Uses
2-Cyanophenylboronic Acid is used in the synthesis of pyridine inhibitors of TAK1. Also participates in the discovery and synthesis of 1,2,4-triazoles as novel allosteric valosine containing protein (VCP) inhibitors. VCP is found highly abundant in various tumor types allowing for a potential target in cancer therapy.
Synthesis
Under nitrogen protection, 7.88 g (55.8 mmol) of 2,2,6,6-tetramethylpiperidine and 2.77 g (65.3 mmol) of lithium chloride (1.17:1 molar ratio to 2,2,6,6-tetramethylpiperidine) in THF were added to a 300 mL flask. A lithium 2,2,6,6-tetramethylpiperidine solution was prepared by slow dropwise addition of 24.2 g (58.2 mmol) of 15% n-butyllithium hexane solution at -10 °C. After cooling the reaction system to -50 °C, 10.93 g (58.2 mmol) of triisopropoxyborane and 4.98 g (48.3 mmol) of benzonitrile were added sequentially dropwise, and the reaction was maintained at this temperature for 3 h. HPLC analysis showed that the area percentage of 2-cyanobenzeneboronic acid in the reaction solution was 98.6%, and the by-product, 1 -phenyl-1 -(2,2,6,6-tetramethylpiperidin- 1-yl)methylimine had an area percentage of 1.38%. The reaction solution was poured into 38 mL of 3N HCl for hydrolysis and 150 mL of ethyl acetate was added for extraction to separate the aqueous phase. The organic phase was washed with 50 mL of 0.2N HCl and quantitatively analyzed by HPLC to confirm that the yield of 2-cyanophenylboronic acid was 95.0% and it contained 0.45% of 1-phenyl-(2,2,6,6-tetramethylpiperidin-1-yl)methylimine.
