Potassium Carbonate → HCID 86698811, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), 2,3-dihydrobenzofuran-5-boronic acid (65.0 mg, 0.39 mmol) in EtOH (0.5 mL) and toluene (0.5 mL) was added 2 N aqueous potassium carbonate solution (0.5 mL, 1.0 mmol). The reaction mixture was degassed with N2 for 5 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.7 mg, 0.018 mmol) and degassed with N2 for another 5 minutes. The suspension was sealed in a pressure tube and heated to 130° C. for 1 hour. As the reaction progressed, the suspension became clear, turned to orange and then dark brown. The reaction mixture was diluted with EtOAc (5 mL) and water (5 mL), and filtered through a syringe filter. The aqueous layer was acidified to pH 5 by 1 N HCl solution, and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material 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 50.0% H2O/50.0% MeCN in 8.5 min, 50.0% H2O/50.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min) to provide the title compound (24.8 mg, 22% yield). MS (ES+) 315.1 (M+H)+. Retention time=2.68 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