Potassium Carbonate → 1-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-N,N-dimethylpiperidin-4-amine

Participants

Reaction Conditions

Reaction Steps

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (50.0 mg, 0.102 mmol, prepared in Example 7, step B), N,N-dimethylpiperidin-4-amine (39.2 mg, 0.306 mmol), copper(I)iodide (3.88 mg, 0.0204 mmol), (S)-pyrrolidine-2-carboxylic acid (4.70 mg, 0.0408 mmol), K2CO3 (70.5 mg, 0.510 mmol) and DMF (10 mL). The reaction mixture was stirred at 100° C. overnight. Then the reaction was cooled to room temperature and partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (35.8 mg, 71.6%). LRMS (APCI pos): >98% purity, 254 nm, m/e 491 (M+1).

Provenance & Evidence