Ultrasonic-Assisted Synthesis of Pyrazolo[3,4-d]pyrimidin-4-ol Tethered with 1,2,3-Triazoles and Their Anticancer Activity

Article abstract of DOI:10.1134/S1068162020050106

Abstract: In the presents work synthesis and characterization of new heterocyclic derivatives containing pyrazolo[3,4-d]pyrimidine linkage with 1,4-disubstituted-1,2,3-triazoles via methylene-oxy group. The selected synthesized compounds were tested for their in-vitro anticancer activity against various cancer cell lines. Synthesis of compounds was done under ultrasonic-assisted Huisgen 1,3-dipolar cycloaddition reaction with good yields. Some of the newly synthesized compounds demonstrated good to moderate anticancer activity, most of compounds shows activity against renal cancer cell lines.

Full text of DOI:10.1134/S1068162020050106

ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2020, Vol. 46, No. 5, pp. 803–813. © Pleiades Publishing, Ltd., 2020.
Ultrasonic-Assisted Synthesis of Pyrazolo[3,4-d]pyrimidin-4-ol
Tethered with 1,2,3-Triazoles and Their Anticancer Activity
Prakash L. Kalavadiyaa, Vimal H. Kapuparaa, Dinesh G. Gojiyaa, Tejal D. Bhatta, Sanjay D. Hadiyala,
and Dr. Hitendra S. Joshia, 1
aDepartment of Chemistry, Saurashtra University, Gujrat, Rajkot-360005 India
Received December 23, 2019; revised March 11, 2020; accepted March 19, 2020
Abstract—In the presents work synthesis and characterization of new heterocyclic derivatives containing pyr-
azolo[3,4-d]pyrimidine linkage with 1,4-disubstituted-1,2,3-triazoles via methylene-oxy group. The selected
synthesized compounds were tested for their in-vitro anticancer activity against various cancer cell lines. Syn-
thesis of compounds was done under ultrasonic-assisted Huisgen 1,3-dipolar cycloaddition reaction with
good yields. Some of the newly synthesized compounds demonstrated good to moderate anticancer activity,
most of compounds shows activity against renal cancer cell lines.
Keywords: pyrazolo[3,4-d]pyrimidin-4-ol,1,4-disubstituted-1,2,3-triazole derivatives, in-vitro anticancer
screening, ultrasonic-assisted mild reaction conditions
DOI: 10.1134/S1068162020050106
INTRODUCTION
using Cu(I) catalysed click reaction. Previously many
synthetic routes were reported for the synthesis of
1,4-disubstituted-1,2,3-triazole using cycloaddition
reaction of 1,3-dipolar organic azide and terminal
alkyne in the presence of Cu(I) catalyst [16–19].
Nitrogen-containing heterocyclic compounds are
widely distributed in nature including amino acids,
purines, pyrimidines and many other natural prod-
ucts. The purine is fused heterocyclic ring containing
pyrimidine and imidazole ring, the chemical compo-
sition of purine is related to pyrazolopyrimidine. Pyra-
zolopyrimidine is a fused nitrogen containing hetero-
cyclic ring system which considered as privileged core
skeleton in the biologically active compounds and like a
bioisostere of natural purine. Several pyrazolopyrimidine
derivatives received great attention due to their biological
and pharmacological activities [1–3]. In the current
work on pyrazolo[3,4-d]pyrimidines are reported to
encompass pharmacological potential as antiviral, [4]
antimicrobial, [5, 6] antitumor [7–9], Parkinson’s dis-
ease [10], skin cancer cell lines (G-361) [11], CNS cancer
(SF-268) [12] and human leukemia (HL-60) [13].
Numerous compounds bearing this moiety are also well
known for various therapeutic effects.
Over the past few years, 1,4-disubstituted-1,2,3-
triazoles have been an important class of compounds,
due to their widely pharmacology activities and key
intermediate in many industrial application such as
agrochemical [20, 21], additives [22], pigment [23,
24], metal chelators [25], photostabilizers [26, 27] and
corrosion inhibitors [28, 29]. The 1,2,3-triazole het-
erocycles are well-known privilege medicinal scaffolds
because of their significant biological activity. A few
examples are shown in Fig. 1, including antimicrobial
[30–32], antiallergic [33], anti-HIV [34], antituber-
cular [35–37] and antitumor agents [38]. To the best
of our knowledge and literature review, very few bio-
logical active hybrid molecules reported containing
both pyrazolopyrimidine and 1,2,3-triazole skeleton
(Fig. 2). Compound (a, b) are used as key intermedi-
ates in constructing the cross-linked deoxyoligonucle-
1,2,3-Triazole is a five-member heterocyclic ring
contains three nitrogen and two carbon atoms. Mainly
two isomeric forms of triazole have existed namely otides duplex [39]. 3,6-Dimethyl-1-phenyl-5-((1-
1,2,3-triazole and 1,2,4-triazole. Generally disubsti- aryl-1H-1,2,3-triazol-4-yl)-methyl)-1H-pyrazolo[3,4-
d]pyrimidin-4(5H)-ones (c) were reported for moder-
ate anticancer activity against HCT-116, MCF-6 cell
lines at 100 μM concentration and for 5-lipoxygenase
inhibition activities [40]. 5-((1-(3-chlorophenyl)-1H-
1,2,3-triazol-4-yl)methyl)-1-phenyl-1,5-dihydro-4H-
pyrazolo[3,4-d]pyrimidin-4-one (d) were reported for
their potent anticancer activity against C6 rat and U87
human glioma cell lines 10 μM concentration [41].
tuted-1,2,3-triazole are further subdivided into two
class, namely 1,4-disubstituted-1,2,3-triazoles and
1,5-disubstituted-1,2,3-triazoles. 1,5-Disubstituted
triazoles have been synthesized using different cata-
lysts and methos like RuAAC [14] and Nickel(II) [15].
1,4-Disubstituted triazoles have been synthesized
1 Corresponding author: e-mail: drhsjoshichem@gmail.com.
803

804
PRAKASH L. KALAVADIYA et al.
F
O
S
O
O
HO
HN
N
N
N
N
N
N
N
N
F
O
O
S
N
N
O
OH
O
OH
OH
N
S
N
N
H
Tazobactam
β-lactam antibiotic
N
H2N
Fluconazole
antifungal
Cefatrizine
β-lactam antibiotic
N
O
N
N
N
O
N
N
N
N
HN
O
N
N
O
S
5
N
N
N
O
N
O
N
O
Anti-cancer activity
Anti-cancer activity
Anti-HIV activity
Fig. 1. Marketed drug and biologically active 1,2,3-triazole containing molecules.
H
NH2
N
O
N
N
N
N
N
N
N
O
N
O
N
N3
N
N
O
N
N
O
O
N
OH
HN
H2N
HN
H2N
N
N
HO
N
N
OH
OH
HO
N
HO
N
(a)
(b)
O
O
O
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
F3C
N
N
N
Cl
(c)
(d)
(e)
Fig. 2. Biologically active pyrazolopyrimidine and triazole containing hybrid compounds.
Compound (e) showed potent activity against pancre- out further purification. The preparation of 2-
atic cancer cell lines (Fig. 2) [42].
(ethoxymethylene) malononitrile (I) according to
previously reported reaction of malononitrile, triethyl
orthoformate and acetic anhydride [43, 44], then
Michael addition of phenylhydrazine on (I) to give 5-
amino-1-phenyl-1H-pyrazole-4-carbonitrile (II) [44,
Our efforts focused on the synthesize of biologi-
cally active new 1,2,3-triazole derivatives attached to
pyrazolo[3,4-d]pyrimidine linkage with methylene-
oxy ether. Based on all above-mentioned literature
and extension of our studies on the development of 45]. The resulting aminocyanopyrazole (II) was given
new triazole derivatives, we have developed the ultra-
sonic-assisted mediated synthesis of new derivatives of
1,2,3-triazole containing pyrazolopyrimidine using
1,3-dipolar cycloaddition reaction of substituted
azides and alkynes in the presence of Cu(I) catalysed,
the synthesized compounds have been screening for
their in-vitro anticancer activity against various types
of cancer and their different cell lines.
intermolecular condensation reaction through reflux-
ing in formic acid to afford 1-phenyl-1,5-dihydro-4H-
pyrazolo[3,4-d]pyrimidin-4-one (III) [45, 46], fur-
ther pyrazolo[3,4-d]pyrimidin-4-one (III) was heated
in phosphorus oxychloride to afforded 4-chloro-1-
phenyl-1H-pyrazolo[3,4-d]pyrimidine (IV) [45–47].
Resulting chloro pyrazolo[3,4-d]pyrimidine (IV) react
with propargyl alcohol in the presence of potassium
tert-butoxide to afforded 1-phenyl-4-(prop-2-yn-1-
yloxy) -1H-pyrazolo[3,4-d]pyrimidine (V). The syn-
thesis of desire triazole compounds using Copper(I)-
catalyzed azide-alkyne cycloaddition (CuAAC) reac-
tion of the terminal alkyne (V) react with various aro-
matic or aliphatic azide in the presence of Cu(I) to
afforded desired triazole compounds (VI–XXII). The
synthesized targeted compounds carried out as out-
RESULTS AND DISCUSSION
Chemistry
We have initially examined the synthesis of title
compounds were carried out by both conventional and
ultrasonic-assisted method, according to result it’s
clear that ultrasonic approach to be extremely fast,
providing to excellent yield (82–94%) have been with- lined in Scheme 1.
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ULTRASONIC-ASSISTED
805
N
O
N
Cl
N
N
N
NH
N
N
N
N
i
ii
iv
iii
N
NH2
N
N
O
N
N
(I)
(II)
(III)
(IV)
R
N
N
N
H
N
R =
O
N
O
O
N-Subtituted phenylacetamide
N
N
v
vi
N
N
N
N
N
Substituted phenyl
(V)
(VI−XXII)
(i) Ethyl orthoformate, acetic anhydride, 130 °C, 8 h; (ii) phenylhydrazine, EtOH, 80°C, 10 h;
(iii) formic acid, 110°C, 12 h; (iv) POCl3, 80°C, 2 h; (v) propargyl alcohol, t-BuOK, THF, 30 min;
(vi) various azide, CuSO4, Na-ascorbate, DMF : t-BuOH : water, 10 to 20 min
Cl
F
H
H
N
H
N
H
N
H
N
N
Cl
O
O
O
O
O
F
Cl
(VI)
(VII
(VIII)
(IX)
(X)
H
N
H
N
H
N
H
N
H
N
N
N
N
O
O
O
O
O
NO2
(XI)
(XII)
(XIII)
(XIV)
(XV)
NO2
O
O
Cl
F
H
N
F
Cl
O
O
(XVI)
(XVII)
(XVIII)
(XIX)
(XX)
(XXI)
(XXII)
Scheme 1. Synthetic route for desire compounds (VI) to (XXII).
Therefore, the protocol of the ultrasonic mediated reaction of azide and terminal alkyne in the presence
of Cu(II) catalyst and Sodium ascorbate as a co-catalyst.
reactions was reduced significant energy and fulfil the
green chemistry approaches. Moreover, the ultrasonic
reaction is faster, easier and more reliable compared to
conventional methods, thus a variety of compounds
were synthesized by these type of approaches, but only
some reports are available for the click chemistry by
using ultrasonic irradiation method in organic chem-
istry/drug discovery. Based on previously reported
ultrasonic-assisted method is a great role in synthetic
organic chemistry, so we are promoted to use this type
Some limited study performed in order to establish
an effective and mild reaction conditions for the syn-
thesis of compounds (VI–XXII). Initially, we perform
reaction at conventional method in the presences of
Cu(I) catalysed in various solvents or mixture of sol-
vents, based on previously reported conventional
method shown in Table 1 entry 1 to 7. In order to
shorter reaction time as well as mild reaction condi-
tions, the reaction performs under the ultrasonic irra-
of mild reaction conditions for the synthesis of desired diation using Digital ultrasonic cleaner to gave lower
compounds, which was prepared from cycloaddition yield at first 5 to 10 minutes but good yield observed at
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 5 2020

806
PRAKASH L. KALAVADIYA et al.
Table 1. Optimization of reaction conditions for the synthesis of compound VI
Entry
Solvent
Catalyst
Time, h
Yield, %
37a
52a
65a
84a
62a
72a
18a
94b
75b
67b
(I)
MeOH
CuSO4, Na-ascorbate
CuSO4, Na-ascorbate
CuSO4, Na-ascorbate
12
(II)
DMF : MeOH (1 : 1)
12
(III)
(IV)
(V)
DMF : t-BuOH (1 : 1)
8
DMF : t-BuOH : Water (1 : 1 : 1) CuSO4, Na-ascorbate
6
8
DMF : Water (1 : 1)
BuOH : Water (1 : 1)
Water
CuSO4, Na-ascorbate
CuSO4, Na-ascorbate
CuSO4, Na-ascorbate
(VI)
(VII)
(VIII)
(IX)
(X)
8
12
DMF : t-BuOH : Water (1 : 1 : 1) CuSO4, Na-ascorbate
DMF : t-BuOH : Water (1 : 1 : 1) CuI (10%)
DMF : t-BuOH : Water (1 : 1 : 1) CuBr (10%)
20 min
20 min
30 min
aConventional method; bultrasonic-assisted method at room temperature.
3380 cm–1 in compounds (VI) to (XVI), C–H stretch-
20 minutes shown in Table 1 entry 8 to 10. Based on all
the above trial reaction, the model reaction conditions
for preparation of targeted compounds using ultra-
sonic irradiation and DMF : t-BuOH : water (1 : 1 : 1)
as a solvent (Table 1, entry 4 and 8) to achieve good
yields, shorter reaction times and no required any
purification.
ing of aliphatic CH2 shown peak near 3080 cm–1 and
C–H bending observed near 1360–1450 cm–1. The
C=O stretching of amide bond shown peak around
1600–1720 cm–1 in compounds (VI) to (XVII), in com-
pound (XVII) C=O stretching shown at 1604 cm–1 due
to presence of benzylic amine. In mass spectrometry
we observed molecular ion peak with natural abun-
dance and their related fragmentation pattern, in all
mass spectrum data we observed most stable fragment
of compounds cleavage from ether bond between tri-
azole ring and pyrazolopyrimidine ring it’s observed at
m/z 211.9.
