Synthesis of fluoroalkylated dihydroazolo[1,5-a]pyrimidines and their ring-chain isomerism

Article abstract of DOI:10.3987/COM-08-11524

Cyclisation of ethyl 2-ethoxymethylidene-3-polyfluoroalkyl-3-oxopropionates with 3-amino-1H-[1,2,4]triazole, 3-amino-5-methylpyrazole, ethyl 3-aminopyrazole-4-carboxylate and ethyl 5-aminoimidazole-4-carboxylate hydrochloride results in the formation of p

Full text of DOI:10.3987/COM-08-11524

HETEROCYCLES, Vol. 78, No. 2, 2009
435
HETEROCYCLES, Vol. 78, No. 2, 2009, pp. 435 - 447. © The Japan Institute of Heterocyclic Chemistry
Received, 15th August, 2008, Accepted, 29th September, 2008, Published online, 6th October, 2008.
DOI: 10.3987/COM-08-11524
SYNTHESIS OF FLUOROALKYLATED
DIHYDROAZOLO[1,5-a]PYRIMIDINES AND THEIR RING-CHAIN
ISOMERISM
1*
1
1
Marina V. Goryaeva, Yanina V. Burgart, Victor I. Saloutin, Elena V.
2
2
Sadchikova, and Evgeny N. Ulomskii
1
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian
Academy of Sciences, Ekaterinburg, 620041, Russian Federation. Fax: +7 343
3
74 5954. E-mail: pmv@ios.uran.ru;
2Ural State Technical University - UPI, Ekaterinburg, 620002, Russian Federation
Abstract – Cyclisation of ethyl 2-ethoxymethylidene-3-polyfluoroalkyl-3-oxo-
propionates with 3-amino-1H-[1,2,4]triazole, 3-amino-5-methylpyrazole, ethyl
3
-aminopyrazole-4-carboxylate and ethyl 5-aminoimidazole-4-carboxylate
hydrochloride results in the formation of polyfluoroalkylated
dihydroazolo[1,5-a]pyrimidines. The latter are subject to ring-chain isomerisation
in solutions depending on the solvent and the “length” of the fluoroalkyl
substituent to yield ethyl 3-polyfluoroalkyl-3-oxo-2-[(azol-3-yl)aminomethyli-
dene]propionates via opening of the heterocycle at the C-N bond. Dehydration of
dihydroazolo[1,5-a]pyrimidine were realized.
INTRODUCTION
Azolo[a]pyrimidines containing a bridging nitrogen atom are structural analogues (isosteres) of purine
1
bases and can therefore disturb the metabolism and hinder the protein biosynthesis. New families of
2
antiviral compounds have been found among these compounds. Syntheses of such azolopyrimidines
widely employ condensations of 1,3-dielectrophiles with aminoazoles that contain an NH group at the
3
4
α-position. Convenient 1,3-dielectrophiles include 1,3-dicarbonyl compounds and unsaturated ketones. It
is most promising to synthese azolo[a]pyrimidines with functional groups that are capable of various
conversions. Compounds suitable for this purpose include 1,3-dicarbonyl compounds functionalised at
5
6
position 2. In fact, 2-arylmethylidene- and 2-ethoxymethylidene-3-oxoesters are suitable for building
azolo[1,5-a]pyrimidines containing an alkoxycarbonyl fragment. distinctive feature of
A

436
HETEROCYCLES, Vol. 78, No. 2, 2009
polyfluoroalkylated derivatives of 3-oxoesters in these syntheses is that they can form stable
tetrahydroazolo[1,5-a]pyrimidines with a gem-aminoalcohol fragment at the polyfluoroalkyl
4a,5d
substituent.
RESULTS AND DISCUSSION
In this work, aimed at the synthesis of potential biologically-active compounds, we have studied the
reactions of ethyl 2-ethoxymethylidene-3-oxo-3-polyfluoroalkylpropionates 1a-c with aminoazoles
(
3-amino-1H-[1,2,4]triazole 2, 3-amino-5-methylpyrazole 3a, ethyl 3-aminopyrazole-4-carboxylate 3b
and ethyl 5-aminoimidazole-4-carboxylate hydrochloride 4).
It has been found that esters 1a-c on refluxing in 1,4-dioxane with aminoazoles 2, 3a,b, 4 undergo
conjugate substitution - addition at the ethoxymethylidene - fluoroacyl fragment to give
dihydroazolo[1,5-a]pyrimidines 5a-c, 7a-d, 9a,b (Scheme 1). The reaction could not be repeated by
heating to reflux in ethanol or by heating in DMF at ~ 80 ºC.
N
O
F
H N
F
2
R
HO
R
NH EtO
N
EtO C
N
N
2
EtO C
N
N
2
N
N
N
2
N
F
iii
-H O
R
N
NH
N
N
2
O H
H
6
a-c
5
'a-c
5a-c
2
H N
R
2
OEt
OEt
N
1
F
F
R
O
HO
R
R
N
2
F
EtO
1
H
R
R
R
EtO C
N
EtO C
1
2
2
N
N
3a,b
N
1
R
F
R
i
R
N
O
O
iii
-H O
N
NH
2
N
1
a-c
O H
N
H
R
2
2
R
7
'a-d
7a-d
8a-c
H N
CO Et
2
2
F
O
HO
R
EtO
EtO C
HN
N
HCl
2
EtO C
2
N
.
4
N
N
F
R
N
N
ii
O H
N
H
CO Et
H
2
9
'a,b
9a,b
F
1
2
1
2
F
1
7
8
: R = CF (a), (CF ) H (b), C F (c); 3: R = Me, R = H (a); R = H, R = CO Et (b); 5, 6: R = CF (a), (CF ) H (b), C F (c);
3
2 2
3
7
2
3
2 2
3
2
7
F
1
2
F
1
2
F
1
2
F
1
: R = CF , R = Me, R = H (а); R = C F , R = Me, R = H (b); R = CF , R = H; R = CO Et (c); R = (CF ) H, R = H; R = CO Et (d);
3
3
7
3
2
2 2
2
F
1
2
F
1
2
F
1
2
F
: R = CF , R = Me, R = H (a); R = CF , R =H, R = CO Et (b); R = CF , R =H, R = CO Et; 9: R = CF (а), (CF ) H (b).
3
3
2
3
2
3
2 2
Scheme 1. Conditions: i, 1,4-dioxane, ∆; ii, NaOAc; iii, AcOH, ∆
Condensation of 2-ethoxymethylidene-substituted acetoacetic ester with 3-amino-1H-[1,2,4]triazole and
6
b
3
-aminopyrazoles is known to give 6-ethoxycarbonylazolo[1,5-a]pyrimidines.
X-Ray diffraction analysis of crystalline compound 5b (Figure 1) reveals that it is ethyl
-hydroxy-7-tetrafluoroethyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate, in which XRD
7

