Reaktion #43411

Reaktionsgleichung

1,1-dimethylethyl [2-[3-(dimethylamino)-2-fluoroacryloyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

phosphorus tribromide

phosphorus tribromide

→

product

Ausbeute 57.4%

8-Bromo-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine

Ausbeute 57.4%

Lösungsmittel

trifluoroacetic acid dichloromethane

water

potassium carbonate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeevaporated
2. 2
   workup.ADDITIONThe residue was treated with ˜50 ml 2M ammonia in methanol until basic and
3. 3
   Sonstigeevaporated
4. 4
   SonstigeThis residue was dried in vacuo
5. 5
   Sonstigethen chromatographed
6. 6
   Wascheneluting with 0-10% methanol in ethyl acetate affording a solid (3.64 g), 8-hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine
7. 7
   workup.DISSOLUTION8-Hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine (3.64 g) was dissolved in N,N-dimethylformamide (20 ml)
8. 8
   FiltrationFiltration
9. 9
   Sonstigedrying in vacuo

Vorschrift

A solution of 1,1-dimethylethyl [2-[3-(dimethylamino)-2-fluoroacryloyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate (2.15 g, 6.02 mmol) in trifluoroacetic acid/dichloromethane (20 ml/20 ml) was stirred at room temperature for 0.5 hour under argon and evaporated. The residue was treated with ˜50 ml 2M ammonia in methanol until basic and evaporated. This residue was dried in vacuo then chromatographed eluting with 0-10% methanol in ethyl acetate affording a solid (3.64 g), 8-hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine. 8-Hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine (3.64 g) was dissolved in N,N-dimethylformamide (20 ml) and treated with phosphorus tribromide (0.68 ml, 7.22 mmol). After 1 hour, more phosphorus tribromide (0.68 ml, 7.22 mmol) was added. After 0.5 hour the mixture was diluted with water and basified with solid potassium carbonate. Filtration and drying in vacuo afforded the product (0.95 g, 57%).

Quelle