Study of regioselectivity of reactions between 3(5)-aminopyrazoles and 2-acetylcycloalkanones

Article abstract of DOI:10.1134/S1070428012080131

Regioselectivity was examined of reactions between nine 3(5)-aminopyrazoles and 2-acetylcyclopentanone and 2-acetylcyclohexanone under various conditions. A series of cyclopenta[e]pyrazolo-[1,5-a]pyrimidines was obtained. The highest regioselectivity of the reaction was observed in alcohol at 20°C in the presence of a catalytic quantity of trifl uoroacetic acid. The regiostructure of compounds was established by ₁H and ¹³C NMR spectroscopy. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012080131

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 8, pp. 1111−1120. © Pleiades Publishing, Ltd., 2012.
Original English Text © A.A. Petrov, A.N. Kasatochkin, E.E. Emelina, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 8, pp. 1113−1121.
Study of Regioselectivity of Reactions
between 3(5)-Aminopyrazoles
and 2-Acetylcycloalkanones
A. A. Petrov, A. N. Kasatochkin, and E. E. Emelina
St. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: aap47@hotmail.ru
Received March 28, 2012
Abstract—Regioselectivitywasexaminedofreactionsbetweennine3(5)-aminopyrazolesand2-acetylcyclopentanone
and 2-acetylcyclohexanone under various conditions. A series of cyclopenta[e]pyrazolo-[1,5-a]pyrimidines was
obtained. The highest regioselectivity of the reaction was observed in alcohol at 20°С in the presence of a catalytic
quantity of trifluoroacetic acid. The regiostructure of compounds was established by 1Н and 13С NMR spectroscopy.
DOI: 10.1134/S1070428012080131
cyclohexane fragment to the pyrazolopyrimidine frame
appears to be practically important for the synthesis of
new biologically active compounds [21–23].
Derivatives of pyrazolo[1,5-a]pyrimidines, purine
analogs, are an important class of fused heterocyclic com-
pounds exhibiting a wide range of physiological activity
depending on the nature and the position of substituents
in the molecule [1]. Pyrazolo[1,5-a]pyrimidines are
a privileged structure, among their derivatives substances
have been found exhibiting anxiolytic activity [2], they
are inhibitors of tyrosine kinase [3], antagonists of sero-
tonin receptor 5-HT3 [4], neuropeptide Y1 receptor [5],
cyclin-dependent kinase 1, 2, and 9 [6]. Several efficient
drugs are known of the depressant and hypnotic action
(zaleplon [7], indiplon [8], ocynaplon [9]).
In the synthesis of substituted pyrazolo[1,5-a]
pyrimidines several isomeric products may form as
a result of the attack of the nucleophilic sites of the
3(5)-aminopyrazole (NH2, N1) at several electrophilic
centers of polyfunctional compounds.
In the present study we investigated the regioselectivity
of the reaction between 3(5)-aminopyrazoles Ia–Ii and
2-acetylcycloalcanones containing five-and six-mem-
bered rings (Scheme 1).
In the last two decades various methods of synthesis
were published of pyrazolo-[1,5-a]pyrimidine deriva-
tives, the principal among which was the two-component
cyclocondensation of 5(3)-aminopyrazoles with 1,3-di-
electrophilic reagents like 1,3-dicarbonyl compounds,
α,β-unsaturated carbonyl compounds, alkoxymethylene-
1,3-dicarbonyl compounds, β-enaminoketones, acetylene
ketones [10–13]. Among the applied procedures multi-
component reactions, reactions without solvents, reac-
tions with nonclassic activation (microwave, ultrasound)
should be mentioned [14, 15]. The use of cyclic reagents
provides a possibility to obtain fused pyrazolo[1,5-a]
pyrimidines [16–24]. The development of a method
permitting the introduction of the fused cyclopentane or
The reactions were carried out under various condi-
tions: at the room or lower temperature in alcohol using as
catalyst trifluoroacetic acid (procedures а, b), in tradition
way by boiling in butanol and acetic acid (procedure c),
by fusion without solvent (procedure d), at microwave
activation (procedure e), and also in dimethyl sulfoxide
(procedure f) (see EXPERIMENTAL). The yields of
products were sufficiently high in all cases (74–92%),
the regioisomers content in the reaction mixture was
1
monitored by Н NMR spectroscopy; therewith the
spectra showed the practical absence of impurities (Table
1). The conclusions on the regiostructure of the reaction
products were done based on the analysis of the data of
1Н and 13С NMR spectra.
1111

PETROV et al.
1112
Scheme 1.
R2
R2
R2
O
N
O
N
R1
R1
NH2
R1
+
+
N
N
N
N
(CH2)n
(CH2)n
HN
N
(CH2)n
IVа_IVi, VIа_VIh
Iа_Ii
II, III
Vb_Vi, VIIа_VIIh
I, IV–VII, R1 = Me, R2 = H (a); R1 = 4-MeC6H4, R2 = H (b); R1 = H, R2 = CN (c), Ph (d), 4-ClC6H4 (e), 4-MeOC6H4 (f);
R1 = Me, R2 =Ph (g), 4-MeOC6H4 (h), 2-MeOC6H4 (i). n = 1 (II, IV, V), 2 (III, VI, VII).
С5–С6 (VIIа–VIIi), and the opposite effect of the reac-
tion conditions on the regioisomers ratio is observed: The
highest yields of compound VId is obtained in the reac-
tion proceeding at higher temperature (60–67%) (Table
1). The application of DMSO as a solvent changes the
regioselectivity of the reaction leading the a considerable
increase of the compound VIId fraction (Table 1). Simi-
lar increase in the fraction of the regioisomer containing
a cycloalkane ring fused at the С5–С6 bond we observed
at the use of 2-trifluoroacetylcycloalkanone as dielec-
trophile. This fact is related to the change in the ratio of
the intermediate hydroxy forms at prolonged keeping the
solution in DMSO [18].
As seen from the data of Table 1 the 3(5)-amino-4-
phenylpyrazole reacts with 2-acetylcyclopentanone with
a high regioselectivity. The highest regioselectivity was
observed in the reaction carried out in alcohol at low
temperature in the presence of a catalytic amount of
trifluoroacetic acid. In the reaction proceeding at a high
temperature (boiling in butanol or acetic acid, fusion,
microwave activation) the relative fraction of minor
product Vd grows. The nature of the substituent in the
pyrazole ring also somewhat affects the ratio of the reac-
tion products: The fraction of compound IV is maximum
for pyrazoles containing a methyl group in the position 5
(3) or a p-methoxyphenyl group in the position 4 (Table
2). We succeeded to isolate the prevailing isomers IVc–
IVg, IVi by recrystallization from DMF.
