Reactions of tetrahydropyrido[4,5-d][1,2,4]triazolo[1,5-a]-pyrimidin-4-ones with activated alkynes. Synthesis of [1,2,4]triazolo[1′,5′:1,2] pyrimido[4,5-d]azocines

Article abstract of DOI:10.1007/s11172-012-0213-4

Triazolo[1′,5′:1,2]pyrimido[4,5-d]azocines were synthesized by the tandem expansion of the tetrahydropyridine ring in tetrahydropyridotriazolopyrimidines by the action of activated alkynes. Under these conditions, triazolopyridopyrimidines benzylated at the nitrogen atom of the pyrimidine moiety undergo the Hofmann cleavage of the tetrahydropyridine ring to form 5-vinyltriazolo[1,5-a]pyrimidines.

Full text of DOI:10.1007/s11172-012-0213-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 8, pp. 1603—1608, August, 2012
1603
Reactions of tetrahydropyrido[4,5ꢀd][1,2,4]triazolo[1,5ꢀa]ꢀpyrimidinꢀ4ꢀones
with activated alkynes. Synthesis of
[1,2,4]triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocines
L. G. Voskressensky,a T. N. Borisova,a M. V. Ovcharov,a E. A. Sorokina,a V. N. Khrustalev,b and A. V. Varlamova
aPeoples´ Friendship University of Russia,
6 ul. MiklukhoꢀMaklaya, 117198 Moscow, Russian Federation.
Fax: +7 (495) 955 0779. Eꢀmail: lvoskressensky@sci.pfu.edu.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Eꢀmail: vkh@xray.ineos.ac.ru
Triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocines were synthesized by the tandem expansion of
the tetrahydropyridine ring in tetrahydropyridotriazolopyrimidines by the action of activated
alkynes. Under these conditions, triazolopyridopyrimidines benzylated at the nitrogen atom of
the pyrimidine moiety undergo the Hofmann cleavage of the tetrahydropyridine ring to form
5ꢀvinyltriazolo[1,5ꢀa]pyrimidines.
Key words: tandem ring expansion, tandem cleavage, [1,2,4]triazolo[1´,5´:1,2]pyrimidoꢀ
[4,5d]azocines, 5ꢀvinyltriazolo[1,5ꢀa]pyrimidines.
Tandem transformations of fused tetrahydropyridines
by the action of alkynes containing electronꢀwithdrawing
substituents is a fairly efficient method for the synthesis of
tetrahydroazocines fused to the pyrrole,1 thiophene,2 inꢀ
dole,3 benzene,4 and pyrimidine5 heterocycles. Recently,
we have shown6 that the annulation of the isoxazole, thiꢀ
azole, or thiadiazole rings to the pyrimidine ring of tetraꢀ
hydropyrido[4,3ꢀd]pyrimidines results in the change in the
pathway of the transformation of their tetrahydropyridine
moiety by the action of activated alkynes. Instead of the
expansion of the tetrahydropyridine moiety to form the
azocine moiety, the former undergoes the Hofmann cleavꢀ
age to give 5ꢀ or 7ꢀvinylꢀsubstituted azolopyrimidines 1
(Scheme 1).6
sion to give triazolopyrimidoazocine 2 (see Scheme 1).6 It was
of interest to find the factors responsible for this pathway
of transformations of triazoleꢀfused pyridopyrimidines.
Pyridotriazolopyrimidines 3 and 4 were synthesized by
the condensation of 1ꢀbenzylꢀ and 1ꢀmethylꢀ3ꢀmethoxyꢀ
carbonylpiperidinꢀ4ꢀones, respectively, with 3ꢀaminoꢀ5ꢀ
methylthio[1,2,4]triazole in polyphosphoric acid (PPA)
according to a procedure described previously.7 Comꢀ
pound 5 was prepared according to a procedure described
in our earlier publication5 (Scheme 2).
