Synthesis of methyl 7-aryl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a] pyrimidine-5-carboxylates and their reaction with hydrazine hydrate

Article abstract of DOI:10.1134/S1070428011070189

Fusion of methyl 4-(2-thienyl)-2,4-dioxobutanoate with 1H-tetrazol-5-amine monohydrate and aromatic aldehyde gave methyl 7-aryl-6-(2-thenoyl)-4,7- dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylates which reacted with an equimolar amount of hydrazine hydrate

Full text of DOI:10.1134/S1070428011070189

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 7, pp. 1077–1082. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.L. Gein, V.V. Mishunin, E.P. Tsyplyakova, M.I. Vakhrin, P.A. Slepukhin, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 7, pp. 1060–1064.
Synthesis of Methyl 7-Aryl-6-(2-thenoyl)-4,7-dihydro-
tetrazolo[1,5-a]pyrimidine-5-carboxylates and Their Reaction
with Hydrazine Hydrate
V. L. Geina, V. V. Mishunina, E. P. Tsyplyakovab, M. I. Vakhrina, and P. A. Slepukhinc
a Perm State Pharmaceutical Academy, Federal Health and Social Development Agency,
ul. Lenina 48, Perm, 614990 Russia
e- mail: perm@pfa.ru
b Perm Institute (Branch), Russian State University of Trade and Economics,
bul’var Gagarina 57, Perm, 614070 Russia
c Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
Received April 6, 2010
Abstract—Fusion of methyl 4-(2-thienyl)-2,4-dioxobutanoate with 1H-tetrazol-5-amine monohydrate and
aromatic aldehyde gave methyl 7-aryl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylates
which reacted with an equimolar amount of hydrazine hydrate at 180–190°C under solvent-free conditions to
produce 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-5(6H)-ones.
DOI: 10.1134/S1070428011070189
Three-component condensation of methyl 4-R-2,4-
dioxobutanoates with aromatic aldehyde and 5-amino-
tetrazole gives methyl 6-acyl-7-aryl-4,7-dihydrotetra-
zolo[1,5-a]pyrimidine-5-carboxylates [1–4]. While
continuing our studies on such reactions with 4-het-
aryl-2,4-dioxobutanoic acid esters with a view to
search for new biologically active compounds among
tetrazole derivatives we examined three-component
condensation of methyl 4-(2-thienyl)-2,4-dioxobuta-
noate with 5-aminotetrazole and aromatic aldehydes.
By heating the reactants at 130–140°C under solvent-
free conditions we obtained the corresponding methyl
7-aryl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrim-
idine-5-carboxylates Ia–Il (Scheme 1).
in the thiophene ring (a triplet at δ 6.89–7.36 ppm and
two doublets at δ 7.40–7.67 and 7.81–7.95 ppm), and
a downfield singlet at δ 11.02–11.50 ppm from the NH
proton in position 4 of the heteroring. The IR spectra
of Ia–Il contained absorption bands belonging to
stretching vibrations of the ketone carbonyl group at
1624–1644 cm–1, ester carbonyl group at 1728–
1744 cm–1, and N–H bond at 3112–3360 cm–1.
The presence of a γ-dicarbonyl fragment in mole-
cules Ia–Il makes them convenient for building up
fused heterocyclic systems. Reaction of compounds
Ia–Il with an equimolar amount of hydrazine hydrate
at 180–190°C under solvent-free conditions led to the
formation of 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo-
[1′,5′:1,2]pyrimido[4,5-d]pyridazin-5(6H)-ones IIa–IIl
(Scheme 1). Compounds IIa–IIl are potentially tauto-
meric, and they can exist as structures A and B. On the
basis of spectral data they were assigned lactam struc-
ture A. In the 1H NMR spectra of IIa–IIl we observed
a singlet from 9-H at δ 7.00–7.17 ppm, a multiplet
centered at δ 6.95–7.24 ppm due to aromatic protons,
signals from protons in the thiophene ring (a triplet at
δ 6.15–6.98 ppm and two doublets at δ 6.54–7.42 and
7.30–7.55 ppm), a singlet from N4H at δ 11.44–
Compounds Ia–Il were isolated as colorless crystal-
line substances which were readily soluble in DMSO
and DMF, soluble in glacial acetic acid on heating,
poorly soluble in ethanol, and insoluble in water,
diethyl ether, and chloroform. Compounds Ia–Il dis-
played in the 1H NMR spectra a three-proton singlet at
δ 3.38–3.40 ppm from the methoxy group in position 5
of the heteroring, a singlet at δ 6.59–7.12 ppm from the
7-H proton, a set of signals in the region δ 6.38–
7.42 ppm from aromatic protons, signals from protons
1077

GEIN et al.
