Cyanoacetic acid → 2-cyano-N-(4-methoxypyridin-3-yl)acetamide

Participants

Reaction Steps

4-Methoxypyridin-3-amine (22 g, 177.2 mmol) and 2-cyanoacetic acid (19.60 g, 230.4 mmol) were slurried in THF (1 L). The mixture was cooled in an ice bath and DMAP (28.15 g, 230.4 mmol) was added followed by 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (50.95 g, 265.8 mmol). The mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was partially concentrated, then diluted with ethyl acetate/water. The organic phase was isolated and washed with saturated NaHCO3, then brine, dried (MgSO4), filtered and concentrated. The residue was slurried in ether/petrol to give 2-cyano-N-(4-methoxypyridin-3-yl)acetamide 8 as a yellow solid (26.4 g, 78%). LC-MS (M+H)+ 192.0; 1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 8.86 (s, 1H), 8.28 (d, 1H), 7.15 (d, 1H), 4.00 (s, 2H), 3.92 (s, 3H).

Provenance & Evidence