1,2-Dichloroethane → 4-[(1-Cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid ethyl ester

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Reaction Steps

A mixture of 1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.15 mmol), 2 M NaOH (3 mL), MeOH (3 mL) and THF (3 mL) was stirred at r.t. overnight, then concentrated to approximately one-third of its original volume. 1 M HCl was added to acidify the mixture, and the resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. To the residue were then added HOBt (33 mg, 0.24 mmol), CH2Cl2 (3 mL), and EDC (53 mg, 0.28 mmol), and the resulting mixture was stirred for 10 min. 4-Amino-butyric acid ethyl ester HCl salt (41 mg, 0.24 mmol) and Hunig's base (0.1 mL, 0.56 mmol) were added, and the mixture was stirred for 48 h. The mixture was diluted with EtOAc and washed with 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-30% EtOAc/hexanes+1% AcOH) to give 39 mg of the title compound. MS: (+) m/z 492.44 (M+1).

Provenance & Evidence