The spectral data and physical parameter of newly
synthesized triazole derivatives (VI) to (XXII) are well-
characterized with the assigned structure of com-
pounds, 1H and 13C NMR, mass and FT-IR spectra of
the compounds are given in supplementary material
and are in good agreement with the proposed structure
of the compounds.
All the newly synthesized compounds were charac-
terized by using FT-IR, 1H NMR, 13C NMR and mass
1
spectrometry analysis. In particular H NMR spec-
trum of targeted compounds, we observed singlet peak
at δ 10.101–11.125 ppm due to presence of aliphatic
amide proton (–CONH) in compounds (VI) to (XVI),
in the compound (XI) the –CONH peak moved in
high deshilded region due to –NO2 group and also
shown one singlet peak in deshielded region for the
‒CH proton of triazole ring, in aliphatic azide (VI) to
(XVI) shown at around δ 8.38 ppm, in aromatic azide
(XVIII) to (XXII) the –CH peck move in deshilded
region around δ 9.00 ppm. The aliphatic –CH2
between triazole ring and amide bond is shown singlet
at δ 5.364–5.594 ppm (VI) to (XVI), in compound
XVII –CH2 peck shightly move in deshilded region
due to attched with phenyl ring. Another singlet of
methylene-oxy –CH2 observed at δ 5.376–5.847 ppm
more deshielded due to directly attached with elec-
tronic withdrawing group. In 13C NMR spectrum,
show deshielded peak at δ 164 ppm for the presence of
C=O bond in compounds (VI) to (XVI), the another
peck in deshilded region at 162 ppm show C–O bond
of pyrimidne ring.the fused aromatic carbon of pyra-
zolopyrimidine ring shown at δ103 ppm due to elec-
tronic rich. The both aliphatic –CH2 carbon are
shown around δ52–60 ppm. In deshilded region com-
pound (IX), (X), (XIX) and (XX) shown doublet of
BIOLOGICAL EVALUATION
In Vitro Anticancer Screening
of the Synthesized Compounds
In previously reported studies of pyrazolo[3,4-
d]pyrimidine link with triazole molecules, it gives
promising anticancer activity (Fig. 2, compound c and
d), in these compound presence of amide bond in pyr-
azolo[3,4-d]pyrimidin-4-one. Due to the fact that we
have design hybrid pyrazolopyrimidine containing tri-
azole molecules linked with methylene-oxy group and
addition of aliphatic amide group to improve the bio-
logical activity. In our current in vitro anticancer pri-
mary screening studies, some compounds found as a
C–F coupling. In the FT-IR spectral data, we moderated anticancer agent against different cancer
observed sharp peak of N–H stretching value at 3250– cell lines. Primary in vitro anticancer screening, com-
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ULTRASONIC-ASSISTED
Renal Cancer
807
100
80
60
40
20
0
VII
IX
XI
XIII
XIV
Compounds
XV
XVIII
XVI XIX
XX
XXII
XXI
VIII
X
XII
Fig. 3. In vitro anticancer screening data of synthesized compounds against renal cancer cell line.
pound (XVIII) give good activity against breast cancer
EXPERIMENTAL
(T-47D), (XIV) give moderate activity against Non-
Small Cell Lung Cancer (HOP-92), Ovarian Cancer
(OVCAR-8) and Renal Cancer (SN12C), (XI) and
(XXI) give moderate activity against Renal Cancer
(A498) and (XXII) also give moderate activity against
Renal Cancer (UO-31). Pyrazolopyrimidine-triazole
compounds give good activities against different type
of cancer, these type hybrid compound given multiple
action of mechanism, [48] based on literature plausi-
ble action of mechanism reported as mTOR inhibitors,
[41] exhibiting antiproliferative effect against cells,
inhibited cancer cell migration and induce cell cycle
arrest at G1 phase [49]. Most of all synthesized com-
pounds show moderate anticancer activity against
renal cancer cell line, the graph of a renal cancer cell
line are shown in Fig. 3. The compounds (XI), (XIII),
(XIV), (XIX) and (XXII) give moderate activity and
some compounds moderated active against more than
one cancer cell line, some compounds are given less
activity or non-active against 60-cell line. The mean
graph plot of GI50 values are given in Table 2, and one-
dose graph given in the supplementary material.
Materials and Methods
All purchased chemicals used without further puri-
fication. Reactions were monitored by thin-layer
chromatography (TLC) on silica gel-G plates (G60
F254). Ultrasonic irradiation experiments were car-
ried out in Digital ultrasonic cleaner (LMUC-12).
Melting points were determined using an open capil-
lary melting point apparatus. FT-IR data were
recorded on a Shimadzu FT-IR-8400 instrument in
cm–1 (KBr). NMR spectra were recorded on a Bruker
1
Avance 400 MHz spectrometer (400 MHz for H
NMR and 101 MHz for 13C NMR) in deuterated sol-
vents like DMSO-d6 and CDCl3 with respect to
tetramethylsilane as a standard. NMR data predated
using MestReNova, 1H NMR chemical shifts are des-
ignated using the following abbreviations as well as
their combinations: s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet, br = broad signal, coupling
constants in Hz. Mass spectra were recorded on a Shi-
madzu GC-MS-QP-2010 mass spectrometer in ESI
(70 eV) model using direct inlet probe technique and
m/z is reported in atomic units per elementary charge.
CONCLUSIONS
The selected synthesized compounds were evalu-
ated for in vitro anti-cancer activity at National Can-
cer Institute (NCI) Bethesda, Maryland, USA. under
the Development Therapeutic Program DTP. They
evaluated for anti-cancer activity against 60 different
human cell line of different type of cancer like Leuke-
mia, Non-Small Cell Lung, Colon, CNS, Melanoma,
Ovarian, Renal, Prostate and Breast cancer. In a pri-
mary screening of compounds tested only one dose
against 60-cell lines at 10–5 M concentration and 75 μL
volume. The one-dose data was reported as a mean
graph of the percent growth of treated cells and the
One-dose assay is growth relative to the no-drug con-
trol, and relative to the time zero number of cells. This
In a summary, the present work we developed a
simple, rapid and effective synthesis of pyrazolopy-
rimidine triazole derivative from 1,3-dipolar cycload-
dition reaction of alkyne with various aromatic and
aliphatic azide using Cu(II) catalyst in the presence of
Sodium ascorbate. The use of ultrasonic irradiation
method effectively shorter reaction time and higher
yield compared to the conventional method. In the
in vitro anti-cancer screening, some compounds were
given moderate to good anti-cancer activity against
60-human cell line and some compounds react as less
active or non-active against cancer cell line.
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808
Table 2. In vitro anticancer screening of synthesized compounds
60 cell line assay in one dose at 1 × 10–5 M concentration
PRAKASH L. KALAVADIYA et al.
