1,2,4-Triazino[5,6,1-i,j]quinolines: a new type of tricyclic analogs of fluoroquinolones

Article abstract of DOI:10.1023/A:1015872302756

The interaction of C-aryl-substituted amidrazones and S-methylisothiosemicarbazide with 3-ethoxy-2-polyfluorobenzoylacrylates results in corresponding N-(quinolin-1-yl)amidines that undergo conversion into derivatives of 1,2,4-triazino[5,6,1-i,j]quinoline by heating in acetic anhydride.

Full text of DOI:10.1023/A:1015872302756

Russian Chemical Bulletin, International Edition, Vol. 51, No. 4, pp. 663—667, April, 2002
663
1,2,4ꢀTriazino[5,6,1ꢀi,j]quinolines:
a new type of tricyclic analogs of fluoroquinolones
G. N. Lipunova, E. V. Nosova, N. N. Mochul´skaya, A. A. Andreiko, O. M. Chasovskikh, and V. N. Charushinꢀ
Ural State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458. Eꢀmail: charushin@prm.uran.ru
The interaction of Cꢀarylꢀsubstituted amidrazones and Sꢀmethylisothiosemicarbazide with
3ꢀethoxyꢀ2ꢀpolyfluorobenzoylacrylates results in corresponding Nꢀ(quinolinꢀ1ꢀyl)amidines
that undergo conversion into derivatives of 1,2,4ꢀtriazino[5,6,1ꢀi,j]quinoline by heating in
acetic anhydride.
Key words: Cꢀarylꢀsubstituted amidrazones, Sꢀmethylisothiosemicarbazide, Nꢀ(quinolinꢀ
1ꢀyl)amidines, 1,2,4ꢀtriazino[5,6,1ꢀi,j]quinolines.
Recently, polycyclic derivatives of 6ꢀfluoroꢀ4ꢀoxoꢀ
1,4ꢀdihydroquinolineꢀ3ꢀcarboxylic acid (the soꢀcalled
"fluoroquinolones") have been the subject of increasing
interest because they exhibit not only high antibacterial,
but also antiviral, antitumor, and other types of acꢀ
tivity.1 Previously,2,3 we have reported the synthesis of
1,3,4ꢀthia(oxa)diazino[6,5,4ꢀi,j]quinolones from derivaꢀ
tives of 2ꢀpolyfluorobenzoylacrylic acid and (thio)semiꢀ
carbazides. This work concerns the annelation of the
1,2,4ꢀtriazine ring to the quinolone skeleton.
For this purpose, we studied the interaction
of 3ꢀethoxyꢀ2ꢀpolyfluorobenzoylacrylates (1a,b) with
Cꢀarylꢀsubstituted amidrazones 2a—c (Scheme 1). The
reactions of benzamidrazone (2a) and pꢀnitrobenzamidrꢀ
azone (2c) with acrylates 1a,b in ethanol at room temꢀ
perature resulted in the corresponding Nꢀsubstituted benzꢀ
amidrazones 3a,b,d. The interaction of 1a with pꢀmethꢀ
oxybenzamidrazone 2b under the same conditions gave a
mixture of acrylate 3c with compound 4c (a product of
spontaneous cyclization of 3c) in a 1 : 2 ratio (according
to 1H NMR data). To complete the cyclization of 3c
into 4c and to convert acrylates 3a—d into Nꢀ(quinolinꢀ
1ꢀyl)carbamidines 4a—d (in 82 to 89% yields), heating
in toluene under reflux for 2 to 3 h is required.
signal of the H(5) proton (eight lines with a ddd patꢀ
tern) in the interval δ 7.9—8.1 is also observed in the
1H NMR spectra of derivatives 4a,c—e (Table 1).
