Trifluoroacetic acid → 4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline

HRID 1791691ノート

反応式

HRID 1791691 の反応式
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:28]=[CH:27][C:12]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([OH:26])=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[C:11]([F:29])[CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:39][CH2:38]1>CN(C=O)C.O>[Cl:8][C:9]1[CH:28]=[CH:27][C:12]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH2:45][CH2:44][CH2:43][N:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[C:11]([F:29])[CH:10]=1

参加物

7

反応物 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 218748183-(4-Methyl-piperazin-1-yl)propyl-4-toluene sulphonateHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 218748154-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline収率 48.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

A mixture of the trifluoroacetic acid salt of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (3.2 g, 7.4 mmol), potassium carbonate (6.1 g, 44.2 mmol) and 3-(4-methyl-1-piperazinyl)propyl-4-toluene sulphonate (3.0 g, 9.6 mmol) in DMF (60 ml) was stirred at 90° C. for 5 hours and allowed to cool to ambient temperature. The reaction mixture was poured into water (700 ml) and extracted 5 times with ethyl acetate. The combined extracts were washed with water, saturated aqueous sodium hydrogen carbonate, water and saturated brine. The ethyl acetate solution was dried over magnesium sulphate, filtered and the solvent removed under vacuum to give a residue which was purified by silica column chromatography, eluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1). The relevant fractions were combined and evaporated under vacuum to give a residue which was triturated with ether, filtered and dried to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (1.64 g, 48%).

後処理

  1. temperatureto cool to ambient temperature
  2. extractionextracted 5 times with ethyl acetate
  3. washThe combined extracts were washed with water, saturated aqueous sodium hydrogen carbonate, water and saturated brine
  4. dry with materialThe ethyl acetate solution was dried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customto give a residue which
  8. customwas purified by silica column chromatography
  9. washeluting with dichloromethane/methanol/0.880 aqueous ammonia (100/8/1)
  10. customevaporated under vacuum
  11. customto give a residue which
  12. customwas triturated with ether
  13. filtrationfiltered
  14. customdried

出典と根拠

ORDレコード
ord-dc4b8fce3c9d43948548a1d1d49422d6
出典データセット
uspto-grants-2006_07
特許番号
US07074800B1

反応ノート

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