Cesium carbonate → (R)-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

In a 5 mL microwave tube was weighed 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.00 g, 2.084 mmol; Example 313, Step 1), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-i-propyl-1,1′-biphenyl (0.099 g, 0.208 mmol), cesium carbonate (2.037 g, 6.25 mmol), potassium (R)-((4-(tert-butoxycarbonyl)-2-methylpiperazin-1-yl)methyl)trifluoroborate (prepared similarly according to Example 270, Stepl, from (R)-4-N-boc-2-methyl-piperazine (Sigma Adrich, Inc.), 0.701 g, 2.188 mmol,), palladium acetate (0.023 g, 0.104 mmol) followed by purging with argon. The solids were then treated with THF (10.00 mL), water (1.0 mL) and heated under a microwave irradiation at 85° C. overnight. The mixture was filtered through a short path of Celite® (diatomaceous earth), washed with ethyl acetate (3×), and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (100% DCM to 5% MeOH in DCM) to obtain the desired product (R)-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 (1.01 g, 1.535 mmol, 73.7% yield) as a yellow foam. m/z (ESI, +ve ion) 658 (M+H)+.

Provenance & Evidence