Sodium Carbonate → HCID 178518666, compound

Temperature

100 °C

Boronic acid solution 0.1 M was prepared in Toluene/EtOH (1/1). Boronic acid solution (100 mmol, 1000 μL) was added to vials. A suspension of 5-(3-bromophenyl)-7-((4-methoxyphenyl)amino)-5H-pyrazolo[3′,4′:4,5]pyrido[2,3-d]pyrimidin-3-ol (16) 0.1 M was prepared in Toluene/EtOH (1/1). Suspension of intermediate 56 (500 μL, 50 mmol) was added into each vial. Saturated Na2CO3 (500 μL) was added to each vial. Add catalytic amount of BDtBFPdCl2 to each vial at a time followed by purging with N2 with pipette and cap the vial immediately. The reactions were shaken at 100° C. for at least 16 h. EtOAc (2 mL) was added to each vial. Water (0.5 mL) was added to each vial. Vortex vials and water layer was removed. Additional water (1500 μL) was added to each vial, vortex and remove the water layer. Repeat water washing sequence again. Solvents were removed to dryness. Residue was dissolved in DMSO (1 mL) (may need heat to dissolve or add one drop TFA) and purified by reverse phase HPLC. To obtain 5-(4′-fluoro-[1,1′-biphenyl]-3-yl)-7-(4-methoxyphenyl)amino)-2H-pyrazolo[3′,4′:4,5]pyrido[2,3-d]pyrimidin-4(5H)-one (Compound 133) (11.2 mmol, 22%) LC-Mass: m/e 479 (M+1).

1. additionwas added into each vial
2. additionAdd catalytic amount of BDtBFPdCl2 to each vial at a time
3. customby purging with N2 with pipette
4. customcap the vial immediately
5. additionEtOAc (2 mL) was added to each vial
6. additionWater (0.5 mL) was added to each vial
7. customVortex vials and water layer was removed
8. additionAdditional water (1500 μL) was added to each vial, vortex and
9. customremove the water layer
10. customSolvents were removed to dryness
11. dissolutionResidue was dissolved in DMSO (1 mL) (may need heat to dissolve or add one drop TFA)
12. custompurified by reverse phase HPLC

ORD record

ord-a3e4e666c73a4d9ebd70d2168b4eeae0

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012466B2