Sodium Carbonate → HCID 178489374, compound

A mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (254 mg, 0.53 mmol), a mixture of 2-(3-bromo-phenyl)-1-methyl-1H-imidazole and 2-(3-chloro-phenyl)-1-methyl-1H-imidazole (200 mg, 0.48 mmol each) and 1,1′-bis(diphenylphosphino)-ferrocenepalladium(II)-dichloride dichlormethane adduct (20 mg, 0.024 mmol) in acetonitrile (5 mL) and aqueous solution of sodium carbonate (2M, 0.48 mL) was irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min. Sodium sulfate was added to the crude reaction mixture and the solids were filtered over Celite. The solids were washed with acetonitrile and the combined filtrate was concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded a white solid which was dissolved in 5 mL trifluoroacetic acid. The mixture was stirred at room temperature for 1 h and the solvent was evaporated. The crude product was dissolved in 1 mL of methanol and 200 μL of ethylenediamine was added. After 15 min, 1 mL of DMSO was added and the mixture was directly purified by mass-triggered preparative reverse phase HPLC to give 3-(2-Methoxy-phenyl)-5-[3-(1-methyl-1H-imidazol-2-yl)-phenyl]-1H-pyrazolo[3,4-b]pyridine formic acid salt as a colorless solid (82 mg, 0.019 mmol, 40% yield). As the formic acid salt: 1H NMR (500 MHz, DMSO-d6) δ 8.89 (d, J=2 Hz, 1H), 8.37 (d, J=2 Hz, 1H), 8.15 (s, 1H), 8.01 (t, J=2 Hz, 1H), 7.79 (dt, J1=8 Hz, J2=1 Hz, 1H), 7.70 (dt, J1=8 Hz, J2=1.5 Hz, 1H), 7.65 (dd, J1=7.5 Hz, J2=2 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.28 (d, J=1.5 Hz, 1H), 7.20 (d, J=8 Hz, 1H), 7.08 (td, J1=7.5 Hz, J2=1 Hz, 1H), 7.0 (d, J=1 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H). MS: m/z 382.2 (M+H+).

1. customwas irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min
2. customreaction mixture
3. filtrationthe solids were filtered over Celite
4. washThe solids were washed with acetonitrile
5. concentrationthe combined filtrate was concentrated
6. customPurification by flash silica gel chromatography
7. customafforded a white solid which
8. customthe solvent was evaporated
9. dissolutionThe crude product was dissolved in 1 mL of methanol
10. addition200 μL of ethylenediamine was added
11. waitAfter 15 min
12. addition1 mL of DMSO was added
13. customthe mixture was directly purified by mass-triggered preparative reverse phase HPLC

ORD record

ord-aac4f3cffb844c05a3893720bdd16451

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268994B2