Reaktion #314991

Reaktionsgleichung

tri-t-butylphosphonium

tert-butyl 4-chloro-1H-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

1,4-dioxane

water

→

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

Lösungsmittel

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIn an argon-purged
2. 2
   Sonstigesealed tube
3. 3
   SonstigeThe tube was sealed
4. 4
   Sonstigethe tube was sealed
5. 5
   Temperaturheated to 100° C
6. 6
   workup.WAITAfter ˜105 min
7. 7
   Temperaturheating
8. 8
   Temperaturthe reaction mixture was cooled to RT
9. 9
   TrocknenThe filtrate was dried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe crude product was purified by column chromatography on 120 g silica gel column
13. 13
    Sonstige(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
14. 14
    Sonstige80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
15. 15
    SonstigeA viscous brown oil was obtained
16. 16
    Sonstigeat RT
17. 17
    Sonstigefor several hours
18. 18
    Sonstigecrystals were formed
19. 19
    TemperaturThe oil was cooled to 0° C.
20. 20
    Sonstigelight yellow solid precipitated out
21. 21
    workup.ADDITIONafter adding small amounts of hexanes
22. 22
    workup.ADDITIONa little bit of ether in addition
23. 23
    FiltrationThe light yellow solid was filtered
24. 24
    Waschenwashed with cold hexanes
25. 25
    Sonstigedried under vacuum

Vorschrift

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 tetrafluroroborate (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.

Quelle