Methylamine → Deferiprone

Participants

Reaction Steps

Deferiprone was synthesized as described previously. (Gale et al, Res Comun Chem Pathol Pharmacol Vol. 73, No. 3, September 1991) An aqueous suspension of 3-hydroxy-2-methyl-pyrone, maltol, (Aldrich Chemical Co., Milwaukee, Wis., 50 gm, 396 nmol) and NH2CH3 (Aldrich Chemical Co., Milwaukee, Wis., 3 eq, 92 ml, 1.18 mol, 12.88 M) in distilled, degassed H2O was heated under reflux for 12 hours. The solution was allowed to cool to room temperature. The excess methyl amine was removed under reduced pressure and the brown mixture was carefully concentrated to a volume of approximately 200 ml. Reagent grade acetone (50 ml) was added to this brown suspension and the solid recovered by filtration. The solid was washed with 1200 ml of acetone and briefly allowed to dry. To this crude solid was added 2 g of Norite and 2 g of Celite 545 (fisher Scientific, Pittsburgh, Pa.) and the crude solid was dissolved in a minimal amount of hot water. The Celite/Norite matrix was removed from the solution by filtration. The pure crystalline compound was recovered by filtration to give 29.8 g (54%) of the title compound. All recovery and transfer procedures were performed with a porcelain spatula rather than stainless steel equipment due to the potent iron chelating property of 1,2-dimethyl-3-hydroxypyrid-4-one. Analytically pure 1,2-dimethyl-3-hydroxypyrid-4-one was obtained by a single recrystallization from H2O. Other alkyl-substituted pyridones can be prepared by similar measures.

Provenance & Evidence