Synthesis of 8,9-dihydro[1,2,4]triazolo[1,5-a]-quinazolin-6(7H)-one derivatives

Article abstract of DOI:10.1134/S1070428013040027

Regioselectivity of the reactions of 1H-1,2,4-triazol-3-amines with 2-acyl-5,5-dimethylcyclohexane-1,3-diones and 2-dimethylaminomethylidene-5,5- dimethylcyclohexane-1,3-dione was studied. In all cases, the products were substituted 8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones whose structure was determined by ¹H and ¹³C NMR spectroscopy.

Full text of DOI:10.1134/S1070428013040027

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 4, pp. 502–507. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.A. Petrov, A.N. Kasatochkin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 4, pp. 520–525.
Dedicated to the 100th Anniversary of Corresponding Member
of the Russian Academy of Sciences A.A. Petrov
Synthesis of 8,9-Dihydro[1,2,4]triazolo[1,5-a]-
quinazolin-6(7H)-one Derivatives
A. A. Petrov and A. N. Kasatochkin
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: aap47@hotmail.ru
Received November 21, 2012
Abstract—Regioselectivity of the reactions of 1H-1,2,4-triazol-3-amines with 2-acyl-5,5-dimethylcyclo-
hexane-1,3-diones and 2-dimethylaminomethylidene-5,5-dimethylcyclohexane-1,3-dione was studied. In all
cases, the products were substituted 8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones whose structure
was determined by 1H and 13C NMR spectroscopy.
DOI: 10.1134/S1070428013040027
Triazolo[1,5-a]pyrimidines constitute an important
class of fused heterocyclic compounds whose bio-
logical activity depends on the nature and position of
substituents in their molecules [1]. Triazolo[1,5-a]py-
rimidine derivatives showed herbicidal, fungicidal
[2, 3], antimicrobial [4], antitumor [5, 6], antioxidant
[3], antimalarial [7], and anticonvulsant [8] activity
and were found to inhibit kinases [9].
An efficient method of synthesis of triazolopyrimi-
dines is based on annulation of a pyrimidine ring to tri-
azole with via condensation of 3-amino-1,2,4-triazole
derivatives with 1,3-bielectrophiles. The use of cyclic
electrophiles leads to the formation of cycloalkane-
annulated triazolo[1,5-a]-pyrimidines [10–15].
3-Aminotriazoles were reported to react with cyclic
bielectrophiles (enamino ketones, 2-hydroxymethyli-
denecycloalkanones, 2-acetylcycloalkanones, homo-
and heterocyclic β-oxo esters) to give one or two
isomeric products [11, 16–20].
3-Aminotriazoles Ia–Ic reacted with 2-acyl-5,5-
dimethylcyclohexane-1,3-diones IIa–IIc on heating in
boiling acetic acid or butanol in regioselective fashion
to give 8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-
6(7H)-ones IIIa–IIIi in 64–84% yield (Scheme 1). On
the other hand, the reaction of 2-trifluoroacetyl-5,5-di-
methylcyclohexane-1,3-dione (IId) with aminotriazole
Scheme 1.
R2
O
N
N
R1 = H, Ph, NH2
N
R2 = Me, Ph, PhCH2
O
O
O
Me
O
N
R1
Me
N
R1
NH2
BuOH
R2
IIIa–IIIi
+
Me
Me
HN
N
H
N
N
Ia–Ic
IIa–IId
N
R1 = H, R2 = CF3
HN
Me
Me
IV
I, R1 = H (a), Ph (b), NH2 (c); II, R2 = Me (a), Ph (b), PhCH2 (c), CF3 (d); III, R1 = H, R2 = Me (a), Ph (b), PhCH2 (c); R1 = NH2,
R2 = Me (d), Ph (e), PhCH2 (f); R1 = Ph, R2 = Me (g), Ph (h), PhCH2 (i).
