Potassium Carbonate → HCID 131725045, compound

Participants

Reaction Conditions

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-bromoethyl methyl ether (20 uL, 0.208 mmol) and potassium carbonate (52 mg, 0.378 mmol) was mixed in DMF (2 mL). The mixture was heated at 65° C. 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-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide, acetate salt (75 mg, 68%). 1H NMR (DMSO-d6) δ 1.90 (m, 2H), 2.22 (m, 4H), 2.54 (m, 2H), 3.02 (m, 2H), 3.26 (s, 3H), 3.46 (m, 2H), 3.94 (m, s, 3H), 4.66 (m, 1H), 7.30 (d, J=8.19 Hz, 1H), 7.34 (s, 1H), 7.74 (d, J=7.84 Hz, 1H), 7.90 (d, J=10.33 Hz, 1H), 7.99 (m, 1H), 8.24 (s, 1H), 8.30 (d, J=8.23 Hz, 1H), 9.89 (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