1078
Scheme 1.
O
OMe
NH
O
O
N
NH
+
RCHO
+
·H2O
S
N
S
OMe
NH2
N
N
N
N
O
OH
N
R
Ia–Il
H
N
OH
NH
N
O
N
N
S
S
NH
N2H4 ·H2O
N
N
N
N
N
N
R
R
N
N
B
IIa–IIl
A
R = 4-HO-3-MeO (a), 4-HO-3-EtO (b), 3-HO (c), 4-HO (d), 3,4-(MeO)2 (e), 2,4-(MeO)2 (f), 2,5-(MeO)2 (g), 2,4-Cl2 (h),
4-i-Pr (i), 4-MeOCO (j), 4-t-Bu (k), 4-EtO (l).
11.85 ppm, and a singlet from N6H at δ 13.18–
13.42 ppm. The IR spectra of IIa–IIl contained
absorption bands due to stretching vibrations of the
ketone carbonyl group at 1618–1670 cm–1 and N–H
bonds at 3120–3264 cm–1.
crystallization from ethanol. The bicyclic fragment in
the molecule of methyl 7-phenyl-6-(2-thenoyl)-4,7-di-
hydrotetrazolo[1,5-a]pyrimidine-5-carboxylate (Fig. 1)
is bent along the N5···C4 axis. The dihedral angle be-
tween the C4C3C2N5 and N1N2N3N4N5C1C4 planes is
11°, the maximal deviation of atoms from the mean-
square planes being 0.015 Å. The endocyclic double
bonds are localized without appreciable conjugation
effect. All bond lengths and bond angles fall into the
corresponding standard ranges. Packing of methyl
7-phenyl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]py-
rimidine-5-carboxylate molecules in crystal is prima-
rily determined by formation of intermolecular hydro-
gen bonds NH···N which give rise to dimers, the inter-
atomic distance N5···N4 being 2.889(3) Å [–x + 1,
–y + 1, –z + 2] (Fig. 2).
The molecular and crystalline structures of methyl
7-phenyl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]py-
rimidine-5-carboxylate [4] were determined by X-ray
analysis of a single crystal which was obtained by slow
N3
N2
N4
C7
C1
N5
N1
C6
C8
C4 C5
EXPERIMENTAL
C9
C10
C2
C3
C13
The IR spectra were recorded on a Specord M80
spectrometer from samples dispersed in mineral oil.
The H NMR spectra were measured on a Bruker
DRX 500 instrument at 500.13 MHz from solutions in
DMSO-d6 using tetramethylsilane as internal refer-
ence. The mass spectra (electron impact, 70 eV) were
recorded on an INCOS 50 spectrometer.
O2
C15
C11
1
C12
C16
O3
C14
C17
O1
S1
Fig. 1. Structure of the molecule of methyl 7-phenyl-6-(2-
thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carbox-
ylate according to the X-ray diffraction data. Non-hydrogen
atoms are shown as thermal vibration ellipsoids with a prob-
ability of 50%.
X-Ray analysis of methyl 7-phenyl-6-(2-thenoyl)-
4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carbox-
ylate. The X-ray diffraction data were acquired on
an Xcalibur 3 automatic diffractometer with a CCD
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

SYNTHESIS OF METHYL 7-ARYL-6-(2-THENOYL)-4,7-DIHYDROTETRAZOLO...