The application of MW activation significantly ac-
celerated the process but did not improve the selectivity of
the reaction as compared with the boiling of the reagents
in butanol (Table 1). In Table 2 the data are presented on
the effect of the structure of 3(5)-aminopyrazoles Iа–Ih
on the regioisomers ratio: The contcnt of reaction prod-
At the same time in the reaction of 3(5)-amino-4-
phenylpyrazole with 2-acetylcyclohexanone always
a mixture is obtained of pyrazolopyrimidines fused to
a cyclohexane ring at the bonds С6=С7 (VIа–VIi) and
Table 1. The ratio of products IVd–Vd of reaction of 3(5)-amino-4-phenylpyrazole (Id) with 2-acetylcyclopentanone and prod-
ucts VId–VIId of reaction with 2-acetylcyclohexanone
Ratio of
Ratio of
Reaction conditions
Overall yield, %
86
Overall yield, %
–
(IVd)–(Vd), %а
(VId)–(VIId), %а
–20°С, C2H5OH, cat CF3COOH, 3 days
95 : 5
–
0°С, CH3OH, cat CF3COOH, 3 days
20°С, C2H5OH, cat CF3COOH, 1 days
120°С, CH3COOH, 3 h
94 : 6
93 : 7
92
88
80
86
77
82
88
44:56
44:56
67:33
60:40
62:38
64:36
32:68
90
90
82
76
80
76
86
91 : 9
120°С, BuOH, 3 h
85 : 15
86 : 14
86 : 14
81 : 19
Fusion, 160°С, 2 min
MW activation, 800 W, 2 min
20°С, DMSO, 8 days
а The relative content of regioisomers was estimated from 1Н NMR spectra based on the intensity of the methyl and methylene protons.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

STUDY OF REGIOSELECTIVITY OF REACTIONS BETWEEN 3(5)-AMINOPYRAZOLES
1113
Table 2. The ratio of obtained regioisomers (IVа–IVi)–(Vа–Vi) and (VIа–VIi)–(VIIа–VIIi) in reactions of 3(5)-aminopyrazoles
Iа–Ii and 2-acetylcycloalkanones II, III
2-Acetylcyclopentanone (II)
2-Acetylcyclohexanone (III)
C2H5OH,
Fusion,
160°С
C2H5OH, CF3COOH,а
Fusion,
160°С
Amino-
pyrazole
no.
CF3COOH,а 20°С
20°С
Yield, %c
Yield, %c
Ratio
(IV)–(V), %b
Ratio
(IV)–(V), % b
Ratio
(VI)–(VII), % b
Ratio
(VI)–(VII), % b
Ia
Ib
Ic
Id
Ie
If
100 : 0
88 : 12
84 : 16
93 : 7
82
100 : 0 d
87 : 13
87 : 13
86 : 14
85 : 15
86 : 14
87 : 13
85 : 15
83 : 17
35 : 65
30 : 70
33 : 67
44 : 56
38 : 62
39 : 61
44 : 56
36 : 64
–
74
78
83
85
85
82
82
80
–
48 : 52
40 : 60
46 : 54
62 : 38
49 : 51
50 : 50
50 : 50
58 : 42
–
74
88 (38)
90 (44)
90 (52)
84 (54)
82 (50)
86
91 : 9
93 : 7
Ig
Ih
93 : 7
>99 : 1
95 : 5
Ii
82 (50)
а Catalyst.
b The relative content of regioisomers was estimated from 1Н NMR spectra based on the intensity of the methyl and methylene protons..
c Yield of regioisomers mixture. The yield of prevailing isomer after recrystallization from DMF is given in parentheses.
d Our own and published data [17].
was detected by high-resolution mass spectrometry: In
a solution in DMSO of a mixture of aminopyrazole Id
and 2-acetylcyclopentanone II after 3 days masses [M +
H]+ 250.1339 and 268.1446 were found.
ucts VI, VII is comparable, and we have failed to isolate
individual compounds VIа–VIh, VIIа–VIIh either by
repeated crystallization, or by chromatography.
Hence the reaction of aminopyrazoles with 2-acetyl-
cyclopentanone is far more regioselective than the reac-
tion with 2-acetylcyclohexanone: In the former case in
the reaction mixture the regioisomer prevails containing
a cycloalkane ring fused at the С6=С7 bond, in the latter
the content of regioisomers is comparable. The observed
products ratio is well consistent with the data on the
heats of formation of compounds obtained calculated by
MNDO/3 method: The difference in the heats of forma-
tion is considerably greater for the regioisomers with
the fused cyclopentane ring than those with the fused
cyclohexane ring [–1.860 (IVd, Vd), –0.755 kcal mol−1
(VId,VIId)].
The proof of the regiostructure of compounds we
synthesized was based on the comparison of the chemical
shifts of protons and carbon atoms of the methyl groups in
the 1Н (δ2.44–2.64, 2.72–2.76 ppm) and 13С (δ22.5–23.0,
12.8 ppm) NMR spectra with the characteristic chemical
shifts of the corresponding protons and carbon atoms in
the spectra of previously studied compounds [11, 12, 18,
25, 26], and also on the XRD data [27]. The additional
independent criterion of the regioisomers assignment was
the difference in the values of 5JHH between the methylene
protons of the fused cycloalkanes. The homoallyl constant
of the fragment СН2–С=С–СН2 in compounds IVа–IVi,
VIа–VIh is 5JHH ~1.5 Hz, whereas in the regioisomeric
compounds Vа–Vi, VIIа–VIIh the constant 5JHH of the
fragment СН2–С–С–СН2 is essentially smaller, and we
have not observed it.
The sequence of the cyclocondensation stages of
3(5)-aminopyrazoles I with 2-acetylcycloalcanones II,
III is shown in Scheme 2. In the first stage the exocyclic
NH2 group of aminopyrazole reacts with the acetyl or
carbonyl group of the dicarbonyl compound forming
intermediates А (А') or B (B'). Then in succession two
water molecules are eliminated with the formation of
final products IV–VII. The presence of the intermediate
compound C (and/or C’) alongside products IVd,Vd
Therefore the method was developed for the prepa-
ration of 7,8-dihydro-6Н-cyclopenta[e]pyrazolo[1,5-a]
pyrimidines. The reaction of 3(5)-aminopyrazoles with
2-acetylcyclohexanone gave a mixture of 6,7,8,9-tetrahyd
ropyrazolo[1,5-a]quinazolines and 5,6,7,8-tetrahydropyr
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

PETROV et al.
1114
Scheme 2.
