α-Amino azoles in the synthesis of heterocycles: VI. Synthesis and structure of cycloalkane-annulated pyrazolo[1,5-a]pyrimidines

Article abstract of DOI:10.1134/S1070428009090139

Reactions of 4-aryl-1H-pyrazol-5(3)-amines with 2-acylcycloakanones and 2-acyl-5,5-dimethylcyclohexane-1,3-diones led to the formation of regioisomeric 6,7,8,9-tetrahydropyrazolo[1,5-a]quinazoline, 5,6,7,8-tetrahydropyrazolo[5,1-b] quinazoline, and 7,8-di

Full text of DOI:10.1134/S1070428009090139

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 9, pp. 1390–1401. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.A. Petrov, A.N. Kasatochkin, E.E. Emelina, Yu.V. Nelyubina, M.Yu. Antipin, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 9, pp. 1403–1414.
α-Amino Azoles in the Synthesis of Heterocycles:
VI.* Synthesis and Structure of Cycloalkane-Annulated
Pyrazolo[1,5-a]pyrimidines
A. A. Petrova, A. N. Kasatochkina, E. E. Emelinaa, Yu. V. Nelyubinab, and M. Yu. Antipinb
a St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: aap47@hotmail.ru
b Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
Received November 26, 2008
Abstract—Reactions of 4-aryl-1H-pyrazol-5(3)-amines with 2-acylcycloakanones and 2-acyl-5,5-dimethyl-
cyclohexane-1,3-diones led to the formation of regioisomeric 6,7,8,9-tetrahydropyrazolo[1,5-a]quinazoline,
5,6,7,8-tetrahydropyrazolo[5,1-b]quinazoline, and 7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyrimidine
derivatives. The product structure was determined by X-ray analysis and 1H and 13C NMR spectroscopy.
DOI: 10.1134/S1070428009090139
Extensive development of synthetic approaches to
polyfunctional pyrazolo[1,5-a]pyrimidine derivatives
is stimulated by the fact that compounds possessing
pyrazole and pyrimidine fragments are promising as
potential biologically active substances. Several ef-
ficient medical agents exhibiting sedative and soporific
activity (such as Zaleplon [2], Indiplon [3], and
Ocinaplon [4]) are known; some compounds of this
series have been patented as antidiabetic [5] and anti-
phlogistic agents [6], antidepressants [7], and analge-
sics [8, 9]. Pronounced biological activity of pyrazolo-
[1,5-a]pyrimidine derivatives was noted in [10–17].
The goal of the present work was to study regio-
selectivity in the formation of cycloalkane-annulated
pyrazolo[1,5-a]pyrimidines and determine characteris-
tic 13C NMR spectral parameters of particular regio-
isomers. We examined reactions of 5(3)-amino-4-aryl-
1H-pyrazoles Ia–Id with 2-acylcycloalkanones III–
VII and three-component condensation of 5(3)-amino-
4-aryl-1H-pyrazoles Ia and Id with dimedone and
aldehydes.
zolopyrimidines fused at the C6–C7 bond to cyclo-
hexene ring. The reaction begins with nucleophilic
attack by the amino nitrogen atom of pyrazole I at the
carbon atom of the ethoxymethylidene or acetyl group
in II or III, respectively. In the first case, the primary
linear adduct, 5,5-dimethyl-2-{[(3-methyl-4-phenyl-
1H-pyrazol-5-yl)amino]methylidene}cyclohexane-1,3-
dione (A), was isolated as individual substance, while
in the second case, 3-hydroxy-5,5-dimethyl-2-{1-[(4-
phenyl-1H-pyrazol-3-yl)imino]ethyl}cyclohex-2-en-1-
one (B) was detected as intermediate product by
1H NMR (Scheme 1). The formation of an analogous
intermediate compound was observed previously in the
reaction of 5-methoxymethylidene-2,2-dimethyl-1,3-
dioxane-4,6-dione with 5(3)-aminopyrazoles [18]. In
the 1H NMR spectrum of compound A, the NH proton
in the pyrazole ring resonated at δ 12.82 ppm, and the
exocyclic CH= and NH protons gave doublets at δ 8.65
and 12.76 ppm, respectively, with a coupling constant
3J of 13.1 Hz. The downfield position of the latter NH
signal indicates formation of intramolecular hydrogen
bond NH···O. The structure of intermediate B was de-
Aminopyrazoles I reacted with 2-ethoxymethyli-
dene-5,5-dimethylcyclohexane-1,3-dione (II) and
2-acetyl-5,5-dimethylcyclohexane-1,3-dione (III) to
give only substituted 6,7,8,9-tetrahydropyrazolo-
[1,5-a]quinazolines which may be regarded as pyra-
1
termined by H NMR monitoring of the reaction
of aminopyrazole Id with acetyldimedone III in
1
DMSO-d6 at 20°C. After 2 days, the H NMR spec-
trum of the reaction mixture contained signals be-
longing to the initial compounds and those assignable
to structure B; in particular, signals from the pyrazole
* For communication V, see [1].
1390

α-AMINO AZOLES IN THE SYNTHESIS OF HETEROCYCLES: VI.
1391
Scheme 1.
O
OEt
O
Me
N
N
O
Ar
Ar
O
Me
Me
Me
Me
II
N
N
Me
N
Me
N
H···O
H
Me
A
VIIIc
O
O
O
Me
Me
O
O
Me
Me
N
N
O
Ar
Me
N
Ar
R
Me
Me
R
III
N
N
Me
N
H
H
Me
IXa, IXb, IXd
B
HC(OEt)3, dimedone
MeC(OEt)3, dimedone
VIIId
IXd
Ar
O
O
R
NH2
Me
N
NH
Me
Ar
( )n
Ia–Id
N
N
N
Ar
R
IV, V
R
+
( )n
N
N
N
( )n
Me
X, XI
XII, XIII
O
O
CF3
CF3
Ph
N
N
N
Ph
VI
+
N
N
N
CF3
XIV
XV
O
O
CF3
CF3
Ar
Me
Me
H
N
Me
Me
O
N
N
O
Ar
VII
+
N
N
H
N
O
Me
Me
XVI
XVIIa
I, VIII, IX, R = H, Ar = Ph (a), 4-ClC6H4 (b); R = Me, Ar = Ph (c), 4-ClC6H4 (d); X, XII, R = H, Ar = 4-ClC6H4; XI, XIII, R = Me,
Ar = 4-ClC6H4; XVI, XVIIa, Ar = 4-ClC6H4; IV, X, XII, n = 0; V, XI, XIII, n = 1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

PETROV et al.
