2-(Benzylamino)isonicotinic acid synthesis

Yield:-

Reaction Conditions:

Stage #1:2-chloro-4-pyridinenitrile;benzylamine with pyridine at 80; for 2 h;
Stage #2: with hydrogenchloride;water in 1,4-dioxane at 80; for 2 h;
Stage #3: with sodium hydrogencarbonate in 1,4-dioxane;water

Steps:

102
Synthesis of 2-Benzylaniino-isonicotinic acid (12p_a): 2-Chloroisonicotinonitrile (1 g, 7.2 mmol) and benzyl amine (1.6 mL, 14.4 mmol) were dissolved in pyridine (20 mL) and heated to 80⁰C for 2 hours. The solvent was then removed and the product purified by column chromatography (1:4 EtOAc/hexanes). The product (367 mg, 1.8 mmol) was then heated to 80⁰C in 4N HCl (4 mL) for 2 hours. The reaction was neutralized with sat'd NaHCO₃(aq) and extracted with CH₂Cl₂.

References:

CHEMOCENTRYX, INC. WO2007/51062, 2007, A2 Location in patent:Page/Page column 142