Reacción #43411

Ecuación de reacción

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

phosphorus tribromide

phosphorus tribromide

→

product

Rendimiento 57.4%

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

Rendimiento 57.4%

Disolventes

trifluoroacetic acid dichloromethane

water

potassium carbonate

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroevaporated
2. 2
   workup.ADDITIONThe residue was treated with ˜50 ml 2M ammonia in methanol until basic and
3. 3
   Otroevaporated
4. 4
   OtroThis residue was dried in vacuo
5. 5
   Otrothen chromatographed
6. 6
   Lavadoeluting 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
   FiltraciónFiltration
9. 9
   Otrodrying in vacuo

Procedimiento

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%).

Fuente