HETEROCYCLES, Vol. 78, No. 2, 2009
437
data show the existence of an O(1)…H(1) intramolecular hydrogen bond (IMHB). The IMHB parameters
for compound 5b are as follows: the intramolecular distance O(1)…H(1) is 1.89(0) Ǻ; the O(1) –
H(1)…O(3) and C(8) – O(1)…H(1) angles are 148.28° and 99.03°. The existence of an IMHB in
triazolopyrimidine 5b is also supported by its IR spectrum where a low-frequency shift of the
-1
ethoxycarbonyl group's stretching vibration absorption band (1682 cm ) is observed in comparison with
-1 7
the values of C=O groups in α,β-unsaturated esters (1730-1710 cm ).
Figure 1. The general view of compound 5b
A comparison of the IR spectra of compounds 5a,c nujol did not reveal considerable differences in their
features.
The IR spectra of compounds 7a,b nujol contain one intense ethoxycarbonyl group’s absorption band at
-1
1
680-1670 cm . In the IR spectra of products 7c,d, 9a,b, having two ethoxycarbonyl groups, two
-1
absorption bands at 1673-1672 and 1690-1689 cm are observed.
Based on the above data, it is believed that the compounds 5a-c, 7a-d, 9a,b in the solid state exist as
cyclic form of dihydroazolo[1,5-a]pyrimidines.
The structure of products 5a-c, 7a-d, 9a,b in solutions was studied by NMR spectroscopy.
1
The H NMR spectra of compounds 5a-c, recorded in (CD
3
)
2
SO, contain signals of ethoxy-group protons,
singlet signals of two methine protons (H(2), H(5)) and broadened low-field singlet signals of NH and
OH protons. These signals should be assigned to the resonance absorption of protons in bicyclic form 5.
1
9
The F NMR spectrum of product 5a contains a singlet signal of the fluorine atoms at the trifluoromethyl
3
5d
group at δ ~ 83.94 ppm, which is typical for the CF
3
group at the sp -hydridized carbon atom in form 5.
However, the H and F NMR spectra of compound 5c, recorded in (CD SO, as well as containing the
set of signals belonging to cyclic form 5 (80 %), is also two additional sets of signals corresponding to the
1
19
3 2
)

438
HETEROCYCLES, Vol. 78, No. 2, 2009
(
Z)-5' (11 %) and (E)-5' (9%) isomers. Ethyl-2-(het)arylmethylidene-3-oxo-3-fluoroalkylpropionates
8
have previously discovered to exist in a mixture of Z,E-isomeric forms.
1
3
Furthermore the C NMR spectrum 5c in (CD
Z)-5' and (E)-5' open-chain isomers. In this spectrum, the signals of carbon atoms at the
heptafluoropropyl substituent are significant; they have the shape of a triplet due to interactions with the
nearby fluorine atoms of the α-CF group. The two low-field triplet signals (δ 179.43 and 180.74 ppm)
3 2
) SO confirms the presence of the bicyclic form 5 and the
(
2
are due to the resonance absorption of the C(3) carbonyl atoms of the (Z)- 5' and (E)- 5' forms, whereas a
triplet signal of resonance absorption of the C(7) atom of the predominant cyclic form 5 is observed at
3
5d
8
6.53 ppm, which is characteristic of the sp -hybridised carbon atom.
8
Earlier , assignment of signals of C(1) and C(3) atoms for the (Z)-5' and (E)-5' isomers was performed.
Thus the signal of the C(1) atom in the ethoxycarbonyl of the (Z)- 5' form is observed in lower field
(
165.09 ppm) in comparison with the corresponding signal of the (E)-5' form (164.11 ppm), whereas the
signals of the C(3) carbonyl atom at the polyfluoroacyl fragment of isomeric forms (Z)-5' and (E)-5' are
8
arranged in the opposite order.
1
19
3 2
In the Н and F NMR spectra of trifluoromethylated compounds 7a,c in (CD ) SO are observed signals
1
19
corresponding to the only cyclic form 7. However the Н and F NMR spectra of compounds 7b,d
F
having longer fluoroalkyl substituents (R = (CF
2
)
2
H, C
3
F
7
) contain in addition to the signals of cyclic
form 7, the signals of the (Z)-7' and (E)-7' isomers of open forms.
1
19
According to the data of the Н and F NMR spectroscopy in (CD
mixture of (Z)-9' and (E)-9' isomers of open forms ((2-[(imidazolyl)aminomethylidene]-3-oxo-
-polyfluoroalkylpropionates)) and cyclic (1,4-dihydroimidazo[1,5-a]pyrimidine) form 9.
The discovery of the ability of heterocycles 5c, 7b, 7d, 9a,b to undergo open-chain isomerism in
3 2
) SO the compounds 9a,b exist as a
3
1
19
(
3
CD )SO prompted us to study the H and F NMR spectra of compounds 5, 7, 9 in various solvents. The
result of this study is depicted in Table, where the existence of compounds 5, 7, 9 depends on the NMR
solvent used.
1
It is found that the H NMR spectra of compounds 5b,c, 7b,d and 9a in (CD ) CO contain, in addition to
3
2
the signals corresponding to cyclic form, also signals of the Z- and E-isomers of open form 5', 7', 9'. In
1
contrast, the H NMR spectra of compounds 5a, 7a,c in (CD
3
)
2
CO show that only cyclic form are present.
CN show that the cyclic form and the Z-
1
However, the H NMR spectra of compounds recorded in CD
3
and E-isomers are presented not only for compounds 5b,c, 7b,d, 9a but for the product 5a as well (Table
1
).
1
H NMR spectra of compound 9b in (CD
3
)
2
3
CO and CD CN contain non-cyclic form (Z)-9'b and (E)-9'b
(
Table 1).
1
The signals of the cyclic form are found in the H NMR spectra of compounds 5a-c, 7a-d measuring in

