Reaction #41045

Reaction equation

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

2-Fluorophenyl-boronic acid

Na2CO3

2-(dicyclohexylphosphino)biphenyl

→

title compound

Yield 76.6%

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

Yield 76.6%

Solvents

DME water

Conditions

Workup

1. 1
   OtherThe solvents were evaporated under vacuum
2. 2
   workup.DISSOLUTIONthe crude was redissolved in ethyl acetate
3. 3
   Washwashed with water
4. 4
   DryingThe organic phase was dried (Na2SO4)
5. 5
   Otherevaporated
6. 6
   Otherthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)
7. 7
   Washwashing with MeOH
8. 8
   Washeluting with MeOH/NH3 95:5

Procedure

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.

Source