The reactions of compounds 3—5 with methyl propiolꢀ
ate and acetylacetylene were performed in refluxing
methanol. As in the case of Nꢀphenylethylꢀsubstituted triꢀ
azolopyridopyrimidine 5, the main direction of the reacꢀ
tion involved the tetrahydropyridine ring expansion. After
0.5—24 h, triazolopyrimidoazocines 6—9 were obtained
in 52—85% yields (Scheme 3).
Only the reaction of Nꢀphenylethylꢀsubstituted tetraꢀ
hydropyrido(methylthio)triazolopyrimidine with methyl
propiolate resulted in the tetrahydropyridine ring expanꢀ
Scheme 1
R = Me, Pri, Br, CH2CH2Ph; X = H, CO2Me; Y = CO2Me, COMe
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1587—1591, August, 2012.
1066ꢀ5285/12/6108ꢀ1603 © 2012 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 8, August, 2012
Voskressensky et al.
Scheme 2
C(17)
O(2)
O(1)
C(16)
O(3)
C(14)
N(13)
N(12)
C(2)
C(25)
S(1)
C(1)
C(3)
C(15)
C(23)
C(24)
C(18)
N(4)
C(5)
C(7)
C(22)
C(19)
C(20)
C(11)
N(8)
N(10)
C(9)
C(6)
C(21)
Fig. 1. Molecular structure of compound 7 with displacement
ellipsoids drawn at the 50% probability level.
R = Me (3), Bn (4), CH2CH2Ph (5)
Since pyridotriazolopyrimidines 3—5 can exist in soꢀ
lution as mixtures of tautomers A, B, and C (see Refs 8
and 9), the resulting azocines 6—9 can adopt three tautoꢀ
meric forms of the triazolopyrimidine moiety. A single
crystal of triazolopyrimidoazocine 7 was obtained by the
crystallization from DMSO, and the threeꢀdimensional
structure of 7 was established by Xꢀray diffraction (Fig. 1).
The triazolopyrimidine moiety is almost planar and
exists in the tautomeric form B, which is unambiguousꢀ
ly evidenced by the C(9)—N(10) (1.319(2) Å) and
C(11)—N(12) (1.327(2) Å) bond lengths in the triazole
ring. The tetrahydroazocine moiety adopts a distorted boat
conformation. These results suggest that the tetrahydroꢀ
pyridine ring expansion occurs in the tautomeric form B.
To confirm this suggestion, we performed the benzylaꢀ
tion of pyridotriazolopyrimidine 4 with benzyl chloride in
DMF in the presence of sodium hydride (Scheme 4).
According to the Xꢀray diffraction data (Fig. 2), the
benzylation occurs at the pyrimidine nitrogen atom, and
the tautomeric form B in compound 10 is fixed, which is
unambiguously evidenced by the N(1)—C(2) (1.323(2) Å)
and N(3)—C(3A) (1.320(2) Å) bond lengths. The tetrahyꢀ
dropyridine moiety in compound 10 adopts an unsymꢀ
metrical chair conformation (the carbon atom C(6) and
the nitrogen atom N(7) deviate from the mean plane passꢀ
ing through the other atoms of the ring by 0.339(4) and
–0.426(3) Å, respectively). The triazolopyrimidine moiꢀ
ety is nearly planar. The phenyl rings are almost perpenꢀ
Scheme 3
i. MeOH, refluxing.
Compound
6
7
8
9
R
Y
Me
CO2Me
Bn
CO2Me
Bn
COMe
CH2CH2Ph
COMe

Synthesis of triazolopyrimido[4,5ꢀd]azocines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 8, August, 2012
1605
Scheme 4
C(17)
C(16)
C(18)
C(15)
C(13)
C(14)
C(12)
N(4)
C(3A)
N(3)
C(4A)
C(6)
C(5)
N(7)
C(2)
S(1)
C(8A)
N(10)
C(19)
C(20)
C(8)
C(25)
C(24)
C(23)
C(9)
N(1)
C(11)
C(21)
O(1)
dicular to the plane of the triazolopyrimidine moiety (the
angles between the corresponding planes are 80.89(5) and
87.06(5)).
