Synthesis of acyclic nucleosides based on 1,2,4-triazolo[3,2-c][1,2,4] triazin-7-ones

Article abstract of DOI:10.1007/s11172-008-0346-7

A new class of acyclic nucleosides based on 6-phenyl-1,2,4-triazolo[3,2-c] [1,2,4]triazin-7-ones was synthesized and structurally characterized for the first time.

Full text of DOI:10.1007/s11172-008-0346-7

Russian Chemical Bulletin, International Edition, Vol. 57, No. 11, pp. 2423—2430, November, 2008
2423
Synthesis of acyclic nucleosides based on
1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones*
T. S. Shestakova,a L. S. Luk´yanova,a T. A. Tseitler,a S. L. Deev,b E. N. Ulomskii,a V. L. Rusinov,a
M. I. Kodess,b and O. N. Chupakhina,b
aUral State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 0458. Eꢀmail: deevsl@yandex.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: chupakhin@ios.uran.ru
A new class of acyclic nucleosides based on 6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ
7ꢀones was synthesized and structurally characterized for the first time.
Key words: acyclic nucleosides, antiviral drugs, 1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones,
alkylation, deacylation.
Anomalous nucleosides belong to a group of comꢀ
pounds most widely used as antiviral medications. Their
activity is manifested in different steps of a pathogenic
process, from infection of normal cells to persistence and
reproduction of virions. The structures of antiviral anomaꢀ
lous nucleosides should reproduce or mimic the most
substantial structural elements of natural nucleosides that
provide the resistance of organisms to viral infections.
The design of such nucleosides is generally based on
the modification of one of the constituents of natural
compounds, viz., the furanose ring or a nucleic base.1 For
example, acyclic nucleosides 9ꢀ(2ꢀhydroxyethoxymethyl)ꢀ
guanine (Acyclovir)2 or 9ꢀ[4ꢀhydroxyꢀ3ꢀ(hydroxymethyl)ꢀ
butyl]guanine (Penciclovir)3 are considered as structural
analogs of guanosine, in which the cyclic ribose residue is
replaced by an aliphatic chain bearing oxygenꢀcontaining
groups. These compounds have found use as antiherpetic
drugs, as well as for the inhibition of cytomegaloviruses.
Ribavirin (1ꢀβꢀDꢀribofuranosylꢀ1,2,4ꢀtriazoleꢀ3ꢀcarboxꢀ
amide), which is a medication used for the treatment of
influenza A and B viruses and hepatitis B and C viruses,1,4
can be cited as an example of the design of antiviral drugs
by modifying a heterocyclic base. The usefulness of the
concept of structural analogies in the search for new antiꢀ
viral medications was demonstrated by the synthesis of
anomalous nucleosides modified at both the heterocyclic
moiety and the carbohydrate residue. Thus tricyclic anaꢀ
logs of Acyclovir (3ꢀ[(2ꢀhydroxyethoxy)methyl]ꢀ9ꢀoxoꢀ
imidazo[1,2ꢀa]purine derivatives) showing significant
antiherpetic activity were synthesized;5,6 Acyclovir and
Ganciclovir analogs containing the substituted pyrimiꢀ
dine moiety are active against HIV7,8 and hepatitis B
viruses.9,10 Various acyclic nucleosides based on 2,3ꢀdiꢀ
hydrofuro[2,3ꢀd]pyrimidinꢀ2ꢀones proved to be efficient
against the Herpes simplex virus and the human immunoꢀ
deficiency virus.11
In the present study, we performed the synthesis of
anomalous nucleosides based on 2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀ
triazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (1a—c) containing
acyclic fragments with the terminal hydroxy group at the
N(4) atom. Hence, we synthesized nucleosides, which
are anomalous in both the aglycone and glycoside
moieties. The choice of 1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ
7ꢀones (1a—c) as bases was determined, on the one hand,
by the structural similarity with purines and, on the other
hand, by the fact that representatives of this class of comꢀ
pounds exhibited antiviral activity.12,13
The fusion of heterocycles 1a—c with an excess of
(2ꢀacetoxyethoxy)methyl acetate (2) at 150 °C in the
presence of ZnCl2 regioselectively affords 4ꢀ(2ꢀacetoxyꢀ
ethoxy)methylꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]ꢀ
triazinꢀ7ꢀones 3a—c. The deacetylation of compounds
3a—c gives derivatives 4a—c containing the Nꢀ(2ꢀhyꢀ
droxyethoxy)methyl fragment present in the antiviral
medication Acyclovir. The yields of compounds 4a—c
were 30—46% (Scheme 1).
* Dedicated to Professor A. F. Pozharskii on the occasion of his
70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2374—2380, November, 2008.
1066ꢀ5285/08/5711ꢀ2423 © 2008 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Shestakova et al.
Scheme 1
1, 3, 4: R = H (a), Me (b), SMe (c)
We used the ability of 1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]ꢀ
triazinꢀ7ꢀones (1a—c) to react with iodoꢀ and bromoꢀ
alkanes under basic conditions14,15 to synthesize
N(4)ꢀhydroxyalkyl derivatives of nucleosides. We alkyꢀ
lated heterocyclic compounds 1a—c with 4ꢀbromobutyl
acetate (5) and 4ꢀbromobutꢀ2ꢀenyl acetate (6) in DMF in
the presence of sodium carbonate (Scheme 2).
It is known that acyclic nucleosides synthesized with
the use of compound 5 are structural analogs of Acyclovir.16
Purine derivatives with the 4ꢀhydroxybutenyl substituent
show significant antiherpetic activity in cell cultures.17
Acyclic nucleosides based on adenine and 3ꢀdeazaadenine
containing the (Z)ꢀ4ꢀhydroxybutenyl group in the alkyl
moiety are analogs of Neplanocin A and were described
as potential inhibitors of Sꢀadenosylhomocysteine hydroꢀ
lase.18,19
The deacylation of compounds 7a—c with sodium
methoxide afforded nucleosides 9a—c in 62—74% yields.
Hydroxy derivatives 10a—c were prepared from comꢀ
pounds 8a—c by acidꢀcatalyzed methanolysis.
The alkylation of heterocyclic compounds 1a—c with
chloroethyl acetate (11) was carried out in the presence
of cesium carbonate in DMF; compounds 12a—c were
obtained in 29—38% yields (Scheme 3). In the presence of
potassium or sodium carbonate, no alkylation of heterocyclic
compounds 1a—c with chloroethyl acetate 11 took place.
It should be noted that this is the first example of
alkylation of 1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones
with chloro derivatives.
The treatment of acyl derivatives 12a—c with sodium
methoxide afforded Nꢀhydroxyethyltriazolotriazines
13a—c.