Entry Yield, %
active cell lines
mean growth %
growth of most sensitive cell
(VI)
94
87
92
94
82
85
90
82
87
–
–
–
(VII)
(VIII)
(IX)
(X)
(XI)
(XII)
(XIII)
(XIV)
Leukemia (MOLT-4)
Renal Cancer (A498)
95.17
95.96
91.64
98.00
91.92
89.09
94.11
–25.05
–29.83
–31.12
–13.33
–40.88
–34.17
–37.33
–40.90
–36.56
–40.10
–31.37
–23.06
–
Leukemia (SR)
Leukemia (RPMI-8226)
Renal Cancer (A498)
CNS Cancer (SNB–75)
Renal Cancer (UO–31)
Non–Small Cell Lung Cancer (HOP-92)
Ovarian Cancer (OVCAR-8)
Renal Cancer (SN12C)
Renal Cancer (UO-31)
Ovarian Cancer (OVCAR-4)
–
Breast Cancer (T-47D)
Renal Cancer (TK-10)
Non–Small Cell Lung Cancer (NCI-H522)
Renal Cancer (A498)
93.71
(XV)
84
92
90
92
94
88
84
85
91.84
94.35
–
100.85
98.16
102.77
99.66
90.73
(XVI)
(XVII)
(XVIII)
(XIX)
(XX)
–73.56
–36.64
–27.39
–32.07
–41.04
(XXI)
(XXII)
Renal Cancer (UO-31)
allows the detection of both growth inhibition (values after addition the reaction mixture was stirred for
between 0 and 100) and lethality (values less than 0).
30 minutes room temperature. The reaction moni-
tored by TLC, after completion of the reaction solvent
remove under reduced pressure, then after water was
added and product was extract using pet. ether, com-
bine organic layer and dry using sodium sulphate, sol-
vent remove under reduced pressure to afford light yel-
low colour solid product (7.8 g, yield 89.66%, mp 82–
86°C, exact mass: 250.09).
Synthesis procedure of 2-(ethoxymethylene) malo-
nonitrile (I). This compound synthesis to accourding
literature [43, 44], yield 47.34%, mp 66–68°C, exact
mass: 122.05.
Synthesis procedure of 5-amino-1-phenyl-1H-pyr-
azole-4-carbonitrile (II). This compound synthesis to
accourding literature [44, 45], yield 87.53%, mp 132–
134°C, exact mass: 184.07.
Synthesis procedure of 1-phenyl-1,5-dihydro-4H-
pyrazolo[3,4-d]pyrimidin-4-one (III). This compound
synthesis to accourding literature [45, 46], Yield
72.04%, mp > 250°C, exact mass: 212.07.
Synthesis procedure of 4-chloro-1-phenyl-1H-pyr-
azolo[3,4-d]pyrimidine (IV). This compound synthe-
sis to accourding literature [45–47], yield 93.31%, mp
134–136°C, exact mass: 230.04.
General synthetic process for substituted 2-chloro-
N-phenylacetamide derivatives. To a solution of vari-
ous aniline (1.0 equiv ) in acetone were added chloro-
acetyl chloride (1.1 equiv ) and reaction mixture stirred
at room temperature for 2–3 h, reaction was monitored
by TLC, after completion of reaction mixture poured in
cold water, the separated solid product collected and
washed with cold water and dry in vacuum filter to
afford 2-chloro-N-phenylacetamide derivatives.
Synthesis procedure of 1-phenyl-4- (prop-2-yn-1-
General synthetic process for substituted 2-azido-
yloxy)-1H-pyrazolo[3,4-d]pyrimidine (V). To a solu- N-phenylacetamide derivatives. To a solution of
tion of propargyl alcohol (2.33 g, 41.73 mmol) in 2-chloro-N-phenylacetamide derivatives (1.0 equiv)
50 mL dry THF under nitrogen atmosphere and stirred in DMF were added sodium azide (3.0 equiv) and
solution under cooling. Then after added portion-wise reaction mixture stirred at room temperature for 10–
potassium tert-butoxide (5.07 g, 45.21 mmol) and the 12 h, reaction was monitored by TLC, after complica-
resulting reaction mixture was stirred for 20 minutes at tion of reaction mixture poured in cold water, the sep-
same temperature. Then after solution of 4-chloro-1- arated solid collected and washed with cold water and
phenyl-1H-pyrazolo[3,4-d]pyrimidine (IV) (8.0 g, dry in vacuum filter to afford 2-azido-N-phenylacet-
34.78 mmol) in dry THF was added drop wise and amide derivatives.
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ULTRASONIC-ASSISTED
809
General synthetic process for substituted Azidoben- 5.78 (2H, s, C22 –OCH2), 5.40 (2H, s, H32 –
COCH2). 13C NMR (101 MHz, DMSO) δ 164.63
(C30 C=O), 162.81 (C12 C–O), 155.84 (C8), 154.23
(C10), 141.35, 139.77, 138.31, 133.16, 133.12, 130.67,
129.33, 127.17, 126.86, 123.51, 121.01, 118.66, 117.59,
103.50 (C7), 59.89 (C22 –OCH2), 52.18 (C32 –CH2)
zene derivatives. Take a RBF and charge with various
aniline derivatives (1.0 equiv) dissolved in 6 N HCl
solution and stir for 15 minutes were drop wise added
solution of sodium nitrite (1.5 equiv) at 0–5°C tem-
perature and reaction mixture stirred for 45 minutes at
same temperature. Then solution of sodium azide
(1.5 equiv) was added under cooling and reaction mix-
ture stirred at room temperature for 4–6 h. Reaction
monitor by TLC, after completion of reaction mixture
was poured in water and extract with ethyl acetate. The
organic layer combine and dry over sodium sulphate
and solvent remove under reduce pressure to afford
azidobenzene derivatives.
General synthetic procedure for N-substituted aryl-
2-(4-(((1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-
yl)oxy)methyl)-1H-1,2,3-triazole-1-yl) acetamides (VI
to XVI). To an equimolar mixture of 1-phenyl-4-
(prop-2-yn-1-yloxy)-1H-pyrazolo[3,4-d]pyrimidine
(V) and substituted 2-azido-N-arylacetamide in RBF
were added DMF : t-BuOH : H2O (1 : 1 : 1) and cata-
lytic amount of sodium ascorbate and aqueous copper
sulphate solution, resulting reaction mixture was
placed in ultrasonic for 15 to 25, the reaction was
monitor by TLC. After completion of the reaction, the
reaction mixture poured in cold water, collected the
separated solid and washed with ammonium chloride
solution to remove copper than after further washed
with water and small amount of methanol and dry over
vacuum, to afford (VI) to (XVI) (yield 82–94%).
FT-IR data (ν, cm–1): 3309.96, 3093.92, 2955.04,
1681.98, 1597.11, 1550.82, 1435.09, 1357.93, 1319.35,
1234.48, 1172.76, 1095.6, 979.87, 895, 786.98, 756.12,
686.68, 632.67, 547.8, 439.78. Mass (m/z): exact mass:
460.12, found mass: 459.70.
N-(2-Chlorophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl) oxy) methyl)-1H-1,2,3-tri-
azol-1-yl)acetamide (VIII). Yield: 92%, Off-white
solid, mp: 162–164°C; 1H NMR (DMSO-d6,
400 MHz) δ 10.10 (1H, s, H29 –CONH), 8.80 (1H, s,
H10 pyrimidine), 8.54 (1H, s, H13 pyrazole), 8.38
(1H, s, H19 triazole), 8.19 (2H, d, J = 88.0 Hz, Ar–
H), 7.74 (1H, d, J = 8.0 Hz, Ar–H), 7.60 (2H, t, J =
7.7 Hz, Ar–H), 7.53 (1H, d, J = 7.9 Hz, Ar–H), 7.41
(1H, t, J = 7.4 Hz, Ar–H), 7.35 (1H, t, J = 7.6 Hz,
Ar–H), 7.23 (1H, t, J = 7.8 Hz, Ar–H), 5.78 (2H, s,
H22 –OCH2), 5.49 (2H, s, H32 –COCH2). 13C NMR
(101 MHz, DMSO) δ 164.84 (C32 C=O), 162.80 (C12
C–O), 155.83 (C8), 154.22 (C10), 141.34, 138.31,
134.09, 133.12, 129.62, 129.32, 127.55, 127.21, 126.85,
126.74, 126.26, 125.89, 121.00, 103.50 (C7), 59.89
(C22 –OCH2), 51.92 (C32 –CH2). FT-IR data (ν, cm–1):
3255.95, 3086.21, 1921.16, 1689.7, 1604.83, 1550.82,
1442.8, 1311.64, 1226.77, 1165.04, 1103.32, 1057.03,
979.87, 887.28, 748.41, 648.1, 563.23, 455.22. Mass
(m/z): exact mass: 460.12, found mass: 459.80.
N-(4-Chlorophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-tri-
azol-1-yl) acetamide (VI). Yield: 94%, Tan solid, mp:
204–206°C; 1H NMR (DMSO-d6, 400 MHz) δ 10.66
(1H, s, H29 –CONH), 8.80 (1H, s, H10 pyrimidine),
8.56 (1H, s, H13 pyrazole), 8.38 (1H, s, H19 triazole),
8.20 (2H, d, J = 8.0 Hz, Ar–H), 7.61 (4H, t, J = 7.7 Hz,
Ar–H), 7.47–7.36 (3H, m, Ar–H), 5.78 (2H, s,
H22 –OCH2), 5.39 (2H, s, H32 –COCH2). 13C NMR
(101 MHz, DMSO) δ 164.35 (C30 C=O), 162.80 (C12
C–O), 155.83 (C8), 154.22 (C10), 141.33, 138.31,
137.32, 133.12, 129.32, 128.84, 127.33, 127.16, 126.85,
121.00, 120.72, 103.50 (C7), 59.89 (C22 –OCH2),
N-(4-Fluorophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-tri-
azol-1-yl) acetamide (IX). Yield: 94%, Tan solid, mp:
194–196°C; 1H NMR (DMSO-d6, 400 MHz) δ 10.59
(1H, s, H29 –CONH), 8.81 (1H, s, H10 pyrimidine),
8.56 (1H, s, H13 pyrazole), 8.38 (1H, s, H19 triazole),
8.24–8.15 (2H, m, Ar–H), 7.66–7.56 (4H, m, Ar–
H), 7.42 (1H, t, J = 7.4 Hz, Ar–H), 7.19 (2H, t, J =
8.9 Hz, Ar–H), 5.78 (2H, s, H22 –OCH2), 5.38 (2H,
13
s, H32 –COCH2). C NMR (101 MHz, DMSO) δ
52.17 (C32 –CH2). FT-IR data (ν, cm–1): 3255.95,
3093.92, 2955.04, 1674.27, 1604.83, 1550.82, 1496.81,
1435.09, 1319.35, 1242.2, 1172.76, 1095.6, 1057.03,
979.87, 895, 825.56, 748.41, 686.68, 648.1, 563.23,
501.51, 424.35. Mass (m/z): exact mass: 460.12, found
mass: 459.70.
164.09 (C30 C=O), 162.81 (C12 C–O), 159.39 (C28
C–F), 157.01 (C28 C–F), 155.84 (C8), 154.23 (C10),
141.31, 138.31, 134.77, 134.74, 133.13, 129.33, 127.16,
126.86, 121.01, 120.93, 115.63, 115.41, 103.50 (C7),
59.90 (C22 –OCH2), 52.12 (C32 –CH2). FT-IR data
(ν, cm–1): 3263.66, 3093.92, 2955.04, 1674.27,
1604.83, 1550.82, 1512.24, 1435.09, 1319.35, 1226.77,
1165.04, 1095.6, 1057.03, 979.87, 895, 840.99, 786.98,
756.12, 686.68, 563.23, 516.94. Mass (m/z): exact
mass: 444.15, found mass: 443.70.
N-(3-Chlorophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl) oxy) methyl)-1H-1,2,3-tri-
azol-1-yl) acetamide (VII). Yield: 87%, Brown solid,
1
mp: 194–196°C; H NMR (DMSO-d6, 400 MHz) δ
N-(2-Fluorophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl) oxy) methyl)-1H-1,2,3-tri-
azol-1-yl)acetamide (X). Yield: 82%, Tan solid, M.P.:
188–190°C; 1H NMR (DMSO-d6, 400 MHz) δ 10.38
10.72 (1H, s, H29 –CONH), 8.81 (1H, s, H10 pyrim-
idine), 8.56 (1H, s, H13 pyrazole), 8.38 (1H, s, H19
triazole), 8.24–8.15 (2H, m, Ar–H), 7.78 (1H, t, J =
2.1 Hz, Ar–H), 7.66–7.56 (2H, m, Ar–H), 7.52–7.33
(3H, m, Ar–H), 7.16 (1H, dd, J= 8.1 Hz, 2.2 Hz, Ar–H), (1H, s, H29 –CONH), 8.80 (1H, s, H10 pyrimidine),
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 5 2020

810
PRAKASH L. KALAVADIYA et al.
8.56 (1H, s, H13 pyrazole), 8.39 (1H, s, H19 triazole), 7.41 (1H, t, J = 7.4 Hz, Ar–H), 7.15 (1H, dd, J = 7.4,
8.19 (2H, d, J = 8.0 Hz, Ar–H), 7.91 (1H, td, J = 4.8, 4.8 Hz, Ar–H), 5.78 (2H, s, H22 –OCH2), 5.48 (2H,
s, H32 –COCH2). FT-IR data (ν, cm–1): 3302.24,
3140.22, 3047.63, 1689.7, 1597.11, 1550.82, 1435.09,
1303.92, 1234.48, 1165.04, 1095.6, 1057.03, 979.87,
895, 779.27, 686.68, 648.1, 563.23, 509.22. Mass
(m/z): exact mass: 427.15, found mass: 426.90.
