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

Participants

Reaction Conditions

Reaction Steps

N2-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-methyl-1H-2-indolecarboxamide (250 mg, 0.503 mmol), 1-bromo-2-fluoroethane (47 ul, 0.629 mmol), Potassium carbonate (87 mg, 0.629 mmol) and Sodium iodide (10 mg, 0.066 mmol) were mixed in DMF (3 mL). The reaction mixture was heated at 80° C. overnight. The crude reaction mixture was purified by reverse phase preparative HPLC using acetonitrile/water (50 mM ammonium acetate buffer) as mobile phase to give N2-(4-{4-amino-1-[1-(2-fluoroethyl)-4-piperidyl]-1H-pyrazolo [3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (221 mg, 81%). 1H NMR (DMSO-d6) δ 1.91 (m, 2H), 2.26 (m, 4H), 2.66 (m, 1H), 2.73 (m, 1H), 3.05 (m, 2H), 3.97 (s, 3H), 4.04 (s, 3H), 4.61 (m, 1H), 4.61 (m, 1H), 4.64 (m, 1H), 7.15 (m, 1H), 7.33 (m, 4H), 7.58 (d, J=8.46 Hz, 1H), 7.70 (d, J=7.95 Hz, 1H), 8.11 (d, J=8.14 Hz, 1H), 8.25 (s, 1H), 9.44 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 0.8 mL/min.): RT=2.17 min. MH+=543.3.

Provenance & Evidence