반응 #43411

반응 방정식

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

phosphorus tribromide

phosphorus tribromide

→

product

수율 57.4%

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

수율 57.4%

용매

trifluoroacetic acid dichloromethane

water

potassium carbonate

반응 조건

후처리

1. 1
   기타evaporated
2. 2
   workup.ADDITIONThe residue was treated with ˜50 ml 2M ammonia in methanol until basic and
3. 3
   기타evaporated
4. 4
   기타This residue was dried in vacuo
5. 5
   기타then chromatographed
6. 6
   세척eluting 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
   여과Filtration
9. 9
   기타drying in vacuo

실험 절차

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%).

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