Scheme 2
or
1, 7—10: R = H (a), Me (b), SMe (c)
5, 7: R´ = C(1´)H2—C(2´)H2—C(3´)H2—C(4´)H2—OAc
6, 8: R´ = C(1´)H2—C(2´)H=C(3´)H—C(4´)H2—OAc
9: R″ = CH2—CH2—CH2—CH2—OH
10: R″ = CH2—CH=CH—CH2—OH
Scheme 3
1, 12, 13: R = H (a), Me (b), SMe (c)

Synthesis of acyclic nucleosides
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008 2425
In the IR spectra of compounds 3a—c, 7a—c, 8a—c,
and 12a—c, two strong absorption bands at 1688—1745
cm–1 are assigned to stretching vibrations of the carbonyl
group of the heterocycle and the acetyl group. In the
spectra of compounds 4a—c, 9a—c, 10a—c, and 13a—c,
the presence of the only band of the carbonyl group at
1680—1715 cm–1 and the appearance of the OH absorption
band at 3320—3530 cm–1 confirm the removal of the
Oꢀacetyl group.
The 1H NMR spectra of compounds 3a—c, 4a—c,
7a—c, 8a—c, 9a—c, 10a—c, 12a—c, and 13a—c show
signals for the corresponding alkyl and heterocyclic moiꢀ
eties. The appearance of a signal for the hydroxy group in
the 1H NMR spectra of compounds 4a—c, 9a—c, 10a—c,
and 13a—c, which was assigned based on NMR experiꢀ
ments following deuterium exchange with CF3COOD,
also confirmed the removal of the acetyl group. The
coupling constant (11 Hz) between the protons of the
—CH=CH— fragment corresponds to the cis confiꢀ
guration20 of the butenyl substituent in compounds 8a—c
and 10a—c.
C(8)
C(7)
C(9)
C(10)
C(6)
C(5)
C(2)
N(4)
N(3)
O(1)
N(5)
C(3)
C(1)
N(2)
C(12)
C(14)
C(13)
N(1)
C(4)
O(2)
C(15)
C(11)
Fig. 1. Molecular structure of compound 9b.
Table 1. Selected bond lengths (d) and bond angles (ω) in molꢀ
ecule 9b
The determination of the positions of the Nꢀalkyl
substituents and the assignment of the signals in the H
1
and 13C NMR spectra of nucleosides were performed by
2D NMR correlation experiments (2D COSY, HSQC,
and HMBC). The positions of the alkyl moieties in comꢀ
pounds 7a,c and 12a were determined by the analysis
of the fine structure of the signal for the bridgehead
atom C(3a) in the coupled 13C—1H NMR spectra. Thus
the 13C NMR spectra of compounds 7a and 12a contain
signals for C(3a) at δ 151.13 and 151.32, respectively, as
doublets of triplets. The presence of the methylthio group
in the 1,2,4ꢀtriazole ring of compound 7c results in a
reduction in the multiplicity of the signal for the atom
C(3a) at δ 151.71 to a triplet. The presence of the triplet
components in the signals for the atoms C(3a) in the
coupled 13C—1H NMR spectra of compounds 7a,c and
12a confirms the introduction of the alkyl moieties into
the triazine ring.
In all cases, the alkylation of 6ꢀphenylꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (1a—c) proceeds at the N(4)
atom of the triazine ring. This conclusion is confirmed
by the Xꢀray diffraction data for 4ꢀ(4ꢀhydroxybutyl)ꢀ
2ꢀmethylꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ
7ꢀone (9b) and 4ꢀ(4ꢀhydroxybutꢀ2ꢀenyl)ꢀ6ꢀphenylꢀ1,2,4ꢀ
triazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (10a) (Figs 1 and 2,
respectively; Tables 1 and 2). In the crystals of comꢀ
pounds 9b and 10a, the triazole and triazine rings form a
virtually planar bicyclic system, which is not conjugated
with the phenyl substituent. In heterocyclic compounds
9b and 10a, the dihedral angles between the planes of the
triazine and benzene rings are 37.4° and 31.9°, respecꢀ
tively. The geometric parameters of triazolo[3,2ꢀc][1,2,4]ꢀ
triazines 9b and 10a have standard values.15,21 In addiꢀ
tion, the Xꢀray diffraction data for compound 10a unamꢀ
Bond
d/Å
Angle
ω/deg
120.2(1)
108.7(1)
125.0(1)
126.2(11)
120.8(1)
O(1)—C(3)
N(4)—C(2)
N(4)—N(3)
N(5)—C(1)
N(5)—N(1)
N(5)—C(3)
N(3)—C(1)
N(3)—C(12)
N(2)—C(1)
N(2)—C(4)
C(2)—C(5)
C(2)—C(3)
O(2)—C(15)
C(5)—C(6)
C(5)—C(10)
1.207(2)
1.305(2)
1.358(2)
1.358(2)
1.380(2)
1.397(2)
1.352(2)
1.468(2)
1.312(2)
1.377(2)
1.477(2)
1.487(2)
1.418(2)
1.389(2)
1.395(2)
C(2)—N(4)—N(3)
C(1)—N(5)—N(1)
C(1)—N(5)—C(3)
N(1)—N(5)—C(3)
C(1)—N(3)—N(4)
C(1)—N(3)—C(12) 122.0(1)
N(4)—N(3)—C(12) 117.0(1)
C(1)—N(2)—C(4)
N(2)—C(1)—N(3)
N(2)—C(1)—N(5)
N(3)—C(1)—N(5)
N(4)—C(2)—C(5)
N(4)—C(2)—C(3)
C(5)—C(2)—C(3)
O(1)—C(3)—N(5)
O(1)—C(3)—C(2)
N(5)—C(3)—C(2)
C(6)—C(5)—C(2)
C(10)—C(5)—(C2)
101.9(1)
129.0(1)
111.6(1)
119.4(1)
115.6(1)
124.2(1)
120.3(1)
122.7(1)
127.0(1)
110.3(1)
121.6(1)
119.9(1)
C(12)—C(13) 1.510(2)
N(1)—C(4) 1.321(2)
C(14)—C(15) 1.507(2)
C(14)—C(13) 1.522(2)
N(3)—C(12)—C(13) 112.4(1)
C(4)—N(1)—N(5) 101.9(1)
C(15)—C(14)—C(13) 111.5(1)
C(12)—C(13)—C(14) 112.5(1)
N(1)—C(4)—N(2)
115.9(1)
N(1)—C(4)—C(11) 123.1(1)
N(2)—C(4)—C(11) 121.0(1)
O(2)—C(15)—C(14) 113.8(2)
biguously confirm the cis configuration of the Nꢀalkyl
moiety.
To summarize, we synthesized a new class of acyclic
nucleosides based on 2ꢀsubstituted 6ꢀphenylꢀ1,2,4ꢀtriaꢀ
zolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones.

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Shestakova et al.
Column chromatography was performed on silica gel
Alfa Aesar (Avocado Research Chemical Ltd, Silica gel 60,
0.035—0.070 vv (220—440 mesh)).
C(9)
O(1)
C(10)
C(5)
C(8)
C(7)
Xꢀray diffraction study of compounds 9b and 10a was carried
out on an automated Xcalibur 3 diffractometer equipped with a
CCD detector (ω/2θꢀscanning technique, MoꢀKα radiation,
graphite monochromator) according to a standard procedure.
Both structures were solved by direct methods and refined
by the leastꢀsquares method using the SHELXSꢀ9722 and
SHELXLꢀ9723 program packages with anisotropic displacement
parameters (isotropic displacement parameters for H atoms).
Absorption corrections were not applied because of the low
absorption coefficients.
N(4)
C(2)
N(3)
C(4)
C(3)
C(6)
C(1)
N(2)
N(1)
N(5)
O(2)
C(11)
C(13)
C(14)
Fig. 2. Molecular structure of compound 10a.
The geometric characteristics of compounds 9b and 10a are
listed in Tables 1 and 2, respectively. The Xꢀray data collection
and refinement statistics are given in Table 3.
6ꢀPhenylꢀ2ꢀRꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀones
(1a—c) were synthesized according to a procedure described
earlier.24
C(12)
(2ꢀAcetoxyethoxy)methyl acetate (2) was synthesized accordꢀ
ing to a procedure described earlier.25
4ꢀ(2ꢀAcetoxyethoxymethyl)ꢀ6ꢀphenylꢀ2ꢀRꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (3a—c). Catalytic amounts of
anhydrous ZnCl2 were added to mixtures of (2ꢀacetoxyethoxy)ꢀ
methyl acetate (2) (1.23 g, 7.04 mmol) and 6ꢀphenylꢀ2ꢀRꢀ1,2,4ꢀ
triazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (1a—c) (2.30 mmol). The
reaction mixtures were kept at 150 °C for 0.5 h and the reaction
products were isolated by silica gel column chromatography
using the ethyl acetate—hexane system (2 : 1) as the eluent.
4ꢀ(2ꢀAcetoxyethoxymethyl)ꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc]ꢀ
Table 2. Selected bond lengths (d) and bond angles (ω) in molꢀ
ecule 10a
Bond
d/Å
Angle
ω/deg
O(1)—C(2)
N(3)—C(1)
N(3)—N(4)
N(3)—C(2)
N(5)—C(1)
N(5)—C(4)
N(2)—C(3)
N(2)—N(1)
N(1)—C(1)
C(11)—C(12)
N(4)—C(4)
C(12)—C(13)
C(13)—C(14)
C(5)—C(6)
C(5)—C(10)
C(10)—C(9)
C(9)—C(8)
C(14)—O(2)
C(6)—C(7)
C(8)—C(7)
1.211(1)
1.363(1)
1.379(1)
1.394(2)
1.315(2)
1.370(2)
1.308(1)
1.342(1)
1.3503(2)
1.490(2)
1.312(2)
1.315(2)
1.493(2)
1.392(2)
1.394(2)
1.389(2)
1.375(2)
1.422(18)
1.378(2)
1.373(2)
C(1)—N(3)—N(4)
C(1)—N(3)—C(2)
N(4)—N(3)—C(2)
C(1)—N(5)—C(4)
C(3)—N(2)—N(1)
N(2)—N(1)—C(1)
109.15(10)
124.91(10)
125.79(9)
101.27(10)
120.67(10)
121.12(9)
[1,2,4]triazinꢀ7ꢀone (3a,
R = H). The yield was 61%,
m.p. 94 °C. 1H NMR (400 MHz), δ: 1.97 (s, 3 H, OAc); 3.91
(m, 2 H, H(3´)); 4.14 (m, 2 H, H(4´)); 5.78 (s, 2 H, H(1´));
7.51—7.55 (m, 3 H, Hm, Hp); 8.00 (m, 2 H, Ho); 8.46 (s, 1 H,
H(2)). 13C NMR (100 MHz), δ: 20.57 (CO—CH3); 62.78
(C(4´)); 67.63 (C(3´)); 82.58 (C(1´)); 128.23 (Cm); 128.65 (Co);
129.84 (Cp); 131.96 (Cipso); 139.82 (C(6)); 149.17 (C(7)); 151.35
(C(3a)); 153.20 (C(2)); 170.25 (CO—CH3). Found (%): C,
54.78; H, 4.51; N, 21.36. C15H15N5O4. Calculated (%): C, 54.71;
H, 4.56; N, 21.27. IR, ν/cm–1: 1740, 1710 (C=O).
N(2)—N(1)—C(11) 117.57(9)
C(1)—N(1)—C(11) 121.30(10)
N(5)—C(1)—N(1)
N(5)—C(1)—N(3)
N(1)—C(1)—N(3)
N(2)—C(3)—C(2)
N(2)—C(3)—C(5)
C(2)—C(3)—C(5)
O(1)—C(2)—N(3)
O(1)—C(2)—C(3)
N(3)—C(2)—C(3)
130.01(11)
111.19(10)
118.80(11)
123.73(11)
116.14(10)
120.11(10)
121.84(11)
127.44(12)
110.68(9)
4ꢀ(2ꢀAcetoxyethoxymethyl)ꢀ2ꢀmethylꢀ6ꢀphenylꢀ1,2,4ꢀtriꢀ
azolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (3b, R = Me). The yield was
1
65%, m.p. 82 °C. H NMR (400 MHz), δ: 1.97 (s, 3 H, OAc);
N(1)—C(11)—C(12) 110.74(10)
C(4)—N(4)—N(3)
N(4)—C(4)—N(5)
2.46 (s, 3 H, C(2)—Me); 3.89 (m, 2 H, H(3´)); 4.13 (m, 2 H,
H(4´)); 5.73 (s, 2 H, H(1´)); 7.50—7.54 (m, 3 H, Hm, Hp); 7.99
(m, 2 H, Ho). 13C NMR (100 MHz), δ: 14.27 (C(2)—Me); 20.57
(CO—CH3); 62.80 (C(4´)); 67.56 (C(3´)); 82.53 (C(1´)); 128.21
(Cm); 128.62 (Co); 129.80 (Cp); 132.04 (Cipso); 139.78 (C(6));
148.68 (C(7)); 151.53 (C(3a)); 162.71 (C(2)); 170.27 (CO—CH3).
Found (%): C, 55.94; H, 4.88; N, 20.64. C16H17N5O4. Calcuꢀ
lated (%): C, 55.98; H, 4.96; N, 20.41. IR, ν/cm–1: 1735, 1715
(C=O).
