Glycine → [(6-Benzyl-1-cyano-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carbonyl)-amino]-acetic acid

HRID 919759Notes

Reaction equation

HRID 919759 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:24]#[N:25])[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].[NH2:26][CH2:27][C:28]([OH:30])=[O:29].C[O-].[Na+]>>[CH2:17]([N:11]1[CH:10]=[CH:9][C:8]2[C:7]([C:24]#[N:25])=[N:6][C:5]([C:3]([NH:26][CH2:27][C:28]([OH:30])=[O:29])=[O:4])=[C:14]([OH:15])[C:13]=2[C:12]1=[O:16])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 3

HCID 750GlycineHCID 10942334Sodium MethoxideHCID 682976046-Benzyl-1-cyano-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carboxylic acid methyl ester

Product 1

HCID 68297418[(6-Benzyl-1-cyano-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carbonyl)-amino]-acetic acidYield 107.7%

Procedure

A mixture of 6-benzyl-1-cyano-4-hydroxy-5-oxo-5,6-dihydro-[2,6]naphthyridine-3-carboxylic acid methyl ester (27 mg, 0.081 mmol), glycine (805 mg, 10.7 mmol), and NaOMe solution (16 mL, 8.06 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., 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 1. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was dried over MgSO4 and concentrated. The crude residue was dissolved in saturated NaHCO3 and washed with ether. The aqueous layer was acidified to pH about 1 with 4 M HCl and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 33 mg of the title compound. MS: (+) m/z 379.00 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customsolvent 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 materialthe combined organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe crude residue was dissolved in saturated NaHCO3
  9. washwashed with ether
  10. extractionextracted with EtOAc
  11. dry with materialThe organic layer was dried over MgSO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-dfb30d5b281b47b38dc8170f75e79d2e
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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