Cascade 1,3-dipolar Cycloaddition/SO2 extrusion approach for the rapid synthesis of tetraaryl-substituted pyrazoles with Aggregation Induced Emission characteristics

Article abstract of DOI:10.1016/j.tet.2020.131568

A highly efficient strategy was developed for the straightforward synthesis of tetraaryl-substituted pyrazoles. The cascade process consists of a regioselective 1,3-dipolar cycloaddition of benzosultam-3-ylidenes with nitrile imines and a subsequent elimination of SO₂. The title compounds exhibit high fluorescence quantum yields and Aggregation Induced Emission (AIE) characteristics.

Full text of DOI:10.1016/j.tet.2020.131568

Tetrahedron 76 (2020) 131568
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cascade 1,3-dipolar Cycloaddition/SO2 extrusion approach for the
rapid synthesis of tetraaryl-substituted pyrazoles with Aggregation
Induced Emission characteristics
Guorui Cao, Xiang Liu, Long Wang, Yanshun Li, Dawei Teng*
State Key Laboratory Base of Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042,
China
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient strategy was developed for the straightforward synthesis of tetraaryl-substituted
pyrazoles. The cascade process consists of a regioselective 1,3-dipolar cycloaddition of benzosultam-3-
ylidenes with nitrile imines and a subsequent elimination of SO2. The title compounds exhibit high
fluorescence quantum yields and Aggregation Induced Emission (AIE) characteristics.
© 2020 Elsevier Ltd. All rights reserved.
Received 5 July 2020
Received in revised form
28 August 2020
Accepted 31 August 2020
Available online 3 September 2020
Keywords:
Tetraaryl-substituted pyrazoles
1,3-Dipolar cycloaddition
Benzosultam-3-ylidenes
Regioselective
Aggregation induced emission
1. Introduction
substituted pyrazoles in three steps involving cyclocondensation
of dibenzoylmethane with aryl hydrazines, bromination with N-
Pyrazoles represent an important class of five-membered het-
erocycles composed of three carbons and two nitrogens in adjacent
positions. They exist in natural products [1] (L-a-Amino-b-(pyr-
bromosuccinimide and Suzuki coupling with arylboronic acids
(Scheme 1, eq 1). Foroumadi reported a novel condensation method
between benzoin and phenyl hydrazine followed by cyclization
with aryl aldehydes to afford corresponding tetraaryl-substituted
pyrazoles as promising 15-lipoxygenase inhibitors [9c]. Fuse’s
group accomplished the tetraaryl-substituted pyrazole synthesis
through a sequential cross-coupling approach based on 3-iodo-1H-
pyrazole [9d] and unsubstituted pyrazole [9e] respectively (Scheme
1, eq 2). These approaches generally suffer from several additional
drawbacks, such as multistep synthetic operations, limited sub-
strate scope and the use of transition metal catalyst. Therefore,
developing a new protocol for the synthesis of tetraaryl-substituted
pyrazoles with mild conditions, a short synthetic route and broad
substrate applicability is always highly desirable.
azolyl-N)-propanoic acid, Pyrazofurin, Formycin, Fluviol A, etc),
commercial drugs [2] (rimonabant and celebrex) and display a wide
range of remarkable pharmacologicaldanti-hyperglycemic, anal-
gesic, antipyretic, anti-inflammatory, antibacterial, hypoglycemic
and sedative-hypnoticdactivities [3]. Furthermore, these com-
pounds show intriguing photophysical properties as optical
brighteners [4], UV stabilizers [5], fluorescence sensors [6] and
OLED materials (Fig. 1). [7].
Although many synthetic strategies have been reported for the
construction of substituted pyrazole derivatives [8], the methods
devoted to tetraaryl-substituted pyrazoles are still limited [9]. In
recent years, the most frequently used methods include the
condensation of dicarbonyl compounds with substituted hydra-
zines and stepwise arylation of the pyrazole scaffold. Peruncher-
alathan [9a] and Venkatasubbaiah [9b] synthesized tetraaryl-
The 1,3-dipolar cycloaddition reaction is among the most
prominent reactions to build five-membered heterocycles with
good regio-, diastereo-, and enantioselectivity in a single step [10].
Benzosultam-3-ylidenes have been reported as highly efficient
dipolarophiles to react with azomethine ylide [11,12] and nitrones
[13]
leading
to
spiropyrrolidinyl-benzosultams
and
spiroisoxazolidinyl-benzosultams respectively. In our previous
* Corresponding author.
E-mail address: dteng@qust.edu.cn (D. Teng).
https://doi.org/10.1016/j.tet.2020.131568
0040-4020/© 2020 Elsevier Ltd. All rights reserved.

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
1e2). Furthermore, polar and aprotic solvents could also afford 3aa
in slightly lower yields (entries 3e4). It is interesting to see that the
cascade reactions are accelerated in polar and protic solvents
because of solvent hydrogen bonding [17] and that methanol
proved to be the best solvent (entries 5e6). Several bases were
tested in methanol (entries 7e10) and it was shown that K2CO3
gave the best result, whereas when using pyridine as a single base,
none of the desired product was detected in the reaction mixture.
When the reactions were performed at lower temperature (0 ꢀC)
and higher temperature (50 ꢀC), the yield of tetraaryl-substituted
pyrazole was slightly decreased (entries 11e12). Use of K2CO3 as
base at 25 ꢀC provided tetraarylpyrazole in 86% yield, and as such
was established as the optimal protocol for this 1,3-dipolar cyclo-
addition/SO2 extrusion study.
Fig. 1. Some pyrazoles and derivatives with biological and optical properties.
Having established the optimized reaction conditions, we tested
a variety of nitrile imine precursors and benzosultam-3-ylidenes to
probe the versatility of our newly developed 1,3-dipolar cycload-
dition/SO2 extrusion approach to tetraaryl-substituted pyrazoles
(Table 2). In reactions of 3-phenylidenebenzosultam 1a, hydrazo-
noyl chlorides 2a-b derived from electron-rich hydrazines are more
reactive than hydrazonoyl chlorides 2c-d derived from electron-
poor analogues and afford tetraaryl-substituted pyrazoles in bet-
ter yields. The electronic effect of C-substituted-phenyl imines from
2e-h on the activity of 1,3-dipolar cycloaddition/SO2 extrusion was
then investigated. The hydrazonoyl chlorides 2e-f bearing electron-
donating (methyl, methoxyl) substituents on the benzoyl chloride
moiety gave the corresponding products in better yields than
hydrazonoyl chlorides 2g-h bearing electron-withdrawing (chloro,
fluoro) substituents. Hydrazonyl chlorides 2i containing electron-
donating substituent both on the benzoyl chloride moiety and
the phenylhydrazone moiety participated in the reaction success-
fully to afford the desired product 3ai in excellent yields.
As shown in Table 2, it was found that a variety of 3-(para-
substituted-phenylidene)-benzosultams 1a-f underwent smooth
cycloaddition/SO2 extrusion with C-phenyl-N-phenyl nitrile imine
precursor 2j and provided tetraaryl-substituted pyrazoles 3aj-3fj in
good yields (80e85%). The structural assignment of the tetraaryl-
substituted pyrazole 3bj was based on X-ray analysis [18], and
the regiochemistry of other products was assigned by analogy.