4.3, 2.2 Hz, Ar–H), 7.60 (2H, t, J = 7.9 Hz, Ar–H),
7.42 (1H, t, J = 7.4 Hz, Ar–H), 7.36–7.25 (1H, m,
Ar–H), 7.25–7.13 (1H, m, Ar–H), 5.78 (2H, s, H22
‒OCH2), 5.48 (2H, s, H32 –COCH2). 13C NMR
(101 MHz, DMSO) δ 164.77 (C30 C=O), 162.80
(C12 C–O), 155.83 (C8), 154.64 (C24 C–F), 154.22
(C10), 152.20 (C24 C–F), 141.32, 138.31, 133.12,
129.32, 127.20, 126.84, 125.73, 125.65, 125.46, 125.34,
124.48, 123.73, 120.99, 115.70, 115.51, 103.49 (C7),
59.89 (C22 –OCH2), 51.97 (C32 –CH2). FT-IR data
2-(4-(((1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(pyridin-3-
yl)acetamide (XIV). Yield: 87%, White solid, mp: 168–
170°C; 1H NMR (DMSO-d6, 400 MHz) δ 10.78 (1H, s,
H29 –CONH), 8.81 (1H, s, H10 pyrimidine), 8.56
(1H, s, H13 pyrazole), 8.40 (1H, s, H19 triazole),
8.24–8.15 (2H, m, Ar–H), 8.03 (1H, d, J = 8.3 Hz,
Ar–H), 7.66–7.55 (2H, m, Ar–H), 7.42 (2H, t, J =
7.4 Hz, Ar–H), 5.79 (2H, s, H22 –OCH2), 5.44 (2H, s,
(ν, cm–1): 3255.95, 3086.21, 1928.88, 1674.27,
1604.83, 1550.82, 1496.81, 1435.09, 1357.93, 1327.07,
1219.05, 1172.76, 1095.6, 1057.03, 972.16, 941.29,
887.28, 794.7, 756.12, 686.68, 578.66, 462.93. Mass
(m/z): exact mass: 444.15, found mass: 443.80.
H32 –COCH2). FT-IR data (ν, cm–1): 3379.4,
3255.95, 3063.06, 3009.05, 2283.79, 1936.6, 1890.3,
1705.13, 1604.83, 1489.1, 1427.37, 1319.35, 1226.77,
1157.33, 1095.6, 979.87, 895, 794.7, 756.12, 694.4,
648.1, 563.23, 509.22. Mass (m/z): exact mass: 427.15,
found mass: 426.90.
N-(4-Nitrophenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl) oxy)methyl)-1H-1,2,3-
triazol-1-yl)acetamide (XI). Yield: 85%, White solid,
1
mp: 206–208°C; H NMR (DMSO-d6, 400 MHz) δ
11.12 (1H, s, H29 –CONH), 8.81 (1H, s, H10 pyrim-
idine), 8.56 (1H, s, H13 pyrazole), 8.40 (1H, s, H19
triazole) 8.26 (2H, d, J = 8.8 Hz, Ar–H), 8.20 (2H, d,
J = 8.0 Hz, Ar–H), 7.84 (2H, d, J = 8.8 Hz, Ar–H),
7.61 (2H, t, J = 7.8 Hz, Ar–H), 7.42 (1H, t, J = 7.4 Hz,
Ar–H), 5.79 (2H, s, H22 –OCH2), 5.48 (2H, s, C32
N-(4-Methylpyridin-2-yl)-2-(4-(((1-phenyl-1H-
pyrazolo[3,4-d]pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)acetamide (XV). Yield: 84%, White solid,
1
mp: 180–182°C; H NMR (DMSO-d6, 400 MHz) δ
–COCH2). FT-IR data (ν, cm–1): 3309.96, 3101.64,
1913.45, 1720.56, 1604.83, 1558.54, 1504.53, 1442.8,
1342.5, 1257.63, 1172.76, 1103.32, 979.87, 848.71,
756.12, 686.68, 640.39, 493.79. Mass (m/z): exact
mass: 471.14, found mass: 470.90.
10.97 (1H, s, H29 –CONH), 8.81 (1H, s, H10 pyrim-
idine), 8.57 (1H, s, H13 pyrazole), 8.38 (1H, s, H19
triazole), 8.25–8.16 (3H, m, Ar–H), 7.87 (1H, s, Ar–
H), 7.61 (2H, t, J = 7.9 Hz, Ar–H), 7.42 (1H, t, J = 7.4
Hz, Ar–H), 7.00 (1H, d, J = 5.2 Hz, Ar–H), 5.79
(2H, s, H22 –OCH2), 5.45 (2H, s, H32 –COCH2),
N-(3,4-Dimethylphenyl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]Pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-tri-
azol-1-yl)acetamide (XII). Yield: 90%, Brown solid,
2.30 (3H, s, H33 –CH3). FT-IR data (ν, cm–1):
3302.24, 3147.93, 3070.78, 2962.76, 1890.3, 1681.98,
1604.83, 1558.54, 1504.53, 1458.23, 1419.66, 1350.22,
1319.35, 1211.34, 1165.04, 1095.6, 1049.31, 979.87,
887.28, 825.56, 756.12, 725.26, 686.68, 648.1, 601.81,
447.5. Mass (m/z): exact mass: 441.17, found mass:
440.90.
1
mp: 166–168°C; H NMR (DMSO-d6, 400 MHz) δ
10.46 (1H, s, H29 –CONH), 8.80 (1H, s, H10 pyrim-
idine), 8.56 (1H, s, H13 pyrazole), 8.38 (1H, s, H19
triazole), 8.20 (2H, d, J = 8.0 Hz, Ar–H), 7.60 (2H, t,
J = 7.8 Hz, Ar–H), 7.47–7.35 (2H, m, Ar–H), 7.31
(1H, dd, J = 8.1, 2.3 Hz, Ar–H), 7.07 (1H, d, J = 8.2 Hz,
Ar–H), 5.78 (2H, s, H22 –OCH2), 5.36 (2H, s, H32 –
COCH2), 2.17 (6H, d, J = 7.4 Hz, H33 H34 –CH3).
N-(Naphthalen-1-yl)-2-(4-(((1-phenyl-1H-pyra-
zolo[3,4-d]pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-tri-
azol-1-yl)acetamide (XVI). Yield: 92%, Light pink
solid, mp: 198–200°C; 1H NMR (DMSO-d6,
400 MHz) δ 10.48 (1H, s, H29 –CONH), 8.81 (1H, s,
H10 pyrimidine), 8.56 (1H, s, H13 pyrazole), 8.44
(1H, s, H19 triazole), 8.19 (3H, t, J = 8.8 Hz, Ar–H),
7.97 (1H, d, J = 7.7 Hz, Ar–H), 7.81 (1H, d, J =
8.2 Hz, Ar–H), 7.73 (1H, d, J = 7.5 Hz, Ar–H), 7.56
(5H, dq, J = 30.5, 7.9 Hz, Ar–H), 7.42 (1H, t, J = 7.5 Hz,
Ar–H), 5.80 (2H, s, H22 –OCH2), 5.59 (2H, s, H38
FT-IR data (ν, cm–1): 3309.96, 3093.92, 1681.98,
1604.83, 1550.82, 1504.53, 1435.09, 1357.93, 1319.35,
1226.77, 1165.04, 1103.32, 1057.03, 972.16, 887.28,
817.85, 756.12, 632.67, 547.8, 501.51, 439.78. Mass
(m/z): exact mass: 454.19, found mass: 454.
