Sodium Bicarbonate → 6-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-3-nitropyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

200 mg (0.57 mmol) of the compound from example 33A were initially charged in dimethylformamide (5.3 ml) under argon, then 0.43 ml (0.85 mmol) of hexabutylditin and 160 mg (0.92 mmol) of 6-chloro-3-nitropyridin-2-amine were added, and the reaction mixture was purged with argon for 10 min. Subsequently, 231 mg (0.28 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (1:1) were added and the reaction mixture was stirred at 110° C. overnight. The mixture was then cooled to RT, saturated aqueous sodium hydrogencarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was extracted by stirring in dichloromethane/methanol (1:1), and the solids were filtered off and dried under high vacuum. This gave 95 mg (54% purity, 15% of theory) of the title compound. The filtrate was chromatographed on silica gel (eluent: 20:1 cyclohexane/ethyl acetate) and the product fractions were concentrated. The residue was suspended in methanol, the solids were filtered off and drying under high vacuum afforded a further 30 mg (15% of theory) of the title compound in solid form. The fractions were combined and converted without further purification (purity approx. 60%).

Provenance & Evidence