Benzosultam-3-ylidenes containing ortho-substituted phenyl (1g,
1h), meta-substituted phenyl (1i) and heteroaryl moiety (1j) were
also suitable substrates for this reaction and gave products 3gj and
3ha-3ja. It is particularly worth noting that pyrazoles containing a
2-aminophenyl group (3lj, 3la) were also smoothly prepared in
moderate yields. Hydrazonyl chlorides containing heteroaryl moi-
ety (2k) gave the tetraaryl-substituted pyrazoles 3hk in moderate
yield. However, hydrazonoyl chlorides 2l-m bearing strong
electron-withdrawing (nitro, trifluoromethyl) substituents can not
afford corresponding tetraaryl-substituted pyrazoles.
Scheme 1. Representative synthetic approach to tetraaryl-substituted pyrazoles.
research, we found that benzosultam-3-ylidenes, having exocyclic
double bond and sulfamoyl group, are of special interest in the
synthesis of five-membered heteroaromatic compounds as they
can be easily transformed into sprio-frameworks and further
extrude SO2 to afford trisubstituted isoxazoles [14]. With respect to
the reported interesting electronic properties of polysubstituted
pyrazoles as potential intense blue light emitters [15], the
continuing quest for tailor-made functional tetraaryl-substituted
pyrazoles by highly efficient methods, and as part of our previous
efforts on exploring important heterocyclic compounds, we herein
wish to report a cascade 1,3-dipolar cycloaddition/SO2 extrusion
approach using benzosultam-3-ylidenes, which should facilitate
the synthesis of tetraaryl-substituted pyrazoles (Scheme 1, eq 3).
Furthermore, the photophysical properties of obtained compounds
and their Aggregation Induced Emission (AIE) behaviour are
investigated.
2. Results and discussion
Although tetraaryl-substituted pyrazoles have been reported to
show an important enhancement in their light emission upon ag-
gregation [9a], our interest is in the potential improvement of
electronic properties of tetraaryl-substituted pyrazoles containing
a 2-methylamino-phenyl group. The photophysical properties of
tetraaryl-substituted pyrazoles 3 were examined in THF solution.
The electronic absorption spectra of the tetraaryl-substituted pyr-
azoles display absorption maxima (lmax,abs) between 233 and
293 nm with molar extinction coefficients ranging from 9400 to
118,700 l molꢁ1 cmꢁ1 (see the Supporting Information). All inves-
tigated representatives exhibited strong blue luminescence in THF
with emission maxima (lmax,em) between 415 and 429 nm with
large Stokes shifts ranging from 10,400 to 14,000 cmꢁ1. Five
tetraaryl-substituted pyrazoles (3aa, 3ah, 3aj, 3ej, 3fj) reveal high
Initially, the reaction of isolable (Z)-3-benzylidene-1-methyl-
benzosultam 1a [11] and nitrile imine precursor 2a [16] were used
as a model to optimize reaction conditions including the solvents,
bases and reaction temperature as reported in Table 1. In all of the
reactions examined, HRMS and 1H NMR spectroscopy analyses on
the isolated product revealed a proposed aromatization of the
initially formed spirobenzosultam-pyrazoline to
a tetraaryl-
substituted pyrazole. To our delight, a highly regioselective con-
version was observed, and a single product 3aa was obtained
exclusively. The effect of six different solvents was first investigated
using triethylamine as the base at 25 ꢀC (entries 1e6). Among them
were the apolar and aprotic dichloromethane and toluene, in which
the desired 1,3-dipolar cycloaddition/SO2 extrusion are generally
performed leading to tetraaryl-substituted pyrazole 3aa (entries
fluorescence efficiency with fluorescence quantum yields
Фf
ranging between 0.62 and 0.83. It should be noted that the pyrazole
2

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
Table 1
Optimization of the 1,3-dipolar cycloaddition/SO2 extrusion strategy.a.
Entry
Solvent
Base
Temp (◦C)
Time(h)
Yieldb(%)
1
2
3
4
5
6
7
8
DCM
Toluene
THF
DMF
MeOH
EtOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Pyridine
DBU
KOH
25
25
25
25
25
25
25
25
25
25
0
5
5
5
5
0.5
0.5
10
2
0.5
0.5
0.5
0.5
73
71
66
68
81
80
NR
74
84
86
83
84
9
10
11
12
K2CO3
K2CO3
K2CO3
50
a
Reaction condition: (Z)-alkene 1a (0.2 mmol), hydrazonoyl chloride 2a (0.3 mmol), base (0.5 mmol), solvent (1 mL).
b
Isolated yields. The other regionisomer was not detected by1H NMR.
3fj exerted higher fluorescence quantum yield
compared with other tetraaryl-substituted pyrazoles reported
before [9a,9e].
The synthesized tetraaryl-substituted pyrazoles are soluble in
THF, but insoluble in water. When excited at 270 nm, the dilute
solution of 3ae in THF shows a weak emission band at 421 nm with
(
Ф
f
¼
0.83)
a gram-scale synthesis was carried out under the optimized con-
ditions. Gratifyingly, the desired tetraaryl-substituted pyrazole
derivative 3aa could be obtained in 78% yield (1.2 g, Scheme 4).
Basis on the experimental results above and the previous
studies of cycloaddition reactions involving hydrazonoyl chloride
[20], we proposed the following plausible mechanism for this
cascade 1,3-dipolar cycloaddition/SO2 extrusion reaction, as shown
in Scheme 5. In the presence of K2CO3, the nitrile imine was
generated from the dehydrochlorination of hydrazonyl chloride 2a
with two zwitterionic resonance forms [21]. In keeping with a
HOMOdipolar-LUMOdipolarophile interaction, allenic 6b proceeds a
regioselective 1,3-dipolar reaction with 3-phenylidenebenzosultam
1a to give spiro [pyrazolin-3,30-benzosultam] intermediate 7.
Extrusion of SO2 from intermediate 7 generates azaxylylene 8,
which undergoes [1,5]-sigmatropic hydrogen shift [22] to furnish
the aromatic tetraaryl-substituted pyrazole 3aa.
fluorescence quantum yield (Фf) of 0.38. Excitingly, a sustainable
increase in fluorescence emission intensity was observed when the
water fraction was increased from 0% to 70% in the H2O-THF
mixture (Fig. 2). The quantum yields of the aggregates of tetraaryl-
substituted pyrazole 3ae at 70: 30 (H2O: THF) composition
increased to 0.93 which is about 2.5 fold higher than that in pure
THF.
Owing to the possibility of benzosultam-3-ylidenes 1 undergo-
ing E-Z isomerisation under the reaction conditions, we then
turned our attention to test the reactivity of E-alkene 1a with nitrile
imine precursor 2j in order to validate its applicability (Scheme 2).
Importantly, (E)-1a was also suitable for this reaction delivering
tetraaryl-substituted pyrazoles 3aj in 80% yield. Encouraged by this
result, we chose a mixture of E-Z isomers 1a (mole ratio 1:1) as the
substrate and performed the reaction under the optimized condi-
tions to give product 3aj in 83% yield. In addition, we have extended
the scope of the reaction to the formation of 1,3,5-triaryl-4-alkyl-
pyrazoles 3mj-3nj by using 3-alkylene-benzosultams 1m-1n.
To further demonstrate the utility of this cascade strategy in
organic synthesis, we carried out the 1,3-dipolar cycloaddition/SO2
extrusion of ethyl 2-(benzosultam-3-ylidene)-acetate (Z)-1o with
hydrazonyl chloride 2k (Scheme 3a). Compared with previous
method [19], the reaction is highly regioselective and only one
tetraaryl-substituted pyrazole derivative 3ok was isolated. After
cyclization under basic conditions, the pyrazolo [ [4,5]-c]quinoline-
4-one 4ok, which was found to exhibit significant inhibitory to-
wards [3H]flunitrazepam binding from bovine brain membranes
[19], was obtained in 84% yield (70% total isolated yield two steps
from 1o). Thus, the procedure reported herein could provide reli-
able methodology for testing the relationship between structure
and pharmacological activity of pyrazolo [ [4] [3-c]]quinolin-4-
ones. Finally, by treating compound 3gj in Buchwald-Hartwig re-
action conditions, dibenzo [b,f]pyrazolo [3,4-d]azepine 5gj can be
obtained in 88% yield (Scheme 3b).
3. Conclusions
In summary, we have developed an efficient protocol for the
construction of tetraaryl-substituted pyrazoles by a cascade 1,3-
dipolar cycloaddition/SO2 extrusion of benzosultam-3-ylidenes
with nitrile imines. Compared with traditional syntheses, our
new method has the advantages of step economy, milder reaction
conditions, transition-metal free process, and higher overall yields.
This approach was successfully applied in the convenient synthesis
of a potent inhibitor of benzodiazepine (BZD) receptor and tetra-
cyclic dibenzo [b,f]pyrazolo [3,4-d]azepine derivative. In addition,
the absorption and emission spectra of the new tetraaryl-
substituted pyrazoles (containing 2-methylamino-phenyl group)
were measured. Compound 3fj showed high fluorescence quantum
yields (Фf ¼ 0.83). Tetraaryl-substituted pyrazole 3ae was demon-
strated to be AIE active when aggregated. We expect that these
results will have great impact on the drug discovery and on the
development of tailor-made luminescent materials.
4. Experimental section
4.1. General
In order to further test the scalability of this cascade procedure,
All reagents were purchased from commercial suppliers and
3

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
Table 2
Substrate scope of tetraaryl-substituted pyrazoles.a.
a
Reaction conditions: (Z)-1 (0.2 mmol), 2 (0.3 mmol) and potassium carbonate (0.5 mmol) in
methanol (1 mL) were stirred at room temperature for 0.5 h bIsolated yield.
used without purification. All reactions were monitored by TLC.
Chromatography refers to open column chromatography on silica
gel (100e200 mesh). Melting points were uncorrected values. 1H
NMR spectra were recorded at 500 MHz and 13C NMR spectra were
recorded at 125 MHz by using a Bruker Avance 500 M spectrometer
and referenced internally to solvent signals. Mass spectra were
performed on an Ultima Global spectrometer with an ESI source.
The X-ray single-crystal diffraction was performed on Saturn 724þ
instrument. The absorbance spectra were recorded on a Hitachi U-
4100 spectrometer. The fluorescence spectra were recorded on a
Hitachi F-4600 Fluorescence Spectrometer. The fluorescence
spectra were corrected for the instrumental response.
4

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
Fig. 2. (a) Fluorescence spectra of 3ae (10ꢁ5 M) in water/THF mixtures with increasing
amounts of water (fw ¼ 0e90 vol%). (b) The changes in the fluorescence emission
relativeintensities of 3ae with the water contents in the water/THF mixture vs intensity
in pure THF.
Scheme 5. Plausible mechanism for the 1,3-dipolar cycloaddition/SO2 extrusion
reaction.
The relative fluorescence quantum yields were determined with
Quinine sulfate as a standard and were calculated using the
following Equation:
Fx
¼
FsðFx = FsÞðAs = AsÞðlexs
=
lexxÞðnx = nsÞ
in which represents the quantum yield, F stands for the inte-
Ф
grated area under the corrected emission spectrum, A is the
absorbance at the excitation wavelength, lex is the excitation
wavelength, n is the refractive index of the solution (because of the
low concentrations of the solutions (10ꢁ5 molLꢁ1), the refractive
indices of the solutions were replaced with those of the solvents),
and the subscripts x and s refer to the unknown and the standard,
respectively.
Scheme 2. Scope of benzosultam-3-ylidenes.
4.2. General procedure for the synthesis of starting materials 1 and
2
Benzosultam-3-ylidenes 1a-k and 1m-n were synthesized ac-
cording to the reference, [11] and benzosultam-3-ylidene 1l was
synthesized according to the procedure [23]. Nitrile imine precur-
sor 2 were synthesized according to the literature [24].
4.3. General procedure for the synthesis of 3
In a 5 mL round-bottom flask, benzosultam-3-ylidenes 1
(0.2 mmol) and hydrazonoyl chloride 2 (0.3 mmol, 1.5 equiv) were
dissolved in methanol (1 mL, 0.2 M). Then, to this solution potas-
sium carbonate (69 mg, 0.5 mmol, 2.5 equiv) was added slowly at
0 ꢀC. Then the reaction mixture was stirred at room temperature for
0.5 h. After that, saturated aqueous NH4Cl (2 mL) was added and the
organics extracted with ethyl acetate (1 mL ꢂ 3). The combined
organic layers were dried over Na2SO4 and evaporated to remove
solvent under reduced pressure. The residue was subjected to
column chromatography on silica gel (100e200 mesh) using pe-
troleum ether/ethyl acetate (30:1e80:1) as eluent to afford the
corresponding compound 3.
Scheme 3. Derivatization of 1,3-dipolar cycloaddition/SO2 extrusion strategy.
4.3.1. 5-(2-methylamino-phenyl)-3,4-diphenyl-1-p-tolyl-1H-
pyrazole (3aa)
Scheme 4. Gram-scale reaction for the synthesis of 3aa.
71 mg, 86% yield, white solid, petroleum ether/ethyl
5

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
acetate ¼ 50:1, Rf ¼ 0.2, mp 154e156 ꢀC; 1H NMR (500 MHz, CDCl3):
2H, J ¼ 8.7 Hz), 6.62 (t,1H, J ¼ 7.5 Hz), 6.58 (d,1H, J ¼ 8.2 Hz), 3.82 (s,
d
7.59e7.57 (m, 2H), 7.34e7.31 (m, 3H), 7.27e7.21 (m, 3H), 7.20e7.18
3H), 2.50 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d 159.3, 150.0,
(m, 3H), 7.11e7.08 (m, 4H), 6.93 (d, 1H, J ¼ 7.4 Hz), 6.62 (t, 1H,
147.2, 139.8,138.6,132.8, 131.7, 130.4, 129.7, 129.6, 128.7, 128.2,127.1,
126.7, 125.6, 124.1, 120.7, 117.3, 115.7, 113.7, 110.9, 55.2, 30.6; HRMS
(ESI-TOFþ): m/z Calcd. For C29H26N3O [(M þ H)þ]: 432.2076. Found:
432.2075.
J ¼ 7.4 Hz), 6.57 (d, 1H, J ¼ 8.2 Hz), 2.51 (s, 3H), 2.32 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3):
d 150.0, 147.4, 138.7, 137.4, 137.0, 133.1,
132.8, 131.8, 130.3, 129.6, 129.3, 128.5, 128.3128.2,127.7, 126.7, 124.0,
120.8, 117.1, 115.7, 110.7, 30.6, 21.0; HRMS (ESI-TOFþ): m/z Calcd. For
C
29H26N3 [(M þ H)þ]: 416.2127. Found: 416.2125.
4.3.7. 5-(2-methylamino-phenyl)-1,4-diphenyl-3-(4-chlorophenyl)
-1H-pyrazole (3 ag)
4.3.2. 5-(2-methylamino-phenyl)-3,4-diphenyl-1-(4-methoxy
phenyl)-1H-pyrazole (3 ab)
63 mg, 73% yield, white solid, petroleum ether/ethyl
acetate ¼ 70:1, Rf ¼ 0.2, mp 158e160 ꢀC; 1H NMR (500 MHz, CDCl3):
76 mg, 88% yield, white solid. Petroleum ether/ethyl
d 7.52e7.51 (m, 2H), 7.38e7.36 (m, 2H), 7.31e7.27 (m, 4H),
acetate ¼ 30:1, Rf ¼ 0.2, mp 170e172 ꢀC; 1H NMR (500 MHz, CDCl3):
7.24e7.20 (m, 5H), 7.10e7.08 (m, 2H), 6.91 (d, 1H, J ¼ 7.3 Hz), 6.61 (t,
d
7.57e7.56 (m, 2H), 7.30e7.28 (m, 5H), 7.24e7.21 (m, 1H), 7.19e7.18
1H, J ¼ 7.4 Hz), 6.57 (d, 1H, J ¼ 8.2 Hz), 2.51 (s, 3H)$13C{1H} NMR
(m, 3H), 7.10e7.09 (m, 2H), 6.93 (d, 1H, J ¼ 7.3 Hz), 6.80 (d, 2H,
(125 MHz, CDCl3): d 149.1, 147.4, 139.7, 139.0, 133.7, 132.4, 131.7,
J ¼ 8.4 Hz), 6.63 (t, 1H, J ¼ 7.3 Hz), 6.58 (d, 1H, J ¼ 8.1 Hz), 3.78 (s,
131.6, 130.5, 129.7, 129.5, 128.8, 128.5, 128.4, 127.3, 127.0, 124.1, 121.1,
117.1, 115.2, 110.7, 30.5; HRMS (ESI-TOFþ): m/z Calcd. For C28H23ClN3
[(M þ H)þ]: 436.1581. Found: 436.1577.
3H), 2.51 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d 158.6, 149.9,
147.1, 138.6, 133.1, 133.0,132.8, 131.8, 130.3, 129.6, 128.5, 128.3, 128.2,
127.7, 126.7, 125.6, 120.6, 117.3, 115.8, 113.9, 110.9, 55.4, 30.7; HRMS
(ESI-TOFþ): m/z Calcd. For C29H26N3O [(M þ H)þ]: 432.2076. Found:
432.2075.
4.3.8. 5-(2-methylamino-phenyl)-1,4-diphenyl-3-(4-fluorophenyl)-
1H-pyrazole (3ah)
59 mg, 70% yield, white solid, petroleum ether/ethyl
4.3.3. 5-(2-methylamino-phenyl)-3,4-diphenyl-1-(4-chlorophenyl)
-1H-pyrazole
acetate ¼ 50:1, Rf ¼ 0.2, mp 141e143 ꢀC; 1H NMR (500 MHz, CDCl3):
d
7.56e7.53 (m, 2H), 7.38e7.36 (m, 2H), 7.30e7.27 (m, 2H),
(3ac) 66 mg,76% yield, white solid, petroleum ether/ethyl
7.25e7.19 (m, 5H), 7.09e7.08 (m, 2H), 7.01 (t, 2H, J ¼ 8.7 Hz), 6.91 (d,
acetate ¼ 60:1, Rf ¼ 0.2, mp 179e180 ꢀC; 1H NMR (500 MHz, CDCl3):
1H, J ¼ 7.3 Hz), 6.60 (t,1H, J ¼ 7.4 Hz), 6.56 (d, 1H, J ¼ 8.2 Hz), 2.51 (s,
1
d
7.57e7.55 (m, 2H), 7.33e7.31 (m, 5H), 7.26e7.24 (m, 3H), 7.19e7.18
3H). 13C{1H} NMR (125 MHz, CDCl3):
d
162.6 (d, JC-F ¼ 246.8 HZ),
(m, 3H), 7.09e7.08 (m, 2H), 6.92 (d, 1H, J ¼ 7.5 Hz), 6.64 (t, 1H,
149.4, 147.5, 139.7, 138.9, 132.5, 131.7, 130.5, 130.2 (d, 3JC-F ¼ 8.1 Hz),
129.5,129.2,129.1,128.8,128.3,127.2,126.9,124.1,120.9,117.0,115.3,
115.2 (d,2JC-F ¼ 21.5 HZ), 110.6, 30.5; HRMS (ESI-TOFþ): m/z Calcd.
For C28H23FN3 [(M þ H)þ]: 420.1876. Found: 420.1873.
J ¼ 7.4 Hz), 6.59 (d, 1H, J ¼ 8.2 Hz), 2.52 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3):
d 150.6, 147.2, 138.7, 138.3, 132.8, 132.7, 132.4,
131.7, 130.7, 129.5, 128.9, 128.4, 128.3, 128.2, 127.9, 126.9, 125.1,
121.4, 117.4, 115.3, 110.9, 30.6; HRMS (ESI-TOFþ): m/z Calcd. For
C
28H23ClN3 [(M þ H)þ]: 436.1581. Found: 436.1582.
4.3.9. 5-(2-methylamino-phenyl)-4-phenyl-1,3-di-p-tolyl-1H-
pyrazole (3ai)
4.3.4. 5-(2-methylamino-phenyl)-3,4-diphenyl-1-(4-fluorophenyl)-
1H-pyrazole (3ad)
79 mg, 92% yield, white solid, petroleum ether/ethyl
acetate ¼ 40:1, Rf ¼ 0.2, mp 153e175 ꢀC; 1H NMR (500 MHz, CDCl3):
59 mg, 71% yield, white solid, petroleum ether/ethyl
d
7.46 (d, 2H, J ¼ 7.9 Hz), 7.26e7.18 (m, 6H), 7.13e7.07 (m, 6H), 6.92
acetate ¼ 40:1, Rf ¼ 0.2, mp 166e167 ꢀC; 1H NMR (500 MHz, CDCl3):
(d,1H, J ¼ 7.4 Hz), 6.62 (t,1H, J ¼ 7.4 Hz), 6.58 (d,1H, J ¼ 8.2 Hz), 2.50
d
7.50e7.49 (m, 2H), 7.29e7.23 (m, 5H), 7.18e7.14 (m, 1H), 7.12e7.10
(s, 3H), 2.36 (s, 3H), 2.31 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
(m, 3H), 7.03e7.01 (m, 2H), 6.90 (t, 2H, J ¼ 8.5 Hz), 6.84 (d, 1H,
d 150.0, 147.2, 138.5, 137.4, 136.8, 132.8, 131.7, 130.2, 129.5, 129.3,
J ¼ 7.5 Hz), 6.54 (t, 1H, J ¼ 7.4 Hz), 6.49 (d, 1H, J ¼ 8.3 Hz), 2.45 (s,
128.9, 128.3, 128.1, 126.6, 124.0, 120.6, 117.2, 115.8, 110.7, 30.6, 21.3,
21.0; HRMS (ESI-TOFþ): m/z Calcd. For C30H28N3 [(M þ H)þ]:
430.2283. Found: 430.2283.
1
3H). 13C{1H} NMR (125 MHz, CDCl3):
d
161.5 (d, JC-F ¼ 245 HZ),
150.3, 147.4, 138.9, 136.0, 132.9, 132.5, 131.7, 130.6, 129.5, 128.4,
128.3, 128.2, 127.9, 126.9, 125.9 (d, 3JC-F ¼ 8.4 HZ), 121.1, 117.1, 115.6
(d, 2JC-F ¼ 22.9 HZ) 115.2, 110.6, 30.5; HRMS (ESI-TOFþ): m/z Calcd.