We failed to perform cyclization of compounds 4a—e
into their tricyclic analogs 5a—e by refluxing in toluene
(in the presence of potassium carbonate) or in acetoniꢀ
trile (in the presence of KF or DBU), i.e., under the
conditions we used previously for the synthesis of polyꢀ
cyclic fluoroquinolones.2—5 However, heating of comꢀ
pounds 4a,b,d,e in acetic anhydride was found to be a
useful procedure for the synthesis of tricyclic quinolones
5a,b,d,e. Treatment of compound 4c in the same manꢀ
ner leads to its transformation into N,Nꢀdiacetyl derivaꢀ
tive of aminoquinolone 8 accompanied by destruction of
the amidrazone fragment.
The structure of fused 1,2,4ꢀtriazino[5,6,1ꢀi,j]quinoꢀ
lines 5a,b,d,e was confirmed by 1H and
19F NMR spectroscopy data and by mass spectra (see
Tables 3 and 4). The 1H NMR spectra exhibit a signal of
only one NH group in the region δ 10.4—11.0. The multiꢀ
plicity of the signal of H(8) proton in the 1H NMR spectra
of derivatives 5a,d,e (X = H) is reduced to a dd patꢀ
tern observed in the region δ 7.2—7.3 (Table 3). The
19F NMR spectra of compounds 5a,d,e exhibit characꢀ
teristic dd patterns for F(9) and F(10) in the regions
δ 136.0—137.0 and 152.0—153.5, respectively (Table 4).
The possibility of the synthesis of close structural
analogs of the known fluoroquinolone antibacterial
agents6—8 can be illustrated taking acid hydrolysis of the
ester group of compound 5a and replacement of the
F(10) atom in carboxylic acid 6a by the pyrrolidine resiꢀ
due (compound 7a) as examples. The structures of deꢀ
rivatives 6a and 7a were confirmed by spectral data (see
Tables 3 and 4).
Compound 4e was synthesized by the reaction of
Sꢀmethylisothiosemicarbazide (2d) with 3ꢀethoxyꢀ2ꢀtetraꢀ
fluorobenzoylacrylate (1a) in toluene without isolation
of intermediate acrylate 3e. The structures of quinolones
4a—e were confirmed by 1H and 19F NMR spectroscopy
and by mass spectra (see Tables 1 and 2). In addition to
the signal of the αꢀproton, H(2), of the pyridine ring (a
1
singlet in the region δ 8.1—8.4) the H NMR spectra of
compounds 4a—e exhibit a broadened singlet from two
NH groups in the region δ 7.5—7.9. A characteristic
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 613—616, April, 2002.
1066ꢀ5285/02/5104ꢀ663 $27.00 © 2002 Plenum Publishing Corporation

664
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Lipunova et al.
Scheme 1
1: X = H (a), F (b);
2: R = Ph (a), 4ꢀMeOC6H4 (b),
4ꢀNO2C6H4 (c), SMe (d);
3—5: X = H (a, c—e), F (b);
R = Ph (a, b), 4ꢀMeOC6H4 (c),
NO2C6H4 (d), SMe (e)
Thus, we have first synthesized new fluorinated deꢀ
Experimental
rivatives of 1,2,4ꢀtriazino[5,6,1ꢀi,j]quinoline, that is,
compounds 5—7, which represent a novel class of fused
fluoroquinolones.