R2
R2
R1
R1
NH2
NH2
N
HN
N
NH
I-5A
I-3A
II, III
R2
R2
R2
R2
H
H
N
H
N
N
R1
H
N
R1
OH
(CH2)n
R1
OH
(CH2)n
OH
R1
N
N
HN
N
HN
HO
N
N
N
O
HO
(CH2)n
(CH2)n
O
OH
B'
А
А'
B
R2
R2
N
R2
R2
H
N
H
N
H
H
N
N
R1
R1
R1
R1
N
N
n(CH2)
N
HN
HN N
O
(CH2)n
O
N
(CH2)n
HO
C'
(CH2)n
OH
C
D'
D
R2
R2
N
N
R1
R1
N
N
N
N
(CH2)n
(CH2)n
IV, VI
V, VII
azolo[5,1-b]quinazolines with the predominant formation
of one of the regioisomers depending on the structure of
3(5)-aminopyrazole and the reaction conditions.
instrument Bruker Daltonics microTOF at the positive
electrospray ionization (ESI). 3(5)-Amino-5(3)-methyl-
1Н-pyrazole (Ia), 3(5)-amino-4-cyano-1Н-pyrazole (Ic),
and 2-acetylcyanoalcanols were purchased from Acros
Organics.
EXPERIMENTAL
3(5)-Amino-1Н-pyrazoles Iа–Ii. General procedure.
To a solution of 25 mmol of ketonitrile in 50 ml of ethanol
and 5 ml of acetic acid was added dropwise 50 mmol of
hydrazine hydrate. The reaction mixture was stirred at
50°С for 2 h, another 10 ml of acetic acid was added, and
the mixture was boiled for 5 h more. On cooling to room
temperature the formed mixture was poured into 200 ml
of ice water, neutralized with a solution of ammonium
hydroxide to рН 9. The formed precipitate was filtered off,
1Н and 13С NMR spectra were registered on a spec-
trometer Bruker DPX-30 (300.13 and 75.47 MHz) at
22°С, solvents DMSO-d6 (for aminopyrazoles), CDCl3
(for reaction products). Chemical shifts were measured
with respect to the residual protons of the deuterated
solvent: CDCl3 (7.28, 77.00 ppm), DMSO-d6 (2.50,
39.50 ppm). Elemental analyses were determined with
the use of high resolution mass spectrometry on an
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

STUDY OF REGIOSELECTIVITY OF REACTIONS BETWEEN 3(5)-AMINOPYRAZOLES
1115
dried in air, crystallized from acetonitrile or ethyl acetate.
at 0°C (or –20°C) with 2 ml of alcohol containing 2 drops
of trifluoroacetic acid, after 72 h the separated precipitate
was filtered off, washed with alcohol, dried, and analyzed.
5-Amino-3-(4-methylphenyl)-1Н-pyrazole (Ib).
Yield 72%, mp 146–148°C (acetonitrile) (147–150°C
[28]). 1H NMR spectrum, δ, ppm: 2.29 s (3Н, СН3), 4.75
br.s (2Н, NH2), 5.72 s (1Н, СН=), 7.17 d (2Н, С6Н4,
J 8.0 Hz), 7.52 d (2Н, С6Н4, J 8.0 Hz). Found [M +
H]+ 174.1046. С10Н12N3. Calculated [M + H]+ 174.1026.
b. 1 mmol of aminopyrazole and 1 mmol of
acetylcycloalkanone was mixed at 20°C with 2 ml of
alcohol containing 2 drops of trifluoroacetic acid, after
24 h the separated precipitate was filtered off, washed
with alcohol, dried, and analyzed.
3(5)-Amino-4-phenyl-1Н-pyrazole (Id). Yield 75%,
mp 173–174°C (acetonitrile) (174–176°C [29]). 1H NMR
spectrum,δ, ppm: 4.76 s (2H, NH2), 7.11 t (1Н, Ph), 7.32 t
(2H, Ph), 7.49 d (2H, Ph), 7.67 s (1H, CH), 11.69 s (1H,
NH). Found [M + H]+ 160.0882. С9Н10N3. Calculated
[M + H]+ 160.0869.
c.Amixture of 1 mmol of aminopyrazole and 1 mmol
of acetylcycloalkanone was added to 5 ml of acetic acid or
butanol, the solution obtained was boiled for 3 h, cooled
to room temperature, evaporated to dryness at a reduced
pressure, the residue was washed in succession with water
and alcohol, dried, and analyzed.
3(5)-Amino-4-(4-chlorophenyl)-1Н-pyrazole (Ie).
Yield 80%, mp 146–147°C (acetonitrile) (141–143°C
[29]). H NMR spectrum, δ, ppm: 4.85 s (2H, NH2),
7.34–7.55 m (4H, C6H4), 7.71 (1H, CH), 11.78 s (1H,
NH). Found [M + H]+ 194.0493. С9Н9ClN3. Calculated
[M + H]+ 194.0480.
d.Amixture of 1 mmol of aminopyrazole and 1 mmol
of acetylcycloalkanone was heated on an oil bath at 160°C
for 2 min. On cooling the reaction mixture to room tem-
perature the solid product was treated with alcohol (5 ml),
the precipitate was filtered off, dried, and analyzed.
1
3(5)-Amino-4-(4-methoxyphenyl)-1Н-pyrazole (If).
Yield 70%, mp 202–203°C (acetonitrile) (200°C [30]).
1H NMR spectrum, δ, ppm: 3.74 (3H, CH3O), 4.52 br.s
(1.4H, NH2-3A), 4.98 br.s (0.6H, NH2-5A), 6.89–7.43
(4H, C6H4), 7.61 br.s (1H, СH), 11.65 br.s (1H, NH).
Found [M + H]+ 190.0998. С10Н12N3O. Calculated [M +
H]+ 190.0975.
e. 1 mmol of aminopyrazole and 1 mmol and
acetylcycloalkanone was subjected to microwave irradia-
tion at 800 W for 2 min. Then the reaction mixture was
treated with alcohol, the solid precipitate was filtered off,
dried, and analyzed.
f. 1 mmol of aminopyrazole and 1 mmol of
acetylcycloalkanone was dissolved in 5 ml of dimethyl
sulfoxide, the mixture was kept at 20°C for 8 days, af-
terwards it was poured into 50 ml of water, the separated
precipitate was filtered off, washed with alcohol, dried,
and analyzed.
3(5)-Amino-5(3)-methyl-4-phenyl-1Н-pyrazole
(Ig). Yield 73%, mp 138–139°C (acetonitrile) (138–
140°C [31]). 1H NMR spectrum, δ, ppm: 2.17 s (3H, Me),
4.45 s (2H, NH2), 7.17–7.39 m (4H, C6H4), 11.29 с (1H,
NH). Found [M + H]+ 174.1041. С10Н12N3. Calculated
[M + H]+ 174.1026.
