Fluoro-containing heterocycles: V. Cyclization of 3-azolylamino-2-polyfluorobenzoylacrylates

Article abstract of DOI:10.1023/A:1012498322793

The heating of ethyl 3-azolylamino-2-polyfluorobenzoylacrylates in acetonitrile in the presence of KF gave rise to derivatives of 1-azolyl-substituted quinolones or azolo[1,5-a]pyrimidines.

Full text of DOI:10.1023/A:1012498322793

Russian Journal of Organic Chemistry, Vol. 37, No. 4, 2001, pp. 570 576. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 4, 2001,
pp. 604 610.
Original Russian Text Copyright
2001 by Lipunova, Nosova, Kodess, Charushin, Rozin, Chasovskikh.
Fluoro-containing Heterocycles: V.* Cyclization
of 3-Azolylamino-2-polyfluorobenzoylacrylates**
G. N. Lipunova1, E.V.Nosova1, M.I.Kodess2,
V.N.Charushin2, Yu.A.Rozin1, and O.M.Chasovskikh1
1Ural State Technical University, Yekaterinburg, 620002 Russia
2Institute of Organuc Synthesis, Ural Division, Russian Academy of Sciences, Yekaterinburg, 620219 Russia
Received May 5, 2000
Abstract The heating of ethyl 3-azolylamino-2-polyfluorobenzoylacrylates in acetonitrile in the presence of
KF gave rise to derivatives of 1-azolyl-substituted quinolones or azolo[1,5-a]pyrimidines.
In our preceding studies we extensively used
cyclization of 3-hydrazido derivatives of 2-polyflyoro-
benzoylacrylic acids in the synthesis of [i,j]-annealed
quinolonecarboxylic acids [2, 3] (Scheme 1). In
these tricyclic systems the quinolone carcass is
anneled with six-membered oxadiazine or thiadiazine
rings, and they may be regarded as analogs of the
Scheme 2.
known
marbofloxacin.
antibacterial
agents,
ofloxacin
and
quinolone carcass. A single example concerns a pre-
paration of derivatives of pyrrolo[3,2,1-i,j]quino-
line-5-carboxylic acid by building up of a pyridone
fragment (Scheme 2) [5].
Scheme 1.
Proceeding from the data of the previous research
[2, 3, 6] we presumed that the reaction between
2-aminazoles IIa, b with ethyl 2-polyfluorobenzoyl-3-
ethoxyacrylates (Ia, b) can provide derivatives of
1-azolylsubstituted quinolones IV capable of further
cyclization into tetracyclic compounds V.
Actually we succeeded in carrying out the first
part of the scheme. The reaction of compounds Ia, b
and IIa, b in ethanol at 18 20 C gave rise to
3-azolylamino-2-polyfluorobenzoylacrylates (IIIa d)
(Scheme 3). The structure of these compounds was
1
confirmed with H NMR spectra. For instance, same
as initial acrylate Ia compound IIIa in solution
X = O, S; Y = H, F.
exists as two geometrical isomers with respect to the
1
C2 C3 bond as shows the presence in the H NMR
The other methods of synthesis of [i,j]-fused
fluoroquinolones are also known [4]; however in the
literature are hardly mentioned cases of
five-membered cycles annealed at facets [i,j] of a
spectrum of a double set of proton signals from the
ester group, =CH NH fragment, and from pyrazole
and tetrafluorobenzoyl substituents.
a
Cyclization of acrylates III was carried out in boil-
ing acetonitrile in the presence of KF within 2 4 h.
We found that depending on the substituents X and Y
the reaction occurs along different pathways. In cycliz-
ation of ethyl 2-pentafluorobenzoyl-3(pyrazol-3-yl)-
aminoacrylate (IIIb) was obtained 1-substituted
*
For communication IV, see [1].
The study was carried out under financial support from the
Ministry of Science of the Russian Federation, grant
no. 9.1.06, and from Russian Foundation for Basic
Research, grant no. 00-15-97390.
**
1070-4280/01/3704-0570$25.00 2001 MAIK Nauka/Interperiodica

FLUORO-CONTAINING HETEROCYCLES: V.
571
Scheme 3.
