2-Amino-6-chloronicotinamide

58584-92-2

64321-24-0

General procedure for the synthesis of 2-amino-6-chloronicotinamide (Inter.3) from 2-amino-6-chloronicotinic acid (Inter.2): Thionyl chloride (3.3 eq.) was added drop-wise to an anhydrous THF solution of 0.3 M 2-amino-6-chloronicotinic acid (1 eq.) under inert atmosphere. The reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the mixture was concentrated in vacuum to give a crude yellow solid residue. The crude solid was dissolved in THF in the same volume as the initial reaction volume and concentrated again under vacuum to give a yellow solid residue. After repeating this dissolution and concentration process once, the residue was dissolved in THF (prepared as a 0.3 M solution) and ammonia was passed into the solution for 1 hour. The resulting precipitate was removed by filtration and the filtrate was concentrated under vacuum to give a yellow precipitate. The precipitate was ground in water at 50 °C and subsequently dried to afford the target compound 2-amino-6-chloronicotinamide (92% yield, 93% purity). The product was analyzed by LC-MS, m/z (ESP): 172 [M + H]+, retention time (R/T) = 3.19 min. The purity of the product met the requirements for use and no further purification was required.