Synthesis of 2-(1-alkyl(aryl)-4-oxo-5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acid derivatives

Article abstract of DOI:10.1016/S0022-1139(01)00354-2

Methods for synthesis of previously unknown 2-(1-alkyl(aryl)-4-oxo-5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acids and their esters from the copper chelate of ethyl pentafluorobenzoylpyruvate were developed. 1-Aryl(alkyl)-3-ethoxalyl-5,6,7,8-tetrafluoro-quinolin-4-ones react with o-phenylenediamine and o-aminophenol to give the corresponding quinolin-3-ylquinoxalones and quinolin-3-ylbenzoxazines. The same heterocycles act with o-aminothiophenol to yield ethyl-2-(7-(2-aminophenylthio)-1-aryl-5,6,8-trifluoro-quinolon-3-yl)-2- (2-mercaptophenylimino)glioxylates. Interaction of 1-aryl-3-ethoxalyl-(heteryl)-5,6,7,8-tetrafluoroquinolones with morpholine gives 7-mono- and 5,7-disubstituted products depending on the reaction conditions.

Full text of DOI:10.1016/S0022-1139(01)00354-2

Journal of Fluorine Chemistry 108 ꢀ2001) 187±194
Synthesis of 2-ꢀ1-alkylꢀaryl)-4-oxo-5,6,7,8-tetra¯uoro-1,
4-dihydroquinolin-3-yl)glyoxylic acid derivatives
A.S. Fokin, Ya.V. Burgart, V.I. Saloutin*, O.N. Chupakhin
Institute of Organic Synthesis, Urals Division, Russian Academy of Sciences, GSP-147, 620219 Ekaterinburg, Russia
Received 6 November 2000; accepted 11 January 2001
Abstract
Methods for synthesis of previously unknown 2-ꢀ1-alkylꢀaryl)-4-oxo-5,6,7,8-tetra¯uoro-1,4-dihydroquinolin-3-yl)glyoxylic acids and their
esters from the copper chelate of ethyl penta¯uorobenzoylpyruvate were developed. 1-Arylꢀalkyl)-3-ethoxalyl-5,6,7,8-tetra¯uoro-quinolin-4-
ones react with o-phenylenediamine and o-aminophenol to give the corresponding quinolin-3-ylquinoxalones and quinolin-3-ylbenzoxazines.
The same heterocycles act with o-aminothiophenol to yield ethyl-2-ꢀ7-ꢀ2-aminophenylthio)-1-aryl-5,6,8-tri¯uoro-quinolon-3-yl)-2-
ꢀ2-mercaptophenylimino)glioxylates. Interaction of 1-aryl-3-ethoxalyl-ꢀheteryl)-5,6,7,8-tetra¯uoroquinolones with morpholine gives 7-mono-
and 5,7-disubstituted products dependingon the reaction conditions. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Ethyl penta¯uorobenzoylpyruvate; 3-Ethoxalyl-5,6,7,8-tetra¯uoroquinolin-4-ones; 2-ꢀ1-Alkylꢀaryl)-5,6,7,8-tetra¯uoro-4-oxo-1,4-dihydroquino-
lin-3-yl)glyoxylic acids; o-Phenylenediamine; o-Aminophenol; o-Aminothiophenol; Morpholine
1. Introduction
is transformation of ¯uorobenzoylacetic acids by the Gould±
Jacobs reaction [1±3].
The substituted ¯uoroquinolone-3-carboxylic acids have
attracted considerable attention in recent years [1±4]. This is
mainly due to the fact that compounds of this class have been
used as antibacterial agents in medicine for example cipro-
¯oxacin, o¯o¯oxacin, pe¯oxacin. In this context, develop-
ment of modi®cation paths of a ¯uoroquinolone structure is
of considerable interest for investigating new effective
drugs.
In the present paper, 2-ꢀ1-alkylꢀaryl)-5,6,7,8-tetra¯uoro-
4-oxo-1,4-dihydroquinolin-3-yl)glyoxylic acids and their
esters were obtained. The reactions of derivatives of these
compounds with nucleophiles are described.
The copper chelate of ethyl penta¯uorobenzoylpyruvate
1 was used as the startingcompound for synthesis of
¯uoroquinolone-3-glyoxylic acid. Decomposition of chelate
1 by dry gaseous hydrogen chloride in anhydrous ether
yields ethyl penta¯uorobenzoylpyruvate 2. The latter
without additional puri®cation was treated with triethy-
lorthoformate in the presence of acetic anhydride to form
a-ethoxymethylenesubstituted ethyl penta¯uorobenzoylpyr-
uvate 3 ꢀScheme 1). Use of copper chelate 1 as the starting
material instead of free ligand 2 is because of conversion of
the latter into 2-ethoxycarbonyl-5,6,7,8-tetra¯uorochro-
mone [5].
In contrast to its ¯uorobenzoylacetic analogs [5], the
ethoxymethylene derivative 3 is readily hydrolyzed to give
the startingethyl penta¯uorobenzoylpyruvate 2, which con-
verted into stable 2-ethoxycarbonyl-5,6,7,8-tetra¯uorochro-
mone under the reaction conditions. In order to reduce the
formation of by-products and to increase yields of end
compounds, unstable ethers 2 and 3 were not isolated from
the reaction.
Interaction of compound 3 with various amines ꢀammo-
nia, methylamine, ethylamine, cyclopropylamine, n-hexy-
lamine and o-toluidine) results in the formation of acyclic
precursors of quinolones Ð ethyl-4-alkylꢀaryl)amino-2-
oxo-3-penta¯uorobenzoylbut-3-enoates 4a±f ꢀScheme 1).
2. Results and discussion
2.1. Synthesis of derivatives of 2-,1-alkyl,aryl)-4-oxo-
5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acids
One of known methods for synthesis of ¯uorine-contain-
ing1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acids
* Correspondingauthor. Fax: ‡7-3432-745954.
E-mail address: saloutin@ios.uran.ru ꢀV.I. Saloutin).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 3 5 4 - 2

188
A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
Scheme 1.
There are quite stable compounds. The compounds 4a±f in
the presence of triethylamine upon heatingin a dry aprotic
solvent ꢀtoluene, chloroform) undergo intramolecular cycli-
zation to form the corresponding3-ethoxalyl-5,6,7,8-tetra-
¯uoroquinolones 5a±f ꢀScheme 1). The cyclization proceeds
through intramolecular substitution of the o-¯uorine atom in
the penta¯uorophenyl substituent by the amino group.
The products 4a±f exist as a mixture of Z- and E-isomers
showingtwo sets of identical signals in the 1H and 19F NMR
spectra and thus the presence of two isomers in all cases.
When ethers 5a±c were heated with a boilingmixture of
concentrated acetic and hydrochloric acids, quinolone-3-
glyoxylic acids 6a±c were obtained ꢀScheme 1).
substitution of an aromatic ¯uorine atom at position C-7 by
the 2-aminophenylthiogroup of the second molecule of the
dinucleophile. The possibility of nucleophilic substitution in
this case may be caused by high nucleophility of the sulfur
atom of this reagent. Further this reaction demonstrates the
preferred attack of nucleophile at a-carbonyl rather an ester
group.
Attempts to subject product 9 to further cyclization into
quinolonylbenzothiazinone upon re¯uxingtoluene or n-
butanol failed.
2.3. Reactions of derivatives of 2-,1-alkyl,aryl)-4-oxo-
5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acids
with morpholine
2.2. Reactions of 2-,1-alkyl,aryl)-3-ethoxycarbonyl-
5,6,7,8-tetrafluoro-1,4-dihydroquinolin-4-ones) with
dinucleophiles
Interaction of 3-ethoxalylsubstituted quinolone 5c with an
excess of morpholine in DMSO at the room temperature
gives product 10 as the result of mono-substitution of
¯uorine at position C-7. When the quinolone 5c was re¯uxed
in pyrydine with an excess of morpholine, the product of 5,7-
disubstitution 11 was obtained ꢀScheme 3).
Replacement of the ethoxalyl group by the heterocyclic
quinoxalonyl fragment in quinolones does not change the
direction of their reactions with morpholine. Thus, 7-mono-
substituted product 12 was derived from 3-quinolonylqui-
noxaline 7a in DMSO at room temperature. Boiling
compound 7a in pyridine affords 5,7-disubstituted hetero-
cycle 13 ꢀScheme 4).
The quinolones 5 have great synthetic possibilities for the
further modi®cation due to the presence of an a-dicarbonyl
fragment, including the creation of new heterocyclic com-
pounds. Interaction with nucleophilic reagents can proceed
both at one carbonyl group and at the a-dicarbonyl fragment.
Moreover, aromatic nucleophilic substitution of ¯uorine
atoms is typical for these heterocycles.
In the present work, the reactions of quinolones 5 with
aromatic dinucleophiles: o-phenylenediamine, o-aminophe-
nol, o-aminothiophenol were studied. It has been found that
quinolones 5b,c upon re¯uxingin alcohol with the double
excess of o-phenylenediamine and o-aminophenol afford the
correspondingquinolonylquinoxalones 7a,b and quinolo-
nylbenzoxazinones 8a,b ꢀScheme 2).
Thus, usingDMSO as the solvent promotes the selective
substitution of ¯uorine atom at position C-7 of the quino-
lones while boilingin pyridine leads to formation of 5,7-
disubstituted products.
In contrast to o-phenylenediamine and o-aminophenol, o-
aminothiophenol reacts with heterocycle 5c to form the
product 9 ꢀScheme 2). The structure of the latter is the
result of two parallel processes: the addition of one molecule
of o-aminothiophenol at the a-carbonyl and the nucleophilic
In conclusion, new 1-arylꢀalkyl)-3-ethoxalyl-5,6,7,8-
tetra¯uoroquinolin-4-ones prepared in the present work
have the reactivity of a-dicarbonyl compounds in interaction
with dinucleophiles giving quinoxalinone and benzoxazi-
none derivatives. Moreover, the aromatic nucleophilic

A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
189
Scheme 2.
substitution of ¯uorine atoms is also characteristic for these
heterocycles.
recorded on a Tesla BS-587A instrument ꢀ1H: 80 MHz,
usingTMS as internal standard, 19F: 75 MHz, usingC F6
6
as internal standard). Microanalyses were performed with a
Carlo Erba CHNS-O EA 1108 elemental analyzer.
3. Experimental details
3.1. Materials
Meltingpoints were measured in open capillaries and are
reported uncorrected. Infrared spectra were recorded on a
Specord 75 IR spectrometer. 1H- and 19F-NMR spectra were
The copper chelate of ethyl penta¯uorobenzoylpyruvate 1
was prepared by the method described previously [6].
Scheme 3.

190
A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
Scheme 4.
3.2. Synthesis of derivatives of 2-,1-alkyl,aryl)-4-oxo-
5,6,7,8-tetrafluoro-1,4-dihydroquinolon-3-yl)glyoxylic
acids
3.2.1.2. Compound 4d. Yield, 3.16 g, 32%; m.p. 1978C.
1H-NMR ꢀCDCl3, a mixture of Z and E isomers, ratio
1:1) d: 1.32, 1.35 ꢀ3H, 2t, 2CH3, JꢀHÀH† ˆ 7:0 Hz); 4.19,
4.30 ꢀ2H, 2q, 2CH2, JꢀHÀH† ˆ 7:0 Hz); 7.38 ꢀ1H, br.s, NH);
7.67, 7.76 ꢀ1H, 2d, =CH, JꢀHÀH† ˆ 14:1 Hz,); 9.97, 10.09
ꢀ1H, 2d, NH, JꢀHÀH† ˆ 13:8 Hz) ppm. 19F-NMR ꢀCDCl3, a
mixture of Z and E isomers, ratio 1:1) d: 0.04, 2.32 ꢀ2F, 2m);
8.42, 11.32 ꢀ1F, 2m); 18.56, 21.62 ꢀ2F, 2m) ppm. IR: 3380,
3255 ꢀNH); 1720 ꢀCO2Et); 1660 ꢀC=O); 1625 ꢀC6F5C=O);
1610 ꢀC=C) cmÀ1. Analysis: found: C, 46.44; H, 2.39; F,
28.31; N, 4.16. Calculated for C13H8F5NO4: C, 46.30; H,
2.39; F, 28.17; N, 4.15%.