NMR Spectra were recorded on a Bruker WMꢀ250 specꢀ
trometer (250 MHz for 1H) and on a Bruker DRXꢀ400 specꢀ
1
Table 1. H NMR spectral parameters of compounds 4a—e (DMSOꢀd6)
Comꢀ
pound
δ, J/Hz
H(2) (s)
H(5) (ddd)
R
NH
(br.s, 2 H)
Me
(t)
OCH2
(q)
4a
4b
4c
4d
4e
8.18
8.17
8.23
8.34
8.13
8.02 (3J = 10.3,
7.51 (m, 3 H, H(3´), H(4´), H(5´));
7.92 (m, 2 H, H(2´), H(6´))
7.5
7.7
7.5
7.9
7.6
1.32
1.27
1.27
1.28
1.28
4.23
4.21
4.22
4.23
4.21
4J = 8.3, 5J = 1.5)
—
7.54 (m, 3 H, H(3´), H(4´), H(5´));
7.89 (m, 2 H, H(2´), H(6´))
8.01 (3J = 10.8,
4J = 8.1, 5J = 1.5)
3.84 (s, 3 H, OMe); 7.06 (d, 2 H, H(3´), H(5´),
3J = 8.9); 7.89 (d, 2 H, H(2´), H(6´), 3J = 8.9)
8.01 (3J = 10.6,
4J = 8.1, 5J = 1.5)
8.16 (d, 2 H, H(2´), H(6´), J = 8.8);
3
8.38 (d, 2 H, H(3´), H(5´), 3J = 8.8)
7.92 (3J = 10.5,
4J = 8.4, 5J = 1.5)
2.47 (s, 3 Н, SMe)

1,2,4ꢀTriazino[5,6,1ꢀi,j]quinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
665
Table 2. 19F NMR spectral parameters (DMSOꢀd6) and mass spectra of compounds 4a—e
Comꢀ
pound
δ , J/Hz
Mass spectrum, m/z (Irel (%))
F
F(5)
F(6) (ddd)
F(7)
F(8)
4a
4b
4c
4d
4e
—
138.55 (3JF,F = 22.8,
3JF,H = 10.3,
154.04 (ddd,
3JF,F = 18.5,
3JF,F = 22.8,
4JF,H = 8.3)
145.65 (dd,
3JF,F = 18.5,
4JF,F = 3.8)
389 [M]+ (36), 369 (24), 341 (38),
317 (78), 297 (100), 199 (36), 119 (42),
104 (30), 77 (65)
4JF,F = 3.8)
153.25 (dd,
3JF,F = 21.6,
4JF,F = 13.5)
151.22 (3JF,F = 22.2,
3JF,F = 21.6,
4JF,F = 15.7)
163.05 (dd,
3JF,F = 22.2,
3JF,F = 21.6)
144.74 (ddd,
3JF,F = 21.0,
4JF,F = 13.5,
5JF,F = 6.9)
409 [M]+ (47), 387 (9), 359 (14),
335 (79), 334 (44), 320 (69), 77 (100)
—
—
—
138.22 (3JF,F = 23.5,
3JF,H = 10.9,
4JF,F = 3.9)
153.74 (ddd,
3JF,F = 19.3,
3JF,F = 23.5,
4JF,H = 8.1)
145.82 (dd,
3JF,F = 19.3,
4JF,F = 3.9)
419 [M]+ (49), 347(16), 226(14),
199(17), 150(16), 149(100), 134(34),
133(28), 92(18), 77(29)
137.96 (3JF,F = 23.3,
3JF,Н = 10.6,
4JF,F = 3.5)
153.37 (ddd,
3JF,F = 23.2,
3JF,F = 19.1,
4JF,Н = 8.1)
146.41 (dd,
3JF,F = 19.1,
4JF,F = 3.5)
138.05 (3JF,F = 23.4,
3JF,H = 10.5,
4JF,F = 3.8)
153.47 (ddd,
3JF,F = 19.5,
3JF,F = 23.4,
4JF,H = 8.4)
146.14 (dd,
3JF,F = 19.5,
4JF,F = 3.8)
359 [M]+ (49), 287(34), 271(14),
199(62), 169(16), 89(99), 88(36)
1
Table 3. H NMR spectral parameters of compounds 5a,b,d,e, 6a, and 7a (DMSOꢀd6)
Comꢀ
pound
δ, J/Hz
H(5)
(s)
H(8)
R
R(10)
—
NH
(br.s, 1 Н)
COOEt
COOH
(br.s)
5a
8.28
7.25 (dd,
3J = 10.7,
4J = 7.5)
7.59 (m, 3 H, H(3´), H(4´), H(5´)),
