Potassium Phosphate, Tribasic → 3-(3,5-Difluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (0.05 g, 0.22 mmol) is suspended in 1,4-dioxane (1 ml). The reaction mixture is sonicated to give a very fine suspension and placed in a microwave vial containing 3,5-difluoro phenylboronic acid (38 mg, 0.24 mmol). To this is added a solution of tris(dibenzylileneacetone) di palladium(0) (0.002 g, 0.0022 mmol) in 1,4-dioxane (0.5 ml) followed by a solution of tricyclohexyl phosphine (0.0015 g, 0.0053 mmol) in 1,4-dioxane (0.5 ml) and 1.27M aqueous potassium phosphate solution (0.294 ml, 0.374 mmol). The resulting mixture is flushed with argon and heated using microwave radiation at 150° C. for 30 minutes. The reaction mixture is treated with DMSO (2 ml) and filtered through a 2 g silica cartridge washing with EtOAc:MeOH (10:1, 4 ml). The filtrate is concentrated in vacuo and the resulting residue is dissolved in NMP (4 ml) and loaded onto an Isolute™ SCX column (silica based cation exchange sorbent) eluting with MeOH (4 ml) and 1M NH3 in MeOH (6 ml). The appropriate fractions are combined and concentrated in vacuo to afford the title compound.

1. customThe reaction mixture is sonicated
2. customto give a very fine suspension
3. customThe resulting mixture is flushed with argon
4. temperatureheated
5. customat 150° C.
6. customfor 30 minutes
7. additionThe reaction mixture is treated with DMSO (2 ml)
8. filtrationfiltered through a 2 g silica cartridge
9. washwashing with EtOAc:MeOH (10:1, 4 ml)
10. concentrationThe filtrate is concentrated in vacuo
11. dissolutionthe resulting residue is dissolved in NMP (4 ml)
12. washeluting with MeOH (4 ml) and 1M NH3 in MeOH (6 ml)
13. concentrationconcentrated in vacuo

ORD record

ord-dcb8e476121a4279a427cf73d6d867ca

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901134B2