3.2.1. Synthesis of ethyl-4-alkylamino-2-oxo-3-
pentafluorobenzoylbut-3-enoates ,4a,d,e) ,nc)
Anhydrous gaseous hydrogen chloride was passed
through a solution of chelate 1 ꢀ10 g, 29.3 mmol) in
100 ml of dry ether for 2 h. Ether was removed in vacuum
at 208C. Acetic anhydride ꢀ6.64 ml, 78.2 mmol) and triethy-
lorthoformate ꢀ7.32 ml, 43.8 mmol) were added. The reac-
tion mixture was re¯uxed for 2 h. Excess of reagents was
removed in vacuum. The residue was dissolved in 100 ml of
anhydrous ethanol. The correspondinggaseous amine was
passed through the solution for 10 min. The resulting pre-
cipitate was ®ltered and recrystallized from methanol to give
product 4.
1
3.2.1.3. Compound 4e. 1.85 g, 18%; m.p. 2248C. H-NMR
ꢀCDCl3, a mixture of Z and E isomers, ratio 1:1) d: 1.34 ꢀ3H,
br.t, 2CH3, JꢀHÀH† ˆ 7:3 Hz); 3.29 ꢀ3H, 2d, CH3, JꢀHÀH†
ˆ
5:2 Hz); 4.20, 4.27 ꢀ2H, 2q, 2CH2, JꢀHÀH† ˆ 7:3 Hz); 7.54
ꢀ0.5H, d.t, =CH, JꢀHÀH† ˆ 14:3, JꢀHÀF† ˆ 1:5 Hz, Z-isomer),
8.25 ꢀ0.5H, d, CH, JꢀHÀH† ˆ 14:3 Hz, E-isomer);10.75, 11.13
ꢀ1H, 2br.s, NH) ppm. 19F-NMR ꢀCDCl3, a mixture of Z and E
isomers, ratio1:1)d: 0.07, 2.16 ꢀ2F, 2m);7.97, 10.85ꢀ1F, 2m);
18.64,21.8ꢀ2F,2m)ppm.IR:3200ꢀNH);1735,1720ꢀCO2Et);
3.2.1.1. Compound 4a. Yield, 4.82 g, 45%; m.p. 158±1598C.
1H-NMR ꢀCDCl3, a mixture of Z and E isomers, ratio 1:1)
d: 1.26±1.55 ꢀ6H, m, CH3); 3.32±4.10 ꢀ2H, m, CH2); 4.23,
4.27 ꢀ2H, 2q, CH2); 7.61 ꢀ0.5H, d.t, =CH, JꢀHÀH† ˆ 13:8,
JꢀHÀF† ˆ 1:5 Hz, Z-isomer), 8.28 ꢀ0.5H, d, CH,
JꢀHÀH† ˆ 13:8 Hz, E-isomer); 10.86, 11.23 ꢀ1H, 2d, NH,
JꢀHÀH† ˆ 13:8 Hz) ppm. 19F-NMR ꢀCDCl3, a mixture of
Z and E isomers, ratio 1:1) d: 0.09, 2.12 ꢀ2F, 2m); 7.94,
10.84 ꢀ1F, 2m); 18.69, 21.84 ꢀ2F, 2m) ppm. IR: 3200 ꢀNH);
1730 ꢀCO2Et); 1650 ꢀC=O); 1620 ꢀC6F5C=O); 1590 ꢀC=C)
cmÀ1. Analysis: found: C, 49.21; H, 3.39; F, 25.99; N, 3.91.
Calculated for C15H12F5NO4: C, 49.31; H, 3.31; F, 26.00; N,
3.83%.
1660, 1650 ꢀC=O); 1610 ꢀC6F5C=O); 1595 ꢀC=C) cmÀ1
.
Analysis: found: C, 48.01; H, 2.81; F, 27.16; N, 3.89.
Calculated for C14H10F5NO4: C, 47.88; H, 2.87; F, 27.05;
N, 3.99%.
3.2.2. Synthesis of ethyl-4-alkyl,aryl)amino-2-
oxo-3-pentafluorobenzoylbut-3-enoates ,4b,c, f) ,nc)
Anhydrous gaseous hydrogen chloride was passed
through a solution of chelate 1 ꢀ10 g, 29.3 mmol) in

A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
191
100 ml of dry ether to brown color of the reaction mass.
Ether was removed in vacuum at 208C. Acetic anhydride
ꢀ6.64 ml, 78.2 mmol) and triethylorthoformate ꢀ7.32 ml,
43.8 mmol) were added. The reaction mixture was re¯uxed
for 2 h. Excess of reagents was removed in vacuum. The
residue was dissolved in 60 ml of anhydrous methanol. To
the solution, the correspondingamines ꢀ29.3 mmol) in 20 ml
of anhydrous methanol was added. The reaction mixture was
re¯uxed for 10 min. After cooling, the resulting precipitate
was ®ltered and recrystallized from methanol to give com-
pound 4.
3.2.3. Synthesis of 1-alkyl,aryl)-3-ethoxalyl-5,6,7,8-
tetrafluoro-1,4-dihydroquinolin-4-ones ,5a±f) ,nc)
To a solution of compound 4 ꢀ5.0 mmol) in 30 ml of dry
toluene, triethylamine ꢀ2.53 g, 15.0 mmol) was added. The
reaction mixture was re¯uxed for 15 min. After cooling, the
solution was washed with 5% HCl and water to pH ꢁ 7,
dried over MgSO4. The solvent was removed in vacuum.
The product 5 was obtained by recrystallization from metha-
nol.
3.2.3.1. Compound 5a. Yield, 1.57 g, 91%; m.p. 168±
1
1708C. H-NMR ꢀCDCl3) d: 1.39 ꢀ3H, t, CH3, JꢀHÀH†
ˆ
3.2.2.1. Compound 4b. Yield, 4.32 g, 39%; m.p. 1438C.
1H-NMR ꢀCDCl3, a mixture of Z and E isomers, ratio
1:1) d: 0.78±1.08 ꢀ4H, m, CH2); 1.34 ꢀ3H, t, CH3,
JꢀHÀH† ˆ 7:3 Hz); 2.86±3.25 ꢀ1H, m, CH); 4.24, 4.28
ꢀ2H, 2q, CH2, JꢀHÀH† ˆ 7:3 Hz); 7.68 ꢀ0.5H, d.t, =CH,
JꢀHÀH† ˆ 14:1, JꢀHÀF† ˆ 1:5 Hz, Z-isomer), 8.37 ꢀ0.5H, d,
CH, JꢀHÀH† ˆ 14:1 Hz, E-isomer); 10.84, 11.26 ꢀ1H, 2br.d,
NH, JꢀHÀH† ˆ 14:1 Hz) ppm. 19F-NMR ꢀCDCl3, a mixture
of Z and E isomers, ratio 1:1) d: 0.09, 2.21 ꢀ2F, 2m); 8.01,
11.13 ꢀ1F, 2m); 18.63, 21.87 ꢀ2F, 2m) ppm. IR: 3170 ꢀNH);
1730 ꢀCO2Et); 1650 ꢀC=O); 1610 ꢀC6F5C=O); 1590 ꢀC=C)
cmÀ1. Analysis: found: C, 51.15; H, 3.19; F, 25.09; N, 3.83.
