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

Participants

Reaction Conditions

Reaction Steps

BuLi 1.6M in hexane (46.5 ml, 0.0744 mol) was added dropwise at −70° C. to a mixture of 1-methyl-1H-imidazole (0.0744 mol) in THF (70 ml) under N2 flow. Chlorotriethyl-silane (0.0765 mol) was added dropwise at −70° C. The mixture was stirred at −70° C. for 15 minutes. BuLi 1.6M in hexane (41 ml, 0.0659 mol) was added dropwise at −70° C. The mixture was stirred at −70° C. for 15 minutes. A solution of intermediate 6 (0.0425 mol) in THF (150 ml) was added dropwise 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 twice with water, separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (15-35μm) (eluent: DCM/MeOH/NH4OH 97/3/0.5). The pure fractions were collected and the solvent was evaporated. Part (0.5 g) of the residue (14.6 g, 72%) was crystallized from 2-propanone/CH3CN. The precipitate was filtered off and dried under a vacuo, yielding 0.17 g of 2-chloro-4-(3-chlorophenyl)-α-(4-fluorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol (intermediate 7), mp. 212° C.

Provenance & Evidence