Sodium Methoxide → {2-[(7-Benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethoxy}-acetic acid

HRID 919802Notes

Reaction equation

HRID 919802 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][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].[NH2:24][CH2:25][CH2:26][O:27][CH2:28][C:29]([OH:31])=[O:30].C[O-].[Na+]>CO.C([O-])(O)=O.[Na+]>[CH2:16]([N:10]1[C:9](=[O:23])[C:8]2[CH:7]=[N:6][C:5]([C:3]([NH:24][CH2:25][CH2:26][O:27][CH2:28][C:29]([OH:31])=[O:30])=[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

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 111709562-(2-aminoethoxy)acetic AcidHCID 682977357-Benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester

Product 1

HCID 60151262{2-[(7-Benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethoxy}-acetic acidYield 32.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (20 mg, 0.065 mmol), (2-amino-ethoxy)-acetic acid (39 mg, 0.32 mmol), and NaOMe (14 mg, 0.26 mmol) in MeOH (2 mL) was heated at 140° C. in a microwave reactor for 6 h. Solvent was evaporated in vacuo, and the residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH about 1, and the organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (0-2% MeOH/EtOAc+1% AcOH) to give a yellow solid. The solid was then dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 1 with 4 M HCl, and the resulting precipitate was collected by filtration and dried to give 8.3 mg of the title compound as an off-white solid. MS: (+) m/z 398.29 (M+1).

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was partitioned between EtOAc and water
  3. addition1 M HCl was added
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (0-2% MeOH/EtOAc+1% AcOH)
  7. customto give a yellow solid
  8. washwashed several times with ether
  9. filtrationthe resulting precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-524ef5a78b724331820ebd749d4c86f1
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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