I, Y = H (a), F (b); II, VI, VII, X = CH (a), N (b); III, X = CH, Y = H (a), F (b); X = N, Y = H (c), F (d);
VIII, NR2 = pyrrolidin-1-yl, X = CH (a), N (b); NR2 = morpholino, X = N (c).
quinolone IVb. In the mass spectrum of compound
IVb is present a molecular peak with m/z 355 and
also a strong peak (100%) corresponding to an ion
[M COOC2H4]+ . In the IR spectrum of compound
forming the desired cyclization are probably due to
the high strain in the fused system V.
It is interesting that the cyclization of tetrafluoro-
benzoyl analog IIIa occurs in dissimilar way: here
forms not a quinolone structure of IV type but a
derivative of pyrazolo[1,5-a]pyrimidine (VIIa). The
structure of the latter was proved by 1H and 19F NMR
spectra. In the mass spectrum of compound VIIa is
present a peak of the molecular ion m/z 339, in the
19F NMR spectrum appear signals from four fluorine
atoms. In the IR spectrum of the compound in the
C=O vibrations region is observed a single band
1
IVb appear absorption bands at 1730 and 1640 cm
of the stretching vibrations from carbonyls in the
ester group and quinolone fragment respectively. In
the 19F NMR spectrum are observed the signals from
four fluorine atom; therewith the chemical shifts,
multiplicity of signals, and coupling constants are
similar to those in the 19F NMR spectra of the other
derivatives of 1,4-dihydro-4-oxo-5,6,7,8-tetrafluoro-
quinoline-3-carboxylic acid that we have prepared
1
1
from the ester group at 1725 cm . Unlike the initial
before [2]. The H NMR spectrum is consistent with
1
acrylate IIIa, compound VIIa in the H NMR spec-
the structure IVb, and in distinction from the initial
acrylate IIIb the doublet of NH group is lacking, and
the signal of the CH= proton appears as a singlet.
trum has no signals from two NH groups, and the
characteristic multiplet belonging to the proton of the
polyfluorobenzene fragment corresponds to the
coupling thereof with four fluorine atoms of the ring.
Thus all data indicate that in the concurrent reaction
with the participation of a carbonyl group forms
compound VIIa.
The attempt to perform further cyclization of
compound IVb with the use of a stronger agent for
binding HF, diazabicycloundec-7-ene (DBU), failed.
Note that in the mass spectrum of compound IVb the
ion peak [M HF]+ is lacking; this peak usually is
present among fragment peaks of compounds prone
to further cyclization [2, 6]. The difficulty in per-
The cyclization of ethyl 2-tetrafluorobenzoyl-3-
(1,2,4-triazol-3-yl)aminoacrylate (IIIc) takes
a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

572
LIPUNOVA et al.
Table 1. Yields, melting points, and elemental analyses of compounds synthesized
Found, %
Calculated, %
H
Compd.
Yield, %
mp,
C
Formula
no.
C
H
N
C
N
IIIa
IIIb
IIIc
IIId
82
73
76
71
70
74
60
56
61
60
50
140 142
132 134
146 148
178 180
244 246
84 86
102 104
85 87
118 120
104 106
148 150
50.61
48.19
41.10
44.81
50.49
53.29
49.10
55.90
55.50
53.40
48.03
3.24
2.81
2.91
2.58
2.58
2.58
2.32
2.31
4.31
4.11
3.31
11.61
11.09
15.52
14.70
12.01
12.53
16.35
10.41
18.02
17.42
13.28
C15H11F4N3O3
C15H10F5N3O3
C14H10F4N4O3
C14H9F5N4O3
C15H9F4N4O3
C15H9F4N3O2
C14H8F4N4O2
C19H17F3N3O2
C18H16F3N5O2
C18H16F3N5O3
C17H13F3N4O6
50.43
48.01
40.93
44.69
50.71
53.11
49.41
55.75
55.24
53.07
47.89
3.10
2.69
2.79
2.41
2.55
2.67
2.35
2.16
4.12
3.96
3.05
11.76
11.20
15.64
14.89
11.83
12.39
16.47
10.27
17.90
17.19
13.15
IVb
VIIa
VIIb
VIIIa
VIIIb
VIIIc
XV
similar course, and arises only one of the two
Thus the cyclization product of acrylate IIIc may
have a structure of triazolo[1,5-a]pyrimidine or tri-
azolo[4,3-a]pyrimidine. Basing on the literature data
on the structure of 1,2,4-triazolopyrimidines obtained
from 3-amino-1,2,4-triazole and -diketones [7 10]
we considered as more probable the structure of
triazolo[1,5-a]pyrimidine (VIIb).
