反应详情

温度

80 °C

To a 100 mL round-bottomed flask were added 6-tert-butyl-2-[3-chloro-2-(hydroxymethyl)phenyl]-8-fluorophthalazin-1(2H)-one (671 mg, 1.86 mmol, prepared according to US2010/0222325), sodium cyanide (365 mg, 7.44 mmol) and DMSO (10 mL) to give a light yellow suspension. The mixture was stirred at 80° C. for 16 hrs. Additional sodium cyanide (182 mg, 3.72 mmol) was added and the mixture was further stirred at 80° C. for 60 hrs. The mixture was cooled to room temperature and extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane) to give 7-tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile as a yellow solid (390 mg, 57% yield).

1. customprepared
2. customto give a light yellow suspension
3. stirringthe mixture was further stirred at 80° C. for 60 hrs
4. temperatureThe mixture was cooled to room temperature
5. extractionextracted with ethyl acetate and water
6. washThe organic layer was washed with water and brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. customSolvents were evaporated
10. customthe residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane)