Cesium carbonate → (S)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)-3-methylpiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (8.99 g, 18.73 mmol), potassium (S)-((4-(tert-butoxycarbonyl)-2-methylpiperazin-1-yl)methyl)trifluoroborate (6.00 g, 18.73 mmol), diacetoxypalladium (0.210 g, 0.937 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.893 g, 1.873 mmol), and cesium carbonate (18.31 g, 56.2 mmol) in THF (100 mL) and water (10.0 mL) was heated at 80° C. overnight. After cooling to ambient temperature, the mixture was passed through a short plug of Celite® (diatomaceous earth), washing with EtOAc (3×30 mL). The combined organic filtrates were concentrated and purified by flash chromatography (silica gel, 5% to 50% ethyl acetate/hexanes) to give (S)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)-3-methylpiperazine-1-carboxylate (10.39 g, 15.80 mmol, 84% yield) as a pale-yellow foam. m/z (ESI, +ve ion) 658 (M+H)+.

Provenance & Evidence