Diisopropylethylamine → 3,6-dichloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxamide

Participants

Reaction Steps

To a stirred solution of 3,6-dichloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylic acid (85 mg, 0.28 mmol) in DMF (2 ml) was added DIPEA (73 μl, 0.42 mmol) and HATU (127 mg, 0.33 mmol). The reaction was stirred at room temperature for 5 min after which time 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 52 mg, 0.31 mmol) was added and the reaction was stirred at room temperature for 16 h. The reaction mixture was then poured onto 50 ml of water and the aqueous phase was extracted with EtOAc (3×50 ml), washed with brine (50 ml) dried (Na2SO4) and evaporated to give an oil. The product was then purified using a 5 g silica Isolute column eluting with 0% to 5% MeOH in DCM and evaporated to give a glassy solid which was triturated with diethyl ether and filtered to afford the title compound as a white powder (50 mg, 41%). LC-MS 95%, m/z=439.0/440.8, 1H NMR (500 MHz, Chloroform-d) δ 11.33 (br. s, 1H), 8.20 (br. s, 1H), 6.79 (s, 1H), 5.93 (s, 1H), 4.51 (s, 2H), 4.02 (dd, J=11.4, 3.8 Hz, 2H), 3.92-3.72 (m, 1H), 3.39 (t, J=11.3 Hz, 2H), 2.78 (s, 3H), 2.38 (s, 3H), 2.27 (s, 3H), 1.89 (tt, J=12.0, 6.2 Hz, 2H), 1.83-1.52 (m, 2H).

Provenance & Evidence