Triethylamine → 5-(3-(Cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of N-cyclopropyl-7-iodo-6-methylbenzo[d]isoxazol-3-amine (0.100 g, 0.32 mmol), triethylamine (0.17 ml, 1.25 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.95 ml of 1.0 M in THF solution, 0.95 mmol), 2-(dicyclohexylphosphino)-2′-methylbiphenyl (0.023 g, 0.065 mmol) and palladium acetate (0.0036 g, 0.016 mmol) in 2.0 mL of dioxane in a sealed glass tube was heated in a microwave at 100° C. for 20 min. After cooling to RT, the reaction mixture was transferred to a 50 mL round-bottom flask and treated with 5-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one (0.089 g, 0.26 mmol) and sodium carbonate (1.0 mL of 2.0 M aqueous solution). Tetakis(triphenylphosphine)palladium (0) (9 mg) was added, and the reaction mixture was heated at 110° C. in an oil bath for 5 h. It was cooled to RT, treated with 5 mL of 1 N NaOH and 60 mL of EtOAc. The organic phase was separated, washed with brine, separated from the aqueous layer, then dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on SiO2(EtOAc/hexane=80/20) to give the title compound as a yellow crystalline solid. MS (ESI, pos.ion) m/z: 448.1 (M+1).

Provenance & Evidence