1079
detector acording to standard procedure [MoKα irradia-
tion, graphite monochromator, ω-scanning, tempera-
ture 295(2) K] from a 0.26×0.08×0.02-mm colorless
needle-shaped crystal. No correction for absorption
was introduced. The structure was solved by the direct
method and was refined by the full-matrix least-
squares procedure (by F2) in anisotropic approximation
for all non-hydrogen atoms using SHELXTL-97 soft-
ware package [5]. The positions of hydrogen atoms
were determined from the spatial electron density
peaks and were refined in isotropic approximation
according to the riding model. Triclinic crystal system,
space group P-1; unit cell parameters: a = 5.9618(9),
b = 10.9349(16), c = 13.1581(17) Å; α = 96.821(11)°,
β = 97.889(11)°, γ = 91.868(12)°; V = 842.6(2) Å3; Z =
2. C17H13N5O3S. Total of 4018 reflection intensities
were measured in the range 3.15 < θ < 26.37°,
3280 reflections were independent (Rint = 0.0470), and
1312 reflections were characterized by I > 2σ(I)
(235 calculated parameters). The completeness for θ =
25.50° was 95.7%. The low reflectance of the needle-
shaped crystal related to its small scattering volume,
made it impossible to match a satisfactory weight
scheme (S = 0.805). The final divergence factors were
R1 = 0.0407, wR2 = 0.0326 [for reflections with I >
2σ(I)] and R1 = 0.1463, wR2 = 0.0378 (for all reflec-
tions). The maximal and minimal residual electron
densities were 0.178 and –0.218 eÅ–3, respectively.
The X-ray diffraction data for methyl 7-phenyl-6-(2-
thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-car-
boxylate were deposited to the Cambridge Crystallo-
graphic Data Centre (entry no. CCDC 826877) and are
available at http://www.ccdc.cam.ac.uk/.
Compounds Ib–Il were synthesized according to
a similar procedure.
Methyl 7-(3-ethoxy-4-hydroxyphenyl)-6-(2-
thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-
carboxylate (Ib). Yield 2.35 g (55%), mp 229–231°C.
IR spectrum, ν, cm–1: 3472 (OH), 3360 (NH), 1728
(C=O, ester), 1624 (C=O). 1H NMR spectrum, δ, ppm:
1.20 t and 3.87 q (3H and 2H, OEt), 3.39 s (3H,
OCH3), 6.60 s (1H, 7-H), 6.75 m (3H, Harom); 7.00 t,
7.60 d, 7.85 d (3H, 2-thienyl); 8.94 s (1H, OH), 11.16 s
(1H, NH). Found, %: C 53.38, 53.35; H 3.96, 3.99;
N 16.32, 16.36. C19H17N5O5S. Calculated, %: C 53.39;
H 4.01; N 16.38.
Methyl 7-(3-hydroxyphenyl)-6-(2-thenoyl)-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylate
(Ic). Yield 2.26 g (59%), mp 212–213°C. IR spectrum,
ν, cm–1: 3552 (OH), 3200 (NH), 1744 (C=O, ester),
1
1636 (C=O). H NMR spectrum, δ, ppm: 3.40 s (3H,
OCH3), 6.55 m (4H, Harom), 6.70 s (1H, 7-H); 7.00 t,
7.55 d, 7.85 d (3H, 2-thienyl); 9.40 s (1H, OH), 11.30 s
(1H, NH). Found, %: C 53.28, 53.25; H 3.46, 3.49;
N 18.32, 18.23. C17H13N5O4S. Calculated, %: C 53.26;
H 3.42; N 18.27.
Methyl 7-(4-hydroxyphenyl)-6-(2-thenoyl)-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylate
(Id). Yield 1.98 g (51%), mp 241–243°C. IR spectrum,
Methyl 7-(4-hydroxy-3-methoxyphenyl)-6-(2-
thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-
carboxylate (Ia). A mixture of 0.01 mol of methyl
4-(2-thienyl)-2,4-dioxobutanoate, 0.01 mol of 1H-tet-
razol-5-amine monohydrate, and 0.01 mol of 4-hy-
droxy-3-methoxybenzaldehyde was heated for 30 min
at 130–140°C until gaseous products no longer
evolved. The mixture was cooled to room temperature
and treated with ethanol, and the precipitate was
filtered off and recrystallized from glacial acetic acid.
