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

HRID 919950Notes

Reaction equation

HRID 919950 reaction equation
C[O:2][C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[N:19][CH:18]=[CH:17][N:16]=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]=[CH:31][CH:30]=1)=[CH:8]2)=O.[NH2:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40].C[O-].[Na+]>>[CH2:21]([N:11]1[C:12]2[C:7](=[C:6]([OH:35])[C:5]([C:3]([NH:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:2])=[N:14][C:13]=2[C:15]2[CH:20]=[N:19][CH:18]=[CH:17][N:16]=2)[CH:8]=[C:9]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:10]1=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 1363772421-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyrazin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 1359812443-[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyrazin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acidYield 73.6%

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyrazin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (40 mg, 0.086 mmol), β-alanine (768 mg, 8.62 mmol) and NaOMe solution (13 mL, 6.47 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 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 4, and the resulting precipitate was isolated by filtration to give 33 mg of the title compound as a light yellow solid. MS: (+) m/z 522.29 (M+1).

Workup

  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

Sources & evidence

ORD record
ord-13a004858d9343dfabb65b7d163d7fb8
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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