1,4-Dioxane → N-[5-{4-[5-({[2-Hydroxy-3-(4-morpholinyl)propyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-2-(methyloxy)-3-pyridinyl]methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

1-[({5-[6-Bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]-3-(4-morpholinyl)-2-propanol (100 mg, 0.346 mmol), N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (81 mg, 0.247 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (25.35 mg, 0.0345 mmol) and potassium phosphate tribasic (110.5 mg, 0.5195 mmol) were added to a mixture of 1,4-dioxane (2.5 ml) and water (0.25 ml). The reaction mixture was heated under microwave irradiation at 80° C. for 30 mins and then 100° C. for 10 mins. The mixture was then 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 by 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) and stirred at room temperature for 1 h. The mixture was neutralised with addition of 2M HCl, dissolved in DMSO, filtered through a filter tube and purified by high pH MDAP (Method E). The appropriate fractions and waste were evaporated to dryness in vacuo. The residue was dissolved in 1:1 DMSO/water and purified by preparative HPLC using the following method:

Provenance & Evidence