1392
NH proton (δ 12.85 ppm) and hydroxy proton involved
in OH···N hydrogen bonding (δ 14.85 ppm) were
present. Intermediate compounds A and B undergo
thermal intramolecular cyclization with formation of
tetrahydropyrazolo[1,5-a]quinazolines VIIIc and IXa,
IXb, and IXd.
none (VI) with 5(3)-aminopyrazole Ia. The reaction in
acetic acid at 15°C afforded 3-(4-chlorophenyl)-9-(tri-
fluoromethyl)-5,6,7,8-tetrahydropyrazolo[5,1-b]quina-
zoline (XV) as the only product. In this case, the cyclo-
hexane ring is fused at the C5–C6 bond of pyrazolo-
[1,5-a]pyrimidine, and the CF3 group is attached to C9
(Scheme 1). When the reaction was carried out in
DMSO at 20°C or by fusion, the products were com-
pound XV and 18–30% of 3-(4-chlorophenyl)-5-tri-
fluoromethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]quina-
zoline (XIV), the latter being formed via cyclohexane
annulation at the C6–C7 bond of pyrazolo[1,5-a]pyrim-
idine. 5,5-Dimethyl-2-(trifluoroacetyl)cyclohexane-
1,3-dione (VII) reacted with aminopyrazole Ib under
different conditions to produce a mixture of com-
pounds XVI and XVIIa (Scheme 1). In this case,
nucleophilic attack by the amino nitrogen atom of pyr-
azole Ib is directed at the carbonyl carbon atom of the
trifluoroacetyl group in triketone VII, and subsequent
intramolecular cyclization and dehydration yield
3-(4-chlorophenyl)-8,8-dimethyl-5-trifluoromethyl-
6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-6-one
(XVI). Presumably, intermediate C formed as a result
of nucleophilic attack by the exocyclic nitrogen atom
of aminopyrazole I on the endocyclic carbonyl carbon
atom of triketone VII does not undergo intramolecular
cyclization to give structure D but decomposes into
3-[4-(4-chlorophenyl)-5-methyl-1H-pyrazol-3-yl-
amino]-5,5-dimethylcyclohex-2-en-1-one (XVIIa) and
trifluoroacetic acid (Scheme 2). It should be noted that
initial 2-(trifluoroacetyl)dimedone (VII) also decom-
poses during the process to give dimedone and tri-
fluoroacetic acid. Table 1 contain the product ratios
XVI:XVIIa obtained under different conditions.
An alternative approach to compounds VIII and IX
is based on three-component condensation of amino-
pyrazoles I with ortho esters (triethyl orthoformate and
triethyl orthoacetate) and dimedone (Scheme 1). Anal-
ogous three-component cyclocondensation of 5(3)-ami-
no-3(5)-methyl-1H-pyrazole with formaldehyde and
dimedone under microwave irradiation was reported to
afford 2,8,8-trimethyl-6,7,8,9-tetrahydropyrazolo-
[1,5-a]quinazolin-6-one [19].
We found that the regioselectivity of the reaction of
aminopyrazoles I with 2-acylcycloalkanones is deter-
mined by the nature of the acyl group and ring size.
Aminopyrazoles I reacted with 2-acetylcycloalkanones
IV and V under different conditions (on heating in
boiling acetic acid or ethanol or in ethanol at room
temperature in the presence of a catalytic amount of
trifluoroacetic acid) to produce a mixture of pyrazolo-
pyrimidines fused at the C6–C7 (X, XI) or C5–C6 bond
(XII, XIII) to carbocycle (Scheme 1). For instance, the
reaction of aminopyrazole Ib with 2-acetylcyclohex-
anone (V) in boiling acetic acid gave a mixture of
3-aryl-5-methyl-6,7,8,9-tetrahydropyrazolo[1,5-a]-
quinazoline XI and 3-aryl-9-methyl-5,6,7,8-tetrahydro-
pyrazolo[5,1-b]quinazoline XIII at a ratio of 3:2,
whereas the isomer ratio was 1:1 when the reaction
was carried out in ethanol at 17°C in the presence of
a catalytic amount of trifluoroacetic acid. We failed to
isolate compounds XI and XIII from the reaction mix-
ture by multiple crystallization or chromatographically,
Three-component condensation of dimedone with
aldehydes XVIIIa–XVIIIc and aminopyrazoles Ia and
Id in acetic acid with simultaneous mixing of the
components, as well as two-component reaction of
3-[4-(4-chlorophenyl)-5-methyl-1H-pyrazol-3-ylami-
no]-5,5-dimethylcyclohex-2-en-1-one (XVIIb) with
benzaldehyde (XVIIIa), in 5 h produced only the cor-
1
and their ratio was estimated by H NMR. In analo-
gous reaction with 2-acetylcyclopentanone (IV) the
major product (~95%) was 3-aryl-5-methyl-7,8-dihy-
dro-6H-cyclopenta[e]pyrazolo[1,5-a]pyrimidine (X).
Different regioselectivity was observed in the reac-
tion of cyclic diketone, 2-(trifluoroacetyl)cyclohexa-
Scheme 2.
Me
Me
Ar
Ar
H
Me
Me
Me
Me
N
N
Ar
HO
N
O
–CF3COOH
N
N
N
NH
H
HN
N
O
O
CF3
CF3
O
XVIIa
C
D
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

α-AMINO AZOLES IN THE SYNTHESIS OF HETEROCYCLES: VI.
1393
Scheme 3.
Ar
O
H
N
Me
Me
Ar
R1
NH2
R1
+
R2CHO
+
N
N
Me
Me
N
NH
O
R2
O
Ia, Id
XVIIIa–XVIIIc
XIXa–XIXc
Ar
O
H
N
O
XVIIIa
Me
Id
+
XIXa
NH
a
Me
Me
N
O
Me
Me
XVII
O
R2
HN
N
O
Ar
Ph
Me
Me
O
XVIIIa
Me
N
R1
Id
XIXa
N
Ph
Me
b
N
NH
XX
Me
XXI
I, R1 = H, Ar = Ph (a), R1 = Me, Ar = 4-ClC6H4 (d); XVII, Ar = 4-ClC6H4; XVIII, R2 = Ph (a), Et (b), i-Pr (c);
XIX, R1 = Me, Ar = 4-ClC6H4, R2 = Ph (a); R1 = H, Ar = Ph, R2 = Et (b), i-Pr (c).
responding 9-substituted 6,6-dimethyl-3-phenyl-
5,6,7,9-tetrahydropyrazolo[5,1-b]quinazolin-8(4H)-
ones XIXa–XIXc (Scheme 3; cf. [20]). It might be
expected that the reaction of Schiff base XX with
dimedone would give rise to isomeric 5-substituted
8,8-dimethyl-3-phenyl-5,7,8,9-tetrahydro-4H-pyrazolo-
[1,5-a]quinazolin-6-one XXI; however, the only prod-
uct was compound XIXa (Scheme 3).
methylidenecyclohexane-1,3-dione E which give rise
to adduct G, while the second pathway is the rear-
rangement E → G. Analogous schemes were proposed
for the reaction of 2-aminobenzimidazole with al-
dehydes and cyclohexane-1,3-dione in water under
microwave activation [21] and for the three-component
condensation of aldehydes with aromatic amines and
dimedone [22].
