反应详情

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (40 mg, 0.125 mmol), (R)-3-amino-4-phenyl-butyric acid HCl salt (270 mg, 1.25 mmol) (PepTech Corporation), and NaOMe (101 mg, 1.88 mmol) in 2-methoxyethanol (10 mL) was refluxed for 1.5 h. The resulting mixture was concentrated in vacuo, and the residue was partitioned between EtOAc and water. Hydrochloric acid (1 M) was added with vigorous stirring until pH ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH). The compound isolated was then dissolved in MeOH (2 mL) and treated with 2 M NaOH (2 mL) for 2 h. Hydrochloric acid (1 M) was added to acidify the mixture, and the mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The residue was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH) to give 33 mg of the title compound. MS: (+) m/z 468.06 (M+1).

1. temperaturewas refluxed for 1.5 h
2. concentrationThe resulting mixture was concentrated in vacuo
3. customthe residue was partitioned between EtOAc and water
4. additionHydrochloric acid (1 M) was added
5. dry with materialThe organic layer was dried over MgSO4
6. concentrationconcentrated
7. customThe crude product was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH)
8. customThe compound isolated
9. extractionthe mixture was extracted with EtOAc
10. dry with materialThe organic layer was dried over MgSO4
11. concentrationconcentrated
12. customThe residue was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH)