Potassium Carbonate → 6-Chloro-5-(4-(1-methylpiperidin-4-yl)phenyl)-1H-indazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (92.0 mg, 0.27 mmol), oven dried potassium acetate (116 mg, 1.18 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (22 mg, 0.027 mmol) and 4-(4-bromophenyl)-1-methylpiperidine (65 mg, 0.26 mmol) in 1,4-dioxane (2.6 mL) was degassed with N2 for 10 minutes, sealed in a pressure tube, and heated to 100° C. for 2 hours. The cooled reaction mixture was filtered through cotton and concentrated in vacuo to give a dark solid. To the dark solid was added 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (59.8 mg, 0.22 mmol), 2 N aqueous potassium carbonate solution (0.4 mL, 0.87 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (18 mg, 0.022 mmol). The reaction mixture was diluted with degassed toluene (0.8 mL) and EtOH (0.8 mL), sealed in a pressure tube and heated at 100° C. for 1.5 hours then 75° C. for an additional 16 hours. The cooled reaction mixture was concentrated in vacuo. The resulting dark solid was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 8.5 min, HOLD at 0% H2O/100% MeCN to 10.0 min. Flow: 25 mL/min) to give the title compound (8.2 mg, 9% yield). MS (ES+) 370.2 (M+H)+. Retention time=2.00 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Provenance & Evidence