502

SYNTHESIS OF 8,9-DIHYDRO[1,2,4]TRIAZOLO[1,5-a]QUINAZOLIN-6(7H)-ONE
503
Ia in acetic acid or dimethyl sulfoxide under different
conditions (rate and order of reactant addition, tem-
perature) afforded compound IV (Scheme 1). Presum-
ably, due to relatively low reactivity of aminotriazole
Ia and low stability of triketone IId [21] the latter
undergoes decomposition to release dimedone which
reacts with Ia to produce 3-(1H-1,2,4-triazol-3-yl-
amino)-5,5-dimethylcyclohex-2-en-1-one (IV). Com-
pound IV was also synthesized by heating aminotri-
azole Ia with dimedone in acetic acid (see Experi-
mental). The physical constants and spectral param-
eters of both samples of IV were identical.
dine. The structure of triazoloquinazolines IIIa, IIIb,
IIId, IIIe, IIIg, and IIIh was also confirmed by the
characteristic chemical shifts of the methyl carbon
atoms and ipso-carbon atoms in the phenyl groups of
model azolo[1,5-a]pyrimidines [1, 22], δC, ppm: ~25
(5-CH3), ~17 (7-CH3), ~136.5 (5-Ci), ~131 (7-Ci).
Isomeric triazolo[1,5-a]pyrimidines with an aryl
group on C9 and cyclohexane ring fused to the C5−C6
bond, 9-aryl-6,6-dimethyl-6,7-dihydro[1,2,4]triazolo-
[5,1-b]qunazolin-8(5H)-ones, were synthesized previ-
ously by three-component condensation of aminotri-
azoles with aromatic aldehydes and dimedone,
followed by oxidation of hexahydro derivative with
ceric ammonium nitrate or 2,3,5,6-tetrachloro-1,4-
benzoquinone [23].
The structure of compounds IIIa–IIIi was con-
1
firmed by the H and 13C NMR and high-resolution
1
mass spectra. The H NMR spectra of IIIa–IIIi in
CDCl3 contained signals from protons of two methyl
and two methylene groups in the cyclohexene frag-
ment, a singlet at δ 8.53–8.62 ppm (IIIa–IIIc) from
the CH proton in the triazole ring, and signals from
substituents on C2 and C5. The position of substituents
in the pyrimidine ring was determined on the basis of
known data on the chemical shifts of C5 and C7 in
triazolo[1,5-a]pyrimidines: the C5 signal is located in
the 13C NMR spectra in a considerably weaker field as
compared to C7 [1]. In the 13C NMR spectra of IIIa
and IIIb recorded without decoupling from protons,
three downfield signals belong to the carbonyl carbon
atom, C5, and C2 [1]. The quartet signal at δC 165.8 ppm
in the spectrum of IIIa in CDCl3 should be assigned
to C5 linked to methyl group, and the triplet at
δC 153.4 ppm arises from C9a, indicating annulation of
cyclohexene ring at the C6–C7 bond of triazolopyrimi-
A probable reaction mechanism implies initial
formation of enamino ketone by reaction of the amino
group in aminotriazole with the carbonyl carbon atom
in the 2-acyl group of 2-acylcyclohexane-1,3-dione.
The subsequent aza cyclization and elimination of
water yields compounds IIIa–IIIi. The three-com-
ponent condensation of aminotriazole Ia with dime-
done (V) and triethyl orthoacetate (X) in DMF resulted
in the formation of a complex mixture of products, the
major component being enamino ketone IV.
We made an attempt to synthesize isomeric tetra-
hydrotriazolo[1,5-a]quinazolines and tetrahydrotri-
azolo[5,1-b]quinazolines by two- and one-step three-
component reactions of aminotriazole Ia with dime-
done (V) and more reactive triethyl orthoformate or
dimethylformamide dimethyl acetal (VI, DMF–DMA)
Scheme 2.
