反应详情

A solution of 3-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-2-methyl-6-(trifluoromethyl)pyridine 1-oxide (60 mg, 0.12 mmol) in acetic anhydride (2 mL) in a sealed tube was stirred at 130° C. for 6 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was diluted with EtOAc, washed with saturated aqueous NaHCO3, water, then saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 45 mg of the crude product as a light brown foam. A portion of the product (15 mg) was purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 7.5 mg of the title compound as a yellow powder. HPLC/MS: retention time=2.90 min, [M+H]+=554.1.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. additionThe residue was diluted with EtOAc
3. washwashed with saturated aqueous NaHCO3, water
4. dry with materialsaturated aqueous NaCl, dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto afford 45 mg of the crude product as a light brown foam
8. customA portion of the product (15 mg) was purified
9. washeluted with a linear gradient of 50% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm)
10. concentrationThe desired fractions were concentrated under reduced pressure
11. dissolutionThe residue was dissolved in EtOAc
12. washwashed with saturated aqueous NaHCO3 once
13. dry with materialwater twice, then saturated aqueous NaCl, dried over Na2SO4
14. customevaporated
15. dissolutionThe residue was dissolved in acetonitrile
16. temperaturefrozen