N,N'-Dimethylethylenediamine → 2-(ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile

Participants

Reaction Conditions

Reaction Steps

Compound (100b) (1.00 g), copper iodide (0.248 g), cesium carbonate (2.12 g), and 4-bromo-2-(ethylamino)benzonitrile (0.932 g) were suspended in 1,4-dioxane (10 mL), and N,N′-dimethylethylenediamine (0.560 mL) was added to the suspension, followed by stirring at 150° C. for 20 hr. The reaction solution was distributed between chloroform and water. The organic layer was washed with a 2 N aqueous sodium hydroxide solution and dried over magnesium sulfate, and then the solvent was distilled away. The residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain 2-(ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile (1.13 g, 77%) as a white solid. 2-(Ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile (0.700 g) was dissolved in DMSO (10 mL), and a 30% hydrogen peroxide solution (0.310 mL) and a 4 N aqueous sodium hydroxide solution (1.16 mL) were added to the resulting solution, followed by stirring at room temperature for 10 min. Water was added to the reaction solution, and the precipitate was collected by filtration and was dried under reduced pressure to obtain compound (109) (0.655 g, 90%) as a white solid.

Provenance & Evidence