A simple synthesis of 1Н-pyrazolo[3,4-b]pyridines

Article abstract of DOI:10.1007/s10593-017-2165-y

[Figure not available: see fulltext.] 3-Acetyl-4,6-diaryl-2-methylaminopyridines were synthesized via rearrangement of quaternary 4,6-diaryl-3-cyano-2-methylpyridinium salts. Annulation of the pyrazole ring of pyrazolo[3,4-b]pyridines was achieved by N-ni

Full text of DOI:10.1007/s10593-017-2165-y

DOI 10.1007/s10593-017-2165-y
Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
A simple synthesis of 1Н-pyrazolo[3,4-b]pyridines
Ekaterina E. Sizova1, Evgenii V. Arshinov1, Yana A. Kotsareva1,
Larisa V. Glizdinskaya1, Galina P. Sagitullina1*
1 F. M. Dostoevskii Omsk State University,
55а Mir Ave., Omsk 644077, Russia; е-mail: sagitullina@chemomsu.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(9), 1026–1032
Submitted June 16, 2017
Accepted August 7, 2017
3-Acetyl-4,6-diaryl-2-methylaminopyridines were synthesized via rearrangement of quaternary 4,6-diaryl-3-cyano-2-methylpyridinium
salts. Annulation of the pyrazole ring of pyrazolo[3,4-b]pyridines was achieved by N-nitrosation of the methylamino group of the pyri-
dine and reduction of N-nitroso group to the hydrazine group with simultaneous intramolecular closure of the pyrazole ring.
Keywords: 3-acetyl-4,6-diaryl-2-methylaminopyridines, 4,6-diaryl-2-methylpyridine-3-carbonitriles, 1Н-pyrazolo[3,4-b]pyridines, quaternary
pyridinium salts, Dimroth rearrangement.
1H-Pyrazolo[3,4-b]pyridines exhibit a wide range of
biological activity, in particular antimicrobial,1a,b
antibacterial,1c antimalarial,1d antiviral,1e antitumor,1f,g and
anti-leishmaniasis1h activity.
intramolecular alkylation of the pyrazole ring with an
indolinium cation, and aromatization of the desired product
accompanied by C–N bond cleavage of the indole pyrrole
ring.5a
The three-component one-pot Hantzsch synthesis, the
reaction of 1-phenyl-2-(phenylsulfonyl)ethanone, an
aromatic aldehyde, and 3-amino-5-phenylpyrazole yielded
The inhibitory activity of pyrazolo[3,4-b]pyridines
against the inflammatory cytokines IL-6 has been revealed,
they are considered promising agents for the treatment of
rheumatoid arthritis. Pyrazolo[3,4-b]pyridines are orexin
receptor antagonists and can be used to treat insomnia.
They exhibit the properties of inhibitors of glycogen
synthase (GSK-3) involved in the phosphorylation of Tau
protein, the consequence of which is Alzheimer's disease.2
Drugs based on 1H-pyrazolium[3,4-b]pyridines, carta-
zolate, tracazolate, and etazolate are used to treat diseases
of the nervous system, while riociguat is employed as an
effective tool in the treatment of pulmonary hypertension
(Fig. 1).3
The main routes for the formation of the bicyclic
structure of pyrazolo[3,4-b]pyridines are the reactions of
annulation of the pyridine moiety to a pyrazole ring and
annulation of the pyrazole moiety to a pyridine ring.4
An original two-component one-pot synthesis of 5-aryl-
pyrazolo[3,4-b]pyridines via the reaction of 3-formyl-
indoles with 5-aminopyrazoles in the presence of a Lewis
acid has been published. The formation of pyrazolo[3,4-b]-
pyridines undergoes the stages of imine formation,
O
Me
HN
CO2Me
NH2
N
N
H2N
Br
N
N
N
H
N
HO
GSK-3 inhibitor
N
N
N
n-Bu
Me
Me
NH
NH
F
EtO2C
R
N
Riociguat
N
EtO2C
N
N
N
Et
N
N
R = H Cartazolate
R = Me Tracazolate
Et
Etazolate
Figure 1. Biologically active derivatives of 1Н-pyrazolo[3,4-b]-
pyridines.
0009-3122/17/53(09)-1026©2017 Springer Science+Business Media New York
1026

Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
Scheme 1
Ar1
Ar1
Ar1
Ar1
1. Me2SO4, 90°C
1–7 days
Air
CN
Me
CN
CN
Me
CN
Me
EtONa
oxidation
+
+
N
Me
EtOH,
4–15 h
2. NaClO4
H2O, rt
Ar
N
Ar
Me
ClO4
H2N
Ar
N
H
Ar
O
–
1a–g
A
2a–g
3a–g
a Ar = Ar1 = Ph; b Ar = Ar1 = 4-MeC6H4; c Ar = Ar1 = 4-MeOC6H4; d Ar = Ph, Ar1 = 4-ClC6H4;
e Ar = 4-MeOC6H4, Ar1 = Ph; f Ar = Ph, Ar1 = 4-MeOC6H4; g Ar = 4-BrC6H4, Ar1 = 4-MeOC6H4
4-aryl-3,6-diphenylpyrazolo-1H-[3,4-b]pyridines. Aromatiza-
tion of the 1,4-dihydropyridone moiety of pyrazolo[3,4-b]-
pyridine takes place by elimination of a phenylsulfinic acid
molecule.5b
In the same manner, pyrazolo[3,4-b]pyridines with the
carboxyl group at position 6 and the nitro group at position
5 of the pyridine ring were obtained.5c,d
In 2017, a new method for the synthesis of functionally
substituted pyrazolo[3,4-b]pyridines by cyclocondensation
of 4-acyl-1H-pyrrole-2,3-dione with 3-methyl-1-phenyl-1H-
pyrazole-5-amine was published. 4-Acylpyrrole-2,3-dione
serves as the Michael acceptor, whereas 5-aminopyrazole
serves as the donor in the Michael reaction. After
cyclization of the Michael adduct with the participation of
the amino group of pyrazole and the acyl group of 4-acyl-
pyrrole-2,3-dione, a tricyclic molecule is formed in which
cleavage of the C–N bond of the pyrrole-2,3-dione ring
takes place with the formation of pyrazolo[3,4-b]pyridine.5e
The known methods for synthesizing 3-amino-1H-pyra-
zolo[3,4-b]pyridines by annulaling the pyrazole moiety to
pyridine ring are based on the interaction of 2-halo-,
2-methoxy-, and 2-methylsulfanylpyridine-3-carbonitriles
with hydrazine.4
by alkylation of pyridines 2a–g with dimethyl sulfate
(Scheme 1).
For the synthesis of pyridines 4a–g, a double rearrange-
ment of quaternary 3-cyanopyridinium salts 3a–g was
used, the final stage being the Dimroth rearrangement.6 The
rearrangement of salts 3a–g into 3-acetyl-4,6-diaryl-
2-methylaminopyridines 4a–g was carried out by heating
with aqueous-alcoholic alkali (Scheme 2). In the first stage
of the reaction, the hydroxide ion attacks position 2 of
pyridinium salt 3a–g to form the pseudo base A, a neutral
analog of the anionic σ-complex. After cleavage of the C–N
bond of the pyridine ring and rotation of the C(3)–C(4)
bond of the open form B, the cyano group reacts with the
electron-deficient carbon atom to form a new C–N bond of
the cyclic amidine C. The Dimroth rearrangement proceeds
via the addition of hydroxide ion at position 6 of the
amidine C, which leads to the formation of an anionic
σ-complex D, in which the polarized C–N bond breaks.
