Acetic Acid → 1-[4-(4-methylpiperazino)cyclohexyl]-3-{4-[(phenethylamino)(phenyl)methyl]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

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Reaction Steps

To a solution of cis-3-{4-[amino(phenyl)methyl]phenyl}-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (50 mg, 0.10 mmol), phenylacetaldehyde (13 mg) and glacial acetic acid (0.013 mL) in 1,2-dichloroethane (1 mL) under nitrogen was added sodium triacetoxyborohydride (2 equivs., 43 mg). The solution was stirred for 18 h then concentrated in vacuo, partitioned between dichloromethane (10 mL) and saturated aqueous NaHCO3 (10 mL) and the organic layer separated. The aqueous layer was further extracted with dichloromethane (4×10 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and evaporated to dryness. Purification was effected using mass actuated preparative RP-HPLC (Micromass/Gilson, Hypersil BDS C18, 5 μm, 100×21.2 mm column; 0-100% acetonitrile and 0.05M ammonium acetate, buffered to pH 4.5, over 12.5 min at 25 mL/min) to afford 1-[4-(4-methylpiperazino)cyclohexyl]-3-{4-[(phenethylamino)(phenyl)methyl]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine (28 mg); RP-HPLC (10 to 90% CH3CN in 0.1 N aqueous ammonium acetate, buffered to pH 4.5, over 12 min at 2 mL/min using a Waters Symmetry C18, 250×4.6 mm column) Rt=12.269 min, 95.2%; m/z (MH+) 601.3.

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