C(22)
Fig. 2. Molecular structure of compound 9 with displacement
We expected that the tandem reactions of triazolopyrꢀ
idopyrimidine 10 with acetylacetylene and methyl propioꢀ
late in methanol would give triazolopyrimidoazocines.
However, we obtained not the expected tetrahydrotriazolꢀ
opyrimidoazocines but products of the Hofmann cleavage
of the tetrahydropyridine ring, viz., 5ꢀvinyl[1,2,4]triꢀ
azolo[1,5ꢀa]pyrimidines 11 and 12 in 85 and 89% yields,
respectively (Scheme 5).
Apparently, due to the electronꢀdonating effect of the
enamine group fixed by the benzyl radical in the zwitterꢀ
ion D, the electron deficiency on the methylidene group in
position 7 decreases so that the nucleophilic attack on this
group is hardly possible. The anionic center of the zwitterꢀ
ion D deprotonates methanol, and the ammonium ion F
ellipsoids drawn at the 50% probability level.
undergoes the Hofmann cleavage by the action of resultꢀ
ing methoxide anion.
These results suggest that the tetrahydropyridine ring
expansion of tetrahydrotriazolopyridopyrimidines 3—5 to
form the azocine moiety, as compared with their anaꢀ
logs, tetrahydropyridopyrimidines, fused to the isoxazole,
thiazole, and thiadiazole rings, takes place due to the
electronꢀwithdrawing effect of triazole, which leads to
an increase in the electron deficiency on the methꢀ
ylidene group in position 7. The expansion of the tetraꢀ
hydropyridine ring occurs apparently in the tautomeric
Scheme 5
Y = CO2Me (11), COMe (12)

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 8, August, 2012
Voskressensky et al.
Table 1. Principal crystallographic characteristics and the strucꢀ
ture refinement statistics for compounds 7•(CH3)2SO and 9
form A, which is transformed into the more stable form B
in azocine.
Therefore, we performed for the first time the efficient
synthesis of tetrahydrotriazolopyrimido[4,5ꢀd]azocines
representing a new heterocyclic system.
Compound
7•(CH3)2SO
9
Molecular formula
Crystal dimensions/mm3
Molecular weight
T/K
C22H27N5O4S2
0.22×0.26×0.30 0.02×0.21×0.24
C23H23N5OS
489.61
100
417.52
120
Experimental
Crystal system
Space group
a/Å
b/Å
c/Å
Monoclinic
P21/c
Monoclinic
P21/c
The IR spectra were recorded on an Infralyum FT–801 Fouꢀ
rierꢀtransform infrared spectrometer as KBr pellets. The LCMS
spectra were obtained using a system composed of an Agilent
1100 liquid chromatograph, an Agilent Technologies LC/MSD
VL mass spectrometer (electrospray mode, atmosphericꢀpresꢀ
sure chemical ionization), and an ELSD Sedex 75 detecꢀ
tor. Highꢀresolution mass spectra were measured on a JEOL
JMSꢀT100LPꢀDART 100 instrument (DART ionization). The
1H NMR spectra were recorded on Brukerꢀ400 and JEOL
JNMꢀECA600* instruments (for 1H, operating at 400 and
600 MHz, respectively) in CDCl3 or DMSOꢀd6 using residual
signals of the solvents or SiMe4 as the internal standard. The
elemental analysis was performed on a Carlo Erba 1106 instruꢀ
ment. The melting points were measured in open capillaries on
a SMP10 instrument. The course of the reactions was monitored
by TLC using Silufol UVꢀ254 and Sorbfile plates (visualization
was performed in an UV chamber rated at 254 nm, with iodine
vapor or a KMnO4 solution, 3 g L–1). All solvents used in the
work were purified by distillation and dried. Methyl propiolate,
acetylacetylene, and dimethyl acetylenedicarboxylate were purꢀ
chased from Acros Organics and Merck and were used without
additional purification.
