6-Fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid

Chemical Properties

Yellow Solid

Uses

A labelled metabolite of Prulifloxacin (P838885). Ulifloxacin is a new quinolone antibiotic and it is effective against pneumonia.

Uses

A metabolite of Prulifloxacin (P838885). Ulifloxacin is a new quinolone antibiotic and it is effective against pneumonia.

Definition

ChEBI: Ulifloxacin is a member of quinolines.

Biological Activity

Ulifloxacin is an orally available, broad-spectrum fluoroquinolone antibacterial agent. Ulifloxacin is an active metabolite of Prulifloxacin. It potently inhibits bacterial DNA gyrase and topoisomerase IV.

Synthesis

The general procedure for the synthesis of 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazolo[3,2-a]quinoline-3-carboxylic acid from ethyl 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1,4-dihydro-[1,3]thiazolo[3,2-a]quinoline-3-carboxylate was as follows: 1. ethyl 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazolo[3,2-a]quinoline-3-carboxylate (100 g, 0.265 mol) was dissolved in water (600 ml) at 25-30 °C with stirring. 2. potassium hydroxide solution (50 g of potassium hydroxide flakes dissolved in 200 ml of water) was slowly added to this solution. 3. the reaction mixture is heated to 80-85°C and stirred at this temperature for 1 hour. 4. After completion of the reaction, the reaction mixture was cooled down to 25-30 °C. The reaction mixture was then cooled down to 25-30 °C. 5. The pH of the reaction mixture was adjusted to 6.5-7.0 using a 1:1 aqueous solution of acetic acid. 6. The reaction mixture was stirred at room temperature for 1 hour to allow the product to fully precipitate. 7. The precipitated solid was collected by filtration and washed with distilled water (2 x 100 mL). 8. The solid was slurried in methanol (300 ml) at 25-30 °C for 1 h. The reaction mixture was stirred for 1 h at room temperature. 9. After filtration, the solid was washed with methanol (2 x 50 ml). 10. The product was dried under vacuum at 70-75 °C to afford 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (90 g, 97% yield, 96% HPLC purity).

References

[1] Patent: WO2012/1357, 2012, A1. Location in patent: Page/Page column 22
[2] Patent: CN103113392, 2016, B. Location in patent: Paragraph 0024; 0037; 0038; 0039
[3] Patent: CN107383069, 2017, A. Location in patent: Paragraph 0063; 0064
[4] Journal of Medicinal Chemistry, 1992, vol. 35, # 25, p. 4727 - 4738
[5] Patent: WO2009/93268, 2009, A1. Location in patent: Page/Page column 15