反应详情

温度

24 °C

To t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-formylpyridazin-3-yl)carbamate (1.4 g, 3.6 mmol) in ethanol (10 mL) and water (2 mL) was added hydroxylamine hydrochloride (0.27 g, 3.8 mmol) followed by sodium acetate (0.32 g, 3.8 mmol) and stirred at 24° C. for 30 min. The crude reaction mixture was concentrated and diluted with EtOAc. The organic layer was washed with satd. aq. NaHCO3 and brine, then dried over sodium sulfate, filtered, and concentrated. The crude mixture was then diluted in THF (2 mL) and pyridine (57 mg, 0.72 mmol) then treated with NCS (0.58 g, 4.35 mmol) and heated to 40° C. for 1.5 h. The crude mixture was then treated with methyl propiolate (0.30 g, 3.56 mmol) and TEA (0.36, 3.56 mmol), and the reaction was stirred for 45 min. The reaction mixture was concentrated and diluted with EtOAc, and then washed with satd. aq. NaHCO3 and brine. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by reverse phase chromatography to give a white solid (0.53 g, 31%).

1. customThe crude reaction mixture
2. concentrationwas concentrated
3. additiondiluted with EtOAc
4. washThe organic layer was washed with satd
5. dry with materialaq. NaHCO3 and brine, then dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. additionThe crude mixture was then diluted in THF (2 mL)
9. temperatureheated to 40° C. for 1.5 h
10. stirringthe reaction was stirred for 45 min
11. concentrationThe reaction mixture was concentrated
12. additiondiluted with EtOAc
13. washwashed with satd
14. dry with materialThe organic layer was dried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. custompurified by reverse phase chromatography