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

Reaction equation

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

Participants

Reactant 3

HCID 239Beta-Alanine

HCID 10942334Sodium Methoxide

HCID 682972811-Benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 601516833-{[1-Benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acidYield 75%

Procedure

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (55 mg, 0.12 mmol), β-alanine (863 mg, 9.7 mmol) and NaOMe solution (14.5 mL, 7.3 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 3. The organic layer was washed with brine, dried over MgSO4, and concentrated. The crude solid 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 46 mg of the title compound. MS: (+) m/z 512.27 (M+1).