反应详情

A microwave vessel was charged with 2-(4-iodo-pyrazol-1-yl)-2-methyl-propionic acid ethyl ester (50 mg, 0.162 mmol), bis(pinacolato)diboron (50 mg, 0.195 mmol), potassium acetate (48 mg, 0.486 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (6.6 mg, 0.008 mmol), and DMA (0.6 mL). The vessel was flushed with nitrogen and capped. The reaction mixture was microwaved at 130° C. for 30 min. 3-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (48 mg, 0.13 mmol) and dichlorobis(triphenylphosphine) palladium(0) (5.7 mg, 0.008 mmol) were added, followed by DMA (0.4 mL) and a 2 M aqueous solution of potassium carbonate (0.5 mL). The reaction mixture was microwaved at 130° C. for 1 h. Solid sodium sulfate was added to soak up the water, and the liquid layer was filtered through a 0.45 um filter. The crude mixture was diluted to 2 mL with DMSO and purified directly by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier) to provide 11 mg of 2-methyl-2-{4-[6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinolin-3-yl]-pyrazol-1-yl}-propionic acid as a cream-colored solid (19% yield).

1. customThe vessel was flushed with nitrogen
2. customcapped
3. customThe reaction mixture was microwaved at 130° C. for 30 min
4. customThe reaction mixture was microwaved at 130° C. for 1 h
5. filtrationthe liquid layer was filtered through a 0.45 um
6. filtrationfilter
7. additionThe crude mixture was diluted to 2 mL with DMSO
8. custompurified directly by mass-triggered HPLC (5-95% CH3CN/H2O, 0.1% HCOOH modifier)