Reaction of 1-substituted 3,5-diamino-1,2,4-triazoles with β-keto esters: synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4]triazolo-[4,3-a]pyrimidin-5-ones

Article abstract of DOI:10.1016/j.tet.2010.03.009

Reaction of 3,5-diamino-1-R-1,2,4-triazoles (R=Ph, Bn) with β-keto esters results in the reversible formation of N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted enaminoesters (8). Subsequent transformations depended on the reaction conditions. Compounds 8 undergo intermolecular reactions of condensation and amidation in the absence of solvent. However, in the presence of acetic acid they form 3-amino-5-oxo-2-R-2,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidin-4-ium-8-id es (10) followed by rearrangement to 3-amino-1-R-[1,2,4]triazolo[4,3-a]pyrimidin-5-ones (11). The transformation of 10 into 11 represents a new type of rearrangement in the azolopyrimidine series. Heating of enaminoesters 8 in ethanol with sodium ethoxide present, proved to be a suitable method for the preparation of the mesoionic compounds 10.

Full text of DOI:10.1016/j.tet.2010.03.009

Tetrahedron 66 (2010) 3301–3313
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reaction of 1-substituted 3,5-diamino-1,2,4-triazoles with b-keto esters:
synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4]triazolo-
[4,3-a]pyrimidin-5-ones
,
a
b
Victor M. Chernyshev a , Alexander V. Astakhov , Zoya A. Starikova
*
a South-Russia State Technical University, 346428 Novocherkassk, Russian Federation
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of 3,5-diamino-1-R-1,2,4-triazoles (R¼Ph, Bn) with
b-keto esters results in the reversible for-
Received 19 November 2009
Received in revised form 5 February 2010
Accepted 1 March 2010
mation of N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted enaminoesters (8). Subsequent transformations
depended on the reaction conditions. Compounds 8 undergo intermolecular reactions of condensation
and amidation in the absence of solvent. However, in the presence of acetic acid they form 3-amino-5-
oxo-2-R-2,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidin-4-ium-8-ides (10) followed by rearrangement to
3-amino-1-R-[1,2,4]triazolo[4,3-a]pyrimidin-5-ones (11). The transformation of 10 into 11 represents
a new type of rearrangement in the azolopyrimidine series. Heating of enaminoesters 8 in ethanol with
sodium ethoxide present, proved to be a suitable method for the preparation of the mesoionic com-
pounds 10.
Available online 6 March 2010
Keywords:
[1,2,4]Triazolo[4,3-a]pyrimidin-5-ones
Mesoionic
Rearrangement
Ó 2010 Elsevier Ltd. All rights reserved.
1-Substituted 1H-1,2,4-triazole-3,5-
diamines
b
-Keto esters
Condensation
1. Introduction
7-one (5)when treated with warm alcoholic alkali or whenheatedat
210–215 ꢀC.6b According to patent data, triazole 1 (Ar¼Ph) forms
The cyclocondensation of aminoazoles with
b
-keto esters is
diamides 6 in refluxing xylene with an excess of ethyl acetoacetate.7
However, this information was subsequently revised, and the re-
actionproducts wereclaimed tobe amides2 (Fig.1).6c Inouropinion,
the structures of compounds 2–6 were not accurately proven owing
to the absence of any analytical data except elemental analysis in the
cited literature.
a powerful method for the preparation of azolopyrimidinones with
a nodal nitrogen atom.1,2 These compounds are analogs of purine
bases3 and exhibit various types of biological activity, including
antihypertensive,1g serotonin antagonist,1e,4a anti-inflammatory,4b
analgesic,4c antimicrobial,4d,e antifungal,4f cytotoxic,4g,h and anti-
tumor activities.4i Theycan also serve as synthetic precursors for the
preparation of pharmacologically valuable amino derivatives of
azolopyrimidines.1h,5 Condensation of N-unsubstituted 3(5)-amino-
It iswellknownthatthe interaction of1-substituted3-amino- and
5-amino-1,2,4-triazoles with 1,3-bielectrophiles, such as 1,3-diketo-
nes8a,b or diethyl ethoxymethylenemalonates8c leads to 1,2,4-tri-
azolo[4,3-a]pyrimidine derivatives. Consequently, under certain
conditionsthe reaction of 1-substituted 3-amino- and 5-amino-1,2,4-
triazoles with b-keto esters would be expected to afford triazolopyr-
imidinones and would thus be a suitable method for the preparation
of these compounds.
1,2,4-triazoles with various b-keto esters results in the predominant
formation of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and represents
a significant method of preparation of this type of compounds.2,5a So
far, the analogous reaction of 1-substituted 3-amino- and 5-amino-
1,2,4-triazoles has not been thoroughly investigated. According to
the literature data,6 1-aryl-substituted 3,5-diamino-1,2,4-triazoles
(1) and ethyl acetoacetate (7a) form products 2–4 depending on the
molar ratio and heating temperaturein a solventless reaction (Fig.1).
Compound 4 affords a derivative of 1,2,4-triazolo[1,5-a]pyrimidin-
This article reports our results from the reinvestigation of the
reaction of 1-R-3,5-diamino-1,2,4-triazoles (1a, R¼Ph, 1b, R¼Bn)
with b-keto esters. Furthermore, it describes some interconversion
between the products formed. The choice of diamines 1 as substrates
was predicated on having greatly varied nucleophilicity of amino
groups in positions 3 and 5 of triazole ring.9 We believe that
1-substituted 3,5-diamino-1,2,4-triazoles are convenient models
for a comparative investigation of the reactivity of 3-amino- and
* Corresponding author. Tel.: þ7 903 437 24 03; fax: þ7 86 352 276 19; e-mail
address: chern13@yandex.ru.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.009

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V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
Figure 1. Structures of products of the reaction of 1-substituted 3,5-diamino-1,2,4-triazoles (1) with ethyl acetoacetate according to the literature data.6,7
5-amino-1,2,4-triazoles toward electrophiles. Moreover, this would
afford a new approach to the selective synthesis of triazolopyr-
imidinones with different annulation of triazole and pyrimidine.
100 ꢀC. The yields of 1a and 9 increased with longer heating time
(Table 2). The results obtained allowed us to assume that the for-
mation of compounds 4a, 8a, and 9 may be described by four major
reactions (Scheme 2). Apparently, the first three reactions are re-
versible and relatively fast. The fourth reaction is irreversible and
relatively slow.
2. Results and discussion
We first reproduced the literature results of the reaction of
Table 2
compounds 1 and b
-keto esters.6,7 According to Papini’s findings,
HPLC data from monitoring the decomposition of compound 8a at 100 ꢀC
heating of 1-arylsubstituted 3,5-diamino-1,2,4-triazoles with ethyl
acetoacetate (7a) in molar ratios from 1:1 to 1:2 at 100–120 ꢀC
without solvent resulted in the formation of compounds 2 (Fig.1).6a
However, we established that a mixture of three major products
(4a, 8a, and 9) was formed in the reaction of compound 1a with
ester 7a in the absence of solvent at 100–105 ꢀC and molar ratios of
1a:7a from 1:1 to 1:2 (Scheme 1). Compound 9 is sparingly soluble
in most organic solvents and was isolated by crystallization. Prod-
ucts 4a and 8a were separated by column chromatography. In ac-
cordance with HPLC analysis of the reaction mixtures, prolongation
of the reaction time decreased the yield of 8a and increased the
yield of 9, and also caused the appearance of several small peaks of
unidentified compounds (Table 1).
Entry
Yield in 4 h (%)
Yielda in 60 h (%)
1a
8a
9
14
69
2
37
39
20
4
4a
15
a
There were several small peaks observed from unidentified compounds.
We were not able to detect compound 2 (or its isomer with an
acetoacetamide group) in the reaction mixtures, which according
to the literature data was the main product under these con-
ditions.6a Papini claimed that compound 2 was also obtained by
refluxing diamine 1a with excess of the ester 7a in xylene.6c
Scheme 1. The reaction of compounds 1a and 7a without solvent at 100–105 ꢀC.
Table 1
However, Bavley assigned the structure 6 to the reaction product
(Fig. 2).7 By reproducing the described procedures,6c,7 we obtained
compound 9 as the main product in both cases. Therefore, we
concluded that impure compound 9 was obtained rather than
compounds 2 (Ar¼Ph) and 6, as was described in the literature,6a,c,7
and that the inconsistencies in elemental analysis were caused by
impurities. It is noteworthy that Papini also described the synthesis
of compound 3 (Ar¼Ph, Fig. 1) by heating diamine 1a with neat
HPLC data from monitoring the reaction between 1a and 7a without solvent at
100–105 ꢀC
Entry Molar ratio 1a:7a¼1:1
Molar ratio 1a:7a¼1:2
Yield in 4 h (%) Yielda in 60 h (%) Yield in 4 h (%) Yielda in 60 h (%)
1a
8a
9
27
56
12
5
8
22
56
7
17
64
4
8
36
12
22
4a
15
b
-keto ester 7a at 140–150 ꢀC in the molar ratio of 1a:7a of 2:1.6a
a
There were several small peaks observed from unidentified compounds.
However, again we obtained compound 9 in 40% yield under
these conditions. The melting point and other properties described
by Papini for compound 3 are in good agreement with the prop-
erties of compound 9. Therefore, taking into account current data
Using HPLC, we also determined that pure compound 8a grad-
ually decomposed to give a mixture of diamine 1a and products 9
and 4a when heated past its melting point and maintained at

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3303
Scheme 2. The major reactions of formation of compounds 4a, 8a, and 9 from 1a and 7a under solvent free conditions at 100–105 ꢀC.
Table 3
Yields of compounds 8a–j
on the structure of acyl derivatives of 1-substituted 3,5-diamino-
1,2,4-triazoles,9a,b,d we concluded that Papini obtained compound 9
rather than its isomer 3. The highest yield and purity of compound
9 was obtained by heating compounds 1a and 7a without solvent at
140–150 ꢀC for 1 h or refluxing them in xylene for 5 h at the molar
ratio of 1a:7a¼1:1.
Compound
b
-Keto ester
R
R1
R2
Alk
Yield, %
8a
8b
8c
8d
8e
8f
8g
8h
8i
7a
7b
7c
7d
7e
7f
7g
7a
7e
7f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Bn
Bn
H
n-Bu
Bn
4-MeC6H4
Cl
H
H
H
Cl
H
Me
Me
Me
Me
Me
n-Pr
i-Pr
Me
Me
n-Pr
Et
Et
Et
Et
Et
Et
Me
Et
Et
Et
60 (a), 75 (b)
40 (a)
40 (a)
41 (a)
57 (b)
45 (a)
42 (a)
73 (a)
46 (a)
54 (a)
The properties of compound 4a, obtained by the present authors
from heating of 1a with an excess of 7a, are in good agreement with
the one described by Papini and Checchi for compound
4
(Ar¼Ph).6b Considering the modern knowledge of tautomerism of
C-amino-1,2,4-triazoles and their derivatives10 as well as triazolyl
substituted enaminoesters,11 it is reasonable to conclude that the
tautomeric form 4a is more appropriate for describing the structure
of the compound synthesized. The literature procedure6b was used
for the synthesis of compound 4a, reducing the reaction time to 1 h
to improve the yield and selectivity.
8j
NH2 (6.48–6.65 ppm in DMSO-d6) was typical for 1-substituted
5-amino-1,2,4-triazoles.9a–c,12 If these reactions had occurred at the
5-NH2 thesignaloftheaminogroupinthecompoundsformedshould
be in the 4.5–5.4 ppm range like those from other 1-substituted
3-amino-1,2,4-triazoles.9a–c,12 The direction of the reactions was
unambiguously established by the NOESY spectra of compounds 8a
and 9, which both contain correlation peaks between the spatially
close protons of 5-NH2 and the phenyl group. In analogy to other
enaminones, compounds 4a, 8, and 9 can exist as E and Z stereo-
isomers.11,13 According to the 1H and 13C NMR spectra, compounds
4a and 8 are (Z)-isomers because the signals of their enaminoester
fragments are in close agreement with the literature data for the
(Z)-enaminoesters.13a–d The (E)-isomer was only detected in un-
crystallized samples of compound 8a, that had been obtained by
refluxing the reagents in tetrahydrofuran (content of (E)-isomer
19%) or acetic acid (contentof (E)-isomer 47%).1H NMR spectra of the
(E) and (Z) isomers of 8a are substantially different. The H-2 and
NH signals of the enaminoester fragment (see Scheme 3) of the
(Z)-isomer were observed at 4.75 and 10.59 ppm, respectively,
whereas the same signals of the (E)-isomer were found at 6.31 and
9.09 ppm, respectively. Differentiation of the (E) and (Z) isomers of
compound 8awas based on the NOESY spectrum, inwhich the cross-
peak between the H-2 and CH3 at C-3 was observed only for the
(Z)-isomer. The assignment of signals in the 13C NMR spectra was
performed on the basis of the HMBC spectrum of compound 8a,
which contained correlation peaks between the protons of the
ethoxy group (4.06 ppm) and the carbonyl carbon (169.5 ppm), the
protons of the methyl group (2.32 ppm) and C-2 (88.1 ppm), and H-2
(4.75 ppm) and C-3 (157.1 ppm). The signals of the carbons that
The synthesis of compound 8a was accomplished by refluxing
diaminotriazole 1a with a small excess of b-keto ester 7a in either
ethanol or tetrahydrofuran. Compounds 8b–j were synthesized
analogously in 40–73% yields (Scheme 3, Table 3). It should be
noted that the enaminoesters 8a–j are quite stable, which is in
contrast to similar derivatives of C-amino-1,2,4-triazoles unsub-
stituted at the cyclic nitrogen atom. These latter compounds are
usually not isolatable because of rapid cyclization into [1,2,4]tri-
azolo[1,5-a]pyrimidin-7-ones.2f
Scheme 3. Synthesis of compounds 8a–j. Reaction conditions: (a) EtOH (or MeOH for
8g), reflux; (b) THF, reflux.
The structures of compounds 4a, 8, and 9 were confirmed by both
elemental analysis and spectral data (IR, 1H, and 13C NMR, and mass
spectroscopy). The direction of the condensation and acylation re-
actions of diamines 1 at the 3-NH2 conforms with the previously
observed selectivity of reactions of 1-substituted 3,5-diamino-1,2,4-
triazoles with electrophiles,9 and it was corroborated by 1H NMR
spectra of compounds 8a–j and 9, in which the signal of unreacted

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V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
showed no correlation peaks with any protons were assigned to the
triazole ring. Owing to the absence of a cross-peak between the H-2
and the protons of the methyl group in the NOESY spectrum of
compound 9, this substance was concluded to exist in the (E)-isomer
form.
Eventually, it was concluded that for the conditions described
above, the interaction between compounds 1 and 7 does not result
in the formation of annulated products. It is known that the syn-
thesis of triazolopyrimidines is generally performed by condensa-
clearly confirmed by heating of pure compound 10a in the presence
of acetic acid at 150–160 ꢀC for 10 h. The HPLC analysis of the
resulting mixture revealed that all of compound 10a had been
consumed and that compound 11a had formed in 18% yield. We
also observed several new sparingly soluble and unidentified
compounds, indicating that the rearrangement was accompanied
by substantial decomposition of compound 10a. Compound 11a is
more thermally stable, and the degree of decomposition was only
12% after heating for 10 h at the same conditions as those for 10a.
tion of aminotriazoles with
reflux.2 Therefore, we investigated the reaction of diamines 1a,b
with -keto esters 7a–h in the presence of acetic acid to probe the
b
-keto esters in glacial acetic acid under
The reactions of compounds 1a,b with b-keto esters 7a–d,f,g
occurred analogously to those described above, affording the mix-
tures of compounds 10b–d,f–i and 11b–d,f–i (Scheme 4, Table 4).
However, only compounds 11e (13%) and 11j (14%) were obtained
from the reaction of 1a with 7e and 7h (R1¼H, R2¼CF3, Alk¼Et),
respectively. Compound 10e was detected chromatographically and
not isolated owing to a very low yield. The corresponding mesoionic
CF3-substituted triazolopyrimidinone 10j was not detected even by
HPLC and thin-layer chromatography. Apparently, this is a result of
the mesoionic [1,2,4]triazolo[4,3-a]pyrimidin-5-ones containing
electron withdrawing substituents in the positions 6 and 7 being
unstable. Additionally, it is clear that the thermal instability of the
mesoionic compounds 10 is responsible for the low total yield of
triazolopyrimidinones in the reactions of diaminotriazoles 1a,b with
b
possibility of synthesis of annulated heterocycles.
The HPLC analysis revealed that compound 8a, isolated from the
reaction mixture, was initially formed when heating compounds 1a
and 7a to reflux in glacial acetic acid. Upon further heating, the
enaminoester 8a gradually disappeared and two new compounds
were formed. Following isolation by column chromatography and
analysis they were proven to be the isomeric [1,2,4]triazolo[4,3-
a]pyrimidin-5-ones 10a and 11a (Scheme 4). It was also established
that higher yields of the triazolopyrimidines could be achieved by
gradual evaporation of acetic acid when heating the reaction
mixture until its temperature reached 145–150 ꢀC and then main-
tained at 145–150 ꢀC for five hours (Table 4).
b
-keto esters 7a–h.
The rearrangement of compounds 10 into compounds 11 was
concluded to be irreversible because compounds 10 were not
detected in the reaction mixtures after heating of pure compounds
11 at 150–160 ꢀC in the presence of acetic acid. This indicates that
compounds 11 are substantially more thermodynamically stable
than compounds 10.
One of the most investigated rearrangements of azolopyr-
imidines is the Dimroth rearrangement of 1,2,4-triazolo[4,3-a]py-
rimidines into the thermodynamically more stable 1,2,4-
triazolo[1,5-a]pyrimidines.1b,2a,f,8a,14 It is noteworthy that the
rearrangement observed in the present investigation results in the
formation of 1-substituted 3-amino-[1,2,4]triazolo[4,3-a]pyrimidin-
5(1H)-ones 11 instead of the expected 1-substituted 2-amino-
[1,2,4]triazolo[1,5-a]pyrimidin-7(1H)-ones 12 (Scheme 4). As far as
we are aware, an analogous rearrangement of azolopyrimidines has
not been described in the literature. While the mechanism of this
rearrangement needs a separate investigation, it is appropriate to
propose that it is analogous to the ANRORC mechanism of Dimroth
rearrangement.15 However, instead of N4–C5 bond cleavage, the
fission occurs at the C7–N8 bond, followed by rotation around the
N–CO bond, and finally reformation of the ring (Scheme 5). A water
or acetic acid molecule can act as a nucleophile. The Dimroth rear-
rangement is probably hindered by an intramolecular hydrogen
bond between the amino and carbonylgroups, which strengthen the
4–5 bond. Nevertheless, other possible mechanisms of the observed
rearrangement cannot be ruled out.
Scheme 4. The reaction of compounds 1 and 7 in the presence of AcOH at 140–150 ꢀC.
Table 4
Yields of compounds 10a–j and 11a–j isolated from the reaction of 1a,b with 7a–h in
the presence of AcOH at 140–150 ꢀC for 5 h
Compound
R
R1
R2
Compound (yield, %)
a
b
c
d
e
f
g
h
i
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Bn
Ph
H
n-Bu
Bn
4-MeC6H4
Cl
H
H
H
H
H
Me
Me
Me
Me
Me
n-Pr
i-Pr
Me
n-Pr
CF3
10a (10), 11a (21)
10b (19), 11b (35)
10c (11), 11c (42)
10d (23), 11d (23)
11e (13)a
10f (12), 11f (21)
10g (27), 11g (38)
10h (10), 11h (20)
10i (14), 11i (28)
11j (14)a
j
a
Compounds 10e and 10j were not isolated.
According to HPLC analysis, the yield of compound 10a de-
creased and the yield of 11a increased with prolonged reaction
time. For example, after heating for 3 h the yields of compounds
10a and 11a amounted to 17% and 18%, respectively, while after 20 h
compound 10a was not detected in the reaction mixture, and the
yield of triazolopyrimidinone 11a rose to 30%. This observation led
to the hypothesis that the mesoionic compound 10a gradually
rearranges into compound 11a (Scheme 4). This rearrangement was
Scheme 5. The proposed mechanism of the rearrangement of compounds 10.

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3305
formed from either alternative direction of the cyclization of
enaminoesters 8 or Dimroth rearrangement of compounds 10
(Fig. 3). The signal of C-3 is shifted upfield by 18–23 ppm in com-
parison with the analogous signal of C-2 in compounds 12. The main
difference between the spectra of isomers 10 and those of 11 is ob-
served for the signal of C-6, which is shifted upfield by 6.2–9.0 ppm
for compounds 10. It is also notable that the differences between the
chemical shifts of the triazole carbons C-3 and C-8a in compounds 10
(6.5–9.0 ppm) are significantly higher than in compounds 11 (less
than 1.9 ppm). Moreover, in the spectra of compounds 10 the signals
of C-5 and C-7 are shifted downfield by 0.3–1.3 ppm and 1.3–
3.2 ppm as compared to those from the spectra of isomeric com-
pounds 11. Assignments of the signals in the 13C NMR spectra were
accomplished with the HSQC and HMBC spectra of compounds
10b,h,11h and the proton coupled 13C spectra of 10a,d,g,i and 11a,d,i.
Figure 2. Ring-bond-redistribution graphs (G2) and codes for the observed re-
arrangement and for the Dimroth15b,17c rearrangement according to the Babaev-Zefirov
classification.17
This rearrangement relates to degenerate ring transformations,
because it results in the formation of the same heterocyclic sys-
tem,15b,c and it represents a rare example of fission of the 7–8 bond
in the azaindolizine system for which cleavage of the 4–5 bond is
more typical.16 We can see that this rearrangement differs from the
Dimroth rearrangement by considering the rearrangement of the
pyrimidine cycle (Fig. 2), which occurs via the interchange of an
endocyclic heteroatom by an adjacent exocyclic heteroatom.15b In
the case of compounds 10, the Dimroth rearrangement should re-
sult in replacement of N-3 by N-7 (see numbering at Fig. 2).
However, we observed the interchange of two endocyclic atoms (C
and N) by their analogous atoms of the side chain (Scheme 5, Fig. 2).
According to the Babaev–Zefirov ring-bond-redistribution (RBR)
graphs classification17 of heterocyclic ring transformations, a topo-
logical difference between the Dimroth and the observed rear-
rangements is illustrated by Figure 2. The observed rearrangement
has a code of 664-(a)(a)-NNE, whereas the code for the Dimroth
rearrangement of azines is 665-(a)(a)-NNE.15b,17b,c Topologically
the observed rearrangement is similar to the rearrangement of
5-hydroxyflavones (Scheme 6),18 which has the same type, class
and sort, but relates to another family.17c
Figure 3. The characteristic signals in the 13C NMR spectra of compounds 10–13.
UV spectroscopy in neutral solution was successfully used to
differentiate between isomeric triazolopyrimidinones.2b–d We
found considerable differences in the UV spectra of the isomeric
compounds 10a–g and 11a–g. Compounds 10a–g show two ab-
sorption bands appearing at 234–238 nm (high intensity) and 335–
348 nm (low intensity), whereas compounds 11a–g display three
maxima at 220–231 nm (medium intensity), 270–276 nm (low in-
tensity), and 331–349 nm (high intensity). The UV spectra of the
benzyl derivatives 10h,i and 11h,i are quite similar and unsuitable
for the identification of the isomers.
The structure of compounds 10 and 11 was confirmed un-
ambiguously by X-ray diffraction studies of compounds 10a and
11d. In the ensuing discussion of the structures, the crystallo-
graphic numbering system will be used (Figs. 4 and 5). The X-ray
diffraction data of the molecule of triazolopyrimidinone 10a shows
that it is non-planar, with the plane of the phenyl group and the
plane of the triazole cycle having a dihedral angle of 34.6ꢀ. In ad-
dition, there is a small dihedral angle of 3.3ꢀ between the planes of
the triazole and the pyrimidine rings. The greatest deviation from
the plane of the triazole ring is observed for C(7) (0.142 Å). The
nitrogen atom of the amino group is in a trigonal pyramidal con-
figuration (sum of valence angles is 356.2ꢀ) and deviates from the
triazole plane by only 0.02 Å. There is an intramolecular hydrogen
bond N(3)H/O(1) in the molecule [N(3)/O 2.782(1), N–H 0.87,
O/H 2.10 Å, angle OHN 135ꢀ]. The O(1)–C(5) bond length of
1.234(2) Å is in agreement with the corresponding values in other
[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones and related systems
(1.203–1.248 Å).21 The bonds C(7)–N(8) and N(8)–C(8a) have al-
most equal lengths of 1.351(2) and 1.346(2) Å, respectively. It
should be noted that the N(4)–C(3) bond (1.369(2) Å) is longer than
the N(2)–C(3) and N(3)–C(3) bonds (1.341(2) Å and 1.324(1) Å, re-
spectively). This makes it reasonable to assume that the resonance
structures A and B (Scheme 7) are the main contributors to the
description of the structure of compounds 10.
Scheme 6. The rearrangement of 5-hydroxyflavones,18 its G2 RBR graph and code.17c
The structures of compounds 10 and 11 were confirmed by
elemental analysis and spectral data. The 1H NMR spectra of com-
pounds 10 and 11 display signals for one tautomeric form only. The
two proton singlet of the amino group supports the proposed
amino tautomer for both compounds 10 and 11 in DMSO solutions.
There are substantial differences between the spectra of the iso-
mers. Thus, the signal of amino group of compounds 10 is observed
at 8.38–8.45 ppm, whereas for the compounds 11 it is shifted up-
field to 6.86–7.24 ppm. The signal of H-6 is found at 5.14–5.22 ppm
for 10a,f–i and at 5.54–5.75 ppm for isomeric 11a,f–i. Furthermore,
the relatively narrow multiplet of the phenyl protons at 7.47–
7.68 ppm indicates that the benzene and triazole cycles are not
coplanar in compounds 10a–g, while the three multiplets of the
phenyl protons in a reasonably wide range (7.23–8.11 ppm) indicate
coplanarity19 between the same groups in compounds 11a–g,j.
The 13C NMR spectra of compounds 10 and 11 are quite similar to
the spectrum of compound 13.2b,c On the other hand, they differ
considerably from the spectra of isomers 12,20a,b which could be

