1-Hydroxybenzotriazole → tert-butyl 4-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate

Participants

Reaction Steps

A 50 mL round-bottomed flask was charged with tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate (63.5 mg, 0.1157 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (54.21 mg, 0.2315 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (110.9 mg, 0.5787 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (78.20 mg, 0.5787 mmol), N-ethyl-N-isopropylpropan-2-amine (0.2066 ml, 1.157 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction was 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 100/1 to 10/1, v/v) to afford product (56.8 mg, 64.17%). LRMS (APCI pos) m/e 765 (M+1).

Provenance & Evidence