Pyridine → 6-Chloro-2-[(2-methoxy-ethyl)-methyl-amino]-nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-2-[(2-methoxy-ethyl)-methyl-amino]-nicotinamide (3) (14 g, 58 mmol) in acetonitrile (anhydrous, 360 mL) were added pyridine (37.5 mL, 463.8 mmol) and POCl3 (21.2 mL, 232 mmol). The reaction was heated at 55° C. for 3 hours. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. The solution was extracted with EtOAc (3×200 mL). The combined organic layer was dried over MgSO4, filtered, and evaporated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 5%-30% EtOAc/hexanes gradient, to afford 11.6 g (90% yield) of the desired product. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.61 (d, J=7.4 Hz, 1 H), 6.58 (d, J=7.8 Hz, 1 H), 3.87 (t, J=5.3 Hz, 2 H), 3.64 (t, J=5.3 Hz, 2 H), 3.38 (s, 3 H), 3.36 (s, 3 H).

Provenance & Evidence