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

HRID 346567

Reaktionsgleichung

Reaktionsgleichung von HRID 346567
[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

Komponenten

5

Edukt 3

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

Produkt 1

HCID 107906057-Benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazolineAusbeute 62,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-350db24fa5e547baa4985fd9b7d8d401
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07173038B1

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