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), water (11.7 mL) were added. The reaction was stirred at rt for 5 min. Then palladium acetate (0.246 g, 1.10 mmol) and tri-t-butylphosphonium tetrafluororoborate (0.637 g, 2.19 mmol) were added. The tube was sealed and heated to 100° C. After 1 h 45 min, the reaction was monitored and found to be complete. The reaction mixture was cooled to rt and passed through a pad of celite, washing with 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, small amounts of crystalline colonies 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 obtained. MS m/z=403 [M+1]+. Calcd for C23H22N4O3: 402.17.

1. customIn an argon-purged
2. customsealed tube
3. customThe tube was sealed
4. temperatureheated to 100° C
5. waitAfter 1 h 45 min
6. temperatureThe reaction mixture was cooled to rt
7. washwashing with EtOAc
8. dry with materialThe filtrate was dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by column chromatography on 120 g silica gel column
12. custom(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
13. custom80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
14. customA viscous brown oil was obtained
15. customat rt
16. customfor several hours
17. customsmall amounts of crystalline colonies were formed
18. temperatureThe oil was cooled to 0° C.
19. customlight yellow solid precipitated out
20. additionafter adding small amounts of hexanes
21. additiona little bit of ether in addition
22. filtrationThe light yellow solid was filtered
23. washwashed with cold hexanes
24. customdried under vacuum