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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
Notes
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Reaction equation

HRID 1788053 reaction equation
[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4a4fac1bba674e4796294de9779081be
Source dataset
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07511138B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes