Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents

Article abstract of DOI:10.1016/j.bmc.2010.06.013

Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen-Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H- pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI₅₀ values ranging from 0.04 to 11.4 μM, from the in vitro assays.

Full text of DOI:10.1016/j.bmc.2010.06.013

Bioorganic & Medicinal Chemistry 18 (2010) 4965–4974
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Synthesis of novel pyrazolic analogues of chalcones and their
3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole
derivatives as potential antitumor agents
a
b
a
a
c,
*
Braulio Insuasty a, , Alexis Tigreros , Fabián Orozco , Jairo Quiroga , Rodrigo Abonía , Manuel Nogueras
,
*
Adolfo Sanchez c, Justo Cobo c
a Heterocyclic Compounds Research Group, Department of Chemistry, Universidad del Valle, A. A. 25360, Cali, Colombia
b Department of Chemistry, Universidad Nacional de Colombia, A. A. 14490, Bogotá D.C., Colombia
c Department of Inorganic and Organic Chemistry, Universidad de Jaén, 23071 Jaén, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were
synthesized from a Claisen–Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with sev-
eral acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of
chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-
1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in
DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer
Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed
remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell
Received 8 March 2010
Revised 28 May 2010
Accepted 4 June 2010
Available online 9 June 2010
Keywords:
Claisen–Schmidt reaction
Pyrazolic chalcones
Functionalized dihydropyrazoles
Cyclocondensation reaction
Antitumoral agents
lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 to 11.4
the in vitro assays.
lM, from
Ó 2010 Elsevier Ltd. All rights reserved.
Microwave irradiation
1. Introduction
yields and better selectivities, being a valuable alternative to
accomplish more efficient syntheses of a variety of organic com-
pounds with a considerable simplicity of operation and milder reac-
tion conditions, when combined with the solvent-free approach,
as it provides an opportunity to work with open vessels.20–28
In this way, targeting the preparation of the mentioned nitrogen
containing heterocycles, we report herein the regioselective syn-
thesis and citotoxic activities of (E)-1-aryl-3-(3-aryl-1-phenyl-
1H-pyrazol-4-yl)prop-2-en-1-ones 5/6a–h (pyrazolic chalcones)
and 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-
pyrazoles 7a–h and their N-acetyl derivatives 8/9a–h by using
microwave-assisted reaction conditions. Compounds 7a–h and 8/
9a–h were obtained as racemic mixtures in all cases.
The
a,b-unsaturated ketones (chalcones) are considered to be
precursors of flavonoids and isoflavonoids when found as natu-
rally-occurring compounds, but it could be considered that
their true importance is extended in two branches. The biological
activity associated with them, including anti-inflammatory,1–3
antimitotic,4 anti-leishmanial,5 anti-invasive,6,7 anti-tuberculosis,8
anti-fungal,9 anti-malarial,10,11 anti-tumor, and anti-oxidant prop-
erties;12 as well as their recognized synthetic utility in the prepa-
ration of pharmacologically-interesting heterocyclic systems like
pyrazolines, which have also been largely studied owing to
their pharmacological activities, which includes anti-tumor,13
anti-inflammatory,14 anti-parasitary,15 anti-depressive, anticon-
vulsant,16 antimicrobial,17 antinociceptives18 and nitric oxide syn-
thase inhibitors, associated with diseases such as Alzheimer,
Huntington, and inflammatory arthritis.19
2. Results and discussion
2.1. Chemistry
On the other hand, microwave radiation has gained the attention
of chemists during the last decades due to its unique advantages,
such as shorter reaction times, cleaner reaction products, higher
In order to obtain the pyrazolic chalcones, the corresponding 4-
formylpyrazolic precursors 4 were initially synthesized from the
phenylhydrazones 3 (prepared by condensation of the respective
acetophenones 1 and phenylhydrazine 2); following a similar
procedure described by Kira et al.29 In this sense, the Vilsmeier–
* Corresponding authors. Fax: +57 2 33392440 (B.I.); +34 953211876 (M.N.).
E-mail addresses: brainsu@univalle.edu.co (B. Insuasty), mmontiel@ujaen.es
(M. Nogueras).
0968-0896/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2010.06.013

4966
B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
R1
Haack reagent (POCl3/DMF) was employed affording compounds 4
in 75–78% yield (Scheme 1). Compounds 4 were characterized by
using IR, NMR, and MS techniques. Their analytical and spectro-
scopic data agreed with those reported in the literature29 for the
same compounds. Subsequently, the Claisen–Schmidt condensation
of the obtained aldehydes 4 with the acetophenones 1a–h afforded
the corresponding pyrazolic chalcones 5/6a–h, (Scheme 1).
B
H
1'
3
N
N
N
5'
4'
N
R1
5
1
NH2NH2
C
A
DMF, MW
R2
a-h
R1 = NO2
The structure elucidation of compounds 5/6a–h was based on
the spectral data (IR, 1H NMR, 13C NMR, and mass spectrometry).
The IR spectra showed mainly absorption bands at 1662–1626
and 1521–1606 cmꢀ1 assigned to (C@O, C@N) and (C@C) function-
alities, respectively. Particularly, the derivatives 5a–h and 6a
showed typical absorption bands at 1337–1508 cmꢀ1 due to their
NO2 stretching vibrations. In the 1H NMR spectra of products 5/6
the H-6 and H-7 appears each one as a doublet at d = 7.67–
7.87 ppm and d = 7.60–7.69 ppm, respectively, with coupling con-
stant between them of 3J = 13.0–15.9 Hz, which agrees with a trans
configuration. Analysis of 13C, DEPT-135 and 2D-heteronuclear
NMR spectra (HSQC and HMBC) provided the final structural eluci-
dation of compounds 5 and 6. Thus, the signal for C-6 is in the
range of d 118.6–123.5 ppm, the signal for C-7 appears at d
132.1–134.8 ppm, while the C@O carbon atom appears at d
186.8–189.0 ppm. Finally, the mass spectra of compounds 5/6
showed well-defined molecular ions with a characteristic fragmen-
tation pattern involving the loss of the phenyl group in all cases.
Continuing with the synthetic approach, the microwave irradia-
tion of a mixture of the chalcones 5a–h (1.0 mmol) and hydrazine
(1.3 mmol) in the presence of DMF as solvent (0.2 mL), afforded
the desired products 7a–h in good yields (Scheme2). When thesame
reaction was carried out starting with chalcones 5/6a–h in the pres-
ence of acetic acid (0.5 mL) instead of DMF, formation of different
products was observed and identified as the corresponding N-acetyl
derivatives 8/9a–h (Scheme 2). This finding suggests that the acetic
acid acted not only as solvent but also as acetylating agent.
O
R1
N
N
R2
O
a-h
NH2NH2
N
N
N
N
AcOH, MW
R2
a-h, R1 = NO2
a-h,
R
1 = Cl
R2
a
b
c
d
e
f
NO2
F
Cl
Br
H
CH3
g
h
CH3O
3’,4’-OCH2O-
Scheme 2. Synthesis of the new pyrazoles 7a–h and their N-acetyl derivatives
8/9a–h.
Thus, the 40-HA and 40-HB appear each one as a double-doublet at
d = 2.94–3.28 ppm and d = 3.44–3.95 ppm, respectively, with
2JAB = 16.1–18.0 Hz., while 50-H appears as a double-doublet at
d = 5.08–5.82 ppm with JAX = 10.1–11.0 Hz for 7, JAX = 5.4–5.6 Hz
for 8/9 and JBX = 10.8–13.4 Hz for 7–9. The NH protons of com-
pounds 7 were not observed except for 7b which appears as a sin-
glet at d = 7.19 ppm. The main signals in the 13C NMR for
compounds 7–9 correspond to C-40 at d 39.5–42.2 ppm, C-50 at d
51.4–55.7 ppm and the quaternary C-30 at d 148.2–153.3 ppm.
Finally, mass spectra of compounds 7–9 showed also well-defined
molecular ions.
3
3
3
Compounds 7–9 were obtained as racemic mixtures and were
fully characterized by detailed (IR, NMR, and MS) measurements
(Section 4). The IR spectra showed the expected absorption bands
between 3289–3309 and 1600–1676 cmꢀ1 corresponding to the
NH functionality for products 7 and to the C@O functionality for
products 8/9, respectively. In the 1H NMR spectra of compounds
7–9 the two methylenic 40-H protons and the stereogenic 50-H
proton of the pyrazolinic moiety form an ABX spin system.
2.2. Anticancer activity
The two-stage screening process started with the evaluation of
eight compounds (5c, 6b, 6g, 7b, 7g, 8c, 9d, and 9g) selected by NCI,
against the 60 cell lines at a single dose of 1.0 lM. The output from
H
N
O
H
N
the single dose screen was reported as a mean graph available for
analysis by the COMPARE program. The results of the primary assay
showed that compounds 6b, 6g, 7b, 7g, 8c, and 9d were essentially
inactive, while compounds 5c and 9g were declared active
(Table 1).
Subsequently, a secondary screening process was performed, in
order to determine the cytostatic activity of such compounds,
against the 60 cell panel representing leukemia, melanoma and
EtOH, H2SO4
75 ºC
N
H2N
+
R1
R1
R1 = NO2
,
Cl
1. (POCl3 / DMF)
2. NaHCO3 / H2O
70 ºC
OHC
R1
B
O
R2
O
6
3
1 a-h
R1
Table 1
7
N
N
N
EtOH, KOH
C
N
Results of primary anticancer assay for eight com-
pounds selected by the NCI
5
R2
1
Δ
a-h 75-78%
, R1 = NO2; 6, R1 = Cl
A
Compound
Activitya
5c
6b
6g
7b
7g
8c
9d
9g
A
R2
NA
NA
NA
NA
NA
NA
A
a
NO2
b
F
c
d
e
f
Cl
Br
H
CH3
g
h
CH3O
3’,4’-OCH2O-
a
Activity denoted as: A = active; NA = not active.
Scheme 1. Synthesis of the novel pyrazolic chalcones 5/6a–h.

B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
4967
Table 2
Table 2 (continued)
In vitro testing expressed as growth inhibition of cancer cell lines for compounds 5c
and 9ga
Panel/cell line
Compounds
5c
9g
Panel/cell line
Compounds
b
c
b
c
GI50
(lM)
LC50
(lM)
GI50
(l
M)
LC50 (lM)
5c
9g
MDA-MB-468
HS 578T
2.91
2.55
>100
>100
—
—
>100
>100
b
c
b
c
GI50
(l
M)
LC50
(l
M)
GI50
(
lM)
LC50 (lM)
Leukemia
RPMI-8226
SR
CCRF-CEM
HL-60(TB)
K-562
a
Data obtained from NCI’s in vitro disease-oriented human tumor cell lines
1.86
2.76
—
>100
0.09
0.87
>100
>100
>100
>100
>100
>100
1.73
1.57
—
>100
8.06
—
screen.31–33
b
GI50 was the drug concentration resulting in a 50% reduction in the net protein
increase (as measured by SRB staining) in control cells during the drug incubation.
Determined at five concentration levels (100, 10, 1.0, 0.1, and 0.01 M).
LC50 is a parameter of citotoxicity and reflects the molar concentration needed
to kill 50% of the cells.
—
—
—
—
—
—
l
c
MOLT-4
Non-small cell lung cancer
EKVX
HOP-62
4.97
>100
>100
>100
>100
>100
>100
>100
>100
>100
—
—
—
1.77
1.98
2.20
0.04
—
>100
—
>100
—
—
>100
—
26.0
3.77
4.99
—
6.41
—
cancers of the lung, colon, brain, ovary, breast, prostate, and kid-
ney; where the testing results were expressed according to the
next three parameters: GI50 which is the molar concentration of
the compounds required to inhibit the growth of that cell line by
50% (relative to untreated cells). TGI as the molar concentration
that causes total growth inhibition, and LC50 which is a parameter
of citotoxicity and reflects the molar concentration needed to kill
50% of the cells.30 The compounds were evaluated at five concen-
NCI-H226
NCI-H23
NCI-H460
NCI-H522
HOP-92
NCI-H322M
A549/ATCC
—
—
>100
>100
—
Colon
COLO 205
HCT-116
HCT-15
HT29
KM12
SW-620
HCC-2998
2.09
2.75
—
—
—
—
2.16
1.94
3.09
—
—
3.48
2.21
—
—
tration levels (100, 10, 1.0, 0.1, and 0.01 lM) and the test consisted
>100
>100
>100
>100
—
of a 48 h continuous drug exposure protocol using sulforhodamide
B (SRB) protein assay to estimate cell growth. Details of this eval-
uation method, and the complementary information related with
the activity pattern over all cell lines, have been published.31–33
As shown in Table 2, compound 5c presented remarkable activity
against 37 human tumor cell lines, being the most sensitive to
growth inhibition K-562 of leukemia panel with GI50 value of
>100
>100
>100
>100
>100
—
>100
>100
CNS
SF-295
SF-539
U251
SF-268
SNB-19
SNB-75
2.32
3.95
2.09
3.12
4.90
1.55
74.1
>100
>100
>100
>100
24.0
2.48
1.87
1.71
4.55
—
>100
—
—
>100
>100
>100
0.09
of 0.10
l
M and UO-31 of renal cancer panel displaying a GI50 value
M (citotoxicity expressed as LC50 with values >100 lM
l
for both cell lines). Likewise, compound 9g (active against 28 hu-
man tumor cell lines) was found especially effective against the
cell line HOP-92 of non-small cell lung cancer panel exhibiting a
2.76
Melanoma
LOX IMVI
MALME-3M
MDA-MB-435
SK-MEL-5
UACC-257
UACC-62
SK-MEL-2
M14
SK-MEL-28
—
2.44
—
>100
>100
11.4
6.99
—
>100
>100
>100
>100
>100
>100
57.9
1.66
—
—
1.79
>100
2.40
—
—
remarkable GI50 value of 0.04
GI50 of 1.57 M (LC50 >100 M) for cell line SR of leukemia panel.
In summary, derivatives 5c and 9g showed significant activities
with GI50 ranges of 0.09–26.0 M and 0.04–4.55 M, respectively;
where most of the GI50 values of the screening process resulted in a
sensitive range inferior of 20 M denoting an outstanding activity
lM (LC50 >100 lM), as well as a
>100
>100
—
>100
>100
>100
>100
>100
l
l
l
l
l
>100
>100
—
—
—
in both cases. The values of citotoxicity associated with com-
pounds 5c and 9g and measured as LC50 are in most of the cell lines
Ovarian
IGROV1
3.54
1.96
—
4.64
6.32
>100
12.5
>100
>100
—
>100
>100
>100
>100
—
—
—
1.80
—
>100
—
>100
—
>100
>100
>100
>100 lM (Table 2).
OVCAR-3
OVCAR-4
NCI/ADR-RES
OVCAR-8
OVCAR-5
SK-OV-3
3. Conclusion
1.81
2.14
As a part of our current research work focused on the develop-
ment of new bioactive heterocyclic compounds, the synthesis and
anticancer screening of the novel pyrazolic chalcones 5/6a–h, pyr-
azoles 7a–h and their N-acetyl derivatives 8/9a–h have been per-
formed. The anticancer evaluation data revealed that among the
eight compounds studied, derivatives 5c and 9g exhibited high
activity patterns against different cancer cell lines with remarkable
values in panels of non-small cell lung cancer, leukemia, and renal
cancer. Owing to the significant results obtained, chemical studies
are being conducted to improve the antitumor activity of such
compounds, as well as other biological studies focused on antiviral
and antifungal activity.
Renal
A498
3.14
4.27
4.56
2.08
—
3.12
0.10
3.94
>100
>100
>100
9.87
>100
>100
>100
>100
—
>100
—
—
ACHN
CAKI-1
RXF 393
SN12C
TK-10
UO-31
786-0
1.82
1.96
1.82
—
—
—
—
>100
>100
>100
—
—
Prostate
DU-145
PC-3
—
—
>100
—
—
2.35
>100
>100
Breast
MCF7
MDA-MB-231/ATCC
BT-549
T-47D
4. Experimental
—
>100
>100
>100
>100
—
1.88
—
>100
—
>100
—
2.45
2.25
1.12
Melting points were determined on a Buchi Melting Point
Apparatus and are uncorrected. IR spectra were performed on a
Shimadzu FTIR 8400 spectrometer in KBr disks. The 1H and 13C
1.90

4968
B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
NMR spectra were run on a Bruker DPX 400 spectrometer operat-
ing at 400 MHz and 100 MHz, respectively, using DMSO-d6 as sol-
vent and TMS as internal standard. The mass spectra were obtained
on a Hewlett Packard HP Engine-5989 spectrometer (equipped
with a direct inlet probe) operating at 70 eV. The elemental analy-
ses were carried out on a LECO CHNS-900 elemental analyzer.
Reactions under microwave irradiation were performed using a
CEM Discover™ monomode system with power/time control using
a ramp of 100–300 W.
(CpC), 138.0 (CiB), 138.5 (CiA), 147.2 (CpB), 149.7 (C-3), 187.5
(C-8) ppm. MS (70 eV) m/z (%): 429 (13, M+), 244 (61), 139 (100),
77 (90). Anal. Calcd for C24H16ClN3O3: C, 67.12; H, 3.79; N, 9.69.
Found: C, 67.20; H, 3.85; N, 9.74.
4.1.4. (E)-1-(4-Bromophenyl)-3-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (5d)
Yellow solid, 95% yield; mp: 220 °C. FTIR (KBr),
m
(cmꢀ1): 1660
(C@O and C@N); 1599 (C@C); 1508 and 1352 (NO2); 1H NMR
(400 MHz, DMSO-d6) d 7.41 (t, 1H, HpA, J = 7.65 Hz), 7.72 (d, 2H,
HoC, J = 8.27 Hz), 7.56 (t, 2H, HmA, J = 7.24 Hz), 7.62 (d, 1H, H-7,
J = 15.50 Hz), 7.80 (d, 1H, H-6, J = 15.7 Hz), 7.93 (d, 2H, HoA,
J = 8.48 Hz), 7.95 (d, 2H, HmC, J = 8.30 Hz), 7.96 (d, 2H, HoB,
J = 7.92 Hz), 8.33 (d, 2H, HmB, J = 7.96 Hz), 9.16 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 117.8 (C-4), 123.1 (CmB), 122.4
(C-6), 126.2 (CpC), 126.8 (CpA), 128.6 (CoB), 128.8 (C-5), 128.9
(CoA), 129.4 (CmC), 129.7 (CmA), 131.0 (CoC), 133.1 (C-7), 136.4
(CiC), 138.0 (CiB), 138.5 (CiA), 147.2 (CpB), 149.7 (C-3), 187.7
(C-8) ppm. MS (70 eV) m/z (%): 473 (7, M+), 183 (100), 244 (57),
77 (70). Anal. Calcd for C24H16BrN3O3: C, 60.77; H, 3.40; N, 8.86.
Found: C, 60.80; H, 3.48; N, 8.79.
4.1. General procedure for the synthesis of the pyrazolic
chalcones 5/6a–h
To a solution of 3-aryl-1-phenylpyrazol-4-carboxaldehyde 4
(1.0 mmol), acetophenone 1 (1.0 mmol) and ethanol (30.0 mL), a
pellet of KOH was added. The reaction mixture was stirred at ambi-
ent temperature until formation of a precipitate. The solid obtained
was isolated by filtration, washed and recrystalized from a (1:1)
EtOH/DMF mixture.
4.1.1. (E)-1-(4-Nitrophenyl)-3-[3-(4-nitrophenyl)-1-phenyl-1H-
pyrazol-4-yl]prop-2-en-1-one (5a)
Green solid, 76% yield; mp: 244 °C. FTIR (KBr)
m
(cmꢀ1): 1661
4.1.5. (E)-3-[3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
(C@O and C@N); 1517 and 1342 (NO2); 1584 (C@C); 1H NMR
(400 MHz, DMSO-d6) d 7.41 (t, 1H, HpA, J = 7.14 Hz), 7.56 (t, 2H,
HmA, J = 8.20 Hz), 7.61 (d, 1H, H-7, 15.51 Hz), 7.68 (d, 1H, H-6,
15.30 Hz), 7.92 (d, 2H, HoA, J = 7.05 Hz), 7.97 (d, 2H, HoB,
J = 8.89 Hz), 7.98 (d, 2H, HoC, J = 8.55 Hz), 8.25 (d, 2H, HmC,
J = 8.60 Hz), 8.30 (d, 2H, HmB, J = 8.88 Hz), 9.19 (s, 1H, H-5) ppm;
13C NMR (100 MHz, DMSO-d6) d 117.1 (C-4), 122.7 (C-6), 123.3
(CmB), 126.3 (CpA), 126.6 (CoA), 128.3 (CmA), 128.6 (CoB), 128.7
(CoC), 128.9 (C-5), 129.3 (CmC), 134.8 (C-7), 136.3 (CiC), 137.6
(CiA), 138.4 (CiB), 144.4 (CpC), 147.2 (CpB), 149.8 (C-3), 188.6
(C-8) ppm. MS (70 eV) m/z (%): 440 (12, M+), 279 (100), 77 (39).
Anal. Calcd for C24H16N4O5: C, 65.45; H, 3.66; N, 12.77. Found:
C, 65.54; H, 3.70; N, 12.69.
phenyl-prop-2-en-1-one (5e)
Yellow solid, 92% yield; mp: 190 °C. FTIR (KBr),
m
(cmꢀ1): 1626
(C@O and C@N), 1595 (C@C), 1507 and 1339 (NO2); 1H NMR
(400 MHz, DMSO-d6) d 7.42 (t, 1H, HpA, J = 7.00 Hz), 7.49 (d, 2H,
HmC, J = 7.56 Hz), 7.55 (t, 2H, HmA, J = 7.15 Hz), 7.60 (t, 1H, HpC,
J = 8.15 Hz), 7.62 (d, 1H, H-7, J = 15.35 Hz), 7.67 (d, 1H, H-6,
J = 15.30 Hz), 7.91 (d, 2H, HoA, J = 7.40 Hz), 7.96 (d, 2H, HoB,
J = 7.40 Hz), 7.98 (d, 2H, HoC, J = 8.15 Hz), 8.32 (d, 2H, HmB,
J = 7.39 Hz), 9.15 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)
d 118.0 (C-4), 123.0 (C-6), 124.1 (CmB), 126.0 (CoC), 126.3 (CpA),
127.4 (CpC), 127.8 (C-5), 128.0 (CoA), 128.3 (CmA), 128.7 (CoB),
129.6 (CmC), 133.1 (C-7), 135.0 (CiC), 137.9 (CiB), 139.0 (CiA),
147.6 (CpB), 149.7 (C-3), 189.0 (C-8) ppm. MS (70 eV) m/z (%):
395 (36, M+), 119 (100), 77 (78). Anal. Calcd for C24H17N3O3: C,
72.90; H, 4.33; N, 10.63. Found: C, 72.98; H, 4.33; N, 10.59.
4.1.2. (E)-1-(4-Fluorophenyl)-3-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (5b)
Yellow solid, 76% yield; mp: 221 °C. FTIR (KBr),
m
(cmꢀ1): 1659
4.1.6. (E)-1-(4-Methylphenyl)-3-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (5f)
(C@O and C@N); 1602 (C@C); 1507 and 1343 (NO2); 1H NMR
(400 MHz, DMSO-d6) d 6.61 (d, 2H, HoC, J = 8.89 Hz), 7.41 (t, 1H,
HpA, J = 8.89 Hz), 7.59 (t, 2H, HmA, J = 7.86 Hz), 7.68 (d, 1H, H-7,
J = 15.51 Hz), 7.87 (d, 1H, H-6, J = 15.30 Hz), 7.93 (d, 2H, HoA,
J = 8.40 Hz), 7.95 (d, 2H, HoB, J = 8.88 Hz), 8.17 (d, 2H, HmC,
J = 8.89 Hz), 8.37 (d, 2H, HmB, J = 8.89 Hz), 9.42 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 115.8 (CoC), 118.7 (C-4), 122.0
(C-6), 124.0 (CmB), 126.8 (CoA), 127.5 (CpA), 129.2 (CoB), 129.3
(C-5), 129.7 (CmA), 131.1 (CmC), 133.3 (C-7), 138.3 (CiB), 138.8
(CiA), 147.2 (CpB), 150.3 (C-3), 163.7 (CpC), 166.2 (CiC), 187.0
(C-8) ppm. MS (70 eV) m/z (%): 413 (32, M+), 244 (65), 123 (100),
77 (56). Anal. Calcd for C24H16FN3O3: C, 69.73; H, 3.90; N, 10.16.
Found: C, 69.70; H, 3.95; N, 10.18.
Yellow solid, 89% yield; mp: 214 °C. FTIR (KBr),
m
(cmꢀ1): 1661
(C@O and C@N), 1596 (C@C), 1509 and 1350 (NO2); 1H NMR
(400 MHz, DMSO-d6) d 2.40 (s, 3H, H–CH3), 7.34 (d, 2H, HmC,
J = 7.65 Hz), 7.40 (t, 1H, HpA, J = 7.45 Hz), 7.56 (t, 2H, HmA,
J = 7.45 Hz), 7.64 (d, 1H, H-7, J = 15.51 Hz), 7.69 (d, 1H, H-6,
J = 15.92 Hz), 7.91 (d, 2H, HoC, J = 7.60 Hz), 7.93 (d, 2H, HoA,
J = 8.30 Hz), 7.96 (d, 2H, HoB, J = 7.31 Hz), 8.33 (d, 2H, HmB,
J = 7.24 Hz), 9.15 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6) d
20.3 (C–CH3), 117.9 (C-4), 118.6 (CoC), 122.9 (C-6), 123.1 (CmB),
126.7 (CpA), 127.6 (CoA), 128.5 (CmC), 128.6 (CoB), 128.7 (C-5), 128.8
(CmA), 132.1 (C-7), 134.9 (CpC), 138.1 (CiB), 138.5 (CiA), 142.5 (CiC),
147.1 (CpB), 149.6 (C-3), 188.0 (C-8) ppm. MS (70 eV) m/z (%): 409
(38, M+), 244 (28), 119 (100), 77 (31). Anal. Calcd for C25H19N3O3: C,
73.34; H, 4.68; N, 10.26. Found: C, 73.44; H, 4.70; N, 10.16.
4.1.3. (E)-1-(4-Chlorophenyl)-3-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (5c)
Yellow solid, 91% yield; mp: 224 °C. FTIR (KBr),
m
(cmꢀ1): 1660
4.1.7. (E)-1-(4-Methoxyphenyl)-3-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (5g)
(C@O and C@N); 1600 (C@C); 1507 and 1350 (NO2); 1H NMR
(400 MHz, DMSO-d6) d 7.42 (t, 1H, HpA, J = 7.03 Hz), 7.55 (d, 2H,
HmA, J = 7.03 Hz), 7.57 (d, 2H, HoA, J = 6.82 Hz), 7.60 (d, 1H, H-7,
J = 13.24 Hz), 7.67 (d, 1H, H-6, J = 13.03 Hz), 7.93 (d, 2H, HoC,
J = 7.63 Hz), 7.96 (d, 2H, HoB, J = 8.89 Hz), 8.01 (d, 2H, HmC,
J = 8.01 Hz), 8.33 (t, 2H, HmB, J = 8.89 Hz), 9.17 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 117.8 (C-4), 118.6 (C-6), 122.4
(CoC), 123.1 (CmB), 126.7 (CpA), 126.8 (CoA), 128.6 (CoB), 128.8
(C-5), 129.0 (CmA), 129.3 (CmC), 133.0 (C-7), 136.0 (CiC), 137.3
Yellow solid, 75% yield; mp: 205 °C. FTIR (KBr),
m
(cmꢀ1): 1657
(C@O and C@N), 1599 (C@C), 1507 and 1347 (NO2), 1222 (O–CH3);
1H NMR (400 MHz, DMSO-d6) d 3.87 (s, 3H, H–OCH3), 7.08 (d, 2H,
HmC, J = 9.10 Hz), 7.41 (t, 1H, HpA, J = 7.44 Hz), 7.58 (t, 2H, HmA,
J = 8.48 Hz), 7.67 (d, 1H, H-7, J = 15.51 Hz), 7.87 (d, 1H, H-6,
J = 15.28 Hz), 7.94 (d, 2H, HoC, J = 9.12 Hz), 7.95 (d, 2H, HoA,
J = 8.48 Hz), 8.08 (d, 2H, HoC, J = 9.10 Hz), 8.37 (d, 2H, HmB,
J = 9.10 Hz), 9.17 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)

B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
4969
d 55.6 (C–OCH3), 114.0 (CmC), 117.8 (C-4), 122.3 (CmB), 122.4 (C-6),
124.1 (CoC), 127.0 (CoA), 128.0 (C-5), 129.0 (CoB), 129.5 (CmA),
129.7 (CiC), 132.2 (CpA), 133.3 (C-7), 137.6 (CiA), 138.2 (CiB),
146.1 (CpB), 149.7 (C-3), 163.8 (CpC), 188.6 (C-8) ppm. MS
(70 eV) m/z (%): 425 (9, M+), 135 (100), 77 (45). Anal. Calcd for
J = 15.50 Hz), 7.70 (d, 2H, HoA, J = 7.86 Hz), 7.84 (d, 1H, H-6,
J = 15.51 Hz), 7.94 (d, 2H, HmB, J = 8.47 Hz), 8.10 (d, 2H, HmC,
J = 8.68 Hz), 9.41 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)
d 117.8 (C-4), 118.7 (C-6), 121.2 (CmB), 127.2 (CpA), 128.7 (CoC),
128.9 (CoB), 129.0 (C-5), 129.7 (CmA), 130.0 (CoA), 130.3 (CmC),
130.7 (CiB), 133.6 (CiA), 134.2 (C-7), 138.0 (CpC), 138.8 (CpB),
151.6 (C-3), 163.9 (CiC), 187.4 (C-8) ppm. MS (70 eV) m/z (%):
418 (10, M+), 279 (100), 77 (38). Anal. Calcd for C24H16Cl2N2O: C,
68.75; H, 3.85; N, 6.68. Found: C, 68.79; H, 3.80; N, 6.65.
C25H19N3O4: C, 70.58; H, 4.50; N, 9.88. Found: C, 70.65; H, 4.48;
N, 9.85.
4.1.8. (E)-1-(3,4-Methylenedioxyphenyl)-3-[3-(4-nitrophenyl)-
1-phenyl-1H-pyrazol-4-yl]prop-2-en-1-one (5h)
Green solid, 80% yield; mp: 169 °C. FTIR (KBr),
m
(cmꢀ1): 1657
4.1.12. (E)-1-(4-Bromophenyl)-3-[3-(4-chlorophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (6d)
(C@O and C@N), 1598 (C@C), 1507 and 1347 (NO2), 1264 y 1102
(O–CH2–O); 1H NMR (400 MHz, DMSO-d6) d 6.07 (s, 2H, H–CH2),
6.98 (d, 2H, HmC, J = 8.03 Hz), 7.39 (t, 1H, HpA, J = 7.53 Hz), 7.47
Yellow solid, 96% yield; mp: 192 °C. FTIR (KBr),
m
(cmꢀ1): 1659
(C@O and C@N), 1597 (C@C); 1H NMR (400 MHz, DMSO-d6) d 7.42
(t, 1H, HpA, J = 7.51 Hz), 7.59 (t, 2H, HmA, J = 8.27 Hz), 7.62 (d, 2H,
HoC, J = 8.48 Hz), 7.68 (d, 1H, H-7, J = 15.52 Hz), 7.70 (d, 2H, HoB,
J = 8.69 Hz), 7.80 (d, 2H, HmC, J = 8.48 Hz), 7.83 (d, 1H, H-6,
J = 15.54 Hz), 7.94 (d, 2H, HoA, J = 7.65 Hz), 8.02 (d, 2H, HmB,
J = 8.69 Hz), 9.41 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)
d 117.8 (C-4), 118.7 (CoA), 121.2 (C-6), 127.2 (CpA), 127.3 (CiB),
128.9 (CoC), 129.0 (C-5), 129.7 (CmA), 130.0 (CmC), 130.2 (CmB),
130.7 (CiC), 131.8 (CoB), 133.4 (CpC), 134.3 (C-7), 136.5 (CpB),
138.8 (CiA), 151.6 (C-3), 187.6 (C-8) ppm. MS (70 eV) m/z (%):
462 (5, M+), 464 (9), 279 (100), 77 (44). Anal. Calcd for C24H16
ClBrN2O: C, 62.16; H, 3.48; N, 6.04. Found: C, 62.10; H, 3.52; N,
6.14.
0
(s, 1H, Ho C), 7.54 (t, 2H, HmA, J = 7.53 Hz), 7.60 (d, 1H, H-7,
J = 15.48), 7.63 (d, 1H, H-6, J = 15.57), 7.66 (d, 2H, HoC,
J = 8.03 Hz), 7.88 (d, 2H, HoA, J = 7.78 Hz), 7.91 (d, 2H, HoB,
J = 8.78 Hz), 8.31 (d, 2H, HmB, J = 8.79 Hz), 9.11 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 102.4 (C–CH2), 108.5 (CmC),
119.0 (C-4), 119.6 (CoA), 123.5 (C-6), 124.3 (CmB), 125.1 (CoC),
0
127.9 (CpA), 129.4 (Co C), 129.6 (CoB), 129.7 (C-5), 130.0 (CmA),
132.8 (CiC), 132.9 (C-7), 138.2 (CpC), 139.1 (CpB), 139.4 (CiA),
0
148.1 (CiB), 148.5 (C-3), 150.7 (Cm C), 187.7 (C-8) ppm. MS
(70 eV) m/z (%): 439 (11, M+), 279 (100), 149 (100), 77 (44). Anal.
Calcd for C25H17N3O5: C, 68.33; H, 3.90; N, 9.56. Found: C, 68.28;
H, 3.88; N, 9.58.
4.1.9. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
4.1.13. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
(4-nitrophenyl)-prop-2-en-1-one (6a)
phenyl-prop-2-en-1-one (6e)
Green solid, 88% yield; mp: 234 °C. FTIR (KBr),
m
(cmꢀ1): 1662
Yellow solid, 78% yield; mp: 175 °C. FTIR (KBr), m
(cmꢀ1): 1662
(C@O and C@N), 1521 and 1348 (NO2), 1521 (C@C); 1H NMR
(400 MHz, DMSO-d6) d 7.39 (t, 1H, HpA, J = 6.61 Hz), 7.55 (t, 2H,
HmA, J = 8.27 Hz), 7.57 (d, 2H, HoB, J = 8.06 Hz), 7.60 (d, 1H, H-7,
15.50 Hz), 7.69 (d, 2H, HmB, J = 8.48 Hz), 7.70 (d, 1H, H-6,
15.70 Hz), 7.91 (d, 2H, HoA, J = 7.65 Hz), 8.17 (d, 2H, HoC,
J = 8.68 Hz), 8.32 (d, 2H, HmC, J = 8.89 Hz), 9.15 (s, 1H, H-5) ppm.
13C NMR (DMSO-d6) d 117.13 (C-4), 118.5 (CoA), 121.7 (C-6),
122.9 (CmC), 126.6 (CpA), 128.1 (CoB), 128.7 (CoC), 128.8 (C-5),
128.9 (CmA), 129.3 (CmB), 130.4 (CiB), 133.15 (CpB), 134.8 (C-7),
138.5 (CiA), 142.4 (CiC), 149.4 (CpC), 151.1 (C-3), 187.8 (C-8)
ppm. MS (70 eV) m/z (%): 429 (8, M+), 279 (100), 77 (60). Anal.
Calcd for C24H16ClN3O3: C, 67.06; H, 3.75; N, 9.78. Found: C,
67.19; H, 3.70; N, 9.77.
(C@O and C@N), 1606 (C@C); 1H NMR (400 MHz, DMSO-d6) d 7.42
(t, 1H, HpA, J = 7.44 Hz), 7.58 (t, 2H, HmA, J = 8.69 Hz), 7.60 (t, 1H,
HpC, J = 7.03 Hz), 7.61 (d, 2H, HmB, J = 7.65 Hz), 7.61 (d, 2H, HmC,
J = 7.42 Hz), 7.63 (d, 2H, HoB, J = 7.60 Hz), 7.69 (d, 1H, H-7,
J = 15.71 Hz), 7.71 (d, 2H, HoA, J = 8.48 Hz), 7.81 (d, 1H, H-6,
J = 15.48 Hz), 8.10 (d, 2H, HoC, J = 7.75 Hz), 9.43 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 117.8 (C-4), 118.7 (C-6), 121.7
(CmB), 127.2 (CpA), 127.3 (CiB), 128.2 (CoC), 128.7 (CmC), 128.9
(C-5), 129.7 (CpC), 129.8 (CmA), 130.0 (CoA), 130.8 (CoB), 133.6
(CpB), 133.8 (C-7), 137.6 (CiC), 138.9 (CiA), 151.6 (C-3), 188.7
(C-8) ppm. MS (70 eV) m/z (%): 384 (24, M+), 279 (100), 77 (95).
Anal. Calcd for C24H17ClN2O: C, 74.90; H, 4.45; N, 7.28. Found:
C, 74.94; H, 4.40; N, 7.32.
4.1.10. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
4.1.14. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
(4-fluorophenyl)-prop-2-en-1-one (6b)
(4-methylphenyl)-prop-2-en-1-one (6f)
Yellow solid, 75% yield; mp: 166 °C. FTIR (KBr),
m
(cmꢀ1): 1660
Yellow solid, 76% yield; mp: 176 °C. FTIR (KBr), m
(cmꢀ1): 1660
(C@O and C@N), 1600 (C@C); 1H NMR (400 MHz, DMSO-d6) d 7.42
(t, 1H, HpA, J = 8.69 Hz), 7.44 (d, 2H, HoC, J = 8.89 Hz), 7.60 (t, 2H,
HmA, J = 8.48 Hz), 7.64 (d, 2H, HoB, J = 7.44 Hz), 7.68 (d, 1H, H-7,
J = 15.3 Hz), 7.70 (d, 2H, HoA, J = 8.68 Hz), 7.87 (d, 1H, H-6,
J = 15.5 Hz), 7.94 (d, 2H, HmB, J = 7.45 Hz), 8.17 (d, 2H, HmC,
J = 8.89 Hz), 9.41 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)
d 115.8 (CoC), 117.8 (C-4), 118.7 (CmB), 121.4 (C-6), 127.3 (CpA),
128.7 (CoB), 128.9 (C-5), 129.7 (CmA), 130.0 (CoA), 130.7 (CiB),
131.1 (CmC), 133.9 (C-7), 134.3 (CpB), 138.8 (CiA), 151.6 (C-3),
163.7 (CiC), 166.2 (CpC), 187.2 (C-8) ppm. MS (70 eV) m/z (%):
402 (9, M+), 279 (100), 77 (49). Anal. Calcd for C24H16ClFN2O: C,
71.55; H, 4.00; N, 6.95. Found: C, 71.50; H, 3.96; N, 6.99.
(C@O and C@N), 1595 (C@C); 1H NMR (400 MHz, DMSO-d6) d 2.41
(s, 3H, H–CH3), 7.39 (d, 2H, HmC, J = 8.30 Hz), 7.42 (t, 1H, HpA,
J = 8.04 Hz), 7.60 (t, 2H, HmA, J = 8.48 Hz), 7.63 (d, 2H, HoB,
J = 7.64 Hz), 7.66 (d, 1H, H-7, J = 15.93 Hz), 7.70 (d, 2H, HoA,
J = 8.68 Hz), 7.87 (d, 1H, H-6, J = 15.51 Hz), 7.85 (d, 2H, HmB,
J = 7.68 Hz), 8.01 (d, 2H, HoC, J = 8.27 Hz), 9.42 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 21.1 (C–CH3), 117.8 (C-4), 118.7
(C-6), 118.7 (CmC), 121.7 (CmB), 127.2 (CpA), 128.9 (CoB), 129.1
(C-5), 129.7 (CmA), 130.0 (CoA), 130.4 (CoC), 130.8 (CiB), 130.9
(CpC), 133.3 (C-7), 133.5 (CpB), 138.9 (CiA), 143.5 (CiC), 151.5
(C-3), 188.0 (C-8) ppm. MS (70 eV) m/z (%): 398 (4, M+), 279
(100), 119 (40), 77 (39). Anal. Calcd for C25H19ClN2O: C, 75.28; H,
4.80; N, 7.02. Found: C, 75.30; H, 4.84; N, 7.12.
4.1.11. (E)-1-(4-Chlorophenyl)-3-[3-(4-chlorophenyl)-1-phenyl-
1H-pyrazol-4-yl]prop-2-en-1-one (6c)
4.1.15. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
Yellow solid, 90% yield; mp: 185 °C. FTIR (KBr),
m
(cmꢀ1): 1660
(4-methoxyphenyl)-prop-2-en-1-one (6g)
(C@O and C@N), 1598 (C@C); 1H NMR (400 MHz, DMSO-d6) d 7.42
(t, 1H, HpA, J = 7.03 Hz), 7.58 (t, 2H, HmA, J = 8.47 Hz), 7.62 (d, 2H,
HoB, J = 7.47 Hz), 7.65 (d, 2H, HoC, J = 8.69 Hz), 7.68 (d, 1H, H-7,
Yellow solid, 79% yield; mp: 167 °C. FTIR (KBr), m
(cmꢀ1): 1659
(C@O and C@N), 1597 (C@C), 1219 (O–CH3); 1H NMR (DMSO-d6) d
3.88 (s, 3H, H–OCH3), 7.11 (d, 2H, HmC, J = 8.89 Hz), 7.42 (t, 1H, HpA,

4970
B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
0
0
0
0
0
0
J = 7.45 Hz), 7.60 (t, 2H, HmA, J = 8.27 Hz), 7.62 (d, 2H, HoB,
J = 7.76 Hz), 7.65 (d, 1H, H-7, J = 15.51 Hz), 7.71 (d, 2H, HoA,
J = 8.48 Hz), 7.87 (d, 1H, H-6, J = 15.51 Hz), 7.95 (d, 2H, HmB,
J = 8.47 Hz), 8.10 (d, 2H, HoC, J = 8.89 Hz), 9.40 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 55.5 (C–OCH3), 114.0 (CmC),
117.9 (C-4), 118.7 (C-6), 121.7 (CmB), 127.2 (CpA), 128.8 (CoB),
128.9 (C-5), 129.6 (CmA), 130.0 (CoA), 130.4 (CiC), 130.5 (CoC),
130.8 (CiB), 132.8 (C-7), 133.5 (CpB), 138.9 (CiA), 151.4 (C-3),
163.1 (CpC), 186.8 (C-8) ppm. MS (70 eV) m/z (%): 414 (20, M+),
279 (100), 77 (49). Anal. Calcd for C25H19ClN2O2: C, 72.37; H,
4.62; N, 6.75. Found: C, 72.41; H, 4.68; N, 6.70.
J4a –5 = 10.13 Hz), 3.49 (dd, 1H, H-4b0, J4b –4a = 16.36 Hz, J4b –5
=
10.75 Hz), 5.13 (t, 1H, H-50, J5 –4a = 10.44 Hz, J5 –4b = 11.00 Hz),
7.13 (m, 1H, Hp-C), 7.19 (s, 1H, NH), 7.33 (t, 2H, Hp-A,
J = 7.65 Hz), 7.50 (t, 2H, Hm-A, J = 7.26 Hz), 7.65 (m, 2H, Hm-C,),
7.86 (d, 2H, Ho-A, J = 7.65 Hz), 8.04 (d, 2H, Ho-B, J = 8.89 Hz), 8.26
(d, 2H, Hm-B, J = 8.69 Hz), 8.45 (s, 1H, H-5). 13C NMR (100 MHz,
DMSO-d6) d 39.7 (C-40), 54.5 (C-50), 114.5 (Co-C), 118.2 (Co-A),
122.8 (Cm-B), 123.7 (C-4), 126.0 (Cp-A), 126.9 (Cm-C), 127.3 (C-5),
128.2 (Co-B), 128.8 (Cm-A), 138.9 (Ci-A), 139.1 (Ci-B), 146.0 (Cp-B),
147.1 (Cp-C), 148.2 (C-3), 148.7 (Ci-C), 152.8 (C-30). MS (70 eV)
m/z (%): 427 (100, M+), 305 (6), 345 (10), 77 (12). Anal. Calcd for
0
0
0
0
C24H18FN5O2: C, 67.44; H, 4.24; N, 16.38. Found: C, 67.48; H,
4.1.16. (E)-3-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-
4.19; N, 16.30.
(3,4-methylenedioxyphenyl)-prop-2-en-1-one (6h)
Yellow solid, 82% yield; mp: 152 °C. FTIR (KBr),
m
(cmꢀ1): 1657
4.2.3. 4-[3-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-5-yl]-3-(4-
nitrophenyl)-1-phenyl-1H-pyrazole (7c)
(C@O and C@N), 1589 (C@C), 1258 and 1094 (O–CH2–O); 1H NMR
(400 MHz, DMSO-d6) d 6.17 (s, 2H, H–CH2), 7.11 (d, 2H, HmC,
J = 8.27 Hz), 7.42 (t, 1H, HpA, J = 7.24 Hz), 7.59 (t, 2H, HmA,
Yellow solid, 92% yield; mp: 224 °C, FTIR (KBr),
m
(cmꢀ1): 3309
(NH), 1669 (C@N), 1596 (C@C, Ar), 1501 and 1340 (NO2). 1H NMR
0
0
0
J = 7.65 Hz), 7.61 (s, 1H, Ho C), 7.63 (d, 2H, HoB, J = 7.86 Hz), 7.64
(400 MHz, DMSO-d6) d 2.99 (dd, 1H, H-4a0, J4a –4b = 16.29 Hz,
0
0
0
0
0
0
(d, 1H, H-7, J = 15.30 Hz), 7.70 (d, 2H, HoA, J = 8.68 Hz), 7.78 (d,
2H, HoC, J = 8.27 Hz), 7.84 (d, 1H, H-6, J = 15.46 Hz), 7.94 (d, 2H,
HmB, J = 7.86 Hz), 9.39 (s, 1H, H-5) ppm. 13C NMR (100 MHz,
DMSO-d6) d 102.1 (C–CH2), 108.1 (CmC), 117.9 (C-4), 118.7 (CmB),
121.6 (C-6), 124.6 (CoC), 128.8 (C-5), 128.9 (CoB), 129.2 (CpA),
J4a –5 = 10.75 Hz), 3.55 (dd, 1H, H-4b0, J4b –4a = 16.36 Hz, J4b –5
=
10.75 Hz), 5.11 (t, 1H, H-50, J5 –4a = 10.81 Hz, J5 –4b = 11.15 Hz),
7.35 (t, 1H, Hp-A, J = 7.44 Hz), 7.44 (d, 2H, Ho-C, J = 8.47 Hz), 7.53
(t, 2H, Hm-A, J = 7.44 Hz), 7.65 (d, 2H, Hm-C, J = 8.48 Hz), 7.96 (d,
2H, Ho-A, J = 7.65 Hz), 8.08 (d, 2H, Ho-B, J = 11.30 Hz), 8.32 (d, 2H,
Hm-B, J = 11.37 Hz), 8.65 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-
d6) d 39.8 (C-40), 55.2 (C-50), 118.4 (Co-A), 123.0 (Cm-B), 124.0
(C-4), 124.1 (Co-C), 124.9 (Co-B), 126.7 (Cp-A), 127.7 (C-5), 128.7
(Cm-C), 129.6 (Cm-A), 130.0 (Cp-C), 132.0 (Ci-C), 139.2 (Ci-A), 139.4
(Ci-B), 146.7 (Cp-B), 147.9 (C-3), 148.3 (C-30). MS (70 eV) m/z (%):
443 (100, M+), 305 (7), 77 (19). Anal. Calcd for C24H18ClN5O2:
C, 64.94; H, 4.09; N, 15.78. Found: C, 64.90; H, 4.19; N, 15.88.
0
0
0
0
0
129.4 (Co C), 129.7 (CmA), 130.0 (CoA), 130.8 (CiB), 132.3 (CpB),
0
133.0 (C-7), 133.5 (CiA), 138.9 (Cm C), 138.9 (CpC), 148.0 (CiC),
151.5 (C-3), 186.4 (C-8) ppm. MS (70 eV) m/z (%): 428 (11, M+),
279 (39), 149 (100), 77 (41). Anal. Calcd for C25H17ClN2O3: C,
70.01; H, 4.00; N, 6.53. Found: C, 70.11; H, 3.96; N, 6.60.
4.2. General procedure for synthesis of pyrazoles 7a–h
A mixture of chalcone 5a–h (1.0 mmol), hydrazine hydrate
(1.3 mmol) and DMF (0.2 mL) was placed into an open Pyrex-glass
vessel and subjected to microwave irradiation with magnetic stir-
ring for 5 min and with a maximum power of 300 W. Reaction pro-
gress was monitored by TLC and the precipitate formed was
filtered off and recrystallized from ethanol, affording compounds
7a–h. The N-acetyl derivatives 8/9a–h were obtained from chal-
cones 5/6a–h following the same procedure and using AcOH in-
stead of DMF.
4.2.4. 4-[3-(4-Bromophenyl)-4,5-dihydro-1H-pyrazol-5-yl]-3-(4-
nitrophenyl)-1-phenyl-1H-pyrazole (7d)
Yellow solid, 96% yield; mp: 231 °C, FTIR (KBr),
m
(cmꢀ1): 3296
(NH), 1676 (C@N), 1595 (C@C, Ar), 1502 and 1341 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.96 (dd, 1H, H-4a0, J4a –4b = 16.13 Hz,
0
0
J4a –5 = 10.13 Hz), 3.52 (dd, 1H, H-4b0, J4b –4a = 16.23 Hz, J4b –5
=
0
0
0
0
0
0
10.75 Hz), 5.08 (t, 1H, H-50, J5 –4a = 10.54 Hz, J5 –4b = 11.36 Hz),
7.33 (t, 1H, Hp-A, J = 8.48 Hz), 7.51 (t, 2H, Hm-A, J = 7.44 Hz), 7.55
(s, 2H, Ho-C), 7.58 (s, 2H, Hm-C), 7.80 (d, 2H, Ho-A, J = 7.65 Hz),
8.05 (d, 2H, Ho-B, J = 9.10 Hz), 8.30 (d, 2H, Hm-B, J = 8.89 Hz), 8.63
0
0
0
0
13
4.2.1. 3-(4-Nitrophenyl)-4-[3-(4-nitrophenyl)-4,5-dihydro-1H-
pyrazol-5-yl]-1-phenyl-1H-pyrazole (7a)
(s, 1H, H-5). C NMR (100 MHz, DMSO-d6) d 40.1 (C-40), 55.7
(C-50), 119.0 (Co-A), 121.7 (Ci-C), 124.3 (Cm-B), 124.5 (C-4), 127.2
(Cp-A), 127.9 (Co-C), 129.2 (Co-B), 129.9 (Cm-A), 130.1 (C-5), 131.9
(Cm-C), 139.6 (Ci-A), 139.9 (Ci-B), 147.2 (Cp-B), 148.4 (C-3), 149.0
(C-30), 149.2 (Cp-C). MS (70 eV) m/z (%): 487 (100, M+), 33 (31),
77 (42). Anal. Calcd for C24H18BrN5O2: C, 59.03; H, 3.72; N, 14.34.
Found: C, 59.12; H, 3.69; N, 14.44.
Yellow solid, 94% yield; mp: 242 °C, FTIR (KBr),
m
(cmꢀ1): 3300
(NH), 1675 (C@N), 1595 (C@C, Ar), 1506 and 1345 (NO2). 1H
NMR (400 MHz, DMSO-d6) d 3.07 (dd, 1H, H-4a0, J4a –4b = 16.54 Hz,
0
0
J
= 10.54 Hz), 3.63 (dd, 1H, H-4b0, J4b –4a = 16.34 Hz, J4b –5
=
0
0
0
0
4a0 –50
11.37 Hz), 5.21 (t, 1H, H-50, J5 –4a = 10.96 Hz, J5 –4b = 11.40 Hz),
7.45 (t, 1H, Hp-A, J = 7.45 Hz), 7.51 (t, 2H, Hm-A, J = 8.47 Hz), 7.84
(d, 2H, Ho-A, J = 7.86 Hz), 7.93 (d, 2H, Ho-C, J = 8.89 Hz), 8.07 (d,
2H, Ho-B, J = 8.69 Hz), 8.24 (d, 2H, Hm-B, J = 8.69 Hz), 8.33 (d, 2H,
Hm-C, J = 8.87 Hz), 8.68 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-
d6) d 39.5 (C-40), 55.6 (C-50), 118.4 (Co-A), 121.4 (Cm-C), 123.0
(Cm-B), 124.0 (C-4), 124.8 (Co-B), 125.0 (Co-C), 126.8 (Cp-A), 127.5
(C-5), 129.6 (Cm-A), 139.1 (Ci-A), 139.4 (Ci-B), 139.6 (Ci-C), 146.3
(Cp-B), 146.9 (Cp-C), 147.9 (C-3), 148.8 (C-30). MS (70 eV) m/z (%):
454 (100, M+), 426 (13), 345 (10), 77 (21). Anal. Calcd for
0
0
0
0
4.2.5. 3-(4-Nitrophenyl)-1-phenyl-4-[3-phenyl-4,5-dihydro-1H-
pyrazol-5-yl]-1H-pyrazole (7e)
Yellow solid, 90% yield; mp: 207 °C, FTIR (KBr),
m
(cmꢀ1): 3310
(NH), 1663 (C@N), 1595 (C@C, Ar), 1503 and 1337 (NO2). 1H
NMR (400 MHz, DMSO-d6) d 3.00 (dd, 1H, H-4a0, J4a –4b = 16.20 Hz,
0
0
J
= 10.45 Hz), 3.55 (dd, 1H, H-4b0, J4b –4a = 16.35 Hz, J4b –5
=
0
0
0
0
4a0 –50
11.20 Hz), 5.11 (t, 1H, H-50, J5 –4a = 10.46 Hz, J5 –4b = 11.33 Hz),
7.32 (t, 1H, Hp-A, J = 7.49 Hz), 7.49 (d, 2H, Hm-C, J = 8.15 Hz), 7.51
(t, 2H, Hm-A, J = 7.03 Hz), 7.63 (d, 2H, Ho-C, J = 7.44 Hz), 7.88 (d,
2H, Ho-A, J = 7.65 Hz), 8.06 (d, 2H, Ho-B, J = 8.49 Hz), 8.28 (d, 2H,
Hm-B, J = 8.69 Hz), 8.54 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-
d6) d 39.6 (C-40), 54.5 (C-50), 118.2 (Co-A), 120.0 (Co-C), 122.8
(Cm-B), 123.8 (C-4), 124.9 (Co-B), 126.0 (Cp-A), 127.3 (Cp-C), 127.4
(C-5), 128.2 (Cm-C), 128.9 (Cm-A), 132.8 (Ci-C), 138.9 (Ci-A), 139.2
(Ci-B), 146.6 (Cp-B), 147.6 (C-3), 148.9 (C-30). MS (70 eV) m/z (%):
409 (100, M+), 244 (19), 118 (17), 77 (15). Anal. Calcd for
0
0
0
0
C24H18N6O4: C, 63.43; H, 3.99; N, 18.49. Found: C, 63.50; H, 3.93;
N, 18.52.
4.2.2. 4-[3-(4-Fluorophenyl)-4,5-dihydro-1H-pyrazol-5-yl]-3-(4-
nitrophenyl)-1-phenyl-1H-pyrazole (7b)
Yellow solid, 89% yield; mp: 217 °C, FTIR (KBr),
m
(cmꢀ1): 3289
(NH), 1679 (C@N), 1590 (C@C, Ar), 1505 and 1346 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.99 (dd, 1H, H-4a0, J4a –4b = 16.29 Hz,
0
0

B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
4971
0
0
0
0
0
0
C24H19N5O2: C, 70.40; H, 4.68; N, 17.10. Found: C, 70.46; H, 4.60;
N, 17.20.
J4b –4a = 17.32 Hz, J4b –5 = 11.96 Hz), 5.24 (t, 1H, H-50, J5 –4a
=
0
0
5.40 Hz, J5 –4b = 12.00 Hz), 7.32 (t, 2H, Hp-A, J = 7.04 Hz), 7.47 (t,
2H, Hm-A, J = 7.48 Hz), 7.82 (d, 2H, Ho-C, J = 8.89 Hz), 7.87 (d, 2H,
Ho-A, J = 8.66 Hz), 8.03 (d, 2H, Ho-B, J = 8.74 Hz), 8.17 (d, 2H,
Hm-B, J = 8.65 Hz), 8.30 (d, 2H, Hm-C, J = 8.70 Hz), 8.47 (s, 1H,
H-5) ppm. 13C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 41.3
(C-40), 52.0 (C-50), 118.2 (Co-A), 122.8 (Cm-C), 122.9 (Cm-B), 124.0
(C-4), 126.1 (Cp-A), 127.0 (C-5), 128.6 (Co-C), 128.8 (Co-B), 128.8
(Cm-A), 138.8 (Ci-A), 139.1 (Ci-B), 139.4 (Ci-C), 146.0 (Cp-B), 146.3
(Cp-C), 148.0 (C-3), 152.3 (C-30), 165.9 (C@O) ppm. MS (70 eV)
m/z (%): 454 (100, M+), 426 (11), 407 (11), 77 (25). Anal. Calcd
for C26H20N6O5: C, 62.90; H, 4.06; N, 16.93. Found: C, 62.93; H,
4.03; N, 16.90.
4.2.6. 3-(4-Nitrophenyl-1-phenyl-4-[3-(4-methylphenyl)-4,5-
dihydro-1H-pyrazol-5-yl]-1H-pyrazole (7f)
Yellow solid, 91% yield; mp: 249 °C, FTIR (KBr),
m
(cmꢀ1): 3300
(NH), 1675 (C@N), 1592 (C@C, Ar), 1506 and 1345 (NO2). 1H
NMR (400 MHz, DMSO-d6) d 2.32 (s, 3H, H–CH3), 2.98 (m, 1H,
H-4a0), 3.48 (m, 1H, H-4b0), 5.12 (m, 1H, H-50), 7.17 (d, 2H, Ho-C,
J = 8.07 Hz), 7.34 (t, 1H, Hp-A, J = 7.50 Hz), 7.51 (t, 2H, Hm-A,
J = 7.37 Hz), 7.51 (d, 2H, Hm-C, J = 8.07 Hz), 7.87 (d, 2H, Ho-A,
J = 8.27 Hz), 8.06 (d, 2H, Ho-B, J = 8.68 Hz), 8.27 (d, 2H, Hm-B,
J = 8.68 Hz), 8.46 (s, 1H, H-5). RMN 13C (100 MHz, DMSO-d6) d
19.9 (C–CH3), 39.7 (C-40), 54.4 (C-50), 118.2 (Co-A), 122.9 (Co-C),
123.8 (Cm-B), 124.8 (C-4), 124.9 (Co-B), 126.5 (Cp-A), 127.2 (C-5),
128.4 (Ci-C), 129.0 (Cp-C), 129.6 (Cm-A), 137.0 (Cm-C), 138.9 (Ci-
A), 139.2 (Ci-B), 147.6 (Cp-B), 149.1 (C-3), 153.0 (C-30). MS (70 eV)
m/z (%): 423 (82, M+), 245 (21), 131 (61), 77 (100). Anal. Calcd
for: C25H21N5O2: C, 70.91; H, 5.00; N, 16.54. Found: C, 70.98; H,
5.10; N, 16.52.
