One-pot three-component synthesis of a series of 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles in the presence of aluminum oxide as a nanocatalyst

Article abstract of DOI:10.1007/s10593-018-2229-7

[Figure not available: see fulltext.] One-pot three-component reaction of arylglyoxals, 3-aryl-3-oxopropanenitriles, and 5-amino-1-aryl-3-methylpyrazoles using various solvent systems and different catalysts under reflux conditions afforded the corresponding 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]- pyridine-5-carbonitrile derivatives. The best yields (70–91%) were obtained using Al2O3 as a nanocatalyst in H₂O–EtOH, 1:1, under reflux conditions. The simplicity of workup procedure, the novelty of pyrazolopyridines, green solvent system, easy preparation of a nanocatalyst, and good to excellent yields of the products are the advantages of this synthetic strategy. The structures of all products were confirmed by FT-IR, ¹H and¹³C NMR, and mass spectral data.

Full text of DOI:10.1007/s10593-018-2229-7

DOI 10.1007/s10593-018-2229-7
Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
One-pot three-component synthesis of a series
of 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles
in the presence of aluminum oxide as a nanocatalyst
Fatemeh Majidi Arlan1*, Jabbar Khalafy1, Ramin Maleki2
1 Department of Organic Chemistry, Faculty of Chemistry, Urmia University,
P. O. Box 57153-165, Urmia, Iran; e-mail: majiidi@yahoo.com
2 Research Department of Analytical Chemistry,
Iranian Academic Center for Education, Culture and Research,
P. O. Box 57155-397, Urmia, Iran; e-mail: malekichem@gmail.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(1), 51–57
Submitted July 25, 2017
Accepted after revision December 21, 2017
One-pot three-component reaction of arylglyoxals, 3-aryl-3-oxopropanenitriles, and 5-amino-1-aryl-3-methylpyrazoles using various
solvent systems and different catalysts under reflux conditions afforded the corresponding 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitrile derivatives. The best yields (70–91%) were obtained using Al2O3 as a nanocatalyst in H2O–EtOH, 1:1, under
reflux conditions. The simplicity of workup procedure, the novelty of pyrazolopyridines, green solvent system, easy preparation of a
nanocatalyst, and good to excellent yields of the products are the advantages of this synthetic strategy. The structures of all products were
confirmed by FT-IR, 1H and 13C NMR, and mass spectral data.
Keywords: arylglyoxals, pyrazolo[3,4-b]pyridines, multicomponent reaction, nanocatalyst, one-pot reaction.
The synthesis of nitrogen-containing heterocyclic com-
pounds have attracted much attention due to their wide
biological and pharmaceutical activities.1–3 The presence of
two or more different heterocyclic moieties in a single
molecule unites properties of all the heterocyclic skeletons
present and may enhance the pharmacological or biological
activity. Therefore, the design of novel polycyclic hetero-
cycles by combining various structurally diverse motifs
have recently received considerable attention due to
numerous applications.4–7
Fused heterocyclic compounds such as pyrazolo-
pyridines are an important class of organic compounds with
biological and pharmacological activities, such as anti-
bacterial,8 antimicrobial,9,10 antileishmanial,11,12 antiprolife-
rative,13 cytotoxic and anti-biofilm,14 antioxidant,15 anti-
malarial,16 anticancer,17 and GSK-3 inhibiting.18
In continuation of our studies in the field of new hetero-
cyclic compound synthesis,24–30 herein, we report a one-pot
three-component procedure toward a series of new 4-aroyl-
1,6-diaryl-3-methyl-1H-pyrazlo[3,4-b]pyridine-5-carbonitriles
in the presence of different catalysts under reflux
conditions. In comparison to the methods reported before,
our method provides pyrazolo[3,4-b]pyridines in good to
high yields and using green solvent system.4,5
In our initial studies, 1-(3-chlorophenyl)-3-methyl-1H-
pyrazol-5-amine (1b), 3-(4-chlorophenyl)-3-oxopropane-
nitrile (2a), and phenylglyoxal hydrate (3a) were chosen as
starting compounds for the test reaction (Scheme 1). We
did not observe the formation of the desired product even
after 24 h upon stirring the reaction mixture in the absence
of a catalyst at room temperature. Refluxing the reaction
mixture using various catalysts and different solvent
systems (Table 1) gave solid precipitate, which was
separated in 15–89% yield. It was characterized by IR,
NMR spectroscopy and MS spectrometry to be the desired
1H-pyrazolo[3,4-b]pyridine 4i.
Multicomponent reactions (MCRs) play an important
role in the synthesis of heterocyclic compounds by multiple
bond-making or bond-breaking through environmentally
and economically useful one-pot procedures.19–23 MCRs in
green solvents and using green catalysts can be a powerful
tool in organic synthesis.