Yield 2.21 g (53%), mp 234–237°C. IR spectrum, ν,
cm–1: 3542 (OH), 3360 (NH), 1728 (C=O, ester), 1632
a
c
0
b
1
(C=O). H NMR spectrum, δ, ppm: 3.38 s (3H,
COOCH3), 3.58 s (3H, OCH3), 6.59 s (1H, 7-H),
6.77 m (3H, Harom); 7.00 t, 7.60 d, and 7.86 d (3H,
2-thienyl); 9.00 s (1H, OH), 11.17 s (1H, NH). Found,
%: C 52.15, 52.35; H 3.56, 3.59; N 16.89, 16.92.
C18H15N5O5S. Calculated, %: C 52.30; H 3.66; N 16.94.
Fig. 2. A fragment of crystal packing of methyl 7-phenyl-
6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-
carboxylate.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

GEIN et al.
1080
ν, cm–1: 3500 (OH), 3328 (NH), 1736 (C=O, ester),
1632 (C=O). H NMR spectrum, δ, ppm: 3.40 s (3H,
OCH3), 6.75 s (1H, 7-H), 6.60 m (4H, Harom); 7.10 t,
7.65 d, 7.95 d (3H, 2-thienyl); 9.55 s (1H, OH), 11.30 s
(1H, NH). Found, %: C 53.26, 53.25; H 3.45, 3.42;
N 18.22, 18.24. C17H13N5O4S. Calculated, %: C 53.27;
H 3.41; N 18.26.
ν, cm–1: 3220 (NH), 1728 (C=O, ester), 1640 (C=O).
1H NMR spectrum, δ, ppm: 1.07 m and 1.13 m [6H,
CH(CH3)2], 2.75 m [1H, (CH3)2CH], 3.40 s (3H,
OCH3), 6.76 s (1H, 7-H); 6.89 t, 7.56 d, 7.83 d (3H,
2-thienyl); 7.11 m (4H, Harom), 11.30 s (1H, NH).
Found, %: C 58.64, 58.63; H 4.66, 4.67; N 17.11,
17.15. C20H19N5O3S. Calculated, %: C 58.67; H 4.68;
N 17.10.
1
Methyl 7-(3,4-dimethoxyphenyl)-6-(2-thenoyl)-
4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carbox-
ylate (Ie). Yield 2.11 g (49%), mp 239–241°C. IR
spectrum, ν, cm–1: 3280 (NH), 1744 (C=O, ester), 1628
Methyl 7-(4-methoxycarbonylphenyl)-6-(2-
thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-
carboxylate (Ij). Yield 2.41 g (56%), mp 251–252°C.
IR spectrum, ν, cm–1: 3320 (NH), 1728 (C=O, ester),
1
(C=O). H NMR spectrum, δ, ppm: 3.38 s (3H,
1
COOCH3), 3.58 s (3H, OCH3), 3.62 s (3H, OCH3),
6.77 s (1H, 7-H), 6.70 m (3H, Harom); 7.03 t, 7.67 d,
7.82 d (3H, 2-thienyl); 11.22 s (1H, NH). Found, %:
C 53.32, 53.37; H 4.04, 4.03; N 16.32, 16.34.
C19H17N5O5S. Calculated, %: C 53.39; H 4.01; N 16.38.
1644 (C=O). H NMR spectrum, δ, ppm: 3.40 s and
3.77 s (3H each, OCH3), 6.91 s (1H, 7-H), 7.06 m (4H,
Harom); 7.36 t, 7.62 d, 7.83 d (3H, 2-thienyl); 11.39 s
(1H, NH). Found, %: C 53.65, 53.63; H 3.54, 3.57;
N 16.49, 16.45. C19H15N5O5S. Calculated, %: C 53.64;
H 3.55; N 16.46.
