Reaction #41048

Reaction equation

Pyridine 4-boronic acid

Na2CO3

2-(dicyclohexylphosphino)biphenyl

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

→

title compound

Yield 32.0%

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

Yield 32.0%

Solvents

ethyl acetate

DME water

Conditions

Workup

1. 1
   Otherthe mixture was placed in a microwave oven
2. 2
   Temperatureheated at 150° for 20 minutes
3. 3
   Washwashed with water
4. 4
   DryingThe organic phase was dried (Na2SO4)
5. 5
   Otherevaporated
6. 6
   workup.DISSOLUTIONthe crude was dissolved in MeOH
7. 7
   Washwashing with MeOH
8. 8
   Washeluting with MeOH/NH3 95:5
9. 9
   OtherThe residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1)

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, 46 mg, 0.09 mmol) was dissolved in degassed DME-water solution (5-1, 1 mL). Pyridine 4-boronic acid (22 mg, 0.18 mmol), Na2CO3 (20 mg, 0.18 mmol), 2-(dicyclohexylphosphino)biphenyl (7 mg, 0.02 mmol) and Pd(PPh3)4 (20 mg, 0.02 mmol) were added and the mixture was placed in a microwave oven and heated at 150° for 20 minutes. The mixture was diluted with ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was dissolved in MeOH and loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5. The residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1) to give the title compound (13 mg, 32% yield) as free base.

Source