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

HRID 920074
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HRID 920074 반응식
CO[C:3]([C:5]1[C:6]([OH:39])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[N:14]=1)[N:11]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:10](=[O:28])[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1)=[CH:8]2)=[O:4].[NH2:40][CH2:41][CH2:42][C:43]([OH:45])=[O:44].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:21]([N:11]1[C:12]2[C:7](=[C:6]([OH:39])[C:5]([C:3]([NH:40][CH2:41][CH2:42][C:43]([OH:45])=[O:44])=[O:4])=[N:14][C:13]=2[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:38])[F:37])[CH:30]=2)[C:10]1=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 682974461-Benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

생성물 1

HCID 682973943-{[1-Benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid수율 40.2%

시약·촉매·용매 1

HCID 516892
Sodium Bicarbonate
용매

실험 절차

A mixture of 1-benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (29 mg, 0.055 mmol), β-alanine (487 mg, 5.5 mmol) and NaOMe solution (8.8 mL, 4.4 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 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (10-100% 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, and the resulting precipitate was isolated by filtration to give 13 mg of the title compound. MS: (+) m/z 589.24 (M+1).

후처리

  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 3-4
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (10-100% EtOAc/hexanes+1% AcOH)
  9. customThe product isolated
  10. washwashed several times with ether
  11. customthe resulting precipitate was isolated by filtration

출처 및 근거

ORD 기록
ord-8f0efbba2c6f4d029fa17e6023a1003a
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09271970B2

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