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

HRID 1410934Notes

Reaction equation

HRID 1410934 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][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]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][CH2:31][CH2:32][C:33]([OH:35])=[O:34].C[O-].[Na+]>>[CH:16]1([CH2:15][N:11]2[C:12]3[C:7](=[C:6]([OH:29])[C:5]([C:3]([NH:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:4])=[N:14][CH:13]=3)[CH:8]=[C:9]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:10]2=[O:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

4

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 682976181-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 601518223-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acidYield 62.5%

Procedure

A mixture of 1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (35 mg, 0.089 mmol), β-alanine (795 mg, 8.9 mmol) and NaOMe solution (13 mL, 6.7 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 with vigorous stirring until pH was about 2. The organic layer was dried over MgSO4 and concentrated. The crude product was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 25 mg of the title compound as a light yellow solid. MS: (+) m/z 450.30 (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
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe crude product was dissolved in saturated NaHCO3
  8. washwashed several times with ether
  9. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-9647dca607b24661b71939332f6a1397
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

Loading…