22.5841(8)
11.2441(4)
9.0681(3)
96.1750(10)
2289.37(14)
4
11.4893(7)
13.3297(9)
13.3537(9)
93.5780(10)
2041.1(2)
/deg
V/Å3
Z4
dcalc/g cm–3
F(000)
1.420
1032
0.273
61.6
30106
7122
5713
302
1.359
880
0.184
60.0
23628
5942
3845
272
/mm–1
2max/deg
Number of reflections
measured unique
with I > 2(I)
Number of parameters
refinement
R1 (I > 2(I))
wR2 (based on all data)
GOOF
0.0388
0.0958
1.002
0.0544
0.1389
1.008
Tmin/Tmax
(max/min)/eÅ–3
0.923/0.942
0.450/–0.299
0.957/0.996
0.375/–0.336
Xꢀray diffraction study of compounds 7 and 9. The unit cell
parameters and intensities of reflections were measured on Brukꢀ
er SMART APEX II CCD (compound 7) and Bruker SMART
1K CCD (compound 9) automated threeꢀcircle diffractometers
(MoꢀK radiation, graphite monochromator, ꢀ and ꢀscanꢀ
ning technique). Absorption corrections were applied using the
SADABS program (version 2.0310 for 7 and version 2.0111 for 9).
Principal crystallographic data are given in Table 1. The strucꢀ
tures of compounds 7 and 9 were solved by direct methods and
refined by the fullꢀmatrix leastꢀsquares method using F2 with
anisotropic displacement parameters for nonhydrogen atoms. In
the crystal structure of compound 7, there is one dimethyl sulfꢀ
oxide molecule of solvation per asymmetric unit. In both strucꢀ
tures, the hydrogen atoms were positioned geometrically and
refined isotropically with fixed positional (a riding model) and
thermal (Uiso(H) = 1.5Ueq(C) for CH3 groups and Uiso(H) =
= 1.2Ueq(C) for all other groups) parameters. All calculations
were carried out with the use of the SHELXTL program packꢀ
age.12 Tables of atomic coordinates, bond lengths, bond angles,
torsion angles, and anisotropic displacement parameters for comꢀ
pounds 7•(CH3)2SO and 9 were deposited with the Cambridge
Crystallographic Data Centre.
triazole (2.35 g, 20 mmol) in polyphosphoric acid (20 mL) was
heated at 80 C for 8—20 h (the course of the reaction was
monitored by TLC, chloroform—methanol, 9 : 1, as the eluent).
The reaction mixture was cooled, water (50 mL) was added, and
the mixture was neutralized with a 15% NaOH solution. The
crystals that formed were filtered off, washed with water and
ethanol, and recrystallized from DMF.
7ꢀMethylꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]ꢀ
[1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ9(4H)ꢀone (3). Yield 30%, colorꢀ
less crystals, m.p. 198—200 C. Found (%): C, 47.60; H, 5.01;
N, 27.76. C10H13N5OS. Calculated (%): C, 47.79; H, 5.21;
N, 27.87. IR, /cm–1: 1695 (C=O). 1H NMR (400 MHz,
DMSOꢀd6), : 2.50 (s, 3 H, NCH3); 2.51—2.54 (m, 2 H,
C(6)H2); 2.55—2.61 (m, 2 H, C(5)H2); 2.56 (s, 3 H, SCH3);
3.45 (s, 2 H, C(8)H2). MS (ESI+), m/z: 282 [M + H]+.
7ꢀBenzylꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetrahydropyrido[4,3ꢀd]ꢀ
[1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ9(4H)ꢀone (4). Yield 75%, colorꢀ
less crystals, m.p. 250—252 C (with decomposition). Found (%):
C, 58.55; H, 5.34; N, 21.47. C16H17N5OS. Calculated (%):
C, 58.70; H, 5.23; N, 21.39. IR, /cm–1: 1639 (C=O). 1H NMR
(400 MHz, DMSOꢀd6), : 2.56 (s, 3 H, SCH3); 2.73 (m, 2 H,
C(6)H2); 2.77 (m, 2 H, C(5)H2); 3.30 (s, 2 H, CH2Ph); 3.74
(s, 2 H, C(8)H2); 7.28—7.38 (m, 5 H, Ph). MS (ESI+), m/z:
328 [M + H]+.