101.02(10)
117.36(11)
C(13)—C(12)—C(11) 125.57(13)
C(6)—C(5)—C(3)
C(10)—C(5)—C(3)
119.75(11)
121.69(12)
O(2)—C(14)—C(13) 111.33(12)
Experimental
4ꢀ(2ꢀAcetoxyethoxymethyl)ꢀ2ꢀmethylthioꢀ6ꢀphenylꢀ1,2,4ꢀtriꢀ
azolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (3c, R = SMe). The yield was
50%, m.p. 123 °C. H NMR (400 MHz), δ: 1.98 (s, 3 H, OAc);
2.67 (s, 3 H, SMe); 3.89 (m, 2 H, H(3´)); 4.14 (m, 2 H, H(4´)),
5.70 (s, 2 H, H(1´)); 7.51—7.54 (m, 3 H, Hm, Hp); 7.99 (m, 2 H,
Ho). 13C NMR (100 MHz), δ: 13.51 (SMe); 20.57 (CO—CH3);
62.76 (C(4´)); 67.58 (C(3´)); 82.52 (C(1´)); 128.23 (Cm); 128.61
(Co); 129.90 (Cp); 131.93 (Cipso); 140.23 (C(6)); 147.85 (C(7));
151.89 (C(3a)); 165.50 (C(2)); 170.22 (CO—CH3). Found (%):
The 1H NMR spectra were recorded on Bruker WMꢀ250
and Bruker DRXꢀ400 instruments in DMSOꢀd6 with Me4Si as
the internal standard. The 2D NMR correlation experiments
were performed and the 13C NMR spectra (100 MHz) were
recorded on a Bruker DRXꢀ400 spectrometer in DMSOꢀd6.
The IR spectra were measured on a Perkin Elmer Spectrum
One B Fourierꢀtransform infrared spectrometer equipped with a
diffuse reflection attachment.
1

Synthesis of acyclic nucleosides
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008 2427
Table 3. Crystallographic data and the Xꢀray data collection and refinement statistics
Parameter
9b
10a
Molecular formula
Molecular weight
Т/K
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
γ/deg
Ζ
C
15H17N5O2
299.34
295(2)
Triclinic
P–1
C14H13N5O2
283.29
295(2)
Monoclinic
P2(1)/n
7.8396(6)
6.7342(5)
25.3722(12)
90.00
8.6817(10)
9.0154(12)
10.2608(16)
115.948(12)
91.466(14)
99.687(10)
2
90.313(5)
90.00
4
λ/Å
0.71073
0.71073
1339.47(16)
–10 < h < 9
–8 < k < 8
–33 < l < 33
1.405
V/Å3
707.37(17)
–10 < h < 10
–11 < k < 11
–12 < l < 12
1.405
Ranges of hkl indices
dcalc/g cm–3
μ/mm–1
0.098
0.099
θꢀScan range/deg
3.08—26.37
9159/2861
1914
2.72—28.31
13115/3306
2229
Number of measured/independent reflections
Number of reflections with I > 2σ(I)
R1 (I > 2σ(I))
0.0356
0.0400
wR2 (based on all reflections)
Number of refined parameters
GOOF
Residual electron density/Å–3 (min/max)
0.0908
267
1.000
–0.185/0.169
0.1171
211
1.000
–0.186/0.215
C, 51.18; H, 4.46; N, 18.18. C16H17N5O4S. Calculated (%):
C, 51.20; H, 4.53; N, 18.66. IR, ν/cm–1: 1715, 1736 (C=O).
4ꢀ(2ꢀHydroxyethoxymethyl)ꢀ6ꢀphenylꢀ2ꢀRꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (4a—c). The corresponding
4ꢀ(2ꢀacetoxyethoxymethyl)ꢀ6ꢀphenylꢀ2ꢀRꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (3a—c) (3.00 mmol) was added to a
solution of MeONa, which was prepared from sodium metal
(0.07 g, 3.04 mmol), in anhydrous MeOH (20 mL). The reacꢀ
tion mixture was refluxed for 1 h, cooled, and neutralized with
acetic acid. The solvent was evaporated in vacuo. The reaction
product was isolated by silica gel column chromatography using
the ethyl acetate—hexane system (7 : 1) as the eluent.
Compound 4a (R = H). The yield was 46%, m.p. 88 °C. 1H
NMR (250 MHz), δ: 3.52 (q, 2 H, H(4´), J = 5.2 Hz); 3.76 (t, 2
H, H(3´), J = 5.2 Hz); 4.42 (t, 1 H, OH, J = 5.2 Hz); 5.77 (s, 2
H, (H1´)); 7.47—7.50 (m, 3 H, Hm, Hp); 8.04 (m, 2 H, Ho), 8.28
(s, 1 H, H(2)). Found (%): C, 54.35; H, 4.44; N, 24.54.
C13H13N5O3. Calculated (%): C, 54.35; H, 4.53; N, 24.39. IR,
ν/cm–1: 1695 (CO), 3501 (OH).
J = 5.2 Hz); 3.75 (t, 2 H, H(3´), J = 5.2 Hz); 4.41 (t, 1H, OH, J
= 5.2 Hz); 5.70 (s, 2 H, H(1´)); 7.44—7.50 (m, 3 H, Hm, Hp);
8.03 (m, 2 H, Ho). Found (%): C, 50.43; H, 4.34; N, 20.96.
C14H15N5O3S. Calculated (%): C, 50.45; H, 4.51; N, 21.02. IR,
ν/cm–1: 1690 (CO), 3475 (OH).
4ꢀBromobutyl acetate (5)26 and (Z)ꢀ4ꢀbromobutꢀ2ꢀenyl acetate
(6)27 were synthesized according to procedures described earlier.
4ꢀ(4ꢀAcetoxybutyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc]ꢀ
[1,2,4]triazinꢀ7ꢀones (7a—c). A suspension of 6ꢀphenylꢀ2ꢀRꢀ
1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (1a—c) (9.40 mmol) in
a 17% aqueous Na2CO3 solution (6 mL) was stirred at room
temperature for 0.5 h. The precipitate was filtered off, dried, and
dissolved in DMF (10 mL). 4ꢀBromobutyl acetate (5) (1.79 g,
9.20 mmol) was added to the reaction solution. The reaction
mixture was heated at 100 °C for 2 h and then cooled. Water
(200 mL) was added to the mixture, and the precipitate was
filtered off and crystallized from isopropyl alcohol.
Compound 7a (R = H). The yield was 40%, m.p. 74 °C.
1H NMR (400 MHz), δ: 1.71 (m, 2 H, H(3´)); 1.98 (m, 2 H,
H(2´)), 1.99 (s, 3 H, OAc); 4.05 (t, 2 H, H(4´) J = 6.5 Hz); 4.44
(t, 2 H, H(1´), J = 6.9 Hz); 7.47—7.54 (m, 3 H, Hm, Hp); 8.02
(m, 2 H, Ho); 8.44 (s, 1 H, H(2)). Coupled 1H—13C NMR (100 MHz),
δ: 20.63 (q, CO—CH3, 1J = 129.2 Hz), 24.20 (tm, C(2´),
1J = 128.2 Hz); 24.93 (tm, C(3´), 1J = 127.0 Hz); 53.50 (tt, C(1´),
1J = 142.7 Hz, 2J = 4.1 Hz); 63.23 (tt, C(4´), 1J = 147.1 Hz,
Compound 4b (R = Me). The yield was 37%, m.p. 125 °C. 1H
NMR (250 MHz), δ: 2.48 (s, 3 H, C(2)—Me); 3.52 (q, 2 H,
H(4´), J = 5.1 Hz); 3.74 (t, 2 H, H(3´), J = 5.1 Hz); 4.42 (t, 1 H,
OH, J = 5.1 Hz); 5.72 (s, 2 H, H(1´)); 7.44—7.49 (m, 3 H, Hm,
Hp); 8.03 (m, 2 H, Ho). Found (%): C, 55.80; H, 4.86; N, 23.21.
C14H15N5O3. Calculated (%): C, 55.81; H, 4.98; N, 23.26. IR,
ν/cm–1: 1692 (CO), 3490 (OH).
1
2J = 4.1 Hz); 128.16 (dm, Cm, J = 160.6 Hz); 128.43 (dm, Co,
Compound 4c (R = SMe). The yield was 30%, m.p. 142 °C.
1J = 162.4 Hz); 129.54 (dt, Cp, J = 161.3 and 7.4 Hz); 132.33
(t, Cipso, J = 7.2 Hz); 138.84 (t, C(6), 3J = 3.7 Hz); 149.12 (s,
1H NMR (250 MHz), δ: 2.68 (s, 3 H, SMe), 3.53 (q, 2 H, H(4´),

2428
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Shestakova et al.
C(7)); 151.13 (dt, C(3a), 3J = 9.3 and 2.7 Hz); 153.24 (d, C(2),
1J = 210.8 Hz); 170.30 (qt, CO—CH3, 2J = 6.6 Hz, 3J = 3.3 Hz).
Found (%): C, 58.08; H, 5.12; N, 21.36. C16H17N5O3. Calcuꢀ
lated (%): C, 58.71; H, 5.20; N, 21.41. IR, ν/cm–1: 1729, 1704
(C=O).
Compound 7b (R = Me). The yield was 50%, m.p. 78 °C.
1H NMR (400 MHz), δ: 1.70 (m, 2 H, H(3´)); 1.96 (m, 2 H,
H(2´)); 1.99 (s, 3 H, OAc); 2.45 (s, 3 H, C(2)—Me); 4.05 (t,
2 H, H(4´), J = 6.5 Hz); 4.40 (t, 2 H, H(1´), J = 6.9 Hz);
7.47—7.53 (m, 3 H, Hm, Hp); 8.01 (m, 2 H, Ho). 13C NMR
(100 MHz), δ: 14.30 (C(2)—Me); 20.66 (CO—CH3); 24.20
(C(2´); 24.94 (C(3´)); 53.44 (C(1´)); 63.27 (C(4´)); 128.16 (Cm);
128.41 (Co); 129.51 (Cp); 132.42 (Cipso); 138.82 (C(6)); 148.65
(C(7)); 151.35 (C(3a)); 162.73 (C(2)); 170.33 (CO—CH3).
Found (%): C, 59.88; H, 5.63; N, 20.65. C17H19N5O3. Calcuꢀ
lated (%): C, 59.82; H, 5.57; N, 20.53. IR, ν/cm–1: 1733, 1702
(C=O).
Compound 7c (R = SMe). The yield was 75%, m.p. 110 °C.
1H NMR (400 MHz), δ: 1.70 (m, 2 H, H(3´)); 1.95 (m, 2 H,
H(2´)); 1.99 (s, 3 H, OAc); 2.66 (s, 3 H, SMe), 4.05 (t, 2 H,
H(4´), J = 6.4 Hz); 4.37 (t, 2 H, H(1´), J = 7.0 Hz); 7.47—7.54
(m, 3 H, Hm, Hp); 8.01 (m, 2 H, Ho). 1H—13C NMR
(100 MHz), δ: 13.49 (q, SMe, 1J = 142.5 Hz), 20.66 (q,
CO—CH3, 1J = 129.2 Hz); 24.11 (tm, C(2´), 1J = 127.8 Hz);
24.89 (tm, C(3´), 1J = 126.8 Hz); 53.40 (tt, C(1´), 1J = 142.8 Hz,
J = 4.0 Hz), 63.26 (tt, C(4´), 1J = 147.1 Hz, J = 4.1 Hz), 128.19
(dm, Cm, 1J = 161.5 Hz); 128.42 (ddd, Co, J = 161.9, 7.4, and
5.7 Hz); 129.64 (dt, Cp, J = 161.8 and 7.4 Hz); 132.30 (m, Cipso);
139.34 (t, C(6), 3J = 3.8 Hz); 147.84 (s, C(7)); 151.71 (t, C(3a),
3J = 2.8 Hz); 165.48 (q, C(2), 3J = 4.8 Hz); 170.33 (qt,
CO—CH3, J = 6.6 and 3.4 Hz). Found (%): C, 54.62; H, 4.76;
N, 18.90. C17H19N5O3S. Calculated (%): C, 54.69; H, 5.09; N,
18.77. IR, ν/cm–1: 1700, 1688 (C=O).
4ꢀ(4ꢀAcetoxybutꢀ2ꢀenyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (8a—c). A suspension of 6ꢀphenylꢀ
2ꢀRꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (1a—c) (9.40 mmol)
in a 17% aqueous Na2CO3 solution (6 mL) was stirred at room
temperature for 0.5 h. The precipitate was filtered off, dried, and
dissolved in DMF (10 mL). (Z)ꢀ4ꢀBromobutꢀ2ꢀenyl acetate (6)
(1.77 g, 9.20 mmol) was added to the reaction solution. The
reaction mixture was heated at 100 °C for 2 h and cooled. Then
water (200 mL) was added, and the precipitate was filtered off
and crystallized from isopropyl alcohol.
3J = 11.0 Hz, 3J = 6.5 Hz, 4J = 1.3 Hz); 7.48—7.51 (m, 3 H,
Hm, Hp); 8.00 (m, 2 H, Ho). 13C NMR (100 MHz), δ: 14.30
(C(2)—Me); 20.62 (CO—CH3); 50.79 (C(1´)), 59.81 (C(4´)),
126.47 (C(2´)), 128.17 (Cm), 128.40 (Co), 129.03 (C(3´)), 129.60
(Cp), 132.29 (Cipso), 139.10 (C(6)), 148.60 (C(7)), 151.15
(C(3a)), 162.78 (C(2)), 170.17 (CO—CH3). Found (%): C,
60.08; H, 5.03; N, 20.84. C17H17N5O3. Calculated (%): C, 60.18;
H, 5.01; N, 20.65. IR, ν/cm–1: 1714, 1740 (C=O).
