反应详情

温度

90 °C

5-Iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione (Prep40, 80 mg, 0.16 mmol) was dissolved in degassed DME-water solution (5-1, 10 mL). 0.2-Fluorophenyl-boronic acid (33 mg, 0.23 mmol), Na2CO3 (34 mg, 0.32 mmol), 2-(dicyclohexylphosphino)biphenyl (14 mg, 0.04 mmol) and Pd(PPh3)4 (46 mg, 0.04 mmol) were added and the mixture stirred for 3 hours at 90° C. The solvents were evaporated under vacuum and the crude was redissolved in ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) followed by SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 to give the title compound (58 mg, 76% yield) as free base.

1. customThe solvents were evaporated under vacuum
2. dissolutionthe crude was redissolved in ethyl acetate
3. washwashed with water
4. dry with materialThe organic phase was dried (Na2SO4)
5. customevaporated
6. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)
7. washwashing with MeOH
8. washeluting with MeOH/NH3 95:5