The formation of the same products in the two- and
three-component reactions led us to propose two pos-
sible ways of formation of 5,6,7,9-tetrahydropyrazolo-
[5,1-b]quinazolin-8(4H)-ones XIX. Following path a,
initially formed enaminoketone XVII reacts with alde-
hyde, and subsequent intramolecular cyclization yields
final product XIX. According to path b, the reaction of
aminopyrazole with aldehyde gives Schiff base XX,
and attack by the α-carbon atom of dimedone molecule
on the electron-deficient CH=N carbon atom in XX,
followed by closure of pyrimidine ring, leads to final
product XIX.
Unlike three-component condensations with form-
aldehyde [19], the dihydropyrimidine fragment in
Table 1. Product ratios in the reaction of aminopyrazole
Ib with 2-(trifluoroacetyl)dimedone (VII) under different
conditions
Solvent (catalyst) Temperature, °C Ratio XVI:XVIIa
Butanol (AcOH)
AcOH
118
118
020
020
020
1:4
2:1
a99:1a0
AcOH
b
Ethanol (AcOH)
–
The reaction of Schiff base XX with dimedone is
likely to involve intermediate formation of structure E
(Scheme 4) which can be converted into the second
intermediate G in two ways. The first of these consists
of decomposition of E into aminopyrazole I and 2-R2-
DMSO
1:9
a
According to the 1H NMR data, the major product was dimedone
formed as a result of decomposition of initial compound VII;
overall yield of XVI and XVIIa ~20%.
b
Dimedone was the only product.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

PETROV et al.
1394
Scheme 4.
O
R2
O
Ar
R1
+
NH2
O
Me
Me
Ar
N
NH
H
R1
F
R2
N
Ar
Me
Me
O
R1
N
N
NH
O
O
R2
N
NH
Ar
R1
NH2
O
Me
Me
XX
E
N
N
Me
Me
R2
O
G
G
XIXa
1H and 13C NMR spectra, and X-ray diffraction data.
The chemical shifts of carbon nuclei in the pyrimidine
ring and methyl group were compared with the data
reported by us previously [25–27] and those given in
[28] (Table 2). The 13C NMR spectra of VIIIc and
VIIId contained doublet signals in the region δC 146 –
147 ppm (1JCH = 188 Hz). Comparison with the data
for model pyrazolopyrimidines [25–28] possessing
N=C5H–C (δC 148.5–149 ppm) and N–C7H=C frag-
ments (δC 134.2–135 ppm) showed that molecules
VIIIc and VIIId possess an N=C5H–C fragment and
a cyclohexene ring fused at the C6–C7 bond of the pyr-
azolo[1,5-a]pyrimidine core. The structure of com-
pounds IXa–IXc and X–XIII unambiguously followed
from the chemical shifts of carbon nuclei in the pyri-
midine ring and methyl group and the corresponding
data for the N–C(CH3)=C and N=C(CH3)–C fragments
given in Table 2.
XIXa–XIXc does not undergo dehydrogenation during
the synthesis, regardless of the aldehyde nature (the
reactions were performed with both aliphatic and
aromatic aldehydes). We failed to effect oxidation of
compounds XIXa–XIXc according to procedures com-
monly used for analogous structures, such as bromina-
tion–dehydrobromination with bromine or N-bromo-
succinimide in acetic acid, treatment with sodium
nitrite in acetic acid or with tetrachloro-1,4-benzoqui-
none in THF, or carrying out the reaction in the pres-
ence of nitrobenzene. In all cases, either complex mix-
tures of products were obtained or the initial com-
pound remained unchanged. It should be noted that
5(3)-amino-3(5)-methyl-1H-pyrazole having no sub-
stituent in position 4 reacts with dimedone and alde-
hydes in boiling ethanol with high regioselectivity to
produce tricyclic compounds with different structure,
4,7,8,9-tetrahydro-2H-pyrazolo[3,4-b]quinolin-5(6H)-
ones [23]; here, the reaction centers in the initial pyra-
zole molecule are nitrogen atom in the exocyclic
amino group and C4. On the other hand, three-com-
ponent condensation of 5(3)-amino-3(5)-phenyl-1H-
pyrazole with a cyclic 1,3-diketone and aromatic alde-
hydes in ethanol at 20°C under ultrasonic activation
afforded 9-aryl-2-phenyl-4,5,6,7,8,9-hexahydropyra-
zolo[5,1-b]quinazolin-8-ones in good yields [24]. Mix-
tures of tricyclic dihydropyrimidine and dihydropyri-
dine derivatives were obtained by heating 5(3)-amino-
pyrazole with cyclic 1,3-diketones and aldehydes in
boiling ethanol, and the product ratio strongly depend-
ed on the structure of the dicarbonyl compound [20].
The other independent criterion for structural as-
signment of regioisomers X–XIII is the difference in
the coupling constants 5JHH between methylene protons
in the fused cycloalkane ring. The coupling constant
5JHH for the CH2–C=C–CH2 fragment in X and XI was
~1.5 Hz, whereas the corresponding coupling constant
for the CH2–C–C–CH2 fragment in regioisomers XII
and XIII is considerably smaller (no coupling was
observed).
The structure of compound IXa was also proved by
X-ray analysis of a single crystal (Fig. 1). The methyl
group in molecule IXa is attached to C5, and the cy-
clohexane fragment is fused to the pyrazolopyrimidine
core at the C5a–C9a bond. The heterocyclic fragment
The structure of the synthesized compounds was
determined on the basis of their elemental analyses,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

α-AMINO AZOLES IN THE SYNTHESIS OF HETEROCYCLES: VI.
1395
Table 2. Characteristic 13C chemical shifts of pyrazolo[1,5-a]pyrimidines [25–28] and compounds VIII–XVI
Fragment
δC, ppm (published data)
Carbon atom
δC, ppm (compound no.)
N=CH–C
148.5–149.0
134.2–135.0
148.0–149.0
17.0–17.6
C5
146.2–146.9 (VIII)
–
N–CH=C
C7
N–C(CH3)=C
N–C(CH3)=C
N=C(CH3)–C
N=C(CH3)–C
N=C(CF3)–C
N–C(CF3)=C
C9
142.0 (XIII)
8-CH3, 9-CH3
C5
14.1 (XII), 14.9 (XIII)
156.1 (IX), 158.2–159.0 (X, XI)
22.8 (IX), 25.5–26.7 (X, XI)
144.5 (XIV), 142.1 (XVI)
129.9 (XV)
a158.0–159.0a
24.5–25.5
5-CH3
C5
C9
145.2–146.0
131.5–134.5
a
If a strong electron-withdrawing substituent (e.g., CN group) is present in position 3, the chemical shift is ~163–165 ppm [27].
