反应详情

2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (210 mg, 0.70 mmol) was dissolved in 30 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (360 mg, 0.95 mmol), 1-bromo-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine hydrochloride 11c (214 mg, 0.70 mmol) and N,N-diisopropylethylamine (0.4 mL, 2.10 mmol). After stirring for 12 hours, the reaction mixture was added with 50 mL of H2O, extracted with dichloromethane (80 mL×3). The organic phase was combined, concentrated under reduced pressure, added with 100 mL of ethyl acetate, washed successively with saturated sodium carbonate solution (40 mL), H2O (40 mL) and saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 4-[[3-[1-bromo-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carbonyl]-4-fluoro-phenyl]methyl]-2H-phthalazin-1-one 11 (185 mg, yield 48.0%) as a white solid.

1. extractionextracted with dichloromethane (80 mL×3)
2. concentrationconcentrated under reduced pressure
3. additionadded with 100 mL of ethyl acetate
4. washwashed successively with saturated sodium carbonate solution (40 mL), H2O (40 mL) and saturated sodium chloride solution (40 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe resulting residue was purified by thin layer chromatography with elution system