The rotation of the C(2)–C(3) bond in the formed open
form E provides a spatial convergence of the carbonyl
group and the primary amino group, their interaction
completing the formation of the pyridine ring of
compounds 4ag. As a result of the Dimroth rearrangement
the endocyclic and exocyclic nitrogen atoms change places
(Scheme 2).6
In this paper, we employ a novel method of annulaling the
pyrazole moiety to pyridine ring to access 1H-pyrazolo[3,4-b]-
pyridines.
The initial Hantzsch 4,6-diarylpyridine-3-carbonitriles
2a–g were synthesized in a single step by the interaction of
chalcones 1a–g with 3-aminocrotononitrile. Intermediate
1,4-dihydropyridines A are oxidized by atmospheric
oxygen. Quaternary pyridinium salts 3a–g were obtained
Annulation of the pyrazole ring of pyrazolo[3,4-b]-
pyridines 6a–g was carried out by N-nitrosation of the
secondary amino group of pyridines 4a–g followed by
reduction of the N-nitroso group in compounds 5a–g to the
hydrazine group with concurrent intramolecular closure of
the pyrazole ring with the participation of the acetyl group
Scheme 2
1027

Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
1
(Scheme 3). Both reaction steps are carried out at room
1384, 818. H NMR spectrum, δ, ppm: 2.45 (3H, s) and
2.48 (3H, s, ArСН3, Ar1СН3); 2.93 (3H, s, 2-CH3); 7.31–
7.35 (2H, m, H-3,5 Ar1); 7.35–7.39 (2H, m, H-3,5 Ar); 7.55–
7.58 (2H, m, H-2,6 Ar1); 7.66 (1H, s, H-5); 7.99–8.03 (2H,
m, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 21.3; 21.4; 24.4;
105.4; 117.4; 117.6; 127.4 (2С); 128.4 (2С); 129.7 (4С);
133.8; 135.1; 140.1; 140.6; 153.8; 159.1; 162.7. Found, %:
C 84.49; H 6.02; N 9.40. C21H18N2. Calculated, %:
C 84.53; H 6.08; N 9.39.
temperature.
Scheme 3
Ar1
N
Ar1
N
Me
N
Ac
N
NaNO2
4a–g
Zn
NO
AcOH
AcOH
<10°C
then rt, 1 h
N
Ar
Ar
rt, 1 h
Me
Me
5a g
–
6a g
–
4,6-Bis(4-methoxyphenyl)-2-methylpyridine-3-carbo-
nitrile (2c). Yield 20.48 g (62%), colorless crystals, mp 173–
174°С (THF) (mp 172–173°С (EtOH)8c).
a Ar = Ar1 = Ph; b Ar = Ar1 = 4-MeC6H4; c Ar = Ar1 = 4-MeOC6H4;
d Ar = Ph, Ar1 = 4-ClC6H4; e Ar = 4-MeOC6H4, Ar1 = Ph;
Ar = Ph, Ar = 4-MeOC6H4; Ar = 4-BrC6H4, Ar = 4-MeOC6H4
1
1
f
g
4-(4-Chlorophenyl)-2-methyl-6-phenylpyridine-3-carbo-
nitrile (2d). Yield 20.12 g (66%), colorless crystals, mp 177–
178°С (AcOH) (mp 178–178.5°С (EtOH)8d). IR spectrum,
To conclude, a simple and effective synthesis of 1H-py-
1
razolo[3,4-b]pyridines has been developed. The double
rearrangement of the quaternary 4,6-diaryl-3-cyano-
2-methylpyridinium salts is completed by the Dimroth
rearrangement of the pyridine ring to form 3-acetyl-4,6-
diaryl-2-methylaminopyridines. Annulation of the pyrazole
ring of pyrazolo[3,4-b]pyridines is carried out by N-nitro-
sation of 3-acetyl-4,6-diaryl-2-methylaminopyridines with
sodium nitrite in acetic acid and reduction of N-nitroso-
pyridine with zinc dust in acetic acid to 2-hydrazino-
pyridine with simultaneous intramolecular reaction of
hydrazine and acetyl groups.
ν, cm–1: 2215, 1581, 1537, 1094, 833. H NMR spectrum,
δ, ppm: 2.92 (3H, s, 2-CH3); 7.48–7.54 (5H, m, H-3,5 Ar1,
Н-3,4,5 Ph); 7.56–7.60 (2H, m, H-2,6 Ar1); 7.64 (1H, s,
H-5); 8.05–8.10 (2H, m, H-2,6 Ph). 13C NMR spectrum,
δ, ppm: 24.1; 105.6; 117.0; 117.7; 127.5 (2С); 129.0 (2С);
129.3 (2С); 129.8 (2С); 130.5; 134.9; 136.3; 137.6; 152.6;
159.4; 162.9. Found, %: C 74.90; H 4.35; N 9.14.
C19H13ClN2. Calculated, %: C 74.88; H 4.30; N 9.19.
6-(4-Methoxyphenyl)-2-methyl-4-phenylpyridine-3-car-
bonitrile (2e). Yield 20.43 g (68%), colorless crystals,
mp 145–146°С (AcOH) (mp 138.5–139 °С (EtOH)8d).
IR spectrum, ν, cm–1: 2216, 1585, 1538, 1254, 1031, 820.
1H NMR spectrum, δ, ppm: 2.90 (3H, s, 2-CH3); 3.88 (3H,
s, OCH3); 6.99–7.04 (2H, m, H-3,5 Ar); 7.50–7.57 (3H, m,
H-3,4,5 Ph); 7.60–7.65 (3H, m, H-5, Н-2,6 Ph); 8.03–8.09
(2H, m, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 24.4; 55.4;
104.9; 114.4 (2С); 117.0; 117.4; 128.4 (2С); 129.0 (4С);
129.8; 130.3; 136.8; 153.7; 158.8; 161.6; 162.7. Found, %:
C 80.06; H 5.41; N 9.40. C20H16N2O. Calculated, %:
C 79.98; H 5.37; N 9.33.
Experimental
IR spectra were registered on a Simex FT-801
1
spectrometer in KBr pellets. H and 13C NMR spectra were
acquired on a Bruker Avance DRX-400 spectrometer (400
and 100 MHz, respectively) in DMSO-d6 (compounds 3a–g)
and in CDCl3 (remaining compounds). Chemical shifts
were assigned relative to the signal of the solvent (DMSO-d6:
1
2.50 ppm for Н nuclei, 39.5 ppm for 13С nuclei; CDCl3:
7.26 ppm for 1Н nuclei, 77.0 ppm for 13С nuclei). 13C NMR
spectra were recorded with J-modulation. Elemental
analysis was performed on a PerkinElmer 2400 Series II
CHN-analyzer. Melting points were determined on a
Boetius heating bench. Monitoring of the reaction progress
and assessment of the purity of synthesized compounds
was done by TLC on Silufol UV-254 plates.
4-(4-Methoxyphenyl)-2-methyl-6-phenylpyridine-3-car-
bonitrile (2f). Yield 22.53 g (75%), colorless crystals,
mp 159–160°С (AcOH) (mp 157°С (EtOH)8e). IR spectrum,
ν, cm–1: 2215, 1584, 1539, 1248, 1028, 830. H NMR
1
spectrum, δ, ppm: 2.91 (3H, s, 2-CH3); 3.89 (3H, s, OCH3);
7.03–7.09 (2H, m, H-3,5 Ar1); 7.45–7.53 (3H, m, H-3,4,5
Ph); 7.59–7.62 (2H, m, Н-2,6 Ar1); 7.65 (1H, s, H-5); 8.04–
8.11 (2H, m, H-2,6 Ph). 13C NMR spectrum, δ, ppm: 24.4;
55.4; 105.5; 114.5 (2С); 117.6; 117.7; 127.4 (2С); 128.8; 128.9
(2С); 129.9 (2С); 130.2; 137.9; 153.5; 159.1; 161.1; 162.8.
