Reaktion #422453
ord-9575426c854f483cb02bd8db10d2c8b1
Reaktionsgleichung
Edukte
Reagenzien
Reaktionsbedingungen
Aufarbeitung
- 1Temperaturheated
- 2Sonstigethe resulting product which precipitated out
- 3Filtrationwas collected by filtration
- 4Waschenwas washed with sat. NaHCO3, brine
- 5Trocknendried (MgSO4)
- 6Einengenconcentrated in vacuo
- 7Sonstigepurified by chromatography on silica eluting with 0-20% MeOH/DCM
- 8SonstigeThe resulting solid was purified by preparative LC-MS
- 9Wascheneluting with 0.1% diethylamine 30-70% acetonitrile/water
- 10SonstigeThe product fractions were partitioned between EtOAc and NaHCO3
- 11SonstigeThe organic portion was separated
- 12Trocknendried (MgSO4)
- 13Einengenconcentrated in vacuo
Vorschrift
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;