Hydrochloric Acid → (tert-butoxycarbonyl-methyl-amino)-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid

Participants

Reaction Steps

To 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 (0.545 g, 1.1 mmol) and (3-Bromo-phenyl)-(tert-butoxycarbonyl-methyl-amino)-acetic acid (0.39 g, 1.1 mmol) in a 20 mL microwave reaction flask was added THF (3 mL), acetonitrile (3 mL), and sodium carbonate (1 N in water, 3 mL, 6 mmol). The resulting suspension was purged with nitrogen for 1 minute. Dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (39 mg, 48 μmol) was added and the purging was continued for another minute. The flask was sealed and was irradiated in a microwave reactor to 90° C. for 10 minutes. The reaction mixture was adjusted to pH 4 by addition of 1 N hydrochloric acid, extracted with ethyl acetate (10 mL×3). The combine organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane to afford (tert-butoxycarbonyl-methyl-amino)-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid as a off white solid (490 mg, 72%). MS: m/z 619 (M+H+).

Provenance & Evidence