Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel

Article abstract of DOI:10.1016/j.bmc.2013.06.060

A series of compounds containing dihydroquinazolinone moiety was designed and synthesized. Amine bridge part was changed in comparison with known anthranilic diamides insecticides. Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compounds 5a and 5k showed 80% larvicidal activities against oriental armyworm at the concentration of 5 mg/L. The present study also explored the possible effects of target compounds on the high voltage-gated calcium channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole-cell patch clamp and calcium imaging technique. The results showed that compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua weakly. The peak currents only increased by 6% of the initial value at the end of the 10-min recording after treated with 0.22 μM 5a, while chlorantraniliprole has an opposite effect. The effects of 5a on the intracellular calcium ion concentration ([Ca²⁺]_i) in neurons were well investigated. The experimental results indicated that these novel compounds have different mechanism compared with chlorantraniliprole.

Full text of DOI:10.1016/j.bmc.2013.06.060

Accepted Manuscript
Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one deriv‐
atives targeting calcium channel
Yunyun Zhou, Qi Feng, Fengjuan Di, Qiaoxiao Liu, Duoyi Wang, Youwei Chen,
Lixia Xiong, Haibin Song, Yuxin Li, Zhengming Li
PII:
S0968-0896(13)00600-7
DOI:
http://dx.doi.org/10.1016/j.bmc.2013.06.060
BMC 10953
Reference:
To appear in:
Bioorganic & Medicinal Chemistry
Received Date:
Revised Date:
Accepted Date:
8 May 2013
25 June 2013
25 June 2013
Please cite this article as: Zhou, Y., Feng, Q., Di, F., Liu, Q., Wang, D., Chen, Y., Xiong, L., Song, H., Li, Y., Li,
Z., Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel,
Bioorganic & Medicinal Chemistry (2013), doi: http://dx.doi.org/10.1016/j.bmc.2013.06.060
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Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com
Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives
targeting calcium channel
Yunyun Zhoua §, Qi Fengb §, Fengjuan Dia, Qiaoxiao Liua, Duoyi Wanga, Youwei Chena, Lixia Xionga,
Haibin Songa, Yuxin Lia *, Zhengming Lia *
a State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China.
b Zhejiang Base of National Southern Pesticide Research Centre, Zhejiang Research Institute of Chemical Industry, Hangzhou 310023, PR China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A series of compounds containing dihydroquinazolinone moiety was designed and synthesized.
Amine bridge part was changed in comparison with known anthranilic diamides insecticides.
Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most
of the compounds showed moderate to high activities at the tested concentrations. In particular,
compound 5a and 5k showed 80 % larvicidal activities against oriental armyworm at the
concentration of 5 mg/L. The present study also explored the possible effects of target
compounds on the high voltage-gated calcium channel and the calcium channels in the
endoplasmic reticulumn in the central neurons isolated from the third instar larvae of Spodoptera
exigua using whole-cell patch clamp and calcium imaging technique. The results showed that
compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua
weakly. The peak currents only increased by 6 % of the initial value at the end of the 10-min
recording after treated with 0.22 μM 5a, while chlorantraniliprole has an opposite effect. The
effects of 5a on the intracellular calcium ion concentration ([Ca2+]i) in neurons were well
investigated. The experimental results indicated that these novel compounds have different
mechanism compared with chlorantraniliprole.
Available online
Keywords:
Anthranilic diamide
Insecticidal activity
Dihydroquinazolinone
Calcium channel
2009 Elsevier Ltd. All rights reserved.
1. Introduction
In our previous work, we found the amine bridge part has a great
impact on the insecticidal activity.20, 21
The majority of insecticides currently available on the market
is affecting signal transmission in the central nervous system.1
Recently, two anthranilic diamide insecticides were discovered
by Dupon,2 namely chlorantraniliprole (Fig. 1, A) and
cyantraniliprole (B),4,5 have been introduced into the market.
They have a novel mode of action targeting at ryanodine
receptors-disrupting calcium homeostasis.3
So far, these two compounds exhibit exceptional broad-
spectrum activity,2 high potency and low mammalian toxicity.
In addition, both are selective activators of insect ryanodine
receptor, causing uncontrolled release of internal calcium and
ultimately leading to death.6 Since the discovery of anthranilic
diamides, most of the modifications were categorized to N-
pyridylpyrazole moiety (a)7-11 and benzamide moiety (b),12-17
while few changes of amine bridge moiety were reported (c).18, 19
Figure 1.
Dihydroquinazolinone moiety as an efficient pharmacophore
was extensively used in pesticide and drug molecule design.22, 23
Until
now,
anthranilic
diamides
containing
2,3-
dihydroquinazoline structure have not been reported. To further
study the role of the amine bridge moiety played in the
———
* Corresponding authors. Tel.: +86 22 23503732 (Z.-M. Li); tel.:
+86 22 23503798 (Y.-X. Li).
biological activities,
a series of compounds which have
dihydroquinazolinone moiety were synthesized.
E-mail addresses: nkzml@vip.163.com (Z.-M. Li);
liyx128@nankai.edu.cn (Y.-X. Li).
Their synthetic routes were shown in Scheme 1-5, and the
insecticidal activity against oriental armyworms was tested
accordingly. The preliminary structure-activity relationship
§ These authors contributed equally to the work.

