Phosphorus tribromide → 8-Bromo-3,7-difluoro-2-methoxy-1,5-naphthyridine

HRID 15133Notes

Reaction equation

HRID 15133 reaction equation
CN(C)C=[C:4]([F:24])[C:5]([C:7]1[C:12]([NH:13][C:14](=O)[O:15][C:16](C)(C)C)=[CH:11][C:10]([F:21])=[C:9](OC)[N:8]=1)=O.P(Br)(Br)[Br:27]>FC(F)(F)C(O)=O.ClCCl.O.C(=O)([O-])[O-].[K+].[K+]>[Br:27][C:11]1[C:10]([F:21])=[CH:9][N:8]=[C:7]2[C:12]=1[N:13]=[C:14]([O:15][CH3:16])[C:4]([F:24])=[CH:5]2

Participants

6

Reactant 2

HCID 24614Phosphorus tribromide2×HCID 686534721,1-Dimethylethyl [2-[3-(dimethylamino)-2-fluoroacryloyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

Product 1

HCID 675272588-Bromo-3,7-difluoro-2-methoxy-1,5-naphthyridineYield 57.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 11430Potassium CarbonateSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

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%).

Workup

  1. customevaporated
  2. additionThe residue was treated with ˜50 ml 2M ammonia in methanol until basic and
  3. customevaporated
  4. customThis residue was dried in vacuo
  5. customthen chromatographed
  6. washeluting with 0-10% methanol in ethyl acetate affording a solid (3.64 g), 8-hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine
  7. dissolution8-Hydroxy-3,7-difluoro-2-(methyloxy)-1,5-naphthyridine (3.64 g) was dissolved in N,N-dimethylformamide (20 ml)
  8. filtrationFiltration
  9. customdrying in vacuo

Sources & evidence

ORD record
ord-19d2d1239f614d5fa50f7a43d9590148
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Reaction notes

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