反应详情

A mixture of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (45 mg, 0.097 mmol), 5-aminovaleric acid (740 mg, 6.32 mmol), and NaOMe solution (10 mL, 4.86 mmol) was refluxed for 16 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 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (5-80% 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 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 19 mg of the title compound. MS: (+) m/z 549.31 (M+1).

1. temperaturewas refluxed for 16 h
2. customsolvent was evaporated in vacuo
3. customThe residue was partitioned between EtOAc and water
4. addition1 M HCl was added
5. extractionThe aqueous layer was extracted with additional EtOAc
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by silica gel chromatography (5-80% EtOAc/hexanes+1% AcOH)
9. customThe product isolated
10. washwashed several times with ether
11. customthe resulting precipitate was isolated by filtration