For C28H23FN3 [(M þ H)þ]: 420.1876. Found: 420.1872.
4.3.10. 5-(2-methylamino-phenyl)-4-phenyl-1,3-diphenyl-1H-
pyrazole (3aj)
65 mg, 81% yield, white solid, petroleum ether/ethyl
4.3.5. 5-(2-methylamino-phenyl)-1,4-diphenyl-3-p-tolyl-1H-
pyrazole (3ae)
acetate ¼ 60:1, Rf ¼ 0.2, mp 148e151 ꢀC;1H NMR (500 MHz, CDCl3):
d
7.60e7.58 (m, 2H), 7.40e7.38 (m, 2H), 7.32e7.28 (m, 5H),
67 mg, 81% yield, white solid, petroleum ether/ethyl
7.25e7.19 (m, 5H), 7.12e7.10 (m, 2H), 6.93 (d, 1H, J ¼ 7.4 Hz), 6.62 (t,
acetate ¼ 50:1, Rf ¼ 0.2, mp 170e171 ꢀC;1H NMR (500 MHz, CDCl3):
1H, J ¼ 7.4 Hz), 6.57 (d, 1H, J ¼ 8.3 Hz), 2.51 (s, 3H). 13C{1H} NMR
d
7.46 (d, 2H, J ¼ 7.9 Hz), 7.37 (d, 2H, J ¼ 7.9 Hz), 7.30e7.26 (m, 2H),
(125 MHz, CDCl3): d 150.3, 147.4, 139.8, 138.8, 133.1, 132.7, 131.7,
7.24e7.18 (m, 5H), 7.13e7.09 (m, 4H), 6.92 (d, 1H, J ¼ 7.4 Hz), 6.61 (t,
130.4, 129.6, 128.7, 128.5, 128.3, 128.2, 127.8, 127.1, 126.8, 124.1, 121.1,
117.1, 115.5, 110.7, 30.5. HRMS (ESI-TOFþ): m/z Calcd. For C28H24N3
[(M þ H)þ]: 402.1970. Found: 402.1967.
1H, J ¼ 7.4 Hz), 6.57 (d, 1H, J ¼ 8.2 Hz), 2.50 (s, 3H), 2.36 (s, 3H). 13
C
{1H} NMR (125 MHz, CDCl3):
d 149.2,146.3,138.8,137.6, 136.4,131.8,
130.7, 129.3,129.1, 128.5,127.9, 127.6, 127.3, 127.1, 126.0,125.6,123.0,
119.9, 116.1, 114.6, 109.7, 29.5, 20.2; HRMS (ESI-TOFþ): m/z Calcd. For
4.3.11. 5-(2-methylamino-phenyl)-4-(4-methoxyphenyl)-1,3-
diphenyl-1H-pyrazole (3bj)
C
29H26N3 [(M þ H)þ]: 416.2127. Found: 416.2128.
69 mg, 80% yield, white solid, petroleum ether/ethyl
4.3.6. 5-(2-methylamino-phenyl)-1,4-diphenyl-3-(4-methoxy
phenyl)-1H-pyrazole (3af)
acetate ¼ 50:1, Rf ¼ 0.2, mp 189e191 ꢀC;1H NMR (500 MHz, CDCl3):
d
7.61e7.60 (m, 2H), 7.39e7.38 (m, 2H), 7.33e7.32 (m, 3H),
71 mg, 83% yield, white solid, petroleum ether/ethyl
7.29e7.27 (m, 2H), 7.25e7.22 (m, 2H), 7.03 (d, 2H, J ¼ 8.4 Hz), 6.93
(d,1H, J ¼ 7.4 Hz), 6.75 (d, 2H, J ¼ 8.4 Hz), 6.62 (t,1H, J ¼ 7.4 Hz), 6.58
(d, 1H, J ¼ 8.2 Hz), 3.76 (s, 3H), 2.55 (s, 3H). 13C{1H} NMR (125 MHz,
acetate ¼ 30:1, Rf ¼ 0.2, mp 156e158 ꢀC; 1H NMR (500 MHz, CDCl3):
d
7.50 (d, 2H, J ¼ 8.7 Hz), 7.37 (d, 2H, J ¼ 7.8 Hz), 7.30e7.27 (m, 2H),
7.24e7.18 (m, 5H), 7.11e7.09 (m, 2H), 6.92 (d, 1H, J ¼ 7.5 Hz), 6.86 (d,
CDCl3): d 158.4, 150.2, 147.5, 139.9, 138.5, 133.2, 131.8, 130.7, 130.4,
6

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
128.7, 128.4, 128.3, 127.7, 127.1, 124.9, 124.1, 120.7, 117.0, 115.6, 113.7,
110.6, 55.1, 30.6. HRMS (ESI-TOFþ): m/z Calcd. For C29H26N3O
[(M þ H)þ]: 432.2076. Found: 432.2078.
4.3.17. 5-(2-methylamino-phenyl)-4-(2-fluorophenyl)-3-phenyl-1-
p-tolyl-1H-pyrazole (3ha)
63 mg, 73% yield, white solid, petroleum ether/ethyl
acetate ¼ 70:1, Rf ¼ 0.2, mp 164e165 ꢀC; 1H NMR (500 MHz, CDCl3):
d
7.62e7.61 (m, 2H), 7.33e7.32 (m, 5H), 7.26e7.20 (m, 2H), 7.15e7.11
4.3.12. 5-(2-methylamino-phenyl)-4-(4-methylphenyl)-1,3-
diphenyl-1H-pyrazole (3cj)
(m, 3H), 7.04e7.00 (m, 2H), 6.97 (d, 1H, J ¼ 7.4 Hz), 6.60 (t, 1H,
J ¼ 7.4 Hz), 6.55 (d, 1H, J ¼ 8.2 Hz), 2.60 (s, 3H), 2.34 (s, 3H). 13C{1H}
68 mg, 82% yield, white solid, petroleum ether/ethyl
NMR (125 MHz, CDCl3):
d
160.3 (d, 1JC-F ¼ 246.2 HZ), 150.4, 147.7,
acetate ¼ 60:1, Rf ¼ 0.2, mp 180e182 ꢀC; 1H NMR (500 MHz, CDCl3):
139.8, 137.4, 137.0, 133.3, 132.5, 131.4, 130.4, 129.4, 129.3, 128.3,
127.8, 127.3, 124.1, 123.8, 121.0 (d,3JC-F ¼ 15.7 Hz), 116.6, 115.6, 115.5,
115.0 (d,3JC-F ¼ 11.5 Hz), 110.2, 30.5, 21.1. HRMS (ESI-TOFþ): m/z
Calcd. For C29H25FN3 [(M þ H)þ]: 434.2033. Found: 434.2027.
d
7.59e7.58 (m, 2H), 7.38e7.30 (m, 5H), 7.26e7.21 (m, 4H),
7.00e6.98 (m, 4H), 6.93 (d, 1H, J ¼ 7.4 Hz), 6.62 (dd, 2H, J ¼ 7.8,
18.4 Hz), 2.51 (s, 3H), 2.29 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d
150.2, 147.5, 139.9, 138.6, 136.3, 133.2, 131.7, 130.3, 129.6, 129.4,
129.0, 128.7, 128.5, 128.3, 127.7, 127.1, 124.1, 121.1, 117.0, 115.6, 110.6,
30.5, 21.2. HRMS (ESI-TOFþ): m/z Calcd. For C29H26N3 [(M þ H)þ]:
416.2127. Found: 416.2125.
4.3.18. 5-(2-methylamino-phenyl)-4-m-tolyl-3-phenyl-1-p-tolyl-
1H-pyrazole (3ia) 68 mg
79% yield, white solid, petroleum ether/ethyl acetate ¼ 70:1,
Rf ¼ 0.2, mp 135e136 ꢀC; 1H NMR (500 MHz, CDCl3):
d 7.58e7.57
4.3.13. 5-(2-methylamino-phenyl)-4-(4-bromophenyl)-1,3-
diphenyl-1H-pyrazole (3dj)
(m, 2H), 7.31e7.26 (m, 5H), 7.22e7.20 (m, 1H), 7.08e7.05 (m,
3H),6.98 (d, 1H, J ¼ 7.5 Hz), 6.92e6.87 (m, 3H), 6.61 (t, 1H,
J ¼ 7.4 Hz), 6.57 (d, 1H, J ¼ 8.2 Hz), 2.51 (s, 3H), 2.31 (s, 3H), 2.17 (s,
79 mg, 82% yield, petroleum ether/ethyl acetate ¼ 50:1, Rf ¼ 0.2,
white solid, mp 157e159 ꢀC; 1H NMR (500 MHz, CDCl3):
d 7.56e7.55
3H). 13C{1H} NMR (125 MHz, CDCl3):
d149.9, 147.3, 138.6, 137.7,
(m, 2H), 7.39e7.22 (m, 11H), 6.96 (d, 2H, J ¼ 8.3 Hz), 6.91 (d, 1H,
137.4,136.9,133.2,132.6,131.7,130.3,129.3,128.4,128.2,128.1, 127.7,
127.5, 126.7, 124.0, 120.9, 117.3, 115.9, 110.8, 30.7, 21.4, 21.1. HRMS
(ESI-TOFþ): m/z Calcd. For C30H28N3 [(M þ H)þ]: 430.2283. Found:
430.2285.
J ¼ 7.4 Hz), 6.63 (t, 1H, J ¼ 7.4 Hz), 6.59 (d, 1H, J ¼ 8.3 Hz), 2.55 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3):
d 150.3, 147.3, 139.6, 138.8,
132.8, 131.7, 131.6, 131.4, 131.2, 130.7, 128.8, 128.5, 128.4, 128.0, 127.3,
124.0, 120.9, 119.9, 117.3, 115.1, 110.8, 30.6. HRMS (ESI-TOFþ): m/z
Calcd. For C28H23BrN3 [(M þ H)þ]: 480.1075. Found: 480.1072.
4.3.19. 5-(2-methylamino-phenyl)-4-(furan-2-yl)-3-phenyl-1-p-
tolyl-1H-pyrazole (3ja)
4.3.14. 5-(2-methylamino-phenyl)-4-(4-chlorophenyl)-1,3-
diphenyl-1H-pyrazole (3ej)
51 mg, 63% yield, white solid, petroleum ether/ethyl
acetate ¼ 70:1, Rf ¼ 0.2, mp 129e130 ꢀC; 1H NMR (500 MHz, CDCl3):
74 mg, 85% yield, white solid, petroleum ether/ethyl
acetate ¼ 60:1, Rf ¼ 0.2, mp 164e165 ꢀC; 1H NMR (500 MHz, CDCl3):
d
7.68 (d, 2H, J ¼ 6.9 Hz), 7.41e7.36 (m, 3H), 7.31e7.25 (m, 4H), 7.08
d
7.59e7.57 (m, 2H), 7.40e7.35 (m, 5H), 7.32e7.29 (m, 2H),
(d, 2H, J ¼ 8.1 Hz), 6.96 (d, 1H, J ¼ 7.4 Hz), 6.68e6.64 (m,
2H),6.29e6.28 (m, 1H), 5.99 (d, 1H, J ¼ 3.2 Hz), 2.71 (s, 3H), 2.31 (s,
7.26e7.24 (m, 2H), 7.17 (d, 2H, J ¼ 8.3 Hz), 7.04 (d, 2H, J ¼ 8.4 Hz),
3H). 13C{1H} NMR (125 MHz, CDCl3):
d 150.3, 147.5, 146.5, 141.7,
6.92 (d,1H, J ¼ 7.4 Hz), 6.63 (t,1H, J ¼ 7.4 Hz), 6.59 (d,1H, J ¼ 8.3 Hz),
2.57 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d 150.3, 147.5, 139.7,
139.0, 137.2, 133.1, 131.4, 130.6, 129.4, 128.2, 128.0, 123.9, 117.1, 115.5,
111.8, 111.0, 110.5, 108.2, 30.8, 21.1. HRMS (ESI-TOFþ): m/z Calcd. For
138.9, 132.8, 132.6, 131.6, 131.3, 130.8, 130.6, 128.8, 128.5, 128.4,
128.0, 127.3, 124.0, 120.0, 117.0, 115.0, 110.5, 30.5; HRMS (ESI-TOFþ):
m/z Calcd. For C28H23ClN3 [(M þ H)þ]: 436.1581. Found: 436.1576.
C
27H24N3O [(M þ H)þ]: 406.1919. Found: 406.1923.
4.3.20. 5-(2-benzylamino-phenyl)-4-(4-fluorophenyl)-1,3-diphenyl
-1H-pyrazole (3kj)
4.3.15. 5-(2-methylamino-phenyl)-4-(4-fluorophenyl)-1,3-
diphenyl-1H-pyrazole (3fj)
83 mg, 84% yield, white solid, petroleum ether/ethyl
70 mg, 83% yield, white solid, petroleum ether/ethyl
acetate ¼ 60:1, Rf ¼ 0.2, m. p.: 151e152 ꢀC; 1H NMR (500 MHz,
acetate ¼ 40:1, Rf ¼ 0.2, mp 161e163 ꢀC; 1H NMR (500 MHz, CDCl3):
CDCl3):
d 7.55e7.54 (m, 2H), 7.40e7.37 (m, 2H), 7.31e7.28 (m, 6H),
d
7.57e7.56 (m, 2H), 7.39e7.29 (m, 7H), 7.27e7.23 (m, 2H),
7.18e7.13 (m, 4H), 7.07e7.04 (m, 2H), 6.96 (d, 1H, J ¼ 7.4 Hz), 6.90 (t,
2H, J ¼ 8.4 Hz), 6.81e6.80 (m, 2H), 6.62 (t, 1H, J ¼ 7.3 Hz), 6.49 (d,
1H, J ¼ 8.2 Hz), 4.18e4.10 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3):
7.08e7.05 (m, 2H), 6.92e6.88 (m, 3H), 6.61 (t, 1H, J ¼ 7.4 Hz), 6.57
(d, 1H, J ¼ 8.2 Hz), 2.56 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d
161.8 (d, 1JC-F ¼ 245.9 HZ), 150.2, 147.6, 139.7, 138.9, 132.9, 131.6,
d
161.9 (d, 1JC-F ¼ 246.5 HZ), 150.3, 145.9, 139.8, 138.7, 132.8, 132.0,
131.2 (d, 3JC-F ¼ 8.0 Hz), 130.5, 128.8, 128.4, 128.3, 127.9, 127.2, 124.0,
120.1, 116.9, 115.3 (d, 2JC-F ¼ 21.2 Hz), 115.0, 110.4, 30.4. HRMS (ESI-
TOFþ): m/z Calcd. For C28H23FN3 [(M þ H)þ]: 420.1876. Found:
420.1877.
