Tetrahydrofuran → HCID 66611795, compound

Participants

Reaction Conditions

Reaction Steps

To a 250 mL round-bottomed flask was added (3R)-tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (1.0 g, 1.489 mmol), 5-fluoro-6-methoxypyridin-3-amine (0.317 g, 2.233 mmol) (Anichem), tetrahydrofuran (20 mL, 247 mmol). The solution was stirred at −40° C. and treated dropwise via addition funnel with lithium bis(trimethylsily)amide (Aldrich) (4.47 mL, 4.47 mmol). The solution was stirred at −40° C. for 30 minutes and quenched with water and NH4Cl (20 ml) each and diluted with EtOAc (20 mL) and the aqueous layer was extracted with EtOAc (2×20 mL). The organic extract was washed with saturated NaCl (20 mL) and dried over sodium sulfate, filtered and concentrated in vacuum. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (40 g), eluting with a gradient of 5% to 50% EtOAc in hexane, to provide (R)-tert-butyl 4-((R)-1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (0.45 g, 0.567 mmol, 38.1% yield), and (R)-tert-butyl 4-((S)-1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (0.35 g, 0.441 mmol, 29.6% yield).

Provenance & Evidence