Reaction #657323

Reaction equation

sodium carbonate

3-Bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine

N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide

→

N-{4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridin-2-yl}acetamide

Yield 17.0%

Solvents

1,4-dioxan

Conditions

Workup

1. 1
   OtherThe reaction mixture is flushed with argon for 5 mins
2. 2
   Othersealed
3. 3
   workup.ADDITIONThe reaction mixture is then poured in water
4. 4
   Extractionextracted with dichloromethane (3×20 mL)
5. 5
   DryingThe organic layer is dried over anhydrous magnesium sulphate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe crude material is purified by column chromatography

Procedure

3-Bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine (150 mg, 0.51 mmol) and N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (148 mg, 0.56 mmol, 1.1 eq) are dissolved in 1.5 mL 1,4-dioxan. To this mixture, bis(tricyclohexylphosphine)palladium(II)-dichloride (57 mg, 0.07 mmol, 0.15 eq) and 0.83 mL sodium carbonate solution (2 molar) are added. The reaction mixture is flushed with argon for 5 mins and then sealed. Next the mixture is heated for 30 min at 150° C. in the microwave (Biotage). The reaction mixture is then poured in water and extracted with dichloromethane (3×20 mL). The organic layer is dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography using silica gel in heptane and ethyl acetate (1:0 to 1:1) as eluent and 0.03 g (17%) of N-{4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridin-2-yl}acetamide are obtained as a white solid.

Source