反应详情

3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (150 mg, 0.66 mmol) and 5-(methylsulfonyl)pyridine-3-boronic acid (200 mg, 0.99 mmol) are suspended in 1,4-dioxane (4 ml). 2M aqueous Na2CO3 (1 ml) is added and the reaction mixture is degassed by bubbling argon through for 5 minutes. Pd(dppf)Cl2 (27 mg, 0.033 mmol) is added and the reaction mixture is heated using microwave radiation at 100° C. for 30 minutes. Water (20 ml) and Et2O (50 ml) are added to the reaction mixture and the resulting grey solid is collected by filtration washing further with water. The solid is suspended in MeOH and excess TFA is added until a solution forms. The organic solvent is reduced in vacuo and the crude residue is purified by reverse phase column chromatography (Isolute™ C18, water/acetonitrile, 0.1% TFA), the appropriate fractions are combined and concentrated in vacuo. The resulting solid is refluxed in EtOH, cooled to room temperature, filtered and dried under vacuum to afford the title compound.

1. customthe reaction mixture is degassed
2. customby bubbling argon through for 5 minutes
3. temperaturethe reaction mixture is heated
4. customat 100° C.
5. customfor 30 minutes
6. filtrationthe resulting grey solid is collected by filtration
7. washwashing further with water
8. additionexcess TFA is added until a solution forms
9. customthe crude residue is purified by reverse phase column chromatography (Isolute™ C18, water/acetonitrile, 0.1% TFA)
10. concentrationconcentrated in vacuo
11. temperatureThe resulting solid is refluxed in EtOH
12. filtrationfiltered
13. customdried under vacuum