4-Chloro-2-fluoroaniline → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride

HRID 1421044ノート

反応式

HRID 1421044 の反応式
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.Cl.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][N:27]([CH3:35])[C:28]3[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30][N:29]=3)=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C(O)(C)C>[ClH:1].[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][N:27]([CH3:35])[C:28]4[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30][N:29]=4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[C:4]([F:9])[CH:3]=1

参加物

4

反応物 2

HCID 938984-Chloro-2-fluoroanilineHCID 226249054-chloro-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride

生成物 1

HCID 226249404-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride収率 56%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

4-Chloro-2-fluoroaniline (77 mg, 0.53 mmol) was added to a solution of 4-chloro-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride (140 mg, 0.35 mmol) in isopropanol (5 ml) and the mixture heated at reflux for 1 hour. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/methanol (95/5). The purified solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1 ml of a 5M solution) was added. The volatiles were removed by evaporation, the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride (75 mg, 39%).

後処理

  1. temperaturethe mixture heated
  2. temperatureat reflux for 1 hour
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified by flash chromatography
  10. washeluting with methylene chloride/methanol (95/5)
  11. dissolutionThe purified solid was dissolved in methylene chloride/methanol
  12. additionethereal hydrogen chloride (1 ml of a 5M solution) was added
  13. customThe volatiles were removed by evaporation
  14. customthe residue was triturated with ether
  15. filtrationcollected by filtration
  16. washwashed with ether
  17. customdried under vacuum

出典と根拠

ORDレコード
ord-3bb63b1b99ef498884f853fbda5315cf
出典データセット
uspto-grants-2000_06
特許番号
US06071921

反応ノート

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