反应详情

温度

100 °C

To a stirred solution of 6-bromo-N-((4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.37 g, 0.85 mmol) and 2,2,6,6-tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (1.2 equiv.) in dioxane/water mixture (3 mL+1 mL for 1 mmol), Na2CO3 (3.6 equiv.) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.05 equiv.) was added and argon was purged again for 10 min. Reaction mass was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to afford crude material which was purified by column chromatography over silica gel to afford the desired compound. (38% yield). LCMS: 491.25 (M+1)+; HPLC: 95.01% (@ 254 nm) (Rt; 5.463); 1H NMR (DMSO-d6, 400 MHz) δ 11.55 (s, 1H), 8.87 (s, 1H), 8.26 (s, 1H), 7.79 (s, 1H), 6.80 (s, 1H), 5.91 (s, 1H), 5.22-5.19 (m, 1H), 4.39 (d, 2H, J=4.0 Hz), 2.42-2.40 (m, 4H), 2.24 (s, 3H), 1.49 (d, 6H, J=6 Hz). 1.24 (s, 6H), 1.14 (s, 6H), 1.11 (m, 3H).

1. customsolution purged with argon for 15 min
2. customargon was purged again for 10 min
3. customReaction mass
4. customOn completion, reaction mixture
5. extractionextracted with 10% MeOH/DCM
6. dry with materialCombined organic layers were dried over Na2SO4 and solvent
7. customremoved under reduced pressure
8. customto afford crude material which
9. customwas purified by column chromatography over silica gel