HETEROCYCLES, Vol. 78, No. 2, 2009
439
3 3
CD OD (Table 1). The compounds 7d and 9a,b in CD OD exist as a mixture of the open and cyclic forms.
The heterocycles 5a-c, 7a-d, 9a,b are insoluble in CDCl
3
.
Table 1. Cyclic and open-chain forms ratios according to the NMR data
compounds solvent
F
R
(
СD
3
)
2
SO
CD
3
CN
(CD
3
)
2
CO
3
CD OD
5
a
CF
3
5a, 100 %
5a, 92 %
5a, 100 %
5a, 100 %
5b, 100 %
5c, 100 %
(
(
Z)-5'a, 3 %
Е)-5'a, 5 %
5b
(CF
2
)
2
H 5b, 100 %
5b, 68 %
5b, 59 %
(
(
Z)-5'b, 11 %
Е)-5'b, 21 %
(Z)-5'b, 15 %
(Е)-5'b, 26 %
5c, 28 %
5
c
C
3
F
7
5c, 80 %
5c, 41 %
(
(
Z)-5'c, 11 %
Е)-5'c, 9 %
(Z)-5'c, 32 %
(Е)-5'c, 27 %
7a, 100 %
7b, 19%
(Z)-5'c, 41 %
(Е)-5'c, 31 %
7a, 100 %
7
a
CF
3
7a, 100 %
7b, 40 %
7a, 100 %
7b, 100 %
7b
C
3
F
7
7b, 3 %
(
(
Z)-7'b, 26 %
Е)-7'b, 33 %
(Z)-7'b, 35 % (Z)-7'b, 44 %
(Е)-7'b, 46 %
7c, 100 %
(Е)-7'b, 53 %
7c, 100 %
7
c
CF
3
7c, 100 %
7c, 100 %
7d
9a
9b
(CF
2
)
2
H 7d, 81 %
7d, 60 %
7d, 45 %
7d, 3 %
(
(
Z)-7'd, 7 %
(Z)-7'd, 13 %
(E)-7'd, 27 %
9a, 32 %
(Z)-7'd, 19 %
(E)-7'd, 36 %
9a, 22 %
(Z)-7'd, 19 %
(E)-7'd, 7 %
9a, 69 %
E)-7'd, 12 %
CF
3
9a, 72 %
(
(
Z)-9'a, 10 %
E)-9'a, 18 %
(Z)-9'a, 26 %
(E)-9'a, 42 %
(Z)-9'b, 27 %
(E)-9'b, 73 %
(Z)-9'a, 31 %
(E)-9'a, 47 %
(Z)-9'b, 31 %
(E)-9'b, 69 %
(Z)-9'a, 10 %
(E)-9'a, 21 %
9b, 11 %
2 2
(CF ) H 9b, 19 %
(
(
Z)-9'b, 27 %
E)-9'b, 54 %
(Z)-9'b, 25 %
(E)-9'b, 64 %
1
A specific feature of signals of the open-chain isomers 5', 7', 9' in the H NMR spectrum is the character
of resonance absorption of the =CH and NH protons of their aminomethylidene fragment that are
observed as low-field doublets with a coupling constant of ~ 14 Hz, which is evidence of their
9
trans-configuration. The signals of fluorine atoms of the CF
3
2
and α-CF groups of open form 5'c, 7'b,d
1
9
and 9'a,b in the F NMR spectra in (CD
3
)
2
SO are characterised by a downfield shift (δCF3 90.83-91.82,

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HETEROCYCLES, Vol. 78, No. 2, 2009
δα-CF2((CF2)2H) 42.98-43.11, δα-CF2(C3F7) 49.61-50.23 ppm) with respect to the corresponding signals of
fluorine atoms in cyclic form 9a, 5b (δCF3 81.38, δα-CF2((CF2)2H) 32.29-41.79, δα-CF2(C3F7) 46.13-46.26 ppm).
1
Assignment of the Z- and E-isomers of open form in the H NMR spectra was made using the regularities
that we reveled previously for 2-alkyl(aryl)aminomethylidene-3-fluoroalkyl-3-oxopropionates, according
to which the protons of the =CН and NH groups of the E-isomer are observed in weaker field than the
8
corresponding protons of the Z-isomer.
Dehydration of 4,7-dihydrotriazolo[1,5-a]pyrimidines 5a-c is hindered. In fact, prolonged refluxing (~60
h) in acetic acid is necessary to obtain ethyl 7-polyfluoroalkyl-[1,2,4]triazolo[1,5-a]pyrimidine-
6
-carboxylates 6a-c.
Dehydration of 4,7-dihydropyrazolo[1,5-a]pyrimidine 7a,b,d in boiling acetic acid proceeds easily to
give ethyl-7-(fluoroalkyl)pyrazolo[1,5-a]pyrimidine-6-carboxylates 8a-c.
An attempts to dehydrate dihydroimidazo[1,5-a]pyrimidine 9a,b under similar conditions were
unsuccessful because of their resinification.
To summarize the obtained data, it can be concluded that fluoroalkyl-containing
dihydroazolo[1,5-a]pyrimidines 5, 7, 9 can undergo ring-chain isomerism. Thus, they have cyclic
structures in the solid state, whereas in solution, depending on the solvent and the “length” of the
fluoroalkyl substituent, they may also exist in open-chain form 5', 7', 9'. It should be noted that this kind
of
isomerism
is
not
typical
for
their
non-fluorinated
analogues,
viz,
2
-azolylaminomethylidene-3-oxoalkanoates. The latter compounds are only capable of irreversible
6b
intramolecular condensation to give azolopyrimidines. Ring-chain isomerism becomes possible owing
to the presence of an electron-withdrawing polyfluoroalkyl substituent that prevents easy elimination of a
water molecule and the formation of azolopyrimidines 6, 8, on the one hand, and facilitates the addition
of an amine to give dihydroazolopyrimidines 5, 7, 9 that are stabilized due to formation of the strong
IMHBs, on the other hand.
EXPERIMENTAL
Melting points were measured in open capillaries by apparatus “Stuart SMP3”. The infrared spectra were
recorded on Perkin Elmer Spectrum One FT-IR and Thermo Nicolet 6700 FT-IR spectrometers at
-1
1
13
4
000-400 cm in Nujol mulls. The H and C NMR spectra were measured on a Bruker DRX-400
1
13
19
spectrometer ( H, 400; C, 100.6 MHz) relative to SiMe4. The F NMR spectra were obtained on a
1
9
6 6
Bruker DRX-400 spectrometer ( F, 376 MHz) using C F as an internal standard. The microanalyses
were carried out on a Perkin Elmer PE 2400 series II elemental analyzer.
Ethyl 2-ethoxymethylidene-3-polyfluoroalkyl-3-oxopropionates 1a-c were prepared according to a
8
11
reported procedure, ethyl 5-aminoimidazole-4-carboxylate hydrochloride
4
–
procedure.

