反应详情

DIAD (0.102 mL, 0.52 mmol) was added to 1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol (obtained as described in Example 310, preparation of starting materials) (135 mg, 0.47 mmol), 6-methylpyridazin-3(2H)-one (56.9 mg, 0.52 mmol) and triphenylphosphine (136 mg, 0.52 mmol) in THF (5 mL). The resulting solution was stirred at ambient temperature for 3 days. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 2M ammonia in methanol and evaporated to give crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-[4-[(6-methylpyridazin-3-yl)oxy]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (22.00 mg, 12%) as a solid.

1. customThe crude product was purified by ion exchange chromatography
2. washThe desired product was eluted from the column
3. customevaporated
4. customto give crude product
5. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
6. additionFractions containing the desired compound
7. customwere evaporated to dryness