Compound 8c (R = SMe). The yield was 67%, m.p. 104 °C.
1H NMR (400 MHz), δ: 2.04 (s, 3H, OAc); 2.66 (s, 3 H, SMe);
4.81 (dd, 2 H, H(4´), 3J = 6.5 Hz, 4J = 1.3 Hz); 5.08 (dd,
2 H, H(1´), 3J = 6.5 Hz, 4J = 1.1 Hz); 5.81 (dtt, 1 H, H(2´),
3
4
3J = 11.0 Hz, J = 6.5 Hz, J = 1. Hz1); 5.92 (dtt, 1 H, H(3´),
3J = 11.0 Hz, 3J = 6.5 Hz, 4J = 1.3 Hz); 7.48—7.52 (m, 3 H, Hm,
Hp); 8.00 (m, 2 H, Ho). 13C NMR (100 MHz), δ: 13.50 (SMe);
20.62 (CO—CH3); 50.79 (C(1´)); 59.81 (C(4´)); 126.25 (C(2´));
128.20 (Cm); 128.40 (Co); 129.16 (C(3´)); 129.72 (Cp); 132.16
(Cipso); 139.60 (C(6)); 147.79 (C(7)); 151.45 (C(3a)); 165.55
(C(2)); 170.16 (CO—CH3). Found (%): C, 54.89; H, 4.49;
N, 18.88. C17H17N5O3S. Calculated (%): C, 54.98; H, 4.58;
N, 18.87. IR, ν/cm–1: 1728, 1692 (C=O).
4ꢀ(4ꢀHydroxybutyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc]ꢀ
[1,2,4]triazinꢀ7ꢀones (9a—c). 4ꢀ(4ꢀAcetoxybutyl)ꢀ1,2,4ꢀtriꢀ
azoloꢀ[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (7a—c) (3.00 mmol) was added
to a solution of MeONa, which was prepared from sodium metal
(0.07 g, 3.04 mmol)) in anhydrous MeOH (20 mL). The reacꢀ
tion mixture was refluxed for 1 h, cooled, and neutralized with
acetic acid. The solvent was evaporated in vacuo. Reaction prodꢀ
ucts 9a—c were isolated from the residue by silica gel column
chromatography using the ethyl acetate—hexane system (2 : 1)
as the eluent.
Compound 9a (R = H). The yield was 74%, m.p. 87 °C.
1H NMR (250 MHz), δ: 1.56 (m, 2 H, H(3´)); 2.02 (m, 2 H,
H(2´)); 3.47 (q, 2 H, H(4´), J = 5.7 Hz); 4.21 (t, 1 H, OH,
J = 5.1 Hz); 4.45 (t, 2 H, H(1´), J = 7.0 Hz); 7.43—7.48 (m,
3 H, Hm, Hp), 8.04 (m, 2 H, Ho), 8.26 (s, 1 H, H(2)). Found (%):
C, 58.94; H, 5.43; N, 24.57. C14H15N5O2. Calculated (%):
C, 58.95; H, 5.26; N, 24.56. IR, ν/cm–1: 1696 (CO), 3548 (OH).
Compound 9b (R = Me). The yield was 70%, m.p. 166 °C.
1H NMR (400 MHz), δ: 1.53 (m, 2 H, H(3´)); 1.95 (m, 2 H,
H(2´)); 2.45 (s, 3 H, C(2)—Me); 3.44 (td, 2 H, H(4´), J = 6.1
and 5.1 Hz); 4.38 (t, 2 H, H(1´), J = 7.2 Hz); 4.45 (t, 1 H, OH,
J = 5.1 Hz); 7.46—7.53 (m, 3 H, Hm, Hp), 8.01 (m, 2 H, Ho).
Found (%) C, 60.27; H, 5.62; N, 23.42. C15H17N5O2. Calcuꢀ
lated (%) C, 60.20; H, 5.69; N, 23.41. IR, ν/cm–1: 1715 (CO),
3408 (OH).
Compound 9c (R = SMe). The yield was 62%, m.p. 134 °C.
1H NMR (250 MHz), δ: 1.56 (m, 2 H, H(3´)); 2.00 (m, 2 H,
H(2´)); 2.67 (s, 3 H, SMe); 3.47 (q, 2 H, H(4´), J = 5.5 Hz);
4.20 (t, 1 H, OH, J = 5.1 Hz); 4.38 (t, 2 H, H(1´) , J = 7.2 Hz),
7.42—7.48 (m, 3 H, Hm, Hp), 8.02 (m, 2 H, Ho). Found (%):
C, 54.37; H, 5.14; N, 21.35. C15H17N5O2S. Calculated (%):
C, 54.38; H, 5.14; N, 21.15. IR, ν/cm–1: 1686 (CO), 3523 (OH).
4ꢀ(4ꢀHydroxybutꢀ2ꢀenyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀones (10a—c). Acetyl chloride (1 mL)
was added dropwise to MeOH (30 mL). Then 4ꢀ(4ꢀacetoxybutꢀ
2ꢀenyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone
(8a—c) (1.5 mmol) was added to the reaction solution. The
reaction mixture was kept at room temperature for 4 h and
neutralized with anhydrous sodium acetate. The solvent was
evaporated in vacuo. The reaction products (10a—c) were isoꢀ
Compound 8a (R = H). The yield was 30%, m.p. 83 °C.
1H NMR (400 MHz), δ: 2.04 (s, 3 H, OAc); 4.82 (dd, 2 H,
H(4´), 3J = 6.5 Hz, 4J = 1.3 Hz); 5.16 (dd, 2 H, H(1´), 3J = 6.5 Hz,
3
3
4J = 1.2 Hz); 5.85 (dtt, 1 H, H(2´), J = 11.0 Hz, J = 6.5 Hz,
3
3
4J = 1.3 Hz); 5.94 (dtt, 1 H, H(3´), J = 11.0 Hz, J = 6.5 Hz,
4J = 1.2 Hz); 7.49—7.54 (m, 3 H, Hm, Hp); 8.01 (m, 2 H, Ho);
8.45 (s, 1 H, H(2)). 13C NMR (100 MHz), δ: 20.63 (CO—CH3),
50.88 (C(1´)), 59.80 (C(4´)), 126.42 (C(2´)), 128.21 (Cm), 128.45
(Co), 129.10 (C(3´)), 129.66 (Cp), 132.22 (Cipso), 139.15 (C(6)),
149.12 (C(7)), 150.94 (C(3a)), 153.29 (C(2)), 170.19 (CO—CH3).
