反应详情

温度

190 °C

A mixture of 2-oxa-5-aza-bicyclo[2.2.1]heptane hydrochloride (223 mg, 1643 μmol) in 10 mL methanol was treated with MP-carbonate (1 g, 3.2 mmol) at 22° C. for 1 h. The mixture was filtered and concentrated. The residue, 6-bromo-1-chlorophthalazine (Example 1, 100 mg, 411 μmol), potassium carbonate (57 mg, 411 μmol) and 5 mL acetonitrile was added to a glass microwave reaction vessel. The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 190° C. for 20 min. The mixture was concentrated under vacuum and N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (124 mg, 411 μmol), tetrakis(triphenylphosphine)palladium (475 mg, 411 μmol), 5 mL DME/EtOH (4:1) and 0.6 mL H2O were added. The mixture was stirred at 90° C. for 1 h., then directly transferred to silica gel and purified via flash chromatography (silica gel) eluting with a gradient of 2% 2 M ammonia in MeOH/DCM to 10% 2 M ammonia in MeOH/DCM to give the title compound (0.21g) as a yellow solid. Found MS (ES+): 401 (M+H)+.

1. filtrationThe mixture was filtered
2. concentrationconcentrated
3. additionwere added
4. stirringThe mixture was stirred at 90° C. for 1 h.
5. custompurified via flash chromatography (silica gel)
6. washeluting with a gradient of 2% 2 M ammonia in MeOH/DCM to 10% 2 M ammonia in MeOH/DCM