2,5-Dimethyl-7,8-dihydro-6Н-cyclopenta[e]-
pyrazolo[1,5-a]pyrimidine (IVa) was synthesized
by procedure b, light-brown crystals, mp 160–161°C
(acetonitrile) (mp 168–169°C [17]). 1Н NMR spectrum,
δ, ppm: 2.32 pentet (2Н, С7Н2), 2.52 s (6Н, 2 СН3),
3.01 t.t (С6Н2, 3J 7.3, 5J 1.4 Hz), 3.36 t.t (2Н, С8Н2, 3J 7.6,
5J 1.4 Hz), 6.36 s (1Н, СН=). 13С NMR spectrum, δ,
ppm: 14.46 (2-CH3), 21.91 (C7H2), 22.54 (5-CH3), 29.36
(C6H2), 29.61 (C8H2), 94.49 (C3H), 120.72 (C5а), 147.78,
149.44 (C3а, C8а), 154.32 (C2), 155.41 (C5). Found [M +
H]+ 188.1217. С11Н14N3. Calculated [M + H]+ 188.1182.
3(5)-Amino-5(3)-methyl-4-(4-methoxyphenyl)-1Н-
pyrazole (Ih). Yield 71%, mp 139–140°C (ethyl acetate).
1H NMR spectrum, δ, ppm: 2.14 s (3H, Me), 3.76 s (3H,
CH3O), 4.42 s (2H, NH2), 6.93–7.27 m (4H, C6H4),
11.09 s (1H, NH). Found [M + H]+ 204.1144. С11Н14N3O.
Calculated [M + H]+ 204.1131.
3(5)-Amino-5(3)-methyl-4-(2-methoxyphenyl)-1Н-
pyrazole (Ii). Yield 71%, mp 67–68°C (acetonitrile).
1H NMR spectrum, δ, ppm: 2.03 s (3H, Me), 3.77 s (3H,
CH3O), 4.16 s (2H, NH2), 6.93–7.27 m (4H, C6H4),
11.29 s (1H, NH). Found [M + H]+ 204.1142. С11Н14N3O.
Calculated [M + H]+ 204.1131.
5-Methyl-2-(4-tolyl)-7,8-dihydro-6Н-cyclopenta[e]
pyrazolo[1,5-a]pyrimidine (IVb) and 8-methyl-2-
(4-tolyl)-6,7-dihydro-5Н-1,4,8а-triaza-s-indacene
(Vb) were synthesized by procedure b. Found [M + H]+
264.1501. С17Н18N3. Calculated [M + H]+ 264.1495.
Chemical shifts of signals of regioisomers are extracted
Reaction of 5-amino-1Н-pyrazoles Iа–Ii with
2-acetylcycloalkanones II, III. а. 1 mmol of amino-
pyrazole and 1 mmol of acetylcycloalkanone was mixe
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

PETROV et al.
1116
from the 1Н NMR spectrum of the reaction mixture .
extracted from NMR spectra of the reaction mixture.
1Н NMR spectrum, δ, ppm: 2.26 pentet (2Н, С6Н2),
2.74 s (3Н, СН3), 2.97 t (2H, С7Н2, 3J 7.3 Hz), 3.09 t (2Н,
С5Н2, 3J 7.3 Hz), 7.24 t (1H, Harom, J 7.3 Hz), 7.45 t (2H,
Harom, J 7.6 Hz), 8.06 d (2H, Harom, J 7.6 Hz), 8.35 s (1Н,
СН=). Some signals of the 13С NMR spectrum, δ, ppm:
14.16 (8-CH3), 23.60 (C6H2), 27.24 (C7H2), 34.44 (C5H2),
109.08 (С3), 140.01 (C2Н). Found [M + H]+ 250.1363.
С16Н16N3. Calculated [M + H]+ 250.1339.
Regioisomer IVb. 1Н NMR spectrum, δ, ppm: 2.35
pentet (2Н, С7Н2), 2.41 s (3Н, СН3C6H4), 2.54 s (3Н,
СН3), 3.00 t.t (С6Н2, 3J 7.3, 5J 1.4 Hz), 3.44 t.t (2Н, С8Н2,
3J 7.6, 5J 1.4 Hz), 6.84 с (1Н, СН=), 7.27 d (2Н, Нm
,
arom
J 8.0 Hz), 7.89 d (2Н, Нoarom, J 8.0 Hz). 13С NMR spec-
trum, δ, ppm: 21.29 (4-CH3C6H4), 21.93 (7-CH2), 22.65
(5-CH3), 29.51 (C6H2), 29.75 C8H2), 91.81 (C3H), 121.54
(C5а), 126.27 (Co), 129.31 (Cm), 130.42 (Cи), 138.42 (Cp),
148.27, 149.82 (C3а, C8а), 155.75 (C2, C5).
5-Methyl-3-(4-chlorophenyl)-7,8-dihydro-6Н-
cyclopenta[e]pyrazolo[1,5-a]pyrimidine (IVe) and
8-methyl-3-(4-chlorophenyl)-6,7-dihydro-5Н-1,4,8а-
triaza-s-indacene (Ve) were synthesized by procedures
b, d. Regioisomer IVe. Light-yellow crystals, mp 176–
1
Regioisomer Vb. Н NMR spectrum, δ, ppm: 2.24
pentet (2Н, С6Н2), 2.41 s (3Н, СН3C6H4), 2.76 s (3Н,
3
СН3), 2.98 t (2H, С7Н2, J 7.4 Hz), 3.44 t (2Н, С5Н2,
3J 7.6 Hz), 6.80 s (1Н, СН=), 7.27 d (2Н, С6Н4, J 8.0 Hz),
7.89 d (2Н, С6Н4, J 8.0 Hz).
1
177°С (DMF). Н NMR spectrum, δ, ppm: 2.36 pentet
(2Н, С7Н2), 2.61 s (3Н, СН3), 3.06 t.t (С6Н2, 3J 7.3, 5J
1.4 Hz), 3.42 t.t (2Н, С8Н2, 3J 7.6, 5J 1.4 Hz), 7.40 d (2Н,
Нmarom, J 8.7 Hz), 8.07 d (2Н, Нoarom, J 8.7 Hz), 8.35 s
(1Н, СН=). 13С NMR spectrum, δ, ppm: 21.72 (С7), 22.98
(СН3), 29.51 (С6), 29.65 (С8), 107.83 (С3), 122.27 (С5а),
126.96, 128.59 (Сm, Сo), 131.03 (Си), 131.18 (Сp), 141.72
(СН=), 144.91 (С3а), 148.45 (С8а), 156.50 (С5).
