反应详情

A solution of N′-(5-(2-chlorophenyl)-4-(4-chlorophenyl)pyridin-2-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetohydrazide (40 mg, 0.075 mmol) and acetic acid (0.25 mL) in ethanol (0.5 mL) was heated in a microwave oven at 180° C. for 45 min. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The obtained residue was taken into EtOAc, and the solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-70%) in hexanes to obtain the product with about 85% purity as an oil. The product was further purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 50% to 100% B, 10 min gradient, 100% B hold for 4 min, (A=90% H2O, 10% MeOH, 0.1% TFA and B=10% H2O, 90% MeOH, 0.1% TFA); Flow rate at 20 mL/min, UV detection at 220 nm) to yield the desired product, which was taken into EtOAc, washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The residue was lyophilized in acetonitrile to afford 9 mg (24% yield, 99% pure) of the title compound as a white powder. HPLC/MS (method A): retention time=3.88 min, [M+H]+=499.0.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. washthe solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified
7. washeluting with a gradient of EtOAc (0-70%) in hexanes
8. customto obtain the product with about 85% purity as an oil
9. customThe product was further purified
10. washEluted with 50% to 100% B, 10 min gradient, 100% B hold for 4 min