反应详情

In an argon-purged sealed tube, tert-butyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (2.77 g, 11.0 mmol), 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine (5.14 g, 16.5 mmol), sodium carbonate (3.49 g, 32.9 mmol), 1,4-dioxane (32.3 ml, 11.0 mmol), and water (11.7 ml, 11.0 mmol) were added. The tube was sealed, and the reaction was stirred at RT for 5 min. Palladium acetate (0.246 g, 1.10 mmol) and tri-t-butylphosphonium tetrafluororoborate (0.637 g, 2.19 mmol) were added, and the tube was sealed and heated to 100° C. After ˜105 min, heating was stopped, the reaction mixture was cooled to RT and passed through a pad of celite with an aid of EtOAc. The filtrate was dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography on 120 g silica gel column using DCM and 95:05 DCM:(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots, then 80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product. A viscous brown oil was obtained. After setting the oil at RT for several hours, crystals were formed. The oil was cooled to 0° C. and light yellow solid precipitated out after adding small amounts of hexanes and a little bit of ether in addition to scratching the wall of the flash with a spatula. The light yellow solid was filtered, washed with cold hexanes, and dried under vacuum. This solid, tert-butyl 4-(2-(4-aminophenoxy)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate was mainly the product according to 1H NMR. MS Calcd for C23H22N4O3: [M]+=402. Found: [M+H]+=403.

1. customIn an argon-purged
2. customsealed tube
3. customThe tube was sealed
4. customthe tube was sealed
5. temperatureheated to 100° C
6. waitAfter ˜105 min
7. temperatureheating
8. temperaturethe reaction mixture was cooled to RT
9. dry with materialThe filtrate was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product was purified by column chromatography on 120 g silica gel column
13. custom(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
14. custom80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
15. customA viscous brown oil was obtained
16. customat RT
17. customfor several hours
18. customcrystals were formed
19. temperatureThe oil was cooled to 0° C.
20. customlight yellow solid precipitated out
21. additionafter adding small amounts of hexanes
22. additiona little bit of ether in addition
23. filtrationThe light yellow solid was filtered
24. washwashed with cold hexanes
25. customdried under vacuum