possible regioisomers, namely VIIb. This is
1
evidenced by a single set of resonances in the H and
19F NMR spectra. In the 19F NMR spectrum of
compound VIIb appear signals of the four fluorine
atoms as in the spectrum of initial acrylate IIIb. The
most intensive peak in the mass spectra corresponds
to the molecular ion with m/z 340. The main frag-
mentation paths of the molecular ion M+ are as
follows: fluorine atom elimination, decomposition of
the ester moiety, cleavage of the tetrafluorophenyl
fragment, and HCN elimination. This fragmentation
pattern completely corresponds to structure VIIb.
As in the IR spectrum of compound VIIa, in the
spectrum of compound VIIb appears the (CO)
The structure of compound VIIb was supported
experimentally by 13C NMR spectra recorded without
decoupling from protons and with usual wide-band
decoupling (Table 2). The coupling 13C 19F allows
unambiguous assignment of the carbon signals of the
polyfluorophenyl substituent. The signal of the nodal
carbon C3a appears at 155.4 ppm as a doublet of
doublets with the coupling constants 15.3 and 9.8 Hz.
The assignment of the latter to 3J(C3a, H5) and 3J(C3a,
H2) was carried out with the use of stationary
selective decoupling from H5 and H2protons.
1
absorption band of the ester group at 1720 cm and
no stretching vibrations of the carbonyl in quinolone
fragment are observed. The 1H NMR spectrum is also
consistent with structure VIIb since there are no
signals from NH groups, but appears a characteristic
multiplet of an aromatic proton at 7.8 ppm. Two
more singlets from aromatic protons are also
observed at 8.8 and 9.4 ppm.
Decoupling from the proton signal at 9.4 ppm
resulted in a change in multiplicity of carbonyl group
carbon and of the doublet from C6 (Table 2). There-
1
fore the signal at 9.4 in the H NMR spectrum was
assigned to H5 proton, and consequently the signal at
8.8 ppm belonged to H2. In the 13C NMR spectrum
with selective decoupling from H5 the C3a signal is
reduced to doublet with a coupling constant 9.8 Hz
corresponding to coupling with H2 atom. Thus the
constant 15.3 Hz is due to the coupling of C3a and H5.
Actually in the 13C NMR spectrum with selective
decoupling from H2 the signal of C3a appears as a
doublet with a coupling constant 3J(C3a, H5) of
15.3 Hz. In the literature [11, 12] were mentioned
similar values of coupling constants: 3J(C3a, H5)
Since compounds VII originate from a nucleo-
philic attack of the carbonyl from the benzoyl moiety,
triazolyl derivative IIIc may give rise to two
alternative adducts VIb and IX.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

FLUORO-CONTAINING HETEROCYCLES: V.
573
15.1 Hz for 5-methyltetrazolo[1,5-a]pyrimidine and
Table 2. 13C NMR spectrum of compound VIIb
3J(C3a, H2) 9.0 Hz for 1,2,4-triazolo[5,1-c][1,2,4]-
triazine.
3
The 9,8 Hz value of the constant J(C3a, H2) is an
additional proof of the triazolo[1,5-a]pyrimidine
structure of compound VIIb and not triazolo[4.3-a]-
pyrimidine one. According to published data in the
spectra of various azoloazines X XII the coupling
between atoms C3a and H1 via a nodal nitrogen atom
is characterized by smaller values of constants than
3J(C3a, H2) [13].
