Beta-Alanine → 3-{[7-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 1410996ノート

反応式

HRID 1410996 の反応式
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](CC1C=CC=CC=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+]>[CH2:9]([N:14]1[C:13]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)=[C:12]2[C:7](=[CH:8][CH:9]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:10](=[O:29])[NH:11]2)[C:6]([OH:36])=[C:5]1[C:3]([NH:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41])=[O:4])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

参加物

5

反応物 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 68297280HCID 68297280、化合物

生成物 1

HCID 867141663-{[7-Benzyl-8-(5-fluoro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid収率 77.3%

試薬・触媒・溶媒 1

HCID 516892Sodium Bicarbonate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d18c8d7141f34cc49179c60d7f44c53e
出典データセット
uspto-grants-2014_12
特許番号
US08921389B2

反応ノート

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