Methyl 7-(2,4-dimethoxyphenyl)-6-(2-thenoyl)-
4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carbox-
ylate (If). Yield 1.96 g (45%), mp 211–213°C. IR
spectrum, ν, cm–1: 3112 (NH), 1744 (C=O, ester), 1632
Methyl 7-(4-tert-butylphenyl)-6-(2-thenoyl)-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylate
(Ik). Yield 2.36 g (55%), mp 241–243°C. IR spectrum,
ν, cm–1: 3220 (NH), 1736 (C=O), 1644 (C=O).
1H NMR spectrum, δ, ppm: 1.17 s (9H, t-Bu), 3.40 s
(3H, OCH3), 6.76 s (1H, 7-H); 7.02 t, 7.59 d, 7.85 d
(3H, 2-thienyl); 7.16 m (4H, Harom), 11.31 s (1H, NH).
Found, %: C 59.61, 59.60; H 5.01, 5.03; N 16.52,
16.55. C21H21N5O3S. Calculated, %: C 59.56; H 5.0;
N 16.54.
1
(C=O). H NMR spectrum, δ, ppm: 3.38 s (3H,
COOCH3), 3.59 s (3H, OCH3), 3.64 s (3H, OCH3),
6.78 s (1H, 7-H), 6.38 m (3H, Harom); 7.00 t, 7.40 d,
7.81 d (3H, 2-thienyl); 11.02 s (1H, NH). Found, %:
C 53.33, 53.36; H 4.05, 4.04; N 16.33, 16.35.
C19H17N5O5S. Calculated, %: C 53.39; H 4.01; N 16.38.
Methyl 7-(2,5-dimethoxyphenyl)-6-(2-thenoyl)-
4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carbox-
ylate (Ig). Yield 2.99 g (70%), mp 216–218°C. IR
spectrum, ν, cm–1: 3112 (NH), 1744 (C=O, ester), 1632
Methyl 7-(4-ethoxyphenyl)-6-(2-thenoyl)-4,7-di-
hydrotetrazolo[1,5-a]pyrimidine-5-carboxylate (Il).
Yield 2.15 g (52%), mp 246–247°C. IR spectrum, ν,
cm–1: 3200 (NH), 1728 (C=O, ester), 1644 (C=O).
1H NMR spectrum, δ, ppm: 1.25 t and 3.90 q (3H and
2H, OEt), 3.40 s (3H, OCH3), 6.75 s (1H, 7-H); 7.00 t,
7.60 d, 7.86 d (3H, 2-thienyl); 7.10 m (4H, Harom),
11.40 s (1H, NH). Found, %: C 55.48, 55.51; H 4.12,
4.14; N 17.05, 17.07. C19H17N5O4S. Calculated, %:
C 55.47; H 4.16; N 17.02.
1
(C=O). H NMR spectrum, δ, ppm: 3.38 s (3H,
COOCH3), 3.58 s (3H, OCH3), 3.68 s (3H, OCH3),
6.77 s (1H, 7-H), 6.82 m (3H, Harom); 7.00 t, 7.42 d,
7.81 d (3H, 2-thienyl); 11.08 s (1H, NH). Found, %:
C 53.35, 53.34; H 4.06, 4.02; N 16.35, 16.36.
C19H17N5O5S. Calculated, %: C 53.39; H 4.01; N 16.38.
Methyl 7-(2,4-dichlorophenyl)-6-(2-thenoyl)-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylate
(Ih). Yield 2.59 g (59%), mp 232–235°C. IR spectrum,
ν, cm–1: 3250 (NH), 1740 (C=O, ester), 1640 (C=O).
1H NMR spectrum, δ, ppm: 3.40 s (3H, COOCH3),
7.12 s (1H, 7-H); 7.25 t, 7.66 d, 7.90 d (3H, 2-thienyl);
7.42 m (3H, Harom), 11.50 s (1H, NH). Found, %:
C 46.84, 46.85; H 2.56, 2.52; N 16.06, 16.04.
C17H11Cl2N5O3S. Calculated, %: C 46.80; H 2.54;
N 16.05.