To study the effect of the amount of catalyst, the
reaction was carried out in the presence of various amounts
0009-3122/18/54(1)-0051©2018 Springer Science+Business Media, LLC
51

Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
Scheme 1. One-pot synthesis
of 1H-pyrazolo[3,4-b]pyridine derivative 4i
Scheme 2. Preparation of the starting compounds 1a,b, 2a,b, 3a–d
Cl
O
O
H2N
CN
OH
OH
N
+
+
N
Cl
2a
3a
Me
1b
Cat.

Me
Cl
N
N
O
N
NC
Cl
4i
Table 1. Optimization of the reaction conditions
The sol-gel procedure was used for synthesis of nano-
Al2O3 according to the literature method with some modi-
fications.35 The SEM image of desired nanocatalyst is
shown in Figure 1.
Solvents
Catalyst (mol %)
Time, h
Yield, %
AcOH
H2O–AcOH
EtOH
–
–
8
6
7
24
7
7
7
7
10
8
8
54
63
78
–
Nano Al2O3 (10)
Nano Al2O3 (20)
Nano Al2O3 (5)
Nano Al2O3 (10)
Nano Al2O3 (20)
–
ZnCl2 (20)
p-TSA (20)
L-proline (20)
concd HCl
Al2O3 (20)
Al2O3 (10)
The one-pot three component reaction of 1-aryl-5-amino-
3-methylpyrazoles 1a,b, 3-oxo-3-phenylpropanenitriles 2a,b,
and arylglyoxal hydrates 3a–d in H2O–EtOH, 1:1, under
reflux conditions in the presence of Al2O3 nanocatalyst
gave the desired 1H-pyrazolo[3,4-b]pyridines 4a–p in 70–
91% yield (Scheme 3). The reaction times and the yields of
products 4a–p are listed in Table 2. The structures of
substituted 4-aroyl-3-methyl-1,6-diaryl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitriles 4a–p were characterized using FT-IR,
1H and 13C NMR, and mass spectral data and
microanalysis. The characteristic singlet at around 2.29–
2.32 ppm was ascribed to the methyl group of the pyrazole
moiety and was present in all new products. In the
13C NMR spectra of products, signals located around
H2O
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
H2O–EtOH
CHCl3
66
89
86
15
53
71
46
57
42
57
7
14
7
H2O–EtOH
of Al2O3 ranging from 5 to 20 mol %, and increasing the
amount of catalyst did not improve the yield. To find the
best solvent for this reaction, we carried out the trial
reaction using various solvent systems such as AcOH, H2O–
AcOH, H2O–EtOH, EtOH, H2O, and CHCl3. Among all
these solvents, H2O–EtOH, 1:1, was proved to be the best
in terms of yield. The acid nature catalysts, such as
concentrated HCl, p-TSA, ZnCl2, AcOH, and L-proline as
an amino acid, gave lower yields. The best result, in terms
of yield (89%) and reaction time (7 h), was obtained when
the reaction was performed using 10 mol % Al2O3 as a
nanocatalyst in H2O–EtOH, 1:1.
After optimizing the reaction conditions, we next
determined the scope of this reaction with diverse
arylglyoxals, 5-amino-1-aryl-3-methylpyrazoles, and 3-aryl-
3-oxopropanenitriles. Starting materials, including 1-aryl-
5-amino-3-methylpyrazoles 1a,b,31 3-oxo-3-phenylpro-
panenitriles 2a,b,32,33 and arylglyoxal monohydrates
3a–d,34 were prepared by the literature-reported methods
(Scheme 2).
Figure 1. The SEM image of Al2O3 nanocatalyst. Particle size
34.9–74.1 nm.
52

Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
Table 2. Reaction conditions and yields of substituted
1H-pyrazolo[3,4-b]pyridines 4a–p
Scheme 3. One-pot synthesis of substituted
1H-pyrazolo[3,4-b]pyridine derivatives 4a–p
Com-
Reaction
time, h
R1
R2
R3
Yield*, %
R1
pound
O
O
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
F
OMe
Cl
H
F
OMe
Cl
H
F
OMe
Cl
6
8
6
7
8
8
7
8
7
7
6
7
8
8
8
8
91
86
75
79
84
81
70
79
89
78
76
85
83
80
76
81
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
OH
OH
CN
H2N
+
+
N
N
R3
R2
H2O, EtOH
2a,b
3a–d
Cl
Me
Me
Me
Me
Me
Cl
Cl
Cl
Cl
Me
Me
Me
Me
1a,b
Nano Al2O3
R1
R2
N
N
N
H
F
OMe
Cl
NC
Me
O
R3
4a–p
* The isolated yields are referred to the recrystallized products.
