Ammonium Chloride → tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Cyclopropylzinc (II) bromide (2.5 mL, 2.49 mmol) was added to a solution of tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (500 mg, 0.995 mmol, see Example 1) and Pd(PPh3)4 (86 mg, 0.075 mmol) in THF (5 mL) under nitrogen, and the reaction mixture was heated to 75° C. (oil bath) for 18 hours under a nitrogen atmosphere. Then the reaction mixture was allowed to cool to room temperature and poured into a saturated aqueous NH4Cl (50 mL) solution and extracted with EtOAc (3×50 mL). The crude product was purified by C-18 reverse phase flash chromatography (Biotage 25M+) using a gradient of 15-90% CH3CN/water on Biotage SP4 unit to provide tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (275 mg, 0.59 mmol, 59.6% yield) as a solid. LCMS (APCI+) m/z 464.2 (M+H).

Provenance & Evidence