9-(4-Hydroxy-3-methoxyphenyl)-8-(2-thienyl)-
4,9-dihydrotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyr-
idazin-5(6H)-one (IIa). A mixture of 0.01 mol of
compound Ia and 0.01 mol of hydrazine hydrate was
heated for 5–10 min at 180–190°C until gaseous
products no longer evolved. The mixture was cooled to
room temperature and treated with ethanol, and the
precipitate was filtered off and recrystallized from
glacial acetic acid. Yield 2.09 g (53%), mp >300°C. IR
spectrum, ν, cm–1: 3208 (NH, OH), 1672 (C=O).
1H NMR spectrum, δ, ppm: 3.55 s (3H, OCH3); 6.53 t,
7.35 d, 7.42 d (3H, 2-thienyl); 7.0 s (1H, 9-H), 7.04 m
Methyl 7-(4-isopropylphenyl)-6-(2-thenoyl)-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylate
(Ii). Yield 2.38 g (58%), mp 245–246°C. IR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

SYNTHESIS OF METHYL 7-ARYL-6-(2-THENOYL)-4,7-DIHYDROTETRAZOLO...
1081
(3H, Harom), 9.00 s (1H, OH), 11.56 s (1H, N4H),
13.28 s (1H, N6H). Found, %: C 51.66, 51.68; H 3.32,
3.34; N 24.82, 24.84. C17H13N7O3S. Calculated, %:
C 51.64; H 3.31; N 24.80.
5(6H)-one (IIf). Yield 2.24 g (55%), mp 291–293°C.
IR spectrum, ν, cm–1: 3120 (NH), 1672 (C=O).
1H NMR spectrum, δ, ppm: 3.50 s (3H, OCH3), 3.62 s
(3H, OCH3); 6.30 t, 6.55 d, 7.41 d (3H, 2-thienyl);
7.17 s (1H, 9-H), 7.04 m (3H, Harom), 11.56 s (1H,
N4H), 13.21 s (1H, N6H). Mass spectrum, m/z (Irel, %):
409 (12.38) [M]+, 350 (100) [C16H11N7OS]+, 272 (6.93)
[C10H7N7OS]+. Found, %: C 52.80, 52.81; H 3.67,
3.69; N 23.96, 23.97. C18H15N7O3S. Calculated, %:
C 52.82; H 3.68; N 23.96.
Compounds IIb–IIl were synthesized in a similar
way.
9-(3-Ethoxy-4-hydroxyphenyl)-8-(2-thienyl)-4,9-
dihydrotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyrida-
zin-5(6H)-one (IIb). Yield 2.29 g (56%), mp 286–
288°C. IR spectrum, ν, cm–1: 3208 (NH, OH), 1672
1
9-(2,5-Dimethoxyphenyl)-8-(2-thienyl)-4,9-dihy-
drotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-
5(6H)-one (IIg). Yield 2.54 g (62%), mp 290–293°C.
IR spectrum, ν, cm–1: 3144 (NH), 1672 (C=O).
1H NMR spectrum, δ, ppm: 3.40 s (1H, OCH3), 3.50 s
(3H, OCH3); 6.15 t, 6.68 d, 7.39 d (3H, 2-thienyl);
7.08 m (3Harom), 7.15 s (1H, 9-H), 11.61 s (1H, N4H),
13.22 s (1H, N6H). Mass spectrum, m/z (Irel, %): 409
(11.31) [M]+, 350 (100) [C16H11N7OS]+, 77 (7.41)
[C6H5]+. Found, %: C 52.83, 52.84; H 3.68, 3.71;
N 23.96, 23.97. C18H15N7O3S. Calculated, %: C 52.81;
H 3.69; N 23.95.
(C=O). H NMR spectrum, δ, ppm: 1.20 t and 3.80 q
(3H and 2H, OEt), 6.95 m (3H, Harom); 6.54 t, 7.35 d,
7.47 d (3H, 2-thienyl); 7.00 s (1H, 9-H), 9.00 s (1H,
OH), 11.65 s (1H, N4H), 13.29 s (1H, N6H). Mass
spectrum, m/z (Irel, %): 409 (14.31) [M]+, 348 (100)
[C16H11N7OS]+, 272 (33.93) [C10H7N7OS]+. Found, %:
C 52.83, 52.85; H 3.65, 3.67; N 23.97, 23.99.