Chemical
shifts,
C, ppm
Carbon
atom
1
nJ(13C, H) or nJ(13C, 19F)
C=O
OCH2
CH3
C2
162.139
61.964
13.423
3J(C, H) 3.0, 3J(C, H5) 1.7
1J(C, H) 149.4, 2J(C, H) 4.5
1J(C, H) 127.2, 2J(C, H) 2.7
157.523 d 1J(C2, H2) 210.7
C3a
C5
155.437 d.d 3J(C3a, H5) 15.3, J(C3a, H2) 9.8
155.706 d J(C , H ) 191.8
114.593 d 2J(C6, H5) 7.8
141.599
3
3J(C3a, H2) 7.7 8.0,
1 5
5
3J(C3a, H1) 5.3 5.8 Hz.
C6
C7
The fluoro-containing derivatives of azolopyr-
imidines (VII) may be potential biologically active
compounds [9]. Therefore we studied substitution of
fluorine atom with amine rests resulting in com-
pounds VIII. The conclusion on replacement of the
fluorine in para-position with respect to the hetero-
C1
114.064
139.897
144.687
146.216
141.294
113.493
2J(C1 , F2 ) 14.0, J(C1 , F3 ) 9.6,
3
4J(C1 , F4 ) 3.9
C2
C3
C4
C5
C6
1J(C2 , F2 )251.45, 2J(C2 , F3 ) 16.1,
4
3J(C2 , F4 ) 12.5, J(C2 , F5 ) 4.0
1J(C3 , F3 )249.25, 2J(C3 , F4 )12.6,
3J(C3 , F5 ) 3.2
1
cyclic substituent follows from the H NMR spectra
2
1J(C4 , F4 )245.48, J(C4 , F3 )10.6,
where the proton of the benzene ring appears as a
doublet of doublets of doublets with the coupling
constants 13.9 14.1, 6.0 6.1, and 2.1 2.4 Hz.
3J(C4 , F2 ) 2.2
1J(C5 , F5 )256.86, 2J(C5 , F4 ) 17.0,
4
3J(C5 , F3 ) 13.0, J(C5 , F2 ) 3.8
2
1J(C6 , H6 ) 174.5; J(C6 , F5 ) 22.1,
Ethyl 2-pentafluorobenzoyl-3-(1,2,4-triazol-3-
yl)aminoacrylate (IIId) at heating in acetonitrile in
the presence of KF (or DBU) failed to give cycliza-
4
3J(C6 , F4 ) 3.5, J(C6 , F3 ) 1.8
Scheme 4.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

574
LIPUNOVA et al.
tion products of type IV or VII. The lack of ability
to form triazolopyrimidine in acrylate IIId in contrast
to IIIc may be ascribed to more difficult cyclization
of pentafluorobenzoyl derivatives than tetrafluoro-
benzoyl compounds [6]. Acrylate IIId also shows low
capability of intramolecular substitution of fluorine
atom. It should be noted that unlike acrylates IIIa, b
in the mass spectrum of compound IIId the strongest
peak (100%) corresponds to the molecular ion, and
the peaks of ions [M HF]+ and [M H2O]+ are
lacking.
operating frequency 100.61 MHz. Mass spectra were
measured on spectrometer Varian MAT 311A under
the following conditions: accelerating voltage 3kV,
cathode emission current 300 A, ionizing electrons
energy 70eV, direct input of the sample into the
source. IR spectra were registered on Specord 75IR
instruments from KBr pellets. Yields, melting points,
and elemental analyses of compounds III, IV, VII,
VIII, XII are presented in Table 1.
Ethyl 3-(azol-3-yl)amino-2-[tetra(penta)fluoro-
benzoyl]acrylates IIIa d. To a dispersion of 0.5 g
(6.0 mmol) of 3-aminopyrazole (IIa) in 15 ml of
ethanol was added 1.9 g (6.0 mmol) of ethyl 2-tetra-
fluorobenzoyl-3-ethoxyacrylate (Ia). The reaction
mixture was stirred for 3 h at 18 20 C, the formed
precipitate of compound IIIa was filtered off and
recrystallized from benzene. Yield 1.8 g (82%).