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V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
2.791(2), N–H 0.87, O/H 2.12 Å, angle OHN is 133ꢀ]. The N(2)–C(3)
and N(8)–C(8a) bonds have pronounced double character
a
(1.298(2) and 1.312(2) Å, respectively). The lengthening of the C(5)–
O(1) [1.239(1) Å] and C(6)–C(7) [1.385(1) Å] bonds as compared to
the average values (1.211 and 1.326 Å, respectively),22 as well as the
shortening of the C(5)–C(6) [1.422(2) Å] and C(7)–N(8) [1.368(2) Å]
bonds with regards to the average values (1.464 Å and 1.45 Å) in-
dicate a pronounced conjugation in the O(1)C(5)C(6)C(7)N(8)
fragment.
At this point, the condensation of diaminotriazoles 1 with b-keto
esters 7 in acetic acid has not afforded the mesoionic triazolopyr-
imidinones 10 in good yields, and thus we tried to find another
method for the selective preparation of these compounds. We
established that enaminoesters 8a–h,j are readily cyclized to com-
pounds 10a–i in high yields under refluxing conditions in ethanol or
methanol in the presence of sodium alcoholates. Apparently, dis-
sociation of hydrogen from the enamine NH or a sufficiently acidic
amino group23 to afford the corresponding nucleophilic anion
precedes the intramolecular acylation, resulting in the formation of
the triazolopyrimidinones 10 (Scheme 8). According to TLC and
HPLC data, the crude samples of compounds 10 did not contain
impurities in detectable amounts, except for compound 10e, which
contained traces of the rearranged product 11e. Fortunately, 11e
could be completely removed by a single crystallization. Thus, the
direction of the cyclization of enaminoesters 8 under basic condi-
tions differs from the analogous cyclization of enaminoesters of
triazoles that are unsubstituted at the endocyclic nitrogen’s, which
produce [1,2,4]triazolo[1,5-a]pyrimidin-7-ones.24
Figure 4. The X-ray crystallographic structure of compound 10a.
Scheme 8. The selective synthesis of mesoionic compounds 10a–i.
Figure 5. The X-ray crystallographic structure of compound 11d.
It is noteworthy that compound 4a was converted to compound
14 in high yield by heating to reflux in an ethanolic solution of
sodium ethoxide for a short time (Scheme 9). Thus, the formation of
the more thermodynamically stable product from two possible
directions of cyclization was accomplished. The 1H and 13C NMR
spectra of compound 14 contain the signals characteristic for both
the (Z)-enaminoester and the pyrimidinone fragments. Assignment
of signals in the 13C NMR spectra was performed using the HMBC
spectrum. The (Z) form of compound 14 was unambiguously con-
firmed by the NOESY spectrum, which contains a cross-peak be-
tween the signals of H-2 (5.06 ppm) and CH3 (2.46 ppm) of the
enaminoester fragment. The absence of cross-peaks between the
enaminoester signals and the protons of the phenyl ring shows that
these groups are remote and that is only possible for compound 14.
The 1H NMR spectrum is in accord with the phenyl and triazole
rings being coplanar and is analogous to compounds 11a–h. Be-
cause the physicochemical properties of the compound 14 are very
close to the ones described for 5 (Fig. 1), it is plausible that com-
pound 14, rather than 5, was obtained in the published work.6b
Hydrolysis of compound 14 in alkaline water–ethanol solution
afforded compound 11a, which could also be obtained in one step
from 4a under analogous conditions (Scheme 9).
Scheme 7. The resonance structures of compounds 10.
The triazolopyrimidine fragment of the molecule 11d is planar,
with the maximal deviation of atoms from the mean-square plane
not exceeding 0.028 Å. The nitrogen atom of the amino group is in
a trigonal pyramidal configuration (sum of valence angles is 356.7ꢀ)
and deviates from the triazole plane by only 0.073 Å. Conjugation
between the unshared electron pair of N(3) and the
p system of the
bicyclic fragment leads to a shortening of the N(3)–C(3) bond
(1.340(1) Å) relative to the standard length of a purely single
Nsp2 –Csp2 bond (1.43–1.45 Å).22 The benzene and triazole rings are
almost coplanar with a dihedral angle of 6.44ꢀ. There is an intra-
molecular hydrogen bond N(3)H/O(1) in the molecule [N(3)/O

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3307
Starting compounds 1a,25 1b,26 and 7d27 were obtained by
known methods. All other chemicals are commercially available.
4.2. (Z)-N-(5-Amino-1-phenyl-1H-1,2,4-triazol-3-yl)-3-(5-
amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)but-2-enamide (9)
Method A. A stirred mixture of triazole 1a (1.00 g, 5.71 mmol)
and ethyl acetoacetate 7a (0.74 g, 5.71 mmol) was heated at
140–150 ꢀC for 1 h, then diluted with ethanol (5 mL) and cooled to
room temperature. The precipitate formed was filtered off and
recrystallized from DMF–ethanol mixture (1:3) to give white-
yellowish prisms (0.47 g, 40%) of 9, mp 240–241.5 ꢀC, lit.6a mp
240–241 ꢀC. IR (ATR)
1577, 1551, 1511. 1H NMR (300 MHz)
1H, CH), 6.48 (s, 2H, NH2), 6.54 (s, 2H, NH2), 7.28–7.54 (m, 10H, 2Ph),
9.73 (s, 1H, NH), 11.52 (s, 1H, NH). 13C NMR (125 MHz)
: 21.9 (CH3),
n
(cmꢁ1): 3432, 3387, 3247, 3102, 1634, 1612,
: 2.30 (s, 3H, CH3), 5.19 (br s,
d
Scheme 9. The synthesis of compounds 11a and 14 from 4a. Reagents and conditions:
(a) EtONa, EtOH, reflux; (b) NaOH, EtOH–H2O, reflux.
d
91.0 (CH), 122.2, 122.4, 126.4, 126.5, 129.2, 129.4, 137.3, 137.4 (car-
bons of phenyls), 153.6, 153.8, 154.3, 154.3 (carbons of triazoles),
156.0 (C-3),167.5 (CO). Anal. Calcd for C20H20N10O: C, 57.68; H, 4.84;
N, 33.63. Found: C, 57.71; H, 4.69; N, 33.34.
Method B. A mixture of triazole 1a (1.00 g, 5.71 mmol), keto ester
7a (0.74 g, 5.71 mmol), and xylene (5 mL) was heated to reflux for
5 h. Then xylene was evaporated to a volume of about 2 mL and the
reaction mixture was cooled to room temperature. The precipitate
formed was filtered off and recrystallized from DMF–ethanol
mixture (1:3) to give 9 (0.67 g, 56%).
3. Conclusion
The direction of the reaction of 1-substituted 3,5-diamino-1,2,4-
triazoles 1 with b-keto esters differs significantly from that of the
analogous reaction of C-amino-1,2,4-triazoles, unsubstituted at the
endocyclic nitrogen atoms. Initially a reversible condensation
occurs to afford the rather stable 5-amino-1-R-1,2,4-triazol-3-yl-
substituted enaminoesters 8, which then, depending on the
reaction conditions, undergo intermolecular condensation and
amidation or cyclization to form mesoionic 3-amino-2-R-
[1,2,4]triazolo[4,3-a]pyrimidin-5-ones (10). In contrast to
[1,2,4]triazolo[4,3-a]pyrimidin-5-ones that are unsubstituted at
N-2, for which the Dimroth rearrangement into the thermody-
namically more stable [1,2,4]triazolo[1,5-a]pyrimidin-7-ones is
inherent, compounds 10 undergo the unusual and irreversible
rearrangement into 3-amino-1-R-[1,2,4]triazolo[4,3-a]pyrimidin-
5-ones (11) under heating conditions. A suitable method for the
synthesis of the mesoionic compounds 10, based on the selective
cyclization of the enaminoesters 8 by heating in alcoholic alkali
solutions, was developed.
4.3. (2Z,20Z)-Diethyl 3,30-(1-phenyl-1H-1,2,4-triazole-3,5-
diyl)bis(azanediyl)dibut-2-enoate (4a)
A magnetically stirred mixture of triazole 1a (1.00 g, 5.71 mmol)
and ethyl acetoacetate 7a (2.96 g, 22.84 mmol) was heated at 140–
150 ꢀC for 1 h, then diluted with ethanol (5 mL) and cooled to room
temperature. The precipitate formed was filtered off and recrys-
tallized from ethanol to give colorless prisms (0.91 g, 40%) of 4a, mp
121–122 ꢀC, lit.6b mp 120–122 ꢀC. IR (ATR)
n
(cmꢁ1): 3206, 3066,
: 1.13,
2984, 2935, 1666, 1627, 1581, 1556, 1529. 1H NMR (300 MHz)
d
1.19 (both t, J¼7.1 Hz, 3H each, OCH2CH3), 2.34, 2.35 (both s, 3H
each, CH3), 3.99, 4.08 (both q, J¼7.1 Hz, 2H each, OCH2CH3), 4.83,
4.98 (both s, 1H each, CH), 7.47–7.63 (m, 5H, Ph), 10.82 (s, 1H, NH),
Substantial difference in nucleophilicity of the amino groups in
the positions 3 and 5 of 1-substituted 3,5-diamino-1,2,4-triazoles
allows to employ the reaction between these compounds and
11.09 (s, 1H, NH). 13C NMR (125 MHz)
d: 14.2, 14.3, 21.1, 21.3, 58.9,
b
-keto esters for the selective synthesis of isomeric [1,2,4]tri-
59.2, 88.9, 92.1, 124.4, 128.8, 129.8, 135.5, 147.4, 155.4, 155.7, 156.7,
169.0, 169.3. MS (EI, 70 eV), m/z (%): 399 (Mþ, 62), 307 (100), 280
(27), 266 (21), 240 (29), 200 (20), 190 (28), 110 (16), 77 (53), 67 (14),
42 (10). Anal. Calcd for C20H25N5O4: C, 60.14; H, 6.31; N, 17.53.
Found: C, 60.28; H, 6.35; N, 17.25.
azolo[4,3-a]pyrimidines.
4. Experimental
4.1. General
4.4. General procedure for the synthesis of compounds 8a–g
The melting points were determined in open capillary tubes in
a Thiele apparatus and are uncorrected. IR spectra were recorded
on a Varian Excalibur 3100 FT-IR spectrometer using a single re-
flection ATR system as a sampling accessory. 1H and 13C NMR
spectra were recorded on a Bruker DRX 500 instrument at 500 MHz
and 125 MHz, respectively, and a Bruker Avance 600 instrument at
600 MHz (150 MHz for 13C) or Varian Unity 300 at 300 MHz
(75 MHz for 13C) in DMSO-d6 and using TMS as an internal stan-
dard. Mass spectra were recorded in the form of m/z (intensity
relative to base 100) on a Finnigan MAT INCOS 50 instrument using
electron impact ionization. UV spectra were obtained with a Spe-
cord UV–vis spectrophotometer in aqueous solutions. Elemental
analyses were determined using a Perkin–Elmer 2400 Elemental
Analyzer. HPLC analyses were performed on a Milichrom-5 chro-
matograph equipped with a Nucleosil-C18 column (acetonitrile/
water as the mobile phase) and a UV detector. Chromatographic
purification of products was accomplished using column chroma-
tography on Al2O3 230–400 mesh.
Method A. A solution of diaminotriazole 1a,b (6 mmol) and ap-
propriate
b-keto ester 7a–f (6.6 mmol) in EtOH (2 mL) or 7g in
MeOH (2 mL) was heated to reflux for 5 h, then water (5 mL) was
added. After cooling, the precipitate formed was isolated by filtra-
tion and recrystallized from ethanol.
Method B. A solution of diaminotriazole 1a (6 mmol) and ap-
propriate b-keto ester 7a,e (6.6 mmol) in 10 mL of tetrahydrofuran
was heated to reflux for 5 h. Then the solution was evaporated to
a volume of about 4 mL and the reaction mixture was diluted with
water (5 mL). The precipitate formed was isolated by filtration and
recrystallized from ethanol.
Method C. A mixture of compound 1a (0.5 g, 2.85 mmol), keto
ester 7a (0.41 g, 3.14 mmol), and acetic acid (1 mL) was refluxed for
15 min, cooled to room temperature, diluted with water (5 mL), and
extracted with chloroform (3ꢂ5 mL). The extract was evaporated to
a volume of about 1 mL and subjected to a column chromatography
(Al2O3, CHCl3) to give compound 8a.