189.8–191.7 ppm were attributed to the carbonyl groups of
arylglyoxal moieties, and signals observed around 13.8–
13.9 ppm were due to the methyl groups of pyrazole
moiety. In the FT-IR spectra, the characteristic absorption
bands at 2218–2222 and 1500–1676 cm–1 could be
assigned to the vibrations of the nitrile and carbonyl
groups, respectively.
Mechanistically, the formation of products 4a–p was
achieved by a sequence of reactions involving the initial
condensation of arylglyoxals with 5-amino-1-aryl-
3-methylpyrazoles, followed by second condensation of the
intermediate with 3-aryl-3-oxopropanenitriles, providing
the corresponding dihydro-1H-pyrazolo[3,4-b]pyridines
through intramolecular heterocyclization and subsequent
tautomerization, which was finally dehydrogenated to the
desired 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitriles via autoxidation (Scheme 4).
We have reported, one-pot three-component synthesis of
a new series of 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo-
[3,4-b]pyridine-5-carbonitrile derivatives in the presence of
Al2O3 as a nanocatalyst. These new pyrazolo[3,4-b]-
pyridines may also have useful biological and pharmaco-
logical properties, and they could also serve as inter-
mediates for new planar polycyclic heterocycles. The
simplicity, ease of product and catalyst isolations, mild
reaction conditions, using green solvents, and good yields
are the main advantages of this procedure.
Experimental
Infrared spectra were recorded on a Thermo-Nicolet
Nexus 670-FT-IR instrument using KBr pellets. 1H and 13C
NMR spectra were recorded on a Bruker Avance AQS 300
spectrometer (300 and 75.5 MHz, respectively) in CDCl3.
Chemical shifts were measured using TMS as internal
standard. Mass spectra were recorded on a Agilent
Technologies 5975C VL MSD instrument with Triple-Axis
detector, electron impact (EI, 70 eV). Melting points were
measured on a Philip Harris C4954718 apparatus and are
uncorrected. The reaction monitoring was accomplished by
TLC on silica gel PolyGram SILG/UV254 plates. The
scanning electron microscopy (SEM) image was obtained
from a JEOL JXA-840 Electron Microscopy Ltd.
Scheme 4. The proposed mechanism for synthesis of substituted 1H-pyrazolo[3,4-b]pyridines catalyzed by Al2O3 as a nanocatalyst
53

Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
Preparation of Al2O3 nanocatalyst. A 0.05 M
m, H Ph); 7.37 (1H, t, J = 7.5, H Ph); 7.03 (2H, d, J = 8.7,
H Ar); 3.92 (3H, s, OCH3); 2.32 (3H, s, CH3). 13C NMR
spectrum, δ, ppm: 190.0; 165.5; 159.0; 150.2; 149.8; 143.2;
138.5; 136.9; 135.6; 132.7; 130.9; 129.3; 129.0; 128.1;
126.8; 126.5; 121.3; 116.2; 114.8; 111.9; 55.8; 13.8. Mass
spectrum, m/z (Irel, %): 480 [M(37Cl)]+ (10), 478 [M]+ (28),
344 (29), 343 [M–(4-MeOC6H4)CO]+ (15), 267 (10), 136 (15),
135 [4-MeOC6H4CO]+ (100), 107 [4-MeOC6H4]+ (19), 92
(27), 77 [Ph]+ (74), 51 (16). Found, %: C 70.09; H 3.82; N 11.41.
C28H19ClN4O2. Calculated, %: C 70.22; H 4.00; N 11.70.
6-(4-Chlorophenyl)-4-[(4-chlorophenyl)carbonyl]-
3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4d). Yield 0.38 g (79%), yellow needles, mp 170–
172°C. IR spectrum, ν, cm–1: 3070, 2927, 2220, 1676,
ethanolic solution of aluminum nitrate was prepared. The
pH of solution was adjusted to 8.5 by addition of 25% NH3
solution in order to form aluminum hydroxide gel. The
formed gel was let to maturate for 24 h at room
temperature, afterward dried at 110°C for 6 h, and then
calcined in an electric furnace for 2 h at 700°C.
Synthesis of pyrazolopyridines 4a–p (General method).
Arylglyoxal hydrate 3a–d (1 mmol) was added to a
solution of 3-oxo-3-phenylpropanenitrile 2a,b (1 mmol) in
H2O–EtOH, 1:1 (5 ml), followed by the addition of 1-aryl-
5-amino-3-methylpyrazole 1a,b (1 mmol) and Al2O3
nanocatalyst (15–18 mg, 10 mol %). The resulting reaction
mixture was refluxed for 6–8 h. The reaction completion
was monitored by TLC (eluent EtOAc–hexane, 2:3). The
precipitate was filtered, washed with water, dried, and
recrystallized from ethanol to give the desired product 4a–p
as white or yellow needles.
