Sodium Methoxide → 3-[(7-Benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-2,2-dimethyl-propionic acid

HRID 919745Notes

Reaction equation

HRID 919745 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:24]#[N:25])[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.[NH2:33][CH2:34][C:35]([CH3:40])([CH3:39])[C:36]([OH:38])=[O:37].C[O-].[Na+]>CCO.C([O-])(O)=O.[Na+]>[CH2:16]([N:10]1[C:9](=[O:23])[C:8]2[C:7]([C:24]#[N:25])=[N:6][C:5]([C:3]([NH:33][CH2:34][C:35]([CH3:40])([CH3:39])[C:36]([OH:38])=[O:37])=[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 682976087-Benzyl-1-cyano-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 601527713-[(7-Benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-2,2-dimethyl-propionic acidYield 63.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (30 mg, 0.090 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (83 mg, 0.36 mmol) and NaOMe (39 mg, 0.72 mmol) in 2 mL of EtOH was heated at 150° C. for 3 h in a CEM microwave reactor. The solvent was evaporated in vacuo, and the residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The residue was chromatographed (5-40% EtOAc/hexanes+2% AcOH) to give a crude solid. The solid was dissolved in saturated NaHCO3 and washed with ether. 1 M HCl was added to the aqueous layer until pH was about 2, and the resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 24 mg of the title compound. MS: (+) m/z 421.02 (M+1).

Workup

  1. customThe solvent 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 residue was chromatographed (5-40% EtOAc/hexanes+2% AcOH)
  7. customto give a crude solid
  8. washwashed with ether
  9. addition1 M HCl was added to the aqueous layer until pH was about 2
  10. extractionthe resulting suspension was extracted with EtOAc
  11. dry with materialThe organic layer was dried over MgSO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-053de336de914c408f1b38e57d0181f6
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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