Beta-Alanine → 3-{[7-Cyclohexylmethyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]amino}-propionic acid

HRID 1411057Notes

Reaction equation

HRID 1411057 reaction equation
CO[C:3]([C:5]1[C:6]([OH:38])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][C:18]([O:21][CH2:22][CH3:23])=[N:19][CH:20]=3)[N:14]=1)[N:11](CC1CCCCC1)[C:10](=[O:31])[C:9]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[CH:8]2)=[O:4].[NH2:39][CH2:40][CH2:41][C:42]([OH:44])=[O:43].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH:32]1([CH2:9][N:14]2[C:13]([C:15]3[CH:20]=[N:19][C:18]([O:21][CH2:22][CH3:23])=[N:17][CH:16]=3)=[C:12]3[C:7](=[CH:8][CH:9]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:10](=[O:31])[NH:11]3)[C:6]([OH:38])=[C:5]2[C:3]([NH:39][CH2:40][CH2:41][C:42]([OH:44])=[O:43])=[O:4])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 682974421-Cyclohexylmethyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 867141783-{[7-Cyclohexylmethyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]amino}-propionic acidYield 76.9%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 1-cyclohexylmethyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (35 mg, 0.068 mmol), β-alanine (607 mg, 6.8 mmol) and NaOMe solution (11 mL, 5.4 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 crude product was purified by silica gel chromatography (5-40% 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 3-4, and the resulting precipitate was isolated by filtration to give 15 mg of the title compound. MS: (+) m/z 572.36 (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 crude product was purified by silica gel chromatography (5-40% 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-a4340347497c4047ad2284ecb378cd6b
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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