Beta-Alanine → HCID 135981278, compound

HRID 920103Notes

Reaction equation

HRID 920103 reaction equation
CO[C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[N:14]=1)[N:11]([CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:10](=[O:27])[C:9]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[CH:8]2)=[O:4].[NH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:25]([CH:22]([CH2:23][CH3:24])[CH2:21][N:11]1[C:12]2[C:7](=[C:6]([OH:34])[C:5]([C:3]([NH:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[O:4])=[N:14][C:13]=2[C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:8]=[C:9]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:10]1=[O:27])[CH3:26]

Participants

5

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 136377254HCID 136377254, compound

Product 1

HCID 135981278HCID 135981278, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.066 mmol), β-alanine (585 mg, 6.6 mmol) and NaOMe solution (10 mL, 4.9 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 partitioned between EtOAc and water. 1 M HCl was added until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (5-90% 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 3, and the resulting precipitate was isolated by filtration to give 14 mg of the title compound as an off-white solid. MS: (+) m/z 515.36 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned between EtOAc and water
  4. addition1 M HCl was added until pH was about 3-4
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (5-90% EtOAc/hexanes+1% AcOH)
  9. customThe product isolated
  10. washwashed several times with ether
  11. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-685b51c8d97342fba936e78967ea6080
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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