1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamide

Participants

Reaction Steps

A solution of 1-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-N,N-dimethylpiperidin-4-amine (39 mg, 0.079 mmol, obtained from Example 93, Step A), 3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid (37 mg, 0.16 mmol), EDCI (91 mg, 0.48 mmol) and HOBT (64 mg, 0.48 mmol) was stirred in DMF (10 mL) for 12 hours. The reaction mixture was poured into saturated aqueous NH4Cl and extracted with EtOAc. The organic layer washed with NaHCO3, 10% aqueous LiCl, dry with Na2SO4, filtered and concentrated. The residue was purified with flash silica gel chromatography (5% MeOH in CH2Cl2) to afford the product (30 mg, 53%) as a white solid. LRMS (APCI pos) m/e 708.3 (M+1).

Provenance & Evidence