O
OMe
OMe
N
NH2
Me
+
+
N
Me
Me
HN
N
Me
O
Ia
V
VI
O
d
Xylene
Me
Ia, xylene
N
a
Me
Me
Me
O
O
H
N
O
N
VI, DMF
N
VII
c
N
Me
Me
HN
N
N
N
Me
Me
N
N
V, xylene
IIIj
IV
N
b
N
Me
N
H
Me
VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013

PETROV, KASATOCHKIN
504
Scheme 3.
Me
Me
Me
O
O
Ia
V
+
VII
a
b
Me
H
N
N
N
N
HN
HN
+
VIII
N
O
N
OH
A
IIIj
Me2N
N
O
O
N
Me
N
NH2
N
VI
+
IV
+
c
N
Me
Me
HN
N
HN
O
Me
Me
Me
B
Ia
VII
in o-xylene and DMF. 8,8-Dimethyl-8,9-dihydro-
[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-one (IIIj) was
the only product formed in two-component condensa-
tions of aminotriazole (Ia) with 2-dimethylamino-
methylidene-5,5-dimethylcyclohexane-1,3-dione (VII)
(path a) and of N,N-dimethyl-N′-(1H-1,2,4-triazol-3-
yl)formimidamide (VIII) with dimedone (path b), re-
action of 3-(1H-1,2,4-triazol-3-ylamino)-5,5-dimethyl-
cyclohex-2-en-1-one (IV) with acetal VI in DMF
(path c), and three-component reaction of Ia with
diketone V and acetal VI in o-xylene (path d)
(Scheme 2). Scheme 3 shows a probable reaction
mechanism. Paths a and b involve intermediate forma-
tion of adduct A which undergoes intramolecular cy-
clization followed by dehydration. According to path c,
3-(1H-1,2,4-triazol-3-ylamino)-5,5-dimethylcyclohex-
2-en-1-one (IV) reacts with dimethylformamide di-
methyl acetal (VI) to produce unstable intermediate B
which decomposes into aminotriazole Ia and diketone
VII, and the latter react with each other to give IIIj.
However, path c is possible only in DMF; no com-
pound IIIj was formed when a mixture of Ia and VII
was heated for 7 h in boiling butanol or o-xylene.
hexene ring to the C6–C7 bond of the triazolopyrimi-
dine fragment unambiguously followed from the posi-
tion and multiplicity of downfield signals arising from
the carbonyl carbon atom (t, 193.6 ppm, J = 6.4 Hz),
C2H=N (d, 157.5 ppm, J = 208.9 Hz) and C5H=N (d,
152.6 ppm, J = 189 Hz), as well as of the signals from
3
C3a (d.d, 156.0 ppm, J = 15.3, 9.6 Hz) and C9a (t.d,
153.2 ppm, 2J = 7.5, 3J = 5.8 Hz).
Thus the two-component condensation of 2-substi-
tuted 1H-1,2,4-triazol-3-amines with 2-acyl-5,5-di-
methylcyclohexane-1,3-diones and three-component
reaction of aminotriazole with dimedone and dimethyl-
formamide dimethyl acetal (or triethyl orthoformate)
regioselectively yield 2,5-substituted 8,8-dimethyl-8,9-
dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded at
22°C on a Bruker DPX-300 spectrometer at 300.13
and 75.47 MHz, respectively, from solutions in
DMSO-d6–CCl4 (1:2) and CDCl3; the chemical shifts
were measured relative to the residual proton and
carbon signals of the solvent: CDCl3 (δ 7.28,
δC 77.00 ppm), DMSO-d6 (δ 2.50, δC 39.50 ppm). The
elemental compositions were determined from the
high-resolution mass spectra which were obtained on
a Bruker Daltonics microTOF instrument (electrospray
ionization, positive ion detection). 1H-1,2,4-Triazol-3-
amine, 1H-1,2,4-triazole-3,5-diamine, triethyl ortho-
formate, triethyl orthoacetate, and dimethylformamide
dimethyl acetal were commercial products (Acros
Organics). 2-Acetyl-, 2-benzoyl-, 2-(phenylacetyl)-,
and 2-trifluoroacetyl-5,5-dimethylcyclohexane-1,3-di-
ones were synthesized according to [24, 25], 5-phenyl-
1H-1,2,4-triazol-3-amine was prepared as described in
Monitoring of the three-component condensation
by high-resolution mass spectrometry revealed the
presence in the reaction mixture of enamino ketone IV
and final product IIIj, whereas more reactive com-
pounds VII and VIII were not detected.
The structure of IIIj was determined by 1H and 13C
NMR spectroscopy and high-resolution mass spec-
trometry, as well as by comparing its melting point and
spectral parameters with published data. The mode of
fusion of the cyclohexene ring was identified both with
account taken of known chemical shifts of C5 and C7 in
triazolo[1,5-a]pyrimidines [1] and on the basis of the
13
proton-coupled C NMR spectra. Fusion of the cyclo-
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SYNTHESIS OF 8,9-DIHYDRO[1,2,4]TRIAZOLO[1,5-a]QUINAZOLIN-6(7H)-ONE
505
[26], and 2-dimethylaminomethylidene-5,5-dimethyl-
cyclohexane-1,3-dione, 5,5-dimethyl-3-(1H-1,2,4-tri-
azol-5-ylamino)cyclohex-2-en-1-one, and N,N-dimeth-
yl-N′-(1H-1,2,4-triazol-3-yl)formimidamide (VIII)
were synthesized according to modified procedures
[27–29].
129.03 d.t (Cp, J = 160.9, 7.3 Hz), 139.07 t (Ci, J =
6.4 Hz), 153.96 d (C3a, J = 9.6 Hz), 154.80 t (C9a, J =
7.8 Hz), 157.72 d (C2, J = 208.9 Hz), 163.17 (C5),
194.26 t (C6, J = 6.0 Hz). Found: m/z 293.1387
[M + H]+. C17H16N4O. Calculated: 293.1397.
5-Benzyl-8,8-dimethyl-8,9-dihydro[1,2,4]triazolo-
[1,5-a]quinazolin-6(7H)-one (IIIc). Yield 76%, color-
Reaction of aminotriazoles Ia–Ic with triketones
IIa–IIc (general procedure). A mixture of 1 mmol of
aminotriazole Ia–Ic and 1 mmol of triketone IIa–IIc
was added to 2 ml of butan-1-ol or 1.5 ml of acetic
acid, and the resulting solution was heated for 16 h
under reflux. The mixture was evaporated to dryness
under reduced pressure, and the residue was dried,
analyzed to determine its composition, and recrystal-
lized from appropriate solvent.
1
less crystals, mp 174–175°C (from EtOH). H NMR
spectrum (CDCl3), δ, ppm: 1.19 s (6H, CH3), 2.58 s
(2H, 9-H), 3.37 s (2H, 7-H), 4.77 s (2H, CH2Ph), 7.16–
7.38 m (5H, Ph), 8.53 s (1H, 2-H). 13C NMR spectrum
(CDCl3), δC, ppm: 28.21 (8-Me), 32.21 (C8), 38.44
(C9), 42.96 (CH2), 52.74 (C7), 114.45 (C5a), 126.50
(Cp), 128.23 and 129.38 (Cm, Co), 137.42 (Ci), 154.10
(C9a), 154.33 (C3a), 157.61 (C2), 166.94 (C5), 194.52
(C6). Found: m/z 307.1546 [M + H]+. C18H18N4O. Cal-
culated: 307.1554.
