反应详情

To a mixture of 1-cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (60 mg, 0.16 mmol) and 3-amino-3-methyl-butyric acid (92 mg, 0.79 mmol) in DMF (1.5 mL) was added NaOMe solid (34 mg, 0.63 mmol). The resultant mixture was stirred in a 150-160° C. oil bath for 4 h. Reaction mixture was diluted with water (60 mL) and basified by 1 N NaOH to pH=10. It was extracted with EtOAc (30 mL), which was discarded. Aqueous layer was acidified by 1 N HCl to pH=3-4. Precipitate was collected and dried. Crude product was then triturated with MeOH (4 mL). Solid was collected and dried in vacuo to provide the title compound 24 mg (0.057 mmol) in 35% yield. LC-MS ESI−: 422.07 (M−1)−.

1. customReaction mixture
2. extractionIt was extracted with EtOAc (30 mL), which
3. customPrecipitate was collected
4. customdried
5. customCrude product was then triturated with MeOH (4 mL)
6. customSolid was collected
7. customdried in vacuo