Reaktion #314954

Reaktionsgleichung

tert-butyl 4-chloro-1-H-pyrrolo[2,3-b]pyridine-1-carboxylate

4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine

sodium carbonate

tri-t-butylphosphonium

→

tert-butyl 4-(2-(4-aminophenoxy)pyridin-3-yl)-1-H-pyrrolo[2,3-b]pyridine-1-carboxylate

Lösungsmittel

water

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIn an argon-purged
2. 2
   Sonstigesealed tube
3. 3
   SonstigeThe tube was sealed
4. 4
   Temperaturheated to 100° C
5. 5
   workup.WAITAfter 1 h 45 min
6. 6
   TemperaturThe reaction mixture was cooled to rt
7. 7
   Waschenwashing with EtOAc
8. 8
   TrocknenThe filtrate was dried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    SonstigeThe crude product was purified by column chromatography on 120 g silica gel column
12. 12
    Sonstige(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
13. 13
    Sonstige80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
14. 14
    SonstigeA viscous brown oil was obtained
15. 15
    Sonstigeat rt
16. 16
    Sonstigefor several hours
17. 17
    Sonstigesmall amounts of crystaline colonies were formed
18. 18
    TemperaturThe oil was cooled to 0° C.
19. 19
    Sonstigelight yellow solid precipitated out
20. 20
    workup.ADDITIONafter adding small amounts of hexanes
21. 21
    workup.ADDITIONa little bit of ether in addition
22. 22
    FiltrationThe light yellow solid was filtered
23. 23
    Waschenwashed with cold hexanes
24. 24
    Sonstigedried under vacuum

Vorschrift

In an argon-purged sealed tube, tert-butyl 4-chloro-1-H-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 tetrafluroroborate (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 crystaline 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)-1-H-pyrrolo[2,3-b]pyridine-1-carboxylate was obtained. MS m/z=403 [M+1]+. Calcd for C23H22N4O3: 402.17.

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