Synthesis of 7ꢀRꢀ2ꢀmethylthioꢀ5,6,7,8ꢀtetrahydropyridoꢀ
[4,3ꢀd][1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ9(4H)ꢀones 3—5 (general
procedure). A solution of 1ꢀalkylꢀ3ꢀcarbomethoxypiperidinꢀ4ꢀ
one hydrochloride (20 mmol) and 3ꢀaminoꢀ5ꢀmethylthio[1,2,4]ꢀ
2ꢀMethylthioꢀ7ꢀ(ethylꢀ2ꢀphenyl)ꢀ5,6,7,8ꢀtetrahydropyridoꢀ
[4,3ꢀd][1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ9(4H)ꢀone (5). Yield
47%, colorless crystals, m.p. 254—256 C (with decomposition).
Found (%): C, 59.63; H, 5.30; N, 20.44. C17H19N5OS. Calculatꢀ
* We thank the staff of the Shared Research and Education Cenꢀ
ter of Peoples´ Friendship University of Russia for recording the
NMR spectra.

Synthesis of triazolopyrimido[4,5ꢀd]azocines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 8, August, 2012
1607
ed (%): C, 59.80; H, 5.61; N, 20.51. IR, /cm–1: 1698 (C=O).
1H NMR (400 MHz, DMSOꢀd6), : 2.47 (t, 2 H, C(6)H2,
J = 7.0 Hz); 2.56 (s, 3 H, SCH3); 2.75 (t, 2 H, C(5)H2, J = 7.0 Hz);
3.26 (m, 2 H, CH2CH2Ph); 3.77 (s, 2 H, C(8)H2); 3.85 (m, 2 H,
CH2CH2Ph); 7.08—7.20 (m, 5 H, Ph). MS (ESI+), m/z: 342
[M + H]+.
Synthesis of triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocines 6—9
(general procedure). Methyl propiolate or acetylacetylene
(0.74 mmol) was added to a solution of the corresponding pyridoꢀ
triazolopyrimidine (3, 4, or 5) (0.20 g, 0.61 mmol) in methanol
(20 mL). The reaction mixture was refluxed for 30—60 min (the
course of the reaction was monitored by TLC, ethyl acetate as
the eluent). The precipitate that formed was filtered off, washed
with methanol, and dried.
as the eluent). Then the mixture was cooled, and water (40 mL)
was added dropwise. The precipitate of triazolopyridopyrimidꢀ
ine 10 that formed was filtered off and recrystallized from acetoꢀ
nitrile. Compound 10 was obtained in a yield of 0.85 g (60%),
yellow crystals, m.p. 220—222 C. Found (%): C, 66.03; H, 5.62;
N, 16.85. C23H23N5OS. Calculated (%): C, 66.16; H, 5.55;
N, 16.77. IR, /cm–1: 1676 (C=O). 1H NMR (600 MHz,
CDCl3), : 2.66—2.63 (m, 2 H, C(5)H2); 2.68 (s, 3 H, SCH3);
2.67—2.74 (m, 2 H, C(6)H2); 3.58 (s, 2 H, N(7)CH2Ph); 3.68
(s, 2 H, C(8)H2); 5.41 (s, 2 H, N(4)CH2Ph); 7.15—7.13 (m, 2 H,
N(7)CH2Ph); 7.27—7.33 (m, 3 H, N(7)CH2Ph); 7.20—7.40
(m, 5 H, N(4)CH2Ph). MS (ESI+), m/z: 418 [M + H]+.