5-Methyl-3-cyano-7,8-dihydro-6Н-cyclopenta[e]
pyrazolo[1,5-a]pyrimidine (IVc) and 8-methyl-3-
cyano-6,7-dihydro-5Н-1,4,8а-triaza-s-indacene (Vc)
were synthesized by procedure b. Regioisomer IVc.
Light-yellow crystals, mp 163–164°С (DMF). 1Н NMR
spectrum, δ, ppm: 2.40 pentet (2Н, С7Н2), 2.64 s (3Н,
СН3), 3.10 t.t (С6Н2, 3J 7.3, 5J 1.4 Hz), 3.44 t.t (2Н, С8Н2,
3J 7.6, 5J 1.4 Hz), 8.31 s (1Н, СН=). 13С NMR spectrum,
δ, ppm: 21.76 (С7Н2), 22.85 (5-CH3), 29.43 (C6H2), 29.69
(C8H2), 80.94 (C3), 113.37 (CN), 125.22 (C5а), 146.79
(C2H), 149.67, 150.13 (C3а, C8а), 160.34 (C5).
Regioisomer Ve. Chemical shifts of signals are
1
extracted from the Н NMR spectrum of the reaction
mixture synthesized by procedure d. 1Н NMR spectrum,
δ, ppm: 2.30 pentet (2Н, С6Н2), 2.76 s (3Н, СН3), 3.03 t
(2H, С7Н2, 3J 7.3 Hz), 3.10 t (2Н, С5Н2, 3J 7.6 Hz), 7.40 d
(2Н, Нarom, J 8.7 Hz), 8.01 d (2Н, Нarom, J 8.7 Hz), 8.32 s
(1Н, СН=). Found [M + H]+ 284.0962. С16Н15ClN3.
Calculated [M + H]+ 284.0949.
Regioisomer Vc. Chemical shifts of signals are
extracted from NMR spectra of the reaction mixture.
1Н NMR spectrum, δ, ppm: 2.30 pentet (2Н, С6Н2),
2.76 s (3Н, СН3), 3.03 t (2H, С7Н2, 3J 7.4 Hz), 3.15 t (2Н,
С5Н2, 3J 7.6 Hz), 8.32 s (1Н, СН=). Some signals of the
13С NMR spectrum, δ, ppm: 14.28 (8-CH3), 23.41 (C6H2),
27.36 (C7H2), 34.50 (C5H2), 145.79 (C2). Found [M +
H]+ 199.0963. С11Н11N4. Calculated [M + H]+ 199.0978.
5-Methyl-3-(4-methoxyphenyl)-7,8-dihydro-6Н-
cyclopenta[e]pyrazolo[1,5-a]pyrimidine (IVf) and
8-methyl-3-(4-methoxyphenyl)-6,7-dihydro-5Н-
1,4,8а-triaza-s-indacene (Vf) were synthesized by
procedures b, d. Regioisomer IVf. Light-brown crystals,
mp 149–150°C (acetonitrile). 1Н NMR spectrum, δ, ppm:
2.35 pentet (2Н, С7Н2), 2.59 s (3Н, СН3), 3.05 t (2H,
5-Methyl-3-phenyl-7,8-dihydro-6Н-cyclopenta[e]
pyrazolo[1,5-a]pyrimidine (IVd) and 8-methyl-3-
phenyl-6,7-dihydro-5Н-1,4,8а-triaza-s-indacene (Vd)
were synthesized by procedure b. Regioisomer IVd.
Light-brown crystals, mp 188–189°C (butanol). 1Н NMR
spectrum, δ, ppm: 2.33 pentet (2Н, С7Н2), 2.59 s (3Н,
СН3), 3.02 t.t (С6Н2, 3J 7.3, 5J 1.4 Hz), 3.39 t.t (2Н, С8Н2,
3
3
С6Н2, J 7.3 Hz), 3.40 t (2Н, С8Н2, J 7.6 Hz), 3.87 s
(3Н, MeO), 7.02 d (2Н, Нmarom, J 8.7 Hz), 8.03 d (2Н,
Нoarom, J 8.7 Hz), 8.32 s (1Н, СН=). 13С NMR spectrum,
δ, ppm: 21.71 (С7), 22.94 (СН3), 29.48, 29.59 (С6, С8),
55.23 (MeO), 108.89 (С3), 114.05 (Сo), 121.81 (С5а),
125.31 (Си), 127.12 (Сm), 141.46 (СН=), 144.62, 148.14
(С3а, С8а), 155.83 (С5), 157.78 (C p).
5
3J 7.6, J 1.4 Hz), 7.25 t (1H, Harom, J 7.3 Hz), 7.45 t
(2H, Нmarom, J 7.6 Hz), 8.12 d (2H, Нoarom, J 7.6 Hz),
8.39 s (1Н, СН=). 13С NMR spectrum, δ, ppm: 21.63 (С7),
22.91 (СН3), 29.42 (С6), 29.58 (С8), 108.90 (С3), 121.16
(С5а), 125.61 (Сp), 125.81, 128.52 (Сm, Сo), 132.59 (Си),
141.83 (СН=), 144.90 (С3а), 148.23 (С8а), 156.17 (С5).
Regioisomer Vf. Chemical shifts of signals are
1
extracted from the Н NMR spectrum of the reaction
mixture, synthesized by procedure d. 1Н NMR spectrum,
δ, ppm: 2.30 pentet (2Н, С6Н2), 2.76 s (3Н, СН3), 3.03 t
Regioisomer Vd. Chemical shifts of signals are
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

STUDY OF REGIOSELECTIVITY OF REACTIONS BETWEEN 3(5)-AMINOPYRAZOLES
1117
(2H, С7Н2, 3J 7.3 Hz), 3.10 t (2Н, С5Н2, 3J 7.6 Hz), 7.40 d
(2Н, Нarom, J 8.7 Hz), 8.01 d (2Н, Нarom, J 8.7 Hz),
8.32 s (1Н, СН=). Found [M + H]+ 280.1447. С17Н18N3O.
Calculated [M + H]+ 280.1444.