Found (%): C, 59.09; H, 4.45; N, 21.65. C16H15N5O3. Calcuꢀ
lated (%): C, 59.08; H, 4.62; N, 21.54. IR, ν/cm–1: 1713, 1745
(C=O).
Compound 8b (R = Me). The yield was 60%, m.p. 70 °C.
1H NMR (400 MHz), δ: 2.04 (s, 3 H, OAc); 2.45 (s, 3 H,
C(2)—Me); 4.81 (dd, 2 H, H(4´), 3J = 6.5 Hz, 4J = 1.3 Hz); 5.11
(dd, 2 H, H(1´), 3J = 6.6 Hz, 4J = 1.3 Hz); 5.84 (dtt, 1 H, H(2´),
3
4
3J = 11.0 Hz, J = 6.6 Hz, J = 1.3 Hz); 5.93 (dtt, 1 H, H(3´),

Synthesis of acyclic nucleosides
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008 2429
149.00 (s, C(7)); 151.32 (dt, C(3a), 3J = 9.2 and 2.8 Hz); 153.32
(d, C(2), 1J = 211.1 Hz); 170.27 (qt, CO—CH3, 2J = 6.8 Hz,
3J = 3.4 Hz). Found (%): C, 56.07; H, 4.28; N, 23.66. C14H13N5O3.
Calculated (%): C, 56.18; H, 4.38; N, 23.40. IR, ν/cm–1: 1736,
1710 (C=O).
Compound 12b (R = Me). The yield was 29%, m.p. 108 °C.
1H NMR (400 MHz), δ: 1.92 (s, 3 H, OAc); 2.46 (s, 3 H,
C(2)—Me); 4.51 (t, 2 H, H(2´), J = 5.3 Hz); 4.63 (t, 2 H, H(1´),
J = 5.3 Hz); 7.49—7.53 (m, 3 H, Hm, Hp); 8.01 (m, 2 H, Ho).
13C NMR (100 MHz), δ: 14.27 (C(2)—Me); 20.52 (CO—CH3);
52.89 (C(1´)); 60.67 (C(2´)); 128.22 (Cm); 128.44 (Co); 129.68
(Cp); 132.18 (Cipso); 139.17 (C(6)); 148.53 (C(7)); 151.53
(C(3a)); 162.86 (C(2)); 170.31 (CO—CH3). Found (%): C,
57.51; H, 4.68; N, 22.49. C15H15N5O3. Calculated (%): C, 57.50;
H, 4.83; N, 22.35. IR, ν/cm–1: 1739, 1706 (C=O).
Compound 12c (R = SMe). The yield was 38%, m.p. 142 °C.
1H NMR (400 MHz), δ: 1.93 (s, 3 H, OAc); 2.66 (s, 3 H, SMe);
4.50 (t, 2 H, H(2´), J = 5.3 Hz); 4.60 (t, 2 H, H(1´), J = 5.3 Hz);
7.50—7.54 (m, 3 H, Hm, Hp); 8.00 (m, 2 H, Ho). 13C NMR
(100 MHz), δ: 13.50 (SMe); 20.52 (CO—CH3); 52.85 (C(1´));
60.62 (C(2´)); 128.25 (Cm); 128.45 (Co); 129.80 (Cp); 132.06
(Cipso); 139.69 (C(6)); 147.70 (C(7)), 151.88 (C(3a)); 165.64
(C(2)); 170.30 (CO—CH3). Found (%): C, 52.01; H, 4.15; N,
20.52. C15H15N5O3S. Calculated (%): C, 52.17; H, 4.35;
N, 20.29. IR, ν/cm–1: 1732, 1706 (C=O).
4ꢀ(2ꢀHydroxyethyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc]ꢀ
[1,2,4]triazinꢀ7ꢀones (13a—c). 4ꢀ(2ꢀAcetoxyethyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ
1,2,4ꢀtriazolo[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (12a—c) (3.00 mmol)
was added to a solution of MeONa, which was prepared from
sodium metal (0.07 g, 3.00 mmol), in anhydrous MeOH (20 mL).
The reaction mixture was refluxed for 1 h, cooled, and neutralꢀ
ized with acetic acid. The solvent was evaporated in vacuo. The
reaction products (13a—c) were isolated from the residue by
column chromatography using the ethyl acetate—hexane system
(3 : 1) as the eluent.
Compound 13a (R = H). The yield was 41%, m.p. 145 °C. 1H NMR
(250 MHz), δ: 3.93 (q, 2 H, H(2´), J = 5.6 Hz); 4.49 (t, 2 H,
H(1´), J = 5.3 Hz), 4.65 (t, 1 H, OH, J = 6.4 Hz), 7.44—7.49
(m, 3 H, Hm, Hp), 8.05 (m, 2 H, Ho), 8.26 (s, 1 H, H(2)). Found
(%): C, 55.99; H, 4.21; N, 27.44. C12H11N5O2. Calculated (%):
C, 56.03; H, 4.31; N, 27.22. IR, ν/cm–1: 1692 (CO), 3485 (OH).
Compound 13b (R = Me). The yield was 35%, m.p. 151 °C.
1H NMR (250 MHz), δ: 2.47 (s, 3 H, C(2)—Me); 3.92 (q, 2 H, H(2´),
J = 5.7 Hz); 4.44 (t, 2 H, H(1´), J = 5.3 Hz); 4.67 (t, 1 H, OH,
J = 6.4 Hz); 7.43—7.48 (m, 3 H, Hm, Hp); 8.04 (m, 2 H, Ho).
Found (%): C, 57.60; H, 4.76; N, 26.01. C13H13N5O2. Calculated (%):
C, 57.56; H, 4.83; N, 25.82. IR, ν/cm–1: 1686 (CO), 3467 (OH).
Compound 13c (R = SMe). The yield was 34%, m.p. 176 °C.
1H NMR (250 MHz), δ: 2.68 (s, 3 H, SMe); 3.91 (q, 2 H, H(2´),
J = 5.6 Hz); 4.42 (t, 2 H, H(1´), J = 5.3 Hz); 4.66 (t, 1 H, OH,
J = 6.4 Hz); 7.43—7.49 (m, 3 H, Hm, Hp); 8.04 (m, 2 H, Ho).
Found (%): C, 51.67; H, 4.17; N, 23.05. C13H13N5O2S. Calcuꢀ
lated (%): C, 51.47; H, 4.32; N, 23.09. IR, ν/cm–1: 1695 (CO),
3491 (OH).
lated from the residue by silica gel column chromatography
using the ethyl acetate—hexane system (4 : 1) as the eluent.
Compound 10a (R = H). The yield was 41%, m.p. 112 °C.
