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

HRID 238113

Reaction equation

HRID 238113 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 stiffing 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. temperaturewas maintained for 4 hours
  3. customThe mixture was partitioned between ethyl acetate and water (200 ml)
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried (MgSO4)
  7. customthe volatiles were removed by evaporation
  8. customThe residue was triturated with isopropanol
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-f15d54af2cc04ecea570d9313002b80c
Source dataset
uspto-grants-2014_02
Patent number
US08642608B2

Linked notes

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