反应详情

A solution of 2-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (26 mg, 0.05 mmol) in DMSO (0.5 mL) and 40 wt. % methylamine in water (0.5 mL) was heated in a microwave oven at 200° C. for 30 min. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (10 mL×2). The combined EtOAc extracts were concentrated under reduced pressure. The crude product 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 90% 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 Na2CO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 16 mg (63%) of the title compound as a yellow powder. HPLC/MS: retention time=3.28 min, [M+H]+=511.2.

1. extractionextracted with EtOAc (10 mL×2)
2. concentrationThe combined EtOAc extracts were concentrated under reduced pressure
3. customThe crude product was purified
4. washeluted with a linear gradient of 50% to 90% 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)
5. concentrationThe desired fractions were concentrated under reduced pressure
6. dissolutionThe residue was dissolved in EtOAc
7. washwashed with saturated aqueous Na2CO3 once
8. dry with materialwater twice, then saturated aqueous NaCl, dried over Na2SO4
9. customevaporated
10. dissolutionThe residue was dissolved in acetonitrile
11. temperaturefrozen