反应详情

温度

-70 °C

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.

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