HETEROCYCLES, Vol. 78, No. 2, 2009
441
3
-Amino-1H-[1,2,4]tria- zole 2, 3-amino-5-methylpyrazole 3a, ethyl 3-aminopyrazole-4-carboxylate 3b
are commercial compounds.
Crystallographic data for 5b: at 295 К, C10
H
10
F
4
N
4
O
3
1
(M = 310.22) are monoclinic, space group P2 /c, a
3
=
16.737(2) Å, b= 8.7692(10) Å, c = 8.8892(10) Å, β = 100.022(10) º, V = 1284.7(3) Å , Z = 4, dcalc
=
-
1
-1
1
.604 g/cm , µ (Mo-K
Xcalibur 3 at 295 К (ω/2θ-scans, Mo-K
reflection (Rint = 0.0211) were used in further refinement. The structure was solved by the direct methods
α
) = 0.157 cm , F(000) = 632. The intensities of 14817 were measured with a
α
, graphite monochromator, CCD-detector) and 3963 independent
1
0
with the set programs SHELXL-97 and refined by full-matrix least-squares method. The refinement
converged to wR = 0.1885 and GOF = 1.000 for all independent reflections (R = 0.0633 for 2225
2
1
reflection with F
compound.1
General procedure A: A mixture of ester 1 (3 mmol) and aminoazole 2, 3a,b (3 mmol) in 1,4-dioxane
20 mL) was refluxed for 16-18 h. The reaction mixture was poured into water. The resulting precipitate
o
>4σ(F
o
)). CCDC 646963 contains the supplementary crystallographic data for this
(
was filtered off and recrystallized from EtOH.
General procedure B: The solution of pyrimidine 5, 7 (1 mmol) in glacial acetic acid was refluxed for
6
-60 h. The reaction mixture was poured into water and was reduced to pH 7. The resulting precipitate
was filtered off and recrystallized from hexane.
General procedure C: A mixture of ester 1a,b (3 mmol), ethyl 5-aminoimidazole-4-carboxylate
2
hydrochloride (0.575 g, 3 mmol) and NaOAc*3H O (0.408 g, 3 mmol) in 1,4-dioxane (20 mL) was
refluxed for 12-14 h. The reaction mixture was poured into water. The resulting precipitate was filtered
off and recrystallized from EtOH.
Ethyl 7-hydroxy-7-(trifluoromethyl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate (5a).
The ester 1a (0.720 g, 3 mmol) gave by procedure A 0.601 g (72 %) of product 5a, mp 184-186 ºС. Anal.
Calcd for C
9
H
9
F
3
N
4
O
3
: C, 38.86; H, 3.26; F, 20.49; N, 20.14. Found: C, 38.86; H, 3.11; F, 20.47; N,
Et), 1599, 1521 (C=C, C=N), 1267-1158
СН ), 4.15 (m, AB-system, ∆AB 0.05 ppm,
), 7.88, 7.91 (both s, 1H each, H(2), Н(5)), 8.48 (s, 1H, NH), 11.77 (br.s,
H, OH) ppm. F NMR (DMSO-d ): δ 83.94 (s, СF ) ppm.
2
0.27 %. IR: ν 3200, 3114, (NH, OH), 2923 (C-H), 1678 (СO
2
-1 1
(
C-F) cm . Н NMR (DMSO-d
6
): δ 1.23 (t, J 7.0 Hz, 3Н, ОСН
2
3
J
AB 10.8, J 7.0 Hz, 2Н, ОСН
2
СН
3
1
9
1
6
3
Ethyl 7-hydroxy-7-(1,1,2,2-tetrafluoroethyl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxy-
late (5b).
The ester 1b (0.817 g, 3 mmol) gave by procedure A 0.633 g (68 %) of product 5b, mp 155-157 ºС. Anal.
1
These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).

