Potassium Carbonate → tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate

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 (100.0 mg, 0.2040 mmol, prepared in Example 7, step B), tert-butyl piperazine-1-carboxylate (114.0 mg, 0.6119 mmol), copper(I)iodide (7.769 mg, 0.04079 mmol), (S)-pyrrolidine-2-carboxylic acid (9.393 mg, 0.08159 mmol), K2CO3 (140.9 mg, 1.020 mmol) and DMSO (10 mL). The reaction mixture was stirred at 100° C. for 4 hours. 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 material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (63.5 mg, 56.75%). LRMS (APCI pos) m/e 549 (M+1).

Provenance & Evidence