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

HRID 919804Notes

Reaction equation

HRID 919804 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].OC(C(F)(F)F)=O.[NH2:38][CH2:39][C:40]([CH3:45])([CH3:44])[C:41]([OH:43])=[O:42].C[O-].[Na+]>CCO>[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:38][CH2:39][C:40]([CH3:45])([CH3:44])[C:41]([OH:43])=[O:42])=[O:4])=[C:14]([OH:15])[C:13]=2[CH:12]=[CH:11]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 682973507-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl esterHCID 1317322153-Amino-2,2-dimethyl-propionic acid TFA salt

Product 1

HCID 682973153-{[7-Benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-2,2-dimethyl-propionic acidYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
140 °C

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 (17 mg, 0.042 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (39 mg, 0.17 mmol), and NaOMe (18 mg, 0.34 mmol) in EtOH (2 mL) was heated at 140° C. for 6 h in a microwave reactor. 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 2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (0-40% EtOAc/CH2Cl2+1% AcOH). The product was then 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 7 mg of the title compound. MS: (+) m/z 491.37 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  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 product was purified by silica gel chromatography (0-40% EtOAc/CH2Cl2+1% AcOH)
  8. dissolutionThe product was then dissolved in saturated NaHCO3
  9. washwashed several times with ether
  10. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-0acd76b6cf794625a4569cce9817e650
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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