Fluorinated benzimidazo[1,2-a]quinolones

Article abstract of DOI:10.1023/A:1023487622561

The reactions of 2-cyanomethylbenzimidazole with polyfluorobenzoyl chlorides afforded 2-(1,3-dihydrobenzimidazol-2-ylidene)-3-oxo-3- polyfluorophenylpropionitriles. Refluxing of the latter compounds hi acetonitrile in the presence of DBU or in dimethylformamide in the presence of amines gave rise to fluorine-containing derivatives of benzimidazo[1,2-a] quinolone.

Full text of DOI:10.1023/A:1023487622561

Russian Chemical Bulletin, International Edition, Vol. 52, No. 2, pp. 457—460, February, 2003
457
Fluorinated benzimidazo[1,2ꢀa]quinolones*
ꢀ
G. N. Lipunova, E. V. Nosova, P. V. Vasil´eva, and V. N. Charushin
Urals State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458. Eꢀmail: charushin@prm.uran.ru
The reactions of 2ꢀcyanomethylbenzimidazole with polyfluorobenzoyl chlorides afforded
2ꢀ(1,3ꢀdihydrobenzimidazolꢀ2ꢀylidene)ꢀ3ꢀoxoꢀ3ꢀpolyfluorophenylpropionitriles. Refluxing of
the latter compounds in acetonitrile in the presence of DBU or in dimethylformamide in the
presence of amines gave rise to fluorineꢀcontaining derivatives of benzimidazo[1,2ꢀa]quinolone.
Key words: 2ꢀcyanomethylbenzimidazole, polyfluorobenzoyl chlorides, 2ꢀ(1,3ꢀdihydroꢀ
benzimidazolꢀ2ꢀylidene)ꢀ3ꢀoxoꢀ3ꢀpolyfluorophenylpropionitriles, benzimidazo[1,2ꢀa]quinoꢀ
lones.
1
[a]ꢀAnnelated derivatives of fluoroquinolonecarbꢀ
oxylic acids are of considerable interest.1 In particular,
benzothia(oxa)zolo[3,2ꢀa]quinolones possessing high anꢀ
tibacterial activity were prepared by condensation of ethyl
2,4ꢀdichloroꢀ5ꢀfluorobenzoylacetate with 2ꢀchlorobenzoꢀ
thia(oxa)zoles in the presence of sodium hydride.2,3
An alternative approach to [a]ꢀannelated quinoꢀ
lones involves acylation of αꢀazahetarylacetonitriles with
2ꢀhaloarenecarboxylic acid chlorides followed by cyclizaꢀ
tion of Cꢀacyl derivatives.4,5 Benzimidazo[1,2ꢀa]quinoꢀ
lone derivatives prepared according to this method exꢀ
hibit antimicrobial activity.6 There are also data on the
use of acetonitrile derivatives in the synthesis of antibacꢀ
terial agents, such as lomefloxacin and fleroxacin.7—10
In the present study, we prepared fluoro derivatives of
benzimidazo[1,2ꢀa]quinolone as part of continuing inꢀ
vestigations on structural modifications of fluoroquinoꢀ
lones.11—15
It was demonstrated that acylation of 2ꢀcyanomethylꢀ
benzimidazole (1) with polyfluorobenzoyl chlorides (2a,b)
afforded 2ꢀ(1,3ꢀdihydrobenzimidazolꢀ2ꢀylidene)ꢀ3ꢀoxoꢀ
3ꢀpolyfluorophenylpropionitriles (3a,b) (Scheme 1). The
1H NMR spectra of compounds 3a,b show signals for the
protons of the benzimidazole fragment as two symmetriꢀ
cal multiplets at δ 7.3 and 7.6 and signals of two NH
groups at δ 13.2 (broadened) as well as a multiplet for one
proton of the tetrafluorobenzene fragment (in the case of
derivative 3a). The mass spectra of compounds 3a,b have
intense molecular ion peaks [M]+ and [M – 19]+.
Compounds 3a,b underwent cyclization into tetraꢀ
cyclic derivatives 4a,b in 66 and 85% yields, respectively,
on refluxing in acetonitrile in the presence of DBU for 5 h.