Found, %: C 79.96; H 5.35; N 9.36. C20H16N2O.
Calculated, %: C 79.98; H 5.37; N 9.33.
3-Aminocrotononitrile supplied by Fluka was used.
Chalcones 1a–g were obtained according to published
methods.7 Synthesis of compound 2а was performed
according to a published method.8а
Synthesis of 4,6-diaryl-2-methylpyridine-3-carbonitriles
2a–g (General method). 3-Aminocrotononitrile (8.21 g,
100 mmol) and chalcone 1a–g (100 mmol) were added to a
solution of Na (2.00 g, 87 mmol) in absolute EtOH (75 ml).
The reaction mixture was heated under reflux for 4–15 h
(TLC control), then stirred at room temperature for 8–12 h.
The formed crystals were filtered off, washed with EtOH.
2-Methyl-4,6-diphenylpyridine-3-carbonitrile (2a). Yield
19.44 g (72%), colorless crystals, mp 118–119°С (EtOH)
(mp 116°С (EtOH);8a,e mp 117.5–118°С (EtOH)8b).
2-Methyl-4,6-bis(4-methylphenyl)pyridine-3-carbo-
nitrile (2b). Yield 19.69 g (66%), colorless crystals, mp 192–
193°С (AcOH). IR spectrum, ν, cm–1: 2215, 1587, 1540,
6-(4-Bromophenyl)-4-(4-methoxyphenyl)-2-methylpy-
ridine-3-carbonitrile (2g). Yield 35.25 g (93%), colorless
crystals, mp 225–226°С (EtOAc). IR spectrum, ν, cm–1:
2214, 1584, 1538, 1254, 1183, 1027, 825. 1H NMR
spectrum, δ, ppm: 2.89 (3H, s, 2-CH3); 3.89 (3H, s, OСН3);
7.03–7.09 (2H, m, H-3,5 Ar1); 7.57–7.66 (5H, m, H-5,
H-3,5 Ar, H-2,6 Ar1); 7.92–7.99 (2H, m, H-2,6 Ar).
13C NMR spectrum, δ, ppm: 24.4; 55.4; 105.9; 114.5 (2С);
117.3; 117.4; 124.9; 128.6; 128.9 (2С); 129.9 (2С); 132.1
(2С); 136.7; 153.7; 157.8; 161.1; 162.9. Found, %:
C 63.40; H 4.02; N 7.40. C20H15BrN2О. Calculated, %:
C 63.34; H 3.99; N 7.39.
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Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
7.75 (5H, m, H Ph); 7.85–7.92 (2H, m, H-2,6 Ar); 8.19
Synthesis of quaternary 4,6-diaryl-3-cyano-2-methyl-
pyridinium 3a–g (General method). A mixture of nitrile
2a–g (5.0 mmol) and freshly distilled Me2SO4 (2.4 ml,
25.0 mmol) was heated at 90°С (reaction time shown
below). After cooling, the reaction mixture was washed
with Et2O (3×10 ml), and the diethyl ether wash decanted.
The residue was dissolved in the minimum amount of
water, and a saturated aqueous NaClO4 (0.64 g, 5.3 mmol)
added. The precipitated perchlorate salt was filtered off,
dried, and purified by recrystallization from EtOH.
(1H, s, H-5). 13C NMR spectrum, δ, ppm: 22.1; 45.0; 56.2;
110.9; 115.1; 115.2 (2С); 124.5; 128.0; 129.7 (2С); 129.8
(2С); 132.0 (2С); 132.5; 133.9; 157.5; 159.1; 162.1; 162.4.
Found, %: C 60.88; H 4.65; N 6.80. C21H19ClN2O5.
Calculated, %: C 60.80; H 4.62; N 6.75.
3-Cyano-4-(4-methoxyphenyl)-1,2-dimethyl-6-phenyl-
pyridinium perchlorate (3f). Reaction time 96 h. Yield
1
1.83 g (88%), colorless crystals, mp 232–233°С. H NMR
spectrum, δ, ppm: 3.09 (3H, s, 2-CH3); 3.88 (3H, s, OСН3);
3.99 (3H, s, 1-CH3); 7.19–7.24 (2H, m, H-3,5 Ar1); 7.66–
7.73 (5H, m, H-3,4,5 Ph, H-2,6 Ar1); 7.93–7.97 (2H, m,
H-2,6 Ph); 8.19 (1H, s, H-5). 13C NMR spectrum, δ, ppm:
22.0; 44.6; 56.2; 110.5; 115.4 (2С); 115.5; 125.5; 127.2;
129.7 (4С); 132.0 (2С); 132.1; 132.6; 157.3; 158.3; 162.2;
163.2. Found, %: C 60.84; H 4.60; N 6.78. C21H19ClN2O5.
Calculated, %: C 60.80; H 4.62; N 6.75.
3-Cyano-1,2-dimethyl-4,6-diphenylpyridinium perchlo-
rate (3a). Reaction time 24 h. Yield 1.50 g (78%), colorless
1
crystals, mp 221–223°С. H NMR spectrum, δ, ppm: 3.13
(3H, s, 2-CH3); 4.00 (3H, s, 1-CH3); 7.63–7.76 (8H, m,
H 4-Ph, H-3,4,5 6-Ph); 7.87–7.94 (2H, m, H-2,6 6-Ph);
8.23 (1H, s, H-5). 13C NMR spectrum, δ, ppm: 22.0; 44.8;
111.7; 115.0; 128.0; 129.7 (4С); 129.7 (2С); 129.8 (2С);
132.2; 132.5; 132.6; 133.8; 158.1; 158.9; 162.2. Found, %:
C 62.40; H 4.51; N 7.35. C20H17ClN2O4. Calculated, %:
C 62.42; H 4.45; N 7.28.
6-(4-Bromophenyl)-3-cyano-4-(4-methoxyphenyl)-1,2-di-
methylpyridinium perchlorate (3g). Reaction time 24 h.
Yield 2.20 g (89%), colorless crystals, mp 204–205°С.
1H NMR spectrum, δ, ppm: 3.09 (3H, s, 2-CH3); 3.88 (3H,
s, OCH3); 3.99 (3H, s, 1-CH3); 7.20–7.25 (2H, m, H-3,5 Ar1);
7.62–7.68 (2H, m, H-3,5 Ar); 7.86–7.97 (4H, m, H-2,6 Ar,
H-2,6 Ar1); 8.20 (1H, s, H-5). 13C NMR spectrum, δ, ppm:
22.0; 44.6; 56.2; 110.6; 115.1; 115.4 (2С); 125.5; 126.0;
127.3; 131.7; 131.8 (2С); 132.0 (2С); 132.7 (2С); 157.2;
157.3; 162.2; 163.3. Found, %: C 50.99; H 3.63; N 5.74.
C21H18BrClN2O5. Calculated, %: C 51.09; H 3.67; N 5.67.
Synthesis of 3-acetylpyridines 4a–g (General method).
10% Aqueous NaOH solution (1.8 ml, 5 mmol) was added
to a suspension of the quaternary pyridinium salt 3a–g
(1 mmol) in EtOH (4 ml). The reaction mixture acquires an
intense burgundy color, which disappears after heating
under reflux for 1–3 h (control by TLC). The mixture was
diluted with water, neutralized with 50% aqueous AcOH,
and cooled. The precipitated crystals were filtered off and
recrystallized from EtOH.
