N-Ethyl 5-bromopicolinamide synthesis

Yield:-

Reaction Conditions:

with benzotriazol-1-ol;1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;triethylamine in tetrahydrofuran;water at 50;

Steps:

6.1

A tetrahydrofuran solution of ethylamine (2M, 24.3 mL), hydroxybenzotriazole hydrate (9.29 g, 60.6 mmol), triethylamine (20.3 ml, 146 mmol), and N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (11.6 g, 60.6 mmol) were added to a mixed solution of tetrahydrofuran (200 ml) of 5-bromopyridine-2-carboxylic acid (4.90 g, 24.3 mmol) with water (50 ml), and this mixture was stirred overnight at 50°C. This reaction solution was concentrated, the residue was dissolved in ethyl acetate, and washed with an aqueous 10% citric acid solution, water and a saturated aqueous sodium bicarbonate solution, and dehydrated with anhydrous sodium sulfate, follwed by concentration under reduced pressure, to obtain a crude product containing 5-bromo-2-(ethylamide)pyridine.

References:

WO2010/24110,2010,A1 Location in patent:Page/Page column 28