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)-1,4-diazepane-1-carboxylate

Participants

Reaction Steps

A 100 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)-1,4-diazepane-1-carboxylate (110.4 mg, 0.1962 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (137.9 mg, 0.5887 mmol, prepared according to Example 19, step C), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (188.1 mg, 0.9811 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (132.6 mg, 0.9811 mmol), N-ethyl-N-isopropylpropan-2-amine (253.6 mg, 1.962 mmol) and DMSO (25 mL). The reaction mixture was stirred at room 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. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (118.3 mg, 77.4%). LRMS (APCI pos): m/e 679 (M−99).

Provenance & Evidence