7.83 (m, 2 H, H(2´), H(6´))
10.6
1.26 (t, 3 H, Me),
4.18 (q, 2 H, OCH2)
—
5b
5d
8.22
8.30
7.52 (m, 3 H, H(3´), H(4´), H(5´)),
7.83 (m, 2 H, H(2´), H(6´))
8.09 (d, 2 H, H(2´), H(6´), 3J = 8.8),
8.35 (d, 2 H, H(3´), H(5´), 3J = 8.8)
—
—
10.4
10.4
1.26 (t, 3 H, Me),
4.18 (q, 2 H, OCH2)
—
—
7.26 (dd,
3J = 10.7,
4J = 8.1)
1.27 (t, 3 H, Me),
4.18 (q, 2 H, OCH2)
5e
6a
7a
8.22
8.45
8.15
7.23 (dd,
3J = 11.0,
4J = 8.2)
2.4 (s, 3 H, SMe)
—
—
11.0
11.1
1.26 (t, 3 H, Me),
4.19 (q, 2 H, OCH2)
—
7.43 (dd,
3J = 10.7,
4J = 7.6)
7.58 (m, 3 H, H(3´), H(4´), H(5´)),
7.89 (m, 2 H, H(2´), H(6´))
—
—
14.9
15.8
6.46 (d,
3J = 10.5)
7.54 (m, 3 H, H(3´), H(4´), H(5´)), 1.92 (m, 4 Н, 10.6
7.89 (m, 2 H, H(2´), H(6´)) (CH2)2)
trometer (376 MHz for 19F). The internal standards were
tetramethylsilane (for 1H) and hexafluorobenzene (for 19F).
Mass spectra were obtained on a Varian MAT 311A instrument
equipped with a direct inlet system at an accelerating voltage of
3 kV, a cathode emission current of 300 µA, and an ionizing
electron energy of 70 eV.
The starting benzamidrazones were synthesized from corꢀ
responding imidate hydrochlorides following the known proceꢀ
dure.9
Ethyl 3ꢀ(4ꢀRꢀbenzimidoylhydrazino)ꢀ2ꢀ(polyfluorobenzoꢀ
yl)acrylates (3a,b,d). To 1 g (5.6 mmol) of pꢀnitrobenzꢀ
amidrazone 2c in ethanol (15 mL), 3ꢀethoxyꢀ2ꢀtetrafluoroꢀ

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Lipunova et al.
Table 4. 19F NMR spectral parameters (DMSOꢀd6) and mass spectra of compounds 5a,d,e, 6a, and 7a
Comꢀ
pound
δ , J/Hz
Mass spectrum, m/z (Irel (%))
F
F(9)
F(10) (dd)
5a
5d
136.38 (dd, 3JF,F = 21.8, 3JH,F = 10.9)
136.12 (dd, 3JF,F = 22.0, 3JF,Н = 10.9)
152.12 (3JF,F = 21.8, 4JF,H = 6.6) 369 [M]+ (43), 324(19), 298(20), 297(100)
152.02 (3JF,F = 22.0, 4JF,Н = 7.5) 414 [M]+ (94), 369(33), 367(78), 343(19),
342(100), 323(13), 322(11), 296(42),
295(13), 284(33), 266(18), 238(21), 136(21)
5e
6a
136.57 (dd, 3JF,F = 22.1, 3JF,Н = 11.0)
133.85 (dd, 3JF,F = 21.7, 3JH,F = 10.7)
153.43 (3JF,F = 22.1, 4JF,Н = 7.8)
150.15 (3JF,F = 21.7, 4JF,H = 6.5) 341 [M]+ (37), 298(20), 297(100), 296(27),
104(15), 77(17), 53(14)
7a
140.92 (d, 3JH,F = 10.5)
392 [M]+ (100), 348(60), 279(17), 245(45),
196(14)
benzoylacrylate 1a (1.8 g, 5.6 mmol) was added. The reaction
mass was stirred for 2 h at room temperature, the bright yellow
precipitate of compound 3d was filtered off and recrystallized
from ethanol. The yield was 2.1 g (84%), m.p. 158—160 °C.