442
HETEROCYCLES, Vol. 78, No. 2, 2009
Calcd for C10
H
10
F
4
N
4
3
O : C, 38.72; H, 3.25; F, 24.50; N, 18.06. Found: C, 38.96; H, 3.20; F, 24.52; N,
1
2
8.03 %. IR: ν 3220, 3108, (NH, OH), 2930 (C-H), 1682 (СO Et), 1614, 1529 (C=C, C=N), 1206-1078
-1 1
(
C-F) cm . Н NMR (DMSO-d ): δ 1.24 (t, J 7.0 Hz, 3Н, ОСН СН ), 4.16 (m, AB-system, ∆ 0.03 ppm,
6
2
3
AB
J
AB 10.7, J 7.0 Hz, 2Н, ОСН
2
СН
3
), 6.70 (d.d.d.d, JH,F 53.2, 51.3, 10.5, 2.4 Hz, 1H, (CF
2
)
2
H), 7.86, 7.91
1
(
both s, 1H each, H(2), H(5)), 8.36 (s, 1H, NH), 11.68 (br.s, 1H, OH) ppm. Н NMR ((CD
3
)
2
СO): δ 5b
(
59 %)1.24 (t, J 7.1 Hz, 3Н, ОСН
0.4, 2.3 Hz, 1H, (CF H), 7.34 (br.s, 1Н, NH), 7.85, 8.09 (both s, 1H each, H(2), H(5)), 10.69 (s, 1H,
OH); (Z)-5b' (15 %) 1.35 (t, J 7.0 Hz, 3Н, ОСН СН ), 4.29 (q, J 7.0 Hz, 2H, ОСН СН ), 6.66 (t.t, JH,F
2.7, 5.9 Hz, 1H, (CF H), 8.48 (br.s, 1H, H(5')), 8.79 (d, J 13.5 Hz, 1H, СH), 11.08 (br.d, J 13.5 Hz, 1H,
NH,), 13.20 (br.s, 1H, NH(1')); (E)-5b' (26 %) 1.34 (t, J 7.0 Hz, 3Н, ОСН СН ), 4.36 (q, J 7.0 Hz, 2H,
ОСН СН ), 6.95 (t.t, JH,F 53.4, 5.8 Hz, 1H, (CF H), 8.52 (br.s, 1H, H(5')), 8.98 (d, J 13.5 Hz, 1H, СH),
2 3 2 3
СН ,), 4.29 (q, J 7.1 Hz, 2Н, ОСН СН ), 6.73 (d.d.d.d, JH,F 52.1, 53.0,
1
2 2
)
2
3
2
3
5
2 2
)
2
3
2
3
2 2
)
1
9
1
2
0.69 (br.d, J 13.5 Hz, 1H, NH), 13.27 (br.s, 1H, NH(1')) ppm. F NMR (DMSO-d ) δ: 26.04 (t.d.d, J
6
F,F
93.71, 9.6, JF,H 53.2 Hz, 1F, CF
2
H), 31.02 (d.d.d.d, JF,F 293.7, 10.6, 1.4, JF,H 51.3 Hz, 1F, CF
2
H), 32.97
(
d.d.d, JF,F 261.2, 19.6, JF,H 10.5 Hz, 1F, CF
2
), 41.66 (d.d.d, JF,F 261.2, 10.6, JF,H 2.4 Hz, 1F, CF
2
) ppm.
Ethyl 7-(1,1,2,2,3,3,3-heptafluoropropyl)-7-hydroxy-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-
carboxylate (5c).
The ester 1c (1.021 g, 3 mmol) gave by procedure A 0.681 g (60 %) of product 5c, mp 136-138 ºС. Anal.
Calcd for C11
H
9
F
7
N
4
O
3
: C, 34.93; H, 2.40; F, 35.16; N, 14.81. Found: C, 34.94; H, 2.11; F, 35.25; N,
4.81 %. IR: ν 3200, 3115 (NH, OH), 3015, 2924 (C-H), 1693 (СO Et), 1602, 1599 (C=C, C=N),
): δ 5c (80 %) 1.25 (t, J 7.2 Hz, 3Н, ОСН СН ), 4.18 (m,
СН ), 7.89, 7.92 (both s, 1H each, H(2), Н(5)),
.56 (s, 1H, NH), 11.81 (br.s, 1H, OH); (Z)-5c' (11 %) 1.25 (t, J 7.1 Hz, 3Н, ОСН СН ), 4.27 (q, J 7.1
1
1
2
-1 1
220-1119 (C-F) cm . Н NMR (DMSO-d
6
2
3
AB-system, ∆AB 0.04 ppm, JAB 10.8, J 7.2 Hz, 2Н, ОСН
2
3
8
2
3
Hz, 2H, ОСН
2
3
СН ), 8.56 (s, 1H, H(5')), 8.60 (d, J 13.9 Hz, 1H, CH), 11.29 (d, J 13.9 Hz, 1H, NH), 14.13
(
br.s, 1H, NH(1')); (E)-5c' (9 %) 1.25 (t, J 7.1 Hz, 3Н, ОСН СН ), 4.26 (q, J 7.1 Hz, 2H, ОСН СН ),
2
3
2
3
8
.58 (s, 1H, H(5')), 8.77 (d, J 13.9 Hz, 1H, CH), 11.81 (d, J 13.9 Hz, 1H, NH), 14.22 (br.s, 1H, NH(1'))
1
9
ppm. F NMR (DMSO-d
6.26 (m, 2F, α-CF ), 82.34 (t, JF,F 11.6 Hz, 3F, CF
α-CF ), 82.94 (t, JF,F 9.3 Hz, 3F, CF ); (E)-5c' (9 %): 39.64 (m, 2F, β-CF
F,F 9.3 Hz, 3F, CF ,) ppm. C NMR (DMSO-d
80%) 14.03 (CH
6
): δ 2c (80 %) 37.44 (m, AB-system, ∆AB 1.40 ppm, JAB 290.0 Hz, 2F, β-CF
2
),
4
2
3
); (Z)-2c' (11%): 38.43 (m, 2F, β-CF
2
), 49.96 (m, 2F,
2
3
2
2
), 49.61 (m, 2F, α-CF ), 82.92 (t,
1
3
J
3
6
): δ 105.81-121.88 (m, С
), 86.53 (t, JC,F 27.2 Hz, C(7)), 96.86 (C(6)), 139.09 (C(5)), 147.19
), 60.86 (OCH ), 101.77 (C(2)), 144.52
C(5')), 151.52 (C(4')), 157.15 (C(3')), 165.09 (C(1)), 179.43 (br.t, JC,F 25.4 Hz, C(3)); (E)-5c' (9 %)
3 7
F ((E)-5c', (Z)-5c', 5c)); 5c
(
(
(
3
), 59.89 (OCH
2
C(3a)), 150.56 (C(2)), 163.98 (C(9)); (Z)-5c' (11 %) 13.74 (CH
3
2
1
1
3.85 (CH
3 2
), 60.69 (OCH ), 100.63 (C(2)), 144.73 (C(5')), 154.90 (C(4)), 156.69 (C(3')), 164.11 (C(1)),
80.74 (br.t, JC,F 25.0 Hz, C(3)) ppm.