N1C2C3C3aN4C4aC8aC9N10 is almost planar: the largest
deviation from the mean-square plane is 0.041 Å (C3).
The cyclohexene ring adopts a distorted chair con-
formation with the C7 and C8 atoms deviating most
from planar structure (by –0.379 and 0.391 Å, respec-
tively). All formally single C–C, C–N, and N–N bonds
in the pyrazolopyrimidine system (Table 3) are appre-
ciably shorter than the corresponding standard bonds
(1.54, 1.47, and 1.45 Å, respectively [29]), indicating
essential delocalization of π and n electrons.
142.8(2)°]. The dimers form a three-dimensional net-
work through weaker C–H···π and C–H···H–C con-
tacts, the minimal C···C distances being 3.344(2) and
3.525(2) Å.
The position of the trifluoromethyl group in XIV–
XVI was unambiguously determined by comparing the
chemical shifts of carbon nuclei in the C–CF3 fragment
with those reported in [25, 30] for the N=C–CF3 and
N–C(CF3)=C fragments in pyrazolopyrimidine deriva-
tives (Table 2). Compounds XIV and XVI displayed in
the 13C NMR spectra quartet signals at δC 144.46 and
142.06 ppm, respectively, indicating that the trifluoro-
methyl group is attached to C5. The CF3 group in iso-
mer XV is located at C9, for the corresponding quartet
signal was observed in a stronger field (δC ~130 ppm).
Molecules IXa in crystal are linked to form cyclic
2
centrosymmetric dimers R2 (6) (Fig. 2) via shortened
C2–H · · · N10 contacts [C · · · N 3.238(2) Å, ∠CHN
C34
The structure of the condensation products of
aminopyrazoles Ia and Id with dimedone and benzal-
dehyde (XVIIIa) or aliphatic aldehydes XVIIIb and
C33
C32
C35
1
XVIIIc was assigned on the basis of their H NMR
spectra. The spectra contained multiplet signals from
aromatic protons, AB pattern from diastereotopic meth-
ylene protons, and signals from alkyl and NH groups
and 9-H. The NH proton appeared as a singlet at δ 9.5–
10 ppm (DMSO-d6), and its position was typical of di-
hydroazolopyrimidine structures having an –NHC=C–
fragment [31]. Therefore, compounds XIXa–XIXc
were identified as 4,5,6,7,8,9-hexahydropyrazolo-
[5,1-b]quinazolin-8-ones. Isomeric 5-R2-8,8-dimethyl-
3-phenyl-8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-
one XXI having an –NHC–C< fragment are charac-
terized by more upfield position of the NH signal (by
2–3 ppm) [31]. Unambiguous proof for the assumed
structure of XIXa–XIXc was obtained by analysis of
two-dimensional 1H NMR spectra which revealed cou-
pling between the NH proton and methylene protons
on C5 (δ 2.55 ppm). No such coupling is possible in
C36
C31
C3
N4
C51
C3a
C5
C5a
C2
O61
C6
C7
N10
C9a
N1
C9
C82
C8
C81
Fig. 1. Structure of the molecule of 5,8,8-trimethyl-3-phenyl-
6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-6-one (IXa)
according to the X-ray diffraction data; non-hydrogen atoms
are shown as thermal ellipsoids with a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

PETROV et al.
1396
Table 3. Bond lengths and bond angles in the molecule of 5,8,8-trimethyl-3-phenyl-6,7,8,9-tetrahydropyrazolo[1,5-a]quin-
azolin-6-one (IXa)
Bond
d, Å
Angle
ω, deg
Angle
ω, deg
N1–C2
N1–N10
C2–C3
C3–C3a
C3a–N4
C3a–N10
N4=C5
C5–C5a
C5a–C9a
C9a–N10
1.337(2)
1.366(1)
1.412(2)
1.396(2)
1.352(2)
1.397(2)
1.322(2)
1.448(2)
1.377(2)
1.362(2)
C2N1N10
C3aN4C5
N1N10C3a
N1N10C9a
C3aN10C9a
N1C2C3
C2C3C3a
N4C3aN10
N4C3aC3
102.9(1)
118.4(1)
112.9(1)
124.5(1)
122.6(1)
114.4(1)
103.8(1)
120.9(1)
133.2(1)
N10C3aC3
C9aC5aC5
C6C5aC9a
C5C5aC6
C5aC9aN10
N10C9aC9
C5aC9aC9
N4C5C5a
105.8(1)
119.4(1)
117.4(1)
123.2(1)
116.7(1)
117.0(1)
126.3(1)
122.0(1)
alternative structure XXI. In addition, no coupling was
observed between the NH proton and proton on the
carbon atom bearing the R2 substituent. The structure
of XIXb was also confirmed by the COLOC spectrum
which also allowed us to assign signals from quater-
nary carbon atoms in the 13C NMR spectrum. The
EXPERIMENTAL
The H and 13C NMR spectra were recorded at
22°C on a Bruker DPX-300 spectrometer with an op-
erating frequency of 300.13 and 75.47 MHz, respec-
tively. The chemical shifts were measured relative to
the residual proton and carbon signals of deuterated
solvents (CHCl3, δ 7.28 ppm; DMSO-d5, δ 2.50 ppm;
CDCl3, δC 76.90 ppm; DMSO-d6, δC 39.50 ppm). The
COLOC spectra were recorded using a pulse sequence
(Bruker software) optimized for a coupling constant
JCH of 8 Hz. Microwave-assisted reactions were per-
formed in a Lyumeks Minotavr-2 reactor at a power
of 200 W.
1
1
key H–13C correlations in the spectrum of compound
XIXb (DMSO-d6) were the following: NH
(δ 9.70 ppm)/C8a (δC 103.05 ppm), C3a (δC 34.12 ppm);
9-H (δ 5.30 ppm, t)/C8a (δC 103.05 ppm), C3a
(δC 134.12 ppm), C4a (δC 151.26 ppm); CH2 (2.20 ppm,
AB)/C8a (δC 103.05 ppm), C4a (δC 151.26 ppm).
To conclude, we have synthesized regioisomeric
tetrahydropyrazolo[1,5-a]quinazoline and tetrahydro-
pyrazolo[5,1-b]quinazoline derivatives by reactions of
5(3)-amino-4-arylpyrazoles with cyclic di- and tri-
ketones.
