D-Phenylalanine → HCID 68297757, compound

HRID 919919Notes

Reaction equation

HRID 919919 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].[NH2:30][C@@H:31]([C:39]([OH:41])=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C[O-].[Na+]>COCCO.C([O-])(O)=O.[Na+]>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:29])[C:5]([C:3]([NH:30][C@H:31]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:39]([OH:41])=[O:40])=[O:4])=[N:14][CH:13]=2)[CH:8]=[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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 71567D-PhenylalanineHCID 10942334Sodium MethoxideHCID 682973581-Benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297757HCID 68297757, compoundYield 43.3%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.16 mmol), D-phenylalanine (514 mg, 3.1 mmol), and NaOMe (126 mg, 2.3 mmol) in 2-methoxyethanol (10 mL) was refluxed for 2 h. After the mixture was cooled to r.t., solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3. The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (0-60% 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 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 36 mg of the title compound as a dull yellow solid. MS: (+) m/z 520.27 (M+1).

Workup

  1. temperaturewas refluxed for 2 h
  2. customsolvent was evaporated in vacuo
  3. customThe residue was partitioned between EtOAc and water
  4. addition1 M HCl was added
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (0-60% EtOAc/hexanes+1% AcOH)
  8. customThe product isolated
  9. washwashed several times with ether
  10. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-7485cd7916354bb89a0f6aad1dff5dcb
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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