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V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
4.4.1. Ethyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)but-2-
enoate (8a). Yield 1.03 g (60%, Method A, pure (Z)-isomer), 1.29 g
(75%, Method B, mixture of (E,Z)-isomers), 0.12 g (15%, Method C,
mixture of (E,Z)-isomers) of colorless plates. Mp 115–116 ꢀC (pure
for C22H25N5O2: C, 67.50; H, 6.44; N, 17.89. Found: C, 67.69; H, 6.36;
N, 17.57.
4.4.5. (E)-Ethyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-2-
(Z)-isomer). IR (ATR) for (Z)-isomer,
n
(cmꢁ1): 3441, 3305, 3131, 2984,
chlorobut-2-enoate (8e). Yield 1.1 g (57%, Method B) of yellowish
1648, 1620, 1578, 1552, 1516. 1H NMR for (Z)-isomer (300 MHz)
d:
needles, mp 144–146 ꢀC. IR (ATR) (cmꢁ1): 3474, 3433, 3315, 3166,
n
1.18 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.32 (s, 3H, CH3), 4.06 (q, J¼7.1 Hz,
2994, 1646, 1608, 1570, 1546, 1501. 1H NMR (300 MHz)
d: 1.25 (t,
2H, OCH2CH3), 4.75 (s, 1H, CH), 6.57 (s, 2H, NH2), 7.48–7.54 (m, 5H,
J¼7.1 Hz, 3H, OCH2CH3), 2.59 (s, 3H, CH3), 4.19 (q, J¼7.1 Hz, 2H,
Ph),10.59 (s,1H, NH).1H NMR for the (E)-isomer (300 MHz)
d: 1.14 (t,
OCH2CH3), 6.65 (s, 2H, NH2), 7.34–7.54 (m, 5H, Ph), 11.06 (s, 1H, NH).
J¼7.1 Hz, 3H, OCH2CH3), 2.31 (s, 3H, CH3), 3.90 (q, J¼7.1 Hz, 2H,
13C NMR (125 MHz)
d: 14.1 (OCH2CH3), 18.3 (CH3), 60.7 (OCH2CH3),
OCH2CH3), 6.31 (s, 1H, CH), 6.49 (s, 2H, NH2), 7.28–7.35 (m, 5H, Ph),
93.8 (C-2 of butenoate), 122.3, 126.7, 129.3, 136.9 (carbons of Ph),
153.8, 154.9, 155.1 (carbons of triazole and C-3 of butenoate), 166.2
(CO). MS (EI, 70 eV), m/z (%): 321 (Mþ, 17), 286 (40), 258 (17), 240
(47), 200 (12), 175 (15), 119 (27), 91 (26), 77 (100), 64 (18), 51 (46),
43 (39), 42 (26). Anal. Calcd for C14H16ClN5O2: C, 52.26; H, 5.01; N,
21.77. Found: C, 52.19; H, 5.11; N, 21.41.
9.09 (s, 1H, NH). 13C NMR (125 MHz) for the (Z)-stereoisomer
d: 14.4
(OCH2CH3), 21.5 (CH3), 58.7 (OCH2CH3), 88.1 (C-2 of butenoate),
122.4, 126.7, 129.5, 137.3 (carbons of Ph), 153.9, 155.5 (carbons of
triazole), 157.1 (C-3 of butenoate), 169.5 (CO). MS (EI, 70 eV) for the
mixture of (E,Z)-stereoisomers, m/z (%): 287 (Mþ, 56), 241 (56), 214
(55), 200 (19), 123 (41), 119 (39), 105 (13), 96 (12), 91 (28), 77 (100),
68 (17), 51 (20), 43 (17). Anal. Calcd for C14H17N5O2: C, 58.52; H, 5.96;
N, 24.37. Found: C, 58.74; H, 5.99; N, 24.25.
4.4.6. (Z)-Ethyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-
hex-2-enoate (8f). Yield 0.85 g (45%, Method A) of colorless plates,
mp 153–154 ꢀC. IR (ATR)
n
(cmꢁ1): 3442, 3303, 3145, 2965, 1648,
4.4.2. (Z)-Ethyl 2-(1-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-
1615, 1579, 1550, 1511. 1H NMR (500 MHz)
d
: 0.93 (t, J¼7.3 Hz, 3H,
ethylidene)hexanoate (8b). Yield 0.82 g (40%, Method A) of colorless
CH2CH2CH3), 1.20 (t, J¼7.1 Hz, 3H, OCH2CH3), 1.57 (m, 2H,
CH2CH2CH3), 2.73 (t, J¼7.6 Hz, 2H, CH2CH2CH3), 4.08 (q, J¼7.1 Hz,
2H, OCH2CH3), 4.86 (s, 1H, CH), 6.56 (s, 2H, NH2), 7.31–7.55 (m, 5H,
needles, mp 123–124 ꢀC. IR (ATR) (cmꢁ1): 3444, 3422, 3288, 3163,
n
2964, 1620,1573,1545,1499. 1H NMR (600 MHz)
d
: 0.88 (t, J¼7.2 Hz,
3H, (CH2)3CH3), 1.21 (t, J¼7.1 Hz, 3H, OCH2CH3), 1.27–1.33 (m, 4H,
CH2(CH2)2CH3), 2.24 (t, J¼7.4 Hz, 2H, CH2(CH2)2CH3), 2.39 (s, 3H,
CH3), 4.10 (q, J¼7.1 Hz, 2H, OCH2CH3), 6.49 (s, 2H, NH2), 7.30
(t, J¼7.2 Hz, 1H, Ph), 7.47 (m, 2H, Ph), 7.53 (d, J¼7.7 Hz, 2H, Ph), 11.31
Ph), 10.59 (s, 1H, NH). 13C NMR (125 MHz)
d: 13.5 (CH2CH2CH3), 14.3
(OCH2CH3), 21.1 (CH2CH2CH3), 34.8 (CH2CH2CH3), 58.6 (OCH2CH3),
87.5 (C-2 of hexenoate), 121.9, 126.3, 129.3, 137.1 (carbons of Ph),
153.7, 155.1, 160.5 (carbons of triazole and C-3 of hexenoate), 169.3
(CO). MS (EI, 70 eV), m/z (%): 315 (Mþ, 49), 287 (14), 270 (10), 254
(29), 242 (64), 228 (19), 212 (19), 200 (15), 187 (14), 175 (13), 160
(10), 134 (11), 119 (48), 105 (12), 91 (30), 77 (100), 68 (20), 51 (22),
43 (27), 41 (23), 39 (19). Anal. Calcd for C16H21N5O2: C, 60.94; H,
6.71; N, 22.21. Found: C, 61.14; H, 6.65; N, 22.05.
(s, 1H, NH). 13C NMR (150 MHz)
d: 13.8 (CH3), 14.2 (CH3), 16.7 (CH3),
21.9 (CH2), 26.0 (CH2), 32.2 (CH2), 59.0 (OCH2CH3), 98.5 (C-2 of
hexanoate), 122.1, 126.3, 129.3, 137.2 (carbons of Ph), 153.6 (C-3 of
hexanoate), 153.6, 156.0 (carbons of triazole), 169.9 (CO). MS (EI,
70 eV), m/z (%): 343 (Mþ, 16), 300 (74), 270 (11), 254 (44), 200 (39),
175 (100), 133 (28), 119 (33), 91 (74), 77 (85), 64 (23), 51 (32), 43
(44). Anal. Calcd for C18H25N5O2: C, 62.95; H, 7.34; N, 20.39. Found:
C, 63.11; H, 7.30; N, 20.07.
4.4.7. (Z)-Methyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-
4-methylpent-2-enoate (8g). Yield 0.76 g (42%, Method A) of color-
less plates, mp 156–157 ꢀC. IR (ATR)
n
(cmꢁ1): 3439, 3291, 3093,
4.4.3. (Z)-Ethyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-2-
2962, 1623, 1581, 1552, 1521, 1500. 1H NMR (300 MHz)
d: 1.12 (m,
benzylbut-2-enoate (8c). Yield 0.91 g (40%, Method A) of colorless
6H, 2CH3), 3.59 (s, 3H, OCH3), 3.85 (m, 1H, CH), 4.80 (s, 1H, CH), 6.60
plates, mp 132–133 ꢀC. IR (ATR)
n
(cmꢁ1): 3430, 3300, 3106, 2984,
(s, 2H, NH2), 7.30–7.53 (m, 5H, Ph), 11.68 (s, 1H, NH). 13C NMR
1640, 1613, 1576, 1543, 1491. 1H NMR (500 MHz)
d
: 1.14 (t, J¼7.1 Hz,
(125 MHz) d: 21.1 (2CH3), 28.4 (CH(CH3)2), 50.3 (OCH3), 83.4 (C-2 of
3H, OCH2CH3), 2.40 (s, 3H, CH3), 3.67 (s, 2H, CH2), 4.09 (q, J¼7.1 Hz,
2H, OCH2CH3), 6.53 (s, 2H, NH2), 7.13–7.54 (m, 10H, 2Ph), 11.47 (s,
pentenoate), 122.2, 126.5, 129.3, 137.1 (carbons of Ph), 153.7, 155.0
(carbons of triazole), 167.1 (C-3 of pentenoate), 170.1 (CO). MS (EI,
70 eV), m/z (%): 301 (Mþ, 31), 254 (11), 242 (22), 119 (17), 93 (17), 91
(31), 77 (100), 68 (19), 65 (16), 59 (20), 51 (38), 43 (63), 42 (18), 41
(35). Anal. Calcd for C15H19N5O2: C, 59.79; H, 6.36; N, 23.24. Found:
C, 59.64; H, 6.50; N, 23.48.
1H, NH). 13C NMR (125 MHz)
d: 14.1 (OCH2CH3), 17.2 (CH3 of bute-
noate), 31.8 (CH2Ph), 59.2 (OCH2CH3), 96.9 (C-2 of butenoate),
122.2, 125.5, 126.4, 127.5, 128.1, 129.3, 137.1, 141.6 (carbons of phe-
nyls), 153.7, 155.3, 155.8 (carbons of triazole and C-3 of butenoate),
169.8 (CO). MS (EI, 70 eV), m/z (%): 377 (Mþ, 5), 286 (16), 200 (21),
176 (21), 144 (12), 135 (10), 128 (25), 119 (47), 91 (64), 77 (100), 65
(24), 51 (29), 43 (19). Anal. Calcd for C18H23N5O2: C, 66.83; H, 6.14;
N, 18.55. Found: C, 66.60; H, 6.06; N, 18.78.
4.4.8. (Z)-Ethyl 3-(5-amino-1-benzyl-1H-1,2,4-triazol-3-ylamino)-
but-2-enoate (8h). Yield 1.32 g (73%, Method A) of colorless plates,
mp 137–138 ꢀC. IR (ATR)
n
(cmꢁ1): 3429, 3295, 3127, 2985, 1627,
1576, 1539, 1496. 1H NMR (300 MHz)
d
: 1.16 (t, J¼7.1 Hz, 3H,
4.4.4. (Z)-Ethyl 3-(5-amino-1-phenyl-1H-1,2,4-triazol-3-ylamino)-2-
OCH2CH3), 2.22 (s, 3H, CH3), 4.03 (q, J¼7.1 Hz, 2H, OCH2CH3), 4.66 (s,
(4-methylbenzyl)but-2-enoate (8d). Yield 0.96 g (41%, Method A) of
1H, CH), 5.00 (s, 2H, CH2), 6.49 (s, 2H, NH2), 7.21–7.33 (m, 5H, Ph),
yellowish needles, mp 142.5–144 ꢀC. IR (ATR)
n
(cmꢁ1): 3464, 3301,
10.48 (s, 1H, NH). 13C NMR (125 MHz)
d: 14.7 (OCH2CH3), 21.6 (CH3),
3092, 2980, 1619, 1581, 1544, 1499. 1H NMR (500 MHz)
d: 1.15 (t,
49.2 (CH2Ph), 58.9 (OCH2CH3), 87.6 (C-2 of butenoate), 127.5, 127.7,
128.8, 137.4 (carbons of Ph), 155.11, 155.13, 157.6 (carbons of triazole
and C-3 of butenoate), 169.6 (CO). MS (EI, 70 eV), m/z (%): 301 (Mþ,
21), 228 (12), 91 (100), 65 (16), 43 (19), 42 (13). Anal. Calcd for
C15H19N5O2: C, 59.79; H, 6.36; N, 23.24. Found: C, 59.88; H, 6.33; N,
23.01.
J¼7.1 Hz, 3H, OCH2CH3), 2.23 (s, 3H, CH3), 2.39 (s, 3H, CH3), 3.61 (s,
2H, CH2), 4.08 (q, J¼7.1 Hz, 2H, OCH2CH3), 6.52 (s, 2H, NH2), 7.03–
7.54 (m, 9H, Ar), 11.46 (s, 1H, NH). 13C NMR (125 MHz)
d: 14.1
(OCH2CH3), 17.1 (CH3 of butenoate), 20.5 (CH3 of methylbenzyl),
31.3 (CH2 of methylbenzyl), 59.2 (OCH2CH3), 97.1 (C-2 of bute-
noate), 122.1, 126.4, 127.4, 128.7, 129.3, 134.3, 137.1, 138.5 (Ar), 153.7,
155.2, 155.8 (carbons of triazole and C-3 of butenoate), 169.8 (CO).
MS (EI, 70 eV), m/z (%): 391 (Mþ, 15), 345 (22), 318 (22), 286 (30),
225 (11), 200 (27), 176 (21), 143 (14), 128 (20), 119 (39), 115 (14), 105
(40), 91 (39), 77 (100), 65 (25), 51 (31), 43 (25), 42 (20). Anal. Calcd
4.4.9. (E)-Ethyl 3-(5-amino-1-benzyl-1H-1,2,4-triazol-3-ylamino)-2-
chlorobut-2-enoate (8i). Yield 0.93 g (46%, Method A) of yellowish
plates, mp 183–184 ꢀC. IR (ATR)
n
(cmꢁ1): 3414, 3312, 3146, 2990,
1619, 1572, 1521, 1495. 1H NMR (500 MHz)
d: 1.24 (t, J¼7.1 Hz, 3H,

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3309
OCH2CH3), 2.21 (s, 3H, CH3), 4.17 (q, J¼7.1 Hz, 2H, OCH2CH3), 5.03 (s,
a volume of 5 mL. According to HPLC analysis, the yield of 11a was
18% and the compound 10a was absent in the reaction mixture.
DMF solution (4 mL) was evaporated to dryness at reduced pres-
sure and the residue was extracted with hot chloroform (5 mL). The
extract was subjected to a column chromatography (Al2O3, CHCl3)
to give 48 mg (yield 15%) of compound 11a.
Method D. A solution of NaOH (90 mg, 2.25 mmol) in water (8 mL)
was added to a magnetically stirred suspension of compound 14
(400 mg,1.13 mmol) in ethanol (15 mL) and the resulted mixture was
heated to reflux for 20 min, then cooled to room temperature and
neutralized by addition of acetic acid. Then the resultant solution was
evaporated to a volume of about 8 mL and diluted with cold water
(10 mL) to give 210 mg (78%) of pure compound 11a.
2H, CH2), 6.52 (s, 2H, NH2), 7.22–7.36 (m, 5H, Ph), 10.93 (s, 1H, NH).
13C NMR (125 MHz)
d: 14.6 (OCH2CH3), 18.6 (CH3), 49.2 (CH2Ph),
61.0 (OCH2CH3), 93.4 (C-2 of butenoate), 127.7, 127.8, 128.8, 137.3
(carbons of Ph), 154.7, 155.2, 155.6 (carbons of triazole and C-3 of
butenoate), 166.7 (CO). MS (EI, 70 eV), m/z (%): 335 (Mþ, 1.5), 91
(100), 65 (17), 43 (14), 39 (13). Anal. Calcd for C15H18ClN5O2: C,
53.65; H, 5.40; N, 20.86. Found: C, 53.81; H, 5.54; N, 20.63.
4.4.10. (Z)-Ethyl 3-(5-amino-1-benzyl-1H-1,2,4-triazol-3-ylamino)-
hex-2-enoate (8j). Yield 1.07 g (54%, Method A) of colorless
plates, mp 142–143 ꢀC. IR (ATR)
n
(cmꢁ1): 3449, 3297, 3127,
2961, 1641, 1615, 1590, 1543, 1521. 1H NMR (600 MHz)
d: 0.82 (t,
J¼6.9 Hz, 3H, CH3), 1.17 (t, J¼7.1 Hz, 3H, OCH2CH3), 1.44 (m, 2H,
CH2), 2.62 (t, J¼7.2 Hz, 2H, CH2), 4.04 (q, J¼7.1 Hz, 2H, OCH2CH3),
4.66 (s, 1H, CH), 5.01 (s, 2H, CH2), 6.43 (s, 2H, NH2), 7.22–7.33
Method E. A solution of NaOH (96 mg, 2.40 mmol) in water
(8 mL) was added to a magnetically stirred suspension of com-
pound 4a (400 mg, 1.00 mmol) in ethanol (15 mL). The resulted
mixture was heated to reflux for 20 min, then treated by analogy
with method D to give 121 mg (50%) of pure compound 11a.
(m, 5H, Ph), 10.44 (s, 1H, NH). 13C NMR (150 MHz)
d: 13.5 (CH3),
14.3 (CH3), 21.1 (CH2), 34.7 (CH2), 48.9 (CH2Ph), 58.5 (OCH2CH3),
86.7 (C-2 of hexenoate), 127.30, 127.35, 128.3, 137.0 (carbons of
Ph), 154.4 (C-3 of triazole), 154.7 (C-5 of triazole), 160.9 (C-3 of
hexenoate), 169.3 (CO). MS (EI, 70 eV), m/z (%): 329 (Mþ, 23),
301 (11), 256 (24), 238 (11), 91 (100). Anal. Calcd for
C17H23N5O2: C, 61.99; H, 7.04; N, 21.26. Found: C, 62.21; H, 7.22;
N, 20.95.
4.6.1. 3-Amino-7-methyl-5-oxo-2-phenyl-5H-[1,2,4]triazolo[4,3-a]-
pyrimidin-2-ium-8-ide (10a). Yield 69 mg (10%, Method A), 352 mg
(73%, Method B) of colorless plates, mp 210–211 ꢀC; Rf¼0.15. IR
(ATR)
n
(cmꢁ1): 3293, 2889, 1687, 1655, 1588, 1503. UV, lmax, nm
(3$10ꢁ3): 234 (22.1) and 344 (11.3). 1H NMR (300 MHz)
3H, CH3), 5.20 (s, 1H, CH), 7.49–7.65 (m, 5H, Ph), 8.38 (s, 2H, NH2).
13C NMR (75 MHz)
: 24.7 (CH3), 90.4 (C-6), 124.5, 128.9, 129.5,
d: 2.12 (s,
4.5. (2Z,20Z)-Diethyl 3,30-(1-phenyl-1H-1,2,4-triazole-3,5-
diyl)bis(azanediyl)dibut-2-enoate (4a), ethyl 3-(5-amino-1-
phenyl-1H-1,2,4-triazol-3-ylamino)but-2-enoate (8a), (E)-N-
(5-amino-1-phenyl-1H-1,2,4-triazol-3-yl)-3-(5-amino-1-
phenyl-1H-1,2,4-triazol-3-ylamino)but-2-enamide (9)
d
134.8 (carbons of Ph), 143.3 (C-3), 151.9 (C-8a), 159.5 (CO), 169.1
(C-7). MS (EI, 70 eV), m/z (%): 241 (Mþ, 91), 212 (11), 123 (33), 119
(44), 105 (16), 94 (23), 91 (22), 77 (100), 68 (21), 64 (20), 51 (57), 42
(17), 39 (69). Anal. Calcd for C12H11N5O: C, 59.74; H, 4.60; N, 29.03.
Found: C, 59.87; H, 4.47; N, 29.21.
A mixture of triazole 1a (1.00 g, 5.71 mmol) and ethyl acetoa-
cetate 7a (1.11 g, 8.57 mmol) was heated at 100–105 ꢀC and stirring
for 60 h, then cooled to room temperature and diluted with 1,2-
dichloroethane (10 mL). The precipitate formed was filtered off and
dried at 100 ꢀC to give crude compound 9 (400 mg, 40%). An ana-
lytical sample was obtained by crystallization of crude 9 from DMF–
ethanol mixture (1:3). The mother liquor was concentrated in
vacuo giving a residue, which was subjected to a column chroma-
tography (Al2O3, CHCl3) to give product 4a (336 mg, 15%) with
Rf¼0.98 and product 8a (410 mg, 25%) with Rf¼0.3.
4.6.2. 3-Amino-6-butyl-7-methyl-5-oxo-2-phenyl-5H-[1,2,4]tri-
azolo[4,3-a]pyrimidin-2-ium-8-ide (10b). Yield 161 mg (19%,
Method A), 363 mg (61%, Method B) of colorless needles, mp 201–
202 ꢀC; Rf¼0.21. IR (ATR)
n
(cmꢁ1): 3199, 2923,1660, 1582,1492. UV,
lmax, nm (3$10ꢁ3): 238 (22.6) and 348 (10.4). 1H NMR (600 MHz)
d:
0.90 (t, J¼7.2 Hz, 3H, (CH2)3CH3), 1.29–1.40 (m, 4H, 2CH2), 2.20 (s,
3H, CH3), 2.35 (t, J¼7.4 Hz, 2H, CH2), 7.47–7.66 (m, 5H, Ph), 8.45 (br
s, 2H, NH2). 13C NMR (150 MHz)
d: 13.9 (CH3), 22.1 (CH2), 22.6 (CH3),
24.2 (CH2), 31.3 (CH2), 102.0 (C-6), 124.1, 128.6, 129.5, 135.1 (carbons
of phenyl), 143.1 (C-3), 149.9 (C-8a), 159.3 (CO), 165.3 (C-7). MS (EI,
70 eV), m/z (%): 297 (Mþ, 14), 254 (100), 200 (34), 119 (24), 91 (20),
77 (79), 65 (22), 55 (12), 53 (21), 51 (30), 43 (20), 39 (29). Anal.
Calcd for C16H19N5O: C, 64.63; H, 6.44; N, 23.55. Found: C, 64.47; H,
6.53; N, 23.28.
4.6. General procedures for the synthesis of compounds
10a–i and 11a–j
Method A. A magnetically stirred mixture of triazole 1a,b
(2.85 mmol), compound 7a–h (3.14 mmol) and acetic acid (2 mL)
was heated to reflux for 15 min, then acetic acid was distilled off
until the temperature of the reaction mixture raised to 145–150 ꢀC.
The reaction mixture was heated at the same temperature and
stirred for 5 h, cooled to room temperature, dissolved in chloroform
and subjected to a column chromatography (Al2O3, CHCl3) to give
products 10a–d, f–i, and 11a–j.
Method B. Compound 8a–h,j (2 mmol) was added to a solution
of sodium (0.14 g, 6.0 mmol) in absolute EtOH or MeOH (10 mL).
The resultant mixture was heated to reflux for 20 min, cooled to
room temperature and neutralized by addition of acetic acid. Then
solvent was evaporated to a volume of about 1 mL and the resultant
solution was diluted with water (5 mL) to give product 10a–i.
Samples for elemental analysis were obtained by crystallization of
crude products from ethanol.
4.6.3. 3-Amino-6-benzyl-7-methyl-5-oxo-2-phenyl-5H-[1,2,4]tri-
azolo[4,3-a]pyrimidin-2-ium-8-ide (10c). Yield 104 mg (11%, Method
A), 616 mg (93%, Method B) of colorless needles, mp 202–203 ꢀC;
Rf¼0.23. IR (ATR)
(3$10ꢁ3): 238 (24.7) and 344 (11.1). 1H NMR (500 MHz)
CH3), 3.75 (s, 2H, CH2), 7.12–7.26 (m, 5H, Ph), 7.50–7.67 (m, 5H, Ph),
8.45 (br s, 2H, NH2). 13C NMR (125 MHz)
: 23.2 (CH3), 29.8 (CH2),
n
(cmꢁ1):3286, 2904,1658,1586,1491. UV, lmax, nm
d: 2.14 (s, 3H,
d
100.7 (C-6), 124.4, 125.5, 127.8, 128.1, 128.9, 129.5, 135.0, 141.6 (car-
bons of phenyls),143.2 (C-3),150.4 (C-8a),159.5 (CO),166.7 (C-7). MS
(EI, 70 eV), m/z (%): 331 (Mþ, 26), 211 (11), 200 (12),143 (11),134 (14),
128 (19),119 (31),115 (12),103 (12), 91 (56), 77 (100), 67 (15), 65 (29),
51 (48), 42 (17), 39 (24). Anal. Calcd for C19H17N5O: C, 68.87; H, 5.17;
N, 21.13. Found: C, 69.05; H, 5.13; N, 21.01.
Method C. A magnetically stirred mixture of compound 10a
(400 mg, 1.66 mmol) and acetic acid (0.4 mL) in a glass ampoule
placed in oil bath was heated at 150–160 ꢀC for 10 h. After cooling
to room temperature the ampoule was unsealed (caution: excessive
pressure!) and the reaction mixture was diluted with DMF to
4.6.4. 3-Amino-7-methyl-6-(4-methylbenzyl)-5-oxo-2-phenyl-5H-
[1,2,4]triazolo[4,3-a]pyrimidin-2-ium-8-ide (10d). Yield 226 mg
(23%, Method A), 553 mg (80%, Method B) of yellowish needles, mp
211.5–212.5 ꢀC; Rf¼0.24. IR (ATR)
n
(cmꢁ1): 3199, 3054, 2920, 1666,
1580, 1492. UV, lmax, nm (3$10ꢁ3): 220 sh (19.9), 238 (23.8), and 347

3310
V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
(10.6). 1H NMR (300 MHz)
d
: 2.12 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.70
(79%, Method B) of colorless plates, mp 179–179.5 ꢀC; Rf¼0.17. IR
(s, 2H, CH2), 7.05 (d, J¼7.9 Hz, 2H, Ar), 7.11 (d, J¼7.9 Hz, 2H, Ar),
(ATR) n ,
(cmꢁ1): 3244, 3107, 2962, 1652, 1583, 1538, 1511. UV, lmax
7.49–7.68 (m, 5H, Ph), 8.43 (br s, 2H, NH2). 13C NMR (150 MHz)
d:
nm (3$10ꢁ3): 225 (18.4), 264 (4.5), and 329 (10.1). 1H NMR
(600 MHz)
: 0.86 (t, J¼6.6 Hz, 3H, CH3), 1.58 (m, 2H, CH2), 2.29 (t,
J¼6.6 Hz, 2H, CH2), 5.14 (s, 1H, CH), 5.22 (s, 2H, CH2), 7.20–7.33 (m,
5H, Ph), 8.39 (br s, 2H, NH2). 13C NMR (150 MHz)
: 13.7 (CH3), 21.2
20.6 (CH3), 23.2 (CH3), 29.4 (CH2), 101.0 (C-6), 124.4, 127.7, 128.7,
128.9, 129.6, 134.3, 135.0, 138.5 (carbons of benzene rings),143.2 (C-
3), 150.3 (C-8a), 159.6 (CO), 167.0 (C-7). MS (EI, 70 eV), m/z (%): 345
(Mþ, 24), 225 (11), 200 (14), 143 (13), 134 (16), 128 (20), 119 (32), 115
(19), 105 (38), 91 (32), 77 (100), 67 (16), 65 (28), 51 (41), 42 (15), 39
(28). Anal. Calcd for C20H19N5O: C, 69.55; H, 5.54; N, 20.28. Found:
C, 69.78; H, 5.66; N, 20.41.
d
d
(CH2), 40.1 (CH2), 49.5 (CH2), 89.8 (C-6), 127.86, 127.91, 128.6, 134.8
(carbons of Ph), 143.3 (C-3), 152.1 (C-8a), 159.3 (CO), 172.5 (C-7). MS
(EI, 70 eV), m/z (%): 283 (Mþ, 3), 91 (100), 65 (21), 39 (17). Anal.
Calcd for C15H17N5O: C, 63.59; H, 6.05; N, 24.72. Found: C, 63.81;
H, 6.11; N, 24.47.
4.6.5. 3-Amino-6-chloro-7-methyl-5-oxo-2-phenyl-5H-[1,2,4]tri-
azolo[4,3-a]pyrimidin-2-ium-8-ide (10e). Yield 629 mg (80%,
4.6.10. 3-Amino-7-methyl-1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidin-
5(1H)-one (11a). Yield 144 mg (21%) of colorless needles, mp 176–
Method B) of yellowish prisms, mp 260–262 ꢀC; Rf¼0.16. IR (ATR)
n
(cmꢁ1): 3348, 3244, 3212, 3064, 1680, 1647, 1587, 1483. UV, lmax
,
177 ꢀC; Rf¼0.75. IR (ATR)
n
(cmꢁ1): 3424, 3262, 3200, 3143, 1702,
nm (3$10ꢁ3): 238 (23.8) and 347 (10.4). 1H NMR (500 MHz)
(s, 3H, CH3), 7.52–7.64 (m, 5H, Ph), 8.40 (s, 2H, NH2). 13C NMR
(125 MHz) : 24.3 (CH3), 96.8 (C-6), 125.3, 129.8, 130.1, 135.0 (car-
d
: 2.31
1678, 1656, 1581, 1499. UV, lmax, nm (3$10ꢁ3): 227 (9.8), 270 (4.1),
and 331 (12.6). 1H NMR (300 MHz)
CH), 7.13 (s, 2H, NH2), 7.26 (m, 1H, Ph), 7.50 (m, 2H, Ph), 8.07 (m, 2H,
Ph). 13C NMR (75 MHz)
: 24.2 (CH3), 99.0 (C-6), 119.1, 125.3, 128.9,
d: 2.25 (s, 3H, CH3), 5.74 (s, 1H,
d
bons of Ph), 143.6 (C-3), 150.1 (C-8a), 155.2 (CO), 165.7 (C-7). MS (EI,
70 eV), m/z (%): 275 (94), 200 (20), 119 (50), 91 (17), 77 (100), 67
(14), 64 (15), 51 (37), 39 (17). Anal. Calcd for C12H10ClN5O: C, 52.28;
H, 3.66; N, 25.40. Found: C, 51.98; H, 3.51; N, 25.43.
d
137.0 (carbons of Ph), 146.1, 146.2 (carbons of triazole), 158.6 (CO),
167.3 (C-7). MS (EI, 70 eV), m/z (%): 241 (Mþ, 51), 133 (18), 126 (32),
109 (74),103 (26), 91 (100), 77 (64), 68 (25), 64 (31), 51 (39), 39 (51).
Anal. Calcd for C12H11N5O: C, 59.74; H, 4.60; N, 29.03. Found: C,
59.50; H, 4.71; N, 29.19.
4.6.6. 3-Amino-5-oxo-2-phenyl-7-propyl-5H-[1,2,4]triazolo[4,3-a]-
pyrimidin-2-ium-8-ide (10f). Yield 92 mg (12%, Method A), 420 mg
(78%, Method B) of colorless needles, mp 147 ꢀC dec; Rf¼0.16. IR
4.6.11. 3-Amino-6-butyl-7-methyl-1-phenyl-[1,2,4]triazolo[4,3-
a]pyrimidin-5(1H)-one (11b). Yield 397 mg (35%) of colorless nee-
(ATR)
n
(cmꢁ1): 3303, 2961, 1678, 1597, 1537, 1520. UV, lmax, nm
(3$10ꢁ3): 234 (24.1) and 336 (10.7). 1H NMR (500 MHz)
d
: 0.91 (t,
dles, mp 155–156 ꢀC; Rf¼0.89. IR (ATR)
n
(cmꢁ1): 3429, 3284, 2951,
J¼7.4 Hz, 3H, CH3), 1.63 (m, 2H, CH2), 2.35 (t, J¼7.5 Hz, 2H, CH2),
1701, 1667, 1577, 1484. UV, lmax, nm (3$10ꢁ3): 220 (10.5), 275 (6.1),
5.20 (s, 1H, CH), 7.49–7.67 (m, 5H, Ph), 8.37 (br s, 2H, NH2). 13C NMR
and 349 (17.1). 1H NMR (300 MHz)
d
: 0.90 (t, J¼7.0 Hz, 3H,
(125 MHz)
d: 14.1 (CH3), 21.7 (CH2), 40.5 (CH2), 90.5 (C-6), 124.9,
(CH2)3CH3), 1.36 (m, 4H, 2CH2), 2.31 (s, 3H, CH3), 2.42 (t, J¼7.3 Hz,
129.3, 130.0, 135.4 (carbons of Ph), 143.8 (C-3), 152.5 (C-8a), 160.2
(CO), 173.2 (C-7). MS (EI, 70 eV), m/z (%): 269 (Mþ, 13), 254 (14), 241
(100), 212 (15), 119 (27), 93(30), 77 (98), 67 (19), 65 (20), 51 (37), 43
(18), 39 (44). Anal. Calcd for C14H15N5O: C, 62.44; H, 5.61; N, 26.01.
Found: C, 62.57; H, 5.49; N, 25.73.
2H, CH2), 7.16 (s, 2H, NH2), 7.23 (m, 1H, Ph), 7.48 (m, 2H, Ph), 8.08
(m, 2H, Ph). 13C NMR (125 MHz)
d: 13.8 (CH2)3CH3, 22.0 (CH2), 22.4
(CH2), 24.3 (CH3), 30.5 (CH2), 110.8 (C-6), 118.4, 124.8, 128.8, 137.2
(carbons of Ph), 143.9, 145.8 (carbons of triazole), 158.7 (CO), 162.6
(C-7). MS (EI, 70 eV), m/z (%): 297 (Mþ, 36), 254 (100), 77 (67), 67
(15), 55 (14), 51 (31), 43 (23), 41 (35), 39 (30). Anal. Calcd for
C16H19N5O: C, 64.63; H, 6.44; N, 23.55. Found: C, 64.87; H, 6.28; N,
23.69.
4.6.7. 3-Amino-7-isopropyl-5-oxo-2-phenyl-5H-[1,2,4]triazolo[4,3-a]-
pyrimidin-2-ium-8-ide (10g). Yield 207 mg (27%, Method A),
463 mg (86%, Method B) of colorless prisms, mp 149 ꢀC dec; Rf¼0.18.
IR (ATR)
n
(cmꢁ1): 3279, 2964, 1678, 1649, 1585, 1533, 1502. UV,
4.6.12. 3-Amino-6-benzyl-7-methyl-1-phenyl-[1,2,4]triazolo[4,3-a]-
pyrimidin-5(1H)-one (11c). Yield 397 mg (42%) of colorless needles,
lmax, nm (3$10ꢁ3): 234 (22.9) and 335 (8.6). 1H NMR (300 MHz)
1.15 (d, J¼6.6 Hz, 6H, 2CH3), 2.62 (m, 1H, CH of i-Pr), 5.22 (s, 1H, CH),
7.50–7.66 (m, 5H, Ph), 8.37 (br s, 2H, NH2). 13C NMR (150 MHz)
d:
mp 223–224 ꢀC; Rf¼0.87. IR (ATR)
n
(cmꢁ1): 3436, 3290, 1670, 1577,
d:
1483. UV, lmax, nm (3$10ꢁ3): 220 sh (15.1), 273 (6.9), and 349 (18.1).
21.5 (2CH3), 36.2 (CH), 88.1 (C-6), 124.6, 129.1, 129.6, 135.9 (carbons
of Ph), 143.2 (C-3), 152.3 (C-8a), 160.1 (CO), 178.0 (C-7). MS (EI,
70 eV), m/z (%): 269 (Mþ, 23), 254 (33), 241 (24), 119 (18), 105 (13),
93 (19), 91 (18), 77 (100), 67 (17), 65 (19), 53 (17), 51 (38), 43 (19), 41
(30), 39 (28). Anal. Calcd for C14H15N5O: C, 62.44; H, 5.61; N, 26.01.
Found: C, 62.21; H, 5.52; N, 25.71.
1H NMR (300 MHz)
(m, 8H, NH2, and Ar), 7.49 (m, 2H, Ar), 8.09 (m, 2H, Ar). 13C NMR
(125 MHz) : 23.0 (CH3), 29.9 (CH2), 109.7 (C-6), 118.8, 125.2, 125.8,
d: 2.27 (s, 3H, CH3), 3.81 (s, 2H, CH2), 7.15–7.27
d
128.0, 128.3, 129.0, 137.3, 140.4 (carbons of phenyls), 144.4, 146.1
(carbons of triazole), 159.2 (CO), 164.0 (C-7). MS (EI, 70 eV), m/z (%):
331 (Mþ, 69), 254 (36), 226 (23), 128 (26), 115 (13), 105 (14), 103
(17), 91 (91), 77 (100), 67 (19), 65 (26), 51 (55), 42 (12), 39 (23).
Anal. Calcd for C19H17N5O: C, 68.87; H, 5.17; N, 21.13. Found: C,
69.09; H, 5.29; N, 20.87.
4.6.8. 3-Amino-2-benzyl-7-methyl-5-oxo-5H-[1,2,4]triazolo[4,3-a]-
pyrimidin-2-ium-8-ide (10h). Yield 81 mg (10%, Method A), 424 mg
(83%, Method B) of colorless plates, mp 191–193 ꢀC; Rf¼0.10. IR
(ATR)
n
(cmꢁ1): 3283, 3081, 1657, 1583, 1538, 1516. UV, lmax, nm
4.6.13. 3-Amino-7-methyl-6-(4-methylbenzyl)-1-phenyl-[1,2,4]tri-
(3$10ꢁ3): 225 (17.0), 264 (4.7), and 330 (10.6). 1H NMR (500 MHz)
2.08 (s, 3H, CH3), 5.15 (s, 1H, CH), 5.23 (s, 2H, CH2), 7.31–7.39 (m, 5H,
Ph), 8.40 (s, 2H, NH2). 13C NMR (125 MHz)
: 25.2 (CH3), 49.8 (CH2),
d:
azolo[4,3-a]pyrimidin-5(1H)-one (11d). Yield 226 mg (23%) of yel-
lowish needles, mp 221–222 ꢀC; Rf¼0.89. IR (ATR)
n
(cmꢁ1): 3432,
d
3309,1667,1577,1503,1479. UV, lmax, nm (3$10ꢁ3): 220 sh (18.4), 276
90.6 (C-6), 128.15, 128.30, 128.97, 135.3 (carbons of Ph), 143.7 (C-3),
152.4 (C-8a), 159.5 (CO), 169.4 (C-7). MS (EI, 70 eV), m/z (%): 255
(Mþ, 0.8), 91 (100), 68 (19), 65 (45), 51 (15), 39 (67). Anal. Calcd for
C13H13N5O: C, 61.17; H, 5.13; N, 27.43. Found: C, 61.33; H, 5.21; N,
27.09.
(7.5), and 348 (18.1). 1H NMR (300 MHz)
d: 2.23 (s, 3H, CH3), 2.52 (s,
3H, CH3), 3.75 (s, 2H, CH2), 7.03–7.12 (m, 4H, Ar), 7.19 (s, 2H, NH2),
7.24 (m,1H, Ph), 7.49 (m, 2H, Ph), 8.09 (m, 2H, Ph).13C NMR (75 MHz)
d: 20.5 (CH3), 22.8 (CH3), 29.4 (CH2), 109.8 (C-6), 118.7, 125.0, 127.8,
128.7, 128.9, 134.6, 137.11, 137.14 (carbons of benzene rings), 144.3,
146.0 (carbons of triazole),159.0 (CO),163.8 (C-7). MS (EI, 70 eV), m/z
(%): 345 (Mþ, 80), 330 (20), 275 (10), 254 (39), 241 (19), 226 (34), 200
(12),143 (20),128 (38),115 (31),105 (61), 91 (66), 77(100), 67(28), 51
4.6.9. 3-Amino-2-benzyl-5-oxo-7-propyl-5H-[1,2,4]triazolo[4,3-a]-
pyrimidin-2-ium-8-ide (10i). Yield 113 mg (14%, Method A), 448 mg