1H NMR spectrum (DMSO-d6), , ppm: 1.08 t (3H,
CH3, isomer 1), 0.99 t (3H, CH3, isomer 2), 4.07 q
(2H, OCH2, isomer 1), 4.02q (2H, OCH2, isomer 2),
6.49 s (1H, H4 , isomer 1), 6.42 s (1H, H4 ,
isomer 2), 7.80 m (1H, H6 , isomer 1), 7.50 m (1H,
The reaction of acrylate Ia with 1-amino-1,2,3-
triazole (XIII) in ethanol at 18 20 C in 2 h afforded
a
mixture of 3-(1,2,3-triazol-1-yl)aminoacrylate
(XIV) and quinolone XV. The heating of the same
mixture in benzene for 3 h yields exclusively quino-
lone XV (Scheme 4).
In this case no reaction with participation of the
carbonyl group of compound XIV is observed. The
1
structure of compound XV was established from H
and 19F NMR and mass spectra. In the mass spectra
is present the molecular ion peak m/z 426, in the
19F NMR spectrum appear signals from three fluorine
atoms. Each fluorine signal is a doublet of doublets
of doublets, and the coupling constants are close in
values to those in the spectra of derivatives of 1,4-di-
hydro-4-oxo-6,7,8-trifluoroquinoline-3-carboxylic
H6 , isomer 2), 7.73 s (1H, H5 , isomer 1), 7.36 s
3
(1H, H5 , isomer 2), 8.76 d (1H, H3, J
13.2 Hz,
HH
3
isomer 1), 8.64 d (1H, H3, J
13.1 Hz, isomer 2),
13.1 Hz, isomer 1), 11.07 d
13.1 Hz, isomer 2), 12.82 s (1H,
HH
3
12.25 d (1H, NH, J
HH
3
(1H, NH, J
HH
NH, isomer 1), 12.74 s (1H, NH, isomer 2), ratio of
isomers 1 and 2 is 2: 1. Mass spectrum m/z (Irel, %):
357 (60), M+ , 338 (16), 311 (56), 292 (56), 265
1
acids we have described before [2]. In the H NMR
spectrum of compound XV the proton signal from
benzene ring appears as a doublet of doublets of
doublets with the coupling constants 10.3, 8.3, and
2.0 Hz. Also are present the signals from two ethyl
groups, and singlets from CH= and OH groups.
1
(100), 177 (64). IR spectrum (KBr), , cm : 1670
(CO), 1640 (CO).
Similarly were prepared compounds IIIb d; they
were crystallized from ethanol.
The presence in the triazole moiety of compound
XV a 5-hydroxy group suggested a possibility of
further cyclization into a tetracyclic structure XIII.
Regretfully this attempt failed either at heating quino-
lone XII in toluene in the presence of K2CO3 or in
acetonitrile in DBU presence. Note that the mass
spectrum of compound XV also does not contain a
peak corresponding to ion [M HF]+ .
Compound (IIIb). 1H NMR spectrum (DMSO-
d6), , ppm: 1.16 t (3H, CH3), 4.08 q (2H, OCH2),
6.40 s (1H, H4 ), 7.63 s (1H, H5 ), 8.81 d (1H, H3,
3JHH 13.3 Hz), 12.41 br.d (1H, NH, JHH 13.1 Hz),
3
12.73 br.s (1H, NH). Mass spectrum, m/z (I , %):
rel.
375 (91) M+ , 355 (16), 329 (76), 310 (40), 283
(100), 258 (23), 195 (57). IR spectrum, KBr,
,
1
cm : 1685 (CO), 1630 (CO).
EXPERIMENTAL
Compound (IIIc). 1H NMR spectrum (DMSO-d6),
, ppm: 1.06 t (3H, CH3), 4.03 q (2H, OCH2),
7.66 m (1H, H6 ), 7.70 s (1H, H5 ), 7.89 s (1H, H3),
11.56 br.s (1H, NH), 13.43 br.s (1H, NH). 19F NMR
spectrum (DMSO-d6), F, ppm: 158.39 s, 157.37 s,
145.83 s, 141.96 s.
Compound (IIId). 1H NMR spectrum (DMSO-d6),
, ppm: 1.19 t (3H, CH3), 4.11 q (2H, OCH2),
8.42 s (1H, H5 ), 8.92 s (1H, H3), 12.4 br.s (1H,
1H NMR spectra were registered in DMSO-d6 and
CDCl3 on spectrometer Bruker WP-250 at operating
frequency 250.135 MHz, internal reference TMS.
