One-pot multicomponent synthesis of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives and evaluation of their cytotoxic activity

Article abstract of DOI:10.1007/s11164-015-2114-2

A series of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives (4a-l) were synthesized via one-pot multicomponent reaction of 5-substituted salicylaldehydes (1a-c), 4-hydroxy-6-methyl-2H-pyran-2-one (2) and 2-hydrazinyl-4-arylthiazoles (3a-d) in acetonitrile using a catalytic amount of piperidine under reflux conditions. This multicomponent approach has advantages such as reduced reaction time and a high product yield percentage when compared with corresponding multistep approaches. All the synthesized compounds were evaluated for their cytotoxic activity against Hep G2 (hepatocellular liver carcinoma) and MCF-7 (breast cancer) cell lines and compared with the standard drug Doxorubicin. Among all the compounds, compounds 4d against Hep G2, 4k against MCF-7 and 4e against both Hep G2 & MCF-7 showed excellent cytotoxic activity.

Full text of DOI:10.1007/s11164-015-2114-2

Res Chem Intermed
DOI 10.1007/s11164-015-2114-2
One-pot multicomponent synthesis of novel 1-thiazolyl-
5-coumarin-3-yl-pyrazole derivatives and evaluation
of their cytotoxic activity
Ravibabu Velpula1 Rajitha Deshineni2
•
•
Rajitha Gali1 Rajitha Bavantula1
•
Received: 8 January 2015 / Accepted: 26 May 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract A series of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives (4a–
l) were synthesized via one-pot multicomponent reaction of 5-substituted salicy-
laldehydes (1a–c), 4-hydroxy-6-methyl-2H-pyran-2-one (2) and 2-hydrazinyl-4-
arylthiazoles (3a–d) in acetonitrile using a catalytic amount of piperidine under
reflux conditions. This multicomponent approach has advantages such as reduced
reaction time and a high product yield percentage when compared with corre-
sponding multistep approaches. All the synthesized compounds were evaluated for
their cytotoxic activity against Hep G2 (hepatocellular liver carcinoma) and MCF-7
(breast cancer) cell lines and compared with the standard drug Doxorubicin. Among
all the compounds, compounds 4d against Hep G2, 4k against MCF-7 and 4e
against both Hep G2 & MCF-7 showed excellent cytotoxic activity.
Keywords One-pot multicomponent reaction Á 1-thiazolyl-5-coumarin-3-yl-
pyrazole Á Cytotoxic activity
Introduction
Cancer is a worldwide death causing disease. Although, clinically, many
chemotherapeutic anticancer drugs are available, they cause several undesirable
side effects to the patients such as reduced bioavailability, toxicity and drug-
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2114-2)
contains supplementary material, which is available to authorized users.
&
Rajitha Bavantula
rajitabhargavi@yahoo.com
1
2
Department of Chemistry, National Institute of Technology, Warangal 506004, Telangana,
India
Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India
123

R. Velpula et al.
resistance [1, 2]. Hence it is a challenging research area for the medicinal chemists
to discover newer and safer anticancer agents that have excellent cytotoxicity to
cancer cells [3]. On the other hand, the development of a multicomponent approach
is of considerable current interest in the field of organic synthesis. The concept of
multicomponent reactions (MCRs) performing more than one transformation in a
single vessel simplifies the work-up procedure, avoids unstable separation of
intermediates, and produces a good product yield via the increased efficiency of the
desired conversion [4, 5]. MCRs have advantages over stepwise reactions in the
above-mentioned aspects and permit rapid access to combinatorial libraries of
complex organic molecules, enabling efficient lead structure identification and
optimal drug discovery.
Pyrazole scaffolds have attracted significant interest in medicinal chemistry over
the past few decades. Several pyrazole derivatives possess a wide range of
biological activities such as anticancer [6], antimicrobial [7], antiviral [8],
antitubercular [9], antioxidant [10], anti-inflammatory [11], antidepressant and
anticonvulsant [12] activities. Pyrazole scaffolds are not only independent, along
with other heterocycles like thiazole and coumarins, but also possess marked
biological activities [13–18]. Thiazoles and coumarins also portray an important
role in medicinal and pharmaceutical chemistry due to their versatile biological
applications, such as antimicrobial [19, 20], anticancer [21, 22], antitumor [23, 24],
antiulcer [25, 26], antiviral [27, 28], antioxidant [29, 30], anticonvulsant [31, 32]
and antihypertensive [33, 34] activities.