Calculated for C16H12F5NO4: C, 50.94; H, 3.25; F, 25.18; N,
3.71%.
7:3 Hz); 1.57 ꢀ3H, d.t, CH3, JꢀHÀH† ˆ 7:0 Hz); 4.31±4.58
ꢀ2H, m, CH2); 8.28 ꢀ1H, s, =CH) ppm. 19F-NMR ꢀCDCl3) d:
2.67 ꢀ1F, m); 14.31 ꢀ2F, m); 20.45 ꢀ1F, m) ppm. IR: 3045
ꢀCH); 1735 ꢀCO2Et); 1660, 1640 ꢀC=O); 1610 ꢀC=C) cmÀ1
.
Analysis: found: C, 52.28; H, 3.06; F, 21.65; N, 3.94.
Calculated for C15H11F4NO4: C, 52.18; H, 3.21; F, 21.65;
N, 4.06%.
3.2.3.2. Compound 5b. Yield, 1.32 g, 74%; m.p. 209±2108C.
1H-NMRꢀCDCl3)d:0.78±0.93ꢀ7H,m,CH3,CH2);4.07±4.27
ꢀ1H, m, CH); 4.38 ꢀ2H, q, CH2, JꢀHÀH† ˆ 7:0 Hz); 8.44 ꢀ1H, s,
=CH) ppm. 19F-NMR ꢀCDCl3) d: 4.57 ꢀ1F, m); 15.61 ꢀ1F, m);
17.50 ꢀ1F, m); 22.44 ꢀ1F, m) ppm. IR: 3030 ꢀCH); 1730
ꢀCO2Et); 1665, 1635 ꢀC=O); 1605 ꢀC=C) cmÀ1. Analysis:
found: C, 53.81; H, 3.10; F, 21.40; N, 3.78. Calculated for
C16H11F4NO4: C, 53.79; H, 3.10; F, 21.27; N, 3.92%.
3.2.2.2. Compound 4c. Yield, 1.85 g, 18%; m.p. 2248C. 1H-
NMR ꢀCDCl3, a mixture of Z and E isomers, ratio 1:1) d:
1.36, 1.38 ꢀ3H, 2t, 2CH3, JꢀHÀH† ˆ 7:1 Hz); 2.42, 2.48 ꢀ3H,
2s, CH3); 4.26, 4.32 ꢀ2H, 2q, 2CH2, JꢀHÀH† ˆ 7:1 Hz); 7.03±
7.40 ꢀ4H, m, C6H4); 7.66 ꢀ0.5H, d.t, =CH, JꢀHÀH† ˆ 13:6,
JꢀHÀF† ˆ 1:5 Hz, Z-isomer), 8.46 ꢀ0.5H, d, CH,
JꢀHÀH† ˆ 13:6 Hz, E-isomer); 12.65, 13.51 ꢀ1H, 2br.d,
NH, JꢀHÀH† ˆ 13:6 Hz) ppm. 19F-NMR ꢀCDCl3, a mixture
of Z and E isomers, ratio 1:1) d: 0.36, 2.44 ꢀ2F, 2m); 8.77,
11.67 ꢀ1F, 2m); 19.41, 22.39 ꢀ2F, 2m) ppm. IR: 3380 ꢀNH);
1735 ꢀCO2Et); 1640 ꢀC=O); 1615 ꢀC6F5C=O); 1590 ꢀC=C)
cmÀ1. Analysis: found: C, 56.11; H, 3.07; F, 22.26; N, 3.39.
Calculated for C20H14F5NO4: C, 56.21; H, 3.30; F, 22.23; N,
3.28%.
3.2.3.3. Compound 5c. Yield, 1.53 g, 75%; m.p. 1978C. 1H-
NMR ꢀCDCl3) d: 1.31 ꢀ3H, t, CH3, JꢀHÀH† ˆ 7:4 Hz); 2.15
ꢀ3H, s, CH3); 4.34 ꢀ2H, q, CH2, JꢀHÀH† ˆ 7:4 Hz); 7.32±7.74
ꢀ4H, m, C6H4); 8.34 ꢀ1H, s, =CH) ppm. 19F-NMR ꢀCDCl3)
d: 6.34 ꢀ1F, m); 29.23±29.89 ꢀ2F, m); 40.74 ꢀ1F, m) ppm. IR:
3045 ꢀCH); 1740 ꢀCO2Et); 1650, 1640 ꢀC=O); 1600 ꢀC=C)
cmÀ1. Analysis: found: C, 58.75; H, 3.19; F, 18.75; N, 3.30.
Calculated for C20H13F4NO4: C, 58.98; H, 3.22; F, 18.66; N,
3.44%.
3.2.3.4. Compound 5d. Yield, 1.0 g, 63%; m.p. 1978C. 1H-
NMR ꢀCDCl3) d: 1.30 ꢀ3H, t, CH3, JꢀHÀH† ˆ 7:0 Hz); 4.31
ꢀ2H, q, CH2, JꢀHÀH† ˆ 7:0 Hz); 8.44 ꢀ1H, s, =CH); 13.24
ꢀ1H, br.s, NH) ppm. 19F-NMR ꢀCDCl3) d: 1.17 ꢀ1F, m); 9.27
ꢀ1F, m); 12.61 ꢀ1F, m); 19.63 ꢀ1F, m) ppm. IR: 3395 ꢀNH);
3060, 3040 ꢀCH); 1735 ꢀCO2Et); 1660, 1635 ꢀC=O); 1600
ꢀC=C) cmÀ1. Analysis: found: C, 49.35; H, 2.06; F, 23.84; N,
4.19. Calculated for C13H7F4NO4: C, 49.23; H, 2.22; F,
23.96; N, 4.42%.