5,5-Dimethyl-2-trifluoroacetylcyclohexane-1,3-di-
one was synthesized according to the procedure re-
ported in [32], 2-acetylcyclohexanone was prepared as
C34
C35
C36
C33
C32
C31
C3
N4
H2A
C3a
C51
C2
C5
C5a
C9a
N10
N1
O61
C6
C81
C8
C9
C7
C82
2
Fig. 2. Centrosymmetric R2 (6) dimer formed by molecules of 5,8,8-trimethyl-3-phenyl-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazo-
lin-6-one (IXa) in crystal.
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α-AMINO AZOLES IN THE SYNTHESIS OF HETEROCYCLES: VI.
1397
described in [33], and 2-trifluoroacetylcyclohexanone
was obtained according to [34].
3-(4-Chlorophenyl)-2,8,8-trimethyl-6,7,8,9-tetra-
hydropyrazolo[1,5-a]quinazolin-6-one (VIIId). Each
of the reactants, 0.4 mmol of aminopyrazole Id,
0.4 mmol of dimedone, and 2.4 mmol of triethyl ortho-
formate, was applied to 1.5 cm3 of silica gel, the sup-
ported reactants were mixed together, and the mixture
was irradiated in a microwave oven over a period of
10 min at a power of 180 W. Two drops of acetic acid
were added to the mixture, and MW irradiation was
continued for 7 min more. The mixture was extracted
with 15 ml of methylene chloride, the solvent was
removed, and the residue was recrystallized. Yield
5,5-Dimethyl-2-[(3-methyl-4-phenyl-1H-pyrazol-
5-ylamino)methylidene]cyclohexane-1,3-dione (A).
A mixture of 5 mmol of 3(5)-methyl-4-phenyl-1H-pyr-
azol-5(3)amine and 5 mmol of 2-ethoxymethylidene-
5,5-dimethylcyclohexane-1,3-dione (II) in diethyl
ether was left to stand overnight. The precipitate was
filtered off, washed with diethyl ether, and dried under
reduced pressure (the product underwent cyclization to
1
VIIIa on heating). Yield 75%. H NMR spectrum
(DMSO-d6), δ, ppm: 0.96 s (6H, CH3), 2.27 s (3H,
CH3), 2.30 s (2H, CH2), 2.34 s (2H, CH2), 7.33–7.50 m
(5H, Ph), 8.65 d (1H, CH, J = 13.1 Hz), 12.76 d (1H,
NH, J = 13.1 Hz), 12.82 br.s (1H, NH). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 9.96 (3′-CH3), 28.02 (CH3),
30.67 [C(CH3)2], 50.61 and 50.73 (CH2), 108.31 (C4′),
108.38 (C=CH), 129.93 (Cp), 128.37 (Cm), 129.37
(Co), 130.67 (Ci), 138.10 (C3′), 144.23, (C5′), 148.70
(CH=NH), 194.93 and 199.40 (C=O). Found, %:
C 70.41; H 6.69. C19H21N3O2. Calculated, %: C 70.57;
H 6.55.
1
45%, mp 211–212°C (from butanol). H NMR spec-
trum (CDCl3), δ, ppm: 1.22 s (6H, CH3), 2.57 s (2H,
CH2), 2.64 s (3H, CH3), 3.34 s (2H, CH2), 7.42–7.64 m
(4H, C6H4), 8.94 s (CH). 13C NMR spectrum (CDCl3),
δC, ppm: 14.33 (CH3), 28.37 (8-CH3), 32.56 (C8),
37.07 (C9), 50.73 (C7), 110.59 (C3), 113.10 (C5a),
128.64 and 129.91 (Co, Cm), 129.58 (Cp), 132.55 (Ci),
146.13 (C3a), 146.91 (C5), 151.56 (C9a), 155.49 (C2),
194.48 (C6). Found, %: C 67.07; H 5.41. C19H18ClN3O.
Calculated, %: C 67.16; H 5.34.
6,7,8,9-Tetrahydropyrazolo[1,5-a]quinazolin-6-
ones IXa–IXd (general procedure). a. A mixture of
0.4 mmol of aminopyrazole Ia and 0.4 mmol of
2-acetyldimedone (III) in 0.5 ml of acetic acid was
heated for 3 h under reflux. The solvent was removed
under reduced pressure, and the residue was washed
with water and recrystallized from butanol.
2-{1-[4-(4-Chlorophenyl)-3-methyl-1H-pyrazol-
5-yl)imino]ethyl}-3-hydroxy-5,5-dimethylcyclohex-
2-en-1-one (B). A mixture of aminopyrazole Ic and
2-acetyldimedone (III) in DMSO-d6 was kept for
1
20 days in an NMR ampule. H NMR spectrum, δ,
ppm: 1.02 s (6H, CH3), 2.32 s (3H, CH3), 2.27 br.s
(2H, CH2), 2.36 br.s (2H, CH2), 2.45 s (3H, CH3),
7.24 d and 7.30 d (2H each, Harom), 12.87 br.s (1H,
NH), 14.84 s (1H, OH).
b. A solution of 0.4 mmol of aminopyrazole Ib and
0.4 mmol of 2-acetyldimedone (III) in 1.5 ml of meth-
anol was heated for 4 h under reflux. The mixture was
cooled, and the precipitate was filtered off and washed
with methanol.
2,8,8-Trimethyl-3-phenyl-8,9-dihydro-7H-pyra-
zolo[1,5-a]quinazolin-6-one (VIIIc). a. A mixture of
aminopyrazole Id and 2-ethoxymethylidene-5,5-di-
methylcyclohexane-1,3-dione (II) was stirred for 5 h at
room temperature and was then heated for 30 min
under reflux. The precipitate was filtered off and re-
crystallized. Yield 80%, mp 196°C (from ethanol).
c. A solution of 0.4 mmol of aminopyrazole Ia, Ib,
or Id and 0.4 mmol of triketone III in 1.5 ml of meth-
anol was stirred for 5 h at room temperature, and the
mixture was left overnight. The precipitate was filtered
off and washed with methanol.
b. Compound A was heated at 100°C over a period
of 10 min. Yield 100%. 1H NMR spectrum (DMSO-d6),
δ, ppm: 1.15 s (6H, CH3), 2.57 s (2H, CH2), 2.60 s
(3H, CH3), 3.35 s (2H, CH2), 7.31–7.73 m (5H, Ph),
8.80 s (CH). 13C NMR spectrum (DMSO-d6), δC, ppm:
14.32 (CH3); 27.82 (8-CH3); 32.24 and 36.37 (C8, C9);
50.09 (C7); 110.38 (C3); 112.90 (C5a); 126.53, 128.34,
128.55, 131.11 (Carom); 145.63 (C3a); 146.25 (C5);
152.28 (C9a); 154.88 (C2); 194.48 (C=O). Found, %:
C 74.53; H 6.37. C19H19N3O. Calculated, %: C 74.73;
H 6.27.
d. A mixture of 0.5 mmol of aminopyrazole Id,
0.5 mmol of dimedone, and 0.5 mmol of triethyl ortho-
acetate in 1.5 ml of butanol was heated for 5 h under
reflux. Acetic acid, 0.3 ml, was then added, and the
mixture was heated for 6 h under reflux. The solvent
was removed under reduced pressure, and the residue
was washed with water and recrystallized from butyl
alcohol.
