Propargyl bromide → 6-Ethyl-5-methyl-2-phenyl-3-propargyl-5,6-dihydropyrimidin-4-one

Participants

Reaction Steps

Oven dried glassware and a nitrogen purge were utilized. 3.22 mL of 1.6 Molar n-butyl lithium in hexanes (5.15 mmol) was added dropwise to a solution of 1.06 g (4.93 mmol) of 6-ethyl-5-methyl-2-phenyl-5,6-dihydropyrimidin-4-one, in 15 mL of dry tetrahydrofuran, at -50 to -60° C. The mixture was stirred for 15 minutes and then 0.8 mL (5.38 mmol) of 80 wt.% propargyl bromide in toluene was added at -65° C. The ice bath was removed after 1.5 hours and the reaction mixture was stirred for an additional 20 hours. The solvent had evaporated overnight. Ether was added and the reaction mixture was washed three times with water followed by three times with 3 Molar hydrochloric acid. The acidic aqueous washes were combined, cooled externally, and 50% sodium hydroxide was added until the pH=10, then extracted three times with ether. The ether extracts were combined, dried over magnesium sulfate, and concentrated to yield 0.68 g of crude product. The crude product was combined with crude product obtained from previous reactions and purified on a six inch plug of basic alumina by washing with 400 mL of methylene chloride. The filtrate was concentrated to yield 6-ethyl-5-methyl-2-phenyl-3-propargyl-5,6-dihydropyrimidin-4-one (Compound 1), as a yellow solid, melting 62°-65° C.

Provenance & Evidence