3.2.2.3. Compound 4f. Yield, 4.57 g, 37%; m.p. 104±
1
1068C. H-NMR ꢀCDCl3, a mixture of Z and E isomers,
ratio 1:1) d: 0.85±1.00 ꢀ2H, m, CH2); 1.23±1.89 ꢀ9H, m,
CH3, CH2); 3.32±3.62 ꢀ2H, m, CH2); 4.25 ꢀ2H, 2q, 2CH2,
JꢀHÀH† ˆ 8:2 Hz); 7.55 ꢀ0.5H, d.t, =CH, JꢀHÀH† ˆ 13:3,
JꢀHÀF† ˆ 1:5 Hz, Z-isomer), 8.25 ꢀ0.5H, d, CH,
JꢀHÀH† ˆ 13:3 Hz, E-isomer); 10.87, 11.20 ꢀ1H, 2br.d,
NH, JꢀHÀH† ˆ 13:3 Hz) ppm. 19F-NMR ꢀCDCl3, a mixture
of Z and E isomers, ratio 1:1) d: 0.05, 2.08 ꢀ2F, 2m); 7.92,
10.81 ꢀ1F, 2m); 18.75, 21.88 ꢀ2F, 2m) ppm. IR: 3200 ꢀNH);
1740 ꢀCO2Et); 1650 ꢀC=O); 1610 ꢀC6F5C=O); 1600 ꢀC=C)
cmÀ1. Analysis: found: C, 54.13; H, 4.75; F, 22.67; N, 3.49.
Calculated for C19H20F5NO4: C, 54.16; H, 4.78; F, 22.54; N,
3.32%.
3.2.3.5. Compound 5e. Yield, 1.19 g, 75%; m.p. 173±
1758C. 1H-NMR ꢀCDCl3) d: 1.40 ꢀ3H, t, CH3,
JꢀHÀH† ˆ 7:0 Hz); 4.25 ꢀ3H, d, CH3); 4.44 ꢀ2H, q, CH2,
JꢀHÀH† ˆ 7:0 Hz); 8.21 ꢀ1H, s, =CH) ppm. 19F-NMR
ꢀCDCl3) d: 5.05 ꢀ1F, m); 13.53 ꢀ1F, m); 15.69 ꢀ1F, m);
23.24 ꢀ1F, m) ppm. IR: 3030 ꢀCH); 1725 ꢀCO2Et); 1665,
1635 ꢀC=O); 1605 ꢀC=C) cmÀ1. Analysis: found: C, 50.89;

192
A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
H, 2.91; F, 22.80; N, 4.48. Calculated for C14H9F4NO4: C,
50.77; H, 2.74; F, 22.94; N, 4.23%.
5 ml of methanol was added. The mixture was re¯uxed
for 2 h. The resultingprecipitate was ®ltered and washed
with methanol to give product 7a ꢀ0.37 g, 64%) as yellow
crystals ꢀm.p. 2558C). 1H-NMR ꢀDMSO-d6) d: 2.29 ꢀ3H, s,
CH3); 7.20±7.83 ꢀ8H, br.s, 2C6H4); 8.09 ꢀ1H, s, =CH); 12.43
ꢀ1H, s, NH) ppm. 19F-NMR ꢀDMSO-d6) d: À0.41 ꢀ1F, m);
11.73±12.96 ꢀ2F, m); 18.48±19.03 ꢀ1F, m) ppm. IR: 3320,
2780, 2720 ꢀNH); 3040 ꢀCH); 1670 ꢀCONH), 1635 ꢀC=O);
1610 ꢀC=N) cmÀ1. Analysis: found: C, 63.74; H, 2.86; F,
16.87; N, 9.27. Calculated for C24H13F4N3O2: C, 63.86; H,
2.90; F, 16.84; N, 9.31%.
1
3.2.3.6. Compound 5f. 1.71 g, 85%; m.p. 1758C. H-NMR
ꢀCDCl3) d: 0.82±1.05 ꢀ2H, m, CH2); 1.09±1.65 ꢀ9H, m, CH3,
2CH2); 1.75±2.02 ꢀ2H, m, CH2); 4.27±4.52 ꢀ2H, m, CH2);
8.25 ꢀ1H, s, =CH) ppm. 19F-NMR ꢀCDCl3) d: 4.37 ꢀ1F, m);
13.25 ꢀ1F, m); 15.69 ꢀ1F, m); 23.13 ꢀ1F, m) ppm. IR: 3050
ꢀCH); 1735 ꢀCO2Et); 1660, 1645 ꢀC=O); 1605 ꢀC=C) cmÀ1
.
Analysis: found: C, 56.92; H, 4.79; F, 18.84; N, 3.20.
Calculated for C19H19F4NO4: C, 56.86; H, 4.77; F, 18.93;
N, 3.49%.
3.3.2. 3-,1-Cyclopropyl-5,6,7,8-tetrafluoro-
1,4-dihydroquinolin-4-on-3-yl)-1,2-dihydroquinoxalin-
2-one ,7b) ,nc)
Similarly product 7b ꢀ0.29 g, 73%) was obtained from
compound 5b ꢀ0.22 g, 2.0 mmol) and o-phenylenediamine
3.2.4. Synthesis of 2-,1-alkkyl,aryl)-4-oxo-5,6,7,8-tetra-
fluoro-1,4-dihydroquinolin-3-yl)glyoxylic acids ,6a±c) ,nc)
A mixture of water ꢀ3.5 ml), acetic ꢀ4.6 ml) and conc.
sulfuric ꢀ0.6 ml) acids was added to compound 5 ꢀ0.69 g,
2.0 mmol). The solution was re¯uxed for 30 min. After
cooling, 10 ml of water was added. The resulting precipitate
was ®ltered and washed with methanol to give compound 6.
