反应详情

A round bottom flask equipped with a reflux condenser and a nitrogen line was charged with palladium acetate (3.4 mg, 0.015 mmol), cesium carbonate (300 mg, 0.92 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (19 mg, 0.030 mmol), 7-bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (Example 127, Step A; 150 mg, 0.307 mmol), and potassium (dimethylaminomethyl)trifluoroborate (Frontier Scientific; 101 mg, 0.613 mmol). To the reaction flask was added a 1,4-dioxane:water mixture (10:1; 1.1 mL) and the reaction flask was immediately evacuated and refilled with nitrogen three times. The reaction mixture was heated at reflux for 16 hours under nitrogen. After cooling to ambient temperature, the reaction mixture was diluted with water, and extracted multiple times with dichloromethane. The combined dichloromethane extracts were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude residue was purified by preparative thin-layer chromatography (silica, 2% 7N ammonia-MeOH:8% MeOH:DCM) to afford the product (84.8 mg) as a white solid. 1H NMR (CDCl3) δ 9.5 (d, 1H), 8.35 (s, 1H), 8.20 (s, 1H), 7.84 (d, 1H), 7.62 (m, 1H), 7.40 (t, 1H), 7.32 (t, 1H), 7.12 (m, 2H), 7.01 (d, 1H), 6.48 (d, 1H), 5.65 (s, 2H), 3.52 (s, 2H), 3.23 (q, 2H), 2.29 (s, 6H), 1.51 (t, 3H).

1. customA round bottom flask equipped with a reflux condenser
2. customwater mixture (10:1; 1.1 mL) and the reaction flask was immediately evacuated
3. additionrefilled with nitrogen three times
4. temperatureThe reaction mixture was heated
5. temperatureat reflux for 16 hours under nitrogen
6. additionthe reaction mixture was diluted with water
7. extractionextracted multiple times with dichloromethane
8. dry with materialThe combined dichloromethane extracts were dried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe crude residue was purified by preparative thin-layer chromatography (silica, 2% 7N ammonia-MeOH:8% MeOH:DCM)