612 mg, 15.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (2.77 g, 6.65 mmol) in DMF (80 ml). After stirring for 30 minutes at ambient temperature, 7-benzyloxy-4-chloro-6-methoxyquinazoline (2 g, 6.65 mmol), (prepared, for example, as described in WO 97/22596, Example 1, but the free base was generated prior to use), was added and stirring was maintained for 4 hours. The mixture was partitioned between ethyl acetate and water (200 ml). The organic layer was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with isopropanol, collected by filtration, washed with ether and dried under vacuum to give 7-benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazoline (1.95 g, 62%).

Workup

  1. additionwas added
  2. stirringstirring
  3. temperaturewas maintained for 4 hours
  4. customThe mixture was partitioned between ethyl acetate and water (200 ml)
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (MgSO4)
  8. customthe volatiles were removed by evaporation
  9. customThe residue was triturated with isopropanol
  10. filtrationcollected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-71910cc300dd44d1862b7773de00c7b8
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

Loading…