Beta-Alanine → 3-{[1-Benzyl-8-(5-fluoro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid

HRID 919994Notes

Reaction equation

HRID 919994 reaction equation
CO[C:3]([C:5]1[C:6]([OH:36])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=3)[N:14]=1)[N:11]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:10](=[O:29])[C:9]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[CH:8]2)=[O:4].[NH2:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:22]([N:11]1[C:12]2[C:7](=[C:6]([OH:36])[C:5]([C:3]([NH:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41])=[O:4])=[N:14][C:13]=2[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)[CH:8]=[C:9]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:10]1=[O:29])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 68297280HCID 68297280, compound

Product 1

HCID 601521123-{[1-Benzyl-8-(5-fluoro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acidYield 38.8%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-benzyl-8-(5-fluoro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (32 mg, 0.067 mmol), β-alanine (593 mg, 6.7 mmol) and NaOMe solution (10 mL, 5.0 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The residue was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4 with 6 M HCl, and the resulting precipitate was isolated by filtration. The crude solid was purified by silica gel chromatography (5-80% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 14 mg of the title compound as a light yellow solid. MS: (+) m/z 539.29 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned between EtOAc and water
  4. addition1 M HCl was added
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in saturated NaHCO3
  9. washwashed several times with ether
  10. customthe resulting precipitate was isolated by filtration
  11. customThe crude solid was purified by silica gel chromatography (5-80% EtOAc/hexanes+1% AcOH)
  12. customThe product isolated
  13. washwashed several times with ether
  14. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-ebf4303d9f7e47f5a039bc674787dc3f
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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