5,8,8-Trimethyl-3-phenyl-6,7,8,9-tetrahydropyr-
azolo[1,5-a]quinazolin-6-one (IXa). Yield 76% (a),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

PETROV et al.
1398
1
mp 172–173°C (from butanol). H NMR spectrum
(DMSO-d6), δ, ppm: 1.10 s (6H, 8-CH3), 2.54 s (2H,
9-H), 2.78 s (3H, 5-CH3), 3.32 s (2H, 7-H), 7.24–
8.15 m (5H, C6H5), 8.85 s (1H, 2-H). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 26.48 (5-CH3), 27.74
(8-CH3), 31.66 (C8), 37.29 (C9), 51.88 (C7), 109.47
(C3), 112.63 (C5a), 125.68, and 128.61 (Co, Cm), 126.19
(Cp), 131.44 (Ci), 142.76 (C3a), 145.31 (C2), 153.44
(C9a), 158.01 (C5), 195.67 (C=O). Found, %: C 74.62;
H 6.37. C19H19N3O. Calculated, %: C 74.73; H 6.27.
Yield 78% (a), mp 204–205°C (from ethanol). 1H NMR
spectrum (CDCl3), δ, ppm: 1.23 s (8-CH3), 2.60 s (2H,
9-H), 2.64 s (3H, CH3), 2.88 s (3H, CH3), 3.37 s (2H,
7-H), 7.44 d (2H, m-H), 7.69 d (2H, o-H). 13C NMR
spectrum (CDCl3, without decoupling from protons),
δC, ppm: 14.50 q (2-CH3), 26.66 q (5-CH3), 28.26 q.m
(CH3), 31.97 m (C8), 38.09 t.m (C9), 52.69 t.m (C7),
108.93 m (C3), 112.71 s (C5a), 128.58 d.d and
130.05 d.d (Co, Cm), 129.87 t (Cp), 132.24 t.t (Ci),
144.61 s (C3a), 152.00 t (C9a), 155.29 q (C2), 159.04 q
(C5), 195.52 t (C=O). Found, %: C 67.81; H 5.79.
C20H20ClN3O. Calculated, %: C 67.89; H 5.70.
X-Ray diffraction data for compound IXa.
A 0.40×0.20×0.20-mm single crystal of IXa was ex-
amined. C19H19N3O. M 305.37. Triclinic crystal sys-
tem, space group P-1; unit cell parameters (120 K): a =
6.1618(4), b = 10.1137(6), c = 13.5510(8) Å; α =
110.901(5), β = 93.235(5), γ = 96.122(5)°; V =
3-(4-Chlorophenyl)-5-methyl-7,8-dihydro-6H-cy-
clopenta[e]pyrazolo[1,5-a]pyrimidine (X). A mixture
of 2 mmol of aminopyrazole Ib and 2 mmol of
2-acetylcyclopentanone (IV) in 3 ml of ethanol con-
taining a catalytic amount of trifluoroacetic acid was
kept for 15 h. The precipitate was filtered off and re-
crystallized. Yield 90%, purity >97%, mp 192–193°C
780.34(9) Å3; Z = 2 (Z′ = 1); F(000) = 324; dcalc
=
1.300 g/cm3; μ = 0.082 mm–1. The unit cell parameters
and intensities of 14449 reflections were measured on
a SMART 1000 CCD diffractometer at 120 K (MoKα
irradiation, graphite monochromator, ω-scanning,
2θmax = 58°). The structure was solved by the direct
method and was refined by the least-squares procedure
in full-matrix anisotropic approximation with respect
to F2hkl. The positions of hydrogen atoms were calcu-
lated from geometry considerations and were refined
in isotropic approximation using the riding model. The
final divergence factors were R1 = 0.0472 [3130 inde-
pendent reflections with I > 2σ(I)] and wR2 = 0.1106
(all 4157 independent reflections). All calculations
were performed using SHELXTL PLUS (Version 5.10)
[35]. The complete set of crystallographic data for
compound IXa (coordinates of atoms, bond lengths,
bond angles, and anisotropic temperature factors) was
deposited to the Cambridge Crystallographic Data
Centre (entry no. CCDC 706950).
1
(from acetonitrile). H NMR spectrum (CDCl3), δ,
ppm: 2.28 m (2H, CH2); 2.55 s (3H, CH3); 2.96 m (2H,
CH2); 3.35 m (2H, CH2); 7.24 t, 7.44 t, and 8.11 d (5H,
H
arom); 8.37 s (1H, CH=). 13C NMR spectrum (CDCl3),
δC, ppm: 21.58 (C7), 22.82 (CH3), 29.37 and 29.51 (C6,
C8), 108.89 (C3), 121.95 (C5a), 125.57 (Cp), 125.78 and
128.43 (Cm, Co), 132.51 (Ci), 141.76 (C2), 144.84 (C3a),
148.19 (C8a), 156.14 (C5). Found, %: C 67.49; H 5.21.
C16H14ClN3. Calculated, %: C 67.72; H 4.97.
3-(4-Chlorophenyl)-2,5-dimethyl-6,7,8,9-tetra-
hydropyrazolo[1,5-a]quinazoline (XIc) and
3-(4-chlorophenyl)-2,9-dimethyl-5,6,7,8-tetrahydro-
pyrazolo[5,1-b]quinazoline (XIIIc). A mixture of
1.3 mmol of aminopyrazole Id and 1.3 mmol of
2-acetylcyclohexanone (V) in 3 ml of ethanol contain-
ing a catalytic amount of trifluoroacetic acid was
heated for 15 h under reflux. The precipitate was
filtered off and recrystallized from ethanol. Yield of
isomer mixture XIc/XIIIc 70%. Found, %: 69.21;
H 5.95. C18H18Cl N3. Calculated, %: C 69.34; H 5.82.
3-(4-Chlorophenyl)-5,8,8-trimethyl-6,7,8,9-tetra-
hydropyrazolo[1,5-a]quinazolin-6-one (IXb). Yield
82%, mp 193–194°C (from ethanol). H NMR spec-
1
1
trum (CDCl3), δ, ppm: 1.21 s (6H, 8-CH3), 2.59 s (2H,
9-H), 2.92 s (3H, 5-CH3), 3.34 s (2H, 7-H), 7.37 d (2H,
m-H), 8.00 d (2H, o-H), 8.44 s (2-H). 13C NMR spec-
trum (CDCl3), δC, ppm: 26.71 (5-CH3), 28.23 (8-CH3),
31.92 (C8), 37.99 (C9), 52.57 (C7), 109.65 (C3), 113.02
(C5a), 127.15 and 128.65 (Co, Cm), 129.83 (Cp), 131.87
(Ci), 143.35 (C3a), 144.77 (C2), 152.75 (C9a), 159.02
(C5), 195.46 (C=O). Found, %: C 67.09; H 5.40.
