Methylamine → Deferiprone

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.

1. distillationin distilled
2. customdegassed H2O
3. temperaturewas heated
4. temperatureunder reflux for 12 hours
5. customThe excess methyl amine was removed under reduced pressure
6. concentrationthe brown mixture was carefully concentrated to a volume of approximately 200 ml
7. additionReagent grade acetone (50 ml) was added to this brown suspension
8. filtrationthe solid recovered by filtration
9. washThe solid was washed with 1200 ml of acetone
10. customto dry
11. additionTo this crude solid was added 2 g of Norite and 2 g of Celite 545 (fisher Scientific, Pittsburgh, Pa.)
12. dissolutionthe crude solid was dissolved in a minimal amount of hot water
13. customThe Celite/Norite matrix was removed from the solution by filtration
14. filtrationThe pure crystalline compound was recovered by filtration

ORD record

ord-6e003add9127493e91524fff428807eb

Source dataset

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06004986