In the H NMR spectra of compounds 4a,b, the broadꢀ
ened oneꢀproton singlet of one NH group is retained,
whereas the signals of the benzimidazole fragment are
manifested as unsymmetrical multiplets shifted downfield
compared to those in the spectra of 3a,b. The mass specꢀ
tra of benzimidazoquinolones 4a,b are characterized by
molecular ion peaks with the highest intensity. The abꢀ
sence of other intense peaks is indicative of stability of the
aromatic tetracyclic system. The 19F NMR spectrum of
compound 4a has signals for three fluorine atoms. It
should be noted that the signals for F(3) and F(2) are
observed as doublets of doublets of doublets, whereas the
signal for F(1) is characterized by a more complex multiꢀ
plicity due, apparently, to the throughꢀspace coupling
with the protons of the benzimidazole fragment.
Fused derivative 4a was generated in 80% yield by
refluxing compound 3a in DMF for 6 h. Heating of comꢀ
pound 3a with pyrrolidine, 4ꢀmethylpiperidine, 3ꢀmethylꢀ
piperidine, or morpholine in DMF led both to cyclization
of 3a and the replacement of one fluorine atom. The
positions and multiplicities of the signals in the H and
19F NMR spectra of derivatives 5a—d provide evidence
that the F(2) atom is replaced. The H NMR spectra of
compounds 5a—d have a doublet of doublets for the H(4)
proton at δ 7.6—7.7 and signals of the NH group, the
amine residue, and the protons of the benzimidazole fragꢀ
ment. The 19F NMR spectrum of compound 5a shows
signals for two metaꢀfluorine atoms.
It should be noted that heating of 3a with 1ꢀethoxyꢀ
carbonylpiperazine in DMF afforded dimethylaminoꢀsubꢀ
stituted quinolone 5e, i.e., cyclization was accompanied
by the replacement of the fluorine atom by the dimethylꢀ
amine residue rather than by the ethoxycarbonylpiperazine
residue (as could be expected). Due to the presence of
two labile fluorine atoms in quinolone 3b, the reaction of
1
1
* Dedicated to Academician G. A. Tolstikov on the occasion of
his 70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 436—439, February, 2003.
1066ꢀ5285/03/5202ꢀ457 $25.00 © 2003 Plenum Publishing Corporation

458
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 2, February, 2003
Lipunova et al.
Scheme 1
2—4: X = H (a), F (b)
5: Y = H; NR2 = pyrrolidinꢀ1ꢀyl (a), 4ꢀmethylpiperidinꢀ1ꢀyl (b), 3ꢀmethylpiperidinꢀ1ꢀyl (c), morpholinꢀ4ꢀyl (d), NMe2 (e);
Y = NR2 = pyrrolidinꢀ1ꢀyl (f)
6: NR2 = pyrrolidinꢀ1ꢀyl (a), 4ꢀmethylpiperidinꢀ1ꢀyl (b)
standard. The 19F NMR spectra were measured on a Bruker
WPꢀ80ꢀSY spectrometer operating at 75.38 MHz with hexaꢀ
fluorobenzene as the internal standard. The mass spectra were
obtained on a Varian MAT 311A spectrometer (accelerating
voltage was 3 kV, cathode emission current was 300 µA, energy
of ionizing electrons was 70 eV, direct inlet of the sample into
the ion source). The IR spectra were measured on a Specord
751R instrument in KBr pellets.
this compound with pyrrolidine in DMF involved both
cyclization and the replacement of the F(2) and F(4)
atoms with the amino residue.
Attempts to hydrolyze nitriles 5a,b by heating in 30%
sulfuric acid failed. The reactions with 60% sulfuric acid
gave rise to compounds 6a,b. Apparently, these reactions
are accompanied by hydrolysis of the CN group but the
resulting acids are unstable and are readily decarboxyꢀ
2ꢀCyanomethylbenzimidazole was prepared by condensaꢀ
tion of cyanoacetic ester with oꢀphenylenediamine according to
a known procedure.17
1
lated. The data from H NMR spectroscopy and mass
spectrometry of compounds 6a,b are consistent with their
structures. In the IR spectrum of compound 6b, a stretchꢀ
ing band of the nitrile group is absent, whereas the specꢀ
trum of compound 5b has this band at 2200 cm–1. The
1H NMR spectra of compounds 6a,b have a singlet of the
H(6) proton at δ 6.2—6.3. These results are in agreement
with the published data on the characteristic features of
hydrolysis of quinolineꢀ3ꢀcarbonitriles and the fact that
the corresponding acids can be subjected to decarboxylaꢀ
tion under drastic conditions.16
2ꢀ(1,3ꢀDihydrobenzimidazolꢀ2ꢀylidene)ꢀ3ꢀoxoꢀ3ꢀ(1,2,3,4ꢀ
tetrafluorophenyl)propionitrile (3a). Tetrafluorobenzoyl chloride
2a (1.5 mL, 15 mmol) was added to a suspension of 2ꢀcyanoꢀ
methylbenzimidazole 1 (1.5 g, 9.6 mmol) in toluene (15 mL).
