Synthesis and Characterization of Triazole-Pyridazine Derivatives

Example 1

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To a solution of 6-chloro-4-((2-methoxy-3-(2-ethyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (101 mg, 0.26 mmol), cyclopropanecarboxamide (110 mg, 1.29 mmol) in dioxane (2.5 mL) and the reaction mixture was purged under N₂ for 5 mins. To this solution was added xantphos (30 mg, 0.052 mmol), Pd₂dba₃ (24 mg, 0.026 mmol) and cesium carbonate (337 mg, 1.03 mmol) and the mixture was stirred at 130° C. for 45 minutes. After cooling to room temperature, the reaction mixture was purified using a 12 gm isco silica gel cartridge, eluted with a 0-10% MeOH/DCM gradient. The pure fractions were concentrated to afford 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(2-ethyl-2H-1,2,3-triazol-4-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (79 mg, 66%) as an off white solid. MS (M+1) m/z: 440.2 [M+H]⁺, LC retention time 1.53 min [I]. ¹H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 11.01 (s, 1H), 9.16 (s, 1H), 8.14 (d, J=7.9 Hz, 2H), 7.72 (dd, J=7.9, 1.5 Hz, 1H), 7.47 (dd, J=8.0, 1.5 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 4.52 (q, J=7.3 Hz, 2H), 3.66 (s, 3H), 2.13-2.05 (m, 1H), 1.52 (t, J=7.3 Hz, 3H), 0.87-0.78 (m, 4H).

The following examples 2-8 were prepared in a similar manner to the preparation of Example 1.