Uses
3-Cyano-6-methyl-2(1H)-pyridinone is a reactant used in the synthesis of Milrinone (M344680), a selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity. 3-It has also been used in the preparation of the N3?-pyridyl thiamine, a potent in vitro thiamine antagonist.
General Description
Supramolecular structures of coordination copper(I) compounds of 3-cyano-6-methyl-2(1
H)-pyridinone has been investigated.
Synthesis
A 950 ml solution of tetrahydrofuran (THF) with 46.5 g of sodium methanolate was added to the reaction vessel and cooled in an ice bath to an internal temperature of 0 to 5°C. Subsequently, a mixed solution of 46.5 g of acetone and 59.6 g of ethyl formate was slowly added with a controlled drip time of 1 hour. After the dropwise addition, the ice bath was removed and the reaction system was allowed to slowly warm up to room temperature within 1 hour. Afterwards, the reaction solution was concentrated under reduced pressure (temperature not exceeding 50°C). The concentrate was transferred to another reaction vessel, 400 ml of aqueous solution of 67 g of cyanoacetamide and an appropriate amount of piperidine acetic acid (as a condensation catalyst) were added, and the reaction was refluxed for 2 hours. Upon completion of the reaction, the reaction was cooled to room temperature and the pH was adjusted with acetic acid to about 5. The reaction mixture was allowed to stand at room temperature overnight and subsequently cooled in an ice bath for 45 minutes for filtration. The filter cake was washed three times with ice water and finally dried under vacuum at 80 °C overnight to afford 65.5 g of the target compound 3-cyano-6-methyl-pyridone (61.0% yield) as a yellow solid.
References
[1] Patent: CN105037261, 2017, B. Location in patent: Paragraph 0048-0049
[2] Molecules, 2018, vol. 23, # 7,
[3] Patent: US6342504, 2002, B1. Location in patent: Page column 50
[4] Journal of Medicinal Chemistry, 1994, vol. 37, # 20, p. 3303 - 3312
[5] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 6, p. 2212 - 2215
