Reaction #40957

Reaction equation

2-Methyl-pyridine 3-boronic acid

Na2CO3

2-Methyl-pyridine 3-boronic acid

Na2CO3

2-(dicyclohexylphosphino)biphenyl

3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione

→

title compound

Yield 66.4%

3-Benzoyl-1-(4-chloro-butyl)-5-(2-methyl-pyridin-3-yl)-1H-pyrimidine-2,4-dione

Yield 66.4%

Solvents

DME water

DME water

Conditions

Workup

1. 1
   Temperaturethe mixture was refluxed for 3 hours
2. 2
   Otherparallel in the same reaction conditions on 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 108 mg, 0.25 mmol)
3. 3
   workup.ADDITIONThe crudes were then mixed
4. 4
   Otherthe solvents were evaporated under vacuum
5. 5
   Otherthe residue was partitioned between ethyl acetate and water
6. 6
   DryingThe organic phase was dried (Na2SO4)
7. 7
   Otherevaporated
8. 8
   Otherthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)
9. 9
   Washwashing with MeOH
10. 10
    Washeluting with MeOH/NH3 95:5

Procedure

3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 541 mg, 1.25 mmol) was dissolved in degassed DME-water solution (5-1, 37.5 mL). 2-Methyl-pyridine 3-boronic acid (325 mg, 1.9 mmol), Na2CO3 (265 mg, 2.5 mmol), 2-(dicyclohexylphosphino)biphenyl (52 mg, 0.15 mmol) and Pd(PPh3)4 (288 mg, 0.25 mmol) were added and the mixture was refluxed for 3 hours. A second batch was run in parallel in the same reaction conditions on 3-Benzoyl-1-(4-chloro-butyl)-5-iodo-1H-pyrimidine-2,4-dione (Prep 44, 108 mg, 0.25 mmol) using 2-Methyl-pyridine 3-boronic acid (65 mg, 0.375 mmol), Na2CO3 (53 mg, 0.5 mmol), 2-(dicyclohexylphosphino)biphenyl (17.5 mg, 0.05 mmol) and Pd(PPh3)4 (57.75 mg, 0.05 mmol) dissolved in degassed DME-water solution (5-1, 7.5 mL). The crudes were then mixed and the solvents were evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) and then loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 to give the title compound (330 mg, 56% yield).

Source