1H NMR (400 MHz), δ: 4.23 (ddd, 2 H, H(4´), 3J = 5.8 and
4
3
5.4 Hz, J = 1.2 Hz); 4.87 (t, 1 H, OH, J = 5.4 Hz); 5.11 (dd,
2 H, H(1´), 3J = 6.5 Hz, 4J = 1.2 Hz); 5.72 (dtt, 1 H, H(2´),
3J = 11.0 and 6.5 Hz, 4J = 1.4 Hz); 5.82 (dtt, 1 H, H(3´),
3J = 11.0 and 5.8 Hz, 4J = 1.2 Hz); 7.48—7.54 (m, 3 H, Hm, Hp);
8.01 (m, 2 H, Ho); 8.45 (s, 1H, H(2)). 13C NMR (100 MHz), δ:
51.18 (C(1´)), 57.33 (C4´), 122.35 (C(2´)), 128.21 (Cm), 128.46
(Co), 129.61 (Cp), 132.82 (Cipso), 135.54 (C(3´)), 139.06 (C(6)),
149.12 (C(7)), 150.93 (C(3a)), 153.28 (C(2)). Found (%): C,
59.30; H, 4.54; N, 24.71. C14H13N5O2. Calculated (%): C, 59.36;
H, 4.59; N, 24.73. IR, ν/cm–1: 1700 (CO), 3368 (OH).
Compound 10b (R = Me). The yield was 70%, m.p. 125 °C.
1H NMR (400 MHz), δ: 2.45 (s, 3 H, C(2)—Me); 4.21 (ddd,
2 H, H(4´), 3J = 5.8 Hz, 5.3, 4J = 1.5 Hz); 4.88 (t, 1 H, OH,
3J = 5.3 Hz); 5.07 (dd, 2 H, H(1´), 3J = 6.5 Hz, 4J = 1.4 Hz);
5.71 (dtt, 1 H, H(2´), 3J = 11.1 Hz, 6.5, 4J = 1.5 Hz); 5.82 (dtt,
3
4
1 H, H(3´), J = 11.1 and 5.8 Hz, J = 1.4 Hz); 7.46—7.53 (m,
3 H, Hm, Hp); 8.00 (m, 2 H, Ho). 13C NMR (100 MHz), δ: 14.33
(C(2)—Me), 51.13 (C(1´)), 57.36 (C(4´)), 122.44 (C(2´)); 128.20
(Cm); 128.43 (Co); 129.59 (Cp); 132.36 (Cipso); 135.45 (C3´);
139.04 (C(6)); 148.63 (C(7)); 151.17 (C(3a)); 162.79 (C(2)).
Found (%): C, 60.53; H, 5.05; N, 23.51. C15H15N5O2. Calcuꢀ
lated (%): C, 60.61; H, 5.05; N, 23.57. IR, ν/cm–1: 1698 (CO),
3329 (OH).
Compound 10c (R = SMe). The yield was 45%, m.p. 146 °C.
1H NMR (400 MHz), δ: 2.66 (s, 3 H, SMe); 4.21 (ddd, 2 H, H(4´),
4
3
3J = 5.8 Hz, 5.3, J = 1.6 Hz); 4.86 (t, 1 H, OH, J = 5.3 Hz);
5.04 (dd, 2 H, H(1´), 3J = 6.5 Hz, 4J = 1.3 Hz); 5.70 (dtt,
1 H, H(2´), 3J = 11.1 Hz, 6.5, 4J = 1.6 Hz); 5.82 (dtt, 1 H, H(3)´,
3J = 11.1 and 5.8 Hz, 4J = 1.4 Hz); 7.49—7.52 (m, 3 H, Hm, Hp);
8.00 (m, 2H, Ho). 13C NMR (100 MHz), δ: 13.51 (SMe); 51.10
(C(1´)); 57.34 (C(4´)); 122.24 (C(2´)); 128.21 (Cm); 128.42 (Co);
129.69 (Cp); 132.24 (Cipso); 135.55 (C(3´)); 139.53 (C(6)); 147.81
(C(7)); 151.49 (C(3a)); 165.52 (C(2)). Found (%): C, 54.56;
H, 4.50; N, 21.02. C15H15N5O2S. Calculated (%): C, 54.71; H,
4.56; N, 21.28. IR, ν/cm–1: 1698 (CO), 3492 (OH).
2ꢀChloroethyl acetate (11) was synthesized according to a
procedure described earlier.28
4ꢀ(2ꢀAcetoxyethyl)ꢀ2ꢀRꢀ6ꢀphenylꢀ1,2,4ꢀtriazolo[3,2ꢀc]ꢀ
[1,2,4]triazinꢀ7ꢀones (12a—c). 6ꢀPhenylꢀ2ꢀRꢀ1,2,4ꢀtriazoloꢀ
[3,2ꢀc][1,2,4]triazinꢀ7ꢀone (1a—c) (5.50 mmol) was added to
a solution of cesium carbonate (0.98 g, 3.00 mmol) in water
(3 mL). The suspension was stirred for 0.5 h and filtered. The
precipitate was dried and dissolved in DMF (10 mL). Chloroethyl
acetate (11) (0.67 g, 5.5 mmol) was added to the solution. The
reaction mixture was heated at 100 °C for 5 h and cooled. Then
cold water (250 mL) was added. The precipitate was filtered off
and crystallized from isopropyl alcohol.
Compound 12a (R = H). The yield was 29%, m.p. 97 °C.
1H NMR (400 MHz), δ: 1.92 (s, 3 H, OAc); 4.53 (t, 2 H, H(2´),
J = 5.3 Hz); 4.68 (t, 2 H, H(1´), J = 5.3 Hz); 7.50—7.55 (m,
3 H, Hm, Hp); 8.02 (m, 2 H, Ho); 8.46 (s, 1 H, H(2)). Coupled
1H—13C NMR (100 MHz), δ: 20.49 (q, CO—CH3, 1J = 129.6 Hz);
This study was financially supported by the Council
on Grants of the President of the Russian Federation
(Program for State Support of Leading Scientific Schools
of the Russian Federation, Grant NShꢀ3758.2008.3),
the Russian Foundation for Basic Research (Projects
1
2
52.93 (tt, C(1´), J = 144.8 Hz, J = 2.6 Hz); 60.66 (tt, C(2´),
1J = 151.0 Hz, 2J = 2.8 Hz); 128.22 (dm, Cm, 1J = 161.1 Hz);
128.46 (dm, Co, 1J = 162.2 Hz); 129.71 (dt, Cp, J = 161.6 and
7.3 Hz); 132.09 (t, Cipso, J = 7.5 Hz); 139.19 (t, C(6), 3J = 3.8 Hz);

2430
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 11, November, 2008
Shestakova et al.
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Education and Science of the Russian Federation (State
Contract No. 02.522.11.2003), and the US Civilian
Research and Development Foundation (CRDF, Program
BRDF, Grant CRDF BM P2MO5).
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Received March 27, 2008;
in revised form July 2, 2008