In view of the above-mentioned biological importance, especially the anticancer
activity of pyrazoles, thiazoles and coumarins, as well as several advantages of
multicomponent reactions for the synthesis of the above two or three moieties
incorporating hybrid molecules [35, 36], here we report efficient one-pot
multicomponent synthesis of 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives as
new compounds having pyrazole, thiazole and coumarin moieties in a single frame.
These compounds were evaluated for their anticancer activity.
Results and discussion
In continuation of our interest regarding synthesis of various biologically active novel
heterocycles [37, 38], we designed synthesis of novel 1-thiazolyl-5-coumarin-3-yl-
pyrazole derivatives. To analyze the synthetic route, the model reaction was carried
out for the synthesis of product 4a by using salicylaldehyde (1a), 4-hydroxy-6-methyl-
2H-pyran-2-one (2) and 2-hydrazinyl-4-arylthiazoles (3a) in acetonitrile with a
catalytic amount of piperidine under reflux conditions. This model reaction was
carried out in multistep as well as single step (one-pot multicomponent reaction
involving sequential addition of reactants) approaches and the reaction time and
percentage of yield for product 4a were calculated. In the multistep reaction, first
salicylaldehyde (1a) reacted with 4-hydroxy-6-methyl-2H-pyran-2-one (2) in
acetonitrile with a catalytic amount of piperidine under reflux conditions for 30 min
to furnish the intermediate 3-acetoacetylcoumarin (6) at a 78-% yield. In the second
step, the resulting intermediate 6 reacted with 2-hydrazinyl-4-phenylthiazole (3a) in
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One-pot multicomponent synthesis of novel…
Table 1 Synthesis of 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives (4a–l)
Entrya
Product
Time (h)
2
Yieldb (%)
88
1
2
3
87
3
3
92
4
3.5
85
5
3
87
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R. Velpula et al.
Table 1 continued
Entrya
Product
Time (h)
2.5
Yieldb (%)
90
6
7
2
92
8
3
88
9
2
92
123

One-pot multicomponent synthesis of novel…
Table 1 continued
Entrya
Product
Time (h)
2
Yieldb (%)
89
10
11
2.5
88
12
2
91
a
Reaction condition Salicylaldehyde derivative (1a–c, 1 mmol), 4-hydroxy-6-methyl-2H-pyran-2-one
(2, 1 mmol), 2-hydrazinyl-4-arylthiazoles (3a–d, 1 mmol), acetonitrile (5 mL), piperidine (Cat.), reflux,
2–3.5 h
b
Isolated yields
All the synthesized compounds were confirmed by their analytical and spectral (IR, 1HNMR, 13CNMR
and mass) studies
acetonitrile under reflux conditions for 2 h, affording the product 4a at 65 % yield.
When the same reaction was carried out in a multicomponent approach we observed a
decreased reaction time (2 h), and the product yield increased (88 %). Hence, we
carried out the one-pot multicomponent reactions involving sequential addition of
salicylaldehyde derivatives (1a–c), 4-hydroxy-6-methyl-2H-pyran-2-one (2) and
2-hydrazinyl-4-arylthiazoles (3a–d) for the synthesis of 1-thiazolyl-5-coumarin-3-yl-
pyrazole derivatives (4a–l; Table 1). A schematic representation and plausible
mechanism for the formation of the products are shown in Scheme 1 and 2,
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R. Velpula et al.
Scheme 1 Synthesis of 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives
Scheme 2 Plausible mechanism for the synthesis of 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives
respectively. The starting compounds 2-hydrazinyl-4-arylthiazoles (3a–d) were
obtained according to the literature procedure [39].
Cytotoxic activity
The cellular viability of the synthesized compounds (4a–l) against MCF-7 (breast
cancer) and Hep-G2 (hepatocellular liver carcinoma) cell lines determined by an
MTT-microcultured tetrazolium assay following the reported protocol [40–42].
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One-pot multicomponent synthesis of novel…
Table 2 Cytotoxicity of
S. no
Product
Hep-G2
MCF-7
1-thiazolyl-5-coumarin-3-yl-
pyrazole derivatives (4a–l)
1
4a
4.21 0.03
6.14 0.06
9.62 0.08
3.74 0.02
3.06 0.01
11.24 0.21
21.68 0.32
18.42 0.20
43.17 0.36
4.87 0.02
3.25 0.01
6.16 0.03
3.01
9.04 0.02
8.72 0.04
9.35 0.04
6.92 0.03
4.42 0.02
6.04 0.04
15.26 0.18
31.54 0.38
29.24 0.27
7.20 0.03
4.03 0.02
13.23 0.05
1.08
2
4b
3
4c
4
4d
5
4e
6
4f
7
4g
8
4h
9
4i
10
11
12
13
4j
4k
4l
Doxorubicin
Activity data (Table 2) revealed that all the compounds show good to moderate
activity against both Hep-G2 and MCF-7 cancer cell lines in the range of IC50
3.06–43.17 lM and 4.03–31.54, respectively, compared to standard drug Doxoru-
bicin (IC50 = half maximal inhibitory concentration). Among all the compounds,
compounds 4d (IC50 3.74 lM), 4e (IC50 3.06 lM) and 4k (IC50 3.25 lM) exhibited
prominent activity against Hep-G2 compared to Doxorubicin (IC50 3.01 lM). In the
case of MCF-7 cell line compounds, 4e (IC50 4.42 lM) and 4k (IC50 4.03 lM)
showed better activity than the remaining compounds and as compared to
Doxorubicin (IC50 1.08 lM). The remaining compounds were moderately active
against both tested cell lines.
Conclusion
In conclusion, we synthesized a novel series of 1-thiazolyl-5-coumarin-3-yl-
pyrazole derivatives by a one-pot multicomponent approach and evaluated them for
their cytotoxicity. Compounds 4d against Hep-G2, 4k against MCF-7 and 4e against
Hep-G2 & MCF-7 showed excellent cytotoxicity. These synthetic methods and
cytotoxicity evaluation may help develop the fields of synthetic organics and
medicine.
Experimental section
Materials
All reagents and solvents were purchased from Aldrich/Merck and used without
further purifications. Melting points were determined in open capillaries using a
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R. Velpula et al.
Stuart SMP30 apparatus and are uncorrected. The progress of the reactions as well
as purity of compounds was monitored by thin layer chromatography (TLC) with
F254 silica-gel pre-coated sheets using hexane/ethyl acetate 8/2 as an eluent;
ultraviolet (UV) light and iodine vapours were used for detection. Infrared (IR)
spectra were recorded on a Perkin-Elmer 100S spectrometer utilizing potassium
bromide (KBr) pellets. Proton nuclear magnetic resonance (1H NMR) and 13C NMR
spectra were obtained at 400 and 100 MHz, respectively, on a Bruker-400 MHz
instrument using deuterated dimethyl sulfoxide (DMSO-d6 as the solvent and
trimethylsilane (TMS) as the internal standard. Elemental analyses were performed
on a Carlo-Erba model EA1108 analytical unit and the values are 0.4 % of the
theoretical values. Mass spectra were recorded on a Jeol JMSD-300 spectrometer.
General procedure for the synthesis of 1-thiazolyl-5-coumarin-3-yl-pyrazole
derivatives (4a–l)
A mixture of salicylaldeyde derivatives (1a–c, 1 mmol) and 4-hydroxy-6-methyl-
2H-pyran-2-one (2, 0.126 g, 1 mmol) in acetonitrile (5 mL) with a catalytical
amount of piperidine were stirred on a magnetic stirrer for 30–60 min under reflux
conditions. After solid separation in the reaction mixture, 2-hydrazinyl-4-arylth-
iazoles (3a–d, 1 mmol) was added and the solution was stirred an additional 1.5–2 h
at the same temperature. After completion of the reaction (monitored by TLC),
separated solid was filtered and washed with excess acetonitrile and dried. The dried
compound was recrystallized from ethanol, affording the analytically pure products.
