Three-component condensations with 5-amino-4-phenylpyrazole

Article abstract of DOI:10.1134/S107042801003019X

Three-component condensation of 3-methyl(or methoxymethyl)-4-phenyl-1H- pyrazol-5-amine with triethyl orthoformate and carbonyl compounds or nitriles containing an activated methylene group (cyclohexane-1,3-diones, acetoacetanilides, benzoylacetone, ethyl

Full text of DOI:10.1134/S107042801003019X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 3, pp. 410–416. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © D.V. Kryl’skii, Kh.S. Shikhaliev, A.S. Chuvashlev, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 3,
pp. 416–422.
Three-Component Condensations with 5-Amino-
4-phenylpyrazole
D. V. Kryl’skii, Kh. S. Shikhaliev, and A. S. Chuvashlev
Voronezh State University, Universitetskaya pl. 1, Voronezh, 394006 Russia
e-mail: alextsh@yandex.ru
Received November 19, 2008
Abstract—Three-component condensation of 3-methyl(or methoxymethyl)-4-phenyl-1H-pyrazol-5-amine with
triethyl orthoformate and carbonyl compounds or nitriles containing an activated methylene group (cyclo-
hexane-1,3-diones, acetoacetanilides, benzoylacetone, ethyl cyanoacetate, malononitrile, 1H-benzimidazol-2-
ylacetonitrile) gave substituted pyrazolopyrimidines and pyrazoloquinazolines.
DOI: 10.1134/S107042801003019X
Heterocyclic compounds containing a pyrazole ring
attract interest due to broad spectrum of their biolog-
ical activity. Fused systems incorporating a pyrazole
fragment are commonly synthesized from 3(5)-amino-
pyrazoles that are convenient building blocks in the
preparation of pyrazolopyrimidines, pyrazolopyridines,
and pyrazolotriazines [1, 2].
azolylaminomethylidene derivatives IV which were
isolated in some cases as individual substances (com-
pounds IVa, IVb). In most cases, the crystalline prod-
uct was a mixture of compounds IV and V, from
which less soluble 5,5-R3,R4-2-{[(3-R1-4-phenyl-1H-
pyrazol-5-yl)amino]methylidene}cyclohexane-1,3-di-
ones IV were isolated by recrystallization from a non-
polar solvent (xylene). Compounds V were isolated by
heating mixtures IV/V in glacial acetic acid in the
presence of anhydrous sodium acetate. Compounds IV
were light yellow crystalline substances, and pyrazolo-
quinazolines V were light yellow substances with
a greenish tint. The reaction of pyrazole Ia with tri-
ethyl orthoformate and benzoylacetone as dicarbonyl
component gave in one step 2,7-dimethyl-3-phenylpyr-
azolo[1,5-a]pyrimidin-6-yl(phenyl)methanone (VI).
Synthetic approaches to fused pyrazole derivatives
are based mainly on reactions of 3(5)-aminopyrazoles
with various cyclizing agents. Examples of two-com-
ponent cyclizations were reported in [1–7]. Three-
component condensations with participation of aromat-
ic aldehydes, cyclic diketones, and 3(5)-aminopyra-
zoles having no substituent in the 4-position were also
described [8, 9]. In this case, the chemoselectivity
problem arises. Komykhov et al. [10] reported on
three-component condensation of N-aryl-3-aminopyr-
azole-4-carboxamides with aldehydes and N-arylaceto-
acetamides.
Barbituric acid derivatives and 6-methyl-2H-pyran-
2,4(3H)-dione reacted with compounds Ia and Ic and
triethyl orthoformate (III) to give linear condensation
products VII and VIII which failed to undergo
intramolecular cyclization under analogous conditions
(Scheme 2).
In the present work we examined three-component
condensations of 3-substituted 4-phenyl-1H-pyrazol-5-
amines with triethyl orthoformate and compounds pos-
sessing an activated methylene group (cyclic and linear
dicarbonyl compounds and nitriles). Analogous reac-
tions of hetarylguanidines were described in [11, 12].