4.2.10. 1-Acetyl-3-(4-fluorophenyl)-5-[3-(4-nitrophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8b)
Yellow solid, 90% yield; mp: 304 °C, FTIR (KBr),
m
(cmꢀ1): 1659
(C@O, C@N), 1596 (C@C, Ar), 1508 and 1347 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.30 (s, 3H, H–COCH3), 3.23 (dd, 1H,
H-4a0, J4a –4b = 17.78 Hz, J4a –5 = 5.58 Hz), 3.70 (dd, 1H, H-4b0,
0
0
0
0
J4b –4a = 17.79 Hz, J4b –5 = 11.99 Hz), 5.24 (t, 1H, H-50, J5 –4a
=
0
0
0
0
0
0
0
0
4.2.7. 4-[3-(4-Methoxyphenyl)-4,5-dihydro-1H-pyrazol-5-yl]-3-
(4-nitrophenyl)-1-phenyl-1H-pyrazole (7g)
5.38 Hz, J5 –4b = 11.58 Hz), 7.22 (m, 2H, Ho-C), 7.33 (t, 2H, Hp-A,
J = 7.24 Hz), 7.49 (t, 2H, Hm-A, J = 7.03 Hz), 7.79 (m, 2H, Hm-C),
7.85 (d, 2H, Ho-A, J = 8.48 Hz), 8.04 (d, 2H, Ho-B, J = 8.69 Hz), 8.26
(d, 2H, Hm-B, J = 8.68 Hz), 8.29 (s, 1H, H-5). 13C NMR (100 MHz,
DMSO-d6) d 20.9 (C–COCH3), 41.6 (C-40), 51.5 (C-50), 114.8 (Co-C),
118.2 (Co-A), 122.7 (Cm-B), 123.4 (C-4), 126.0 (Cp-A), 126.7 (C-5),
128.2 (Cm-C), 128.5 (Co-B), 128.7 (Cm-A), 138.8 (Ci-A), 139.1
(Ci-B), 146.7 (Cp-B), 147.1 (C-3), 152.3 (C-30), 161.5 (Cp-C), 163.9
(Ci-C), 167.1 (C@O). MS (70 eV) m/z (%): 427 (100, M+), 244 (21),
137 (21), 77 (28). Anal. Calcd for C26H20FN5O3: C, 66.52; H, 4.29;
N, 14.92. Found: C, 66.56; H, 4.26; N, 14.88.
Yellow solid, 93% yield; mp: 239 °C, FTIR (KBr),
m
(cmꢀ1): 3300
(NH), 1679 (C@N), 1590 (C@C, Ar), 1504 and 1339 (NO2) 1H NMR
(400 MHz, DMSO-d6) d 2.96 (dd, 1H, H-4a0, J4a –4b = 16.13 Hz,
0
0
J4a –5 = 10.13 Hz), 3.45 (dd, 1H, H-4b0, J4b –4a = 16.23 Hz, J4b –5
=
0
0
0
0
0
0
10.75 Hz), 3.78 (s, 3H, H–OCH3), 5.09 (t, 1H, H-50, J5 –4a = 10.54 Hz,
= 11.36 Hz), 6.92 (d, 2H, Hm-C, J = 8.89 Hz), 7.32 (t, 1H, Hp-A,
0
0
J
50 –4b0
J = 8.48 Hz), 7.49 (t, 2H, Hm-A, J = 7.44 Hz), 7.56 (d, 2H, Ho-C,
J = 8.69 Hz), 7.85 (d, 2H, Ho-A, J = 7.65 Hz), 8.04 (d, 2H, Ho-B,
J = 9.10 Hz), 8.25 (d, 2H, Hm-B, J = 8.89 Hz), 8.43 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 40.0 (C-40), 51.1 (C-50), 53.5
(C–OCH3), 113.9 (Cm-C), 118.4 (Co-A), 123.8 (Cm-B), 124.1 (Cp-A),
124.2 (C-4), 125.8 (Co-B), 126.7 (C-5), 128.9 (Cm-A), 130.6 (Co-C),
139.2 (Ci-A), 139.5 (Ci-B), 147.3 (Cp-B), 149.8 (C-3), 153.2 (C-30),
159.5 (Cp-C), 162.9 (Ci-C) ppm. MS (70 eV) m/z (%): 439 (100,
M+), 133 (14), 77 (21). Anal. Calcd for C25H21N5O3: C, 68.33; H,
4.82; N, 15.94. Found: C, 68.28; H, 4.86; N, 15.90.
4.2.11. 1-Acetyl-3-(4-chlorophenyl)-5-[3-(4-nitrophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8c)
White solid, 91% yield; mp: 311 °C, FTIR (KBr),
m
(cmꢀ1): 1659
(C@O, C@N), 1593 (C@C, Ar), 1508 and 1347 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.94 (dd, 1H, H-4a0, J4a –4b = 16.15 Hz,
0
0
J4a –5 = 5.45 Hz), 2.98 (s, 3H, H–COCH3), 3.50 (dd, 1H, H-4b0,
0
0
J4b –4a = 16.80 Hz, J4b –5 = 10.80 Hz), 5.15 (t, 1H, H-50, J5 –4a
=
0
0
0
0
0
0
0
0
4.2.8. 4-[3-(3,4-Methylenedioxyphenyl)-4,5-dihydro-1H-
pyrazol-5-yl]-3-(4-nitrophenyl)-1-phenyl-1H-pyrazole (7h)
5.49 Hz, J5 –4b = 11.54 Hz), 7.33 (t, 1H, Hp-A, J = 7.48 Hz), 7.52 (d,
2H, Ho-C, J = 8.40 Hz), 7.55 (t, 2H, Hm-A, J = 7.48 Hz), 7.70 (d, 2H,
Hm-C, J = 8.45 Hz), 7.97 (d, 2H, Ho-A, J = 7.65 Hz), 8.05 (d, 2H,
Ho-B, J = 8.69 Hz), 8.30 (d, 2H, Hm-B, J = 8.60 Hz), 8.60 (s, 1H, H-5).
13C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 39.9 (C-40), 55.4
(C-50), 118.2 (Co-A), 123.4 (Cm-B), 123.9 (C-4), 124.1 (Co-C), 125.3
(Co-B), 126.8 (Cp-A), 127.5 (C-5), 128.6 (Cm-C), 129.6 (Cp-C), 129.8
(Cm-A), 132.8 (Ci-C), 139.0 (Ci-A), 139.4 (Ci-B), 146.8 (Cp-B), 147.8
(C-3), 149.3 (C-30), 166.8 (C@O). MS (70 eV) m/z (%): 485 (100,
M+), 340 (22), 77 (41). Anal. Calcd for C26H20ClN5O3: C, 64.27;
H, 4.15; N, 14.41. Found: C, 64.24; H, 4.14; N, 14.44.
Yellow solid, 95% yield; mp: 210 °C, FTIR (KBr),
m
(cmꢀ1): 3298
(NH), 1680 (C@N), 1598 (C@C, Ar), 1505 and 1345 (NO2) 1H NMR
(400 MHz, DMSO-d6) d 2.94 (dd, 1H, H-4a0, J4a –4b = 16.33 Hz,
0
0
J4a –5 = 10.17 Hz), 3.44 (dd, 1H, H-4b0, J4b –4a = 16.34 Hz, J4b –5
=
0
0
0
0
0
0
10.75 Hz), 5.09 (t, 1H, H-50, J5 –4a = 10.54 Hz, J5 –4b = 11.54 Hz),
5.97 (s, 2H, H–CH2), 7.06 (d, 1H, Hm-C, J = 8.06 Hz), 7.19 (s, 1H,
0
0
0
0
0
Ho -C), 7.33 (t, 1H, Hp-A, J = 7.85 Hz), 7.49 (t, 2H, Hm-A,
J = 7.45 Hz), 7.84 (d, 1H, Ho-C, J = 8.07 Hz), 7.85 (d, 2H, Ho-A,
J = 7.65 Hz), 8.03 (d, 2H, Ho-B, J = 8.69 Hz), 8.25 (d, 2H, Hm-B,
J = 8.68 Hz), 8.43 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-d6) d
39.9 (C-40), 54.4 (C-50), 100.4 (C–CH2), 107.4 (Cm-C), 118.2 (Co-A),
4.2.12. 1-Acetyl-3-(4-bromophenyl)-5-[3-(4-nitrophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8d)
0
119.4 (Co-C), 122.9 (Cm-B), 123.7 (C-4), 124.9 (Cm -C), 126.0
(Cp-A), 127.3 (C-5), 128.2 (Co-B), 128.8 (Cm-A), 138.9 (Ci-A), 139.1
(Ci-B), 146.6 (Cp-B), 147.1 (Ci-C), 147.2 (Cp-C), 147.6 (C-3), 150.3
(C-30). MS (70 eV) m/z (%): 453 (100, M+), 423 (10), 406 (9), 77
(22). Anal. Calcd for C25H19N5O4: C, 66.22; H, 4.22; N, 15.44. Found:
C, 66.28; H, 4.12; N, 15.51.
White solid, 96% yield; mp: 318 °C, FTIR (KBr), m
(cmꢀ1): 1658
(C@O, C@N), 1591 (C@C, Ar), 1500 and 1339 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.98 (s, 3H, H–COCH3), 3.21 (dd, 1H,
H-4a0, J4a –4b = 17.79 Hz, J4a –5 = 5.52 Hz), 3.88 (dd, 1H, H-4b0,
0
0
0
0
J4b –4a = 17.99 Hz, J4b –5 = 11.99 Hz), 5.76 (t, 1H, H-50, J5 –4a
=
0
0
0
0
0
0
0
0
5.39 Hz, J5 –4b = 13.18 Hz), 7.31 (t, 2H, Hp-A, J = 6.83 Hz), 7.47 (t,
2H, Hm-A, J = 7.24 Hz), 7.60 (d, 2H, Ho-C, J = 8.48 Hz), 7.66 (d, 2H,
Hm-C, J = 8.68 Hz), 7.83 (d, 2H, Ho-A, J = 8.07 Hz), 8.02 (d, 2H,
Ho-B, J = 8.89 Hz), 8.24 (d, 2H, Hm-B, J = 8.68 Hz), 8.45 (s, 1H, H-
4.2.9. 1-Acetyl-3-(4-nitrophenyl)-5-[3-(4-nitrophenyl)-1-phenyl-
1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8a)
Yellow solid, 94% yield; mp: 260 °C, FTIR (KBr),
m
(cmꢀ1): 1660
(C@O, C@N), 1596 (C@C, Ar), 1502 and 1340 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.30 (s, 3H, H–COCH3), 3.06 (dd, 1H,
5). C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 41.4 (C-40),
13
51.4 (C-50), 118.2 (Co-A), 122.7 (Cm-B), 122.9 (Ci-C), 123.4 (C-4),
126.0 (Cp-A), 126.5 (C-5), 128.7 (Co-B), 128.9 (Cm-A), 130.0 (Cp-C),
H-4a0, J4a –4b = 17.15 Hz, J4a –5 = 5.62 Hz), 3.56 (dd, 1H, H-4b0,
0
0
0
0

4972
B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
130.9 (Co-C), 133.3 (Cm-C), 138.8 (Ci-A), 139.1 (Ci-B), 146.3 (Cp-B),
148.6 (C-3), 152.3 (C-30), 174.7 (C@O). MS (70 eV) m/z (%): 487
(100, M+), 228 (24), 182 (30), 77 (53). Anal. Calcd for C26H20BrN5O3:
C, 58.88; H, 3.80; N, 13.20. Found: C, 58.80; H, 3.86; N, 13.24.