6Н-cyclopenta[e]pyrazolo[1,5-a]pyrimidine (IVi)
was synthesized by procedure b. Light-brown crystals,
mp 200–201°С (acetonitrile). 1Н NMR spectrum, δ, ppm:
2.34 pentet (2Н, С7Н2), 2.44 s (3Н, Me), 2.50 s (3Н,
Me), 3.02 s (2H, С6Н2, J 7.3, J 1.4 Hz), 3.39 t (2Н,
С8Н2, 3J 7.6, 5J 1.4 Hz), 3.82 s (3Н, СН3O), 7.02 d (1Н,
Нarom, J 8.0 Hz), 7.08 t (1Н, Нarom, J 7.3 Hz), 7.35 t (1Н,
Нarom, J 8.0 Hz), 7.45 d (1Н, Нarom, J 7.3 Hz). 13С NMR
spectrum, δ, ppm: 13.78 (Me), 21.96 (С7), 22.78 (Me),
29.40, 29.59 (С6, С8), 105.06 (С3), 111.08 (Co), 120.55
(Сm), 120.99, 121.30 (С5а, Си), 128.28 (Сo), 132.41 (Сm),
146.75, 147.52 (С3а, С8а), 153.29, 155.57 (С2, С5), 157.20
(Сp). Found [M + H]+ 294.1616. С18Н20N3O. Calculated
[M + H]+ 294.1601.
3
5
2,5-Dimethyl-3-phenyl-7,8-dihydro-6Н-
cyclopenta[e]pyrazolo[1,5-a]pyrimidine (IVg) and
2,8-dimethyl-3-phenyl-6,7-dihydro-5Н-1,4,8а-triaza-
s-indacene (Vg) were synthesized by procedures b, d.
Regioisomer IVg. Light-brown crystals, mp 172–173°С
1
(DMF). Н NMR spectrum, δ, ppm: 2.34 pentet (2Н,
С7Н2), 2.54 s (3Н, СН3), 2.66 s (3Н, СН3), 3.03 t.t
3
5
3
(С6Н2, J 7.3, J 1.4 Hz), 3.39 t.t (2Н, С8Н2, J 7.6,
5J 1.4 Hz), 7.29 t (1H, Hparom, J 7.3 Hz), 7.45 t (2H,
Нmarom, J 7.6 Hz), 7.77 d (2H, Hoarom, J 7.6 Hz). 13С NMR
spectrum, δ, ppm: 14.27 (Me), 21.63 (С7), 22.91 (Me),
29.39, 29.59 (С6, С8), 107.77 (С3), 121.45 (С5а), 125.75
(Сp), 128.30, 128.65 (Сm, Сo), 132.91 (Си), 146.25, 147.57
(С3а, С8а), 151.60 (С2),155.87 (С5).
2,8-Dimethyl-3-(2-methoxyphenyl)-6,7-dihydro-
5Н-1,4,8а-triaza-s-indacene (Vi). Chemical shifts of
signals are extracted from the 1Н NMR spectrum of the
1
reaction mixture synthesized by procedure d. Н NMR
spectrum, δ, ppm: 2.19 pentet (2Н, 7-СН2), 2.72 s (3Н,
СН3), 3.00–3.04 m (4H, С6Н2, С8Н2), 3.82 с (3Н, СН3O),
7.01–7.47 (4Н, Нarom).
Regioisomer Vg. Chemical shifts of signals are
extracted from the Н NMR spectrum of the reaction
1
mixture synthesized by procedure d 1Н NMR spectrum,
δ, ppm: 2.22 pentet (2Н, С6Н2), 2.64 s (3Н, СН3), 2.72 s
2,5-Dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-
a]-quinazoline (VIa) and 2,9-dimethyl-5,6,7,
8-tetrahydro-pyrazolo[5,1-b]quinazoline (VIIa) were
synthesized by procedures b, d. Chemical shifts of signals
of regioisomers are extracted from the 1Н NMR spectrum
of the reaction mixture .
Regioisomer VIа. 1Н NMR spectrum, δ, ppm: 1.90 m
(4Н, С7Н2, С8Н2), 2.51 s (3Н, 2-Me), 2.58 s (3Н, 5-Me),
2.68 t (2Н, С6Н2, J 5.8 Hz), 3.17 t (2Н, С9Н2, J 5.8 Hz),
6.47 s (СН=).
Regioisomer VIIа. 1Н NMR spectrum, δ, ppm: 1.90 m
(4Н, С6Н2, С7Н2), 2.51 s (3Н, 2-Me), 2.78 s (3Н, 9-Me),
2.81 br.t (2Н, С8Н2,), 3.08 br.t (2Н, С5Н2), 6.48 s (СН=).
Found [M + H]+ 202.1343. С12Н16N3. Calculated [M +
H]+ 202.1339.
3
(3Н, СН3), 2.97 t (2H, С7Н2, J 7.3 Hz), 3.03 m (2Н,
С5Н2), 7.24 m (1H, Harom), 7.45 m (2H, Harom), 7.71 d (2H,
H
arom, J 7.6 Hz). Found [M + H]+ 264.1492. С17Н18N3.
Calculated [M + H]+ 264.1495.
2,5-Dimethyl-3-(4-methoxyphenyl)-7,8-dihydro-
6Н-cyclopenta[e]pyrazolo[1,5-a]pyrimidine (IVh)
were synthesized by procedure b. Light-brown crystals,
1
mp 162–163°C (butanol). Н NMR spectrum, δ, ppm:
2.34 pentet (2Н, С7Н2), 2.54 s (3Н, 5-Me), 2.63 s (3Н,
2-СН3), 3.03 t (2H, С6Н2, 3J 7.3 Hz), 3.39 t (2Н, С8Н2, 3J
7.6 Hz), 3.87 s (3Н, СН3O), 7.03 d (2Н, Нmarom, J 8.7 Hz),
7.67 d (2Н, Нoarom, J 8.7 Hz). 13С NMR spectrum, δ,
ppm: 14.13 (Me), 21.90 (С7), 22.85 (Me), 29.42, 29.59
(С6, С8), 107.56 (С3), 113.91 (Cm), 121.28 (С5а), 125.35
(Си), 129.85 (Сo), 146.15, 147.50 (С3а, С8а), 151.35,
155.63 (С2, С5), 157.84 (Сp). Found [M + H]+ 294.1609.
С18Н20N3O. Calculated [M + H]+ 294.1601.
5-Methyl-2-p-tolyl-6,7,8,9-tetrahydropyrazolo-
[1,5-a]quinazoline (VIb) and 9-methyl-2-p-tolyl-
5,6,7,8-tetrahydropyrazolo[5,1-b]quinazoline (VIIb)
were synthesized by procedures b, d. Chemical shifts
2,8-Dimethyl-3-(4-methoxyphenyl)-6,7-dihydro-
5Н-1,4,8а-triaza-s-indacene (Vh). Chemical shifts of
signals are extracted from the 1Н NMR spectrum of the
1
of signals of regioisomers are extracted from Н NMR
spectrum of the reaction mixture .