Compounds IVa and IVb characteristically dis-
1
played in the H NMR spectra doublet signals from
the CH= (δ 8.6–8.8 ppm) and NH protons (δ 12.6–
12.9 ppm). Analogous pattern of signal splitting was
observed previously in the spectra of linear products
obtained by three-component condensation of hetaryl-
guanidines with cyclohexanediones and ortho ester [1].
The mass spectrum of IVa contained a strong peak
(Irel 90%) from the molecular ion (m/z 323) and frag-
By heating equimolar mixtures of aminopyrazoles I
and cyclohexanediones II in boiling triethyl orthofor-
mate III we obtained substituted 8,9-dihydropyrazolo-
[1,5-a]quinazolin-6(7H)-ones Va–Vd (Scheme 1). The
reaction involved intermediate formation of linear pyr-
410

THREE-COMPONENT CONDENSATIONS WITH 5-AMINO-4-PHENYLPYRAZOLE
411
Scheme 1.
R1
N
R1
O
NH
N
O
R3
R4
R2
NH
+
+
(EtO)3CH
HN
R4
R3
R2
O
NH2
O
Ia–Ic
IIa–IId
III
IVa, IVb
R1
N
R3
R4
AcONa, AcOH
N
R2
N
O
Va–Vd
Me
O
O
O
N
N
Ph
Me
Me
Ia
+
III
+
N
Ph
VI
I, R1 = Me, R2 = H (a), F (b); R1 = MeOCH2, R2 = H (c); II, R3 = R4 = Me (a); R3 = H, R4 = 2-furyl (b), 4-MeOC6H4 (c), 4-ClC6H4 (d);
IV, R1 = R3 = R4 = Me, R2 = H (a); R1 = Me, R2 = R3 = H, R4 = 2-furyl (b); V, R1 = R3 = R4 = Me, R2 = H (a); R1 = Me, R2 = R3 = H,
R4 = 2-furyl (b); R1 = Me, R2 = F, R3 = H, R4 = 4-MeOC6H4 (c); R1 = MeOCH2, R2 = R3 = H, R4 = 4-ClC6H4 (d).
ment ion peaks with m/z 308, 282, 267, 252, 239, 224,
etc. The base peak was that with m/z 184; it corre-
sponds to methine derivative of aminopyrazole Ia at
the amino group. In the aliphatic region of the 1H NMR
spectrum of IVb we observed a singlet at δ 2.30 ppm
from the methyl group and a multiplet in the region
δ 2.60–2.80 ppm from protons in the cyclohexanedione
fragment. Two protons in the furan ring resonated at
δ 6.06 and 6.28 ppm, and signal from the third proton
in the furan ring was overlapped by aromatic multiplet
1
at δ 7.26–7.52 ppm. The H NMR spectra of com-
pounds Va–Vd lacked doublet signals at δ 8.6–8.8 ppm,
which are typical of CH= proton in IV, and no down-
field signals assignable to NH protons were present
Scheme 2.
N
O
NH
O
R1
R5
N
R5
O
N
N
Ia, Ic
+
III
+
H
Ph
O
N
O
O
N
R5
R5
VIIa, VIIb
NH
N
O
O
O
Me
N
Ia
+
III
+
H
Ph
O
O
Me
O
Me
VIII
VII, R1 = MeOCH2, R5 = H (a); R1 = R5 = Me (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

KRYL’SKII et al.
412
Scheme 3.
R1
N
R6
N
Me
O
H
R6
R2
N
Me
H
Ia, Id
+
III
+
N
N
O
O
IXa–IXc
I, R1 = Me, R2 = H (a), Cl (d); IX, R1 = Me, R2 = H, R6 = Me (a), F3C (b), MeO (c).
(δ 12.6–12.9 ppm). Instead, a singlet appeared at
δ 8.7–8.9 ppm due to proton in the fused pyrimidine
ring (5-H). In the H NMR spectrum of VIIa and
VIIb, the doublet signal from the endocyclic NH pro-
ton was located in a stronger field (δ 11.9–12.0 ppm).
reflux in excess ortho ester III over a period of 15–
30 min; the products were crystalline compounds XI,
XII, and XIV.
1
1
Compound XI displayed in the H NMR spectrum
a set of signals typical of ethoxy group; splitting of
the NH signal into two slightly broadened singlets at
δ 8.42 and 8.53 ppm indicated imino structure B of this
compound. By contrast, compound XII is likely to
exist as the corresponding amino tautomer, as follows
from the presence of a one-proton singlet at δ 8.31 ppm
(5-H) and slightly broadened singlet from two NH2
protons at δ 8.94 ppm. By heating 7-amino-2-methyl-
3-phenylpyrazolo[1,5-a]pyrimidine-6-carbonitrile
(XII) in formamide for 10 h we obtained 8-methyl-7-
phenylpyrazolo[1,5-a]pyrimido[5,4-e]pyrimidin-4-
The reaction of aminopyrazoles Ia and Id with
acetoacetanilides and triethyl orthoformate afforded
2-R1-7-methyl-N,3-diphenylpyrazolo[1,5-a]pyrimi-
dine-6-carboxamides IXa–IXc (Scheme 3). Presum-
ably, the first step of the process is formation of
ethoxymethylidene derivative at the activated methyl-
ene group of acetoacetanilide. Its subsequent reaction
at the amino group in aminopyrazole I is accompanied
by elimination of ethanol molecule, follwed by closure
of pyrimidine ring. Compounds IXa–IXc were isolated
as yellow crystalline substances which are soluble in
dimethylformamide and poorly soluble in most other
organic solvents.
1
amine (XIII). Unlike compound XII, the H NMR
spectrum of XIII contained an additional signal at
δ 9.14 ppm due to proton on C2. Compound XIV gave
rise to strong molecular ion peak in the mass spectrum,
m/z 340 (Irel 90 %), while no IR absorption band was
observed at 2200 cm–1, in keeping with its cyclic
structure.
When aroylacetonitriles were used as carbonyl
component with an activated methylene group, the
condensation products were 3-aryl-2-R1-7-phenylpyra-
zolo[1,5-a]pyrimidine-6-carbonitriles Xa and Xb
(Scheme 4). The mass spectrum of compound Xa con-
tained a strong peak from the molecular ion, m/z 344
(Irel 85%). Other nitriles with an activated methylene
group, namely ethyl cyanoacetate, malononitrile, and
1H-benzimidazol-2-ylacetonitrile, were involved in
three-component condensation with aminopyrazole Ia
and triethyl orthoformate (III) (Scheme 5). The reac-
tions were carried out by heating the reactants under
EXPERIMENTAL
The progress of reactions was monitored, and the
purity of the products was checked, by TLC on Silufol
UV-254 plates. The 1H NMR spectra were recorded on
a Bruker AC-300 (300 MHz) spectrometer from solu-
tions in DMSO-d6 using tetramethylsilane as internal
reference. The mass spectra (electron impact, 70 eV)
Scheme 4.
R1
R7
O
N
CN
N
Id
+
III
+
R2
R7
N
CN
Xa, Xb
X, R1 = Me, R2 = Cl, R7 = H (a), F (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

THREE-COMPONENT CONDENSATIONS WITH 5-AMINO-4-PHENYLPYRAZOLE
413
Scheme 5.
NH2
O
NH
O
O
N
N
N
OEt
N
OEt
Ia
+
III
+
Me
Me
NC
OEt
N
N
H
Ph
Ph
A
XI
B
NH2
N
N
CN
N
N
HCONH2
N
N
NH2
Ia
+
III
+
Me
Me
NC
CN
N
N
Ph
Ph
XII
XIII
NH2
Me
N
CN
N
H
N
N
N
Ia
+
III
+
N
H
Ph
N
XIV
were obtained on an LKB 9000 instrument. The IR
spectra were measured in KBr on a Specord 75IR
spectrometer.
C 69.90; H 5.35; N 11.76. C21H19N3O3. Calculated, %:
C 69.79; H 5.30; N 11.63.
2,8,8-Trimethyl-3-phenyl-8,9-dihydropyrazolo-
[1,5-a]quinazolin-6(7H)-one (Va). Compound IVa,
1.6 g (5 mmol), was ground with 1.5 g of anhydrous
sodium acetate, 5 ml of glacial acetic acid was added,
and the mixture was heated for 30 min under reflux.