131.3 (d, 3JC-F ¼ 7.9 HZ), 130.5, 128.8, 128.5, 128.4, 127.9, 127.2, 127.0,
2
126.8, 124.0, 120.3, 117.1, 115.4 (d, JC-F ¼ 21.5 HZ), 114.9111.0, 47.4.
HRMS (ESI-TOFþ): m/z Calcd. For C34H27FN3 [(M þ H)þ]: 496.2189.
Found: 496.2187.
4.3.16. 5-(2-methylamino-phenyl)-4-(2-bromophenyl)-1,3-
diphenyl-1H-pyrazole (3gj)
4.3.21. 5-(2-amino-phenyl)-1,3,4-triphenyl-1H-pyrazole(3lj)
50 mg, 65% yield, yellow solid, petroleum ether/ethyl
acetate ¼ 30:1, Rf ¼ 0.2, m. p.: 160e161 ꢀC; 1H NMR (500 MHz,
72 mg, 75% yield, white solid, petroleum ether/ethyl
acetate ¼ 60:1, Rf ¼ 0.2, mp 176e177 ꢀC; 1H NMR (500 MHz, CDCl3):
d
7.55e7.52 (m, 2H), 7.46e7.42 (m, 2H), 7.32e7.26 (m, 6H), 7.21e7.11
CDCl3):
d
9.05 (s, 1H), 7.94e7.93 (m, 2H), 7.70 (d, 2H, J ¼ 7.6 Hz), 7.64
(m, 5H), 6.92 (d, 1H, J ¼ 7.2 Hz), 6.57 (t, 1H, J ¼ 7.4 Hz), 6.52 (d, 1H,
(d, 1H, J ¼ 7.8 Hz), 7.59 (s, 1H), 7.48e7.47 (m, 3H), 7.33e7.26 (m, 5H),
J ¼ 8.2 Hz), 2.56 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
d 150.2,
7.21e7.18 (m, 3H), 7.09 (t, 1H, J ¼ 7.6 Hz), 6.93 (t, 1H, J ¼ 7.3 Hz), 6.45
147.3, 139.7, 139.3, 134.2, 132.9, 132.6, 131.5, 130.4, 129.2, 128.8,
128.3, 127.8, 127.5, 127.1, 127.0, 125.0, 124.0,123.5, 120.8, 116.7, 114.9,
110.6, 30.5. HRMS (ESI-TOFþ): m/z Calcd. For C28H23BrN3
[(M þ H)þ]: 480.1075. Found: 480.1078.
(d, 1H, J ¼ 8.0 Hz). 13C{1H} NMR (125 MHz, CDCl3):
d 143.3, 137.3,
132.7, 131.6, 131.1, 131.0, 130.6, 129.2, 129.0, 128.5, 126.3, 124.9,
123.0, 121.3, 120.9, 119.1, 113.7, 111.7. HRMS (ESI-TOFþ): m/z Calcd.
For C27H22N3 [(M þ H)þ]: 388.1814. Found: 388.1818.
7

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
4.3.22. 5-(2-amino-phenyl)-3,4-diphenyl-1-p-tolyl-1H-pyrazole
(3la)
4.4.1. 5-(2-methylamino-phenyl)-4-ethoxycarbonyl-3-phenyl-1-(3-
chlorophenyl)-1H-pyrazole (3ok)
57 mg, 71% yield, yellow solid, petroleum ether/ethyl
65 mg, 76% yield, white solid, mp 166e168 ꢀC; 1H NMR
acetate ¼ 60:1, Rf ¼ 0.2, mp 190e191 ꢀC; 1H NMR (500 MHz, CDCl3):
(500 MHz, CDCl3): d7.90e7.89 (m, 2H), 7.46e7.41 (m, 3H), 7.36 (t,
d
9.02 (s, 1H), 7.96e7.94 (m, 2H), 7.72 (d, 2H, J ¼ 7.4 Hz), 7.64 (d, 1H,
1H, J ¼ 7.3 Hz), 7.26e7.19 (m, 6H), 6.74e6.71 (m, 1H), 3.98e3.76 (m,
J ¼ 7.8 Hz), 7.59 (s, 1H), 7.48e7.47 (m, 3H), 7.34e7.28 (m, 3H), 7.19 (t,
1H, J ¼ 7.7 Hz), 7.14e7.07 (m, 5H), 6.46 (d, 1H, J ¼ 8.0 Hz), 2.32 (s,
2H), 2.97 (s, 3H), 0.97 (t, 3H, J ¼ 6.3 Hz). 13C{1H} NMR (125 MHz,
CDCl3):
d 153.9, 151.5, 140.4, 140.2, 139.9, 133.4, 131.6, 130.4, 128.9,
3H). 13C{1H} NMR (125 MHz, CDCl3):
d
140.0, 136.3, 131.9, 130.6,
128.7, 127.7, 127.2, 127.1, 126.0, 125.9, 124.8, 123.2, 121.0, 105.0, 60.7,
36.6, 13.4. HRMS (ESI-TOFþ): m/z Calcd. For C25H23ClN3O2
[(M þ H)þ]: 432.1479. Found: 432.1475.
130.2,130.1,130.0,129.9,129.6,128.7,128.0,127.5, 127.4, 125.1,123.1,
122.0, 119.9, 118.0, 112.6, 110.6,19.6. HRMS (ESI-TOFþ): m/z Calcd.
For C28H24N3 [(M þ H)þ]: 402.1970. Found: 402.1963.
4.5. Synthesis of 4ok
4.3.23. 5-(2-methylamino-phenyl)-4-(2-fluorophenyl)-3-
(thiophene-2-yl)-1-phenyl-1H-pyrazole (3hk)
A suspension of 3ok (43 mg, 0.1 mmol) and potassium car-
bonate (15 mg, 0.11 mmol, 1.1 equiv) in ethanol (0.5 mL, 0.2 M) was
stirred at reflux in an oil bath for 1 h. After cooling to the room
temperature, The mixture was evaporated to remove solvent under
reduced pressure. The residue was purified by column chroma-
tography (petroleum ether/ethyl acetate ¼ 5:1) to afford the com-
pound 4ok.