1
1580, 1489, 1438, 1220, 1091, 783, 741, 676. H NMR
spectrum, δ, ppm (J, Hz): 8.26 (2H, d, J = 7.8, H Ar); 7.98
(2H, d, J = 8.1, H Ar); 7.87 (2H, d, J = 8.4, H Ar); 7.59–
7.48 (6H, m, H Ar, H Ph); 7.38 (1H, t, J = 7.2, H Ph); 2.32
(3H, s, CH3). 13C NMR spectrum, δ, ppm: 190.7; 159.0;
150.2; 148.6; 142.9; 142.5; 138.4; 137.1; 135.4; 133.3;
131.3; 130.9; 129.9; 129.3; 129.2; 129.1; 128.9; 126.9;
121.3; 116.0; 13.9. Mass spectrum, m/z (Irel, %): 486 [M+4]+
(1), 484 [M(37Cl)]+ (6), 482 [M]+ (8), 346 (45), 345 (42), 344
(100), 343 (65), 329 (15), 267 (12), 200 (34), 141
[37ClC6H4CO]+ (12), 139 [35ClC6H4CO]+ (37), 111 (20), 77
[Ph]+ (47), 51 (27). Found, %: C 66.91; H 3.26; N 11.71.
C27H16Cl2N4O. Calculated, %: C 67.09; H 3.34; N 11.59.
3-Methyl-6-(4-methylphenyl)-1-phenyl-4-phenylcarbonyl-
1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4e). Yield
0.36 g (84%), pale-yellow needles, mp 175–176°C.
IR spectrum, ν, cm–1: 3058, 2923, 2219, 1672, 1590, 1499,
6-(4-Chlorophenyl)-3-methyl-1-phenyl-4-(phenyl-
carbonyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4a).
Yield 0.41 g (91%), white needles, mp 171–173°C.
IR spectrum, ν, cm–1: 3070, 2927, 2220, 1676, 1580, 1489,
1
1438, 1220, 1091, 783, 741, 676. H NMR spectrum,
δ, ppm (J, Hz): 8.27 (2H, d, J = 8.1, H Ar); 8.01–7.89 (4H,
m, H Ar); 7.79–7.68 (1H, m, H Ar); 7.63–7.48 (6H, m,
H Ar); 7.37 (1H, t, J = 7.5, H Ar); 2.31 (3H, s, CH3).
13C NMR spectrum, δ, ppm: 191.9; 162.3; 159.0; 150.2;
149.4; 143.1; 138.4; 137.0; 135.6; 134.9; 130.9; 130.1;
129.5; 129.3; 129.1; 126.9; 121.3; 116.1; 111.9; 97.7; 13.8.
Mass spectrum, m/z (Irel, %): 450 [M(37Cl)]+ (4), 448 [M]+
(13), 347 (11), 346 (53), 345 [M(37Cl)–PhCO]+ (55), 344
(100), 343 [(M)–PhCO]+ (64), 329 (18), 303 (10), 267 (14),
165 (10), 111 (23), 77 [Ph]+ (73), 51 (34). Found, %:
C 72.13; H 3.69; N 12.54. C27H17ClN4O. Calculated, %:
C 72.24; H 3.82; N 12.48.
1
1425, 1387, 1216, 1022, 743, 681. H NMR spectrum,
δ, ppm (J, Hz): 8.35–8.28 (2H, m, H Ar); 7.99–7.87 (3H,
m, H Ar); 7.72 (1H, t, J = 7.2, H Ar); 7.65–7.45 (4H, m,
H Ar); 7.43–7.25 (4H, m, H Ar); 2.70 (3H, s, CH3); 2.32
(3H, s, CH3). 13C NMR spectrum, δ, ppm: 192.1; 162.3;
159.8; 150.4; 143.5; 138.6; 136.9; 135.5; 135.1; 134.7;
130.1; 129.5; 129.4; 129.2 (2C); 126.6; 121.2; 116.4;
114.8; 100.6; 21.5; 13.9. Mass spectrum, m/z (Irel, %): 429
[M+H]+ (37), 428 [M]+ (99), 399 (49), 105 [PhCO]+ (81), 77
[Ph]+ (100), 51 (20). Found, %: C 78.13; H 4.49; N 13.21.
C28H20N4O. Calculated, %: C 78.49; H 4.70; N 13.08.
