Water → 4-(4-Chloro-2-fluoroanilino)-7-((2-cyano4-pyridyl)methoxy)-6-methoxyquinazoline

HRID 279600ノート

反応式

HRID 279600 の反応式
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl.Cl[CH2:25][C:26]1[CH:31]=[CH:30][N:29]=[C:28]([C:32]#[N:33])[CH:27]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([C:32]#[N:33])[CH:27]=4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 226250684-(Chloromethyl)picolinonitrile hydrochlorideHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 226250774-(4-Chloro-2-fluoroanilino)-7-((2-cyano4-pyridyl)methoxy)-6-methoxyquinazoline収率 4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (600 mg, 2 mmol), (prepared as described for the starting material in Example 24), 4-chloromethyl-2-cyanopyridine hydrochloride (620 mg, 3 mmol) and potassium carbonate (1.0 g 7 mmol) in DMF (8 ml) was heated at 80° C. for 30 minutes. The mixture was allowed to cool, poured into water and extracted with ethyl acetate. The combined extracts were dried (MgSO4) and the solvent removed by evaporation and azeotroped with toluene. The residue was triturated with ethyl acetate/hexane, the solid product collected by filtration and purified by column chromatography eluting with ethyl acetate and further chromatography eluting with methylene chloride/methanol (99/1). The purified product was recrystallised from ethyl acetate/hexane to give 4-(4-chloro-2-fluoroanilino)-7-((2-cyano-4-pyridyl)methoxy)-6-methoxyquinazoline (35 mg, 4%).

後処理

  1. custom(prepared
  2. temperatureto cool
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. customthe solvent removed by evaporation
  6. customazeotroped with toluene
  7. customThe residue was triturated with ethyl acetate/hexane
  8. filtrationthe solid product collected by filtration
  9. custompurified by column chromatography
  10. washeluting with ethyl acetate and further chromatography
  11. washeluting with methylene chloride/methanol (99/1)
  12. customThe purified product was recrystallised from ethyl acetate/hexane

出典と根拠

ORDレコード
ord-54b3993b3b574833811d67a176331957
出典データセット
uspto-grants-2002_03
特許番号
US06362336B1

反応ノート

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