反应详情

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).

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