反应详情

[(R)-5-(5-Amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (35 g, 97.4 mmol), 5-cyano-pyridine-2-carboxylic acid (15.87 g, 107.14 mmol) and HOBt hydrate (22.35 g, 146.1 mmol) were dissolved in 185 ml DMF and stirred with ice cooling. When the temperature had reached 0-5° C. EDC (22.33 ml, 126.62 mmol) was added dropwise. The mixture was stirred for 2 h. The ice bath was taken away and stirring was continued for 2 h. The mixture was taken up in EtOAc and water. The phases were separated and the organic phase was washed with 5% aqueous NaHCO3 and brine. The organic phase was dried with MgSO4.H2O and evaporated to provide a beige solid. Crystallisation from EtOAc/hexane gave the title compound as colorless crystals. Yield 44.47 g.

1. customhad reached 0-5° C
2. stirringThe mixture was stirred for 2 h
3. stirringstirring
4. customThe phases were separated
5. washthe organic phase was washed with 5% aqueous NaHCO3 and brine
6. dry with materialThe organic phase was dried with MgSO4.H2O
7. customevaporated
8. customto provide a beige solid
9. customCrystallisation from EtOAc/hexane