1357072-61-7

c-Met inhibitor 1 is an inhibitor of the c-Met receptor signaling pathway useful for the treatment of cancer including gastric, glioblastoma, and pancreatic cancer. IC50 value: Target: c-Met More details please refer to Patent WO 2012015677 A1.

Example 1A: Synthesis of 6-(1-methyl-1H-pyrazol-4-yl)-3-((2-methyl-2H-indazol-5-yl)thio)-[1,2,4]triazolo[4,3-b]pyridazine Under nitrogen protection, 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (50 g, 268 mmol) was dissolved in DMF (750 mL), and 5-iodo-2-methyl-2H-indazole (55.5 g, 215.1 mmol), 2-pyridine carboxylic acid (5.5 g, 44.7 mmol), copper(I) iodide (4 g, 21.0 mmol) and cesium carbonate (212.5 g, 652.2 mmol). The reaction mixture was stirred at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, poured into water (2000 mL) and stirred at room temperature for 30 min. The mixture was extracted with mixed solvents (CHCl3/IPA = 3/1, 2L x 2). The organic layers were combined and washed sequentially with mixed solution (25% NH4OH(aq)/brine = 1/4, 800mL), saturated LiCl(aq) (1L) and saturated brine (1.5L × 2). The organic layer was dried with Na2SO4 and concentrated under reduced pressure to give a brown crude solid product. The crude product was ground with ethyl acetate (800 mL) at room temperature for 3 h. The pure product was collected by filtration to afford 6-(1-methyl-1H-pyrazol-4-yl)-3-((2-methyl-2H-indazol-5-yl)thio)-[1,2,4]triazolo[4,3-b]pyridazine (68 g, 87.2% yield) as a white solid.MS (m/z): 363.0 ( M + H).

[1] PCT Int. Appl. (2012), WO 2012015677 A1 20120202.