The reaction mixture was refluxed for 4 h and cooled. The
precipitate of compound 3a that formed was filtered off, washed
with ethanol, and recrystallized from DMSO. The yield was
1
2.8 g (88%), m.p. > 250 °C. H NMR (DMSOꢀd6), δ: 7.25 (m,
2 H, H(4), H(7)); 7.41 (m, 1 H, H(6´)); 7.56 (m, 2 H, H(5),
H(6)); 13.09 (br.s, 2 H, NH). MS, m/z (Irel (%)): 333 [M]+ (98),
315 (19), 314 (100), 313 (33), 184 (22), 177 (26), 156 (18), 149
(19), 102 (13). Found (%): C, 57.60; H, 2.03; N, 12.75.
C16H7F4N3O. Calculated (%): C, 57.67; H, 2.12; N, 12.61.
2ꢀ(1,3ꢀDihydrobenzimidazolꢀ2ꢀylidene)ꢀ3ꢀoxoꢀ3ꢀ(perfluoroꢀ
phenyl)propionitrile (3b) was prepared analogously to comꢀ
pound 3a. The yield was 83%, m.p. 238—240 °C. 1H NMR
(DMSOꢀd6), δ: 7.27 (m, 2 H, H(4), H(7)); 7.57 (m, 2 H, H(5),
H(6)); 13.19 (br.s, 2 H, NH). MS, m/z (Irel (%)): 351 [M]+
(100), 333 (16), 332 (85), 331 (53), 303 (18), 195 (18), 184 (26),
187 (13), 156 (22), 102 (16). Found (%): C, 54.42; H, 1.80;
The new benzimidazo[1,2ꢀa]quinolone derivatives
synthesized in the present study are the first representaꢀ
tives of the series of fluorineꢀcontaining derivatives and
are of interest as potential biologically active compounds.
Experimental
1
The H NMR spectra were recorded on a Bruker WMꢀ250
spectrometer operating at 250 MHz with Me4Si as the internal

Fluorinated benzimidazo[1,2ꢀa]quinolones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 2, February, 2003
459
N, 11.82. C16H6F5N3O. Calculated (%): C, 54.71; H, 1.72;
N, 11.96.
1.2 Hz); 7.86 (m, 1 H, H(11)); 13.6 (br.s, 1 H, NH). MS,
m/z (Irel (%)): 392 [M]+ (100), 391 (65), 338 (14), 322 (19),
313 (15), 294 (13), 266 (9). IR (KBr), ν/cm–1: 2200 (CN).
Found (%): C, 67.16; H, 4.33; N, 14.09. C22H18F2N4O. Calcuꢀ
lated (%): C, 67.33; H, 4.62; N, 14.27.
1,3ꢀDifluoroꢀ2ꢀ(3ꢀmethylpiperidino)ꢀ5ꢀoxoꢀ5,12ꢀdihydroꢀ
benzimidazo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5c). The yield was
58%, m.p. > 250 °C. 1H NMR (DMSOꢀd6), δ: 0.96 (d, 3 H, Me,
3J = 6.1 Hz); 1.10—1.30 (m, 1 H, CH); 1.83 (m, 4 H, 2 CH2);
2.84 (m, 1 H, NCH); 3.11 (m, 1 H, NCH); 3.45 (m, 2 H,
NCH2); 7.32 (m, 1 H, H(8)); 7.41 (m, 1 H, H(9) or H(10)); 7.52
(m, 1 H, H(10) or H(9)); 7.70 (dd, 1 H, H(4), 3J = 13.4 Hz, 5J =
1.7 Hz); 7.85 (m, 1 H, H(11)); 13.6 (br.s, 1 H, NH). Found (%):
C, 67.58; H, 4.41; N, 14.46. C22H18F2N4O. Calculated (%):
C, 67.33; H, 4.62; N, 14.27.