2-(4-(((1-Phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(pyridin-2-
yl)acetamide (XIII). Yield: 82%, White solid, mp:
162–164°C; 1H NMR (DMSO-d6, 400 MHz) δ 11.07 –COCH2). FT-IR data (ν, cm–1): 3471.98, 3279.1,
(1H, s, H29 –CONH), 8.80 (1H, s, H10 pyrimidine), 3086.21, 2955.04, 1928.88, 1674.27, 1604.83, 1550.82,
8.55 (1H, s, H13 pyrazole), 8.40 (1H, s, H19 triazole), 1504.53, 1435.09, 1319.35, 1219.05, 1165.04, 1095.6,
8.38–8.35 (1H, m, Ar–H), 8.24–8.15 (2H, m, Ar– 1057.03, 979.87, 887.28, 848.71, 786.98, 686.68,
H), 8.01 (1H, d, J = 8.3 Hz, Ar–H), 7.81 (1H, td, J = 578.66, 509.22. Mass (m/z): exact mass: 476.17, found
7.9, 2.0 Hz, Ar–H), 7.60 (2H, t, J = 7.9 Hz, Ar–H), mass: 475.80.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
Vol. 46
No. 5
2020

ULTRASONIC-ASSISTED
811
General synthetic procedure for 1-substituted aryl- (C28 C–F), 162.70 (C12 C–O), 160.48 (C28 C–F),
4-((1-various substituted aryl-1H-1,2,3-triazol-4-yl) 155.85 (C8), 154.24 (C10), 142.84, 138.30, 133.13,
methoxy)-1H-pyrazolo[3,4-d]pyrimidines (XVII to 133.04, 133.01, 129.32, 126.84, 123.83, 122.67, 122.58,
XXII). To a 1-phenyl-4-(prop-2-yn-1-yloxy)-1H- 120.96, 116.85, 116.62, 103.52 (C7), 59.75 (C22
‒OCH2). FT-IR data (ν, cm–1): 3124.79, 3078.49,
2962.76, 1898.02, 1604.83, 1558.54, 1512.24, 1450.52,
1357.93, 1234.48, 1165.04, 1103.32, 1049.31, 987.59,
902.72, 833.28, 786.98, 756.12, 686.68, 648.1, 601.81,
532.37, 493.79. Mass (m/z): exact mass: 483.12, found
mass: 486.70.
4-((1-(3-Chloro-4-fluorophenyl)-1H-1,2,3-triazol-
4-yl)methoxy)-1-phenyl-1H-pyrazolo[3,4-d]pyrimi-
dine (XX). Yield: 88%, White solid, mp: 152–154°C;
1H NMR (DMSO-d6, 400 MHz) δ 9.06 (1H, s, H19
triazole), 8.81 (1H, s, H10 pyrimidine), 8.56 (1H, s,
H13 pyrazole), 8.25 (1H, dd, J = 6.4, 2.7 Hz, Ar–H),
8.23–8.15 (2H, m, Ar–H), 8.00 (1H, m, Ar–H), 7.70
(1H, t, J = 9.0 Hz, Ar–H), 7.66–7.56 (2H, m, Ar–H),
7.47–7.37 (1H, m, Ar–H), 5.85 (2H, s, H22 –OCH2).
pyrazolo[3,4-d]pyrimidine (5) (1.0 eq) and various
azidoaryl (1.1 eq) in RBF were added DMF : t-BuOH :
H2O (1 : 1 : 1) and catalytic amount of Sodium ascor-
bate and aqueous copper sulphate solution, resulting
reaction mixture was placed in ultrasonic for 10 to
15 minutes, the reaction was monitor by TLC. After
completion of the reaction mixture poured in cold
water, the separated solid collected and washed with
ammonium chloride solution to remove copper than
after further washed with water and small amount of
methanol and dry over vacuum, to afford XVII to XXII
(yield 84–94%).
N-Benzyl-2-(4-(((1-phenyl-1H-pyrazolo[3,4-d]-
pyrimidin-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)
acetamide (XVII). Yield: 90%, Brown solid, mp:
122–124°C; 1H NMR (DMSO-d6, 400 MHz) δ 8.78
(1H, s, H10 pyrimidine), 8.53 (1H, s, H13 pyrazole),
8.42 (1H, s, H19 triazole), 8.19 (2H, d, J = 8.0 Hz, Ar-
H), 7.60 (2H, t, J = 7.8 Hz, Ar–H), 7.46–7.30 (5H, m,
Ar–H), 7.23 (1H, s, Ar–H), 5.73 (2H, s, H22
‒OCH2), 5.64 (2H, s, C29 –CH2). FT-IR data (ν,
13C NMR (101 MHz, DMSO) δ 162.67 (C12 C–O),
158.16 (C28 C–F), 155.85 (C8), 155.70 (C28 C–F),
154.24 (C10), 143.03, 138.30, 133.47, 133.43, 133.11,
129.32, 126.86, 123.92, 122.55, 121.13, 121.05, 120.96,
120.84, 120.65, 118.24, 118.02, 103.52 (C7), 59.68
(C22 –CH2). FT-IR data (ν, cm–1): 3433.41, 3155.65,
3109.35, 2114.05, 1874.87, 1604.83, 1558.54, 1504.53,
1458.23, 1427.37, 1388.79, 1327.07, 1242.2, 1172.76,
1095.6, 1018.45, 979.87, 941.29, 879.57, 825.56,
756.12, 717.54, 686.68, 648.1, 501.51. Mass (m/z):
exact mass: 421.09, found mass: 420.70.
cm–1): 3117.07, 3039.91, 2816.16, 1805.43, 1751.42,
1604.83, 1558.54, 1496.81, 1458.23, 1427.37, 1342.5,
1226.77, 1172.76, 1095.6, 1049.31, 979.87, 887.28,
840.99, 794.7, 756.12, 709.83, 655.82, 555.52, 486.08.
Mass (m/z): exact mass: 483.15, found mass: 483.00.
1-Phenyl-4-((1-phenyl-1H-1,2,3-triazol-4-yl)
4-((1-(4-Chloro-2-nitrophenyl)-1H-1,2,3-triazol-
4-yl)methoxy)-1-phenyl-1H-pyrazolo[3,4-d]pyrimi-
dine (XXI). Yield: 82%, White solid, mp: 172–174°C;
1H NMR (DMSO-d6, 400 MHz) δ 8.95 (1H, s, H19
triazole), 8.80 (1H, s, H10 pyrimidine), 8.57 (1H, s,
H13 pyrazole), 8.43 (1H, d, J = 2.3 Hz, Ar–H), 8.20
(2H, d, J = 8.0 Hz, Ar–H), 8.09 (1H, dd, J = 8.6,
2.4 Hz, Ar–H), 7.98 (1H, d, J = 8.6 Hz, Ar–H), 7.61
(2H, t, J = 7.8 Hz, Ar–H), 7.42 (1H, t, J = 7.4 Hz,
Ar–H), 5.87 (2H, s, H22 –OCH2). FT-IR data (ν,
methoxy)-1H-pyrazolo[3,4-d]pyrimidine
(XVIII).
