反应详情

温度

-78 °C

THF (8.5 mL) was cooled to −78° C. under a nitrogen atmosphere. tBuLi (1.7 mL, 2.9 mmol, 2.0 equiv) was added, followed by the addition of 2-bromo-5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine (370 mg, 1.47 mmol, 1.0 equiv dissolved in 2 mL THF) over 2 min. The reaction as stirred for 45 min at −78° C. Zinc chloride (510 mg, 3.75 mmol, 2.5 equiv dissolved in 5 mL of THF) was added and the reaction was allowed to warm to rt and stirred for 3 h. (t-Bu3P)2Pd (41 mg, 0.015 mmol, 0.10 equiv dissolved in 5 mL of THF) and t-butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (393 mg, 0.1 mmol, 0.07 equiv dissolved in 5 mL of THF) were added and the reaction was refluxed for 4 h followed by dilution with sodium bicarbonate (20 mL), and extraction with ethyl acetate (40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (35% EtOAc/hexanes) to give 245 mg (46%) of tert-butyl 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate.

1. customThe reaction
2. temperatureto warm to rt
3. additionwere added
4. temperaturethe reaction was refluxed for 4 h
5. extractionfollowed by dilution with sodium bicarbonate (20 mL), and extraction with ethyl acetate (40 mL)
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a crude solid that
10. customwas purified by silica gel column chromatography (35% EtOAc/hexanes)