19F NMR spectra of solutions in DMSO-d6 were
recorded on spectrometer Bruker WP-80-SY at
operating frequency 75.38 MHz, internal reference
hexafluorobenzene. 13C NMR spectra were recorded
in DMSO-d6 on spectrometer Bruker DRX-400 at
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

FLUORO-CONTAINING HETEROCYCLES: V.
575
NH), 14.1 br.s (1H, NH). Mass spectrum, m/z
7-[4-(Pyrrolidin-1-yl)-2,3,5-trifluorophenyl]-6-
ethoxycarbonylpyrazolo[1,5-a]pyrimidine (VIIIa).
To a solution of 0.15 g (0.44 mmol) of compound
VIIa in 6 ml of acetonitrile was added 0.2 g
(2.8 mmol) of pyrrolidine. The reaction mixture was
boiled for 3.5 h, and then evaporated. To the residue
was added petroleum ether and ethanol, the separated
precipitate was filtered off and recrystallized from
ethanol. Yield 0.1 g (56%). 1H NMR spectrum
(DMSO-d6), , ppm: 1.24 t (3H, CH3), 1.86 m [4H,
(CH2)2], 3.54 m [4H, N(CH2)2], 4.23 q (2H, OCH2),
(I , %): 376 (100) M+ , 357 (15), 330 (99),
rel.
302 (59), 284 (95), 195 (88), 163 (68). IR spectrum,
1
KBr, , cm : 1680 (CO), 1635 (CO).
Ethyl 4-oxo-1-(pyrazol-3-yl)-5,6,7,8-tetrafluoro-
1,4-dihydroquinoline-3-carboxylate (IVb). To a
dispersion of 0.6 g (1.6 mmol) of acrylate IIIb in
12 ml of anhydrous acetonitrile was added 0.2 g
(3.2 mmol) of KF. The reaction mixture was boiled
for 2 h. On cooling the precipitate was filtered off,
washed with water, and recrystallized from DMSO.
3
4
6.88 s (1H, H3), 7.65 d.d.d (1H, H6 , JHF 13.9, JHF
1
Yield 0.4 g (70%). H NMR spectrum (DMSO-d6),
5
, ppm: 1.26 t (3H, CH3), 4.22 q (2H, OCH2), 6.59 s
(1H, H5 ), 7.88 s (1H, H4 ), 8.27 s (1H, H2), 13.7 s
(1H, NH). 19F NMR spectrum (DMSO-d6), F, ppm:
6.0, JHF 2.1 Hz), 7.73 s (1H, H2), 8.16 s (1H, H5).
7-[4-(Pyrrolidin-1-yl)-2,3,5-trifluorophenyl]-6-
ethoxycarbonyl-1,2,4-triazolo[1,5-a]pyrimidine
(VIIIb). To a solution of 0.55 g (1.6 mmol) of com-
pound VIIb in 10 ml of acetonitrile was added 0.45 g
(6.4 mmol) of pyrrolidine. The reaction mixture was
boiled for 4 h, then cooled, the precipitate was
filtered off and recrystallized from ethanol. Yield
3
3
162.10 d.d (1F, F7, JF4F 22.0, JFF 20.7 Hz), 150.57
t.d (1F, F6, JF4F 21.6, JFF 7.8 Hz), 147.32 d.d (1F,
3
F5, JFF 21.3, JFF 13.3 Hz), 143.78 d.d.d (1F, F8,
3
3JFF 20.8, JFF 13.3, JFF 7.8 Hz). Mass spectrum,
4
4
m/z (I , %): 355 (10) M+ , 311 (11), 310 (22), 283
rel.
1
(100), 263 (13), 258 (30). IR spectrum, KBr,
cm : 1730 (CO), 1640 (CO).