1
Yield: 92%, White solid, mp: 122–124°C; H NMR
(DMSO-d6, 400 MHz) δ 9.04 (1H, s, H19 triazole),
8.81 (1H, s, H10 pyrimidine), 8.57 (1H, s, H13 pyra-
zole), 8.24–8.13 (2H, m, Ar–H), 7.98–7.90 (2H, m,
Ar–H), 7.67–7.56 (4H, m, Ar–H), 7.52 (1H, t, J =
7.4 Hz, Ar–H), 7.42 (1H, t, J = 7.4 Hz, Ar–H), 5.85
(2H, s, H22 –OCH2). 13C NMR (101 MHz, DMSO)
δ 162.71 (C12 C–O), 155.85 (C8), 154.23 (C10),
142.83, 138.30, 136.46, 133.14, 129.89, 129.31, 128.84,
126.83, 123.61, 120.96, 120.23, 103.53 (C7), 59.78
(C22 –CH2). FT-IR data (ν, cm–1): 3132.5, 3086.21,
2962.76, 1959.74, 1898.02, 1805.43, 1597.11, 1558.54,
1504.53, 1435.09, 1350.22, 1319.35, 1234.48, 1165.04,
1095.6, 1049.31, 979.87, 902.72, 848.71, 763.84,
686.68, 632.67, 547.8, 516.94. Mass (m/z): exact mass:
369.13, found mass: 368.80.
cm–1): 3441.12, 3109.35, 1735.99, 1651.12, 1604.83,
1550.82, 1504.53, 1442.8, 1357.93, 1319.35, 1249.91,
1165.0 4, 1111.03, 1033.88, 995.3, 902.72, 840.99,
794.7, 763.84, 694.4, 640.39, 547.8, 516.94, 447.5.
Mass (m/z): exact mass: 448.07, found mass: 447.70.
1-Phenyl-4-((1-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazol-4-yl)methoxy)-1H-pyrazolo[3,4-d]pyrimi-
dine (XXII). Yield: 85%, White solid, M.P.: 146–
1
4-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl) 148°C; H NMR (DMSO-d6, 400 MHz) δ 9.05 (1H,
methoxy)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine (XIX).
s, H19 triazole), 8.82 (1H, s, H10 pyrimidine), 8.57
1
Yield: 94%, Gray solid, mp: 136–138°C; H NMR (1H, s, H13 pyrazole), 8.24–8.16 (2H, m, Ar–H), 7.61
(DMSO-d6, 400 MHz) δ 9.01 (1H, s, H19 triazole), (2H, dd, J = 8.6, 7.4 Hz, Ar–H), 7.47–7.38 (1H, m,
Ar–H), 7.24 (2H, s, Ar–H), 5.85 (2H, s, H22
‒OCH2), 3.89 (6H, s, C32, C34 ‒CH3), 3.72 (3H, s,
8.81 (1H, s, H10 pyrimidine), 8.57 (1H, s, H13 tri-
azole), 8.23–8.16 (2H, m, Ar–H), 8.03–7.93 (2H, m,
Ar–H), 7.65–7.56 (2H, m, Ar–H), 7.53–7.44 (2H,
m, Ar–H), 7.46–7.37 (1H, m, Ar–H), 5.84 (2H, s,
H22 –OCH2). 13C NMR (101 MHz, DMSO) δ 162.93
C33 ‒CH3). FT-IR data (ν, cm–1): 3456.55, 3109.35,
2831.6, 2106.34, 1998.32, 1928.88, 1597.11, 1504.53,
1450.52, 1350.22, 1288.49, 1234.48, 1165.04, 1126.47,
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 5 2020

812
PRAKASH L. KALAVADIYA et al.
7. Celano, M., Schenone, S., Cosco, D., Navarra, M.,
Puxeddu, E., Racanicchi, L., Brullo, C., Varano, E.,
Alcaro, S., Ferretti, E., Botta, G., Filetti, S., Fresta, M.,
Botta, M., and Russo, D., Endocr. Relat. Cancer, 2008,
vol. 15, pp. 499–510.
1041.6, 1003.02, 902.72, 864.14, 771.55, 694.4,
640.39, 524.66. Mass (m/z): exact mass: 459.17, found
mass: 459.00.
https://doi.org/10.1677/ERC-07-0243
ACKNOWLEDGMENTS
8. Manetti, F., Santucci, A., Locatelli, G.A., Maga, G.,
Spreafico, A., Serchi, T., Orlandini, M., Bernardini, G.,
Caradonna, N.P., Spallarossa, A., Brullo, C., Sche-
none, S., Bruno, O., Ranise, A., Bondavalli, F., Hoff-
mann, O., Bologna, M., Angelucci, A., and Botta, M.,
J. Med. Chem., 2007, vol. 50, pp. 5579–5588.
Authors are thankful to the Department of Chemistry,
Saurashtra University, Rajkot for the providing laboratory
facilities and spectral analysis. The authors are also thankful
to the National Cancer Institute [50], a part of the National
Institute of Health (NIH), for the providing anticancer
screening of compounds.
https://doi.org/10.1021/jm061449r
9. Angelucci, A., Schenone, S., Gravina, G.L., Muzi, P.,
Festuccia, C., Vicentini, C., Botta, M., and Bologna, M.,
Eur. J. Cancer, 2006, vol. 42, pp. 2838–2845.
COMPLIANCE WITH ETHICAL STANDARDS
This article does not contain any studies involving
human participants performed by any of the authors and
does not contain any studies involving animals performed
by any of the authors.
https://doi.org/10.1016/j.ejca.2006.06.024
10. Neustadt, B.R., Hao, J., Lindo, N., Greenlee, W.J.,
Stamford, A.W., Tulshian, D., Ongini, E., Hunter, J.,
Monopoli, A., Bertorelli, R., Foster, C., Arik, L., La-
chowicz, J., Ng, K., and Feng, K.I., Bioorg. Med.
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Conflict of Interests
https://doi.org/10.1016/j.bmcl.2006.11.083
11. Devarakonda, M., Doonaboina, R., Vanga, S., Vemu, J.,
Boni, S., and Mailavaram, R.P., Med. Chem. Res.,
2013, vol. 22, pp. 1090–1101.
The authors declare that they have no conflicts of interest.
https://doi.org/10.1007/s00044-012-0084-0
SUPPLEMENTARY MATERIALS
12. Gupta, S., Rodrigues, L.M., Esteves, A.P., Oliveira-
Campos, A.M.F., Nascimento, M.S.J., Nazareth, N.,
Cidade, H., Neves, M.P., Fernandes, E., Pinto, M.,
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In a supplementry material we cover 1H NMR spectra,
13C NMR spectra mass spectra, FT-IR spectra, one-dose
graph of anticancer activity.
Supplementary materials are available for this article at
https://doi.org/10.1134/S1068162020050106 and are acces-
sible for authorized users.
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13. Song, X.J., Shao, Y., and Dong, X.G., Chin. Chem.
Lett., 2011, vol. 22, pp. 1036–1038.
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