(400 MHz, DMSO-d6) d 2.26 (s, 3H, H–COCH3), 3.15 (dd, 1H,
H-4a0, J4a –4b = 17.78 Hz, J4a –5 = 5.38 Hz), 3.83 (dd, 1H, H-4b0,
0
0
0
0
J4b –4a = 16.96 Hz, J4b –5 = 11.79 Hz), 5.73 (t, 1H, H-50, J5 –4a
=
0
0
0
0
0
0
0
0
5.48 Hz, J5 –4b = 11.68 Hz), 6.02 (s, 2H, H–CH2), 6.90 (d, 1H, Ho-C,
0
J = 8.06 Hz), 7.19 (s, 1H, Ho -C), 7.27 (d, 1H, Hm-C, J = 8.06 Hz),
4.2.13. 1-Acetyl-5-[3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-
yl]-3-phenyl-4,5-dihydro-1H-pyrazole (8e)
7.31 (t, 2H, Hp-A, J = 7.03 Hz), 7.47 (t, 2H, Hm-A, J = 7.24 Hz), 7.83
(d, 2H, Ho-A, J = 8.07 Hz), 8.04 (d, 2H, Ho-B, J = 8.40 Hz), 8.24 (d,
2H, Hm-B, J = 8.48 Hz), 8.25 (s, 1H, H-5) ppm. 13C NMR (100 MHz,
White solid, 91% yield; mp: 291 °C, FTIR (KBr),
m
(cmꢀ1): 1658
(C@O, C@N), 1594 (C@C, Ar), 1503 and 1339 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.29 (s, 3H, H–COCH3), 3.00 (m, 1H, H-
4a0), 3.89 (m, 1H, H-4b0), 5.13 (m, 1H, H-50), 7.33 (t, 1H, Hp-A,
J = 7.20 Hz), 7.40 (t, 1H, Hp-C, J = 7.56 Hz), 7.42 (d, 2H, Hm-C,
J = 7.62 Hz), 7.45 (t, 2H, Hm-A, J = 7.44 Hz), 7.66 (d, 2H, Ho-C,
J = 8.40 Hz), 7.84 (d, 2H, Ho-A, J = 8.31 Hz), 8.04 (d, 2H, Ho-B,
J = 8.68 Hz), 8.25 (d, 2H, Hm-B, J = 8.69 Hz), 8.45 (s, 1H, H-5). 13C
NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 41.5 (C-40), 51.4 (C-
50), 118.2 (Co-A), 119.4 (Co-C), 122.8 (Cm-B), 123.3 (Cm-C), 123.5
(C-4), 125.9 (Cp-C), 126.1 (Cp-A), 126.8 (C-5), 128.3 (Cm-A), 128.5
(Co-B), 129.3 (Ci-C), 138.8 (Ci-A), 139.1 (Ci-B), 146.6 (Cp-B), 148.6
(C-3), 153.2 (C-30), 166.9 (C@O). MS (70 eV) m/z (%): 442 (21,
M+), 397 (100), 279 (46), 77 (32). Anal. Calcd for C26H21N5O3: C,
69.17; H, 4.69; N, 15.51. Found: C, 69.18; H, 4.67; N, 15.41.
DMSO-d6) d
21.9 (C–COCH3), 41.7 (C-40), 51.4 (C-50), 100.8
(C–CH2), 107.6 (Cm-C), 118.2 (Co-A), 121.0 (Co-C), 122.7 (Cm-B),
0
123.5 (C-4), 125.1 (Cm -C), 126.0 (Cp-A), 126.7 (C-5), 128.5 (Co-B),
128.7 (Cm-A), 138.8 (Ci-A), 139.1 (Ci-B), 146.7 (Cp-B), 147.1 (Ci-C),
147.2 (Cp-C), 148.5 (C-3), 152.9 (C-30), 166.5 (C@O) ppm. MS
(70 eV) m/z (%): 496 (78, M+), 453 (100), 77 (18). Anal. Calcd for
C27H21N5O5: C, 65.45; H, 4.27; N, 14.13. Found: C, 65.55; H, 4.29;
N, 14.12.
4.2.17. 1-Acetyl-5-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-3-(4-nitrophenyl)-4,5-dihydro-1H-pyrazole (9a)
White solid, 93% yield; mp: 239 °C, FTIR (KBr),
m
(cmꢀ1): 1676
(C@O, C@N), 1597 (C@C, Ar), 1506 and 1343 (NO2). 1H NMR
(400 MHz, DMSOd6) d 2.35 (s, 3H, H–COCH3), 3.28 (dd, 1H, H-4a0,
J4a –4b = 18.89 Hz, J4a –5 = 5.38 Hz), 3.95 (dd, 1H, H-4b0, J4b –4a
=
0
0
0
0
0
0
17.99 Hz, J4b –5 = 11.99 Hz), 5.74 (t, 1H, H-50, J5–4a = 5.27 Hz,
0
0
0
4.2.14. 1-Acetyl-3-(4-methylphenyl)-5-[3-(4-nitrophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8f)
0
0
J4b –5 = 11.89 Hz), 7.30 (t, 2H, Hp-A, J = 7.44 Hz), 7.47 (t, 2H, Hm-A,
J = 8.07 Hz), 7.53 (d, 2H, Ho-B, J = 8.27 Hz), 7.82 (d, 2H, Hm-B,
J = 8.47 Hz), 7.88 (d, 2H, Ho-A, J = 8.09 Hz), 7.97 (d, 2H, Ho-C,
J = 8.89 Hz), 8.30 (d, 2H, Hm-C, J = 8.90 Hz), 8.46 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 21.9 (C–COCH3), 41.9 (C-40), 52.3
(C-50), 118.2 (Co-A), 123.2 (C-4), 123.8 (Cm-C), 126.4 (Cp-A), 126.9
(C-5), 127.6 (Co-C), 128.6 (Co-B), 129.4 (Cm-A), 129.8 (Cm-B),
131.7 (Cp-B), 132.8 (Ci-B), 139.2 (Ci-A), 147.9 (Cp-C), 148.3 (C-3),
152.3 (Ci-C), 152.5 (C-30), 168.0 (C@O) ppm. MS (70 eV) m/z (%):
485 (61, M+), 442 (100), 294 (81), 279 (65), 77 (42). Anal. Calcd
for C26H20ClN5O3: C, 64.27; H, 4.15; N, 14.41. Found: C, 64.20; H,
4.22; N, 14.50
White solid, 90% yield; mp: 296 °C, FTIR (KBr),
m
(cmꢀ1): 1658
(C@O, C@N), 1594 (C@C, Ar), 1505 and 1340 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.28 (s, 3H, H–COCH3), 2.34 (s, 3H, H–
CH3), 3.19 (m, 1H, H-4a0), 3.86 (m, 1H, H-4b0), 5.76 (m, 1H, H-50),
7.24 (d, 2H, Ho-C, J = 8.15 Hz), 7.32 (t, 2H, Hp-A, J = 7.23 Hz), 7.40
(d, 2H, Hm-C, J = 8.15 Hz), 7.46 (t, 2H, Hm-A, J = 7.56 Hz), 7.83 (d,
2H, Ho-A, J = 8.07 Hz), 8.03 (d, 2H, Ho-B, J = 8.69 Hz), 8.24 (d, 2H,
Hm-B, J = 8.68 Hz), 8.25 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-
d6) d 20.1 (C–CH3), 20.9 (C–COCH3), 41.6 (C-40), 51.3 (C-50), 118.2
(Co-A), 122.7 (Cm-B), 123.5 (C-4), 125.9 (Co-C), 126.0 (Cp-A), 126.7
(C-5), 127.3 (Cm-C), 128.1 (Ci-C), 128.3 (Cp-C), 128.5 (Cm-A), 128.7
(Co-B), 138.8 (Ci-A), 139.3 (Ci-B), 146.7 (Cp-B), 147.1 (C-3), 153.2
(C-30), 167.1 (C@O). MS (70 eV) m/z (%): 465 (55, M+), 423 (100),
77 (33). Anal. Calcd for: C27H23N5O3: C, 69.66; H, 4.98; N, 15.04.
Found: C, 69.76; H, 4.94; N, 15.14.
4.2.18. 1-Acetyl-5-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (9b)
White solid, 90% yield; mp: 234 °C, FTIR (KBr),
m
(cmꢀ1): 1652
(C@O, C@N), 1600 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d 2.31
(s, 3H, H–COCH3), 3.23 (dd, 1H, H-4a0, J4a –4b = 17.89 Hz, J4a –5
=
0
0
0
0
4.2.15. 1-Acetyl-3-(4-methoxyphenyl)-5-[3-(4-nitrophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (8g)
5.38 Hz), 3.89 (dd, 1H, H-4b0, J4b –4a = 17.79 Hz, J4b –5 = 12.00 Hz),
0
0
0
0
m
(cmꢀ1): 1654
5.69 (t, 1H, H-50, J5–4a = 5.17 Hz, J4b –5 = 11.89 Hz), 7.28 (t, 2H,
Hp-A, J = 7.44 Hz), 7.46 (t, 2H, Hm-A, J = 8.48 Hz), 7.53 (d, 2H,
Ho-B, J = 8.68 Hz), 7.83 (m, 2H, Ho-C), 7.85 (d, 2H, Hm-B,
J = 8.67 Hz), 7.89 (d, 2H, Ho-A, J = 8.68 Hz), 8.30 (m, 2H, Hm-C),
8.41 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6) d 21.8
(C–COCH3), 42.2 (C-40), 51.6 (C-50), 115.7 (Cm-C), 118.2 (Co-A),
123.5 (C-4), 126.3 (Cp-A), 126.8 (C-5), 128.6 (Co-B), 128.9 (Co-C),
129.4 (Cm-A), 129.7 (Cm-B), 131.7 (Cp-B), 132.7 (Ci-B), 139.2
(Ci-A), 148.2 (C-3), 153.0 (C-30), 161.9 (Ci-C), 164.4 (Cp-C), 167.6
(C@O) ppm. MS (70 eV) m/z (%): 458 (57, M+), 415 (100), 279
(42), 77 (33). Anal. Calcd for C26H20ClFN4O: C, 68.05; H, 4.39; N,
12.21. Found: C, 68.15; H, 4.38; N, 12.31.
0
0
0
White solid, 93% yield; mp: 293 °C, FTIR (KBr),
(C@O, C@N), 1598 (C@C, Ar), 1503 and 1338 (NO2). 1H NMR
(400 MHz, DMSO-d6) d 2.27 (s, 3H, H–COCH3), 3.28 (dd, 1H, H-
4a0, J4a –4b = 17.71 Hz, J4a –5 = 5.50 Hz), 3.80 (s, 3H, H–OCH3), 3.85
0
0
0
0
(dd, 1H, H-4b0, J4b –4a = 18.20 Hz, J4b –5 = 13.44 Hz), 5.73 (t, 1H, H-
0
0
0
0
50, J5–4a = 5.48 Hz, J4b –5 = 13.02 Hz), 6.97 (d, 2H, Hm-C,
J = 8.68 Hz), 7.31 (t, 2H, Hp-A, J = 7.86 Hz), 7.47 (t, 2H, Hm-A,
J = 8.69 Hz), 7.66 (d, 2H, Ho-C, J = 8.89 Hz), 7.83 (d, 2H, Ho-A,
J = 7.65 Hz), 8.03 (d, 2H, Ho-B, J = 8.98 Hz), 8.24 (d, 2H, Hm-B,
J = 9.72 Hz), 8.25 (s, 1H, H-5). 13C NMR (100 MHz, DMSO-d6) d
20.9 (C–COCH3), 41.6 (C-40), 51.2 (C-50), 54.8 (C–OCH3), 113.8
(Cm-C), 118.2 (Co-A), 122.7 (Cm-B), 123.5 (Ci-C), 123.6 (C-4), 125.9
(Cp-A), 126.8 (C-5), 127.5 (Co-C), 128.5 (Co-B), 128.7 (Cm-A), 138.8
(Ci-A), 139.1 (Ci-B), 146.7 (Cp-B), 147.1 (C-3), 152.6 (C-30), 160.6
(Cp-C), 166.9 (C@O). MS (70 eV) m/z (%): 481 (53, M+), 439 (100),
133 (15), 77 (17). Anal. Calcd for C27H23N5O4: C, 67.35; H, 4.81;
N, 14.54. Found: C, 67.30; H, 4.88; N, 14.56.