,
0.4 g (61%). H NMR spectrum (CDCl3), , ppm:
1
1.31 t (3H, CH3), 1.95 m [4H, (CH2)2], 3.73 m [4H,
N(CH2)2], 4.35 q (2H, OCH2), 7.13 d.d.d (1H, H6 ,
7-Tetrafluorophenyl-6-ethoxycarbonylpyrazolo-
[1,5-a]pyrimidine (VIIa). To 0.5 g (1.4 mmol) of
acrylate IIIa in 10 ml of anhydrous acetonitrile was
added 0.16 g (2.8 mmol) of KF, the reaction mixture
was boiled for 2 h, cooled, and the precipitate was
filtered off. The filtrate was evaporated, the residue
was recrystallized from ethanol. Yield 0.35 g (74%).
1H NMR spectrum (CDCl3), , ppm: 1.29 t (3H,
CH3), 4.28 q (2H, OCH2), 6.82 s (1H, H3), 7.23 m
(1H, H6 ), 7.38 s (1H, H2), 9.16 s (1H, H5).
19F NMR spectrum (DMSO-d6), F, ppm: 157.12 m,
153.67 m, 139.87 m, 138.31 m. Mass spectrum, m/z
4
5
3JHF 14.1, JHF 6.1, JHF 2.3 Hz), 8.54 s (1H, H2),
9.34 s (1H, H5).
7-(4-Morpholino-2,3,5-trifluorophenyl)-6-ethoxy-
carbonyl-1,2,4-triazolo[1,5-a]pyrimidine (VIIIb).
To a solution of 0.5 g (1.47 mmol) of compound
VIIb in 8 ml of dimethylformamide was added 0.5 g
(6.0 mmol) of morpholine. The reaction mixture was
boiled for 4 h, cooled, diluted with water, the pre-
cipitate was filtered off and recrystallized from
ethanol. Yield 0.38 g (60%). 1H NMR spectrum
(CDCl3), , ppm: 1.29 t (3H, CH3), 3.40 m [4H,
N(CH2)2], 3.86 m [4H, O(CH2)2], 4.38 q (2H,
(I , %): 339 (85) M+ , 320 (87), 294 (29), 292
rel.
3
4
OCH2), 7.09 d.d.d (1H, H6 , JHF 14.0, JHF 6.0,
1
(100), 266 (21). IR spectrum, KBr, , cm : 1725
(CO).
5JHF 2.4 Hz), 8.55 s (1H, H2), 9.40 s (1H, H5).
7-Tetrafluorophenyl-6-ethoxycarbonyl-1,2,4-tri-
azolo[1,5-a]pyrimidine (VIIb). To 1.6 g (4.5 mmol)
of acrylate IIIc in 10 ml of anhydrous acetonitrile was
added 0.5 g (8.6 mmol) of KF, the reaction mixture
was boiled for 2 h, cooled, and the precipitate was
filtered off. The filtrate was evaporated, the residue
was recrystallized from ethanol. Yield 0.9 g (60%).
1H NMR spectrum (DMSO-d6), , ppm: 1.15 t (3H,
CH3), 4.24 q (2H, OCH2), 7.85 m (1H, H6 ), 8.80 s
(1H, H2), 9.40 s (1H, H5). 19F NMR spectrum
(DMSO-d6), F, ppm: 156.4 m, 151.9 m, 139.2 m,
Ethyl 1-(5-hydroxy-4-ethoxycarbonyl-1,2,3-tri-
azol-1-yl)-4-oxo-6,7,8-trifluoro-1,4-dihydroquino-
line-3-carboxylate (XV). To 0.55 g (2.83 mmol) of
aminotriazole XIII in 15 ml of anhydrous ethanol was
added 0.91 g (2.83 mmol) of ethyl 2-tetrafluoro-
benzoyl-3-ethoxyacrylate (Ia). The reaction mixture
was stirred for 2 h at 18 20 C, then it was evaporated
to 1/3 of its volume, and the separated precipitate was
filtered off. We obtained 1.3 g of a mixture contain-
ing acrylate XIV and quinolone XV. To the pre-
cipitate was added 15 ml of anhydrous benzene, the
reaction mixture was boiled for 3 h, then evaporated,
and the residue was recrystallized from benzene.
137.5 m. Mass spectrum, m/z (I , %): 340 (100)
rel.
