Sodium Carbonate → 5-(2-fluorophenyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

関与物質

反応条件

反応手順

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.

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