Sodium Methoxide → 3-{[7-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-2,2-dimethyl-propionic acid

HRID 1410809ノート

反応式

HRID 1410809 の反応式
CO[C:3]([C:5]1[N:6]=[C:7]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=2)[C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4].OC(C(F)(F)F)=O.[NH2:38][CH2:39][C:40]([CH3:45])([CH3:44])[C:41]([OH:43])=[O:42].C[O-].[Na+]>CCO>[CH2:16]([N:10]1[C:9](=[O:23])[C:8]2[C:7]([C:24]3[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=3)=[N:6][C:5]([C:3]([NH:38][CH2:39][C:40]([CH3:45])([CH3:44])[C:41]([OH:43])=[O:42])=[O:4])=[C:14]([OH:15])[C:13]=2[CH:12]=[CH:11]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

参加物

5

反応物 3

HCID 10942334Sodium MethoxideHCID 682973507-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl esterHCID 1317322153-Amino-2,2-dimethyl-propionic acid TFA salt

生成物 1

HCID 682973153-{[7-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-2,2-dimethyl-propionic acid収率 34%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
140 °C

実験手順

A mixture of 7-benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (17 mg, 0.042 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (39 mg, 0.17 mmol), and NaOMe (18 mg, 0.34 mmol) in EtOH (2 mL) was heated at 140° C. for 6 h in a microwave reactor. After the mixture was cooled to r.t., solvent was evaporated in vacuo. The residue was partitioned between water and EtOAc. 1 M HCl was added with vigorous stirring until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (0-40% EtOAc/CH2Cl2+1% AcOH). The product was then dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2, and the resulting precipitate was isolated by filtration to give 7 mg of the title compound. MS: (+) m/z 491.37 (M+1).

後処理

  1. temperatureAfter the mixture was cooled to r.t.
  2. customsolvent was evaporated in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. addition1 M HCl was added
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (0-40% EtOAc/CH2Cl2+1% AcOH)
  8. dissolutionThe product was then dissolved in saturated NaHCO3
  9. washwashed several times with ether
  10. customthe resulting precipitate was isolated by filtration

出典と根拠

ORDレコード
ord-3cbe0d59d85046eba3f4ff4c903be76b
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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