Réaction #657325

Équation de réaction

3-Bromo-2-phenylpyrazolo[1,5-a]pyrimidine

tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate

Tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate

sodium carbonate

→

4-(2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-amine

Rendement 45.8%

Solvants

1,4-dioxan

water

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture is flushed with argon for 5 mins
2. 2
   Autresealed
3. 3
   Températurethe mixture is heated for 2 h at 120° C
4. 4
   Extractionextracted with ethyl acetate (3×50 mL)
5. 5
   SéchageThe organic layer is dried over anhydrous magnesium sulphate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   AutreThe crude material is purified by column chromatography

Mode opératoire

3-Bromo-2-phenylpyrazolo[1,5-a]pyrimidine (1.0 g, 3.65 mmol) and tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (1.29 g, 4.01 mmol, 1.1 eq) are dissolved in 10 mL 1,4-dioxan. To this mixture bis(tricyclohexylphosphine)palladium(II)-dichloride (269 mg, 0.37 mmol, 0.1 eq) and 9.1 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 90 min at 120° C. in the microwave (Biotage). Tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (214 mg, 1.4 mmol, 0.37 eq) and bis(tricyclohexylphosphine)palladium(II)-dichloride (269 mg, 0.37 mmol, 0.1 eq) are then added and the mixture is heated for 2 h at 120° C. The reaction mixture is then poured in water and extracted with ethyl acetate (3×50 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 0.48 g (44%) of 4-(2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-amine are obtained as a white solid.

Source