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

HRID 919976Notes

Reaction equation

HRID 919976 reaction equation
CO[C:3]([C:5]1[C:6]([OH:37])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([O:21][CH3:22])[CH:20]=3)[N:14]=1)[N:11]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:10](=[O:30])[C:9]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[CH:8]2)=[O:4].[NH2:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42].C[O-].[Na+]>>[CH2:23]([N:11]1[C:12]2[C:7](=[C:6]([OH:37])[C:5]([C:3]([NH:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[O:4])=[N:14][C:13]=2[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([O:21][CH3:22])[CH:20]=2)[CH:8]=[C:9]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:10]1=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 682976601-Benzyl-5-hydroxy-8-(5-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682973363-{[1-Benzyl-5-hydroxy-8-(5-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]amino}-propionic acidYield 69.9%

Procedure

A mixture of 1-benzyl-5-hydroxy-8-(5-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (45 mg, 0.091 mmol), β-alanine (651 mg, 7.30 mmol) and NaOMe solution (11 mL, 5.48 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 organic layer was 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 3-4 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 35 mg of the title compound as a light tan solid. MS: (+) m/z 551.32 (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. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in saturated NaHCO3
  8. washwashed several times with ether
  9. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-13ae4f061120453b8569bf23074112bd
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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