The mixture was poured into 100 ml of cold water, and
the precipitate was filtered off, washed with water,
dried, and recrystallized from toluene. Yield 0.93 g
Initial 3-substituted 4-phenyl-1H-pyrazol-5-amines
were synthesized according to the procedure reported
in [13].
5,5-Dimethyl-2-[(3-methyl-4-phenyl-1H-pyra-
zol-5-ylamino)methylidene]cyclohexane-1,3-dione
(IVa). A mixture of 1.73 g (0.01 mol) of aminopyra-
zole Ia, 1.44 g (0.01 mol) of 5,5-dimethylcyclohexane-
1,3-dione (IIa, dimedone), and 2 ml of triethyl ortho-
formate (III) was heated for 15 min under reflux. The
yellowish precipitate was filtered off, washed with
propan-2-ol, and recrystallized from xylene. Yield
1
(61%), mp 195–196°C. H NMR spectrum, δ, ppm:
1.21 s (6H, CH3), 2.58 s (2H, CH2), 2.64 s (3H, CH3),
3.36 s (2H, CH2), 7.31 t (1H, Harom, J = 7.5 Hz), 7.45 t
(2H, Harom, J = 7.5 Hz), 7.70 d (2H, Harom, J = 7.5 Hz),
8.78 s (1H, 5-H). Found, %: C 74.62; H 6.35; N 13.70.
C19H19N3O. Calculated, %: C 74.73; H 6.27; N 13.76.
1
2.20 g (68%), mp 244–245°C. H NMR spectrum, δ,
ppm: 1.03 s (6H, CH3), 2.22 s (3H, CH3), 2.28 s (4H,
CH2), 7.30–7.56 m (5H, Harom), 8.68 d (1H, =CH,
J = 12 Hz), 12.60 s (1H, 1′-H), 12.81 d (1H, 5′-NH,
J = 12 Hz). Mass spectrum: m/z 323 (Irel 90%) [M]+.
Found, %: C 70.42; H 6.58; N 12.73. C19H21N3O2. Cal-
culated, %: C 70.57; H 6.55; N 12.99. M 323.40.
8-(2-Furyl)-2-methyl-3-phenyl-8,9-dihydropyra-
zolo[1,5-a]quinazolin-6(7H)-one (Vb) was synthe-
sized in a similar way from 1.8 g (5 mmol) of com-
pound IVb. Yield 1.00 g (58%), mp 196–198°C.
1H NMR spectrum, δ, ppm: 2.33 s (3H, CH3), 2.65–
2.88 m (5H, CH, CH2), 6.10 d (1H, C4H3O, J =
5-(2-Furyl)-2-[(3-methyl-4-phenyl-1H-pyrazol-5-
ylamino)methylidene]cyclohexane-1,3-dione (IVb)
was synthesized in a similar way from 1.73 g
(0.01 mol) of aminopyrazole Ia and 1.78 g (0.01 mol)
of diketone IIb. Yield 2.56 g (71%), mp 236–238°C.
1H NMR spectrum, δ, ppm: 2.30 s (3H, CH3), 2.60–
2.80 m (5H, CH, CH2), 6.06 d (1H, C4H3O, J =
4.6 Hz), 6.32 s (1H, C4H3O), 7.34–7.64 m (6H, Harom
,
C4H3O), 8.95 s (1H, 5-H). Found, %: C 73.60; H 5.05;
N 12.36. C21H17N3O2. Calculated, %: C 73.45; H 4.99;
N 12.24.
3-(4-Fluorophenyl)-8-(4-methoxyphenyl)-2-
methyl-8,9-dihydropyrazolo[1,5-a]quinazolin-
6(7H)-one (Vc). A mixture of 1.91 g (0.01 mol) of
aminopyrazole Ib, 2.18 g (0.01 mol) of diketone IIc,
and 4 ml of triethyl orthoformate (III) was heated for
4.6 Hz), 6.28 s (1H, C4H3O), 7.28–7.52 m (6H, Harom
,
C4H3O), 8.70 d (1H, =CH–, J = 12 Hz), 12.67 s (1H,
1′-H), 12.84 d (1H, 5′-NH, J = 12 Hz). Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

KRYL’SKII et al.
