Sodium Carbonate → HCID 136128170, compound

Participants

Reaction Steps

Prepared according to Procedure J using a mixture of 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.2737 g, 0.52 mmol, 1 eq), 4-pyrazoleboronic acid pinacol ester (0.20 g, 1.0 mmol, 2.0 eq), tetrakis(triphenylphosphine)palladium(0) (0.060 g, 0.052 mmol, 10 mol %), and sodium carbonate (2M aq. sol, 1.6 mL, 3.1 mmol, 6 eq) in DMF (3.1 mL). After purification, a mixture of 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine was obtained as tan solid. The tan solid (0.1566 g) was dissolved in DMSO (8 mL) and purified by semi-prep-HPLC on C18 column using 20-70% gradient of CH3CN (0.1% of TFA) in water (0.1% of TFA) over 40 min as eluent to provide 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [PI3Kδ IC50=18 nM] as white solid as a TFA salt and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [PI3Kδ IC50=30 nM] as white solid as a TFA salt. 1H NMR (DMSO-d6) δ ppm 8.18 (1 H, s), 7.88-7.96 (3 H, m), 7.77-7.82 (1 H, m), 7.72-7.77 (1 H, m), 7.49 (1 H, d, J=7.8 Hz), 7.27-7.38 (3 H, m), 5.82 (2 H, d, J=18.4 Hz), 2.54 (3 H, s); Mass Spectrum (ESI) m/e=468.1 (M+1); HPLC: a peak at 6.522 min. 1H NMR (DMSO-d6) δ ppm 8.15 (1 H, s), 7.91-7.96 (1 H, m), 7.89 (2 H, s), 7.78-7.84 (1 H, m), 7.74-7.78 (1 H, m), 7.40-7.49 (1 H, m), 7.18-7.34 (3 H, m), 5.82 (2 H, d, J=27.4 Hz), 2.66 (3 H, s); Mass Spectrum (ESI) m/e=468.1 (M+1); HPLC: a peak at 6.700 min.

Provenance & Evidence