HETEROCYCLES, Vol. 78, No. 2, 2009
443
Ethyl 7-(trifluoromethyl)-5H-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate (6a).
Pyrimidine 5a (0.278 g, 1 mmol) gave by procedure B 0.247 g (95 %) of product 6a, mp 77-78 ºС. Anal.
Calcd for C : C, 41.55; H, 2.71; F, 21.91; N, 21.53. Found: C, 41.69; H, 2.80; F, 21.78; N,
1.69 %. IR: ν 3069, 3018 (C-H), 1719 (СO
NMR (DMSO-d ): δ 1.37 (t, J 7.2 Hz, 3Н, ОСН
H(5)), 10.16 (s, 1H, H(2)) ppm. F NMR (DMSO-d
9
7 3 4 2
H F N O
-1 1
2
2
Et), 1627, 1511 (C=C, C=N), 1191-1129 (C-F) cm . Н
СН ), 4.41 (q, J 7.2 Hz, 2Н, ОСН СН ), 9.05 (s, 1H,
): δ 98.46 (s, СF ) ppm.
6
2
3
2
3
1
9
6
3
Ethyl 7-(1,1,2,2-tetrafluoroethyl)-5H-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate (6b).
Pyrimidine 5b (0.310 g, 1 mmol) gave by procedure B 0.228 g (78 %) of product 6b, mp 93-95 ºС. Anal.
8 4 4 2
Calcd for C10H F N O : C, 41.11; H, 2.76; F, 26.01; N, 19.17. Found: C, 41.25; H, 2.81; F, 25.89; N,
-1
1
8.95 %. IR: ν 3118, 3079, 3029 (C-H), 1707 (СO Et), 1620, 1506 (C=C, C=N), 1164-1071 (C-F) cm .
2
1
Н NMR (DMSO-d
1.8, 6.0 Hz, 1Н, (CF
d.m, JF,H 51.8 Hz, 2F, СF
6
): δ 1.36 (t, J 7.1 Hz, 3Н, ОСН
H), 9.02 (s, 1H, H(5)), 10.12 (s, 1H, H(2)) ppm. F NMR (DMSO-d
H), 48.38 (m, 2F, СF ) ppm.
2
СН
3
), 4.41 (q, J 7.1 Hz, 2Н, ОСН
2
СН
3
), 7.19 (t.t, JH,F
1
9
5
2
)
2
6
) δ: 24.69
(
2
2
Ethyl 7-(1,1,2,2,3,3,3-heptafluoropropyl)-5H-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate (6c).
Pyrimidine 5c (0.378 g, 1 mmol) gave by procedure B 0.234 g (65 %) of product 6с, mp 125-126 ºС.
Anal. Calcd for C11
N, 15.28 %. IR: ν 3049, 3104 (C-H), 1727 (СO
NMR (СDCl ): δ 1.43 (t, J 7.2 Hz, 3Н, ОСН СН
): δ 39.12 (m, 2F, β-СF
7 7 4 2
H F N O : C, 36.68; H, 1.96; F, 36.92; N, 15.55. Found: C, 36.36; H, 2.00; F, 36.94;
-1 1
2
Et), 1622, 1502 (C=C, C=N), 1236-1124 (C-F) cm . Н
), 4.49 (q, J 7.2 Hz, 2Н, ОСН СН ), 8.78 (s, 1H, H(5)),
), 54.73 (m, 2F, α-СF ), 81.86 (t, JF,F
3
2
3
2
3
1
9
9
.39 (s, 1H, H(2)) ppm. F NMR (CDCl
0.0 Hz, 3F, СF ) ppm.
3
2
2
1
3
Ethyl 7-hydroxy-2-methyl-7-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylate
7а).
The ester 1a (0.720 g, 3 mmol) gave by procedure A 0.664 g (76 %) of product 7a, mp 193-195 ºС. Anal.
Calcd for C11 : C, 45.37; H, 4.15; F, 19.57; N, 14.43. Found: C, 45.41; H, 4.08; F, 19.49; N,
(
12 3 3 3
H F N O
1
1
4.46 %. IR: ν 3300, 3119 (NH, OH), 3007, 2961 (C-H), 1669 (СO
2
Et), 1628, 1601 (C=C, C=N),
СН ), 2.14 (s, 3H, CH ), 4.13
-1 1
200-1080 (C-F) cm . Н NMR (DMSO-d
6
): δ 1.22 (t, J 7.0 Hz, 3Н, ОСН
2
3
3
(
m, AB-system, ∆AB 0.05 ppm, JAB 10.8, J 7.0 Hz, 2H, ОСН
2
СН
3
), 5.64 (s, 1H, H(3)), 7.83 (с, 1H, H(5)),
) δ: 84.24 (s, CF ) ppm.
1
9
7
.85 (br.s, 1H, OH), 10.82 (br.s, 1Н, NH(4)) ppm. F NMR (DMSO-d
6
3
Ethyl 7-(1,1,2,2,3,3,3-heptafluoropropyl)-7-hydroxy-2-methyl-4,7-dihydropyrazolo[1,5-a]pyrimi-
dine -6-carboxylate (7b).
The ester 1c (1.021 g, 3 mmol) gave by procedure A 0.822 г (70 %) of product 5c, mp 128-130 ºС. Anal.
Calcd for C13
H
12
F
7
N
3
O
3
: C, 39.91; H, 3.09; F, 33.99; N, 10.74. Found: C, 40.11; H, 3.21; F, 34.07; N,
0.72 %. IR: ν 3241, 3212, 3133 (NH, OH), 3077, 2990 (C-H), 1682 (СO Et), 1637, 1606 (C=C, C=N),
): δ 7b (40 %) 1.22 (t, J 7.1 Hz, 3Н, ОСН СН ), 4.13 (m,
1
1
2
-
1 1
265-1088 (C-F) cm . Н NMR (DMSO-d
6
2
3

444
HETEROCYCLES, Vol. 78, No. 2, 2009
AB-system, ∆AB 0.03 ppm, JAB 10.8, J 7.1 Hz, 2H, ОСН
2
СН
3
), 5.66 (s, 1H, H(3)), 7.85 (d, J 5.0 Hz, 1H,
СН ),
), 6.12 (s, 1H, H(4')), 8.49 (d, J 14.3 Hz, 1H, CH); 11.10 (d, J 14.3 Hz,
Н, NH), 12.48 (s, 1H, NH(1')); (E)-7'b (34 %) 1.24 (t, J 7.0 Hz, 3Н, ОСН СН ), 4.18 (q, J 7.0 Hz, 2H,
СН ), 6.20 (s, 1H, H(4')), 8.66 (d, J 14.5 Hz, 1H, CH), 11.87 (d, J 14.5 Hz, 1Н, NH), 12.55 (s, 1H,
NH(1')) ppm. F NMR (DMSO-d
β-CF ), 46.13 (m, AB-system, ∆AB 1.36 ppm, JAB 278.6 Hz, 2F, α-CF
Z)-7'b (26 %) 38.73 (m, 2F, β-CF ), 50.23 (m, 2F, α-CF ), 83.00 (t, JF,F 9.2 Hz, 3F, CF
9.59 (m, 2F, β-CF ), 49.79 (m, 2F, α-CF ), 82.93 (t, J 9.2 Hz, 3F, CF ) ppm.
Н(5)), 7.94 (s, 1H, OH), 10.90 (d, J 5.0 Hz, 1H, NH(4)); (Z)-7'b (26 %) 1.25 (t, J 7.0 Hz, 3Н, ОСН
2
3
4
1
2 3
.25 (q, J 7.0 Hz, 2H, ОСН СН
2
3
ОСН
2
3
1
9
6
): δ 7b (40 %) 37.14 (m, AB-system, ∆AB 1.10 ppm, JAB 288.5 Hz, 2F,
), 82.33 (t, JF,F11.5 Hz, 3F, CF );
); (E)-7'b (34 %)
2
2
3
(
2
2
3
3
2
2
F,F
3
Diethyl 7-hydroxy-7-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxylate (7c).
The ester 1a (0.720 g, 3 mmol) gave by procedure A 0.702 g (67 %) of product 7a, mp 216 – 218 ºС.
14 3 3 5
Anal. Calcd for C13H F N O : C, 44.71; H, 4.04; F, 16.32; N, 12.03. Found: C, 44.73; H, 3.86; F, 15.99;
N, 11.90 %. IR: ν 3287, 3133 (NH, OH), 2971 (C-H), 1690, 1672 (СO
2
Et), 1607 (C=C, C=N),1230-1104
СН ), 4.18 (m, AB-system,
), 4.25 (q, J 7.0 Hz, 2H, ОСН СН ), 7.79 (d, J 5.1 Hz, 1
H, Н(5)), 7.92 (s, 1H, H(2)), 8.48 (d, JH,F 0.9 Hz, 1H, OH), 10.69 (d, J 5.1 Hz, 1H, NH(4)) ppm. F NMR
DMSO-d ): δ 84.01 (d, JF,H 0.9 Hz, CF ) ppm.
1
(
C-F). Н NMR (DMSO-d
6
): δ 1.24, 1.29 (both t, J 7.0 Hz, 3Н each, 2 ОСН
2
3
∆
AB 0.05 ppm, JAB 10.8, J 7.0 Hz, 2H, ОСН
2
СН
3
2
3
1
9
(
6
3
Diethyl 7-hydroxy-7-(1,1,2,2-tetrafluoroethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxy-
late (7d).
The ester 1b (0.817 g, 3 mmol) gave by procedure A 0.890 g (78 %) of product 7d, mp 178-180 ºС. Anal.
Calcd for C14
H
15
F
4
N
3
O
5
: C, 44.10; H, 3.97; F, 19.93; N, 11.02. Found: C, 43.97; H, 3.82; F, 19.82; N,
Et), 1608 (C=C, C=N),1229-1079
C-F). Н NMR (DMSO-d ): 7d (81 %) 1.24, 1.29 (both t, J 7.1 Hz, 3Н each, 2 ОСН СН ), 4.16 (m,
1
1.16 %. IR: ν 3272, 3132 (NH, OH), 2998 (C-H), 1689, 1673 (СO
2
1
(
6
2
3
AB-system, ∆AB 0.03 ppm, JAB 10.8, J 7.1 Hz, 2H, ОСН
0.8, J 7.1 Hz, 2H, ОСН СН ), 6.68 (d.d.d.d, JH,F 53.5, 51.5, 10.9, 1.6 Hz, 1H, (CF
H(5)), 7.91 (d, J 6.3 Hz, 1H, Н(2)), 8.33 (s, 1H, OH), 10.65 (br.s, 1H, NH(4)); (Z)-7'd (7 %) 1.26, 1.38
both t, J 7.1 Hz, 3Н each, 2 ОСН СН ), 4.30, 4.24 (both q, J 7.1 Hz, 2H each, 2 ОСН СН ), 6.68 (t.t,
H,F 51.5, 7.2 Hz, 1H, (CF H), 8.39 (br.s, 1H, H(5')), 8.67 (br.d, J 13.7 Hz, 1H, CH), 11.84 (br.d, J 13.7
Hz, 1Н, NH), 13.38 (br.s, 1Н, NH(1')); (Е)-7'd (12 %): 1.28, 1.34, (both t, J 7.1 Hz, 3Н each, 2
ОСН СН ), 4.21, 4.32 (both q, J 7.1 Hz, 2H each, 2 ОСН СН ), 6.99 (t.t, JH,F 52.7, 7.3 Hz, 1H, (CF H),
.42 (br.s, 1Н, H(5')), 8.83 (d, J 14.3 Hz, 1H, CH), 12.43 (d, J 14.3 Hz, 1Н, NH), 13.49 (br.s, 1Н, NH(1'))
2
СН
3
), 4.27 (m, AB-system, ∆AB 0.02 ppm, JAB
1
2
3
2 2
)
H), 7.76 (s, 1H,
(
2
3
2
3
J
2 2
)
2
3
2
3
2 2
)
8
1
9
ppm. F NMR (DMSO-d
d.d.d, JF,F 293.4, 10.7, JF,H 51.5 Hz, 1F, CF
.1 Hz, 1F, CF ); (Z)-7'd (25 %) 23.90 (d.m, JF,H 51.5 Hz, 2F, CF
6
): δ 7d (19 %) 26.01 (d.d.t, JF,F 293.4, 9.1, JF,H 53.5 Hz, 1F, CF
H), 32.29 (d.m, JF,F 260.8 Hz, 1F, CF ), 41.79 (d.d, JF,F 260.8,
H), 42.98 (m, 2F, CF ); (Е)-7'd (56 %)
2
H), 31.23
(
2
2
9
2
2
2