414
45 min under reflux. The mixture was cooled, and the
precipitate was filtered off, washed with propan-2-ol,
and recrystallized from toluene. Yield 2.81 g (70%),
11.95 d (1H, 5′-NH, J = 12 Hz), 12.70 s (1H, 1′-H).
Found, %: C 60.23; H 5.13; N 20.55. C17H17N5O3. Cal-
culated, %: C 60.17; H 5.05; N 20.64.
1
mp 252–253°C. H NMR spectrum, δ, ppm: 2.43–
6-Methyl-3-[(3-methyl-4-phenyl-1H-pyrazol-5-
ylamino)methylidene]-3,4-dihydro-2H-pyran-2,4-
dione (VIII) was synthesized in a similar way from
1.73 g (0.01 mol) of aminopyrazole Ia and 1.26 g
(0.01 mol) of 6-methyl-3,4-dihydro-2H-pyran-2,4-di-
one. Yield 1.88 g (61%), mp >300°C. 1H NMR spec-
trum, δ, ppm: 2.12 s (3H, CH3), 2.27 s (3H, CH3),
5.22 s (1H, =CH), 7.24–7.57 m (5H, Harom), 8.80 d
(1H, =CH, J = 12 Hz), 11.65 d (1H, 5′-NH, J = 12 Hz),
12.78 s (1H, 1′-H). Found, %: C 66.12; H 4.94;
N 13.65. C17H15N3O3. Calculated, %: C 66.01; H 4.89;
N 13.58.
2.67 m (5H, CH, CH2), 3.43 s (3H, OCH3), 7.20–
7.64 m (8H, Harom), 9.06 s (1H, 5-H). Found, %:
C 71.70; H 5.10; N 10.39. C24H20FN3O2. Calculated,
%: C 71.81; H 5.02; N 10.47.
8-(4-Chlorophenyl)-2-methoxymethyl-3-phenyl-
8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-one
(Vd) was synthesized in a similar way from 2.03 g
(0.01 mol) of aminopyrazole Ic and 2.22 g (0.01 mol)
of diketone IId. Yield 2.79 g (67%), mp 240–241°C.
1H NMR spectrum, δ, ppm: 2.50–2.71 m (5H, CH,
CH2), 3.41 s (3H, OCH3), 4.62 s (2H, OCH2), 7.31–
7.82 m (9H, Harom), 8.91 s (1H, 5-H). Found, %:
C 68.77; H 4.91; N 10.19. C24H20ClN3O2. Calculated,
%: C 68.98; H 4.82; N 10.06.
2,7-Dimethyl-N-(2-methylphenyl)-3-phenylpyra-
zolo[1,5-a]pyrimidine-6-carboxamide (IXa). A mix-
ture of 1.73 g (0.01 mol) of aminopyrazole Ia, 1.91 g
(0.01 mol) of N-(2-methylphenyl)-3-oxobutanamide,
and 2 ml of triethyl orthoformate (III) was heated for
1 h under reflux. The mixture was cooled, and the
yellow precipitate was filtered off, washed with pro-
pan-2-ol, and recrystallized from DMF. Yield 2.31 g
2,7-Dimethyl-3-phenylpyrazolo[1,5-a]pyrimidin-
6-yl(phenyl)methanone (VI). A mixture of 1.73 g
(0.01 mol) of aminopyrazole Ia, 1.62 g (0.01 mol) of
benzoylacetone, and 2 ml of triethyl orthoformate (III)
was heated for 1 h under reflux. The precipitate was
filtered off, washed with propan-2-ol, and recrystal-
lized from dioxane. Yield 1.99 g (61%), mp 205–
1
(65%), mp 199–200°C. H NMR spectrum, δ, ppm:
2.32 s (3H, CH3), 2.51 s (3H, CH3), 2.68 s (3H, CH3),
7.01–7.70 m (9H, Harom), 8.70 s (1H, 5-H), 9.90 s (1H,
NH). Found, %: C 74.26; H 5.55; N 15.76. C22H20N4O.
Calculated, %: C 74.14; H 5.66; N 15.72.
1
207°C. H NMR spectrum, δ, ppm: 2.50 s (3H, CH3),
2.65 s (3H, CH3), 7.23–7.70 m (10H, Harom), 8.12 s
(1H, 5-H). Found, %: C 76.96; H 5.35; N 12.76.
