Potassium Carbonate → 6-Chloro-5-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-1H-indole-3-sulfonic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-6-chloro-1H-indole (300 mg, 1.30 mmol) and sulfur trioxide pyridine complex (622 mg, 3.91 mmol) in pyridine (2 mL) was sealed in a pressure tube and heated to 100° C. for 48 hours. The reaction mixture was concentrated in vacuo to provide 5-bromo-6-chloro-1H-indole-3-sulfonic acid as a pyridinium salt, which was used directly in the next step without further purification. A mixture of 5-bromo-6-chloro-1H-indole-3-sulfonic acid (100 mg, 0.32 mmol), 4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-2-ol (114 mg, 0.39 mmol), 2N aqueous potassium carbonate solution (0.64 mL, 1.29 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.0 mg, 0.016 mmol) in EtOH (5 mL) was sealed and heated to 130° C. for 2 hours. The reaction mixture was diluted with water (10 mL) and washed with EtOAc (2×10 mL). The aqueous layer was concentrated in vacuo and purified by reversed phase HPLC (Column: Waters Sunfire C18 19×100, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); HOLD at 100.0% H2O/0.0% MeCN for 1.0 min. 100.0% H2O/0.0% MeCN linear to 5.0% H2O/95.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min.) to provide the title compound (2.3 mg, 2%). MS (ES−) 398.0 (M−H)+. Retention time=2.28 minutes (Waters Atlantis dC18 4.6×50, 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