1H NMR (DMSOꢀd6, δ, J/Hz): 1.14 (t, 3 H, OCH2CH3); 4.03
(q, 2 H, OCH2CH3); 7.15 (m, 1 H, H(6″)); 7.35 (br.s, 2 H,
NH); 8.14 (d, 2 H, H(2´), H(6´), J = 8.8); 8.26 (d, 2 H, H(3´),
H(5´), J = 8.8); 8.39 (s, 1 H, H(3)); 12.8 (br.s, 1 H, NH).
Found (%): C, 50.53; H, 3.08; N, 12.40. C19H14F4N4O5. Calꢀ
culated (%): C, 50.22; H, 3.08; N, 12.33.
precipitate was filtered off, anhydrous toluene (15 mL) was
added, and the mixture was refluxed for 4 h. After cooling the
solution, the colorless precipitate of compound 4c was filtered
off and recrystallized from DMSO. The yield was 2.0 g (79%),
m.p. 220—222 °C. Found (%): C, 57.06; H, 4.40; N, 9.60.
C20H16F3N3O4. Calculated (%): C, 57.23; H, 3.82; N, 10.02.
C. To Sꢀmethylisothiosemicarbazide hydroiodide, 2d•HI,
(0.85 g, 3.6 mmol) in anhydrous toluene (15 mL), pyridine
(0.6 mL, 7.2 mmol) and 3ꢀethoxyacrylate 1a (1.2 g, 3.6 mmol)
was added. The reaction mass was kept for 30 min at ∼20 °C
and then refluxed for 3 h. After cooling, the colorless precipiꢀ
tate of compound 4e was filtered off, washed with ethanol, and
recrystallized from DMSO. The yield was 0.95 g (73%),
m.p. 239—241 °C. Found (%): C, 46.86; H, 3.31; N, 11.59.
C14H12F3N3O3S. Calculated (%): C, 46.75; H, 3.34; N, 11.69.
Ethyl 2ꢀRꢀ8ꢀXꢀ9,10ꢀdifluoroꢀ7ꢀoxoꢀ1,7ꢀdihydroꢀ1,2,4ꢀ
triazino[5,6,1ꢀi,j]quinolineꢀ6ꢀcarboxylates (5a,b,d,e). A soluꢀ
tion of compound 4a (0.3 g, 0.8 mmol) in acetic anhydride
(6 mL) was refluxed for 2 h. After cooling, the lightꢀyellow
precipitate of compound 5a was filtered off and recrystallized
from DMSO. The yield was 0.2 g (68%), m.p. >250 °C.
Found (%): C, 61.79; H, 3.51; N, 11.34. C19H13F2N3O3. Calꢀ
culated (%): C, 61.79; H, 3.55; N, 11.38.
Compounds 5b,d were synthesized analogously. To obtain
the tricyclic derivative 5e, a solution of quinolone 4e in acetic
anhydride was kept at 110 °C for 10 h.
Compound 5b, yield 62%, m.p. 223—225 °C. Found (%):
C, 59.23; H, 3.32; N, 10.61. C19H12F3N3O3. Calculated (%):
C, 58.91; H, 3.10; N, 10.88.
Compound 5d, yield 81%, m.p. >250 °C. Found (%): C,
54.92; H, 2.76; N, 13.21. C19H12F2N4O5. Calculated (%): C,
55.04; H, 2.90; N, 13.52.
Compound 5e, yield 76%, m.p. 245—247 °C. Found (%):
C, 49.15; H, 3.47; N, 11.96. C14H11F2N3O3S. Calculated (%):
C, 49.56; H, 3.24; N, 12.39.
Compounds 3a,b were synthesized analogously.
Compound 3a, yield 63%, m.p. 138—140 °C.
1H NMR (DMSOꢀd6, δ): 1.13 (t, 3 H, OCH2CH3); 4.01 (q,
2 H, OCH2CH3); 7.01 (m, 1 H, H(6″)); 7.12 (br.s, 2 H, NH);
7.43 (m, 3 H, H(3´), H(4´), H(5´)); 7.86 (m, 2 H, H(2´),
H(6´)); 8.37 (s, 1 H, H(3)); 12.9 (br.s, 1 H, NH). Found (%):
C, 55.40; H, 3.57; N, 10.17. C19H15F4N3O3. Calculated (%):
C, 55.75; H, 3.69; N, 10.27.
