2-(Dicyclohexylphosphino)biphenyl → [8-(3,5-Bis-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[3-fluoro-1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine

Participants

Reaction Conditions

Reaction Steps

A degassed solution of palladium(II) acetate (2.73 mg, 12.2 μmol) and 2-(dicyclohexylphosphino)biphenyl (8.52 mg, 24.3 μmol) in dioxane (1 mL) was stirred for 10 minutes at room temperature, then added to a solution of 8-(3,5-bis(trifluoromethyl)phenyl)-N-(3-fluoropiperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (68 mg, 152 μmol), 5-chloro-3-methyl-1,2,4-thiadiazole (24.5 mg, 182 μmol) and sodium tert-butoxide (21.9 mg, 228 μmol) in dioxane (2 mL). Through the solution was bubbled argon for 5 minutes, then heated to 150° C. in the microwave for 45 minutes. Again a degassed solution of palladium(II) acetate (3.1 mg, 13.8 mmol) and 2-(dicyclohexylphosphino)biphenyl (9.69 mg, 27.6 μmol) in dioxane (1 mL) was added, followed by 5-chloro-3-methyl-1,2,4-thiadiazole (24.5 mg, 182 μmol) and heated for further 45 minutes to 150° C. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane). The title compound was obtained as colorless oil (30 mg, 36%) as a mixture of cis- and trans-isomers.

Provenance & Evidence