反应详情

Through a mixture of 4-(azetidine-1-carbonyl)-N-(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide (150 mg, 371 μmol) and pyridin-4-ylboronic acid (68.4 mg, 557 μmol) in dioxane (4 ml) and sat. sodium carbonate solution (1 ml) was bubbled nitrogen for 10 minutes, then 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride/dppf (15.2 mg, 18.6 μmol) was added and the resulting mixture was refluxed for 18 hours under nitrogen atmosphere. The solvent was evaporated and the residue was diluted with ethyl acetate and washed with water, the organic layer was separated, dried over magnesium sulfate, filtrated and evaporated. The crude material was applied on silicagel and purified by flash chromatography over a 20 g silicagel column using ethyl acetate/methanol 2-5% as eluent affording 4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide (28 mg, 18.8%) as a white solid. mp: >250° C., MS: m/z=403.0 (M+H+)

1. customwas bubbled nitrogen for 10 minutes
2. temperaturethe resulting mixture was refluxed for 18 hours under nitrogen atmosphere
3. customThe solvent was evaporated
4. additionthe residue was diluted with ethyl acetate
5. washwashed with water
6. customthe organic layer was separated
7. dry with materialdried over magnesium sulfate
8. filtrationfiltrated
9. customevaporated
10. custompurified by flash chromatography over a 20 g silicagel column