1-[2-(Methylamino)-4,6-diphenylpyridin-3-yl]ethanone
(4а). Yield 0.26 g (87%), light-yellow crystals, mp 127–
128°C. IR spectrum, ν, cm–1: 3395, 1646, 1573, 1550,
1271, 763. 1H NMR spectrum, δ, ppm (J, Hz): 1.82 (3Н, s,
СОСН3); 3.21 (3H, d, J = 4.7, NHCH3); 7.04 (1H, s, H-5);
7.41–7.54 (8H, m, Н 4-Ph, H-3,4,5 6-Ph); 7.87 (1H, br. s,
NHCH3); 8.12–8.21 (2H, m, H-2,6 6-Ph). 13C NMR
spectrum, δ, ppm: 28.2; 32.2; 110.2; 114.2; 127.3 (2С);
128.6 (2С); 128.7 (2С); 128.8; 128.9 (2С); 129.6; 138.9;
141.4; 153.3; 157.5; 157.9; 203.9. Found, %: C 79.51;
H 5.91; N 9.32. C20H18N2O. Calculated, %: C 79.44;
H 6.00; N 9.26.
3-Cyano-1,2-dimethyl-4,6-bis(4-methylphenyl)pyridin-
ium perchlorate (3b). Reaction time 48 h. Yield 1.65 g
(80%), colorless crystals, mp 202–204°С. 1H NMR
spectrum, δ, ppm: 2.43 (3H, s) and 2.44 (3H, s, ArCH3,
Ar1CH3); 3.10 (3H, s, 2-CH3); 4.03 (3H, s, 1-CH3); 7.45–
7.52 (4H, m, H-3,5 Ar1, H-3,5 Ar); 7.59–7.64 (2H, m,
H-2,6 Ar1); 7.79–7.85 (2H, m, H-2,6 Ar); 8.16 (1H, s, H-5).
13C NMR spectrum, δ, ppm: 21.5 (2C); 22.0; 44.8; 110.9;
115.3; 127.6; 129.7; 129.8 (4С); 130.2 (2С); 130.4 (2С);
130.9; 142.4; 143.2; 157.7; 158.9; 162.2. Found, %:
C 64.08; H 5.13; N 6.82. C22H21ClN2O4. Calculated, %:
C 64.00; H 5.13; N 6.78.
3-Cyano-4,6-bis(4-methoxyphenyl)-1,2-dimethylpyridin-
ium perchlorate (3с). Reaction time 168 h. Yield 2.14 g
(96%), colorless crystals, mp 212–213°С. 1H NMR spectrum,
δ, ppm: 3.08 (3H, s, 2-CH3); 3.87 (6H, s, 2OСН3); 4.03
(3H, s, 1-CH3); 7.19–7.27 (4H, m, H-3,5 Ar, H-3,5 Ar1);
7.65–7.73 (2H, m, H-2,6 Ar1); 7.89–7.96 (2H, m, H-2,6
Ar); 8.13 (1H, s, H-5). 13C NMR spectrum, δ, ppm: 22.0;
44.7; 56.1; 56.2; 109.9; 115.2 (2С); 115.4 (2С); 115.6;
124.6; 125.7; 127.2; 131.9 (4С); 156.9; 158.5; 162.1;
162.3; 163.1. Found, %: C 59.47; H 4.79; N 6.35.
C22H21ClN2O6. Calculated, %: C 59.40; H 4.76; N 6.30.
4-(4-Chlorophenyl)-3-cyano-1,2-dimethyl-6-phenyl-
pyridinium perchlorate (3d). Reaction time 96 h. Yield
1
1.61 g (77%), colorless crystals, mp 240–242°С. H NMR
spectrum, δ, ppm: 3.12 (3H, s, 2-CH3); 4.05 (3H, s, 1-CH3);
7.69–7.73 (5H, m, H-3,4,5 Ph, H-3,5 Ar1); 7.74–7.78 (2H,
m, H-2,6 Ar1); 7.90–7.97 (2H, m, H-2,6 Ph); 8.28 (1H, s,
H-5). 13C NMR spectrum, δ, ppm: 22.1; 44.9; 111.6; 114.9;
128.1; 129.7 (4С); 129.9 (2С); 131.7 (2С); 132.2; 132.4;
132.5; 137.8; 156.8; 159.0; 162.2. Found, %: C 57.39;
H 3.81; N 6.73. C20H16Cl2N2O4. Calculated, %: C 57.30;
H 3.85; N 6.68.
1-[2-(Methylamino)-4,6-bis(4-methylphenyl)pyridin-3-yl]-
ethanone (4b). Yield 0.28 g (85%), yellow crystals, mp 139–
140°C. IR spectrum, ν, cm–1: 3380, 1635, 1546, 1233,
1181, 822. 1H NMR spectrum, δ, ppm (J, Hz): 1.80 (3Н, s,
СОСН3); 2.41 (3H, s) and 2.43 (3H, s, ArСН3, Ar1СН3);
3.17 (3H, d, J = 4.7, NHCH3); 6.98 (1H, s, H-5); 7.23–7.32
(6H, m, H-3,5 Ar, H Ar1); 7.85 (1H, br. s, NHCH3); 8.00–
8.05 (2H, m, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 21.3;
21.4; 28.2; 32.2; 109.9; 114.0; 127.1 (2С); 128.6 (2С);
129.3 (2С); 129.5 (2С); 136.2; 138.5; 138.9; 139.7; 153.4;
3-Cyano-6-(4-methoxyphenyl)-1,2-dimethyl-4-phenyl-
pyridinium perchlorate (3e). Reaction time 168 h. Yield
1
1.68 g (81%), colorless crystals, mp 193–194°С. H NMR
spectrum, δ, ppm: 3.10 (3H, s, 2-CH3); 3.87 (3H, s, OСН3);
4.08 (3H, s, 1-CH3); 7.19–7.28 (2H, m, H-3,5 Ar); 7.62–
1029

Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
157.5; 157.8; 204.0. Found, %: C 80.05; H 6.70; N 8.52.
(2H, m, H-3,5 Ar1); 7.30–7.34 (2H, m, H-2,6 Ar1); 7.55–
7.60 (2Н, m, Н-3,5 Ar); 7.72 (1H, br. s, NHCH3); 7.97–
8.02 (2H, m, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 28.2;
32.1; 55.4; 109.8; 114.4 (2С); 114.7; 124.0; 128.7 (2С);
129.9 (2С); 131.7 (2С); 133.3; 137.9; 153.0; 156.4; 157.3;
160.5; 204.2. Found, %: C 61.37; H 4.69; N 6.79.
C21H19BrN2O2. Calculated, %: C 61.32; H 4.66; N 6.81.
Synthesis of N-nitrosoaminopyridines 5a–g (General
method). NaNO2 (0.21 g, 3 mmol) was added in portions at
room temperature to a solution or suspension of
N-methylaminopyridine 4a–g (2 mmol) in AcOH (8 ml).
When the addition was complete, the reaction mixture was
stirred for 1 h, diluted with water, and the formed preci-
pitate filtered off and recrystallized from EtOH.
C22H22N2O. Calculated, %: C 79.97; H 6.71; N 8.48.
