Uses
N-(4-Methoxyphenyl)-3-oxobutanamide is an intermediate in the synthesis of Tafenoquine-d3 Succinate is the labelled analog of Tatenoquine (T004760), a new 8-aminoquinoline with an improved therapeutic index and safety profile as compared to primaquine (P733500).Tafenoquine has the potential to become a widely used drug in the prevention and treatment of malaria infection and could replace some currently used drugs as resistant strains of Plasmodium species increase.
Synthesis
GENERAL STEPS: In a 100 mL round-bottomed flask, ethyl acetoacetate (0.03 mol) was added to a stirring solution of p-aminoanisole (0.01 mol) dissolved in 10 mL of PEG-300. The reaction mixture was refluxed at 120 °C for 1.5-2 hours. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to room temperature and subsequently extracted with cold ether (3 x 10 mL). The organic phases were combined and purified by column chromatography (eluent: hexane solution of 10-25% ethyl acetate) to afford the target product N-(4-methoxyphenyl)-3-oxobutylamide (3a-p). The structure of the final product was confirmed by methods reported in the literature.
References
[1] Synthetic Communications, 2000, vol. 30, # 20, p. 3709 - 3718
[2] Heterocycles, 2008, vol. 75, # 11, p. 2681 - 2701
[3] European Journal of Organic Chemistry, 2015, vol. 2015, # 14, p. 3171 - 3177
[4] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 13, p. 1639 - 1641
[5] Journal of Chemical Sciences, 2014, vol. 126, # 1, p. 187 - 195
