Beta-Alanine → 3-[(6-Benzyl-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carbonyl)-amino]-propionic acid

HRID 919756Notes

Reaction equation

HRID 919756 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][C:8]2[CH:9]=[CH:10][N:11]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12](=[O:16])[C:13]=2[C:14]=1[OH:15])=[O:4].[NH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28].C[O-].[Na+]>>[CH2:17]([N:11]1[CH:10]=[CH:9][C:8]2[CH:7]=[N:6][C:5]([C:3]([NH:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[O:4])=[C:14]([OH:15])[C:13]=2[C:12]1=[O:16])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

4

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 68297693Methyl 6-benzyl-4-hydroxy-5-oxo-5,6-dihydro-2,6-naphthyridine-3-carboxylate

Product 1

HCID 682975893-[(6-Benzyl-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carbonyl)-amino]-propionic acidYield 67.2%

Procedure

A mixture of 6-benzyl-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carboxylic acid methyl ester (25 mg, 0.081 mmol), β-alanine (956 mg, 10.7 mmol) and NaOMe solution (16 mL, 8.06 mmol, 0.5 M in MeOH) was refluxed for 16 h. Solvent was evaporated in vacuo, and the residue was partitioned between water and EtOAc. 1 M HCl was added with vigorous stirring until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The crude solid was dissolved in saturated NaHCO3 and washed with ether. The aqueous layer was acidified to pH about 2 with 4 M HCl, and then extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 20 mg of the title compound. MS: (+) m/z 368.00 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customSolvent was evaporated in vacuo
  3. customthe residue was partitioned between water and EtOAc
  4. addition1 M HCl was added
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe crude solid was dissolved in saturated NaHCO3
  8. washwashed with ether
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-f8a122bbd2224095ab64bcf28d15f167
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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