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

HRID 1441463
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HRID 1441463 반응식
[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
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참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-050d282f1ecd48d4880c54adb788942d
출처 데이터셋
uspto-grants-2010_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07655654B2

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