1
ꢀ0.22 g, 2.0 mmol) as yellow crystals ꢀm.p. >3008C). H-
NMR ꢀDMSO-d6) d: 1.12±1.19 ꢀ4H, m, CH2); 3.83±4.16
ꢀ1H, m, CH); 7.11±7.83 ꢀ4H, m, C6H4); 8.26 ꢀ1H, s, =CH);
12.41 ꢀ1H, br.s, NH) ppm. 19F-NMR ꢀDMSO-d6) d: À0.66
ꢀ1F, m); 11.33 ꢀ1F, m); 16.47 ꢀ1F, m); 18.38 ꢀ1F, m) ppm. IR:
3290, 3060, 2760, 2700 ꢀNH); 3045 ꢀCH); 1675 ꢀCONH);
1640 ꢀC=O); 1595 ꢀC=N) cmÀ1. Analysis: found: C, 59.85;
H, 2.78; F, 18.62; N, 10.32. Calculated for C20H11F4N3O2:
C, 59.86; H, 2.76; F, 18.94; N, 10.47%.
3.2.4.1. Compound 6. 0.46 g, 95%; m.p. 168±1708C.
1H-NMR ꢀCDCl3) d: 1.44 ꢀ3H, t, CH3, JꢀHÀH† ˆ 7:0 Hz);
1.29 ꢀ1H, s, OH); 4.51 ꢀ2H, q, CH2, JꢀHÀH† ˆ 7:0 Hz); 8.68
ꢀ1H, s, =CH) ppm. 19F-NMR ꢀCDCl3) d: 2.67 ꢀ1F, m);
13.85±14.77 ꢀ2F, m); 20.45 ꢀ1F, m) ppm. IR: 1735
ꢀCO2H); 1670, 1620 ꢀC=O); 1590 ꢀC=C) cmÀ1. Analysis:
found: C, 49.18; H, 2.05; F, 24.02; N, 4.23. Calculated for
C13H7F4NO4: C, 49.23; H, 2.22; F, 23.97; N, 4.41%.
3.3.3. 3-,1-,2-Methylphenyl)-5,6,7,8-tetrafluoro-
1,4-dihydroquinolin-4-on-3-yl)-1,2-dihydrobenzoxazin-
2-one ,8a) ,nc)
3.2.4.2. Compound 6b. 0.62 g, 94%; m.p. 2408C. 1H-NMR
ꢀCDCl3) d: 1.14±1.21 ꢀ4H, m, CH2); 1.29 ꢀ1H, s, OH);
2.94±3.12 ꢀ1H, m, CH); 8.50 ꢀ1H, s, =CH) ppm. 19F-NMR
ꢀCDCl3) d: 2.70 ꢀ1F, m); 13.85 ꢀ1F, m); 18.88±19.84 ꢀ2F, m)
ppm. IR: 1740 ꢀCO2H); 1680, 1620 ꢀC=O); 1590 ꢀC=C)
cmÀ1. Analysis: found: C, 51.21; H, 2.13; F, 23.17; N, 4.21.
Calculated for C14H7F4NO4: C, 51.08; H, 2.14; F, 23.08; N,
4.25%.
To a solution of compound 5c ꢀ0.41 g, 1.0 mmol) in 20 ml
of n-butanol, o-aminophenol ꢀ0.22 g, 2.0 mmol) in 20 ml of
n-butanol was added. The mixture was re¯uxed for 1 h.
After cooling, the reaction mixture was poured into water
ꢀ30 ml). The resultingwas ®ltered and recrystallized from n-
butanol to give product 8a ꢀ0.29 g, 82%) as yellow crystals
1
ꢀm.p. 2408C). H-NMR ꢀDMSO-d6) d: 2.19 ꢀ3H, s, CH3);
7.40±7.84 ꢀ8H, m, 2C6H4); 8.08 ꢀ1H, s, =CH) ppm. 19F-
NMR ꢀDMSO-d6) d: À0.41 ꢀ1F, m); 11.73±12.96 ꢀ2F, m);
18.48±19.03 ꢀ1F, m) ppm. IR: 3055 ꢀCH); 1765 ꢀCO2); 1645
ꢀC=O); 1610 ꢀC=N); 1590, 1580, 1520, 1510, 1500, 1490
ꢀC=C) cmÀ1. Analysis: found: C, 63.75; H, 2.69; F, 16.75; N,
6.21. Calculated for C24H12F4N2O3: C, 63.72; H, 2.69; F,
16.80; N, 6.19%.
3.2.4.3. Compound 6c. 0.71 g, 93%; m.p. 230±2328C.
1H-NMR ꢀCDCl3) d: 2.15 ꢀ3H, s, CH3); 4.07 ꢀ1H, br.s,
OH); 7.48 ꢀ4H, br.s, C6H4); 8.27 ꢀ1H, s, =CH) ppm.
19F-NMR ꢀCDCl3) d: 2.88 ꢀ1F, m); 14.61 ꢀ2F, m); 20.30
ꢀ1F, m) ppm. IR: 1710 ꢀCO2H); 1690, 1640 ꢀC=O); 1590
ꢀC=C) cmÀ1. Analysis: found: C, 57.22; H, 2.31; F, 19.89; N,
3.91. Calculated for C18H9F4NO4: C, 57.01; H, 2.39; F,
20.04; N, 3.69%.
3.3.4. 3-,1-Cyclopropyl-5,6,7,8-tetrafluoro-
1,4-dihydroquinolin-4-on-3-yl)-1,2-dihydrobenzoxazin-
2-one ,8b) ,nc)
3.3. Reactions of 1-alkyl,aryl)-3-ethoxycarbonyl-5,6,7,8-
tetrafluoro-1,4-dihydroquinolin-4-ones with dinucleophiles
Similarly, product 8b ꢀ0.33 g, 83%) was obtained from
compound 5b ꢀ0.36 g, 1.0 mmol) and o-aminophenol
ꢀ0.22 g, 2.0 mmol) for 10 h as yellow crystals ꢀm.p. 125±
1
3.3.1. 3-,1-,2-Methylphenyl)-5,6,7,8-tetrafluoro-1,4-
dihydroquinolin-4-on-3-yl)-1,2-dihydroquinoxalin-2-one
,7a) ,nc)
To a solution of compound 5c ꢀ0.41 g, 1.0 mmol) in 5 ml
of methanol, o-phenylenediamine ꢀ0.22 g, 2.0 mmol) in
1278C). H-NMR ꢀDMSO-d6) d: 1.13±1.30 ꢀ4H, m, CH2);
3.74±4.20 ꢀ1H, m, CH); 7.41±7.89 ꢀ4H, m, C6H4); 8.30 ꢀ1H,
s, =CH) ppm. 19F-NMR ꢀDMSO-d6) d: 0.18 ꢀ1F, m); 12.01
ꢀ1F, m); 17.07 ꢀ1F, m); 18.57 ꢀ1F, m) ppm. IR: 3040 ꢀCH);
1765 ꢀCO2); 1640 ꢀC=O); 1600 ꢀC=C) cmÀ1. Analysis:

A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
193
found: C, 59.47; H, 2.60; F, 18.44; N, 6.87. Calculated for
C20H10F4N2O3: C, 59.71; H, 59.71; F, 18.98; N, 6.96%.
