Sodium Methoxide → 3-{[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-methyl}-benzoic acid

HRID 920104Notes

Reaction equation

HRID 920104 reaction equation
CO[C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].Cl.[NH2:31][CH2:32][C:33]1[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=1)[C:36]([OH:38])=[O:37].C[O-].[Na+]>CCO.C([O-])(O)=O.[Na+]>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:29])[C:5]([C:3]([NH:31][CH2:32][C:33]3[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=3)[C:36]([OH:38])=[O:37])=[O:4])=[N:14][CH:13]=2)[CH:8]=[C:9]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:10]1=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 162187723-(Aminomethyl)benzoic acid hydrochlorideHCID 682973581-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 601526333-{[(1-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-methyl}-benzoic acidYield 17.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (63 mg, 0.16 mmol), 3-aminomethyl-benzoic acid HCl salt (306 mg, 1.6 mmol) and NaOMe (167 mg, 3.1 mmol) in EtOH (6 mL) was heated at 150° C. in a microwave reactor for 6 h. The solvent was evaporated, and the residue was partitioned between EtOAc and water. 1 M HCl was added until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The residue was dissolved in a 1:1 mixture of THF and MeOH (6 mL). 2 M NaOH (3 mL) was added, and the mixture was stirred at r.t. for 16 h. The mixture was concentrated to approximately one-third of its original volume, and 1 M HCl was added until pH was about 2. The resulting mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2, and the resulting precipitate was isolated by filtration to give 14 mg of the title compound as a yellow solid. MS: (+) m/z 506.29 (M+1).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between EtOAc and water
  3. addition1 M HCl was added until pH was about 2
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in a 1:1 mixture of THF and MeOH (6 mL)
  7. addition2 M NaOH (3 mL) was added
  8. concentrationThe mixture was concentrated to approximately one-third of its original volume, and 1 M HCl
  9. additionwas added until pH was about 2
  10. extractionThe resulting mixture was extracted with EtOAc
  11. dry with materialThe organic layer was dried over MgSO4
  12. concentrationconcentrated
  13. customThe crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH)
  14. customThe product isolated
  15. washwashed several times with ether
  16. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-001c5f79590c43c1a568d3aeabce15f0
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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