6-(4-Chlorophenyl)-4-[(4-fluorophenyl)carbonyl]-
3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4b). Yield 0.40 g (86%), yellow needles, mp 178–
179°C. IR spectrum, ν, cm–1: 3065, 2220, 1675, 1590,
1
1498, 1420, 1390, 1229, 1094, 750, 678. H NMR spectrum,
δ, ppm (J, Hz): 8.32–8.20 (2H, m, H Ar); 8.03–7.89 (4H,
m, H Ar); 7.59–7.48 (4H, m, H Ar); 7.42–7.25 (3H, m,
H Ar); 2.31 (3H, s, CH3). 13C NMR spectrum, δ, ppm:
190.0; 168.9; 159.3; 150.4; 148.9; 143.5; 139.4; 137.3;
135.2; 134.9; 133.1; 130.8; 130.7; 130.3; 129.2; 129.1;
126.7; 126.3; 121.0; 116.8; 112.1; 97.9; 13.8. Mass
spectrum, m/z (Irel, %): 468 [M(37Cl)]+ (5), 466 [M]+ (14),
347 (11), 346 (48), 345 [M(37Cl)–(4-FC6H4)CO]+ (51), 344
(100), 343 [M–(4-FC6H4)CO]+ (62), 330 (18), 267 (14),
123 (29), 95 (16), 77 [Ph]+ (49), 51 (29). Found, %:
C 69.32; H 3.69; N 12.41. C27H16ClFN4O. Calculated, %:
C 69.46; H 3.45; N 12.00.
4-[(4-Fluorophenyl)carbonyl]-3-methyl-6-(4-methyl-
phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4f). Yield 0.36 g (81%), pale-yellow needles,
mp 204–205°C. IR spectrum, ν, cm–1: 3074, 2923, 2221,
1
1673, 1591, 1484, 1425, 1384, 1231, 1091, 776. H NMR
spectrum, δ, ppm (J, Hz): 8.37–8.25 (2H, m, H Ar); 8.08–
7.86 (3H, m, H Ar); 7.60–7.45 (3H, m, H Ar); 7.43–7.31
(3H, m, H Ar); 7.31–7.18 (2H, m, H Ar); 2.47 (3H, s, CH3);
2.31 (3H, s, CH3). 13C NMR spectrum, δ, ppm: 190.1;
165.4; 160.4; 143.5; 138.9; 136.9; 134.7; 133.0; 131.6;
129.5; 129.4; 129.3; 129.2 (2C); 126.7; 126.3; 120.8;
118.9; 116.3; 114.7; 100.5; 97.6; 21.5; 13.8. Mass spectrum,
m/z (Irel, %): 447 [M+H]+ (12), 446 [M]+ (36), 417 (24), 325
(27), 324 [(M+H)–(4-FC6H4)CO]+ (100), 323 (71), 308 (16),
282 (11), 200 (12), 123 [4-FC6H4CO]+ (43), 94 (29), 77 [Ph]+
(37), 51 [C4H3]+ (19). Found, %: C 75.21; H 4.18; N 12.68.
C28H19FN4O. Calculated, %: C 75.32; H 4.29; N 12.55.
6-(4-Chlorophenyl)-4-[(4-methoxyphenyl)carbonyl]-
3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4c). Yield 0.36 g (75%), white needles, mp 206–
207°C. IR spectrum, ν, cm–1: 3055, 2218, 1655, 1583,
1
1500, 1430, 1261, 1170, 1017, 844, 755. H NMR spectrum,
δ, ppm (J, Hz): 8.27 (2H, d, J=7.8, H Ar); 8.00 (2H, d,
J = 8.4, H Ar); 7.89 (2H, d, J = 8.1, H Ar); 7.51–7.58 (4H,
54

Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
4-[(4-Methoxyphenyl)carbonyl)-3-methyl-6-(4-methyl-
(2H, d, J = 8.4, H Ar); 7.48 (1H, t, J = 8.1, H Ar); 7.35–
7.26 (3H, m, H Ar); 2.31 (3H, s, CH3). 13C NMR spectrum,
δ, ppm: 190.0; 168.9; 159.3; 150.4; 148.9; 143.5; 139.4;
137.3; 135.2; 134.9; 133.0; 130.8; 130.7; 130.3; 129.2;
129.1; 126.7; 126.3; 121.1; 116.9; 112.1; 97.9; 13.8. Mass
spectrum, m/z (Irel, %): 504 [M+4]+ (4), 502 [M(37Cl)]+ (23),
500 [M]+ (33), 382 (13), 380 (71), 378 [(M+H)–4-FC6H4CO]+
(100), 377 (19), 343 (37), 267 (11), 176 (13), 165 (13), 148
(12), 123 [4-FC6H4CO]+ (96), 111 [35ClC6H4]+ (47), 95 (58),
75 (55), 51 (11). Found, %: C 64.51; H 3.14; N 11.02.
C27H15Cl2FN4O. Calculated, %: C 64.69; H 3.02; N 11.18.