5,8,8-Trimethyl-8,9-dihydro[1,2,4]triazolo[1,5-a]-
quinazolin-6(7H)-one (IIIa). Yield 80% (in butan-
1-ol), 52% (in acetic acid); colorless crystals,
mp 145°C (from EtOH); published data [29]: mp 143–
2-Amino-5,8,8-trimethyl-8,9-dihydro[1,2,4]tri-
azolo[1,5-a]quinazolin-6(7H)-one (IIId). Yield 66%,
colorless crystals, mp 274–276°C (from BuOH).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.07 s (6H,
8-CH3), 2.52 s (2H, CH2), 2.73 s (3H, 5-CH3), 3.15 s
(2H, CH2), 6.76 s (2H, NH2). 13C NMR spectrum
(CDCl3), δC, ppm: 26.12 (5-Me), 27.80 (8-Me), 31.67
(C8), 37.94 (C9), 51.98 (C7), 112.36 (C5a), 150.93 (C9a),
154.31 (C3a), 162.39 (C5), 168.38 (C2), 195.39 (C6).
Found: m/z 246.1344 [M + H]+. C12H15N5O. Calculat-
ed: 246.1349.
1
145°C. H NMR spectrum (CDCl3), δ, ppm: 1.24 s
(6H, 8-CH3), 2.65 s (2H, CH2), 3.00 s (3H, 5-CH3),
3.41 s (2H, CH2), 8.54 s (1H, 2-H). 13C NMR spectrum
(CDCl3), δC, ppm: 26.73 q (5-Me, J = 129.9 Hz),
28.21 q.m (8-Me, J = 126.2 Hz), 32.23 m (C8),
38.44 t.m (C9, J = 130.9 Hz), 52.64 t.m (C7, J =
129.3 Hz), 114.79 m (C5a), 153.40 t (C9a, J = 7.7 Hz),
154.32 d (C3a, J = 9.3 Hz), 157.41 d (C2, J =
207.9 Hz), 165.82 q (C5, J = 6.7 Hz), 194.90 t (C=O,
J = 6.4 Hz). Found: m/z 231.1234 [M + H]+.
C12H14N4O. Calculated: 231.1240. We also tried to
synthesize compound IIIa according to the following
procedure. A mixture of 0.5 mmol of aminotriazole Ia,
0.5 mmol of dimedone, and 0.5 mmol of triethyl ortho-
acetate in 0.5 ml of dimethylformamide was heated for
8 h under reflux. The mixture was concentrated under
reduced pressure to 2/3 of the initial volume, 2 ml of
acetone was added to the residue, and the precipitate
was filtered off and washed with water. The product
was a complex mixture of compounds; recrystalliza-
tion from butan-1-ol gave 50% of compound IV.
2-Amino-8,8-dimethyl-5-phenyl-8,9-dihydro-
[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-one (IIIe).
Yield 64%, light yellow crystals, mp 257–258°C (from
1
BuOH). H NMR spectrum (DMSO-d6–CCl4), δ, ppm:
1.12 s (6H, CH3), 2.54 s (2H, CH2), 3.25 s (2H, CH2),
6.67 br.s (NH2), 7.41 s (5H, Ph). 13C NMR spectrum
(CDCl3), δC, ppm: 27.90 (8-Me), 32.06 (C8), 38.13
(C9), 51.86 (C7), 112.59 (C5a), 127.39 and 128.71 (Co,
Cm), 128.49 (Cp), 139.68 (Ci), 151.06 (C9a), 154.26
(C3a), 161.12 (C5), 168.72 (C2), 193.80 (C6). Found:
m/z 308.1508 [M + H]+. C17H17N5O. Calculated:
308.1506.
2-Amino-5-benzyl-8,8-dimethyl-8,9-dihydro-
[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-one (IIIf).
Yield 70%, colorless crystals, mp 180–182°C (from
8,8-Dimethyl-5-phenyl-8,9-dihydro[1,2,4]tri-
azolo[1,5-a]quinazolin-6(7H)-one (IIIb). Yield 72%,
colorless crystals, mp 147–148°C (from EtOH).
