Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(1-methylimidazol-2-ylthio)ethoxy)quinazoline

HRID 279613ノート

反応式

HRID 279613 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][CH2:26][S:27][C:28]1[N:29]([CH3:33])[CH:30]=[CH:31][N:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.O>[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][CH2:26][S:27][C:28]4[N:29]([CH3:33])[CH:30]=[CH:31][N:32]=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 3

HCID 11430Potassium CarbonateHCID 226249432-(2-Chloroethylthio)-1-methylimidazole hydrochlorideHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 158860324-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(1-methylimidazol-2-ylthio)ethoxy)quinazoline収率 18.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
90 °C

実験手順

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (350 mg, 0.9 mmol), (prepared as described for the starting material in Example 24), 2-(2-chloroethylthio)-1-methylimidazole hydrochloride (203 mg, 0.95 mmol) and potassium carbonate (303 mg 2.2 mmol) in NMP (20 ml) was heated at 90° C. for 2 hours. The mixture was allowed to cool, diluted with water and extracted with ethyl acetate. The combined extracts were washed with water, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (100/0 increasing to 90/10) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(1-methylimidazol-2-ylthio)ethoxy)quinazoline (75 mg, 17%) as a solid.

後処理

  1. custom(prepared
  2. temperatureto cool
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with water
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (100/0 increasing to 90/10)

出典と根拠

ORDレコード
ord-8cef1e8553834428910f795068de5e67
出典データセット
uspto-grants-2002_03
特許番号
US06362336B1

反応ノート

読み込み中…