Diisopropylethylamine → Tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl)azetidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of 5-{1-[(tert-butoxy)carbonyl]azetidin-3-yl}-2-methyl-3-[methyl(oxan-4-yl)amino]benzoic acid (47 mg, 0.12 mmol) in DMF (2 ml) were added DIPEA (40 μl, 0.23 mmol) and HATU (53 mg, 0.14 mmol) at 0° C. The reaction was stirred at 0° C. for 5 min after which time 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 22 mg, 0.13 mmol) was added and the reaction was warmed room temperature for 16 h. The reaction mixture was then poured onto distilled water (50 ml) and the aqueous phase was extracted with DCM (3×50 ml), washed with brine (50 ml) dried (Na2SO4), filtered 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 afford the title compound as a colourless oil (44 mg, 67%). LC-MS 96%, m/z=539.4, 1H NMR (500 MHz, Chloroform-d) δ 11.68 (s, 1H), 6.95 (t, J=5.8 Hz, 1H), 6.92 (d, J=4.2 Hz, 2H), 5.88 (s, 1H), 4.47 (d, J=5.8 Hz, 2H), 4.20 (t, J=8.7 Hz, 2H), 3.90 (d, J=11.2 Hz, 2H), 3.86-3.73 (m, 2H), 3.62-3.50 (m, 1H), 3.26 (t, J=10.8 Hz, 2H), 2.89 (ddd, J=14.6, 10.8, 3.7 Hz, 1H), 2.55 (s, 3H), 2.33 (s, 3H), 2.20 (s, 3H), 2.14 (s, 3H), 1.75-1.47 (m, 4H), 1.39 (d, J=5.7 Hz, 9H).

Provenance & Evidence