Diisopropylethylamine → HCID 70873586, compound

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 2-[ethyl(oxan-4-yl)amino]-3-methylpyridine-4-carboxylic acid (20 mg, 0.08 mmol) in dry DMF (1.0 ml) at 0° C. under nitrogen, was treated with HATU (37 mg, 0.1 mmol) and DIPEA (26 μl, 0.15 mmol) dropwise. The resulting solution was stirred for 10 minutes and then treated with 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 15 mg, 0.09 mmol). The resulting suspension was stirred at 0° C. for 20 minutes and then stirred at room temperature for 18.5 hours. The reaction mixture was cooled to 0° C. and retreated with HATU (120 mg, 0.31 mmol) and DIPEA (84 μl, 0.48 mmol). After stirring for 10 minutes, 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 49 mg, 0.29 mmol) was added. The reaction mixture was stirred for 1 hour at 0° C. and was then lifted out of the ice bath stirred at room temperature for 48 hours. The reaction mixture was diluted with water (20 ml) and CH2Cl2 (20 ml). The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×15 ml). The combined organic phases were washed with water (2×25 ml), brine (2×25 ml), dried (MgSO4), filtered and concentrated in-vacuo. The crude residue was purified by column chromatography (10 g SNAP cartridge, Isolera, 0-40% MeOH:CH2Cl2 and 0-25% MeOH (containing 10% NH4OH):CH2Cl2) to give 6.7 mg (22% Yield) of the title compound as an off white solid. LC-MS 100%, m/z=399.1; 1H NMR (250 MHz, DMSO) δ 11.49 (s, 1H), 8.32 (t, J=4.9 Hz, 1H), 8.14 (d, J=4.9 Hz, 1H), 6.84 (d, J=4.9 Hz, 1H), 5.86 (s, 1H), 4.26 (d, J=4.7 Hz, 2H), 3.84 (dd, J=10.3, 3.5 Hz, 2H), 3.21 (dt, J=13.6, 4.6 Hz, 5H), 2.19 (s, 3H), 2.15 (s, 3H), 2.11 (s, 3H), 1.62 (dt, J=21.1, 6.6 Hz, 4H), 0.80 (t, J=6.9 Hz, 3H).

Provenance & Evidence