2-(3-Bromophenyl)-2-hydroxyacetic acid → hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,2-dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (4.5 g, 9.7 mmol), (±)-(3-bromo-phenyl)-hydroxy-acetic acid (2.7 g, 11.6 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (355 mg, 0.5 mmol) in THF/Acetonitrile/saturated NaHCO3 (20 ml/20 ml/50 ml) was stirred at 100° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. The crude was purified by reverse phase HPLC afforded hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid (1.7 g, 35% yield). 1H NMR (500 MHz, DMSO-d6) δ 3.86 (s, 3H), 5.05 (s, 1H), 5.14 (s, 2H), 7.10 (m, 1H), 7.21 (d, 1H), 7.40-7.50 (m, 3H), 7.67 (d, 1H), 7.79 (s, 1H).

Provenance & Evidence