Veratrylamine → 2-Chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloro-5-(3,5-dimethylphenyl)nicotinic acid (1-2, 0.200 g, 0.764 mmol, 1 equiv) and 3,4-dimethoxybenzylamine (0.319g, 1.91 mmol, 2.50 equiv) in DMF (5 mL) was added 1-(chloro-1-pyrrolidinylmethylene)-pyrrolidinium hexafluorophosphate (PyClu, 0.383 mg, 1.15 mmol, 1.51 equiv), and diisopropylethylamine (0.667 mL, 3.82 mmol, 5.00 equiv). The resulting mixture was stirred at 23° C. for 20 hours. The reaction mixture was filtered and purified via reverse phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present). The desired fractions were partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (2×50 mL). The combined organic layers were washed with brine then dried over sodium sulfate and concentrated to give 2-chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide (1-3) as a white powder. LRMS m/z (M+H) 262.3 found, 262.1 required.

Provenance & Evidence