1 , 2 , 3 ꢀ T r i f l u o r o ꢀ 5 ꢀ o x o ꢀ 5 , 1 2 ꢀ d i h y d r o b e n z i m i d ꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (4a). A. 1,8ꢀDiazabiꢀ
cyclo[5.4.0]undecꢀ7ꢀene (DBU) (0.46 g, 3.0 mmol) was added
to a solution of compound 3a (1.0 g, 3.0 mmol) in dry MeCN
(15 mL). The reaction mixture was refluxed for 3.5 h and conꢀ
centrated. Water (25 mL) and AcOH (0.5 mL) were added to the
residue. The precipitate of compound 4a that formed was filꢀ
tered off and recrystallized from DMSO. The yield was 0.8 g
1
(85%), m.p. > 250 °C. H NMR (DMSOꢀd6), δ: 7.35 (m, 1 H,
H(4)); 7.44 (m, 1 H, H(8)); 7.54 (m, 1 H, H(9) or H(10)); 7.97
(m, 1 H, H(10) or H(9)); 8.02 (m, 1 H, H(11)); 13.82 (br.s, 1 H,
NH). 19F NMR (DMSOꢀd6), δ : 153.17 (ddd, 1 F, F(2), 3JF,F
=
F
3
4
23.2 Hz, JF,F = 19.5 Hz, JF,H = 7.9 Hz); 136.80 (ddd, 1 F,
4
F(3), 3JF,F = 23.2 Hz, 3JF,H = 10.4 Hz, JF,F = 5.5 Hz); 132.08
1,3ꢀDifluoroꢀ2ꢀmorpholinoꢀ5ꢀoxoꢀ5,12ꢀdihydrobenzimidꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5d). The yield was 79%, m.p.
(m, 1 F, F(1)). MS, m/z (Irel (%)): 313 [M]+ (100), 285 (16),
284 (12), 143 (12). Found (%): C, 61.32; H, 2.10; N, 13.45.
C16H6F3N3O. Calculated (%): C, 61.39; H, 1.93; N, 13.42.
B. A solution of compound 3a (0.4 g, 1.2 mmol) in DMF
(4 mL) was refluxed for 5 h, cooled, and diluted with water. The
precipitate of nitrile 4a that formed was filtered off and recrysꢀ
tallized from DMSO. The yield was 0.3 g (80%).
1
> 250 °C. H NMR (DMSOꢀd6), δ: 3.15 (m, 4 H, N(CH2)2);
3.40 (m, 2 H, OCH2); 3.78 (m, 2 H, OCH2); 7.31 (m, 1 H,
H(8)); 7.40 (m, 1 H, H(9) or H(10)); 7.51 (m, 1 H, H(10) or
H(9)); 7.71 (dd, 1 H, H(4), 3J = 11.8 Hz, 5J = 1.5 Hz); 7.86 (m,
1 H, H(11)); 13.5 (br.s, 1 H, NH). Found (%): C, 63.39; H, 3.65;
N, 14.96. C20H14F2N4O2. Calculated (%): C, 63.15; H, 3.71;
N, 14.73.
1,2,3,4ꢀTetrafluoroꢀ5ꢀoxoꢀ5,12ꢀdihydrobenzimidꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (4b) was prepared according
to procedure A analogously to compound 4a. The yield was 66%,
2ꢀDimethylaminoꢀ1,3ꢀdifluoroꢀ5ꢀoxoꢀ5,12ꢀdihydrobenzimidꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5e). The yield was 69%, m.p.
1
1
m.p. > 250 °C. H NMR (DMSOꢀd6), δ: 7.36 (m, 1 H, H(8));
> 250 °C. H NMR (DMSOꢀd6), δ: 3.16 (s, 6 H, NMe2); 7.31
7.50 (m, 2 H, H(9), H(10)); 8.44 (m, 1 H, H(11)); 13.6 (br.s,
1 H, NH). MS, m/z (Irel (%)): 331 [M]+ (100), 303 (8), 302 (7),
165 (10). Found (%): C, 57.86; H, 1.32; N, 12.58. C16H5F4N3O.
Calculated (%): C, 58.01; H, 1.52; N, 12.68.
(m, 1 H, H(8)); 7.40 (m, 1 H, H(9) or H(10)); 7.52 (m, 1 H,
H(10) or H(9)); 7.69 (dd, 1 H, H(4), 3J = 12.5 Hz, 5J = 1.2 Hz);
7.86 (m, 1 H, H(11)); 13.6 (br.s, 1 H, NH). MS, m/z (Irel (%)):
338 [M]+ (100), 337 (31), 322 (10), 294 (5), 155 (9). Found (%):
C, 63.80; H, 3.24; N, 16.75. C18H12F2N4O. Calculated (%):
C, 63.90; H, 3.57; N, 16.56.