45 mg, 53% yield, yellow solid, petroleum ether/ethyl
acetate ¼ 100:1, Rf ¼ 0.2, mp 146e148 ꢀC; 1H NMR (500 MHz,
CDCl3): d 7.44 (d, 2H), 7.33e7.28 (m, 3H), 7.27e7.24 (m, 2H), 7.20 (t,
3H, J ¼ 9.5 Hz), 7.12e7.07 (m, 2H), 6.99e6.94 (m, 3H), 6.58 (t, 1H,
J ¼ 9.2 Hz), 6.53 (d, 1H, J ¼ 10.3 Hz), 3.86 (br, 1H), 2.62 (s, 3H). 13
C
1
{1H} NMR (125 MHz, CDCl3):
d
160.8 (d, JC-F ¼ 305.9 HZ), 147.8,
146.0,140.2,139.7,135.6,132.9,131.4,130.6,129.9 (d,3JC-F ¼ 10.0 Hz),
128.8, 127.4, 127.3, 125.2, 125.0, 124.3 (d,3JC-F ¼ 4.5 Hz), 123.9, 120.5,
120.4, 116.6, 115.7(d,2JC-F ¼ 27.4 Hz), 114.7(d,2JC-F ¼ 24.1 Hz), 110.2,
30.5; HRMS (ESI-TOFþ): m/z Calcd. For C26H20FN3S [(M þ H)þ]:
426.1440. Found: 426.1143.
4.5.1. 1-(3-chlorophenyl)-5-methyl-3-phenyl-1H-pyrazolo[ [4] [3-
c]]quinolin-4(5H)-one (4ok)
36 mg, 93% yield, white solid, mp 157e158 ꢀC;1H NMR
(500 MHz, CDCl3):
(m, 4H), 7.48e7.43 (m, 4H), 7.32 (d, 1H, J ¼ 7.9 Hz), 7.07e7.06 (m,
1H), 3.79 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
158.6, 152.0,
d
8.14 (d, 2H, J ¼ 7.2 Hz), 7.67 (s, 1H), 7.60e7.53
4.3.24. 5-(2-methylamino-phenyl)-4-methyl-1,3-diphenyl-1H-
pyrazole (3mj) 56 mg
d
141.5,141.4,139.7,135.5,131.4,130.8,130.4,130.2,129.7,128.9,128.0,
127.8, 125.5, 123.1, 121.8, 115.7, 111.6, 110.4, 29.6. HRMS (ESI-TOFþ):
m/z Calcd. For C23H17ClN3O [(M þ H)þ]: 386.1060. Found: 386.1065.
83% yield, white solid, petroleum ether/ethyl acetate ¼ 40:1,
Rf ¼ 0.2, mp 166e168 ꢀC; 1H NMR (500 MHz, CDCl3):
d 7.89 (d, 2H,
J ¼ 7.5 Hz), 7.50 (t, 2H, J ¼ 7.6 Hz), 7.41e7.32 (m, 4H),7.28 (t, 2H,
J ¼ 7.7 Hz), 7.20 (t, 1H, J ¼ 7.3 Hz), 6.97 (d, 1H, J ¼ 7.3 Hz), 6.72e6.67
(m, 2H), 2.80 (s, 3H), 2.17 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
4.6. Synthesis of 5gj
d
151.0, 147.6, 140.1, 138.8, 133.9, 131.4, 130.5, 128.7, 128.5, 127.7,
[Pd2dba3] (4.6 mg, 0.005 mmol, 0.05 equiv), dppf (3.9 mg,
0.007 mmol, 0.07 equiv), and KOtBu (22.4 mg, 0.2 mmol) were
added to a 5 mL round-bottom flask and mixed with toluene (2 mL,
0.05 M) and 3gj (48 mg, 0.1 mmol). The mixture was heated in an
oil bath (at 100 ꢀC) for 12 h under argon atmosphere. The mixture
was evaporated to remove solvent under reduced pressure. The
residue was purified by column chromatography (petroleum ether/
ethyl acetate ¼ 30:1) to afford the compound 5gj.
126.7, 123.3, 116.8, 115.6, 115.4, 110.1, 30.5, 10.0; HRMS (ESI-TOFþ):
m/z Calcd. For C23H22N3 [(M þ H)þ]: 340.1814. Found: 340.1816.
4.3.25. 5-(2-methylamino-phenyl)-4-ethyl-1,3-diphenyl-1H-
pyrazole (3nj)
56 mg, 79% yield, white solid, petroleum ether/ethyl
acetate ¼ 50:1, Rf ¼ 0.2, m. p.: 118e120 ꢀC; 1H NMR (500 MHz,
CDCl3):
d
7.83 (d, 2H, J ¼ 7.5 Hz), 7.49e7.45 (m, 2H), 7.40e7.36 (m,
3H), 7.32 (t, 1H, J ¼ 7.6 Hz), 7.27e7.24 (m, 2H), 7.18 (t, 1H, J ¼ 7.3 Hz),
7.01 (d, 1H, J ¼ 7.0 Hz), 6.72e6.68 (m, 2H), 2.77 (s, 3H), 2.66e2.48
(m, 2H), 1.02 (t, 3H, J ¼ 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3):
4.6.1. N-methyl-1,3-diphenyl-dibenzo[b,f]pyrazolo[ [3] [4-d]]
azepine (5gj)
35 mg, 88% yield, white solid. m. p.: 204e205 ꢀC; 1H NMR
d
150.8, 147.7, 140.0, 138.4, 134.0, 131.4, 130.5, 128.7, 128.5, 127.8,
(500 MHz, CDCl3):
d
7.69 (d, 2H, J ¼ 6.9 Hz), 7.50 (d, 2H, J ¼ 7.6 Hz),
127.7, 126.7, 123.4, 122.0, 116.8, 115.8, 110.1, 30.5, 17.3, 15.2. HRMS
(ESI-TOFþ): m/z Calcd. For C24H24N3 [(M þ H)þ]: 354.1970. Found:
354.1972.
7.42e7.32 (m, 9H), 7.29e7.27 (m, 1H), 7.16 (d, 1H, J ¼ 7.5 Hz),
6.93e6.90 (m, 1H), 6.84 (s, 2H), 3.50 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3):
d 149.8, 140.2, 133.2, 129.8, 129.6, 129.5, 129.1, 128.9, 128.3,
128.0, 127.8, 127.5, 125.4, 53.4. HRMS (ESI-TOFþ): m/z Calcd. For
4.4. Synthesis of 3ok
C
28H22N3 [(M þ H)þ]: 400.1814. Found: 400.1811.
In a 5 mL round-bottom flask, benzosultam-3-ylidenes 1o
(53 mg, 0.2 mmol) and hydrazonoyl chloride 2k (79 mg, 0.3 mmol,
1.5 equiv) were dissolved in CH2Cl2 (0.5 mL, 0.4 M). Then, a solution
of triethylamine (1 M, 0.5 mL, 2.5 equiv) was added dropwise at
0 ꢀC. Then the reaction mixture was stirred at room temperature for
5 h. After that, saturated aqueous NH4Cl (2 mL) was added and the
aqueous layer was extracted with CH2Cl2 (1 mL ꢂ 2). The combined
organic layers were dried over Na2SO4 and evaporated to remove
solvent under reduced pressure. The residue was subjected to
column chromatography (petroleum ether/ethyl acetate ¼ 10:1) to
afford the compound 3ok.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Appendix B. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131568.
8

G. Cao, X. Liu, L. Wang et al.
Tetrahedron 76 (2020) 131568
Commun. 51 (2015) 17148e17151;
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