Citric Acid → 6-Chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (900 mg, 3.27 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (360 mg, 0.49 mmol) was purged with N2. To this mixture was added 4′-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-[1,1′-biphenyl]-2-ol (922 mg, 3.27 mmol) in toluene (5.0 mL) and EtOH (15.0 mL), followed by 2N aqueous potassium carbonate solution (6.0 mL, 12 mmol). The reaction mixture was heated to 100° C. for 48 hours, cooled to room temperature and poured into 1N aqueous citric acid (15 mL). The aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase chromatography (C-18 column, 10-40% MeCN/water) to give the title compound (258 mg, 22% yield) as a solid. MS (ES+) 365.0 (M+H)+. 1H NMR (500 MHz, CD3OD) δ 8.18 (s, 1H), 7.82 (s, 1H), 7.68 (d, 2H), 7.50 (d, 2H), 7.36 (d, 1H), 7.19 (dt, 1H), 6.97-6.92 (m, 2H).

Provenance & Evidence