4-Phenylpiperidine → 2-Methyl-6-methylamino-4-(4-phenylpiperidino)pyrimidine

Participants

Reaction Steps

A mixture of 4-chloro-2-methyl-6-methylaminopyrimidine (525 mg, 3.3 mM; described in J. Pharm. Soc. (Japan) 1966, 86, p. 952) and 4-phenylpiperidine (1.08 g, 6.6 mM) was heated as a melt at 135°-140° C. for 1 hour. The residue, obtained after cooling, was triturated with ether and the mixture separated by filtration. The solid was suspended in a mixture of 50% w/v potassium hydroxide solution (50 ml) and isopropanol (50 ml). The mixture was heated under reflux for 2 hours and cooled. The organic layer was separated and the solvent removed in vacuo. The residue was dissolved in methylene chloride (50 ml), washed with water (2×25 ml), dried (MgSO4) and the solvent evaporated. The residue was purified by flash chromatography on silica (Merck Art. 9385, 100 g), using a mixture of methanol and methylene chloride (1:9 v/v) as eluant, to give 2-methyl-6-methylamino-4-(4-phenylpiperidino)-pyrimidine (700 mg, 75% yield), m.p. 186°-188° C.; microanalysis, found: C, 71.6; H,7.5; N,19.3%; C17H22N4.1/4H2O requires C,71.2; H,7.8; N,19.5%.

Provenance & Evidence