Citric Acid → 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acid

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Reaction Steps

650 mg (1.35 mmol) 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, 449 mg (1.35 mmol max.) of 2-amino-5-iodo-3-methyl-benzoic acid and 55 mg (67 μmol) of dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct were placed in a vial. 10 mL of acetonitrile and 10 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was closed and the mixture irradiated in a Personal Chemistry® Optimizer to 120° C. for 20 min. The crude mixture was distributed between dichloromethane and water, adjusting the pH to 4-5 by addition of 10% aqueous citric acid. The aqueous layer was extracted three times with ethyl acetate. The combined organic phases were washed with a saturated aqueous solution of sodium bromide, dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 551 mg (1.09 mmol, 81%) of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acid as a beige solid. MS: m/z 505.1 (M+H+), 528.1 (M+Na+).

Provenance & Evidence