HETEROCYCLES, Vol. 78, No. 2, 2009
445
2
5.17 (d.m, JF,H 52.7 Hz, 2F, CF
Ethyl 2-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-6-carboxylate (8a).
Pyrimidine 7a (0.291 g, 1 mmol) gave by procedure B 0.235 g (86 %) of product 8a, mp 94-95 ºС. Anal.
Calcd for C11 : C, 48.36; H, 3.69; F, 20.86; N, 15.38. Found: C, 48.26; H, 3.53; F, 20.68; N,
5.68 %. IR: ν 3115, 3097 (C-H), 1717 (СO
NMR (DMSO-d ): δ 1.42 (t, J 7.1 Hz, 3Н, ОСН
ОСН СН ), 6.75 (s, 1H, H(3)), 9.26 (s, 1H, H(5)) ppm. F NMR (DMSO-d
Diethyl 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3,6-dicarboxylate (8b).
Pyrimidine 7c (0.349 g, 1 mmol) gave by procedure B 0.298 g (90 %) of product 8b, mp 95-97 ºС. Anal.
Calcd for C13 : C, 47.14; H, 3.65; F, 17.21; N, 12.69. Found: C, 47.11; H, 3.63; F, 17.18; N,
2.64 %. IR: ν 3062 (C-H), 1712 (СO
2 2
H), 41.32 (m, 2F, CF ) ppm.
10 3 3 2
H F N O
-1 1
1
2
Et), 1618, 1553 (C=C, C=N), 1192-1116 (C-F) cm . Н
СН ), 2.59 (s, 3H, CH ), 4.44 (q, J 7.1 Hz, 2Н,
): δ 96.73 (s, CF ) ppm.
6
2
3
3
1
9
2
3
6
3
12 3 3 4
H F N O
-
1 1
1
2
Et), 1623, 1562 (C=C, C=N), 1219-1156 (C-F) cm . Н NMR
): δ 1.34, 1.36 (both t, J 7.1 Hz, 3Н each, 2 ОСН СН ), 4.34, 4.39 (both q, J 7.1 Hz, 2Н each,
), 8.96 (s, 1H, H(2)), 9.97 (s, 1H, H(5)) ppm. F NMR (DMSO-d ): δ 98.52 (s, CF ) ppm.
(DMSO-d
6
2
3
1
9
2
ОСН
2
СН
3
6
3
Diethyl-7-(1,1,2,2-tetrafluoroethyl)pyrazolo[1,5-a]pyrimidine-3,6-dicarboxylate (8c).
Pyrimidine 7d (0.381 g, 1 mmol) gave by procedure B 0.283 g (78 %) of product 8c, mp 107-109 ºС.
Anal. Calcd for C14 : C, 46.13; H, 3.61; F, 20.92; N, 11.57. Found: C, 46.43; H, 3.61; F, 20.88;
N, 11.59 %. IR: ν 2996 (C-H), 1727, 1719 (СO
NMR (CDCl ): δ 1.42, 1.43 (both t, J 7.1, 7.2 Hz, 3Н each, 2 ОСН
Н each, 2 ОСН СН ), 7.09 (t.t, JH,F 53.3, 5.8 Hz, 1Н, (CF H), 8.68 (s, 1H, H(5)), 8.84 (s, 1H, H(2))
ppm. F NMR (CDCl ): δ 24.83 (d.m, JF-H 53.3 Hz, 2F, CF H), 44.49 (m, 2F, CF ) ppm.
13 4 3 4
H F N O
-1 1
2
Et), 1624, 1598 (C=C, C=N), 1207-1092 (C-F) cm . Н
СН ), 4.47, 4.49 (both q, J 7.1, 7.2 Hz,
3
2
3
2
2
3
2 2
)
1
9
3
2
2
Diethyl 4-hydroxy-4-(trifluoromethyl)-1,4-dihydroimidazo[1,5-a]pyrimidine-3,8-dicarboxylate (9a).
The ester 1a (0.720 g, 3 mmol) gave by procedure C 0.754 g (72 %) of product 9a, mp 185-186 ºС. Anal.
Calcd for C13
H
14
F
3
N
3
O
5
: C, 44.71; H, 4.04; F, 13.32; N, 12.03. Found: C, 44.92; H, 3.90; F, 16.28; N,
Et), 1639, 1611 (C=C, C=N); 1194-1138
): δ 9a (72 %) 1.24, 1.29 (both t, J 7.0 Hz, 3Н each, 2 ОСН СН ), 4.16
m, AB-system, ∆AB 0.05 ppm, JAB 10.8, J 7.0 Hz, 2H, ОСН СН ), 4.28 (q, J 7.0 Hz, 2H, ОСН СН ),
.74 (s, 1H, H(6)), 7.78 (d, J 6.3 Hz, 1H, Н(2)), 8.95 (s, 1H, OH), 10.62 (d, J 6.3 Hz, 1H, NH(1)); (Z)-9'a
10 %) 1.28, 1.38 (both t, J 7.0 Hz, 3Н each, 2 ОСН СН ), 4.36, 4.12 (both q, J 7.0 Hz, 2H each, 2
), 7.90 (br.s, 1H, H(2')), 8.83 (d, J 13.9 Hz, 1H, CH), 11.84 (d, J 13.9 Hz, 1Н, NH), 13.47 (s,
1
1.91 %. IR: ν 3248 (NH, OH); 2999 (C-H), 1719, 1698 (СO
2
-1 1
(
(
C-F) cm . Н NMR (DMSO-d
6
2
3
2
3
2
3
7
(
2
3
2 3
ОСН СН
1
H, NH(1')); (Е)-9'a (18 %): 127, 1.41 ((both t, J 7.0 Hz, 3Н each, 2 ОСН СН ), 5.89, 4.22 (both q, J 7.0
2 3
Hz, 2H each, 2 ОСН
NH), 13.56 (s, 1H, NH(1')) ppm. F NMR (DMSO-d
s, CF ); (Е)-9'a (18 %) 90.83 (s, CF ) ppm.
Diethyl 4-hydroxy-4-(1,1,2,2-tetrafluoroethyl)-1,4-dihydroimidazo[1,5-a]pyrimidine-3,8-dicarboxy-
2 3
СН ), 7.94 (br.s, 1Н, H(2')), 8.66 (d, J 13.7 Hz, 1H, CH), 12.51 (d, J 13.7 Hz, 1Н,
1
9
6
3
): δ 9a (72 %) 81.38 (s, CF ); (Z)-9'a (10 %) 91.82
(
3
3