1H NMR spectrum (DMSO-d6–CCl4), δ, ppm: 1.23 s
(6H, CH3), 2.66 s (2H, CH2), 3.48 s (2H, CH2), 7.45 m
(5H, Ph), 8.62 s (1H, 2-H). 13C NMR spectrum
(CDCl3), δC, ppm: 27.84 q.m (8-Me, J = 126.2 Hz),
32.46 m (C8), 37.91 t.m (C9, J = 130.9 Hz), 51.87 t.m
(C7, J = 129.3 Hz), 115.01 m (C5a), 127.54 d.d (Co, J =
161.0, 6.6 Hz), 128.74 d.t (Cm, J = 160.9, 6.6 Hz),
1
EtOH). H NMR spectrum (CDCl3), δ, ppm: 1.23 s
(6H, CH3), 2.61 s (2H, 9-H), 3.18 s (2H, 7-H), 4.70 s
(CH2Ph), 5.28 (NH2), 7.16–7.25 m (3H, Ph), 7.36 d
13
(2H, Ph, J = 7.3 Hz). C NMR spectrum (CDCl3), δC,
ppm: 28.24 (8-Me), 31.95 (C8), 38.77 (C9), 42.73
(CH2), 52.72 (C7), 112.94 (C5a), 126.34 (Cp), 128.17
and 129.34 (Co, Cm), 137.96 (Ci), 151.44 (C9a), 154.74
(C3a), 165.77 (C5), 167.89 (C2), 194.44 (C6). Found:
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PETROV, KASATOCHKIN
506
m/z 322.1648 [M + H]+. C18H19N5O. Calculated:
or 2 ml of ethanol, three drops of piperidine were
added, the mixture was heated for 7 h under reflux and
evaporated under reduced pressure, and the residue
was recrystallized from ethanol. Yield 80% (in
o-xylene), 72% (in ethanol); colorless crystals,
mp 181–182°C (from EtOH); published data: mp 172–
322.1662.
5,8,8-Trimethyl-2-phenyl-8,9-dihydro[1,2,4]tri-
azolo[1,5-a]quinazolin-6(7H)-one (IIIg). Yield 84%,
colorless crystals, mp 221–222°C (from BuOH).
1H NMR spectrum (CDCl3), δ, ppm: 1.26 s (6H,
8-CH3), 2.65 s (2H, CH2), 3.00 s (3H, 5-CH3), 3.45 s
(2H, CH2), 7.53 m (3H, Ph), 8.37 s (2H, Ph). 13C NMR
spectrum (CDCl3), δC, ppm: 26.80 (5-Me), 28.22
(8-Me), 32.15 (C8), 38.39 (C9), 52.61 (C7), 114.45
(C5a), 127.47 and 128.65 (Co, Cm), 129.89 (Ci), 130.90
(Cp), 152.91 (C9a), 155.03 (C3a), 165.57 (C5), 167.16
(C2), 194.97 (C6). Found: m/z 307.1539 [M + H]+.
C18H18N4O. Calculated: 307.1553.
1
174°C [14], 179–182°C [29]. H NMR spectrum
(CDCl3), δ, ppm: 1.19 s (6H, CH3), 2.59 s (2H, 7-H),
3.56 s (2H, 9-H), 8.51 s (1H, 2-H), 9.19 s (1H, 5-H).
13C NMR spectrum (CDCl3), δC, ppm: 28.30 q.m
(8-Me, J = 126.3 Hz), 29.46 m (C8), 37.44 t.m (C9, J =
131.4 Hz), 50.69 t.m (C7, J = 129.1 Hz), 115.25 m
(C5a), 152.64 d (C5, J = 189.2 Hz), 153.22 t.d (C9a, 2J =
3
3
7.5, J = 5.8 Hz), 155.98 d.d (C3a, J = 15.3, 9.6 Hz),
157.49 d (C2, J = 208.9 Hz), 193.57 t (C6, 2J = 6.4 Hz).
8,8-Dimethyl-2,5-diphenyl-8,9-dihydro[1,2,4]tri-
azolo[1,5-a]quinazolin-6(7H)-one (IIIh). Yield 66%,
colorless crystals, mp 245–246°C (from BuOH).
