反应详情

A mixture comprising 7-bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzyl carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (step 1) (120 mg, 0.212 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) in DMF (5 ml) under N2 was heated at 85° C. for 2 hrs. After cooling to RT, the reaction mixture was partitioned between with EtOAc and water. A precipitate formed which was removed by filtration and discarded. The organic portion was separated and washed with NaHCO3, water, dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica eluting with 0-20% MeOH/DCM and the product fractions were combined and concentrated in vacuo. The product was dissolved in MeOH and passed through a 1 g 2,4,6-trimercaptotriazine silica column under gravity. The column was washed with MeOH and the combined eluents were concentrated in vacuo. The product was triturated with THF (1% MeOH) followed by ether to afford the title compound;

1. customthe reaction mixture was partitioned between with EtOAc and water
2. customA precipitate formed which
3. customwas removed by filtration
4. customThe organic portion was separated
5. washwashed with NaHCO3, water
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by chromatography on silica eluting with 0-20% MeOH/DCM
9. concentrationconcentrated in vacuo
10. dissolutionThe product was dissolved in MeOH
11. washThe column was washed with MeOH
12. concentrationthe combined eluents were concentrated in vacuo
13. customThe product was triturated with THF (1% MeOH)