C21H17N3O. Calculated, %: C 77.04; H 5.23; N 12.83.
2,7-Dimethyl-3-phenyl-N-[2-(trifluoromethyl)-
phenyl]pyrazolo[1,5-a]pyrimidine-6-carboxamide
(IXb) was synthesized in a similar way from 1.73 g
(0.01 mol) of aminopyrazole Ia and 2.45 g (0.01 mol)
of 3-oxo-N-[2-(trifluoromethyl)phenyl]butanamide.
5-[(3-Methoxymethyl-4-phenyl-1H-pyrazol-5-yl-
amino)methylidene]hexahydropyrimidine-2,4,6-tri-
one (VIIa). A mixture of 2.03 g (0.01 mol) of amino-
pyrazole Ic, 1.28 g (0.01 mol) of barbituric acid, and
2 ml of triethyl orthoformate (III) was heated for 1 h
under reflux. The mixture was cooled, and the pre-
cipitate was filtered off, washed with propan-2-ol,
and recrystallized from DMF. Yield 1.84 g (54%),
1
Yield 1.97 g (48%), mp 186–188°C. H NMR spec-
trum, δ, ppm: 2.66 s (3H, CH3), 2.99 s (3H, CH3),
7.21–7.80 m (9H, Harom), 8.67 s (1H, 5-H), 10.21 s
(1H, NH). Found, %: C 64.32; H 4.24; N 13.61.
C22H17F3N4O. Calculated, %: C 64.39; H 4.18; N 13.65.
1
mp >300°C. H NMR spectrum, δ, ppm: 3.32 s (3H,
OCH3), 4.41 s (2H, OCH2), 7.30–7.60 m (5H, Harom),
8.68 d (1H, =CH, J = 12 Hz), 10.80 s and 10.96 s (1H
each, 1-H, 3-H), 11.98 d (1H, 5′-NH, J = 12 Hz), 13.22 s
(1H, 1′-H). Found, %: C 56.56; H 4.36; N 20.57.
C16H15N5O4. Calculated, %: C 56.30; H 4.43; N 20.52.
3-(4-Chlorophenyl)-N-(2-methoxyphenyl)-2,7-
dimethylpyrazolo[1,5-a]pyrimidine-6-carboxamide
(IXc) was synthesized in a similar way from 2.07 g
(0.01 mol) of aminopyrazole Id and 2.07 g (0.01 mol)
of N-(2-methoxyphenyl)-3-oxobutanamide. Yield
1
2.27 g (56%), mp 220–222°C. H NMR spectrum, δ,
1,3-Dimethyl-5-[(3-methyl-4-phenyl-1H-pyrazol-
5-ylamino)methylidene]hexahydropyrimidine-2,4,6-
trione (VIIb) was synthesized in a similar way from
1.73 g (0.01 mol) of aminopyrazole Ia and 1.56 g
(0.01 mol) of 1,3-dimethylbarbituric acid. Yield 1.76 g
(52%), mp >300°C. 1H NMR spectrum, δ, ppm: 2.32 s
(3H, CH3), 3.22 s (3H, CH3), 3.24 s (3H, CH3), 7.30–
7.56 m (5H, Harom), 8.80 d (1H, =CH, J = 12 Hz),
ppm: 2.61 s (3H, CH3), 2.94 s (3H, CH3), 3.82 s (3H,
OCH3), 6.92–8.00 m (8H, Harom), 8.68 s (1H, 5-H),
9.85 s (1H, NH). Found, %: C 65.03; H 4.64; N 13.66.
C22H19ClN4O2. Calculated, %: C 64.95; H 4.71;
N 13.77.
