Cesium carbonate → 4-amino-8-((8-chloro-2-(2-chlorophenyl)-quinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one

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Reaction Conditions

Reaction Steps

To a mixture of 4-aminopyrido[2,3-d]pyrimidin-5(8H)-one (0.05 g, 0.308 mmol), Cs2CO3 (0.1515 g, 0.46 mmol, 1.5 eq), and KI (0.0051 g, 0.0309 mmol, 0.1 eq) in DMF (1 mL) was added 8-chloro-3-(chloromethyl)-2-(2-chlorophenyl)quinoline (0.1 g, 0.309 mmol, 1.0 eq) and the mixture was stirred at 140° C. for 1 h. The mixture was concentrated under reduced pressure. The crude product was purified by column chromatography on a 40 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 14 min and then 100% isocratic of EtOAc for 14 min as eluent to provide 4-amino-8-((8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)pyrido[2,3-d]pyrimidin-5(8H)-one [PI3Kδ IC50=33 nM] as white solid. 1H NMR (DMSO-d6) δ ppm 9.52 (1 H, d, J=4.7 Hz), 8.25 (1 H, s), 8.11 (1 H, d, J=4.7 Hz), 8.09 (1 H, s), 8.04 (1 H, dd, J=8.4, 1.4 Hz), 7.97 (1 H, dd, J=7.6, 1.4 Hz), 7.81 (1 H, d, J=7.8 Hz), 7.63 (1 H, d, J=7.8 Hz), 7.57-7.61 (1 H, m), 7.42-7.53 (3 H, m), 6.14 (1 H, d, J=7.8 Hz), 5.40 (2 H, s). Mass Spectrum (ESI) m/e=448.0 and 450.1 (M+1).

Provenance & Evidence