Diisopropylethylamine → 3-(3-fluoro-4-nitro-phenylsulfanyl)-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine

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Reaction Conditions

Reaction Steps

A solution of trifluoro-methanesulfonic acid 3-fluoro-4-nitro-phenyl ester (1.51 g, 4.74 mmol), diisopropylethylamine (1.5 mL, 8.62 mmol) in DMF (14 mL) under nitrogen was degassed by bubbling in nitrogen for 10 min. Tris(dibenzylideneacetone)dipalladium (99 mg, 0.108 mmol, Strem catalyst) and Xantphos (125 mg, 0.215 mmol) were added together in one portion, followed by 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (1.0 g, 4.31 mmol). The reaction mixture was stirred at 100° C. for 3 h, then it was concentrated in vacuo. The residue was partitioned between saturated aqueous ammonium chloride and 10% methanol in dichloromethane. The aqueous layer was extracted with 10% methanol in dichloromethane, and the combined organic layers were directly adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-10% methanol/dichloromethane afforded 387 mg of 3-(3-fluoro-4-nitro-phenylsulfanyl)-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine as a yellow solid (24% yield): 1H NMR (DMSO-d6) δ 3.90 (s, 3H), 7.20 (dd, 1H), 7.59 (dd, 1H), 7.87 (d, 1H), 8.06 (m, 2H), 8.46 (s, 1H), 8.54 (d, 1H); MS (m/z) 372 [M+H]+.

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