C18H15N7O3S. Calculated, %: C 52.81; H 3.69; N 23.95.
9-(3-Hydroxyphenyl)-8-(2-thienyl)-4,9-dihydro-
tetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-5(6H)-
one (IIc). Yield 2.22 g (61%), mp 295–297°C. IR
spectrum, ν, cm–1: 3220 (NH, OH), 1676 (C=O).
1H NMR spectrum, δ, ppm: 6.32 t, 6.54 d, 7.34 d (3H,
2-thienyl); 7.03 m (4H, Harom), 7.10 s (1H, 9-H), 9.40 s
(1H, OH), 11.75 s (1H, N4H), 13.34 s (1H, N6H).
Found, %: C 52.62, 52.64; H 3.04, 3.06; N 26.85,
26.87. C16H11N7O2S. Calculated, %: C 52.60; H 3.03;
N 26.83.
9-(2,4-Dichlorophenyl)-8-(2-thienyl)-4,9-dihy-
drotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-
5(6H)-one (IIh). Yield 2.75 g (66%), mp 298–299°C.
IR spectrum, ν, cm–1: 3200 (NH), 1672 (C=O).
1H NMR spectrum, δ, ppm: 6.98 t, 7.42 d, 7.47 d (3H,
2-thienyl); 7.12 s (1H, 9-H), 7.24 m (3H, Harom), 11.85 s
(1H, N4H), 13.34 s (1H, N6H). Found, %: C 45.93,
45.94; H 2.16, 2.19; N 23.48, 23.47. C16H9ClN7OS.
Calculated, %: C 45.95; H 2.17; N 23.44.
9-(4-Hydroxyphenyl)-8-(2-thienyl)-4,9-dihydro-
tetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-5(6H)-
one (IId). Yield 2.19 g (60%), mp 304–306°C. IR
spectrum, ν, cm–1: 3264 (NH, OH), 1680 (C=O).
1H NMR spectrum, δ, ppm: 6.50 t, 6.75 d, 7.30 d (3H,
2-thienyl); 7.02 m (4H, Harom), 7.06 s (1H, 9-H), 9.45 s
(1H, OH), 11.65 s (1H, N4H), 13.29 s (1H, N6H).
Found, %: C 52.62, 52.63; H 3.03, 3.04; N 26.84,
26.85. C16H11N7O2S. Calculated, %: C 52.61; H 3.02;
N 26.84.
9-(4-Isopropylphenyl)-8-(2-thienyl)-4,9-dihydro-
tetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-5(6H)-
one (IIi). Yield 2.54 (65%), mp 296–298°C. IR spec-
trum, ν, cm–1: 3152 (NH), 1672 (C=O). 1H NMR spec-
trum, δ, ppm: 1.09 d [6H, (CH3)2CH], 2.77 m [1H,
(CH3)2CH]; 6.80 t, 7.30 d, 7.40 d (3H, 2-thienyl);
7.15 s (1H, 9-H), 7.10 m (4H, Harom), 11.73 s (1H,
N4H), 13.31 s (1H, N6H). Found, %: C 58.32, 58.34;
H 4.36, 4.38; N 25.06, 25.07. C16H17N7OS. Calculated,
%: C 58.30; H 4.39; N 25.05.
9-(3,4-Dimethoxyphenyl)-8-(2-thienyl)-4,9-dihy-
drotetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-
5(6H)-one (IIe). Yield 2.45 g (60%), mp 274–276°C.
IR spectrum, ν, cm–1: 3150 (NH), 1676 (C=O).
