6-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine → N-(7-Cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-3-ylmethyl)amine Hydrochloride

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A mixture of 6-chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine (100 mg, 0.35 mmol) and N-methyl-N-(1-methyl-1H-1,2,4-triazol-3-ylmethyl)amine (150 mg, 1.2 mmol) in triethylamine (1 ml) and dry DMF (1 ml) was stirred and heated at 100° C. in a sealed tube for 16 hours. Upon cooling the volatiles were removed in vacuo, and the residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The aqueous was further extracted with dichloromethane (x2). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 2%→5% methanol-dichloromethane to give the free base as on oil. Treatment with a solution of hydrogen chloride in methanol gave the title compound (40 mg, 30%) as a pale yellow solid. 1H NMR (360 MHz, d6-DMSO) δ 1.86-1.92 (1H, m), 1.96-2.04 (1H, m), 2.20-2.32 (2H, m), 2.40-2.46 (2H, m), 2.97 (3H, s), 3.83 (3H, s), 4.42 (2H, s), 7.54-7.60 (3H, m), 8.26 (1H, s), 8.36 (2H, br d, J=8 Hz), 8.48 (1H, s); MS (ES+) m/e 374 [MH]+.

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