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

HRID 1788062Notes

Reaction equation

HRID 1788062 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Li]CCCC.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]([CH3:46])=[CH:42][CH:41]=3)=[O:39])[CH:27]=2)[N:22]=1>C1COCC1.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:6]3[N:2]([CH3:1])[CH:3]=[N:4][CH:5]=3)([C:40]3[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=3)[OH:39])[CH:27]=2)[N:22]=1

Participants

7

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 17976110[2-Chloro(3-chlorophenyl)-6-quinazolinyl](4-methylphenyl)-methanoneHCID 178418339Butyllithium2×

Product 1

HCID 179761062-chloro-4-(3-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)-alpha-(4-methylphenyl)-6-quinazolinemethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

1-Methyl-1H-imidazole (0.0507 mol) was added at −70° C. to THF (90 ml) under N2 flow. nBuLi (31.5 ml) was added dropwise. The mixture was stirred at −70° C. for 15 minutes. Chlorotriethyl-silane (0.0522 mol) was added dropwise. The mixture was stirred at −70° C. for 15 minutes. nBuLi (28 ml) was added. The mixture was stirred at −70° C. for 15 minutes. A mixture of intermediate 23 (0.029 mol) in THF (115 ml) was added dropwise. The mixture was stirred at −70° C. for 1 hour, poured out into water and extracted with DCM. The organic layer was separated, washed with water, 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; 96/4/0.1). The pure fractions were collected and the solvent was evaporated, yielding 9 g (65%). A sample (0.3 g) was crystallized from 2-propanone, The precipitate was filtered off and dried, yielding 2-chloro-4-(3-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-α-(4-methylphenyl)-6-quinazolinemethanol (intermediate 24), mp. 220° C.

Workup

  1. stirringThe mixture was stirred at −70° C. for 15 minutes
  2. stirringThe mixture was stirred at −70° C. for 15 minutes
  3. additionwas added dropwise
  4. stirringThe mixture was stirred at −70° C. for 1 hour
  5. extractionextracted with DCM
  6. customThe organic layer was separated
  7. washwashed with water
  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; 96/4/0.1)
  12. customThe pure fractions were collected
  13. customthe solvent was evaporated
  14. customyielding 9 g (65%)
  15. customA sample (0.3 g) was crystallized from 2-propanone
  16. filtrationThe precipitate was filtered off
  17. customdried

Sources & evidence

ORD record
ord-c0c0c2a6fe664cd7b77993b86272439d
Source dataset
uspto-grants-2009_03
Patent number
US07511138B2

Reaction notes

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