The mixture was re¯uxed for 3 h. The solvent was removed
in vacuum. The residue was dissolved in 50 ml of chloro-
form and washed with 100 ml of 5% hydrochloric acid and
water to pH ˆ 7. Chloroform layer was separated and dried
over MgSO4. The solvent was removed in vacuum. The
residue was recrystallized from methanol to give product 11
ꢀ0.38 g, 75%) as yellow crystals ꢀm.p. 197±2008C). 1H-
NMR ꢀDMSO-d6) d: 1.33 ꢀ3H, t, CH3, JꢀHÀH† ˆ 7:1 Hz);
2.11 ꢀ3H, s, CH3); 2.96±3.81 ꢀ16H, m, 8CH2); 4.33 ꢀ2H, q,
CH2, JꢀHÀH† ˆ 7:1 Hz); 7.26±7.58 ꢀ4H, m, C6H4); 8.17 ꢀ1H,
s, =CH) ppm. 19F-NMR ꢀDMSO-d6) d: 29.57 ꢀ1F, s); 29.83
ꢀ1F, s) ppm. IR: 3050 ꢀCH); 1735 ꢀCO2Et); 1665, 1630
ꢀC=O); 1595 ꢀC=N, C=C) cmÀ1. Analysis: found: C, 62.18;
H, 5.36; F, 6.98; N, 7.79. Calculated for C28H29F2N3O6: C,
62.10; H, 5.40; F, 7.02; N, 7.76%.
3.3.5. Ethyl-2-,7-,2-aminophenylthio)-1-,2-methylphenyl)-
5,6,8-trifluoro-1,4-dihydroquinolin-4-on-3-yl)-
2-,2-mercaptophenylimino)glyoxylate ,9) ,nc)
To a solution of compound 5c ꢀ0.85 g, 2.1 mmol) in 20 ml
of methanol, o-aminothiophenol ꢀ0.674 ml, 6.3 mmol) was
added. The mixture was re¯uxed for 10 h. After cooling, the
reaction mass was poured into water ꢀ30 ml). The resulting
precipitate was ®ltered and recrystallized from n-butanol
to give product 9 ꢀ0.33 g, 82%) as yellow crystals ꢀm.p.
125±1278C). 1H-NMR ꢀDMSO-d6, a mixture of Z and
E isomers, ratio 1:1) d: 1.11, 1.13 ꢀ3H, 2t, OCH2CH3,
JꢀHÀH† ˆ 7:1 Hz); 1.88, 1.96 ꢀ3H, 2s, CH3); 4.10, 4.12
ꢀ2H, 2q, OCH2CH3, JꢀHÀH† ˆ 7:1 Hz); 5.28 ꢀ2H, br.s,
NH2); 6.40±7.41 ꢀ12H, m, 3C6H4,); 7.34 ꢀ1H, br.s, SH);
7.72, 7.74 ꢀ1H, 2s, CH) ppm. 19F-NMR ꢀDMSO-d6, a
mixture of Z and E isomers, ratio 1:1) d: 16.73, 17.02
ꢀ1F, 2d.d, F-5, Jꢀ5À8† ˆ 17:1 Hz; Jꢀ5À6† ˆ 22:0 Hz); 24.63,
24.66 ꢀ1F, 2d, F-6, Jꢀ6À5† ˆ 22:0 Hz, Jꢀ6À8† ˆ 0 Hz); 46.18,
46.47 ꢀ1F, 2d, F-8, Jꢀ8À5† ˆ 17:1 Hz; Jꢀ8À6† ˆ 0 Hz) ppm.
IR: 3450, 3340 ꢀNH); 3050 ꢀCH); 1740 ꢀCO2Et); 1630
ꢀC=O); 1610, 1580 ꢀC=N, C=C); 1590, 1580, 1520, 1510,
1500, 1490 ꢀC=C) cmÀ1. Analysis: found: C, 61.75; H, 3.80;
F, 9.05; N, 6.76. Calculated for C32H24F3N3O3S2: C, 62.02;
H, 3.90; F, 9.20; N, 6.19%.
3.4.3. 3-,1-,2-Methylphenyl)-7-,morpholin-1-yl)-5,6,8-
trifluoro-1,4-dihydroquinolin-4-on-3-yl)-
1,2-dihydroquinoxalin-2-one ,12) ,nc)
To a solution of compound 7a ꢀ0.45 g, 1.0 mmol) in 10 ml
of DMSO, a mixture of triethylamine ꢀ0.28 ml, 2.0 mmol)
and morpholine ꢀ0.09 g, 1.0 mmol) was added. The reaction
mixture was stored at 208C for 190 h, than poured into
100 ml of 5% hydrochloric acid. The resultingprecipitate
was ®ltered and washed with water. Recrystallization from
isopropyl alcohol gave product 12 ꢀ0.46 g, 88%) as yellow
1
crystals ꢀm.p. 328±3308C). H-NMR ꢀDMSO-d6) d: 2.21
ꢀ3H, s, CH3); 3.03±3.71 ꢀ8H, m, 4CH2); 7.21±7.64 ꢀ8H, m,
2C6H4); 7.75 ꢀ1H, s, =CH); 12.28 ꢀ1H, br.s, NH) ppm. 19F-
NMR ꢀDMSO-d6) d: 11.42 ꢀ1F, d, F-6, Jꢀ6À5† ˆ 18:8 Hz,
Jꢀ6À8† ˆ 0 Hz); 17.11 ꢀ1F, d.d, F-5, Jꢀ5À6† ˆ 18:8 Hz,
Jꢀ5À8† ˆ 13:3 Hz); 25.25 ꢀ1F, d, F-8, Jꢀ8À5† ˆ 13:3 Hz,
Jꢀ8À6† ˆ 0 Hz) ppm. IR: 3150 ꢀNH); 1685 ꢀCO2N); 1620
ꢀC=O); 1590 ꢀC=N, C=C); 1585 ꢀC=C) cmÀ1. Analysis:
found: C, 64.89; H, 4.05; F, 10.70; N, 10.89. Calculated for
C28H21F3N4O3: C, 64.86; H, 4.08; F, 10.99; N, 10.81%.
