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

To a stirred solution of 3-bromo-6-chloro-4-[methyl(oxan-4-yl)amino]pyridine-2-carboxylic acid (73 mg, 0.21 mmol) in DMF (2 ml) were added DIPEA (56 μl, 0.31 mmol) and HATU (95 mg, 0.25 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%, 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, 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 4% MeOH in DCM and evaporated to give a glassy solid which was triturated with diethyl ether and filtered and dried in a vacuum oven at 40° C. for 24 h to afford the title compound as a white powder (50 mg, 41%). LC-MS 99%, m/z=483.1/485.0/486.9, 1H NMR (500 MHz, CDCl3) δ 10.94 (br. s, 1H), 8.14-7.98 (m, 1H), 6.83 (s, 1H), 5.92 (s, 1H), 4.55 (d, J=6.1 Hz, 2H), 4.15-3.94 (m, 2H), 3.93-3.70 (m, 1H), 3.40 (t, J=11.0 Hz, 2H), 2.78 (s, 3H), 2.39 (s, 3H), 2.28 (s, 3H), 1.99-1.82 (m, 2H), 1.79-1.64 (m, 2H).

1. additionwas added
2. extractionthe aqueous phase was extracted with EtOAc (3×50 ml)
3. washwashed with brine (50 ml)
4. dry with materialdried (Na2SO4)
5. customevaporated
6. customto give an oil
7. customThe product was then purified
8. washeluting with 0% to 4% MeOH in DCM
9. customevaporated
10. customto give a glassy solid which
11. customwas triturated with diethyl ether
12. filtrationfiltered
13. customdried in a vacuum oven at 40° C. for 24 h

ORD record

ord-839abb9486d64c33b0865352c5b407d4

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376422B2