1-[4,6-Bis(4-methoxyphenyl)-2-(methylamino)pyridin-3-yl]-
ethanone (4с). Yield 0.32 g (89%), light-yellow crystals,
mp 106–107°C. IR spectrum, ν, cm–1: 3380, 1635, 1546,
1
1242, 1233, 1181, 1032, 825. H NMR spectrum, δ, ppm
(J, Hz): 1.81 (3Н, s, СОСН3); 3.16 (3H, d, J = 4.7,
NHCH3); 3.87 (6H, s, 2ОCH3); 6.93 (1H, s, H-5); 6.95–
7.01 (4H, m, H-3,5 Ar, H-3,5 Ar1); 7.30–7.35 (2H, m,
H-2,6 Ar1); 7.84 (1H, br. s, NHCH3); 8.07–8.12 (2H, m,
H-2,6 Ar). 13C NMR spectrum, δ, ppm: 28.1; 32.1; 55.4
(2С); 109.4; 113.8; 113.9 (2С); 114.3 (2С); 128.6 (2С);
129.9 (2С); 131.6; 133.8; 153.0; 157.4; 157.5; 160.4;
161.0; 203.8. Found, %: C 72.87; H 6.06; N 7.79.
C22H22N2O3. Calculated, %: C 72.91; H 6.12; N 7.73.
1-[(4-(4-Chlorophenyl)-2-(methylamino)-6-phenylpyri-
din-3-yl]ethanone (4d). Yield 0.27 g (79%), yellow crystals,
mp 109–110°C. IR spectrum, ν, cm–1: 3350, 1635, 1543,
1246, 1086, 1007, 778. 1H NMR spectrum, δ, ppm (J, Hz):
1.82 (3Н, s, СОСН3); 3.17 (3H, d, J = 4.7, NHCH3); 6.95
(1H, s, H-5); 7.33–7.38 (2H, m, H-2,6 Ar1); 7.42–7.50 (5H,
m, H-3,5 Ar1, H-3,4,5 Ph); 7.87 (1H, br. s, NHCH3); 8.09–
8.15 (2H, m, H-2,6 Ph). 13C NMR spectrum, δ, ppm: 28.2;
32.4; 110.0; 113.9; 127.2 (2С); 128.6 (2С); 129.2 (2С);
129.7; 129.9 (2С); 135.2; 138.7; 139.8; 152.0; 157.5;
158.1; 203.4. Found, %: C 71.27; H 5.06; N 8.22.
C20H17ClN2O. Calculated, %: C 71.32; H 5.09; N 8.32.
1-[6-(4-Methoxyphenyl)-2-(methylamino)-4-phenyl-
pyridin-3-yl]ethanone (4e). Yield 0.25 g (75%), yellow
crystals, mp 104–105°C. IR spectrum, ν, cm–1: 3382, 1628,
1545, 1251, 1177, 1026, 831, 772, 712. 1H NMR spectrum,
δ, ppm (J, Hz): 1.77 (3Н, s, СОСН3); 3.17 (3H, d, J = 4.7,
NHCH3); 3.87 (3H, s, ОCH3); 6.94 (1H, s, H-5); 6.95–7.00
(2H, m, H-3,5 Ar); 7.38–7.48 (5H, m, H Ph); 7.96 (1H, br. s,
NHCH3); 8.08–8.13 (2H, m, H-2,6 Ar). 13C NMR
spectrum, δ, ppm: 28.2; 32.2; 55.4; 109.5; 113.4; 113.9
(2С); 128.6 (2С); 128.7 (2С); 128.8; 128.8 (2С); 131.5;
141.6; 153.4; 157.5; 157.6; 161.1; 203.6. Found, %: C 75.81;
H 5.99; N 8.41. C21H20N2O2. Calculated, %: C 75.88;
H 6.06; N 8.43.
1-{2-[Methyl(nitroso)amino]-4,6-diphenylpyridin-3-yl}-
ethanone (5a). Yield 0.57 g (86%), light-yellow crystals,
mp 136–137°C. IR spectrum, ν, cm–1: 1702, 1591, 1470,
1
1201, 1117, 977. H NMR spectrum, δ, ppm: 2.04 (3Н, s,
СОСН3); 3.69 (3Н, s, NСН3); 7.39–7.44 (2H, m, H-2,6
4-Ph); 7.45–7.54 (6H, m, H-3,4,5 4-Ph, H-3,4,5 6-Ph); 7.70
(1H, s, H-5); 8.05–8.10 (2H, m, H-2,6 6-Ph). 13C NMR
spectrum, δ, ppm: 30.5; 31.9; 119.5; 127.0 (2С); 127.9;
128.5 (2С); 128.9 (4С); 129.2; 130.1; 137.3; 137.4; 150.1;
150.2; 155.7; 202.3. Found, %: C 72.59; H 5.24; N 12.68.
C20H17N3O2. Calculated, %: C 72.49; H 5.17; N 12.68.
1-{2-[Methyl(nitroso)amino]-4,6-bis(4-methylphenyl)-
pyridin-3-yl}ethanone (5b). Yield 0.69 g (96%), colorless
crystals, mp 163–164°C. IR spectrum, ν, cm–1: 1698, 1591,
1
1461, 1201, 1185, 1111, 823. H NMR spectrum, δ, ppm:
2.05 (3Н, s, СОСН3); 2.43 (6H, s, ArCH3, Ar1CH3); 3.67
(3Н, s, NСН3); 7.27–7.34 (6H, m, H-3,5 Ar, H Ar1); 7.66
(1H, s, H-5); 7.94–7.99 (2H, m, H-2,6 Ar). 13C NMR
spectrum, δ, ppm: 21.2; 21.3; 30.5; 31.9; 119.2; 126.9
(2С); 127.7; 128.4 (2С); 129.6 (2С); 129.7 (2С); 134.6;
134.6; 139.2; 140.3; 150.1; 150.2; 155.7; 202.6. Found, %:
C 73.59; H 5.87; N 11.62. C22H21N3O2. Calculated, %:
C 73.52; H 5.89; N 11.69.
1-{4,6-Bis(4-methoxyphenyl)-2-[methyl(nitroso)amino]-
pyridin-3-yl}ethanone (5c). Yield 0.72 g (92%), colorless
crystals, mp 166–167°C. IR spectrum, ν, cm–1: 1704, 1592,
1463, 1258, 1175, 1027, 837. 1H NMR spectrum, δ, ppm: 2.05
(3Н, s, СОСН3); 3.66 (3Н, s, NСН3); 3.87 (3H, s, Ar1OCH3);
3.88 (3H, s, ArOCH3); 6.96–7.04 (4H, m, H-3,5 Ar, H-3,5
Ar1); 7.31–7.37 (2H, m, H-2,6 Ar1); 7.60 (1H, s, H-5); 8.00–
8.05 (2H, m, H-2,6 Ar). 13C NMR spectrum, δ, ppm: 30.5;
31.9; 55.3; 55.4; 114.3 (2С); 114.4 (2С); 118.7; 127.3; 128.4
(2С); 129.7; 129.8 (2С); 130.0; 149.9; 150.1; 155.3; 160.4;
161.3; 202.8. Found, %: C 67.50; H 5.47; N 10.66.
C22H21N3O4.Calculated, %: C 67.51; H 5.41; N 10.74.
1-{4-(4-Chlorophenyl)-2-[methyl(nitroso)amino]-6-phe-
nylpyridin-3-yl}ethanone (5d). Yield 0.70 g (95%),
colorless crystals, mp 194–195 °C. IR spectrum, ν, cm–1:
1-[4-(4-Methoxyphenyl)-2-(methylamino)-6-phenyl-
pyridin-3-yl]ethanone (4f). Yield 0.27 g (80%), yellow
crystals, mp 118–119°C. IR spectrum, ν, cm–1: 3386, 1631,
1542, 1232, 1029, 835. 1H NMR spectrum, δ, ppm (J, Hz):
1.82 (3Н, s, СОСН3); 3.17 (3H, d, J = 4.7, NHCH3); 3.87
(3H, s, ОCH3); 6.96–7.02 (3H, m, H-5, H-3,5 Ar1); 7.31–
7.37 (2H, m, H-2,6 Ar1); 7.40–7.49 (3H, m, H-3,4,5 Ph);
7.76 (1H, br. s, NHCH3); 8.10–8.15 (2H, m, H-2,6 Ph).