Methyl (2Е)ꢀ3ꢀ{benzyl[(4ꢀbenzylꢀ5ꢀvinylꢀ2ꢀmethylthioꢀ7ꢀ
oxoꢀ4,7ꢀdihydro[1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ6ꢀyl)methyl]ꢀ
amino}acrylate (11). A solution of triazolopyridopyrimidine 10
(0.20 g, 0.48 mmol) and methyl propiolate (0.048 g, 0.55 mmol)
in a mixture of toluene (10 mL) and methanol (5 mL) was reꢀ
fluxed for 2 h (TLC monitoring, Silufol, chloroform—methanol,
9 : 1, as the eluent). The solvent was evaporated in vacuo, and
the residue was recrystallized from an ethyl acetate—hexane mixꢀ
ture. Compound 11 was obtained in a yield of 0.21 g (89%),
yellow crystals, m.p. 140—145 C. Found (%): C, 64.50; H, 5.49;
N, 14.03. C27H27N5O3S. Calculated (%): C, 64.65; H, 5.43;
N, 13.96. IR, /cm–1: 1697 (C=O), 1671 (C=O). 1H NMR
(600 MHz, CDCl3), : 2.68 (s, 3 H, SCH3); 3.61 (s, 3 H, OMe);
4.33 (s, 2 H, NCH2Ph); 4.43 (s, 2 H, C(5´)H2); 4.55 (d, 1 H,
C(2´)H, J = 13.1 Hz); 5.34 (s, 2 H, N(4)CH2Ph); 5.47 (d, 1 H,
CH2=, J = 17.9 Hz); 5.86 (d, 1 H, CH2=, J = 11.7 Hz); 6.31 (dd,
1 H, CH=CH2, J = 11.7 Hz, J = 17.9 Hz); 7.08—7.05 (m, 2 H, Ph);
7.14—7.11 (m, 2 H, Ph); 7.22—7.16 (m, 3 H, Ph); 7.35—7.28
(m, 3 H, Ph); 7.60 (d, 1 H, C(3´)H, J = 13.1). MS HRMS
(DART+), Found: m/z 502.1873 [M + H]+. C27H28N5O3S. Calꢀ
culated: [M + H] = 502.1867.
4ꢀBenzylꢀ6ꢀ({benzyl[(1Е)ꢀ3ꢀoxobutꢀ1ꢀenꢀ1ꢀyl]amino}methꢀ
yl)ꢀ5ꢀvinylꢀ2ꢀmethylthio[1,2,4]triazolo[1,5ꢀa]pyrimidinꢀ7(4H)ꢀ
one (12). Compound 12 was synthesized according to the aboveꢀ
described procedure from compound 10 (0.20 g, 0.48 mmol) and
acetylacetylene (0.045 mL, 0.55 mmol) in a yield of 0.21 g (85%),
yellow crystals, m.p. 170—172 C. Found (%): C, 66.85; H, 5.52;
N, 14.48. C27H27N5O2S. Calculated (%): C, 66.78; H, 5.60;
N, 14.42. IR, /cm–1: 1692 (C=O), 1600 (C=O). 1H NMR
(600 MHz, CDCl3), : 2.04 (s, 3 H, CH3C=O); 2.68 (s, 3 H,
SCH3); 4.36 (s, 2 H, =CHNCH2Ph); 4.45 (s, 2 H, C(5´)H2);
5.11 (br.s, 1 H, =CHCOCH3); 5.34 (s, 2 H, N(4)CH2Ph); 5.47
(d, 1 H, CH2=CH, J = 17.9 Hz); 5.88 (d, 1 H, CH2=CH,
J = 11.7 Hz); 6.29 (dd, 1 H, CH2=CH, J = 11.7 Hz, J = 17.9 Hz);
7.02—7.35 (m, 10 H, Ph); 7.60 (br.s, 1 H, CH=CH). MS (ESI+),
m/z: 486 [M + H]+.
Methyl 7ꢀmethylꢀ2ꢀmethylthioꢀ11ꢀoxoꢀ4,5,6,7,10,11ꢀhexaꢀ
hydro[1,2,4]triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocineꢀ9ꢀcarbꢀ
oxylate (6). Yield 55%, colorless crystals, m.p. 172—174 C.