1-(3-Chlorophenyl)-6-(4-chlorophenyl)-4-[(4-methoxy-
phenyl)carbonyl)]-3-methyl-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (4k). Yield 0.39 g (76%), orange needles,
mp 176–178°C. IR spectrum, ν, cm–1: 3077, 2932, 2220,
1662, 1584, 1487, 1439, 1260, 1169, 1094, 1017, 836, 771,
672. 1H NMR spectrum, δ, ppm (J, Hz): 8.36 (1H, s, H Ar);
8.27 (1H, d, J = 8.1, H Ar); 7.99 (2H, d, J = 6.9, H Ar);
7.88 (2H, d, J = 5.7, H Ar); 7.56–7.41 (4H, m, H Ar); 7.02
(2H, d, J = 8.1, Ar); 3.87 (3H, s, OCH3); 2.31 (3H, s, CH3).
13C NMR spectrum, δ, ppm: 189.8; 165.5; 150.4; 149.9;
143.8; 139.5; 137.2; 135.4; 134.9; 132.7; 130.9; 130.7;
129.8; 129.4; 129.1; 126.6; 126.3; 120.9; 118.8; 116.6;
112.2; 55.8; 13.8. Mass spectrum, m/z (Irel, %): 516 [M+4]+
(10), 514 [M(37Cl)]+ (32), 512 [M]+ (43), 139 (14), 136 (22),
135 [4-MeOC6H4CO]+ (100), 111 [ClC6H4]+ (28), 107
[4-MeOC6H4]+ (29), 91 (32), 77 [Ph]+ (49). Found, %:
C 65.39; H 3.42; N 10.87. C28H18Cl2N4O2. Calculated, %:
C 65.51; H 3.53; N 10.91.
phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4g). Yield 0.32 g (70%), white needles, mp 184–
186°C. IR spectrum, ν, cm–1: 3057, 2924, 2220, 1675,
1590, 1500, 1426, 1388, 1259, 1171, 1020, 784, 676. 1H NMR
spectrum, δ, ppm (J, Hz): 8.31 (2H, d, J = 7.8, H Ar); 8.02–
7.86 (4H, m, H Ar); 7.59–7.45 (4H, m, H Ar); 7.42–7.30
(3H, m, H Ar); 3.92 (3H, s, OCH3); 2.47 (3H, s, CH3); 2.32
(3H, s, CH3). 13C NMR spectrum, δ, ppm: 190.3; 165.4;
162.3; 159.8; 143.5; 138.6; 136.9; 134.7; 132.7; 129.5;
129.4; 129.3; 129.2; 128.2; 126.6; 126.3; 120.9; 118.9;
116.5; 114.7; 100.6; 55.8; 21.5; 13.8. Mass spectrum, m/z
(Irel, %): 458 [M]+ (5), 325 (37), 324 [(M+H)–(4-MeOC6H4)CO]+
(100), 323 (93), 309 (24), 283 (15), 282 (11), 135
[4-MeOC6H4CO]+ (12), 77 [Ph]+ (44), 51 (21). Found, %:
C 75.84; H 4.97; N 12.31. C29H22N4O2. Calculated, %:
C 75.97; H 4.84; N 12.22.
4-[(4-Chlorophenyl)carbonyl]-3-methyl-6-(4-methyl-
phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (4h). Yield 0.37 g (79%), pale-yellow needles,
mp 169–170°C. IR spectrum, ν, cm–1: 3057, 2922, 2219,
1675, 1583, 11467, 1421, 1389, 1217, 1090, 1016, 747,
1
676. H NMR spectrum, δ, ppm (J, Hz): 8.31 (2H, d,
J = 7.2, H Ar); 7.94 (2H, d, J = 6.9, H Ar); 7.61–7.49 (5H,
m, H Ar); 7.42–7.33 (4H, m, H Ar); 2.69 (3H, s, CH3); 2.31
(3H, s, CH3). 13C NMR spectrum, δ, ppm: 190.9; 160.4;
150.4; 148.5; 143.5; 138.9; 138.5; 134.7; 134.2; 133.4;
131.4; 129.9; 129.5; 129.4; 129.2 (2C); 126.7; 126.3;
116.3; 97.6; 21.5; 13.9. Mass spectrum, m/z (Irel, %): 464
[M(37Cl)]+ (7), 462 [M]+ (20), 325 (31), 324 (100), 323 (79),
308 (17), 282 (12), 141 [37ClC6H4CO]+ (17), 140 (10), 139
[35ClC6H4CO]+ (35), 109 (10), 107 (24), 91 (13), 77 [Ph]+
(55), 51 [C4H3]+ (24). Found, %: C 72.46; H 4.05; N 11.95.
C28H19ClN4O. Calculated, %: C 72.65; H 4.14; N 12.10.
