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Gamma-Aminobutyric Acid → 4-{[1-Benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid

HRID 920067
ノート
印刷プレビュー

反応式

HRID 920067 の反応式
CO[C:3]([C:5]1[C:6]([OH:33])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1)=[CH:8]2)=[O:4].[NH2:34][CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:33])[C:5]([C:3]([NH:34][CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[O:4])=[N:14][CH:13]=2)[CH:8]=[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:32])[F:31])[CH:24]=2)[C:10]1=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 119Gamma-Aminobutyric AcidHCID 10942334Sodium MethoxideHCID 682972811-Benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

生成物 1

HCID 682976234-{[1-Benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid収率 38.9%

試薬・触媒・溶媒 1

HCID 516892
Sodium Bicarbonate
溶媒

実験手順

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (40 mg, 0.088 mmol), 4-aminobutyric acid (726 mg, 7.0 mmol) and NaOMe solution (10.6 mL, 5.3 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 until pH was about 3. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% 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 2, and the resulting precipitate was isolated by filtration to give 18 mg of the title compound. MS: (+) m/z 526.32 (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 until pH was about 3
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH)
  9. customThe product isolated
  10. washwashed several times with ether
  11. customthe resulting precipitate was isolated by filtration

出典と根拠

ORDレコード
ord-164166b1b3cb44a59674cbaa3dad69db
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09271970B2

反応ノート

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