Sodium Hydroxide → 9-({5-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane

Participants

Reaction Conditions

Reaction Steps

To a solution of 9-({5-[6-bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane (100 mg, 0.179 mmol) in 1,4 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 (56.6 mg, 0.233 mmol, available from Frontier Scientific Europe), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (26.2 mg, 0.036 mmol) and potassium phosphate tribasic (114 mg, 0.537 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 residue was dissolved in DMSO (2 ml) and purified by Mass Directed Automated Preparative HPLC. The appropriate fractions were blown down under a stream of nitrogen to give a yellow solid. The solid 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 and the residue was freeze dried from 1,4-dioxane/water (1:1, 2 ml) overnight to give the title compound as a cream solid (21 mg).

Provenance & Evidence