1,2-Diiodoethane → 6-Chloro-3-(2-fluorophenyl)-7-iodo-1,2,4-triazolo[4,3-b]pyridazine

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A solution of 6-chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-1,2,4-triazolo[4,3-b]pyridazine (5.0 g, 15.6 mmol), prepared as in Example 25 Step c), and 1,2-diiodoethane (14 g, 50 mmol) in anhydrous THF (150 ml) was added via cannula to a stirred suspension of tris(dimethylamino)-sulfur (trimethylsilyl)difluoride (5.0 g, 18 mmol) in anhydrous THF (200 ml) at room temperature under nitrogen. After 18 h, the mixture was diluted with dichloromethane (400 ml) and washed sequentially with water (300 ml) and brine (200 ml). The organic layer was dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 3% methanol-dichloromethane, gave crude 6-chloro-3-(2-fluorophenyl)-7-iodo-1,2,4-triazolo[4,3-b]pyridazine (3.54 g) as a dark brown solid. This was subjected to the conditions described in Example 27 Step b) to give 3-(2-fluorophenyl)-7-iodo-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (1.32 g, 19% over two steps) as a yellow solid; 1H NMR (360 MHz, CDCl3) δ3.97 (3H, s), 5.51 (2H, s), 7.28 (1H, dd, J=8 and 8 Hz), 7.37 (1H, dd, J=8 and 8 Hz), 7.56-7.64 (1H, m), 7.86 (1H, ddd, J=7, 7 and 1 Hz), 7.90 (1H, s), 8.68 (1H, s); MS (ES+) m/e 452 [MH]+.

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