Sodium Carbonate → N2-{4-[4-amino-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.244 g, 0.629 mmol) in ethylene glycol dimethyl ether (16 mL) was treated with N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.281 g, 0.692 mmol), tetrakis(triphenylphosphine)palladium (0.044 g, 0.038 mmol), and a solution of sodium carbonate (0.160 g, 1.51 mmol) in water (8 mL). The reaction mixture was stirred for 4.5 h at 80° C. The organic solvent was removed under reduced pressure and ethyl acetate (200 mL) was added. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (400 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a step-wise gradient of 10% methanol in dichloromethane to 50% methanol in dichloromethane as the eluent. The column afforded 0.191 g (56%) of pure N2-{4-[4-amino-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.440 (s, 1H), 8.260 (s, 1H), 8.1229-8.1026 (d, 1H, J=8.12 Hz), 7.7184-7.6986 (d, 1H, J=7.92 Hz), 7.5983-7.578 (d, 1H, J=8.08 Hz), 7.345-7.290 (m, 4H), 7.172-7.133 (m, 1H), 4.421-4386 (m, 2H), 4.04 (s, 3H), 3.958 (s, 3H), 3.521-3.500 (m, 4H), 2.349-2.314 (m, 6H), 2.035-2.001 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.05 min (100%), MH+ 541.3.

Provenance & Evidence