Compound 3b, yield 65%, m.p. 104—106 °C.
1H NMR (DMSOꢀd6, δ, J/Hz): 1.15 (t, 3 H, OCH2CH3); 4.03
(q, 2 H, OCH2CH3); 7.16 (br.s, 2 H, NH); 7.44 (m, 3 H,
H(3´), H(4´), H(5´)); 7.87 (m, 2 H, H(2´), H(6´)); 8.37 (d,
1 H, H(3), J = 11.6); 13.0 (br.d, 1 H, NH, J = 11.6). Found (%):
C, 53.68; H, 3.26; N, 9.62. C19H14F5N3O3. Calculated (%):
C, 53.40; H, 3.30; N, 9.83.
5ꢀXꢀ1ꢀ(4ꢀRꢀBenzimidoylamino)ꢀ3ꢀethoxycarbonylꢀ6,7,8ꢀ
trifluoroꢀ4ꢀoxoꢀ1,4ꢀdihydroquinolines (4a—e). A. A solution of
acrylate 3a (0.4 g, 0.98 mmol) in anhydrous toluene (10 mL)
was refluxed for 2 h. After cooling the reaction mass, the colorꢀ
less precipitate of compound 4a was filtered off and recrysꢀ
tallized from DMSO. The yield was 0.32 g (89%), m.p.
252—254 °C. Found (%): C, 61.75; H, 3.56; N, 11.57.
C19H14F3N3O3. Calculated (%): C, 61.79; H, 3.55; N, 11.38.
Compounds 4b,d were synthesized analogously
Compound 4b, yield 82%, m.p. 238—240 °C. Found (%):
C, 55.96; H, 3.07; N, 10.03. C19H13F4N3O3. Calculated (%):
C, 56.03; H, 3.22; N, 10.32.
Compound 4d, yield 89%, m.p. 226—228 °C. Found (%):
C, 52.69; H, 3.45; N, 12.60. C19H13F3N4O5. Calculated (%):
C, 52.53; H, 3.00; N, 12.90.
B. To pꢀmethoxybenzamidrazone 2b (1 g, 6.1 mmol) in
ethanol (15 mL), 3ꢀethoxyacrylate 1a (1.9 g, 6.1 mmol) was
added. The reaction mass was stirred for 3 h at ∼20 °C. The
9,10ꢀDifluoroꢀ7ꢀoxoꢀ2ꢀphenylꢀ1,7ꢀdihydroꢀ1,2,4ꢀtriaziꢀ
no[5,6,1ꢀi,j]quinolineꢀ6ꢀcarboxylic acid (6a). A solution of esꢀ
ter 5a (0.5 g, 1.4 mmol) in 15 mL of HCl—AcOH (1 : 4) mixꢀ
ture was refluxed for 3 h. After cooling, water (25 mL) was
added to the reaction mass and the precipitate was filtered off
and recrystallized from DMSO. The yield was 0.35 g (76%),
m.p. >250 °C. Found (%): C, 59.82; H, 2.70; N, 12.17.
C17H9F2N3O3. Calculated (%): C, 59.82; H, 2.64; N, 12.32.

1,2,4ꢀTriazino[5,6,1ꢀi,j]quinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
667
9ꢀFluoroꢀ7ꢀoxoꢀ2ꢀphenylꢀ10ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ1,7ꢀdihydroꢀ
1,2,4ꢀtriazino[5,6,1ꢀi,j]quinolineꢀ6ꢀcarboxylic acid (7a). To
compound 6a (0.2 g, 0.6 mmol) in anhydrous pyridine (5 mL),
pyrrolidine (0.3 g, 4.2 mmol) was added, and the reaction mass
was refluxed for 6 h. After cooling, the precipitate was filtered
off, 2 M HCl (1.5 mL) and ethanol (1.5 mL) was added, and
the mixture was stirred for 2 h at ∼20 °C. The precipitate of
compound 7a was filtered off and recrystallized from DMSO.
