反应详情

温度

100 °C

6-Bromo-4-{5-[(2-ethyl-4-morpholinyl)methyl}-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole (170 mg, 0.319 mmol), N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (115 mg, 0.351 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (46.7 mg, 0.064 mmol) and potassium phosphate tribasic (203 mg, 0.958 mmol) were added to a microwave vial and dissolved in 1,4-dioxane (5 ml) and water (0.5 ml). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The protected compound was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 4 h. The mixture was evaporated to dryness under a stream of nitrogen. The residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml) and separated with a hydrophilic frit. The solvent was removed under a stream of nitrogen and the crude residue was dissolved in DMSO (2 ml) and purified by Mass Directed Automated Preparative HPLC. The appropriate fraction was blown down under a stream of nitrogen to give a yellow solid. The solid was purified further by high pH MDAP (Method E) and the appropriate fraction was blown down under a stream of nitrogen to give the title compound as a white solid (12 mg).

1. customThe solvent was removed under a stream of nitrogen
2. customthe residue was partitioned between DCM (10 ml) and water (10 ml)
3. customseparated with a hydrophobic frit
4. customthe solvent again removed under a stream of nitrogen
5. dissolutionThe protected compound was dissolved in 1,4-dioxane (1 ml)
6. customThe mixture was evaporated to dryness under a stream of nitrogen
7. customThe residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
8. customseparated with a hydrophilic frit
9. customThe solvent was removed under a stream of nitrogen
10. dissolutionthe crude residue was dissolved in DMSO (2 ml)
11. custompurified by Mass Directed Automated Preparative HPLC
12. customto give a yellow solid
13. customThe solid was purified further by high pH MDAP (Method E)