0
0
0
4.2.19. 1-Acetyl-3-(chlorophenyl)-5-[3-(4-chlorophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (9c)
White solid, 93% yield; mp: 261 °C, FTIR (KBr),
m
(cmꢀ1): 1648
(C@O, C@N), 1601 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d 2.27
(s, 3H, H–COCH3), 3.16 (dd, 1H, H-4a0, J4a –4b = 17.78 Hz, J4a –5
=
0
0
0
0
5.58 Hz), 3.82 (dd, 1H, H-4b0, J4b –4a = 17.78 Hz, J4b –5 = 11.78 Hz),
0
0
0
0
4.2.16. 1-Acetyl-3-(3,4-methylenedioxyphenyl)-5-[3-(4-
nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-
pyrazole (8h)
5.69 (t, 1H, H-50, J5–4a = 5.58 Hz, J4b –5 = 11.78 Hz), 7.27 (t, 2H,
Hp-A, J = 7.44 Hz), 7.44 (m, 2H, Hm-A), 7.48 (d, 2H, Ho-B,
J = 9.10 Hz), 7.81 (d, 2H, Ho-A, J = 8.69 Hz), 7.72 (d, 2H, Hm-C,
J = 9.10 Hz), 7.74 (d, 2H, Hm-B, J = 8.89 Hz), 8.20 (s, 1H, H-5) ppm.
0
0
0
White solid, 90% yield; mp: 285 °C, FTIR (KBr),
(C@O, C@N), 1597 (C@C, Ar), 1508 and 1349 (NO2). 1H NMR
m
(cmꢀ1): 1655

B. Insuasty et al. / Bioorg. Med. Chem. 18 (2010) 4965–4974
4973
13C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 41.4 (C-40), 51.6
(C-50), 118.0 (Co-A), 122.6 (C-4), 126.1 (Cp-A), 126.6 (C-5), 127.7
(Co-C), 128.0 (Cm-C), 128.6 (Co-B), 129.2 (Cm-B), 129.3 (Cp-C),
129.6 (Cm-A), 129.8 (Ci-C), 131.4 (Cp-B), 132.3 (Ci-B), 138.9 (Ci-A),
148.1 (C-3), 152.1 (C-30), 167.1 (C@O) ppm. MS (70 eV) m/z (%):
474 (63, M+), 431 (100), 279 (62), 77 (95). Anal. Calcd for
(s, 3H, H–COCH3), 3.13 (m, 1H, H-4a0), 3.80 (m, 1H, H-4b0), 3.92
(s, 3H, H–OCH3), 5.66 (m, 1H, H-50), 6.98 (d, 2H, Hm-C,
J = 10.96 Hz), 7.23 (t, 2H, Hp-A, J = 7.23 Hz), 7.43 (d, 2H, Ho-C,
J = 10.96 Hz), 7.50 (d, 2H, Ho-B, J = 10.70 Hz), 7.64 (m, 2H, Hm-A),
7.76 (d, 2H, Hm-B, J = 10.75 Hz), 7.82 (d, 2H, Ho-A, J = 6.89 Hz),
8.17 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6) d 20.9 (C–
COCH3), 41.6 (C-40), 51.3 (C-50), 55.0 (C–OCH3), 113.7 (Cm-C),
118.0 (Co-A), 122.9 (Cp-C), 123.6 (C-4), 125.6 (Cp-A), 126.0 (C-5),
127.5 (Co-C), 128.6 (Co-B), 129.2 (Cm-B), 130.2 (Cm-A), 131.5 (Cp-
B), 132.3 (Ci-B), 138.9 (Ci-A), 148.1 (C-3), 152.9 (C-30), 160.6 (Ci-
C), 166.8 (C@O) ppm. MS (70 eV) m/z (%): 470 (100, M+), 364
(52), 279 (60), 77 (80). Anal. Calcd for C27H23ClN4O2: C, 68.86; H,
4.92; N, 11.90. Found: C, 68.80; H, 4.96; N, 11.90.
C26H20Cl2N4O: C, 65.69; H, 4.24; N, 11.79. Found: C, 65.71; H,
4.28; N, 11.84.
4.2.20. 1-Acetyl-3-(4-bromophenyl)-5-[3-(4-chlorophenyl)-1-
phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-pyrazole (9d)
White solid, 96% yield; mp: 259 °C, FTIR (KBr),
m
(cmꢀ1): 1646
(C@O, C@N), 1595 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d 2.27
(s, 3H, H–COCH3), 3.16 (m, 1H, H-4a0), 3.82 (m, 1H, H-4b0), 5.69
(m, 1H, H-50), 7.28 (t, 2H, Hp-A, J = 6.85 Hz), 7.44 (d, 2H, Ho-B,
J = 8.48 Hz), 7.49 (t, 2H, Hm-A, J = 8.48 Hz), 7.60 (d, 2H, Ho-C,
J = 10.54 Hz), 7.64 (d, 2H, Hm-C, J = 8.70 Hz), 7.73 (d, 2H, Hm-B,
J = 8.70 Hz), 7.79 (d, 2H, Ho-A, J = 8.07 Hz), 8.19 (s, 1H, H-5) ppm.
13C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3), 41.3 (C-40), 51.9
(C-50), 118.0 (Co-A), 122.3 (Ci-C), 122.7 (C-4), 125.6 (Cp-A), 126.1
(C-5), 127.2 (Cm-A), 127.7 (Cm-C), 128.9 (Co-B), 129.2 (Cm-B),
129.4 (Cp-C), 130.9 (Co-C), 131.4 (Cp-B), 132.3 (Ci-B), 138.9 (Ci-A),
148.1 (C-3), 152.2 (C-30), 167.1 (C@O) ppm. MS (70 eV) m/z (%):
520 (64, M+), 477 (100), 279 (64), 77 (37). Anal. Calcd for
4.2.24. 1-Acetyl-3-(3,4-methylenedioxyphenyl)-5-[3-(4-
chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-4,5-dihydro-1H-
pyrazole (9h)
White solid, 89% yield; mp: 225 °C, FTIR (KBr),
m
(cmꢀ1): 1649
(C@O, C@N), 1599 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d 2.29
0
0
(s, 3H, H–COCH3), 3.17 (m, 1H, H-4a ), 3.83 (m, 1H, H-4b ), 5.65
(m, 1H, H-50), 6.09 (s, 2H, H–CH2), 6.68 (d, 2H, Ho-C, J = 7.85 Hz),
7.21 (d, 2H, Hm-C, J = 7.44 Hz), 7.30 (t, 2H, Hp-A, J = 7.03 Hz), 7.45
0
(s, 1H, Ho -C), 7.47 (t, 2H, Hm-A, J = 7.24 Hz), 7.53 (d, 2H, Ho-B,
J = 7.86 Hz), 7.82 (d, 2H, Hm-B, J = 7.86 Hz), 7.88 (d, 2H, Ho-A,
J = 7.65 Hz), 8.37 (s, 1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6)
d 20.9 (C–COCH3), 41.3 (C-40), 51.9 (C-50), 101.5 (C–CH2), 108.3
(Co-C), 118.2 (Co-A), 121.8 (Cm-C), 123.6 (C-4), 126.3 (Cp-A), 126.7
(C-5), 128.6 (Co-B), 129.4 (Cm-A), 129.7 (Cm-B), 131.7 (Cp-B),
C26H20BrClN4O: C, 60.07; H, 3.88; N, 10.78. Found: C, 60.14; H,
3.92; N, 10.70.
4.2.21. 1-Acetyl-5-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-3-phenyl-4,5-dihydro-1H-pyrazole (9e)
0
132.7 (Ci-B), 139.2 (Ci-A), 145.3 (Cm -C), 147.7 (Ci-C), 148.2 (C-3),
White solid, 90% yield; mp: 249 °C, FTIR (KBr),
m
(cmꢀ1): 1651
149.0 (Cp-C), 153.6 (C-30), 167.5 (C@O) ppm. MS (70 eV) m/z (%):
(C@O, C@N), 1597 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d 2.27
(s, 3H, H–COCH3), 3.17 (m, 1H, H-4a0), 3.83 (m, 1H, H-4b0), 5.69
(m, 1H, H-50), 7.27 (m, 2H, Hp-A), 7.44 (m, 2H, Hm-A), 7.44 (m,
1H, Hp-C), 7.44 (m, 2H, Ho-B), 7.64 (m, 2H, Hm-C), 7.73 (m, 2H,
Ho-C), 7.73 (m, 2H, Hm-B), 7.80 (d, 2H, Ho-A, J = 8.15 Hz), 8.19 (s,
1H, H-5) ppm. 13C NMR (100 MHz, DMSO-d6) d 20.9 (C–COCH3),
41.5 (C-40), 51.4 (C-50), 118.0 (Co-A), 122.8 (Cm-B), 122.9 (C-4),
125.6 (Co-C), 125.8 (Co-B), 126.1 (Cp-A), 127.7 (C-5), 128.6 (Cp-C),
129.2 (Cm-C), 129.3 (Cm-A), 130.9 (Ci-C), 131.5 (Cp-B), 132.3
(Ci-B), 138.9 (Ci-A), 148.1 (C-3), 153.1 (C-30), 167.1 (C@O) ppm.
MS (70 eV) m/z (%): 440 (59, M+), 397 (100), 279 (64), 104 (39),
77 (52). Anal. Calcd for C26H21ClN4O: C, 70.82; H, 4.80; N, 12.71.
Found: C, 70.80; H, 4.70; N, 12.64.
484 (86, M+), 442 (100), 294 (25), 77 (20). Anal. Calcd for
C27H21ClN4O3: C, 66.87; H, 4.36; N, 11.55. Found: C, 66.80; H,
4.36; N, 11.58.
Acknowledgments
The authors wish to credit The Developmental Therapeutics Pro-
gram (DTP) of the National Cancer Institute of the United States (US)
for performing the screening of compounds. This work was sup-
ported financially by Colciencias, Universidad del Valle, Consejería
de Innovación, Ciencia y Empresa (Junta de Andalucía, Spain) and
The Universidad de Jaén. Authors thank ‘Servicios Técnicos de Inves-
tigación de la Universidad de Jaén’ and the staff for data collection.
4.2.22. 1-Acetyl-5-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-3-(4-methylphenyl)-4,5-dihydro-1H-pyrazole (9f)
References and notes
White solid, 93% yield; mp: 231 °C, FTIR (KBr),
m
(cmꢀ1): 1661
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(C@O, C@N), 1597 (C@C, Ar). 1H NMR (400 MHz, DMSO-d6) d (s,
3H, H–COCH3), 2.30 (s, 3H, H–CH3), 3.22 (m, 1H, H-4a0), 3.80 (m,
1H, H-4b0), 5.82 (m, 1H, H-50), 7.28 (d, 2H, Ho-C, J = 8.22 Hz), 7.33
(t, 2H, Hp-A, J = 7.33 Hz), 7.45 (d, 2H, Hm-C, J = 8.21 Hz), 7.46 (t,
2H, Hm-A, J = 7.56 Hz), 7.56 (d, 2H, Ho-B, J = 7.69 Hz), 7.68 (d, 2H,
Hm-B, J = 7.67 Hz), 7.85 (d, 2H, Ho-A, J = 8.17 Hz), 8.42 (s, 1H, H-5)
ppm. 13C NMR (100 MHz, DMSO-d6) d 20.9 (C–CH3), 21.2 (C–
COCH3), 41.6 (C-40), 52.3 (C-50), 118.4 (Co-A), 122.8 (Cm-B), 124.0
(C-4), 125.5 (Co-C), 126.0 (Cp-A), 126.8 (C-5), 127.9 (Cm-C), 128.0
(Ci-C), 129.0 (Cp-C), 129.5 (Cm-A), 129.6 (Co-B), 139.1 (Ci-A), 139.3
(Ci-B), 147.2 (C-3), 147.6 (Cp-B), 153.3 (C-30), 168.1 (C@O) ppm.
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