反应详情

温度

0 °C

n-BuLi (0.0166 mol) was added slowly at −78° C. to a solution of 2,4-dihydro-4-methyl-3H-1,2,4-triazole-3-thione (0.0082 mol) in THF (50 ml) under N2 flow. The mixture was stirred at 0° C. for 1 hour, then cooled to −78° C. 9-(4-chlorobenzoyl)-7-(3-chlorophenyl)-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one (described in International Application WO98/40383) (0.0046 mol) was added portionwise. The mixture was stirred at room temperature for 4 hours, poured out on ice and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (2.32 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.1 to 96/4/0.1). The pure fractions were collected and the solvent was evaporated. The residue (1 g, 40%). was crystallized from acetonitril. The precipitate was filtered off and dried, yielding 0.52 g (21%) of 7-(3-chlorophenyl)-9-[(4-chlorophenyl)hydroxy(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one hydrate (1:1), melting point 160° C. (intermediate 7).

1. temperaturecooled to −78° C
2. stirringThe mixture was stirred at room temperature for 4 hours
3. additionpoured out on ice
4. extractionextracted with EtOAc
5. customThe organic layer was separated
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customthe solvent was evaporated
9. customThe residue (2.32 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.1 to 96/4/0.1)
10. customThe pure fractions were collected
11. customthe solvent was evaporated
12. customwas crystallized from acetonitril
13. filtrationThe precipitate was filtered off
14. customdried