1-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-4-phe-
nylcarbonyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
(4i). Yield 0.43 g (89%), white needles, mp 178–179°C.
IR spectrum, ν, cm–1: 3079, 2934, 2220, 1661, 1585, 1488,
1-(3-Chlorophenyl)-6-(4-chlorophenyl)-4-[(4-chloro-
phenyl)carbonyl]-3-methyl-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (4l). Yield 0.44 g (85%), light-orange
needles, mp 191–193°C. IR spectrum, ν, cm–1: 3079, 2932,
2219, 1674, 1581, 1487, 1483, 1220, 1090, 1007, 899, 770,
672. 1H NMR spectrum, δ, ppm (J, Hz): 8.36 (1H, s, H Ar);
8.29 (1H, d, J = 8.1, H Ar); 7.99 (2H, d, J = 8.4, H Ar);
7.86 (1H, d, J = 8.1, H Ar); 7.60–7.50 (4H, m, H Ar); 7.51–
7.41 (2H, m, H Ar); 7.33 (1H, d, J = 8.7, H Ar); 2.31 (3H,
s, CH3). 13C NMR spectrum, δ, ppm: 190.5; 159.3; 150.4;
148.8; 143.4; 142.6; 139.4; 137.3; 135.2; 134.9; 130.8;
130.7; 130.3; 129.5; 129.2; 129.1; 126.7; 126.3; 118.8;
115.8; 112.1; 98.1; 13.9. Mass spectrum, m/z (Irel, %): 522
[M+6]+ (1), 520 [M+4]+ (8), 518 [M(37Cl)]+ (22), 516 [M]+
(22), 382 (19), 380 (74), 378 [M(37Cl)–35ClC6H4CO]+ (100),
343 (36), 267 (11), 165 (13), 140 [35ClC6H4CO]+ (25), 138
(68), 134 (15), 113 [37ClC6H4]+ (27), 111 [35ClC6H4]+ (72), 75
(48), 51 [C4H3]+ (10). Found, %: C 62.51; H 3.10; N 10.97.
C27H15Cl3N4O. Calculated, %: C 62.63; H 2.92; N 10.82.
1-(3-Chlorophenyl)-3-methyl-6-(4-methylphenyl)-4-phe-
nylcarbonyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
(4m). Yield 0.38 g (83%), pale-yellow needles, mp 201–
202°C. IR spectrum, ν, cm–1: 3061, 2923, 2221, 1673,
1
1260, 1169, 1094, 1017, 836, 777. H NMR spectrum,
δ, ppm (J, Hz): 8.37 (1H, s, H Ar); 8.29 (1H, d, J = 8.4,
H Ar); 8.00 (2H, d, J = 8.1, H Ar); 7.92 (2H, d, J = 7.8,
H Ar); 7.75 (1H, t, J = 7.2, H Ar); 7.65–7.52 (4H, m,
H Ar); 7.45 (1H, t, J = 7.8, H Ar); 7.32 (1H, d, J = 7.8,
H Ar); 2.29 (3H, s, CH3). 13C NMR spectrum, δ, ppm:
191.7; 159.3; 150.4; 149.5; 143.6; 139.5; 137.2; 135.7;
135.3; 134.9 (2C); 130.9; 130.7; 130.3; 130.1; 129.5;
129.1; 126.7; 126.3; 121.0; 118.8; 115.9; 13.8. Mass
spectrum, m/z (Irel, %): 486 [M+4]+ (14), 484 [M(37Cl)]+ (82),
482 [M]+ (94), 457 (5), 455 (28), 453 (43), 378 (16), 301 (15),
237 (20), 111 (26), 105 [PhCO]+ (100), 77 [Ph]+ (92), 51 (12).
Found, %: C 66.87; H 3.45; N 11.79. C27H16Cl2N4O.
Calculated, %: C 67.09; H 3.34; N 11.59.
1
1-(3-Chlorophenyl)-6-(4-chlorophenyl)-4-[(4-fluoro-
phenyl)carbonyl]-3-methyl-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (4j). Yield 0.39 g (78%), white needles,
mp 208–209°C. IR spectrum, ν, cm–1: 3098, 2945, 2222,
1665, 1584, 1492, 1428, 1231, 1091, 1012, 844, 764, 677,
614. 1H NMR spectrum, δ, ppm (J, Hz): 8.36 (1H, s, H Ar);
8.29 (1H, d, J = 7.8, H Ar); 8.08–7.91 (4H, m, H Ar); 7.57
1590, 1483, 1385, 1027, 775, 742. H NMR spectrum,
δ, ppm (J, Hz): 8.37 (1H, s, H Ar); 8.30 (1H, d, J = 8.1,
H Ar); 8.00–7.87 (4H, m, H Ar); 7.62–7.53 (1H, m, H Ar);
7.43–7.32 (4H, m, H Ar); 7.29–7.20 (2H, m, H Ar); 2.45
(3H, s, CH3); 2.25 (3H, s, CH3). 13C NMR spectrum,
δ, ppm: 195.1; 159.9; 150.5; 143.9; 143.5; 140.9; 139.9;
136.9; 134.9; 134.8; 131.2; 130.6; 129.4; 128.9; 128.2;
55

Chemistry of Heterocyclic Compounds 2018, 54(1), 51–57
125.9; 121.0; 120.5; 118.4; 115.0; 100.9; 98.1; 21.5; 13.8.
