Cesium carbonate → HCID 131725046, compound

Participants

Reaction Steps

N1-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide (100 g, 0.189 mmol), 2-bromoacetamide (28 mg, 0.208 mmol) and cesium carbonate (123 mg, 0.378 mmol) was mixed in DMF (2 mL). The mixture was stirred at room temperature overnight. The crude mixture was purified by reverse phase preparative HPLC (Rainin HPLC, Column: Thermoquest, hyperprep HS C18, 8 um, 250×21.2 mm. Eluents: 5% B/A to 100% B/A in 25 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 21 mL/min.) to give N1-(4-{4-amino-1-[1-(2-amino-2-oxoethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide, acetate salt (70 mg, 63%). 1H NMR (DMSO-d6) δ 1.90 (m, 5H), 2.34 (m, 4H), 2.93 (s, 2H), 2.99 (m, 2H), 3.94 (s, 3H), 4.69 (m, 1H), 7.12 (s, 1H), 7.25 (s, 1H), 7.30 (d, J=8.15 Hz, 1H), 7.34 (s, 1H), 7.75 (d, J=8.15 Hz, 1H), 7.87 (d, J=10.30 Hz, 1H), 7.99 (m, 1H), 8.25 (s, 1H), 8.31 (d, J=8.14 Hz, 1H), 9.90 (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.): MH+=587.2, Rt=2.17 min.

Provenance & Evidence