Glycine → [(1,3-Dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid

HRID 1410706Notes

Reaction equation

HRID 1410706 reaction equation
CO[C:3]([C:5]1[C:6]([OH:36])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=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]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[CH:8]2)=[O:4].[NH2:37][CH2:38][C:39]([OH:41])=[O:40].C[O-].[Na+]>>[CH2:21]([N:11]1[C:12]2[C:7](=[C:6]([OH:36])[C:5]([C:3]([NH:37][CH2:38][C:39]([OH:41])=[O:40])=[O:4])=[N:14][C:13]=2[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=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 750GlycineHCID 10942334Sodium MethoxideHCID 867141081,3-Dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297451[(1,3-Dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acidYield 54.1%

Procedure

A mixture of 1,3-dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (34 mg, 0.071 mmol), glycine (2.85 g, 38 mmol) and NaOMe solution (57 mL, 29 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 dissolved in saturated NaHCO3 and washed with ether. The aqueous layer was acidified to pH about 3, and the resulting mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The residue was further purified by silica gel chromatography (0-80% EtOAc/hexanes+2% AcOH) to give 20 mg of the title compound MS: (+) m/z 521.17 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customthe solvent was evaporated in vacuo
  3. dissolutionThe residue was dissolved in saturated NaHCO3
  4. washwashed with ether
  5. extractionthe resulting mixture was extracted with EtOAc
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was further purified by silica gel chromatography (0-80% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-cc8571ba3f0742c89adbe665c6a8f316
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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