3.4. Reactions of 1-alkyl,aryl)-3-ethoxalyl,heteryl)-
5,6,7,8-tetrafluoro-1,4-dihydroquinolin-4-ones with
morpholine
3.4.1. 3-Ethoxalyl-1-,2-methylphenyl)-7-,morpholin-1-yl)-
5,6,8-trifluoro-1,4-dihydroquinolin-4-one ,10) ,nc)
To a solution of compound 5c ꢀ0.41 g, 1 mmol) in 30 ml
of dry DMSO, morpholine ꢀ0.43 g, 5.0 mmol) was added.
The mixture was stored at 208C for 96 h and than poured into
50 ml of 5% hydrochloric acid. The resultingprecipitate was
®ltered, washed with water and recrystallized from isopro-
pyl alcohol to give product 10 ꢀ0.31 g, 69%) as yellow
3.4.4. 6,8-Difluoro-3-,5,7-di,morpholin-1-yl)-
1-,2-methylphenyl)-1,4-dihydroquinolin-4-on-3-yl)-
1,2-dihydroquinoxalin-2-one ,13) ,nc)
1
crystals ꢀm.p. 226±2288C). H-NMR ꢀDMSO-d6) d: 1.31
To a solution of compound 7a ꢀ0.7 g, 1.6 mmol) in 20 ml
of dry pyridine, morpholine ꢀ1.37 ml, 10.0 mmol) was
added. The mixture was re¯uxed for 10 h. The solvent
was removed in vacuum. The residue was dissolved in
70 ml of chloroform. The chloroform layer was separated,
washed with 100 ml of 5% hydrochloric acid and water to
pH ˆ 7, dried under MgSO4. The solvent was removed. The
residue was recrystallized from isopropyl alcohol to give
product 13 ꢀ0.83 g, 89%) as yellow crystals ꢀm.p. 318±
ꢀ3H, t, CH3, JꢀHÀH† ˆ 7:1 Hz); 2.14 ꢀ3H, s, CH3); 3.03±3.85
ꢀ8H, m, CH2); 4.33 ꢀ2H, q, CH2, JꢀHÀH† ˆ 7:1 Hz); 7.26±
7.58 ꢀ4H, m, C6H4); 8.17 ꢀ1H, s, =CH) ppm. 19F-NMR
ꢀDMSO-d6) d: 14.74 ꢀ1F, d.d, F-6, Jꢀ6À5† ˆ 19:5 Hz,
Jꢀ6À8† ˆ 5:4 Hz); 18.24 ꢀ1F, d.d, F-5, Jꢀ5À6† ˆ 19:5 Hz,
Jꢀ5À8† ˆ 12:2 Hz); 26.92 ꢀ1F, d.d, F-8, Jꢀ8À5† ˆ 12:2 Hz,
Jꢀ8À6† ˆ 5:4 Hz) ppm. IR: 3045 ꢀCH); 1735 ꢀCO2Et);
1665, 1640 ꢀC=O); 1620 ꢀC=N); 1585 ꢀC=C) cmÀ1. Ana-
lysis: found: C, 60.79; H, 4.51; F, 12.12; N, 5.93. Calculated
for C24H21F3N2O5: C, 60.76; H, 4.46; F, 12.01; N, 5.91%.
1
3208C). H-NMR ꢀDMSO-d6) d: 2.22 ꢀ3H, s, CH3); 3.05±
3.71 ꢀ16H, m, 4CH2); 7.44±7.71 ꢀ8H, m, 2C6H4); 7.89 ꢀ1H,
s, =CH); 12.28 ꢀ1H, br.s, NH) ppm. 19F-NMR ꢀDMSO-d6) d:
29.76 ꢀ1F, s); 29.86 ꢀ1F, s) ppm. IR: 1660 ꢀCO2N); 1625
ꢀC=O); 1610, 1595 ꢀC=N, C=C) cmÀ1. Analysis: found: C,
65.33; H, 5.07; F, 6.42; N, 11.72. Calculated for
C32H29F2N5O4: C, 65.66; H, 4.99; F, 6.49; N, 11.96%.
3.4.2. 6,8-Difluoro-5,7-di,morpholin-1-yl)-3-ethoxalyl-1-
,2-methylphenyl)-1,4-dihydro-quinolin-4-one ,11) ,nc)
To a solution of compound 5c ꢀ0.41 g, 1.0 mmol) in 30 ml
of dry pyrydine, morpholine ꢀ0.43 g, 5.0 mmol) was added.

194
A.S. Fokin et al. / Journal of Fluorine Chemistry 108 ,2001) 187±194
[2] G.A. Mokrushina, S.G. Alekseev, V.N. Charushin, O.N. Chupakhin,
Acknowledgements
Zh. Vses. Khim. Obshch. im. D.I. Mendeleeva 36 ꢀ1991) 447 ꢀChem.
Abstr. 118 ꢀ1993) 233776c).
The authors wish to thank the Russian Foundation of
Fundamental Researches for ®nancial support of this work
ꢀgrant no. 00-03-32767a).
[3] D.B. Moran, C.B. Zeigler, T.S. Dunne, N.A. Kuck, Yang-i Lin, J. Med.
Chem. 32 ꢀ1989) 1313.
[4] N. Ishikawe ꢀEd.), Compounds of Fluorine: Synthesis and Application,
Mir, Moscow, 1990, p. 407.
[5] V.I. Saloutin, Z.E. Skryabina, I.T. Bazyl0, P.N. Kondrat0ev, O.N.
Chupakhin, J. Fluor. Chem. 69 ꢀ1994) 126.
[6] V.I. Saloutin, I.T. Bazyl0, Z.E. Skryabina, O.N. Chupakhin, Russ.
Chem. Bull. 42 ꢀ1993) 858.
References
[1] V.T. Andriole ꢀEd.), The Quinolones, Academic Press, New York,
1988.