13C NMR spectrum, δ, ppm: 28.2; 32.1; 55.4; 110.1; 114.3
(2С); 114.4; 127.2 (2С); 128.5 (2С); 129.5; 129.9 (2С);
133.5; 139.0; 152.9; 157.4; 157.7; 160.4; 204.2. Found, %:
C 75.94; H 6.09; N 8.37. C21H20N2O2. Calculated, %:
C 75.88; H 6.06; N 8.43.
1
1696, 1593, 1464, 1212, 1070, 720. H NMR spectrum,
1-[6-(4-Bromophenyl)-4-(4-methoxyphenyl)-2-(methyl-
amino)pyridin-3-yl]ethanone (4g). Yield 0.39 g (95%),
yellow crystals, mp 153–154°C. IR spectrum, ν, cm–1: 3380,
δ, ppm: 2.07 (3Н, s, СОСН3); 3.68 (3Н, s, NСН3); 7.34–
7.38 (2H, m, H-2,6 Ar1); 7.45–7.49 (2H, m, H-3,5 Ar1);
7.50–7.54 (3H, m, H-3,4,5 Ph); 7.65 (1H, s, H-5); 8.05–
8.09 (2H, m, H-2,6 Ph). 13C NMR spectrum, δ, ppm: 30.3;
32.0; 119.2; 127.0 (2С); 127.6; 129.0 (2С); 129.2 (2С);
129.9 (2С); 130.2; 135.6; 135.8; 137.1; 149.0; 150.3;
1
1634, 1545, 1248, 1030, 816. H NMR spectrum, δ, ppm
(J, Hz): 1.81 (3Н, s, СОСН3); 3.14 (3H, d, J = 4.7,
NHCH3); 3.87 (3H, s, OCH3); 6.96 (1H, s, H-5); 6.97–7.01
1030

Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
155.9; 201.8. Found, %: C 65.58; H 4.37; N 11.48.
146.4; 152.1; 156.3. Found, %: С 80.15; H 5.72; N 13.97.
C20H17N3. Calculated, %: C 80.24; H 5.72; N 14.04.
C20H16ClN3O2. Calculated, %: C 65.67; H 4.41; N 11.49.
1-{6-(4-Methoxyphenyl)-2-[methyl(nitroso)amino]-
4-phenylpyridin-3-yl}ethanone (5e). Yield 0.70 g (97%),
colorless crystals, mp 177–178°C. IR spectrum, ν, cm–1:
1691, 1592, 1519, 1459, 1246, 1203, 1179, 1027, 839.
1H NMR spectrum, δ, ppm: 2.02 (3Н, s, СОСН3); 3.67
(3Н, s, NСН3); 3.88 (3H, s, OCH3); 6.98–7.05 (2H, m,
H-3,5 Ar); 7.38–7.44 (2H, m, H-2,6 Ph); 7.45–7.51 (3H, m,
H-3,4,5 Ph); 7.62 (1H, s, H-5); 7.98–8.08 (2H, m, H-2,6 Ar).
13C NMR spectrum, δ, ppm: 30.5; 31.9; 55.4; 114.3 (2С);
118.6; 127.3; 128.4 (2С); 128.5 (2С); 128.9 (2С); 129.1;
129.9; 137.6; 149.9; 150.2; 155.4; 161.3; 202.4. Found, %:
C 69.76; H 5.28; N 11.58. C21H19N3O3. Calculated, %:
C 69.79; H 5.30; N 11.63.
1,3-Dimethyl-4,6-bis(4-methylphenyl)-1Н-pyrazolo-
[3,4-b]pyridine (6b). Yield 0.52 g (80%), colorless
crystals, mp 134–135°C. IR spectrum, ν, cm–1: 1581, 1563,
1
1344, 1185, 817. H NMR spectrum, δ, ppm: 2.29 (3Н, s,
3-СН3); 2.42 (3H, s, Ar1CH3); 2.46 (3H, s, ArCH3); 4.17
(3Н, s, NСН3); 7.28–7.34 (4H, m, H-3,5 Ar, H-3,5 Ar1);
7.40–7.45 (3H, m, H-5, H-2,6 Ar1); 8.04–8.08 (2H, m,
H-2,6 Ar). 13C NMR spectrum, δ, ppm: 15.3; 21.3 (2С);
33.5; 111.7; 114.2; 127.4 (2С); 129.0 (4С); 129.5 (2С); 135.3;
136.7; 138.5; 139.3; 140.2; 146.3; 152.1; 156.3. Found, %:
С 80.78; H 6.41; N 12.80. C22H21N3. Calculated, %:
C 80.70; H 6.46; N 12.83.
4,6-Bis(4-methoxyphenyl)-1,3-dimethyl-1Н-pyrazolo-
[3,4-b]pyridine (6c). Yield 0.56 g (78%), colorless
crystals, mp 137–138°C. IR spectrum, ν, cm–1: 1585, 1563,
1466, 1241, 1177, 1029, 822. 1H NMR spectrum, δ, ppm: 2.29
(3Н, s, 3-СН3); 3.88 (3H, s, Ar1OCH3); 3.90 (3H, s,
ArOCH3); 4.15 (3Н, s, NСН3); 6.99–7.06 (4H, m, H-3,5 Ar,
H-3,5 Ar1); 7.37 (3H, s, H-5); 7.43–7.49 (2H, m, H-2,6 Ar1);
8.10–8.15 (2H, m, H-2,6 Ar). 13C NMR spectrum, δ, ppm:
15.4; 33.5; 55.4 (2С); 111.5; 113.7 (2С); 113.8; 114.1 (2С);
128.8 (2С); 130.3 (2С); 130.6; 132.1; 140.2; 146.0; 152.2;
156.0; 160.1; 160.7. Found, %: С 73.58; H 5.80; N 11.71.
C22H21N3O2. Calculated, %: C 73.52; H 5.89; N 11.69.
4-(4-Chlorophenyl)-1,3-dimethyl-6-phenyl-1Н-pyra-
zolo[3,4-b]pyridine (6d). Yield 0.55 g (83%), colorless
crystals, mp 135–136°C. IR spectrum, ν, cm–1: 1583, 1562,
1497, 1348, 1162, 1090, 820. 1H NMR spectrum, δ, ppm: 2.27
(3Н, s, 3-СН3); 4.17 (3Н, s, NСН3); 7.42 (3H, s, H-5); 7.44–
7.53 (7H, m, H Ar1, H-3,4,5 Ph); 8.13–8.17 (2H, m, H-2,6
Ph). 13C NMR spectrum, δ, ppm: 15.3; 33.6; 111.6; 114.3;
127.5 (2С); 128.6 (2С); 128.8 (2С); 129.4; 130.3 (2С);
134.9; 136.5; 139.3; 139.9; 144.9; 152.1; 156.4. Found, %:
С 71.89; H 4.85; N 12.55. C20H16ClN3. Calculated, %:
C 71.96; H 4.83; N 12.59.
