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

HRID 238113

反応式

HRID 238113 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-f15d54af2cc04ecea570d9313002b80c
出典データセット
uspto-grants-2014_02
特許番号
US08642608B2

関連ノート

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