3-(4-Chlorophenyl)-2-methyl-7-phenylpyrazolo-
[1,5-a]pyrimidine-6-carbonitrile (Xa). A mixture of
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THREE-COMPONENT CONDENSATIONS WITH 5-AMINO-4-PHENYLPYRAZOLE
415
2.07 g (0.01 mol) of aminopyrazole Id, 1.45 g
(0.01 mol) of benzoylacetonitrile, and 2 ml of triethyl
orthoformate (III) was heated for 1 h under reflux. The
mixture was cooled, and the precipitate was filtered
off, washed with propan-2-ol, and recrystallized from
DMF. Yield 2.47 g (72%), mp >300°C. 1H NMR spec-
trum, δ, ppm: 2.58 s (3H, CH3), 7.46–7.95 m (9H,
(0.01 mol) of compound XII and 5 ml of formamide
was heated for 10 h under reflux. The mixture was
cooled, and the precipitate was filtered off and recrys-
tallized from DMF. Yield 1.21 g (44%), mp 206–
1
208°C. H NMR spectrum, δ, ppm: 2.61 s (3H, CH3),
7.26 t (1H, Harom, J = 7.6 Hz), 7.42 t (2H, Harom, J =
7.6 Hz), 7.68 d (2H, Harom, J = 7.6 Hz), 8.10 br.s. (2H,
NH2), 8.50 s (1H, CH), 9.14 s (1H, CH). Found, %:
C 65.44; H 4.48; N 30.37. C15H12N6. Calculated, %:
C 65.21; H 4.38; N 30.42.
H
arom), 8.84 s (1H, 5-H). Mass spectrum: m/z 344
(Irel 85%) [M]+. Found, %: C 69.53; H 3.68; N 16.41.
C20H13ClN4. Calculated, %: C 69.67; H 3.80; N 16.25.
M 344.81.
6-(1H-Benzimidazol-2-yl)-2-methyl-3-phenylpyr-
azolo[1,5-a]pyrimidin-7-amine (XIV). A mixture of
1.73 g (0.01 mol) of aminopyrazole Ia, 1.57 g
(0.01 mol) of 1H-benzimidazol-2-ylacetonitrile, and
3 ml of triethyl orthoformate was heated for 30 min
under reflux. The mixture was cooled, and the precip-
itate was filtered off, washed with propan-2-ol, and
recrystallized from DMF. Yield 2.11 g (62%),
3-(4-Chlorophenyl)-7-(4-fluorophenyl)-2-methyl-
pyrazolo[1,5-a]pyrimidine-6-carbonitrile (Xb) was
synthesized in a similar way from 2.07 g (0.01 mol) of
aminopyrazole Id and 1.63 g (0.01 mol) of 4-fluoro-
benzoylacetonitrile. Yield 2.31 g (64%), mp 248–
1
250°C. H NMR spectrum, δ, ppm: 2.55 s (3H, CH3),
7.54–7.88 m (8H, Harom), 8.90 s (1H, 5-H). Found, %:
C 66.35; H 3.38; N 15.40. C20H12ClFN4. Calculated,
%: C 66.21; H 3.33; N 15.44.
1
mp >300°C. H NMR spectrum, δ, ppm: 2.62 s (3H,
CH3), 7.21–7.78 m (9H, Harom), 8.35 br.s (2H, NH2),
8.55 s (1H, NH), 8.91 s (1H, CH). Mass spectrum:
m/z 340 (Irel 90%) [M]+. Found, %: C 70.61; H 4.65;
N 24.71. C20H16N6. Calculated, %: C 70.57; H 4.74;
N 24.69. M 340.39.
Ethyl 7-imino-2-methyl-3-phenyl-4,7-dihydro-
pyrazolo[1,5-a]pyrimidine-6-carboxylate (XI).
A mixture of 1.73 g (0.01 mol) of aminopyrazole Ia,
1.35 g (0.012 mol) of ethyl cyanoacetate, and 2 ml of
triethyl orthoformate was heated for 30 min under re-
flux. The mixture was cooled, and the precipitate was
filtered off, washed with propan-2-ol, and recrystal-
lized from dioxane. Yield 2.01 g (68%), mp 192–
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 08-03-99022r_ofi).
1
193°C. H NMR spectrum, δ, ppm: 1.42 t (3H,
REFERENCES
CH2CH3, J = 7.1 Hz), 2.60 s (3H, CH3), 4.38 q (2H,
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(2H, Harom, J = 7.6 Hz), 7.68 d (2H, Harom, J = 7.6 Hz),
8.42 s and 8.53 s (1H each, NH), 8.60 s (1H, 5-H).
Found, %: C 64.75; H 5.48; N 18.70. C16H16N4O2. Cal-
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010