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1-Methylimidazole → 2-chloro-4-(3-chlorophenyl)-alpha-(4-methoxyphenyl)-alpha-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol

HRID 1788053
ノート
印刷プレビュー

反応式

HRID 1788053 の反応式
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Cl[Si](CC)(CC)CC.[Cl:20][C:21]1[N:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:38]([C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)=[O:39])[CH:27]=2)[N:22]=1>C1COCC1.CCOC(C)=O.O>[Cl:20][C:21]1[N:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:38]([C:40]3[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=3)([C:11]3[N:7]([CH3:6])[CH:8]=[N:9][CH:10]=3)[OH:39])[CH:27]=2)[N:22]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 17976109[2-Chloro-4-(3-chlorophenyl)-6-quinazolinyl](4-methoxyphenyl)-methanoneHCID 178418339Butyllithium

生成物 1

HCID 179761132-chloro-4-(3-chlorophenyl)-alpha-(4-methoxyphenyl)-alpha-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol収率 59%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

nBuLi (0.0665 mol) was added dropwise at −70° C. to a solution of 1-methyl-1H-imidazole (0.0665 mol) in THF (60 ml) under N2 flow. The mixture was stirred for 15 minutes. Chlorotriethyl-silane (0.0684 mol) was added dropwise. The mixture was stirred for 15 minutes. nBuli (0.059 mol) was added dropwise. The mixture was stirred for 15 minutes. A solution of intermediate 14 (0.038 mol) in THF (150 ml) was added at −70° C. The mixture was stirred at −70° C. for 1 hour and poured out into water. EtOAc was added. The mixture was extracted with EtOAc. The organic layer was washed with water, separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (15-35 μm) (eluent: DCM/MeOH/NH4OH 96/4/0.2). The pure fractions were collected and the solvent was evaporated, yielding 11 g (59%) of 2-chloro-4-(3-chlorophenyl)-α-(4-methoxyphenyl)-α-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol (intermediate 15).

後処理

  1. stirringThe mixture was stirred for 15 minutes
  2. additionnBuli (0.059 mol) was added dropwise
  3. stirringThe mixture was stirred for 15 minutes
  4. stirringThe mixture was stirred at −70° C. for 1 hour
  5. extractionThe mixture was extracted with EtOAc
  6. washThe organic layer was washed with water
  7. customseparated
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated
  11. customThe residue was purified by column chromatography over silica gel (15-35 μm) (eluent: DCM/MeOH/NH4OH 96/4/0.2)
  12. customThe pure fractions were collected
  13. customthe solvent was evaporated

出典と根拠

ORDレコード
ord-4a4fac1bba674e4796294de9779081be
出典データセット
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07511138B2

反応ノート

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