M+ , 321 (32), 312 (29), 311 (16), 295 (92), 293 (91),
1
292 (51), 221 (15), 201 (14), 188 (13). IR spectrum,
Yield 0.9 g (50%). H NMR spectrum (CDCl3), ,
ppm: 1.38 t (3H, CH3), 1.40 t (3H, CH3), 4.35 q
1
KBr, , cm : 1720 (CO).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001

576
LIPUNOVA et al.
(2H, OCH2), 4.43 q (2H, OCH2), 8.09 d.d.d (1H,
pp. 1567 1569.
3
4
5
H5, JHF 10.3, JHF 8.3, JHF 2.0 Hz), 8.30 s (1H,
6. Nosova, E.V., Lipunova, G.N., Mokrushina, G.A.,
Chasovskikh, O.M., Rusinova, L.I., Charushin, V.N.,
and Aleksandrov, G.G., Zh. Org. Khim., 1998,
vol. 34, no. 3, pp. 436 443.
7. Filyakova, V.I., Kuznetzova, O.A., Pashkevich, K.I.,
Rusinov, G.L., and Plechanov, P.V., International
Memorial I. Postovsky Conf. on Org. Chem., Yeka-
terinburg, 1999, p. 60.
8. Desenko, S.M., Orlov, V.D., Shishkin, O.V., Bary-
kin, K.E., Lindeman, S.V., and Struchkov, Yu.T.,
Khim. Geterotsikl. Soed., 1993, no. 10,
pp. 1357 1363.
H2), 10.63 s (1H, OH). 19F NMR spectrum (DMSO-
3
3
d6), F, ppm: 151.61 d.d.d (1F, F7, JFF 23.2, JFF
19.4, JHF 8.3 Hz), 148.04 d.d.d (1F, F8, JFF 19.4,
4
3
4JFF 4.7, JHF 2.0 Hz), 136.48 d.d.d (F6, JFF 23.1,
5
3
3JHF 10.3, JFF 4.7 Hz). Mass spectrum, m/z (I
,
4
rel
%): 426 (12) M+ , 381 (3), 354 (35), 334 (10), 283
(18), 271 (100), 226 (77), 197 (42), 169 (91).
REFERENCES
1. Kotovskaya, S.K., Perova, N.M., Baskakova, Z.M.,
Romanova, S.A., Charushin, V.N., and Chupa-
khin, O.N., Zh. Org. Khim., 2001, vol. 37, no. 4,
pp. 598 603.
2. Charushin, V.N., Lipunova, G.N., Nosova, E.V.,
Sidorova L.P., and Chasovskikch, O.M., Mendeleev
Commun., 1998, no. 4, pp. 131 133.
9. Kofman, T.P., Uvarova, T.A., Kartseva, G.Yu., and
Uspenskaya, T.L., Zh. Org. Khim., 1997, vol. 33,
no. 12, pp. 1867 1876.
10. Vartayan, M.M., Solov,eva, T.Yu., Eliseev, O.L.,
and Panina, M.E., Izv. Akad. Nauk, Ser. Khim.,
1993, no. 7, p. 1322.
3. Lipunova, G.N., Sidorova, L.P., Nosova, E.V.,
Perova, N.M., Charushin, V.N., and Aleksand-
rov, G.G., Zh. Org. Khim., 1999, vol. 35, no. 11,
pp. 1729 1735.
4. Mokrushina, G.A., Nosova, E.V., Lipunova, G.N.,
and Charushin, V.N., Zh. Org. Khim., 1999, vol.
35, no. 10, pp. 1447 1463.
11. Krivopalov, V.P., Mamatyuk, V.I., and Mama-
ev, V.P., Khim. Geterotsikl. Soed., 1990, no. 12,
pp. 1648 1654.
12. Ulomskii, E.N., Rusinov, V.L., Chupakhin, O.N.,
Rusinov, G.L., Chernyshev, A.I., and Aleksand-
rov, G.G., Khim. Geterotsikl. Soed., 1987, no. 11,
pp. 1543 1550.
5. Parikh, V.D., Fray, A.H., and Kleinman, E.F.,
J. Heterocyclic. Chem., 1988, vol. 25, no. 5,
13. Cobb, J. and Cheeseman, G.W.H., Magn. Reson.
Chem., 1986, vol. 24, pp. 231 237.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 4 2001