The yield was 0.15 g (64%), m.p. >250 °C. Found (%): C, 64.02;
H, 4.25; N, 13.98. C21H17FN4O3. Calculated (%): C, 64.28;
H, 4.37; N, 14.28.
Ethyl 1ꢀ(N,Nꢀdiacetylamino)ꢀ6,7,8ꢀtrifluoroꢀ4ꢀoxoꢀ1,4ꢀ
dihydroquinolineꢀ3ꢀcarboxylate (8). A solution of compound 4c
(1.2 g, 2.9 mmol) in acetic anhydride (15 mL) was refluxed for
2.5 h. The reaction mass was cooled and concentrated, and
ethanol (10 mL) was added to the residue. The colorless preꢀ
cipitate was filtered off and recrystallized from ethanol. The
yield was 0.8 g (73%), m.p. 180—182 °C. 1H NMR (DMSOꢀd6,
δ, J/Hz): 1.30 (t, 3 H, OCH2CH3); 2.43 (s, 6 H, 2 COCH3);
4.26 (q, 2 H, OCH2CH3); 8.04 (ddd, 1 H, H(5), J = 10.3, 8.2,
1.5); 8.92 (s, 1 H, H(2)). Mass spectrum (m/z, Irel (%)):
370 [M]+ (5), 328 (69), 313 (10), 283 (13), 282 (19), 267 (20),
263 (11), 257 (13), 256 (100), 225 (15), 214 (17). Found (%):
C, 51.41; H, 3.71; N, 7.46. C16H13F3N2O5. Calculated (%):
C, 51.85; H, 3.51; N, 7.56.
References
1. G. A. Mokrushina, E. V. Nosova, G. N. Lipunova, and
V. N. Charushin, Zh. Org. Khim., 1999, 35, 1447 [Russ. J. Org.
Chem., 1999, 35 (Engl. Transl.)].
2. G. N. Lipunova, E. V. Nosova, V. N. Charushin, L. P.
Sidorova, and O. M. Chasovskikh, Mendeleev Commun.,
1998, 131.
3. G. N. Lipunova, L. P. Sidorova, E. V. Nosova, N. M. Perova,
V. N. Charushin, and G. G. Aleksandrov, Zh. Org. Khim.,
1999, 35, 1729 [Russ. J. Org. Chem., 1999, 35 (Engl. Transl.)].
4. G. N. Lipunova, G. A. Mokrushina, E. V. Nosova, L. I.
Rusinova, and V. N. Charushin, Mendeleev Commun.,
1997, 109.
5. E. V. Nosova, G. N. Lipunova, G. A. Mokrushina, O. M.
Chasovskikh, L. I. Rusinova, V. N. Charushin, and G. G.
Aleksandrov, Zh. Org. Khim., 1998, 34, 436 [Russ. J. Org.
Chem., 1988, 34 (Engl. Transl.)].
6. U. Petersen, S. Bartel, K.ꢀD. Bremm, T. Himmler, A. Krebs,
and T. Schenke, Bull. Soc. Chim. Belg., 1996, 105, 683.
7. M. P. Wentland in The New Generation of Quinolones,
Eds. C. Siporin, C. L. Heifetz, and J. M. Domagala, Marcel
Dekker, London, 1990, 1.
8. L. L. Shen, in Quinolone Antibacterial Agents, Eds D. C.
Hooper and J. S. Wolfson, American Society for Microbiolꢀ
ogy, Washington, 1993, 77.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 00ꢀ03ꢀ
32785a, the RFBRꢀUral Project No. 01ꢀ03ꢀ96427) and
by the U.S. Civilian Research and Development Founꢀ
dation (CRDF) (Grant RECꢀ005).
9. M. O´Rourke, S. A. Lang, Jr., and E. Cohen, J. Med. Chem.,
1977, 20, 723.
Received October 8, 2001;
in revised form January 11, 2002