1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 4-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate

Participants

Reaction Steps

A solution of tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate (100 mg, 0.182 mmol, obtained from Example 82 Step A), 3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid (85.7 mg, 0.365 mmol, obtained from Example 98 Step D), EDCI (210 mg, 1.09 mmol) and HOBT (148 mg, 1.09 mmol) was stirred in DMF (6 mL) for 12 hours. The reaction mixture was poured into saturated aqueous NH4Cl and extracted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3, 10% aqueous LiCl, dry with Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (5% MeOH in CH2Cl2) to afford the product (100 mg, 71.6% yield) as a white solid. LRMS (APCI pos) m/e 766.2 (M+1).

Provenance & Evidence