1H NMR spectrum (CDCl3), δ, ppm: 1.29 s (6H, CH3),
2.68 s (2H, CH2), 3.53 s (2H, CH2), 7.28–7.59 m (8H,
b. A mixture of 1 mmol of aminotriazole Ia and
1.2 mmol of DMF–DMA (VI) in 2 ml of o-xylene was
heated for 15 h. The mixture was evaporated under
reduced pressure to isolate N,N-dimethyl-N′-(1H-1,2,4-
1
13
triazol-3-yl)formimidamide (VIII). H NMR spectrum
Ph), 8.38 s (2H, Ph). C NMR spectrum (CDCl3), δC,
ppm: 28.41 (8-Me), 32.81 (C8), 38.76 (C9), 52.70 (C7),
114.70 (C5a); 127.64, 127.77, 128.75, 128.99 (Co, Cm);
129.67 (Cp), 129.94 (Ci), 131.06 (Cp), 138.43 (Ci),
153.44 (C9a), 155.21 (C3a), 164.06 (C5), 167.91 (C2),
193.66 (C6). Found: m/z 369.1689 [M + H]+.
C23H20N4O. Calculated: 369.1710.
(CDCl3), δ, ppm: 3.17 s and 3.19 s (3H each, NMe),
7.67 s (1H, CH=), 8.59 s (1H, CH=), 12.9 br.s (1H,
NH) (cf. [29]). The product and 1 mmol of dimedone
(V) were dissolved in 1.5 ml of o-xylene, the solution
was heated for 15 h under reflux and evaporated under
reduced pressure, and the residue was recrystallized
from ethanol. Yield 55%.
5-Benzyl-8,8-dimethyl-2-phenyl-8,9-dihydro-
[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-one (IIIi).
Yield 74%, colorless crystals, mp 230–231°C (from
c. A mixture of 1 mmol of compound IV and
1 mmol of DMF–DMA (VI) in 1 ml of DMF was
heated for 12 h under reflux. The solution was
evaporated under reduced pressure to 1/3 of the initial
volume, 3 ml of propan-2-ol was added, and the
precipitate was filtered off and recrystallized from
ethanol. The product was a mixture of enamino ketone
IV and compound IIIj at a ratio of 30:70 according to
the 1H NMR data.
d. A mixture of 1 mmol of aminotriazole Ia,
1 mmol of dimedone (V), and 1.2 mmol of DMF–
DMA (VI) in 2 ml of o-xylene was heated for 24 h
under reflux. The mixture was evaporated under
reduced pressure, and the residue was recrystallized
from ethanol. Yield 84%.
5,5-Dimethyl-3-(1H-1,2,4-triazol-3-ylamino)-
cyclohex-2-en-1-one (IV). A solution of 0.5 mmol of
aminotriazole Ia in 0.5 ml of acetic acid was heated to
the boiling point, 0.5 mmol of 5,5-dimethyl-2-(tri-
fluoroacetyl)cyclohexane-1,3-dione (IId) was slowly
added, and the mixture was heated for 3 h under reflux.
The solvent was removed under reduced pressure, and
the residue was washed with water and dried. Yield
50%, mp 285–287°C (from DMF−i-PrOH, 1:2);
1
BuOH). H NMR spectrum (CDCl3), δ, ppm: 1.23 s
(6H, CH3), 2.61 s (2H, 9-H), 3.44 s (2H, 7-H), 4.79
(2H, CH2Ph), 7.20–7.45 m (5H, Ph), 7.53 m and
8.38 m (5H, Ph), 13C NMR spectrum (CDCl3), δC,
ppm: 28.12 (8-Me), 32.04 (C8), 38.60 (C9), 42.84
(CH2), 52.65 (C7), 114.01 (C5a); 127.46, 128.13, 128.58,
129.36 (Co, Cm); 126.35 and 130.88 (Cp), 129.76 and
137.51 (Ci), 153.49 (C9a), 154.97 (C3a), 166.62 (C2),
167.39 (C5), 194.47 (C6). Found: m/z 383.1858
[M + H]+. C24H22N4O. Calculated: 383.1867.
