Sodium Methoxide → 1H,2H,3H,4H,5H-pyrido[2,3-e][1,4]diazepin-3-one

Participants

Reaction Steps

Raney nickel (3 g) was added to anhydrous methanol (50 mL) under argon and washed with anhydrous methanol (4×50 mL). (3-Cyanopyridin-2-ylamino)-acetic acid ethyl ester (3.35 g, 16.3 mmol) was dissolved in methanol (50 mL) and added to the Raney nickel slurry. The reaction vessel was purged with argon for 10 min. Sodium methoxide solution (16.3 mmol, 3.75 mL) was added and the argon purge was repeated (5 min). The reaction flask was charged with H2 and stirred at room temperature for 48 h. Dilute HCl (16.3 mL of a 1 M solution) was added and the flask was purged with argon for 30 min. The slurry was filtered through celite and the filter cake was washed with 1:1 methanol/water. The filtrate was concentrated and extracted with ethyl acetate (4×100 mL), dried over MgSO4 and concentrated to afford the title compound as a beige solid (850 mg, 30%). 1H NMR (300 MHz, DMSO-d6) δ 8.07 (t, J=5.2 Hz, 1H), 7.82 (dd, J=4.9, 1.5 Hz, 1H), 7.21 (dd, J=7.1, 1.6 Hz, 1H), 6.69 (t, J=5.0 Hz, 1H), 6.43 (dd, J=7.2, 5.0 Hz, 1H), 4.24 (d, J=5.9 Hz, 2H), 3.91 (d, J=5.1 Hz, 2H).

Provenance & Evidence