The chemical shifts of the 5'-H and 8'-H protons and of the protons of the cyclic amine residue were
changed insignificantly. The mass spectra of compounds 1 and 2 were characterized by the presence of intense
peaks for the molecular ions. The presence of [M-45]+ and [M-72]+ peaks is caused by fission of ethoxy and
carbethoxy groups. Further fragmentation occurs with breaking of the oxadiazine ring.
In conclusion, new derivatives of bi- and tricyclic fluoroquinolones have been obtained. Acids 8 are not
only intermediates for the synthesis of new tricyclic fluoroquinolones but are of separate interest, since under
defined conditions two reactive fluoroquinolone fragments may be released, which may possibly lead to a
change in the spectrum of biological activity.
EXPERIMENTAL
The 1H NMR spectra were obtained on a Bruker WP-250 (250 MHz) instrument, solvent was DMSO-d6,
internal standard TMS. The 19F NMR spectra were taken on a Bruker WP-80 (80 MHz) instrument, solvent was
DMSO-d6, internal standard hexafluorobenzene. The mass spectra were recorded on a Varian MAT 311A
spectrometer. Plotting conditions: accelerating voltage 3 kV, cathode emission current 300 µA, energy of
ionizing electrons 70 eV, samples were inserted directly into the ion source.
Hydrazides of 7-Z-1-Ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic Acids (5a-e). A
suspension of 7-Z-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-3-quinoline-carboxylic acid ethyl ester (6 mmol) and
hydrazine hydrate (4.5 ml) in pyridine (10 ml) was maintained for 1 h at 80°C. The reaction mixture was cooled
to room temperature, dissolved in distilled water (40 ml), and acetic acid added to pH 5-6. The precipitated solid
was filtered off, washed with water, with ethanol, and with ether.
Ethyl Esters of 1-(7-Z-1-Ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbamoyl)-5-X-6,7,8-
trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic Acids (6a-e, 7a-e). Ethyl ester 3 or 4 (0.95 mmol) was
added to a suspension of hydrazide 5a-e (0.94 mmol) in absolute toluene (8 ml). The reaction mixture was
boiled for 2 h, then cooled. The precipitate of 6 or 7 was filtered off and recrystallized from acetonitrile.
19F NMR spectrum of compound 7a, , ppm: 161.41 (1F, m); 155.29 (1F, m); 149.80 (1F, m); 143.69 (1F, m);
δ
128.31 (1F, m).
Ethyl Esters of 2-(7-Z-1-Ethyl-6-fluoro-4-oxo-1,4-dihydroquinolinyl)-8-X-9,10-difluoro-7-oxo-7H-
1,3,4-oxadiazino[6,5,4-i,j]quinoline-6-carboxylic Acids (1a-c, 2). Calcined potassium carbonate (1.1 mmol)
was added to a suspension of amide 6a,d,e or 7a (0.85 mmol) in absolute toluene (15 ml). The reaction mixture
was boiled for 3-4 h and cooled. The solid product 1 or 2 was filtered off, washed with water, and recrystallized
from DMSO.
1-(7-Z-1-Ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbamoyl)-5-X-6,7,8-trifluoro-4-oxo-1,4-
dihydroquinoline-3-carboxylic Acids (8, 9). A solution of compound 6a or 7b (1 mmol) in a mixture (25 ml)
of hydrochloric and acetic acids (1:4) was boiled for 3 h. The reaction mixture was cooled, diluted with water,
the solid product 8 or 9 was filtered off, and recrystallized from DMSO.
1-(1-Ethyl-6-fluoro-4-oxo-7-pyrrolidino-1,4-dihydroquinoline-3-carbamoyl)-7-Y-6,8-difluoro-4-oxo-
1,4-dihydroquinoline-3-carboxylic Acids (10a,b). Pyrrolidine or 4-methylpiperazine (6 mmol) was added to a
solution of acid 8 (0.55 g, 1.05 mmol) in pyridine (6 ml). The reaction mixture was boiled for 4 h, then cooled.
The solid product 10a or 10b was filtered off, and recrystallized from DMSO.
The work was carried out with the financial support of the Federal scientific-technical program
"Investigations and development on priority directions on progress of science and technology for civil
purposes", direction "Fundamental problems of contemporary chemistry", project 9.1.06.
927
Nosova