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3311
(61), 43 (18), 39 (36). Anal. Calcd for C20H19N5O: C, 69.55; H, 5.54; N,
20.28. Found: C, 69.39; H, 5.69; N, 20.36.
(100), 65 (16), 39 (14). Anal. Calcd for C15H17N5O: C, 63.59; H, 6.05;
N, 24.72. Found: C, 63.59; H, 6.10; N, 24.59.
4.6.14. 3-Amino-6-chloro-7-methyl-1-phenyl-[1,2,4]triazolo[4,3-a]-
4.6.19. 3-Amino-1-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]-
pyrimidin-5(1H)-one (11e). Yield 102 mg (13%) of yellowish nee-
pyrimidin-5(1H)-one (11j). Yield 118 mg (14%) of colorless needles,
dles, mp 164–165 ꢀC; Rf¼0.82. IR (ATR)
n
(cmꢁ1): 3426, 3412, 3284,
mp 176–177 ꢀC; Rf¼0.85. IR (ATR)
n
(cmꢁ1): 3449, 3347, 3068, 1709,
1705, 1685, 1674, 1653, 1580, 1502, 1481. UV, lmax, nm (3$10ꢁ3): 231
1654, 1595, 1577, 1513. UV, lmax, nm (3$10ꢁ3): 233 (10.6), 272 (4.9),
(10.8), 274 (5.9), and 347 (14.6). 1H NMR (300 MHz)
CH3), 7.18 (s, 2H, NH2), 7.28 (m, 1H, Ph), 7.51 (m, 2H, Ph), 8.05 (m,
2H, Ph). 13C NMR (125 MHz)
: 23.3 (CH3), 105.2 (C-6), 119.0, 125.6,
d
: 2.41 (s, 3H,
and 353 (10.8). 1H NMR (300 MHz)
NH2), 7.33 (m, 1H, Ph), 7.55 (m, 2H, Ph), 8.01 (m, 2H, Ph). 13C NMR
(125 MHz) : 98.0 (C-6), 119.6 (carbon of Ph), 121.9 (CF3), 126.2,
d: 6.28 (s, 1H, CH), 7.24 (s, 2H,
d
d
129.0, 136.7 (carbons of Ph), 143.8, 145.7 (carbons of triazole), 154.3
(CO), 162.6 (C-7). MS (EI, 70 eV), m/z (%): 275 (Mþ, 59), 170 (14), 128
(11), 103 (10), 91 (28), 77 (100), 73 (12), 68 (25), 64 (24), 51 (74), 42
(19), 39 (49). Anal. Calcd for C12H10ClN5O: C, 52.28; H, 3.66; N,
25.40. Found: C, 52.01; H, 3.61; N, 25.65.
129.2, 136.4 (carbons of Ph), 146.5, 152.6, 152.9, 158.8. MS (EI,
70 eV), m/z (%): 295 (Mþ, 49), 91 (51), 77 (93), 69 (38), 64 (35), 51
(100), 42 (16), 39 (28). Anal. Calcd for C12H8F3N5O: C, 48.82; H, 2.73;
N, 23.72. Found: C, 49.12; H, 2.91; N, 24.04.
4.7. HPLC monitoring of the thermal decomposition
of compound (8a)
4.6.15. 3-Amino-1-phenyl-7-propyl-[1,2,4]triazolo[4,3-a]pyrimidin-
5(1H)-one (11f). Yield 161 mg (21%) of colorless needles, mp 118–
120 ꢀC; Rf¼0.76. IR (ATR)
n
(cmꢁ1): 3421, 3262, 3196, 3143, 2960,
1711, 1687, 1583, 1496. UV, lmax, nm (3$10ꢁ3): 227 (12.4), 270 (4.8),
An open glass vial containing the compound 8a (200 mg,
0.696 mmol) was heated to 115–120 ꢀC for complete melting of 8a
and then immediately placed in a thermostat, which maintained
temperature at 100–101 ꢀC. After heating during the necessary time
(Table 2) the content of the vial was dissolved in DMF (10 mL).
Then, 1 mL of the resulted solution was diluted with acetonitrile to
20 mL and analyzed by HPLC (Table 2).
and 337 (14.8). 1H NMR (300 MHz)
d
: 0.91 (t, J¼7.4 Hz, 3H, CH3),1.67
(m, 2H, CH2), 2.45 (m, 2H, CH2), 5.72 (s, 1H, CH), 7.13 (s, 2H, NH2),
7.24 (m, 1H, Ph), 7.49 (m, 2H, Ph), 8.08 (m, 2H, Ph). 13C NMR
(125 MHz) d: 13.5 (CH3), 21.0 (CH2), 39.2 (CH2), 98.7 (C-6), 118.9,
125.2, 128.9, 137.0 (carbons of Ph), 146.16, 146.22 (carbons of tri-
azole), 158.9 (CO), 170.7 (C-7). MS (EI, 70 eV), m/z (%): 269 (Mþ, 77),
254 (31), 241 (100), 137 (13), 91 (45), 77 (79), 67 (33), 51 (48), 39
(62). Anal. Calcd for C14H15N5O: C, 62.44; H, 5.61; N, 26.01. Found: C,
62.18; H, 5.50; N, 26.18.
4.8. Decomposition of compound (11a)
A magnetically stirred mixture of compound 11a (200 mg,
0.83 mmol) and acetic acid (0.2 mL) in a glass ampoule placed in
the oil bath was heated at 150–160 ꢀC for 10 h. After cooling to
room temperature the ampoule was unsealed (caution: excessive
pressure!) and the reaction mixture was diluted with DMF to
a volume of 5 mL. According to HPLC analysis, the conversion of
compound 11a was amounted to 12% and small peaks of un-
identified compounds were observed. The DMF solution (4 mL) was
evaporated to dryness at reduced pressure and the residue was
extracted with hot chloroform (5 mL). The extract was subjected to
a column chromatography (Al2O3, CHCl3) to give 150 mg (75%) of
starting compound 11a. Its melting point and 1H NMR spectrum
were identical with those prepared by method A.
4.6.16. 3-Amino-7-isopropyl-1-phenyl-[1,2,4]triazolo[4,3-a]pyr-
imidin-5(1H)-one (11g). Yield 292 mg (38%) of colorless plates,
mp 143–144 ꢀC; Rf¼0.75. IR (ATR)
n
(cmꢁ1): 3419, 3363, 3294,
2962, 1698, 1650, 1578, 1497. UV, lmax, nm (3$10ꢁ3): 226 (10.1), 270
(4.1), and 336 (11.8). 1H NMR (300 MHz)
2CH3), 2.77 (m, 1H, CH), 5.75 (s, 1H, CH), 7.14 (s, 2H, NH2), 7.25 (m,
1H, Ph), 7.51 (m, 2H, Ph), 8.11 (m, 2H, Ph). 13C NMR (125 MHz)
d
: 1.20 (d, J¼6.9 Hz, 6H,
d
:
21.3 (2CH3), 35.4 (CH of i-Pr), 96.7 (C-6), 118.7, 125.1, 128.9, 137.1
(carbons of Ph), 146.12, 146.27 (carbons of triazole), 159.1 (CO),
175.7 (C-7). MS (EI, 70 eV), m/z (%): 269 (Mþ, 79), 254 (38), 241
(46), 91 (44), 77 (100), 67 (41), 41 (45), 39 (43). Anal. Calcd for
C14H15N5O: C, 62.44; H, 5.61; N, 26.01. Found: C, 62.22; H, 5.74; N,
25.78.
4.6.17. 3-Amino-1-benzyl-7-methyl-[1,2,4]triazolo[4,3-a]pyrimidin-
4.9. (Z)-Ethyl 3-(7-methyl-5-oxo-1-phenyl-1,5-dihydro-
[1,2,4]triazolo[4,3-a]pyrimidin-3-ylamino)but-2-enoate (14)
5(1H)-one (11h). Yield 146 mg (20%) of colorless plates, mp 188–
188.5 ꢀC; Rf¼0.50. IR (ATR)
n
(cmꢁ1): 3391, 3293, 1673, 1648, 1579,
1506. UV, lmax, nm (3$10ꢁ3): 229 (12.6), 257 (4.8), and 325 (11.1). 1H
Compound 4a (1.0 g, 2.50 mmol) was added to a solution of
sodium (0.173 g, 7.5 mmol) in absolute ethanol (30 mL) and the
resulted mixture was heated to reflux for 30 min, then neutralized
by acetic acid. The solution was evaporated to a volume of about
10 mL and diluted with water (15 mL). The precipitate formed was
isolated by filtration and recrystallized from acetonitrile to give
0.73 g of white needles (yield 82%), mp 177–177.5 ꢀC, lit.6b mp 172–
NMR (300 MHz)
d: 2.19 (s, 3H, CH3), 5.11 (s, 2H, CH2), 5.56 (s, 1H,
CH), 6.86 (s, 2H, NH2), 7.29–7.34 (m, 5H, Ph). 13C NMR (125 MHz)
d:
24.2 (CH3), 48.8 (CH2), 96.8 (C-6), 127.8 (3C of Ph), 128.6 (2C of Ph),
135.9 (1C of Ph), 146.0 (C-3), 147.7 (C-8a), 158.8 (CO),167.8 (C-7). MS
(EI, 70 eV), m/z (%): 255 (Mþ, 19), 94 (14), 91 (100), 65 (10), 39 (17).
Anal. Calcd for C13H13N5O: C, 61.17; H, 5.13; N, 27.43. Found: C,
61.34; H, 5.24; N, 27.09.
173 ꢀC. IR (ATR)
NMR (500 MHz)
n
(cmꢁ1): 3070, 2973, 1686, 1616, 1530, 1500. 1H
d: 1.22 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.28 (s, 3H, CH3),
4.6.18. 3-Amino-1-benzyl-7-propyl-[1,2,4]triazolo[4,3-a]pyrimidin-
5(1H)-one (11i). Yield 226 mg (28%) of yellowish plates, mp 181–
2.46 (s, 3H, C4H3), 4.11 (q, J¼7.1 Hz, 2H, OCH2CH3), 5.06 (s, 1H, H-2),
5.81 (s, 1H, H-60), 7.30 (m, 1H, Ph), 7.52 (m, 2H, Ph), 8.08 (m, 2H, Ph),
182 ꢀC; Rf¼0.56. IR (ATR)
n
(cmꢁ1): 3355, 3267, 3224, 2961, 1662,
12.20 (s, 1H, NH). 13C NMR (125 MHz)
d: 14.3 (OCH2CH3), 22.2 (CH3),
1596, 1499. UV, lmax, nm (3$10ꢁ3): 230 (12.0), 258 (4.2), and 327
24.3 (CH3), 59.1 (OCH2CH3), 94.5 (C-2), 99.7 (C-60), 119.4, 126.1,
129.2, 136.8 (carbons of Ph), 141.2, 145.9 (carbons of triazole), 152þ.6
(C-3),158.2 (C-50), 167.4 (COþC-70). MS (EI, 70 eV), m/z (%): 353 (M ,
51), 307 (77), 279 (19), 266 (19), 240 (20), 200 (15), 185 (11), 134
(18), 118 (10), 109 (25), 91 (29), 77 (100), 67 (37), 51 (14), 39 (27).
Anal. Calcd for C18H19N5O3: C, 61.18; H, 5.42; N, 19.82. Found: C,
59.87; H, 5.49; N, 20.05.
(9.2). 1H NMR (600 MHz)
2H, CH2), 2.41 (t, J¼7.4 Hz, 2H, CH2), 5.12 (s, 2H, CH2), 5.54 (s, 1H,
CH), 6.84 (s, 2H, NH2), 7.27–7.34 (m, 5H, Ph). 13C NMR (150 MHz)
d
: 0.89 (t, J¼7.4 Hz, 3H, CH3), 1.60–1.66 (m,
d:
13.5 (CH3), 21.1 (CH2), 39.3 (CH2), 48.8 (CH2), 96.3 (C-6), 127.75,
127.78, 128.5, 135.9 (carbons of Ph), 145.9 (C-3), 147.8 (C-8a), 158.9
(CO), 171.2 (C-7). MS (EI, 70 eV), m/z (%): 283 (Mþ, 31), 255 (46), 91

