Hydrochloric Acid → tert-butoxycarbonylamino-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-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 (0.9 g, 0.19 mmol) and the crude (3-bromo-phenyl)-tert-butoxycarbonylamino-acetic acid (0.69 g, 2.1 mmol) in a 20 mL microwave reaction flask was added THF (6 mL), acetonitrile (6 mL), and sodium carbonate (1 N in water, 6 mL, 6 mmol). The resulting suspension was purged with nitrogen for 1 minute. Dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (62 mg, 76 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 using 1 N hydrochloric acid, extracted with ethyl acetate (10 mL×3). The combined 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-butoxycarbonylamino-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid as a pale yellow solid (520 mg, 50%). MS: m/z 605 (M+H+).

Provenance & Evidence