Glycine → {[7-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-acetic acid

HRID 919739Notes

Reaction equation

HRID 919739 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=2)[C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4].[NH2:31][CH2:32][C:33]([OH:35])=[O:34].C[O-].[Na+]>>[CH2:16]([N:10]1[C:9](=[O:23])[C:8]2[C:7]([C:24]3[CH:25]=[N:26][CH:27]=[C:28]([F:30])[CH:29]=3)=[N:6][C:5]([C:3]([NH:31][CH2:32][C:33]([OH:35])=[O:34])=[O:4])=[C:14]([OH:15])[C:13]=2[CH:12]=[CH:11]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 3

HCID 750GlycineHCID 10942334Sodium MethoxideHCID 682973507-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester

Product 1

HCID 68297428{[7-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-acetic acidYield 57.3%

Procedure

A mixture of 7-benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (30 mg, 0.074 mmol), glycine (740 mg, 9.9 mmol) and NaOMe solution (15 mL, 7.4 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 water and EtOAc. 1 M HCl was added with vigorous stirring until pH was about 3-4. The organic layer was dried over MgSO4 and concentrated. The crude was chromatographed (20-100% EtOAc/hexanes+2% AcOH) to give 19 mg of the title compound as a white solid. MS: (+) m/z 448.95 (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. customThe crude was chromatographed (20-100% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-773ae15ce0cb40798eea93efa8bdde76
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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