3,5-Dimethylphenylboronic acid → N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2,3'-bipyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,5-dichloro-N-(3,4-dimethoxybenzyl)nicotinamide (3-2, 0.100 g, 0.293 mmol) and 3-pyridyl boronic acid (0.172 g, 1.17 mmol) in methanol (1 mL) was added N,N-dicylohexylmethylamine (0.070 mL, 0.322 mmol), and bis(tri-t-butylphosphine)palladium (0.030 g, 0.058 mmol) and the system was stirred at 75° C. in an oil bath overnight. The reaction mixture was cooled to room temperature and concentrated in vacuo to afford a yellow oil. This oil (0.035 g, 0.091 mmol) was re-dissolved in dioxane (0.2 mL) and to it was added 3,5-dimethylphenyl boronic acid (0.075 g, 0.502 mmol), N,N-dicylohexylmethylamine (0.022 mL, 0.100 mmol), and bis(tri-t-butylphosphine)palladium (0.009 g, 0.018 mmol) and the system was stirred overnight at 90° C. in an oil bath. The reaction was then cooled to room temperature, partitioned between ethyl acetate and water and dried over magnesium sulfate. The reaction mixture was filtered and purified via normal phase chromatography (0→10% MeOH in DCM) followed by reverse phase chromatography (10%→65% 0.1% TFA in water: 0.1% TFA in ACN) and free based with saturated sodium carbonate to afford the title compound (1-3) as a white powder. ESI+ MS [MH]+ C28H27N3O3=454.34.

Provenance & Evidence