3312
V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
4.10. X-ray diffraction data
associated with this article can be found in online version at
doi:10.1016/j.tet.2010.03.009.
Single crystal X-ray diffraction experiments for compounds 10a
and 11d (both crystallized from acetonitrile) were carried out with
a Bruker APEX II CCD area detector, using graphite monochromated
References and notes
Mo Ka radiation (l¼0.71073 Å,
u u and 10 s
-scans with a 0.3ꢀ step in
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881–889.
per frame exposure) at 100 K. The structures were solved by direct
method and refined by the full-matrix least-squares against F2 in
anisotropic (for no-hydrogen atoms) approximation. All hydrogen
H(N) atoms were located from the difference Fourier syntheses, the
H(C) atoms were placed in geometrically calculated positions. All
hydrogen H(N) atom positions were refined in isotropic approxi-
mation in riding model with the Uiso(H) parameters equal to 1.2
Ueq(Ni), where U(Ni) are, respectively, the equivalent thermal pa-
rameters of the atoms to which corresponding H atoms are bonded.
Table 5
´
2. (a) Fischer, G. Adv. Heterocycl. Chem. 2007, 95, 143–219; (b) Reiter, J.; Pongo, L.;
Crystallographic data and refinement parameters for 10a and 11d
Dvortsa´k, P. Tetrahedron 1987, 43, 2497–2504; (c) Esses-Reiter, K.; Reiter, J.
´
J. Heterocycl. Chem. 1987, 24, 1503–1508; (d) Reiter, J.; Rivo, E. J. Heterocycl. Chem.
10a
11d
1988, 25, 1497–1502; (e) Reiter, J.; Pongo´, L.; Somorai, T.; Pallagi, I. Monatsh.
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1–10; (g) Suiko, M.; Hayashida, S.; Nakatsu, S. Agric. Biol. Chem. 1982, 46, 2691–
Molecular formula
Formula weight
Color, shape
Crystal size [mm]
Crystal system
Space group
a [Å]
C12H11N5O
241.26
Colorless, plate
0.21ꢂ0.20ꢂ0.14
Orthorhombic
Pbca
14.0320(6)
7.5793(3)
20.6559(9)
90
90
90
2196.8(2)
8
1008
C20H19N5O
345.40
Colorless, needle
0.42ꢂ0.30ꢂ0.25
Rhombohedral
R-3
32.6055(15)
32.6055(15)
8.3815(7)
90
90
120
7716.7(8)
18
3276
b [Å]
c [Å]
a
b
g
[ꢀ]
[ꢀ]
[ꢀ]
V(Å3)
´
´
2695; (h) Magan, R.; Marin, C.; Salas, J. M.; Barrera-Perez, M.; Rosales, M. J.;
Sa´nchez-Moreno, M. Mem. Inst. Oswaldo Cruz 2004, 99, 651–656; (i) qakomska,
I. Inorg. Chim. Acta 2009, 362, 669–681.
Z
F(000)
rcalcd [g cmꢁ3
]
1.459
1.00
1.97O29.99
97.7
26,796
1.338
0.87
2.16O29.98
98.2
18,308
5. (a) Zhai, X.; Zhao, Y.-F.; Liu, Y.-J.; Zhang, Y.; Hun, F.-Q.; Liu, J.; Gong, P. Chem.
Pharm. Bull. 2008, 56, 941–945; (b) Phillips, M. A.; Gujjar, R.; Malmquist, N. A.;
White, J.; El Mazouni, F.; Baldwin, J.; Rathod, P. K. J. Med. Chem. 2008, 51, 3649–
3653; (c) Cavallaro, C. L.; Harikrishnan, L. S.; Chi, F.; Dodd, D.; Purandare, A.
J. Comb. Chem. 2008, 10, 28–30.
Linear absorption,
range [ꢀ]
m
[cmꢁ1
]
q
Completeness of dataset [%]
Diffrn reflns
6. (a) Papini, P. Gazz. Chim. Ital. 1950, 80, 100–106; (b) Papini, P.; Checchi, S. Gazz.
Chim. Ital. 1950, 80, 850–854; (c) Papini, P. Gazz. Chim. Ital. 1952, 82, 735–745.
7. Bavley, A. U.S. Patent 2,406,654, 1946; Chem. Abstr. 1947, 41, 42h.
8. (a) Shaban, M. A. E.; Morgaan, A. E. A. Adv. Heterocycl. Chem. 1999, 73, 131–176;
(b) Golubushina, G. M.; Poshtaruk, G. N.; Chuiguk, V. A. Chem. Heterocycl.
Compd. (Engl. Transl.) 1974, 10, 491–494; (c) Bratulescu, G. Synthesis 2005,
2833–2834.
9. (a) Chernyshev, V. M.; Rakitov, V. A.; Taranushich, V. A.; Blinov, V. V. Chem.
Heterocycl. Compd. (Engl. Transl.) 2005, 41, 1139–1146; (b) Chernyshev, V. M.;
Kosov, A. E.; Gladkov, E. S.; Shishkina, S. V.; Taranushich, V. A.; Desenko, S. M.;
Shishkin, O. V. Russ. Chem. Bull. (Engl. Transl.) 2006, 55, 338–344; (c) Cherny-
shev, V. M.; Rakitov, V. A.; Astakhov, A. V.; Sokolov, A. N.; Zemlyakov, N. D.;
Taranushich, V. A. Russ. J. Appl. Chem. (Engl. Transl.) 2006, 79, 624–630; (d)
Chernyshev, V. M.; Rakitov, V. A.; Taranushich, V. A.; Starikova, Z. A. Chem.
Heterocycl. Compd. (Engl. Transl.) 2007, 43, 776–780.
Unique reflns
3,189 [R(int)¼0.0487]
4,923 [R(int)¼0.0613]
Reflns with [I>2
ls. parameters
Final R(Fhkl): R1
wR2
s(I)]
2,441
2,985
164
0.0403
0.1086
0.965
239
0.0480
0.1046
1.116
Goodness of fit
rmax
/
rmin (eÅꢁ3
)
0.402/ꢁ0.238
0.207/ꢁ0.246
Crystallographic data and refinement parameters for com-
pounds are presented in Table 5. Atomic coordinates, bond lengths,
bond angles, and thermal parameters have been deposited at the
Cambridge Crystallographic Data Centre (CCDC), deposition num-
bers 753133 (compound 10a), and 753134 (compound 11d). These
data can be obtained free of charge via www.ccdc.cam.uk/conts/
retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2
1EZ; fax: þ44 1223 335 033; or deposit@ccdc.cam.ac.uk). Any re-
quest to the CCDC for data should quote the full literature citation
and CCDC reference numbers.
10. (a) Minkin, V. I.; Garnovskii, A. D.; Elguero, J.; Katritzky, A. R.; Denisko, O. V. Adv.
´
heterocycl. Chem. 2000, 76, 157–323; (b) Reiter, J.; Pongo, L.; Lukovits, I. Mon-
atsh. Chem. 1988, 119, 341–348.
´
´
11. Reiter, J.; Pongo, L.; Dvortsak, P. J. Heterocycl. Chem. 1987, 24, 1149–1154.
12. (a) Reiter, J.; Somorai, T.; Jerkovich, G.; Dvortsa´k, P. J. Heterocycl. Chem. 1982, 19,
1157–1164; (b) Reiter, J.; Somorai, T.; Dvortsa´k, P.; Bujta´s, G. J. Heterocycl. Chem.
´
´
1985, 22, 385–394; (c) Reiter, J.; Pongo, L.; Somorai, T.; Dvortsak, P. J. Heterocycl.
Chem. 1986, 23, 401–408.
´
´
13. (a) Chiara, J. L.; Gomez-Sanchez,
A. In The Chemistry of Enamines; Rappoport, Z.,
Ed.; Wiley: Chichester, 1994; pp 279–404; (b) Vainiotalo, P.; Savolainen, P.-L.;
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Acknowledgements
Authors thank the Federal Agency for Education of Russia for the
financial support of this work through the Federal Target Program
‘Research and Educational Personnel of Innovative Russia at 2009–
2013 Years’, State contract P302, project NK-109P/2.
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Supplementary data
Copies of IR, NOESY, HSQC, HMBC, proton, and carbon spectra of
some synthesized compounds are provided. Supplementary data

V.M. Chernyshev et al. / Tetrahedron 66 (2010) 3301–3313
3313
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