Sodium Hydroxide → 4-{5-[(2,2-Dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-6-(1H-indol-4-yl)-1H-indazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-bromo-4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole (176 mg, 0.298 mmol) in dioxane (2.5 ml) and water (0.25 ml) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (102 mg, 0.420 mmol, available from Frontier Scientific Europe), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (43.5 mg, 0.060 mmol) and potassium phosphate tribasic (198 mg, 0.933 mmol). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The mixture was passed through a 1 g silica SPE cartridge, washing with MeOH. 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 crude residue was dissolved in DMSO (2 ml) and purified by Mass Directed Automated Preparative HPLC. The product-containing fractions were blown down under a stream of nitrogen to give a yellow solid. 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 3 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 to give a brown solid (31 mg) that was dissolved in DMSO (750 μL) and purified by Mass Directed Automated Preparative HPLC. The solvent was removed under a stream of nitrogen. The appropriate fraction was blown down under a stream of nitrogen to give the title compound as a pale yellow gum (2.4 mg).

Provenance & Evidence