Synthesis and amination of 1-alkyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acids

Abstract

The class of derivatives of 4-oxoquinoline-and4-oxo-1,8-naphthyridine-3-carboxylic acids and related heterocyclic compounds contains a large group of substances used in medical practice as antibacterial drugs with a broad spectrum of action. Studies in this field were summarized in a number of monographs and reviews [1 -7]. More that three decades of investigation of this group of compounds resulted in the development of four generations of antibacterial drugs offering a broad spectrum of action, with the efficiency increasing from one generation to another. The current generation of these compounds comprises the so-called fluoroquinolone preparations representing compounds containing fluorine atoms in position 6 of the quinoline, naphthyridine, or any other related nucleus. Most characteristic representatives of this group are the commercial drugs ciprofloxacin, ofloxacin, and lomefloxacin. Similar to most other drugs, preparations of the 4-oxoquinoline-3-carboxylic acid group, including the fluorine-containing derivatives, exhibit certain side effects that may sometimes restrict their practical application [7].Extensive investigations into the series of derivatives of 4-oxoquinoline-and 4-oxo-l,8-naphthyridine-3-carboxylic acids, performed to the present time, allowed certain "structure-activity" relationships in this group to be established and some substituents and their positions in the base mole--cules to be determined that impart the maximum antibacterial activity to the final compounds. For example, most active eompotmds are distingxtished by having fluorine atoms as substituents in position 6 of the quinoline or related nucleus. Fluorine and other substituents favoring antibacterial activity are described by the following sequence: F > C1 > Br = Me = CN > SMe = NO2>Ac. The most preferred substituents in po-

Advantageous Use of Ionic Liquids for the Synthesis of Pharmaceutically Relevant Quinolones

“…time: 9.38 min; purity: 96.8 %. The spectroscopic data are in agreement with those reported in the literature …”

“…Next, to explore the scope of the reaction, a set of acrylate intermediates differently functionalized at the arene ring ( 3 , 4 , 5 and 6 ; Table , entries 1–4, [TBMA][MsO]) or at the acrylic nitrogen ( 7 and 8 ; Table , entries 5 and 6, [TBMA][MsO]) were cyclized in [TBMA][MsO] as reaction medium in the presence of K 2 CO 3 at 80 °C. Also, the results were compared with those derived from parallel reactions conducted in DMF (entries 1–6, DMF).…”

“…Also, the results were compared with those derived from parallel reactions conducted in DMF (entries 1–6, DMF). Overall, [TBMA][MsO] proved a good choice for the cyclization of all the acrylates 3 – 8 to the corresponding quinolones 9 , 10 , 11 , 12 , 13 and 14 , (entries 1–6, [TBMA][MsO]) which were obtained in good yields (68–80 %) and in short reaction times (2–5 h). Compared with the cyclization reactions in DMF, (entries 1–6, DMF) in general, the use of the IL gave slightly higher yields.…”

“…>280 °C (lit. : >280 °C). 1 H NMR (400 MHz, [D 6 ]DMSO): δ = 8.67 (s, 1 H, 5‐H), 8.48 (s, 1 H, 2‐H), 8.25 (s, 1 H, 8‐H), 4.19 (q, J = 4.03 Hz, 2 H, OC H 2 CH 3 ), 3.69–3.65 (m, 1 H, cyclopropyl‐CH), 1.26–1.18 (m, 5 H, cyclopropyl‐CH 2 , and OCH 2 C H 3 ), 1.12–1.08 ppm (m, 2 H, cyclopropyl‐CH 2 ).…”