Protocol for the MTT-microcultured tetrazolium assay
MCF-7 and HepG-2 cells were plated into a 96-well plate at a density of
1 9 104 cells/well. Cells were grown overnight in the full medium and then
switched to the low serum media. DMSO was used as a control. After 48 h of
treatment with different concentrations of test compounds, the cells were incubated
with MTT (2.5 mg/mL) in the CO2 chamber for 2 h. The medium was then removed
and 100 lL of DMSO was added to each well to dissolve formazan crystals. After
thorough mixing, the plates were read at 570 nm for optical density, which is
directly correlated with cell quantity. The results are represented as percentage of
cytotoxicity/viability. All the experiments were carried out in triplicates. The IC50
values were calculated from the percentage of cytotoxicity and compared with the
reference drug Doxorubicin. The response parameter calculated was the IC50 value,
which corresponds to the concentration required for 50 % inhibition of cell
viability.
Spectral data
3-(3-Methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4a) White
1
solid; mp. 199–201 °C; IR (KBr, cm-1) tmax: 1712 (C=O), 1602 (C=N); H NMR
(400 MHz, DMSO-d6): d 2.30 (s, 3H), 7.03 (s, 1H), 7.17 (d, 1H, J = 8.0 Hz),
7.36–7.45 (m, 2H), 7.50–7.58 (m, 1H), 7.67–7.70 (m, 2H), 7.80 (d, 1H, J = 6.4 Hz),
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One-pot multicomponent synthesis of novel…
7.93 (d, 2H, J = 7.6 Hz), 8.05 (s, 1H), 8.31 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d 13.6, 112.4, 113.2, 120.4, 124.8, 125.5, 127.5, 129.3, 131.2, 131.4, 133.8, 141.0,
147.1, 148.9, 159.6; Mass (ESI) m/z: 385 [M]?; Anal. Calcd. for C22H15N3O2S: C,
68.55; H, 3.92; N, 10.90. Found: C, 68.73; H, 3.78; N, 10.78.
6-Chloro-3-(3-methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one
(4b) Brown solid; mp. 213–215 °C; IR (KBr, cm-1) tmax: 1718 (C=O), 1600
1
(C=N), 820 (C–Cl); H NMR (400 MHz, DMSO-d6): d 2.31 (s, 3H), 7.20 (s, 1H),
7.38–7.44 (m, 2H), 7.50–7.58 (m, 1H), 7.68–7.72 (m, 1H), 7.8 (d, 1H, J = 8.8 Hz),
7.85–7.87 (m, 1H), 7.93 (d, 2H, J = 8.0 Hz), 8.06 (s, 1H), 8.34 (s, 1H); Mass (ESI)
m/z: 421 [M ? 2]?; Anal. Calcd. for C22H14ClN3O2S: C, 62.93; H, 3.36; N, 10.01.
Found: C, 63.17; H, 3.19; N, 9.87.
6-Bromo-3-(3-methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one
(4c) White solid; mp. 205–206 °C; IR (KBr, cm-1) tmax: 1717 (C=O), 1606
1
(C=N), 735 (C–Br); H NMR (400 MHz, DMSO-d6): d 2.32 (s, 3H), 7.25 (s, 1H),
7.27–7.45 (m, 2H), 7.50–7.58 (m, 1H), 7.69 (t, 1H, J = 7.2 Hz), 7.69–7.87 (m, 2H),
7.93 (d, 2H, J = 8.0 Hz), 8.06 (s, 1H), 8.34 (s, 1H); Mass (ESI) m/z: 464 [M?]?;
Anal. Calcd. for C22H14BrN3O2S: C, 56.91; H, 3.04; N, 9.05. Found: C, 57.16; H,
3.24; N, 8.89.
3-(1-(4-(4-Chlorophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one
(4d) Brown solid; mp. 230–232 °C; IR (KBr, cm-1) tmax: 1720 (C=O), 1604 (C=N),
820 (C–Cl); 1H NMR (400 MHz, DMSO-d6): d 2.29 (s, 3H), 7.21 (s, 1H), 7.37–7.45
(m, 1H), 7.50–7.58 (m, 2H), 7.68–7.76 (m, 2H), 7.85–7.87 (m, 1H), 7.93 (d, 2H,
J = 7.6 Hz), 8.06 (s, 1H), 8.34 (s, 1H); Mass (ESI) m/z: 420 [M?H]?; Anal. Calcd. for
C22H14ClN3O2S: C, 62.93; H, 3.36; N, 10.01. Found: C, 63.18; H, 3.21; N, 9.80.