C19H18ClN3O. Calculated, %: C 67.16; H 5.34.
Major isomer XIc. H NMR spectrum (CDCl3), δ,
ppm: 1.89 m (4H, CH2), 2.50 s (CH3), 2.62 s (2-CH3),
2.70 t.d (2H, 6-H, J = 5.8, 1.5 Hz), 3.13 t.d (2H, 9-H,
J = 5.8, 1.5 Hz), 7.42 d and 7.70 d (2H each, Harom).
13C NMR spectrum (CDCl3), δC, ppm: 14.22 (2-CH3),
20.78 (C7), 21.94 (C8), 22.80 (CH3), 24.12 and 24.34
(C6, C9), 106.48 (C3), 115.62 (C5a), 128.35 and 129.63
(Cm, Co), 131.19 (Cp), 131.42 (Ci), 142.46 (C9a), 144.15
(C3a), 150.26 (C2), 158.21 (C5).
3-(4-Chlorophenyl)-2,5,8,8-tetramethyl-6,7,8,9-
Minor isomer XIIIc. 1H NMR spectrum (CDCl3), δ,
tetrahydropyrazolo[1,5-a]quinazolin-6-one (IXd).
ppm: 1.95 s (4H, CH2), 2.62 (2-CH3), 2.73 s (CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

α-AMINO AZOLES IN THE SYNTHESIS OF HETEROCYCLES: VI.
1399
2.77 s (2H, 8-H), 2.96 m (2H, 5-H), 7.42 d and 7.70 d
(2H each, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 12.73 (9-CH3), 14.30 (2-CH3), 22.27 and
22.57 (C6, C7), 24.74 (C8), 33.66 (C5), 105.83
(C3), 114.93 (C8a), 128.35 and 129.63 (Cm, Co), 131.08
(Cp), 131.49 (Ci), 142.01 (C9), 144.42 (C3a), 150.72
(C2), 158.77 (C4a).
127.60 d.d and 128.89 d.d (Co, Cm), 129.20 t (Cp),
131.69 t.t (Ci), 140.96 d (C3a, J = 6.0 Hz), 142.06 q
(5-CF3, J = 36.9 Hz), 146.46 d (C2, J = 189.0 Hz),
156.10 s (C5a), 192.29 t (C=O, J = 6.2 Hz). Found, %:
C 57.83; H 4.01. C19H15ClF3N3O. Calculated, %:
C 57.95; H 3.84.
3-[4-(4-Chlorophenyl)-1H-pyrazol-3-ylamino]-
5,5-dimethylcyclohex-2-en-1-one (XVIIa) was isolat-
ed from mixture XVI/XVIIa. Yield 10%, mp 262–
263°C (from ethanol). Compound XVIIa was also
synthesized by independent method according to the
procedure described in [23]. Yield 80%, mp 262–
5-Trifluoromethyl-3-phenyl-6,7,8,9-tetrahydro-
pyrazolo[1,5-a]quinazoline (XIV). 1H NMR spectrum
(CDCl3; in a mixture with XV), δ, ppm: 1.94 m,
2.07 m, 2.99 m, and 3.29 m (8H, CH2); 7.42–8.04 m
(5H, Ph); 8.52 (1H, 2-H). 13C NMR spectrum (CDCl3),
1
4
δC, ppm: 21.31 and 22.01 (C7, C8); 22.65 q (C6, JCF
=
263°C (from ethanol). H NMR spectrum (DMSO-d6–
1.5 Hz); 24.68 (C9); 111.08 (C3); 114.40 (C5a);
CCl4, 1:2), δ, ppm: 1.05 s (6H, CH3), 1.97 s (2H,
CH2), 2.33 s (2H, CH2), 4.95 s (1H, CH=), 7.28–
7.48 m (4H, Harom), 7.94 br.s (1H, NH), 12.60 br.s
(1H, NH). Found, %: 64.45; H 5.96. C17H18Cl N3O.
Calculated, %: C 64.66; H 5.75.
1
121.23 q (5-CF3, JCF = 276.2 Hz); 127.22, 128.60,
129.94, 131.75 (C6H5); 141.98 (C2); 141.98 (C3a);
144.46 q (C5, 2JCF = 33.5 Hz); 146.67 (C9a).
9-Trifluoromethyl-3-phenyl-5,6,7,8-tetrahydro-
pyrazolo[5,1-b]quinazoline (XV). A solution of
5.5 mmol of 2-(trifluoroacetyl)cyclohexanone was
mixed at 15°C with 5.0 mmol of aminopyrazole Ia.
The mixture was kept for 24 h and poured into water,
and the precipitate was filtered off and recrystallized.
3-[4-(4-Chlorophenyl)-5-methyl-1H-pyrazol-3-
ylamino]-5,5-dimethylcyclohex-2-en-1-one (XVIIb).
A solution of 2 mmol of aminopyrazole Id and 2 mmol
of dimedone in 10 ml of ethanol was heated for 1 h
under reflux. The mixture was cooled, and the precip-
itate was filtered off and recrystallized [23]. Yield
1
Yield 89%, mp 188°C (from ethanol). H NMR spec-
1
78%, mp 270–271°C (from ethanol). H NMR spec-
trum (CDCl3), δ, ppm: 1.95 m and 3.07 m (8H, CH2),
7.40–8.00 m (5H, Ph), 8.40 s (1H, 2-H). 13C NMR
spectrum (CDCl3), δC, ppm: 21.31, 22.85 (C6, C7);
trum (DMSO-d6–CCl4, 1:2), δ, ppm: 1.00 s (6H, CH3),
1.93 s (2H, CH2), 2.24 s (2H, CH2), 2.32 s (3H, CH3),
5.08 s (1H, CH=), 7.26–7.34 m (4H, Harom), 8.30 br.s
(1H, NH), 12.48 br.s (1H, NH). Found, %: C 65.34;
H 6.31. C18H20ClN3O. Calculated, %: C 65.55; H 6.11.
4
24.46 q (C8, JCF = 4.5 Hz), 34.37 (C5), 108.41 (C3),
1
118.82 (C8a), 121.03 q (9-CF3, JCF = 278.2 Hz),
129.86 q (C9, 2JCF = 35.5 Hz); 127.22, 128.60, 129.94,
131.75 (C6H5); 141.03 (C2); 143.56 (C3a); 160.21 (C4a).
Found, %: C 57.93; H 3.90. C17H13Cl F3N3. Calculated,
%: C 58.05; H 3.73.