1
reaction mixture synthesized by procedure d. Н NMR
Regioisomer VIb. 1Н NMR spectrum, δ, ppm: 1.91 m
(4Н, С7Н2, С8Н2), 2.41 s (3Н, MeС6Н4), 2.51 s (3Н,
5-Me), 2.68 t (2Н, С6Н2, J 5.8 Hz), 3.21 t (2Н, С9Н2,
J 5.8 Hz), 6.79 (СН=), 7.26 d (2Н, Нmarom, J 8.0 Hz),
7.89 d (2Н, Нoarom, J 8.0 Hz).
spectrum, δ, ppm: 2.19 pentet (2Н, С6Н2), 2.72 s (3Н,
СН3), 3.00–3.04 m (4H, С7Н2, С5Н2), 3.82 s (3Н, СН3O),
7.01–7.47 (4Н, Нarom).
2,5-Dimethyl-3-(2-methoxyphenyl)-7,8-dihydro-
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PETROV et al.
1118
1
quinazoline (VIIe) were synthesized by procedures
b, d. Chemical shifts of signals of regioisomers are
extracted from 1Н NMR spectra of the reaction mixture.
Regioisomer VIIb. Н NMR spectrum, δ, ppm:
1.92 m (4Н, С6Н2, С7Н2), 2.41 s (3Н, MeС6Н4), 2.77 s
(3Н, 9-Me), 2.78 br.t (2Н, С8Н2), 2.97 br.t (2Н, С5Н2),
6.76 (СН=), 7.26 d (2Н, Нmarom, J 8.0 Hz), 7.91 d (2Н,
Нoarom, J 8.0 Hz). Found [M + H]+ 278.1658. С18Н20N3.
Calculated [M + H]+ 278.1652.
1
Regioisomer VIe. Н NMR spectrum, δ, ppm: 1.92–
2.02 m (4Н, 2СН2), 2.60 s (Me), 2.72 t.t (2Н, С6Н2, J 5.8,
J 1.5 Hz), 3.17 t.d (2Н, С9Н2, J 5.8, J 1.5 Hz), 7.39 d
(2Н, Нmarom, J 8.7 Hz), 8.04 d (2Н, Нoarom, J 8.7 Hz),
8.31 s (2Н, СН=).
5-Methyl-3-cyano-6,7,8,9-tetrahydropyrazolo-
[1,5-a]quinazoline (VIc) and 9-dimethyl-5,6,7,8-
tetra-hydropyrazolo[5,1-b]quinazoline (VIIc) were
synthesized by procedures b, d. Chemical shifts of signals
of regioisomers are extracted from 1Н NMR spectrum of
the reaction mixture .
Regioisomer VIc. 1Н NMR spectrum, δ, ppm: 1.95 m
(4Н, С7Н2, С8Н2), 2.62 s (3Н, 5-Me), 2.75 br.t (2Н, С6Н2),
3.18 br.t (2Н, С9Н2), 8.27 s (СН=).
Regioisomer VIIc. 1Н NMR spectrum, δ, ppm: 1.94 m
(4Н, С6Н2, С7Н2), 2.77 s (3Н, 9-Me), 2.84 br.t (2Н,
С8Н2), 3.07 br.t (2Н, С5Н2), 8.29 s (СН=). Found [M +
H]+ 213.1140. С12Н13N4. Calculated [M + H]+ 213.1135.
Regioisomer VIIe. 1Н NMR spectrum, δ, ppm: 1.92–
2.02 m (4Н, 2СН2), 2.75 s (Me), 2.83 br.t (2Н, С8Н2),
3.05 br.t (2Н, С5Н2), 7.39 d (2Н, Нmarom, J 8.7 Hz), 8.04 d
(2Н, Нoarom, J 8.7 Hz), 8.33 s (2Н, СН=). Found [M + H]+
298.1119. С17Н17ClN3. Calculated [M + H]+ 298.1096.
5-Methyl-3-(4-methoxyphenyl)-6,7,8,9-tеtра-
гиdрopyrazolo[1,5-a]quinazoline (VIf) and 9-methyl-
3-(4-methoxyphenyl)-5,6,7,8-tetrahydropyrazolo-
[5,1-b]quinazoline (VIIf) were synthesized by procedures
b, d. Chemical shifts of signals of regioisomers are
extracted from 1Н of the reaction mixture .
Regioisomer VIf. 1Н NMR spectrum, δ, ppm: 1.93 m
(4Н, 2СН2), 2.58 s (3Н, Me), 2.72 t.t (2Н, С6Н2, J 5.8,
J 1.5 Hz), 3.14 t.t (2Н, С9Н2, J 5.8, J 1.5 Hz), 3.86 s
(3Н, MеO), 7.00 d (2Н, Нmarom, J 8.7 Hz), 8.00 d (2Н,
Нoarom, J 8.7 Hz), 8.28 s (2Н, СН=).
5-Methyl-3-phenyl-6,7,8,9-tetrahydropyrazolo-
[1,5-a]quinazoline (VId) and 9-methyl-3-phenyl-
5,6,7,8-tetrahydropyrazolo[5,1-b]quinazoline (VIId)
were synthesized by procedures b, d. Chemical shifts
1
of signals of regioisomers are extracted from Н NMR
Regioisomer VIIf. 1Н NMR spectrum, δ, ppm: 1.93 m
(4Н, 2СН2), 2.74 s (3Н, Me), 2.72 br.t ( 2Н, С8Н2),
3.14 br.t (2Н, С5Н2), 3.86 s (3Н, MеO), 7.00 d (2Н,
Нmarom, J 8.7 Hz), 8.00 d (2Н, Нoarom, J 8.7 Hz), 8.30 s
(2Н, СН=). Found [M + H]+ 294.1618. С18Н20N3O.
Calculated [M + H]+ 294.1601.
spectrum of the reaction mixture.
Regioisomer VId. 1Н NMR spectrum, δ, ppm: 1.92–
2.03 m (4Н, 2СН2), 2.59 s (Me), 2.72 t.t (2Н, С6Н2, J 5.8,
J 1.5 Hz), 3.13 t.d (2Н, С9Н2, J 5.8, J 1.5 Hz), 7.23 t
(1H, Hparom, J 7.3 Hz), 7.44 t (2Н, Hmarom, J 7.6 Hz),
8.10 d (2Н, Нoarom, J 7.6 Hz), 8.34 s (2Н, СН=). 13С NMR
spectrum, δ, ppm: 20.84 (С8), 21.95 (С7), 23.02 (СН3),
24.09 (С9), 24.40 (С6), 109.09 (С3), 116.17 (С5а), 125.58
(Сp), 125.81, 128.54 (Сm, Сo), 132.69 (Си), 140.82 (СН=)
143.05 (С3а, С9а), 158.38 (С5).