Supplementary information file containing 1H NMR
spectra of compounds 4a–p and mass spectrum of
compound is available at the journal website at http://
link.springer.com/journal/10593.
Mass spectrum, m/z (Irel, %): 464 [M(37Cl)]+ (7), 462 [M]+
(20), 436 (12), 358 (24), 346 (21), 236 (27), 234 (76), 119
(98), 111 (50), 105 [PhCO]+ (99), 95 (64), 77 [Ph]+ (100), 51
[C4H3]+ (26). Found, %: C 72.71; H 4.06; N 12.19.
C28H19ClN4O. Calculated, %: C 72.65; H 4.14; N 12.10.
1-(3-Chlorophenyl)-4-[(4-fluorophenyl)carbonyl]-
3-methyl-6-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (4n). Yield 0.38 g (80%), yellow needles,
mp 185–187°C. IR spectrum, ν, cm–1: 3074, 2923, 2221,
1673, 1591, 1484, 1384, 1231, 1091, 1031, 776, 743. 1H NMR
spectrum, δ, ppm (J, Hz): 8.41 (1H, s, H Ar); 8.40–8.29
(1H, m, H Ar); 8.01–7.91 (4H, m, H Ar); 7.52–7.35 (4H,
m, H Ar); 7.37 (2H, m, H Ar); 2.48 (3H, s, CH3); 2.30 (3H,
s, CH3). 13C NMR spectrum, δ, ppm: 190.2; 165.4; 159.9;
150.6; 148.8; 143.9; 141.3; 139.6; 134.9; 134.5; 132.9;
131.6; 130.2; 129.6; 126.5; 126.0; 120.6; 118.6; 116.8;
115.0; 100.9; 98.0; 21.5; 13.8. Mass spectrum, m/z (Irel, %):
482 [M(37Cl)]+ (10), 480 [M]+ (29), 451 (20), 234 (26), 123
[4-FC6H4CO]+ (100), 119 (27), 111 [35ClC6H4]+ (26), 95 (59),
91 [Ar2]+ (16), 75 (26). Found, %: C 69.81; H 3.91; N 11.82.
C28H18ClFN4O. Calculated, %: C 69.93; H 3.77; N 11.65.
1-(3-Chlorophenyl)-4-[(4-methoxyphenyl)carbonyl]-
3-methyl-6-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (4o). Yield 0.37 g (76%), pale-yellow
needles, mp 205–206°C. IR spectrum, ν, cm–1: 3061, 2923,
2221, 1653, 1592, 1483, 1385, 1264, 1172, 1088, 1024,
The authors are grateful for support from the Urmia
University.
We also thank Prof. R. H. Prager from the Flinders
University of Australia for proof-reading and language
editing of this article.
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906, 776, 738. H NMR spectrum, δ, ppm (J, Hz): 8.40
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137.0; 136.9; 134.8; 134.5; 130.1; 129.9; 129.5; 129.3;
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(1H, d, J = 7.8, H Ar); 8.38–8.29 (1H, m, H Ar); 7.95 (2H,
d, J = 8.4, H Ar); 7.86 (2H, d, J = 8.4, H Ar); 7.55 (2H, d,
J = 8.4, H Ar); 7.39 (2H, d, J = 8.4, H Ar); 7.37–7.21 (1H,
m, H Ar); 2.48 (3H, s, CH3); 2.31 (3H, s, CH3). 13C NMR
spectrum, δ, ppm: 191.1; 160.6; 148.6; 143.3; 141.3; 139.9;
139.6; 134.9; 134.0; 133.4; 130.9; 130.2; 129.9; 129.7;
129.6; 129.5; 129.0; 126.0; 125.3; 118.1; 115.0; 100.9;
21.5; 13.7. Mass spectrum, m/z (Irel, %): 500 [M+4]+ (3), 498
[M(37Cl)]+ (16), 496 [M]+ (22), 467 (12), 236 (13), 234 (37),
141 [37ClC6H4CO]+ (24), 139 [35ClC6H4CO]+ (72), 133 (12),
119 (100), 113 [37ClC6H4]+ (21), 111 [35ClC6H4]+ (64), 91
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