Preparation and application background and overview of 3-methoxy-2-methyl-1H-pyridin-4-one
3-Methoxy-2-methyl-1H-pyridin-4-one can be used as a pharmaceutical synthesis intermediate. 2-methyl-3-methoxypyridine can be prepared by reacting maltol as a raw material with methyl iodide. Pyranone, prepared by further reacting with ammonia water, can be used to prepare the compound 2-methyl-3-hydroxy-1-((coumarin-3-yl)methyl)pyridin-4(1H)-one. It has iron chelating and monoamine oxidase B inhibitory activity.
Preparation and application of 3-methoxy-2-methyl-1H-pyridin-4-one
Add maltol (7.56g, 60mmol), 100mL acetone, and methyl iodide (9.37g, 66mmol) into a 250mL single-neck bottle. Heat and reflux for 6 hours. After the reaction is completed, cool to room temperature, spin dry the solvent, and add 100mL water to dissolve. , extracted 4 times with dichloromethane (50 mL), the organic layer was dried over anhydrous sodium sulfate, and the organic layer was concentrated to obtain 2-methyl-3-methoxypyrone. The yield is 98%. Add the pyrone (8.65g, 40mmol) obtained by the above reaction, 60mL of 25% ammonia water, and 50mL of ethanol into a 250mL single-neck bottle, and heat and reflux at 75°C for 12h. After the reaction is completed, cool to room temperature, spin dry the solvent to obtain a brown oily liquid, and use Recrystallization from acetone/ethyl acetate gave 3-methoxy-2-methyl-1H-pyridin-4-one as a light yellow solid. The yield is 75%.
Preparation and application of 3-methoxy-2-methyl-1H-pyridin-4-one
3-Methoxy-2-methyl-1H-pyridin-4-one can be used to prepare the compound 2-methyl-3-hydroxy-1-((coumarin-3-yl)methyl)pyridine -4(1H)-one: Add 3-bromomethylcoumarin (717.2mg, 3mmoL) and 3-methoxy-2-methyl-1H-pyridin-4-one (430.5 mg, 2mmol), potassium carbonate (414.6mg, 3mmol), acetonitrile 12mL, water 1.5mL; heat and reflux the reaction until the thin layer chromatography detects the end of the reaction. The solvent was distilled off under reduced pressure, and the intermediate was separated by column chromatography with a yield of 59%. Place the yellow solid (373.41 mg, 1 mmoL) obtained in the previous step into a 50 mL single-necked flask, add 15 mL of anhydrous dichloronitrobenzene borate methane to dissolve, replace with nitrogen 3 times, and stir at -48°C; place in a constant pressure dropping funnel Add 10 mL anhydrous dichloromethane, 1.5 mL 1.0 mol/L boron tribromide (BCl3) anhydrous dichloromethane solution, slowly add dropwise, insulate for 2 hours, transfer to room temperature and continue reaction for 12 hours; add 5 mL methanol dropwise to quench. After the reaction, the solvent was distilled off under reduced pressure to obtain a yellow solid, which was recrystallized from methanol/diethyl ether to obtain 2-methyl-3-hydroxy-1-((coumarin-3-yl)methyl)pyridin-4(1H)-one. Yield 86%.
References
[1] Sodium bicarbonate CN201910555296.6 Coumarin hybrid pyridone compounds with iron chelating and monoamine oxidase B inhibitory activities and their preparation and application
