4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine → 7-chloro-8-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

To a suspension of 8-bromo-7-chloro-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (389 mg, 0.955 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (783 mg, 3.823 mmol) in toluene (7 mL) and 2.0 M aqueous sodium carbonate (2.1 mL) was added (Ph3P)4Pd (165 mg, 0.143 mmol) in one portion, and the resulting yellow mixture was vigorously stirred under argon in a 100° C. oil bath for 2.5 h. HPLC/MS indicated that about 20% of the title compound had formed. Additional (Ph3P)4Pd (50 mg, 0.043 mmol) was added, and the reaction mixture was stirred at 100° C. under argon for 3.5 h more. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The EtOAc phase was washed with water, then saturated aqueous NaCl, dried over Na2SO4, and concentrated under reduced pressure to obtain a crude product, which was purified by silica gel (12 g) column chromatography eluting with a gradient of EtOAc (0-100%) in hexanes to obtain the title compound as a yellow foam (169 mg). HPLC/MS: retention time=2.04 min, [M+H]+=406.

Provenance & Evidence