反应详情

DIAD (20.73 mL, 105.27 mmol) was added dropwise to 4-[4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]phenol (32.0 g, 87.72 mmol), 2-(1-methyl-1H-pyrazol-5-yl)ethanol (prepared as described in Example 513, preparation of starting materials) (16.6 g, 131.58 mmol) and triphenylphosphine (34.5 g, 131.58 mmol) in THF (320 mL) at 0° C. under nitrogen. The resulting solution was stirred at ambient temperature for 3 days. The reaction mixture was evaporated to dryness and re-dissolved in DCM (700 mL), and the solution was washed sequentially with 2M NaOH (200 mL×2) and saturated brine (200 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, eluting with a gradient of 80 to 100% EtOAc in isohexane followed by EtOAc, then a gradient of 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford 6-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (28.7 g, 69.3%) as a solid.

1. customThe reaction mixture was evaporated to dryness
2. dissolutionre-dissolved in DCM (700 mL)
3. washthe solution was washed sequentially with 2M NaOH (200 mL×2) and saturated brine (200 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customto afford crude product
8. customThe crude product was purified by flash silica chromatography
9. washeluting with a gradient of 80 to 100% EtOAc in isohexane
10. customPure fractions were evaporated to dryness