1H NMR spectrum, δ, ppm: 3.57 s (3H, OCH3), 3.64 s
(3H, OCH3); 6.30 t, 6.57 d, 7.30 d (3H, 2-thienyl);
7.04 m (3H, Harom), 7.16 s (1H, 9-H), 11.53 s (1H,
N4H), 13.18 s (1H, N6H). Found, %: C 52.82, 52.84;
H 3.67, 3.70; N 23.96, 23.98. C18H15N7O3S. Calculat-
ed, %: C 52.81; H 3.69; N 23.95.
Methyl 4-[5-oxo-8-(2-thienyl)-4,5,6,9-tetrahydro-
tetrazolo[1′,5′:1,2]pyrimido[4,5-d]pyridazin-9-yl]-
benzoate (IIj). Yield 2.64 g (65%), mp >300°C. IR
1
spectrum, ν, cm–1: 3250 (NH), 1665 (C=O). H NMR
spectrum, δ, ppm: 3.80 s (3H, OCH3); 6.80 t, 7.40 d,
7.55 d (3H, 2-thienyl); 7.10 s (1H, 9-H), 7.20 m (4H,
H
arom), 11.60 s (1H, N4H), 13.20 s (1H, N6H). Found,
9-(2,4-Dimethoxyphenyl)-8-(2-thienyl)-4,9-dihy-
drotetrazolo[1′,5′:l,2]pyrimido[4,5-d]pyridazin-
%: C 53.03, 53.04; H 3.24, 3.27; N 24.08, 24.09.
C18H13N7O3S. Calculated, %: C 53.07; H 3.22; N 24.07.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

GEIN et al.
1082
9-(4-tert-Butylphenyl)-8-(2-thienyl)-4,9-dihydro-
trum, δ, ppm: 1.30 t and 3.90 q (3H, 2H, OEt); 6.85 t,
7.35 d, 7.45 d (3H, 2-thienyl); 7.10 m (4H, Harom), 7.14 s
(1H, 9-H), 11.78 s (1H, N4H), 13.42 s (1H, N6H).
tetrazolo[1′,5′ : 1,2]pyrimido[4,5-d]pyridazin-5(6H)-
one (IIk). Yield 2.67 g (66%), mp 304–306°C. IR
1
spectrum, ν, cm–1: 3200 (NH), 1672 (C=O). H NMR
REFERENCES
spectrum, δ, ppm: 1.15 s (9H, t-Bu); 6.74 t, 7.31 d,
7.41 d (3H, 2-thienyl); 7.07 m (4H, Harom), 7.14 s (1H,
9-H), 11.44 s (1H, N4H), 13.25 s (1H, N6H). Mass
spectrum, m/z (Irel, %): 405 (14.31) [M]+, 350 (100)
[C16H11N7OS]+, 272 (17.62) [C10H7N7OS]+, 134
(33.33) [t-BuC6H5]+. Found, %: C 59.23, 59.24;
H 4.75, 4.76; N 24.13, 24.19. C20H19N7OS. Calculated,
%: C 59.24; H 4.72; N 24.18.
1. Gein, V.L., Gein, L.F., Tsyplyakova, E.P., and Rozo-
va, E.A., Russ. J. Org. Chem., 2003, vol. 39, p. 753.
2. Gein, V.L., Gein, L.F., and Tsyplyakova, E.P., Khim.
Geterotsikl. Soedin., 2003, p. 949.
3. Gein, V.L., Gein, L.F., Tsyplyakova, E.P., and Pano-
va, O.S., Russ. J. Org. Chem., 2007, vol. 43, p. 1382.
4. Gein, V.L., Mishunin, V.V., Tsyplyakova, E.P., Vinoku-
rova, O.V., and Vakhrin, M.I., Khim-Farm. Zh., 2009,
vol. 43, no. 12, p. 46.
9-(4-Ethoxyphenyl)-8-(2-thienyl)-4,9-dihydro-
tetrazolo[1′,5′ : 1,2]pyrimido[4,5-d]pyridazin-5(6H)-
one (IIl). Yield 1.88 g (61%), mp 273–275°C. IR spec-
trum, ν, cm–1: 3110 (NH), 1672 (C=O). 1H NMR spec-
5. Sheldrick, G.M., Acta Crystallogr., Sect. A, 2008, vol. 64,
p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011