1,3ꢀDifluoroꢀ5ꢀoxoꢀ2ꢀpyrrolidinoꢀ5,12ꢀdihydrobenzimidꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5a). A. Pyrrolidine (0.3 mL,
0.26 g, 3.7 mmol) was added to a solution of compound 3a
(0.3 g, 1.0 mmol) in DMF (4 mL). The reaction mixture was
refluxed for 5 h, cooled, and diluted with water. The precipitate
of nitrile 5a that formed was filtered off and recrystallized from
1,3ꢀDifluoroꢀ5ꢀoxoꢀ2,4ꢀdipyrrolidinoꢀ5,12ꢀdihydrobenzimidꢀ
azo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5f) was prepared analogously
from nitrile 3b. The yield was 65%, m.p. 244—246 °C. 1H NMR
(DMSOꢀd6), δ: 1.95 (m, 4 H, (CH2)2); 2.08 (m, 2 H, CH2); 2.20
(m, 2 H, CH2); 3.32 (m, 2 H, NCH2); 3.60 (m, 2 H, NCH2);
3.79 (m, 4 H, N(CH2)2); 7.23 (m, 1 H, H(8)); 7.36 (m, 1 H,
H(9) or H(10)); 7.65 (m, 1 H, H(10) or H(9)); 7.84 (m, 1 H,
H(11)); 19.05 (br.s, 1 H, NH). MS, m/z (Irel (%)): 433 [M]+
(100), 432 (23), 431 (35), 407 (7), 416 (5), 363 (5), 293 (3),
217 (8), 215 (4). Found (%): C, 66.57; H, 4.59; N, 16.15.
C24H21F2N5O. Calculated (%): C, 66.50; H, 4.88; N, 16.15.
1,3ꢀDifluoroꢀ2ꢀ(4ꢀmethylpiperidino)ꢀ5ꢀoxoꢀ5,12ꢀdihydroꢀ
benzimidazo[1,2ꢀa]quinoline (6b). Water (6 mL) and concenꢀ
trated H2SO4 (6 mL) were added to compound 5b (1.3 g,
3.3 mmol). The reaction mixture was refluxed for 5.5 h and
cooled. Then water (20 mL) was added. A solution of NH3 was
added to pH 8. The precipitate of derivative 6b that formed was
filtered off and recrytsallized from DMSO. The yield was 0.95 g
1
DMSO. The yield was 0.27 g (74%), m.p. > 250 °C. H NMR
(DMSOꢀd6), δ: 1.98 (m, 4 H, (CH2)2); 3.75 (m, 4 H, N(CH2)2);
7.27 (m, 1 H, H(8)); 7.37 (m, 1 H, H(9) or H(10)); 7.47 (m,
1 H, H(10) or H(9)); 7.58 (dd, 1 H, H(4), 3J = 13.8 Hz, 5J =
1.3 Hz); 7.77 (m, 1 H, H(11)); 13.4 (br.s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ : 124.19 (m, 1 F, F(1)); 124.46 (dd, 1 F, F(3),
F
3JF,H = 13.8 Hz, 5JF,H = 1.3 Hz). MS, m/z (Irel (%)): 364 [M]+
(100), 363 (54), 338 (3), 322 (9), 294 (13), 280 (12), 266 (6), 182
(5). Found (%): C, 65.39; H, 4.00; N, 14.92. C20H14F2N4O.
Calculated (%): C, 65.99; H, 3.87; N, 15.39.
B. Pyrrolidine (0.6 mL, 0.52 g, 7.2 mmol) was added to a
solution of nitrile 4a (0.6 g, 1.9 mmol) in DMF (5 mL). The
reaction mixture was refluxed for 5 h, cooled, and diluted with
water. The precipitate of compound 5a that formed was filtered
off and recrystallized from DMSO. The yield was 0.45 g (65%).
Compounds 5b—e were prepared from compound 3a using
procedure A.