2,5-Dimethyl-3-phenyl-6,7,8,9-tetrahydro-
pyrazolo[1,5-a]quinazoline (VIg) and 2,9-dimethyl-3-
phenyl-5,6,7,8-tetrahydropyrazolo[5,1-b]quinazoline
(VIIg) were synthesized by procedures b, d. Chemical
shifts of signals of regioisomers are extracted from
1Н NMR spectra of the reaction mixture .
Regioisomer VIg. 1Н NMR spectrum, δ, ppm: 1.90–
2.00 m (4Н, 2СН2), 2.53 s (3Н, 5-Me), 2.66 s (3Н, 2-Mе),
2.70 t.t ( 2Н, С6Н2, J 5.8, J 1.5 Hz), 3.16 t.t (2Н, С9Н2,
J 5.8, J 1.5 Hz), 7.29 t (1H, Hparom, J 7.3 Hz), 7.45 t
(2Н, Hmarom, J 7.6 Hz), 7.77 d (2Н, Нoarom, J 7.6 Hz).
1
Regioisomer VIId. Н NMR spectrum, δ, ppm:
1.92–2.03 m (4Н, 2СН2), 2.75 s (Me), 2.83 m (2Н, С8Н2),
3.06 m (2Н, С5Н2), 7.23 t (1H, Hparom, J 7.3 Hz), 7.44 t
(2Н, Hmarom, J 7.6 Hz), 8.10 d (2Н, Нoarom, J 7.6 Hz),
8.37 s (2Н, СН=). 13С NMR spectrum, δ, ppm: 12.83
(С9СН3), 22.35 (С6), 22.62 (С7), 24.86 (С8), 33.88 (С5),
108.46 (С3), 115.45 (С8а), 125.48 (Сp), 125.81, 128.54
(Сm, Сo), 132.73 (Си), 141.23 (С2), 142.67, 143.35 (С3а,
С9), 158.99 (С4a). Found [M + H]+ 264.1492. С17Н18N3.
Calculated [M + H]+ 264.1495.
1
Regioisomer VIIg. Н NMR spectrum, δ, ppm:
1.90–2.00 m (4Н, 2СН2), 2.66 s (3Н, 2-Mе), 2.73 s (9-
Me), 2.70 br.t (2Н, С8Н2), 3.16 br.t (2Н, С5Н2), 7.29 t
(1H, Hparom, J 7.3 Hz), 7.45 t (2Н, Hmarom, J 7.6 Hz),
7.77 d (2Н, Нoarom, J 7.6 Hz). Found [M + H]+ 278.1658.
С18Н20N3. Calculated [M + H]+ 278.1652.
5-Methyl-3-(4-chlorophenyl)-6,7,8,9-tetrahydro-
pyrazolo[1,5-a]quinazoline (VIe) and 9-methyl-3-
(4-chloro-phenyl)-5,6,7,8-tetrahydropyrazolo[5,1-b]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

STUDY OF REGIOSELECTIVITY OF REACTIONS BETWEEN 3(5)-AMINOPYRAZOLES
1119
2,5-Dimethyl-3-(4-methoxyphenyl)-6,7,8,9-
tetrahydropyrazolo[1,5-a]quinazoline (VIh)
and 2,9-dimethyl-3-(4-methoxyphenyl)-5,6,7,8-
tetrahydropyrazolo-[5,1-b]quinazoline (VIIh) were
synthesized by procedures b, d. Chemical shifts of signals
7. Dündar, Y., Dodd, S., Strobl, J., Boland, A., Dickson, R.,
and Walley, T., Hum Psychopharmacol., 2004, vol. 19,
p. 305.
8. Sullivan, S.K., Petroski, R.E., Verge, G., Gross, R.S., Fos-
ter, A.C., and Grigoriadis, D.E., J. Pharmacol. Exp. Ther.,
2004, vol. 311, p. 537.
9. Berezhnoy, D., Gravielle, M.C., Downing, S., Kostakis, E.,
Basile,A.S., Skolnick, P., Gibbs, T.T., and Farb, D.H., BMC
Pharmacol., 2008, vol. 8, p. 11.
10. Elnagdi, M.H., Elmoghayar, M.R.H., and Elgemeie, G.H.,
Adv. Heterocycl. Chem., 1987, vol. 41, p. 319; El-
Taweel, F.M., J. Hetercyclic, Chem., 2004, vol. 41, p. 109;
Daniels, R.N., Kim, K., Lebois, E.P., Muchalski, H.,
Hughes, M., Craig, W., and Lindsley, C.W., Tetrahedron
Lett., 2008, vol. 49, p. 305; Nagahara, K., Kawano, H.,
Sasaoka, S., Ukawa, C., Hirama, T., and Takada,A., J. Het-
erocycl. Chem., 1994, vol. 31, p. 239.
11. Petrov, A.A., Emelina, E.E., and Firsov, A.V., Zh. Org.
Khim., 2000, vol. 36, p. 1058.
12. Emelina, E.E., Petrov, A.A., and Firsov, A.V., Zh. Org.
Khim., 2001, vol. 37, p. 899.
1
of regioisomers are extracted from Н NMR spectra of
the reaction mixture.
Regioisomer VIh. 1Н NMR spectrum, δ, ppm: 1.90–
1.97 m (4Н, 2СН2), 2.52 s (3Н, Me), 2.69 t.t ( 2Н, С6Н2,
J 5.8, J 1.5 Hz), 3.15 t.t (2Н, С9Н2, J 5.8, J 1.5 Hz),
3.87 s (3Н, MеO), 7.02 d (2Н, Нmarom, J 8.7 Hz), 7.67 d
(2Н, Нoarom, J 8.7 Hz).
1
Regioisomer VIIh. Н NMR spectrum, δ, ppm:
1.90–1.97 m (4Н, 2СН2), 2.62 s (3Н, Me), 2.80 br.t ( 2Н,
С8Н2), 3.15 br.t (2Н, С5Н2), 3.87 s (3Н, MеO), 7.02 d
(2Н, Нmarom, J 8.7 Hz), 7.67 d (2Н, Нoarom, J 8.7 Hz).
Found [M + H]+ 308.1771. С19Н22N3O. Calculated [M
+ H]+ 308.1757.
ACKNOWLEDGMENTS
13. Emelina, E.E. and Petrov, A.A., Zh. Org. Khim., 2009,
vol. 45, p. 427.
14. Kappe, C.O., Dallinger, D., and Murphree, S.S., Practical
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port of the Russian Foundation for Basic Research
(grant no. 10-03-00600а).
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