6-Chloro-3-(1-(4-(4-chlorophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-
chromen-2-one (4e) White solid; mp. 232–234 °C; IR (KBr, cm-1) tmax: 1716
(C=O), 1611 (C=N), 827 (C–Cl);1H NMR (400 MHz, DMSO-d6): d 1H NMR
(400 MHz, DMSO-d6): d 2.32 (s, 3H), 7.37–7.44 (m, 1H), 7.46–7.58 (m, 2H),
7.69–7.73 (m, 1H), 7.86–7.88 (m, 1H), 7.94 (d, 1H, J = 7.6 Hz), 8.08 (d, 2H,
J = 8.0 Hz), 8.25 (s, 1H), 8.35 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d 13.6,
109.4, 113.4, 113.7, 124.0, 126.2, 128.5, 128.7, 128.8, 129.6, 131.9, 139.3, 150.0,
150.1, 158.9; Mass (ESI) m/z: 455 [M?H]?; Anal. Calcd. for C22H13Cl2N3O2S: C,
58.16; H, 2.88; N, 9.25. Found: C, 58.32; H, 3.04; N, 9.07.
6-Bromo-3-(1-(4-(4-chlorophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chro-
men-2-one (4f) Brown solid; mp. 217–219 °C; IR (KBr, cm-1) tmax: 1717 (C=O),
1
1609 (C=N), 827 (C–Cl), 742 (C–Br); H NMR (400 MHz, DMSO-d6): d 2.32 (s,
3H), 7.34–7.44 (m, 1H), 7.46–7.58 (m, 2H), 7.68–7.71 (m, 1H), 7.85–7.90 (m, 1H),
7.94 (d, 2H, J = 7.6 Hz), 8.08 (s, 1H), 8.35 (s, 1H); Mass (ESI) m/z: 498 [M]?;
Anal. Calcd. for C22H13BrClN3O2S: C, 52.98; H, 2.63; N, 8.42. Found: C, 54.41; H,
2.83; N, 8.28.
3-(1-(4-(4-Bromophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one
(4g) Brown; mp. 208–210 °C; IR (KBr, cm-1) tmax: 1722 (C=O), 1601 (C=N), 741
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R. Velpula et al.
(C–Br);1H NMR (400 MHz, DMSO-d6): d 2.31 (s, 3H), 7.36–7.44 (m, 2H), 7.45–7.64
(m, 2H), 7.69–7.73 (m, 1H), 7.73–7.87 (m, 2H), 7.94 (d, 2H, J = 7.6 Hz), 8.09 (s, 1H),
8.35 (s, 1H); Mass (ESI) m/z: 464 [M]?; Anal. Calcd. for C22H14BrN3O2S: C, 56.91; H,
3.04; N, 9.05. Found: C, 57.20; H, 3.22; N, 8.86.
3-(1-(4-(4-Bromophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-6-chloro-2H-chro-
men-2-one (4h) Brown solid; mp. 222–224 °C; IR (KBr, cm-1) tmax: 1716 (C=O),
1612 (C=N), 833 (C–Cl) 735 (C–Br);1H NMR (400 MHz, DMSO-d6): d 2.30 (s,
3H), 7.39–7.76 (m, 3H), 7.69 (t, 1H, J = 7.2 Hz), 7.86 (d, 1H, J = 7.6 Hz), 7.92 (d,
1H, J = 7.2 Hz), 7.98 (d, 2H, J = 7.6 Hz), 8.00 (s, 1H), 8.35 (s, 1H); Mass (ESI)
m/z: 498 [M]?; Anal. Calcd. for C22H13ClBrN3O2S: C, 52.98; H, 2.63; N, 8.42.
Found: C, 53.22; H, 2.80; N, 8.28.
6-Bromo-3-(1-(4-(4-bromophenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chro-
men-2-one (4i) Brown solid; mp. 195–197 °C; IR (KBr, cm-1) tmax: 1719 (C=O),
1
1610 (C=N), 744 (C–Br); H NMR (400 MHz, DMSO-d6): d 2.34 (s, 3H), 6.69 (s,
1H), 7.44 (d, 2H, J = 8.8 Hz), 7.50 (d, 2H, J = 8.8 Hz), 7.63 (d, 1H, J = 8.8 Hz),
7.89 (t, 2H, J = 8.0 Hz), 8.05 (s, 1H), 8.20 (s, 1H); 13C NMR (100 MHz, DMSO-
d6): d 13.6, 109.2, 109.8, 110.3, 111.3, 116.9, 117.8, 119.9, 121.3, 126.9, 127.2,
130.3, 131.2, 131.5, 132.5, 134.7, 136.5, 139.9, 150.4, 151.6, 152.4; Mass (ESI) m/z:
543 [M]?; Anal. Calcd. for C22H13Br2N3O2S: C, 48.64; H, 2.41; N, 7.74. Found: C,
50.03; H, 2.63; N, 7.55.
