Beta-Alanine → 3-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid

HRID 920040노트

반응식

HRID 920040 반응식
CO[C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[N:14]=1)[N:11]([CH2:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[C:10](=[O:28])[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:8]2)=[O:4].[NH2:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH:22]1([CH2:21][N:11]2[C:12]3[C:7](=[C:6]([OH:35])[C:5]([C:3]([NH:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:4])=[N:14][C:13]=3[C:15]3[CH:16]=[CH:17][N:18]=[CH:19][CH:20]=3)[CH:8]=[C:9]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:10]2=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

참가 물질

5

반응물 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 1363772511-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

생성물 1

HCID 1359812653-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid수율 9.7%

시약·촉매·용매 1

HCID 516892Sodium Bicarbonate용매

실험 절차

A mixture of 1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (46 mg, 0.098 mmol), β-alanine (699 mg, 7.8 mmol) and NaOMe solution (11.8 mL, 5.9 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 crude product was purified by silica gel chromatography (5-100% 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 5 mg of the title compound. MS: (+) m/z 527.45 (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
  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 (5-100% 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-7cfed371c56a4a049d6ccef0512934a4
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09271970B2

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