Found (%): C, 50.19; H, 5.03; N, 20.92. C14H17N5O3S. Calcuꢀ
lated (%): C, 50.14; H, 5.11; N, 20.88. IR, /cm–1: 1682 (C=O),
1
1650 (C=O). H NMR (400 MHz, DMSOꢀd6), : 2.56 (s, 3 H,
SCH3); 2.89 (s, 3 H, NCH3); 3.20 (t, 2 H, C(5)H2, J = 6.5 Hz);
3.53 (s, 3 H, OCH3); 3.69 (t, 2 H, C(6)H2, J = 6.5 Hz); 3.79
(s, 2 H, CH2(10)); 7.25 (s, 1 H, C(8)H). MS (ESI+), m/z: 336
[M + H]+.
Methyl 7ꢀbenzylꢀ2ꢀmethylthioꢀ11ꢀoxoꢀ4,5,6,7,10,11ꢀhexaꢀ
hydro[1,2,4]triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocineꢀ9ꢀcarbꢀ
oxylate (7). Yield 88%, colorless crystals m.p. 274—276 C.
Found (%): C, 58.43; H, 5.23; N, 16.96. C20H21N5O3S. Calcuꢀ
lated (%): C, 58.38; H, 5.14; N, 17.02. IR, /cm–1: 1685 (C=O),
1
1646 (C=O). H NMR (600 MHz, DMSOꢀd6), : 2.59 (s, 3 H,
SCH3); 3.05 (t, 2 H, C(5)H2, J = 5.8 Hz); 3.58 (s, 3 H, OCH3);
3.85 (m, 2 H, C(6)H2); 3.85 (s, 2 H, C(10)H2); 4.41 (s, 2 H,
CH2Ph); 7.08—7.11 (m, 2 H, Ph); 7.20—7.23 (m, 3 H, Ph); 7.55
(s, 1 H, C(8)H). MS (ESI+), m/z: 412 [M + H]+.
9ꢀAcetylꢀ7ꢀbenzylꢀ2ꢀmethylthioꢀ5,6,7,10ꢀtetrahydro[1,2,4]ꢀ
triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocinꢀ11(4H)ꢀone (8). Yield
78%, colorless crystals m.p. 265—268 C. Found (%): C, 60.71;
H, 5.29; N, 17.83. C20H21N5O2S. Calculated (%): C, 60.74; H, 5.35;
N, 17.71. IR, /cm–1: 1679 (C=O). 1H NMR (600 MHz,
DMSOꢀd6), : 2.15 (s, 3 H, COCH3); 2.58 (s, 3 H, SCH3);
3.03 (m, 2 H, C(5)H2); 3.83 (m, 2 H, C(6)H2); 3.83 (m, 2 H,
C(10)H2); 4.46 (s, 2 H, CH2Ph); 7.11—7.22 (m, 5 H, Ph);
7.62 (s, 1 H, C(8)H); 12.39 (s, 1 H, NH). MS (ESI+), m/z: 396
[M + H]+.
9ꢀAcetylꢀ2ꢀmethylthioꢀ7ꢀ(2ꢀphenylethyl)ꢀ5,6,7,10ꢀtetraꢀ
hydro[1,2,4]triazolo[1´,5´:1,2]pyrimido[4,5ꢀd]azocinꢀ11(4H)ꢀ
one (9). Yield 77%, colorless crystals m.p. 246—249 C.
Found (%): C, 61.67; H, 5.75; N, 17.19. C21H23N5O2S. Calcuꢀ
lated (%): C, 61.59; H, 5.66; N, 17.10. IR, /cm–1: 1675 (C=O).
1H NMR (400 MHz, DMSOꢀd6), : 1.94 (s, 3 H, COCH3); 2.56
(s, 3 H, SCH3); 2.75 (t, 2 H, CH2CH2Ph, J = 7.4 Hz); 3.26 (m, 2 H,
C(5)H2); 3.47 (t, 2 H, CH2CH2Ph, J = 7.4 Hz); 3.76 (m, 2 H,
C(6)H2); 3.86 (m, 2 H, C(10)H2); 7.09—7.15 (m, 5 H, Ph); 7.19
(s, 1 H, C(8)H). MS (ESI+), m/z: 410 [M + H]+.
References
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1608
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Received July 1, 2011;
in revised form February 8, 2012