3-(1-(4-(4-Methoxyphenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-
2-one (4j) Brown solid; mp. 177–179 °C; IR (KBr, cm-1) tmax: 1717 (C=O), 1607
(C=N), 1154 (C–O–C); 1H NMR (400 MHz, DMSO-d6): d 2.32 (s, 3H), 3.76 (s, 3H),
6.94 (s, 1H), 7.38–7.45 (m, 1H), 7.50–7.58 (m, 2H), 7.71 (t, 2H, J = 7.6 Hz), 7.80 (d,
2H, J = 6,4 Hz), 7.92 (t, 1H, J = 8.0 Hz), 8.05 (s, 1H), 8.34 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): d 13.7, 55.1, 110.5, 112.4, 113.1, 113.2, 116.4, 121.4, 125.5,
126.0, 128.4, 128.6, 129.0, 130.0, 132.8, 133.5, 141.1, 151.8, 158.6, 159.6; Mass (ESI)
m/z: 415 [M]?; Anal. Calcd. for C23H17N3O3S: C, 66.49; H, 4.12; N, 10.11. Found: C,
66.71; H, 4.00; N, 9.89.
6-Chloro-3-(1-(4-(4-methoxyphenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chro-
men-2-one (4k) Brown solid; mp. 203–205 °C; IR (KBr, cm-1) tmax: 1722 (C=O),
1611 (C=N), 1148 (C–O–C), 832 (C–Cl); 1H NMR (400 MHz, DMSO-d6): d 2.30 (s,
3H), 3.67 (s, 3H), 7.37–7.44 (m, 1H), 7.46–7.58 (m, 2H), 7.71 (t, 1H, J = 7.8 Hz), 7.86
(d, 1H, J = 7.6 Hz), 7.94 (d, 1H, J = 8.4 Hz), 8.12 (d, 2H, J = 7.6 Hz), 8.14 (s, 1H),
8.35 (s, 1H); Mass (ESI) m/z: 451 [M ? 2]?; Anal. Calcd. for C23H16ClN3O3S: C,
61.40; H, 3.58; N, 9.34. Found: C, 61.57; H, 3.76; N, 9.06.
6-Bromo-3-(1-(4-(4-methoxyphenyl)thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-2H-chro-
men-2-one (4l) Brown solid; mp. 192–194 °C; IR (KBr, cm-1) tmax: IR (KBr, cm-1
)
max: 1718 (C=O), 1601 (C=N), 1134 (C–O–C), 727 (C–Br); H NMR (400 MHz,
1
t
DMSO-d6): d 2.29 (s, 3H), 3.78 (s, 3H), 7.39–7.55 (m, 1H), 7.57–7.72 (m, 2H), 7.81 (s,
1H), 7.80 (d, 1H, J = 6.4 Hz),7.95 (d, 1H, J = 7.6 Hz), 8.10 (d, 2H, J = 7.6 Hz),
8.21 (d, 1H, J = 8.0 Hz), 8.33 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d 13.6, 54.9,
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One-pot multicomponent synthesis of novel…
106.5, 112.1, 112.4, 116.1, 122.2, 124.0, 126.3, 128.9, 129.8, 134.4, 137.1, 137.5,
151.9, 155.3, 157.6; Mass (ESI) m/z: 494 [M]?; Anal. Calcd. for C23H16BrN3O3S: C,
55.88; H, 3.26; N, 8.50. Found: C, 56.16; H, 3.14; N, 8.32.
Acknowledgments We would like to thank Prof. A. Sadanandam, Biotechnology Department, Kakatiya
University for performing cytotoxic activity. We would like to thank the Director, National Institute of
Technology, Warangal for providing research facilities. The author’s RV, RD and RG thank CSIR-UGC
New Delhi, India for research fellowships.
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