Reaktion #680144

Reaktionsgleichung

tert-butyl 3-(6-aminopyridin-3-yl)azetidine-1-carboxylate

3,5-dibromo-1-methylpyridin-2(1H)-one

cesium carbonate

XantPhos

→

239a

Ausbeute 98.0%

tert-Butyl 3-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridine-3-yl)azetidine-1-carboxylate

Ausbeute 98.0%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. 2
   SonstigeAfter bubbling nitrogen through the resulting suspension for 30 minutes
3. 3
   Sonstigeflush
4. 4
   TemperaturAfter this time the reaction was cooled to room temperature
5. 5
   Filtrationfiltered
6. 6
   SonstigeThe filtrate was partitioned between ethyl acetate (120 mL) and water (60 mL)
7. 7
   SonstigeThe aqueous layer was separated
8. 8
   Extraktionextracted with ethyl acetate (3×80 mL)
9. 9
   WaschenThe combined organic layer was washed with brine (30 mL)
10. 10
    Trocknendried over sodium sulfate
11. 11
    SonstigeThe drying agent was removed by filtration
12. 12
    Einengenthe filtrate was concentrated under reduced pressure
13. 13
    SonstigeThe residue was purified by silica-gel column chromatography
14. 14
    Wascheneluting with 1:4 ethyl acetate/petroleum ether

Vorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), tert-butyl 3-(6-aminopyridin-3-yl)azetidine-1-carboxylate (1.8 g, 7.2 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.9 g, 7.2 mmol), and cesium carbonate (4.7 g, 14.4 mmol). After bubbling nitrogen through the resulting suspension for 30 minutes, XantPhos (418 mg, 0.72 mmol) and tris(dibenzylideneacetone)dipalladium(0) (661 mg, 0.72 mmol) were added. The reaction mixture was subjected to three cycles of vacuum/argon flush and heated at 105° C. for 0.5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (120 mL) and water (60 mL). The aqueous layer was separated and extracted with ethyl acetate (3×80 mL). The combined organic layer was washed with brine (30 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:4 ethyl acetate/petroleum ether to afford the 239a as a yellow solid (3.06 g, 98%). MS-ESI: [M+H]+ 435.

Quelle