反应详情

温度

100 °C

Under nitrogen, 7-bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (Ex 1.1, step 1) (120 mg, 0.212 mmol), pyridine-3-ylboronic acid (33.8 mg, 0.212 mmol), triethylamine (0.030 ml, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) in DMF (3 ml) were heated at 85° C. overnight. A further portion of cesium carbonate (24.34 mg, 0.075 mmol) and PdCl2(dppf).CH2Cl2 adduct (6.10 mg, 7.47 μmol) were added along with 3-(1,3,2-dioxaborinan-2-yl)pyridine (34.6 mg, 0.212 mmol) and heated continued at 85° C. for 26 hrs. A further portion of cesium carbonate (24.34 mg, 0.075 mmol) and PdCl2(dppf).CH2Cl2 adduct (6.10 mg, 7.47 μmol) and 3-(1,3,2-dioxaborinan-2-yl)pyridine (34.6 mg, 0.212 mmol) were added. The reaction was heated at 100° C. for 2 hrs. The reaction mixture was diluted with EtOAc and water and the resulting product which precipitated out was collected by filtration. Further product was contained in the organic phase, which was washed with sat. NaHCO3, brine, dried (MgSO4) and concentrated in vacuo. The crude residue was combined with the precipitated product and purified by chromatography on silica eluting with 0-20% MeOH/DCM. The resulting solid was purified by preparative LC-MS eluting with 0.1% diethylamine 30-70% acetonitrile/water. The product fractions were partitioned between EtOAc and NaHCO3. The organic portion was separated, dried (MgSO4) and concentrated in vacuo to afford the title compound;

1. temperatureheated
2. customthe resulting product which precipitated out
3. filtrationwas collected by filtration
4. washwas washed with sat. NaHCO3, brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. custompurified by chromatography on silica eluting with 0-20% MeOH/DCM
8. customThe resulting solid was purified by preparative LC-MS
9. washeluting with 0.1% diethylamine 30-70% acetonitrile/water
10. customThe product fractions were partitioned between EtOAc and NaHCO3
11. customThe organic portion was separated
12. dry with materialdried (MgSO4)
13. concentrationconcentrated in vacuo