1,3ꢀDifluoroꢀ2ꢀ(4ꢀmethylpiperidino)ꢀ5ꢀoxoꢀ5,12ꢀdihydroꢀ
benzimidazo[1,2ꢀa]quinolineꢀ6ꢀcarbonitrile (5b). The yield was
71%, m.p. 252—254 °C. 1H NMR (DMSOꢀd6), δ: 1.02 (d, 3 H,
Me, 3J = 6.5 Hz); 1.40 (m, 2 H, CH2); 1.50—1.70 (m, 1 H,
CH); 1.76 (m, 2 H, CH2); 3.22 (m, 2 H, NCH2); 3.49 (m, 2 H,
NCH2); 7.32 (m, 1 H, H(8)); 7.41 (m, 1 H, H(9) or H(10)); 7.51
(m, 1 H, H(10) or H(9)); 7.70 (dd, 1 H, H(4), 3J = 11.0 Hz, 5J =
1
(79%), m.p. 228—230 °C. H NMR (DMSOꢀd6), δ: 1.03 (d,
3 H, Me, 3J = 6.5 Hz); 1.41 (m, 2 H, CH2); 1.50—1.70 (m, 1 H,
CH); 1.76 (m, 2 H, CH2); 3.22 (m, 2 H, NCH2); 3.43 (m, 2 H,
NCH2); 6.30 (s, 1 H, H(6)); 7.20 (m, 1 H, H(8)); 7.32 (m, 1 H,
H(9) or H(10)); 7.50 (m, 1 H, H(10) or H(9)); 7.65 (dd, 1 H,
H(4), 3J = 10.9 Hz, 5J = 1.2 Hz); 7.94 (m, 1 H, H(11)); 11.6
(br.s, 1 H, NH). MS, m/z (Irel (%)): 367 [M]+ (100), 366 (47),
298 (11), 297 (12), 288 (12). Found (%): C, 68.98; H, 4.93;
N, 11.69. C21H19F2N3O. Calculated (%): C, 68.65; H, 5.21;
N, 11.43.

460
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 2, February, 2003
Lipunova et al.
1,3ꢀDifluoroꢀ5ꢀoxoꢀ2ꢀpyrrolidinoꢀ5,12ꢀdihydrobenzimidꢀ
6. F. S. Babichev, V. K. Patratii, Yu. M. Volovenko, N. G.
Prodanchuk, V. G. Sinchenko, A. G. Nemazanyi, and T. A.
Silaeva, Khim.ꢀfarm. Zh., 1989, 23, 834 [Pharm. Chem. J.,
1989 (Engl. Transl.)].
7. Sp. Pat. 2026819 (1992); Chem. Abstrs., 1992, 117, 234043c.
8. Sp. Pat. 2026821 (1992); Chem. Abstrs., 1992, 117, 234044d.
9. Sp. Pat. 2010861 (1989); Chem. Abstrs., 1991, 114, 185559c.
10. Sp. Pat. 2010862 (1989); Chem. Abstrs., 1991, 114, 185560w.
11. G. A. Mokrushina, V. N. Charushin, and O. N. Chupakhin,
Khim.ꢀfarm. Zh., 1995, 29, No. 9, 5 [Pharm. Chem. J., 1995
(Engl. Transl.)].
azo[1,2ꢀa]quinoline (6a) was prepared analogously to compound
6b from compound 5a. The yield was 72%, m.p. > 250 °C.
1H NMR (DMSOꢀd6), δ: 1.98 (m, 4 H, (CH2)2); 3.76 (m, 4 H,
N(CH2)2); 6.22 (s, 1 H, H(6)); 7.21 (m, 1 H, H(8)); 7.30 (m,
1 H, H(9) or H(10)); 7.51 (m, 1 H, H(10) or H(9)); 7.68 (dd,
1 H, H(4), 3J = 11.8 Hz, 5J = 1.6 Hz); 7.87 (m, 1 H, H(11));
11.4 (br.s, 1 H, NH). MS, m/z (Irel (%)): 339 [M]+ (100), 338
(52), 313 (24), 285 (18), 178 (15), 73 (23), 64 (84), 57 (32), 55
(29). Found (%): C, 67.54; H, 4.71; N, 12.09. C19H15F2N3O.
Calculated (%): C, 67.24; H, 4.45; N, 12.38.
12. G. N. Lipunova, G. A. Mokrushina, E. V. Nosova, L. I.
Rusinova, and V. N. Charushin, Mendeleev Commun.,
1997, 109.
13. V. N. Charushin, E. V. Nosova, G. L. Lipunova, and M. I.
Kodess, J. Fluorine Chem., 2001, 25.
14. V. N. Charushin, G. N. Lipunova, E. V. Nosova, L. P.
Sidorova, and O. M. Chasovskikh, Mendeleev Commun.,
1998, 131.
15. G. N. Lipunova, E. V. Nosova, N. N. Mochul´skaya, A. A.
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This study was financially supported by the Russian
Foundation for Basic Research (Project Nos. 00ꢀ03ꢀ
32785a and 01ꢀ03ꢀ96427ꢀUrals) and the US Civilian Reꢀ
search and Development Foundation (CRDF, Grant
RECꢀ005).
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Received July 23, 2002;
in revised form October 29, 2002