4,5,6,7,8,9-Hexahydropyrazolo[5,1-b]quinazolin-
8-ones XIXa–XIXc (general procedure). a. A mixture
of 0.4 mmol of aminopyrazole Ia or Id, 0.4 mmol of
aldehyde XVIIIa–XVIIIc, and 0.45 mmol of dime-
done in 0.8 ml of acetic acid was heated for 5 h under
reflux. The solvent was removed under reduced pres-
sure, and the residue was washed with water and re-
crystallized.
3-(4-Chlorophenyl)-8,8-dimethyl-5-trifluoro-
methyl-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazo-
lin-6-one (XVI). A solution of 0.65 mmol of amino-
pyrazole Ib in 0.5 ml of acetic acid was heated to the
boiling point, 2-(trifluoroacetyl)dimedone (VII) was
slowly added, and the mixture was heated for 3 h
under reflux. The solvent was removed under reduced
pressure, and the residue (a mixture of compounds
XVI and XVIIa) was washed with water, dried, and
recrystallized. Yield of XVI 28%, mp 256–259°C
b. A mixture of 0.7 mmol of aminopyrazole I and
0.7 mmol of aldehyde XVIII in 1.5 ml of ethanol
containing one drop of acetic acid was heated for 3 h
under reflux. The solvent was removed under reduced
pressure, 0.75 mmol of dimedone and 1 ml of acetic
acid were added, and the mixture was heated for 5 h
under reflux. The solvent was removed under reduced
pressure, and the residue was washed with water and
recrystallized.
1
(from ethanol). H NMR spectrum (DMSO-d6–CCl4,
1:2), δ, ppm: 1.15 s (6H, CH3), 2.68 s (2H, CH2), 3.49 s
(2H, CH2), 7.53 d and 8.14 d (2H each, Harom), 9.00 s
(1H, CH=). 13C NMR spectrum (DMSO-d6; without
decoupling from protons), δC, ppm: 27.75 q (CH3),
31.93 s (C8), 39.22 t (C9), 51.55 t (C7), 111.61 s
(C9a), 112.21 d.t (C3), 120.59 q (CF3, J = 275.2 Hz),
c. A mixture of 0.4 mmol of 3-[3-(4-chlorophenyl)-
2-methyl-1H-pyrazol-5-ylamino]-5,5-dimethyl-2-cy-
clohex-2-en-1-one (XVIIb) and 0.4 mmol of benzalde-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

PETROV et al.
1400
hyde (XVIIIa) in 0.8 ml of acetic acid was heated
under reflux. The solvent was removed under reduced
pressure, and the residue was washed with water and
recrystallized.
AB system, J = 16.3 Hz), 2.49 and 2.53 (2H, CH2, AB
system, J = 16.7 Hz), 5.13 d (1H, CH, J = 1.5 Hz),
7.20–7.42 m (6H, CH, Harom), 9.55 s (1H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 15.92 (CH3),
21.16 (CH3), 26.47 (CH3), 29.13 (CH3), 31.74 (C6),
35.13 [CH(CH3)2], 39.50 (C7), 49.95 (C5), 58.60 (C9),
104.10 and 104.19 (C3, C8a), 125.73 (Cp), 126.87 (Co),
128.65 (Cm), 131.78 (Ci), 134.42 (C3a), 137.45 (C2),
151.30 (C4a), 193.05 (C8). Found, %: C 75.01; H 7.62.
C21H25N3O. Calculated, %: C 75.19; H 7.51.
3-(4-Chlorophenyl)-2,6,6-trimethyl-9-phenyl-
4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazolin-8-
one (XIXa). Yield 56%, mp 291–292°C (from buta-
1
nol). H NMR spectrum (DMSO-d6–CCl4, 1:2), δ,
ppm: 0.91 s (3H, CH3), 1.02 s (3H, CH3), 2.05 s
(3H, CH3), 2.04 and 2.20 (2H, CH2, AB system, J =
16.0 Hz), 2.55 s (2H, CH2), 6.10 s (1H, CH), 7.18–
REFERENCES
13
7.47 m (9H, Harom), 10.00 s (1H, NH). C NMR spec-
trum (DMSO-d6), δC, ppm: 12.70 (2-CH3); 26.66,
28.78 (CH3); 32.01 (C6), 39.50 (C7), 49.79 (C5), 57.33
(C9), 101.82 (C8a), 105.48 (C3); 126.79, 128.07,
128.46, 130.96 (Co, Cm); 127.16, 130.55, 130.84,
134.30 (Cp, Ci); 142.95 (C3a), 145.59 (C2), 149.63
(C4a), 192.46 (C8). Found, %: C 77.88; H 6.47.
C24H23N3O. Calculated, %: C 78.02; H 6.27.
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1
60%, mp 129–130°C (from CCl4). H NMR spectrum,
δ, ppm: in CDCl3: 0.68 t (3H, CH3), 1.14 s and 1.17 s
(3H each, CH3), 1.98 m and 2.18 m (2H, CH2), 2.32 s
(2H, CH2), 2.42 and 2.45 (2H, CH2, AB system, J =
16.7 Hz), 5.57 t (1H, CH, J = 3.8 Hz), 6.76 br.s (1H,
NH), 7.36–7.43 m (5H, Harom), 7.61 s (1H, CH); in
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and 1.95 m (2H, CH2), 2.16 and 2.25 (2H, CH2, AB
system, J = 16.0 Hz), 2.54 s (2H, CH2), 5.30 m (1H,
CH), 7.24–7.46 m (5H, Harom), 7.65 s (1H, CH),
9.70 br.s (1H, NH). 13C NMR spectrum, δC, ppm: in
CDCl3: 7.75 (CH3CH2), 27.11 (CH3CH2), 27.16 (CH3),
29.11 (CH3), 32.29 (C6), 41.13 (C7), 50.26 (C5), 55.31
(C9), 104.65 and 105.07 (C8a, C3), 126.18 (Cp), 126.75
(Co), 128.70 (Cm), 131.87 (Ci), 133.80 (C3a), 137.90
(C2), 149.60 (C4a), 194.14 (C8); in DMSO-d6: 7.61
(CH3CH2), 26.81 (CH3CH2), 26.87 (CH3), 28.94
(CH3), 31.93 (C6), the C7 signal is overlapped by the
solvent, 50.05 (C5), 54.74 (C9), 103.05 (C8a), 104.07
(C3), 125.85 (Cp), 126.94 (Co), 128.74 (Cm), 131.78
(Ci), 134.12 (C3a), 138.10 (C2), 151.26 (C4a), 193.274
(C8). Found, %: C 74.58; H 7.40. C20H23 N3O. Calcu-
lated, %: C 74.74; H 7.21.
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1
Yield 70%, mp 279–280°C (from ethanol). H NMR
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

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