6-(4-Methoxyphenyl)-1,3-dimethyl-4-phenyl-1Н-pyra-
zolo[3,4-b]pyridine (6e). Yield 0.54 g (82%), colorless
crystals, mp 98–99°C. IR spectrum, ν, cm–1: 1583, 1561,
1344, 1238, 1167, 1035, 826. 1H NMR spectrum, δ, ppm: 2.25
(3Н, s, 3-СН3); 3.88 (3H, s, OCH3); 4.16 (3Н, s, NСН3);
6.99–7.06 (2H, m, H-3,5 Ar); 7.40 (3H, s, H-5); 7.47–7.56
(5H, m, H Ph); 8.09–8.17 (2H, m, H-2,6 Ar). 13C NMR
spectrum, δ, ppm: 15.2; 33.5; 55.4; 111.4; 113.8; 114.1
(2С); 128.3 (2С); 128.5; 128.8 (2С); 129.0 (2С); 132.0;
138.2; 140.2; 146.2; 152.1; 156.0; 160.8. Found, %: С 76.60;
H 5.79; N 12.80. C21H19N3O. Calculated, %: C 76.57;
H 5.81; N 12.76.
1-{4-(4-Methoxyphenyl)-2-[methyl(nitroso)amino]-
6-phenylpyridin-3-yl}ethanone (5f). Yield 0.68 g (94%),
colorless crystals, mp 164–165°C. IR spectrum, ν, cm–1:
1697, 1593, 1514, 1465, 1238, 1199, 1182, 1034, 973, 843.
1H NMR spectrum, δ, ppm: 2.06 (3Н, s, СОСН3); 3.67
(3Н, s, NСН3); 3.87 (3H, s, OCH3); 6.97–7.03 (2H, m,
H-3,5 Ar1); 7.33–7.38 (2H, m, H-2,6 Ar1); 7.45–7.54 (3H,
m, H-3,4,5 Ph); 7.68 (1H, s, H-5); 8.03–8.11 (2H, m, H-2,6
Ph). 13C NMR spectrum, δ, ppm: 30.5; 31.9; 55.4; 114.4
(2С); 119.6; 127.0 (2С); 127.9; 128.9 (2С); 129.5; 129.8
(2С); 130.0; 137.4; 150.0; 150.2; 155.6; 160.4; 202.7. Found,
%: C 69.72; H 5.26; N 11.65. C21H19N3O3. Calculated, %:
C 69.79; H 5.30; N 11.63.
1-{6-(4-Bromophenyl)-4-(4-methoxyphenyl)-2-[methyl-
(nitroso)amino]pyridin-3-yl}ethanone (5g). Yield 0.86 g
(98%), colorless crystals, mp 174–175°C. IR spectrum,
1
ν, cm–1: 1690, 1591, 1466, 1254, 1062, 982, 841. H NMR
spectrum, δ, ppm: 2.05 (3Н, s, СОСН3); 3.65 (3Н, s,
NСН3); 3.87 (3H, s, OCH3); 6.97–7.04 (2H, m, H-3,5 Ar1);
7.31–7.37 (2H, m, H-2,6 Ar1); 7.61–7.64 (2H, m, H-3,5
Ar); 7.65 (1H, s, H-5); 7.91–7.98 (2H, m, H-2,6 Ar). 13C NMR
spectrum, δ, ppm: 30.5; 31.8; 55.4; 114.5 (2С); 119.4;
124.6; 128.2; 128.5 (2С); 129.3; 129.8 (2С); 132.1 (2С);
136.3; 150.2; 150.4; 154.4; 160.5; 202.5. Found, %: C 57.30;
H 4.17; N 9.58. C21H18BrN3O3.Calculated, %: C 57.29;
H 4.12; N 9.54.
Synthesis of 4,6-diaryl-1,3-dimethyl-1Н-pyrazolo[3,4-b]-
pyridines 6a–g (General method). Zinc dust (0.65 g,
10 mmol) was added in portions to a stirred solution of
nitrosoaminopyridine 5a–g (2 mmol) in AcOH (8 ml),
keeping the temperature below 10°C. The mixture was then
stirred at room temperature for 1 h, filtered, and the
inorganic precipitate washed with hot AcOH. The filtrate
was diluted with cold water and neutralized with aqueous
NH3. The crystalline pyrazolopyridine 6a–g was filtered
off, and purified by recrystallization from EtOH.
1,3-Dimethyl-4,6-diphenyl-1Н-pyrazolo[3,4-b]pyridine
(6a). Yield 0.48 g (80%), colorless crystals, mp 97–98°C.
IR spectrum, ν, cm–1: 1582, 1561, 1348, 1151, 775.
1H NMR spectrum, δ, ppm: 2.27 (3Н, s, 3-СН3); 4.18 (3Н,
s, NСН3); 7.42–7.57 (9H, m, Н-5, Н 4-Ph, H-3,4,5 6-Ph);
8.14–8.20 (2H, m, H-2,6 6-Ph). 13C NMR spectrum,
δ, ppm: 15.2; 33.6; 111.8; 114.4; 127.5 (2С); 128.3 (2С);
128.6; 128.8 (2С); 129.0 (2С); 129.3; 138.1; 139.5; 140.2;
4-(4-Methoxyphenyl)-1,3-dimethyl-6-phenyl-1Н-pyra-
zolo[3,4-b]pyridine (6f). Yield 0.61 g (92%), colorless
crystals, mp 123–124°C. IR spectrum, ν, cm–1: 1583, 1562,
1
1514, 1250, 1176, 1031, 834, 773. H NMR spectrum,
δ, ppm: 2.31 (3Н, s, 3-СН3); 3.90 (3H, s, OCH3); 4.17 (3Н,
s, NСН3); 7.02–7.08 (2H, m, H-3,5 Ar1); 7.41–7.54 (6H, m,
H-5, H-2,6 Ar1, H-3,4,5 Ph); 8.13–8.19 (2H, m, H-2,6 Ph).
13C NMR spectrum, δ, ppm: 15.4; 33.5; 55.4; 111.9; 113.8
(2С); 114.4; 127.5 (2С); 128.7 (2С); 129.2; 130.3 (2С);
130.4; 139.5; 140.2; 146.2; 152.2; 156.3; 160.1. Found, %:
1031

Chemistry of Heterocyclic Compounds 2017, 53(9), 1026–1032
3055. (d) Qin, J.; Zhou, W.; Huang, X.; Dhondi, P.; Palani, A.;
С 76.62; H 5.85; N 12.71. C21H19N3O. Calculated, %:
C 76.57; H 5.81; N 12.76.
Aslanian, R.; Zhu, Z.; Greenlee, W.; Cohen-Williams, M.;
Jones, N.; Hyde, L.; Zhang, L. ACS Med. Chem. Lett. 2011,
2, 471.
6-(4-Bromophenyl)-4-(4-methoxyphenyl)-1,3-dimethyl-
1Н-pyrazolo[3,4-b]pyridine (6g). Yield 0.66 g (81%),
colorless crystals, mp 126–127°C. IR spectrum, ν, cm–1:
3. (a) Lavrard, H.; Popowycz, F. Eur. J. Org. Chem. 2017, 600.
(b) Follmann, M.; Griebenow, N.; Hahn, M. G.; Hartung, I.;
Mais, F.-J.; Mittendorf, J.; Schäfer, M.; Schirok, H.; Stasch, J.-P.;
Stoll, F.; Straub, A. Angew. Chem., Int. Ed. 2013, 52, 9442.
(c) Garnock-Jones, K. P. Drugs 2014, 74, 2065.