446
HETEROCYCLES, Vol. 78, No. 2, 2009
late (9b).
The ester 1b (0.817 g, 0.003 mol) gave by procedure C 0.766 g (67 %) of product 9b, mp178-180 ºС.
Anal. Calcd for C14 : 44.10; H, 3.97; F, 19.93; N, 11.02. Found: C, 44.31; H, 3.83; F, 19.91; N,
0.96 %. IR: ν 3242 (NH), 3015 (C-H), 1724, 1674 (СO Et), 1634, 1609 (C=C, C=N), 1254-1114 (C-F)
): δ 9b (19 %): 1.25, 1.30 (both t, J 7.1, 3Н each, ОСН СН ), 4.16, 4.28 (both q,
СН ), 6.67 (d.d.d.d, JH,F 52.0, 51.2, 8.5, 4.2 Hz, 1Н, (CF H), 7.67 (d, J 3.7 Hz,
H, H(2)), 7.76 (s, 1H, H(6)), 8.82 (d, J 3.7 Hz, 1H, NH(1)), 10.55 (br.s, 1H, OH); (Z)-9'b (25 %) 1.29,
.38 (both t, J 7.2, 7.0 Hz, 3Н each, ОСН СН ), 4.29, 4.36 (both q, J 7.2, 7.0 Hz, 2Н each, ОСН СН ),
.67 (t.t, JH,F 52.1, 5.9 Hz, 1Н, (CF H), 7.89 (с, 1Н, СН(2')), 8.80 (d, J 13.7 Hz, 1Н, СН), 11.69 (d, J
3.7 Hz, 1Н, NH), 13.51 (br. s, 1H, NH(1')); (Е)-9'b (56 %): 1.28, 1.40 (both t, J 7.2, 7.0 Hz, 3Н each,
15 4 3 5
H F N O
1
2
-1 1
cm . Н NMR (DMSO-d
J 7.1 Hz, по 2H, ОСН
6
2
3
2
3
2 2
)
1
1
6
1
2
3
2
3
2 2
)
ОСН СН ), 4.39, 4.23 (both q, J 7.0, 7.2 Hz, 2Н each, ОСН СН ), 7.00 (t.t, J 52.3, 5.9 Hz, 1Н,
2
3
2
3
H,F
(
CF
NH(1')) ppm. F NMR (DMSO-d
d.d.m, JF,F 296.6, JF,H 51.2 Hz, 1F, CF
2 2
) H), 7.93 (s, 1Н, CН(2')), 8.93 (d, J 13.7 Hz, 1Н, СН), 12.56 (d, J 13.7 Hz, 1Н, NH), 13.51 (br.s, 1H,
1
9
6
): δ 9b (19 %) 26.85 (d.d.m, JF,F 296.6, JF,H 52.0 Hz, 1F, CF
H), 33.50 (d.m, JF,F 262.0 Hz, 1F, CF ), 38.16 (d.m, JF,F 262.0 Hz,
); (Z)-9'b (25 %) 23.80 (d.t, JF-H 52.1, 8.2 Hz, 2F, CF H), 43.11 (m, 2F, CF ); (Е)-9'b (56 %)
5.27 (d.t, JF,H 52.3, JF,F 7.9 Hz, 2F, CF H), 41.43 (m, 2F, CF ) ppm.
2
H), 30.21,
(
2
2
1
F, CF
2
2
2
2
2
2
ACKNOWLEDGEMENTS
This study was financially supported by the Grant for young scientists and postgraduates of the Ural
branch of the Russian Academy of Sciences for 2008 and by the Program for the support of leading
scientific schools (Grant no. 3758.2008.3).
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