8,8-Dimethyl-8,9-dihydro[1,2,4]triazolo[1,5-a]-
quinazolin-6(7H)-one (IIIj). a. A mixture of 1 mmol
of dimedone (V) and 1.2 mmol of DMF–DMA (VI) in
2 ml of o-xylene was heated for 3 h under reflux.
Evaporation of the mixture under reduced pressure
gave pure 2-(dimethylaminomethylidene)-5,5-dimeth-
ylcyclohexane-1,3-dione (VII) as a yellow solid.
1H NMR spectrum (CDCl3), δ, ppm: 1.06 s (6H, Me),
2.37 s (4H, CH2), 3.17 s and 3.38 s (3H each, NMe),
8.00 s (1H, CH=) (cf. [27]).
Compound VII thus obtained and 1 mmol of
aminotriazole Ia were dissolved in 1.5 ml of o-xylene
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013

SYNTHESIS OF 8,9-DIHYDRO[1,2,4]TRIAZOLO[1,5-a]QUINAZOLIN-6(7H)-ONE
507
1
10. Ali, K.A., Hosni, H.M., Ragab, E.A., and Abd El-
published data [28]: mp 285–287°C. H NMR spec-
trum (DMSO-d6–CCl4), δ, ppm: 1.07 s (6H, CH3),
2.02 s (2H, CH2), 2.37 s (2H, CH2), 6.42 s (1H, CH=),
8.15 s (1H, NH), 9.43 br.s (1H, CH=), 13.49 br.s (1H,
NH). Found: m/z 207.1259 [M + H]+. C10H14N4O. Cal-
culated: 207.1240.
Moez, S.I., Arch. Pharm. Chem., 2012, vol. 345, p. 231.
11. Desenko, S.M., Orlov, V.D., Getmanskii, N.V., Shish-
kin, O.V., Lindeman, S.V., and Struchkov, Yu.T., Khim.
Geterotsikl. Soedin., 1993, no. 4, p. 481.
12. Mustazza, C., Del Giudice, M.R., Borioni, A., and
Gatta, F., J. Heterocycl. Chem., 2001, vol. 38, p. 1119.
Compound IV was also synthesized independently
according to the following procedure. A mixture of
0.05 mol of aminotriazole Ia and 0.05 mol of
dimedone (V) in 2 ml of acetic acid was heated for 4 h
under reflux. The solvent was removed under reduced
pressure, 10 ml of cold water containing 1 ml of
25% aqueous ammonia was added to the residue, and
the precipitate was filtered off, washed with water, and
dried. Yield 95%. The melting point and spectral
parameters of the product coincided with those of
a sample prepared from aminotriazole Ia and triketone
IId as described in [28].
13. Farghaly, T.A., Abdel Hafez, N.A., Ragab, E.A.,
Awad, H.M., and Abdalla, M.M., Eur. J. Med. Chem.,
2010, vol. 45, p. 492.
14. Shikhaliev, Kh.S., Kryl’skii, D.V., Potapov, A.Yu., and
Krysin, M.Yu., Izv. Akad. Nauk, Ser. Khim., 2005,
p. 2805.
15. Bajwa, J.S. and Sykes, P.J., J. Chem. Soc., Perkin
Trans. 1, 1979, p. 3085.
16. Reiter, J. and Rivó, E., J. Heterocycl. Chem., 1989,
vol. 26, p. 971; Reiter, J. and Rivó, E., J. Heterocycl.
Chem., 1988, vol. 25, p. 1497.
17. Reiter, J. and Berecz, G., J. Heterocycl. Chem., 1991,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-00600a).
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18. Esses-Reiter, K. and Reiter, J., J. Heterocycl. Chem.,
1987, vol. 24, p. 1503.
19. Kleschick, W.A. and Bordner, J., J. Heterocycl. Chem.,
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