1
1582, 1562, 1247, 1174, 1050, 828. H NMR spectrum,
δ, ppm: 2.30 (3Н, s, 3-СН3); 3.90 (3H, s, OCH3); 4.15 (3Н,
s, NСН3); 6.99–7.08 (2H, m, H-3,5 Ar1); 7.38 (3H, s, H-5);
7.42–7.49 (2H, m, H-3,5 Ar); 7.57–7.66 (2H, m, H-2,6
Ar1); 8.00–8.07 (2H, m, H-2,6 Ar). 13C NMR spectrum,
δ, ppm: 15.4; 33.5; 55.4; 112.1; 113.8 (2С); 114.0; 123.7;
129.0 (2С); 130.2; 130.3 (2С); 131.9 (2С); 138.4; 140.3;
146.4; 152.1; 154.9; 160.2. Found, %: С 61.63; H 4.51;
N 10.35. C21H18BrN3O. Calculated, %: C 61.78; H 4.44;
N 10.29.
4. (a) Dodiya, D. K.; Trivedi, A. R.; Kataria, V. B.; Shah, V. H.
Curr. Org. Chem. 2012, 16, 400. (b) Schirok, H.; Griebenow, N.;
Fürstner, C.; Dilmac, A. M. Tetrahedron 2015, 71, 5597.
(c) Behnke, D.; Cotesta, S.; Hintermann, S.; Fendt, M.;
Gee, C. E.; Jacobson, L. H.; Laue, G.; Meyer, A.; Wagner, T.;
Badiger, S.; Chaudhari, V.; Chebrolu, M.; Pandit, C.; Hoyer, D.;
Betschart, C. Bioor. Med. Chem. Lett. 2015, 25, 5555.
5. (a) Lee, S.; Park, S. B. Org. Lett. 2009, 11, 5214. (b) Saleh, T. S.;
Eldebss, T. M. A.; Albishri, H. M. Ultrason. Sonochem. 2012,
19, 49. (с) El-borai, M. A.; Rizk, H. F.; Abd-Aal, M. F.;
El-Deeb, I. Y. Eur. J. Med. Chem. 2012, 48, 92.
(d) Gunasekaran, P.; Prasanna, P.; Perumal, S. Tetrahedron
Lett. 2014, 55, 329. (е) Dubovtsev, A. Yu.; Dmitriev, M. V.;
Silaichev, P. S.; Antonov, D. I.; Maslivets, A. N. Synthesis
2017, 49, 2223.
The work was supported by the Russian Foundation for
Basic Research and the Ministry of Education of the Omsk
Region (grant 16-43-550144p_a).
References
6. (a) El Ashry, E. S. H.; El Kilany, Y.; Rashed, N.; Assafir, H.
Adv. Heterocycl. Chem. 1999, 75, 79. (b) Brown, D. J.;
Harper, J. S. J. Chem. Soc. 1965, 5542. (c) Kost, A. N.;
Sagitullin, R. S.; Gromov, S. P. Chem. Heterocycl. Compd.
1979, 15, 87. [Khim. Geterotsikl. Soedin. 1979, 98.]
(d) Gromov, S. P.; Kost, A. N.; Sagitullin, R. S. Zh. Org.
Khim. 1978, 14, 1316. (e) Sagitullina, G. P.; Glizdinskaya, L. V.;
Oleinikova, S. I.; Atavin, E. G.; Sagitullin, R. S. Russ. J. Org.
Chem. 2005, 41, 1367. [Zh. Org. Khim. 2005, 41, 1395.]
(f) Sagitullina, G. P.; Lisitskaya, L. A.; Vorontsova, M. A.;
Sagitullin, R. S. Mendeleev Commun. 2007, 17, 192.
7. (a) Lee, G. S.; Kammermeier, T.; Kaiser, A.; Eibler, E.;
Wiegrebe, W. Arch. Pharm. 1991, 324, 177. (b) Yang, J.-X;
Tao, X.-T.; Yuan, C. X.; Yan, Y. X.; Wang, L.; Liu, Z.; Ren, Y.;
Jiang, M. H. J. Am. Chem. Soc. 2005, 127, 3278.
(c) Szmant, H. H.; Basso, A. J. J. Am. Chem. Soc. 1952, 74,
4397. (d) Bai, X.-G.; Xu, C.-L.; Zhao, S.-S.; He, H.-W.;
Wang, Y.-C.; Wang, J.-X. Molecules 2014, 19, 17256.
8. (a) Treibs, W.; Beger, J. Justus Liebigs Ann. Chem. 1962,
652, 192. (b) Robinson, J. M.; Brent, L. W.; Chau, C.;
Floyd, K. A.; Gillham, S. L.; McMahan, T. L.; Magda, D. J.;
Motycka, T. J.; Pack, M. J.; Roberts, A. L.; Seally, L. A.;
Simpson, S. L.; Smith, R. R.; Zalesny, K. N. J. Org. Chem.
1992, 57, 7352. (c) Matsui, M.; Oji, A.; Hiramatsu, K.;
Shibata, K.; Muramatsu, H. J. Chem. Soc., Perkin Trans. 2
1992, 201. (d) Shibata, K.; Urano, K.; Matsui, M. Bull. Chem.
Soc. Jpn. 1988, 61, 2199. (e) Meyer, E. V. J. Prakt. Chem.
1908, 78, 497.
1. (a) Goda, F. E.; Abdel-Aziz, A. A.-M.; Attef, O. A. Bioorg.
Med. Chem. 2004, 12, 1845. (b) El-Borai, M. A.; Rizk, H. F.;
Beltagy, D. M.; El-Deeb, I. Y. Eur. J. Med. Chem. 2013, 66,
415. (с) Samar, C.; Ismail, A.; Helmi, T.; Khiari, J.; Bassem, J.
J. Bacteriol. Parasitol. 2017, 8, 310. (d) Menezes, C. M. S.;
Sant'Anna, C. M. R.; Rodrigues, C. R.; Barreiro, E. J. J. Mol.
Struct.: THEOCHEM 2002, 579, 31. (e) Bernardino, A. M. R.;
de Azevedo, A. R.; da Silva Pinheiro, L. C.; Borges, J. C.;
Carvalho, V. L.; Miranda, M. D.; de Meneses, M. D. F.;
Nascimento, M.; Ferreira, D.; Rebello, M. A.; da
Silva, V. A. G. G.; de Frugulhetti, I. C. P. P. Med. Chem. Res.
2007, 16, 352. (f) Lin, R.; Connolly, P. J.; Lu, Y.; Chiu, G.;
Li, S.; Yu, Y.; Huang, S.; Li, X.; Emanuel, S. L.;
Middleton, S. A.; Gruninger, R. H.; Adams, M.; Fuentes-
Pesquera, A. R.; Greenberger, L. M. Bioorg. Med. Chem. Lett.
2007, 17, 4297. (g) Huang, S.; Lin, R.; Yu, Y.; Lu, Y.;
Connolly, P. J.; Chiu, G.; Li, S.; Emanuel, S. L.;
Middleton, S. A. Bioorg. Med. Chem. Lett. 2007, 17, 1243.
(h) de Mello, H.; Echevarria, A.; Bernardino, A. M.; Canto-
Cavalheiro, M.; Leon, L. L. J. Med. Chem. 2004, 47, 5427.
2. (a) Bharate, S. B.; Mahajan, T. R.; Gole, Y. R.; Nambiar, M.;
Matan, T. T.; Kulkarni-Almeida, A.; Balachandran, S.;
Junjappa, H.; Balakrishnan, A.; Vishwakarma, R. A. Bioorg.
Med. Chem. 2008, 16, 7167. (b) Roecker, A. J.; Cox, C. D.;
Coleman, P. J. J. Med. Chem. 2016, 59, 504.
(c) Witherington, J.; Bordas, V.; Gaiba, A.; Garton, N. S.;
Naylor, A.; Rawlings, A. D.; Slingsby, B. P.; Smith, D. G.;
Takle, A. K.; Ward, R. W. Bioorg. Med. Chem. Lett. 2003, 13,
1032