(SAR) was also discussed. In order to increase understanding of
the mechanisms of the compounds, the whole-cell patch-clamp
and calcium imaging techniques were used to investigate the
effects of compounds on calcium channels in the central neurons
of S. exigua.
2. Results and discussion
2.1. Chemistry
The synthetic route of compounds 4a-p were shown in
Schemes 1, 2 and 3. Compounds 4a-n were prepared according
24-29
to the reported method
with minor improvements. 2-
Figure 2. Molecular structure of compound 5a and 5b
Aminobenzoic acid with different substituents were treated with
thionyl chloride and then coupled with excessive amine to
provide amides 4a-n. Nevertheless, a reaction in milder
conditions and satisfactory yields to synthesize 4o and 4p was
reported in this paper. 2-Aminobenzoic acid was reacted with
triphosgene or N, N'-carbonyldiimidazole (CDI) to generate the
isatoic anhydride, subsequently reacted with excessive amine to
yield compounds 4o and 4p in excellent yields after filtration.
Compound 1 was achieved by referring to the known
procedure, further reduction to give alcohol 2 by using one
equivalent of lithium aluminum hydride as reductant. When
more than twice of the reducing agent were used, dechlorination
in the 3-position of the pyridine ring was found, which was
confirmed by 1H NMR. The compound 2 was oxidized to 3 with
PCC in high yields and purity.
As shown in Scheme 4, compounds 5a-r were synthesized
from compounds 4a-p and 3a-b using p-toluenesulfonic acid
monohydrate as a catalyst, and this kind of reaction can be
carried out smoothly in toluene.
Compound 6 was obtained from compound 4a reacted with
acetone. However, subsequent reaction with 7 failed to afford 8,
probably owing to steric hindrance of two methyl groups in the
2-poistion of compound 6.
Table 1. Dihedral angles of 5a and 5b
angle (deg)
No.
I
II
plane1
plane2
5a
5b
pyridine ring pyrazole ring 79.78 42.88
pyridine ring benzene ring 22.40 71.55
III pyrazole ring benzene ring 81.89 87.39
2.3. Structure-activity relationship (SAR).
The larvicidal activities of 5a-s and commercial
chlorantraniliprole
against
oriental
armyworms
were
summarized in Table 2. The bioassay results indicated that most
of the compounds showed moderate to good insecticidal
activities. Especially compounds 5a and 5k showed 80 %
larvicidal activities at the concentration of 5 mg/L.
Activities varied significantly depending upon the types of
substituents on the 3-position dihydroquinazolinone. Compared
with 3-CH2CH3 and 3-OCH3 in dihydroquinazolinone,
compounds with 3-H and 3-CH3 substituents showed higher
insecticidal activities against oriental armyworm, with the
sequence of 5a = 5k > 5b > 5h > 5f > 5e > 5d, suggesting that in
the 3-position of dihydroquinazolinone, small substituents have a
positive effect on the larvicidal activities. When the substituent
is t-Bu, it shows no activity at 50 mg/L.
2.2. Crystal structure analysis
Compound 5a was recrystallized from ethyl acetate to give
colorless crystals (0.26 mm × 0.22 mm × 0.20 mm) suitable for
X-ray single-crystal diffraction with the following
crystallographic parameters: a = 9.369 (2) Å, b = 12.973 (3) Å, c
= 15.592 (4) Å, α = 90º，β = 104.521 (4)º, γ = 90º, V = 1834.5
(7) Å3, Dc = 1.691 g cm-3, μ = 2.552 mm-1, F (000) = 936, R =
0.0287, wR = 0.0690, Z = 4. Compound 5b was recrystallized
from ethyl acetate/petroleum ether (60-90 ℃) to give colorless
crystals (0.20 mm × 0.18 mm × 0.10 mm) suitable for X-ray
single-crystal diffraction with the following crystallographic
parameters: a = 13.089(4) Å, b = 11.032(4) Å, c = 14.270(5) Å,
α = 90º, β = 109.241 (4)º, γ = 90º, V = 1945.3 (11) Å3, Dc = 1.650
g cm-3, μ = 2.413 mm-1, F (000) = 968, R = 0.0335, wR = 0.0725,
Z = 4. Their structures are shown in Fig. 2. The dihedral angels
of 5a and 5b are shown in Table 1.
Generally, the average bond lengths and bond angles of ring
system (pyridine, pyrazole and dihydroquinazolinone ring) are
normal ranges.30-36 As shown in Fig. 2, in the compound 5a, the
phenyl ring is vertically with both the pyridine ring and pyrazole
ring with the dihedral angles of 79.78º and 81.89º. The pyridine
ring is nearly planar with pyrazole ring with a small dihedral
angle (θ) of 22.40º. In the compound 5b, the pyridine ring is
oblique with pyrazole ring and phenyl ring with dihedral angle
(θ) of 42.88º and 71.55º respectively. From the crystal structure,
the dihedral angles are not the same between compound 5a and
5b, resulting in a difference in insecticidal activity.
Furthermore, different substituents in the benzene ring had
diverse influence on activity. When R1 was fixed as CH3, the
bioactivity of compounds with different R2 indicated the
sequence of 6-Cl, 8-CH3 (5a) > 8-CH3 (5j) >> H (5i), and
compounds with 3-cyclopropyl showed
a similar trend.
However, when R1 was fixed as isopropyl, the compounds with
CH3 group in 8-position of the benzene ring exhibited lower
activities, this trend is not consistent with that when R1 was CH3.
In addition, the dechlorination at the 3-position of the pyridine
ring led to a significant decrease in activity, such as 5q and 5r.
Surprisingly, the bioassay showed that the compound 5a
exhibited significantly higher insecticidal activity than 5s,
indicating that the C-N bond of 1-position in
dihydroquinazolinone has significant effect on the activity.
The larvicidal activities of compounds 5a and 5d against S.
exigua was also tested. The results indicate that compound 5a
has 100 % morality at 25 mg/L, and compound 5d shows 40 %
larvicidal activities at the concentration of 50 mg/L. Further
studies on SAR are currently underway in our laboratories.
2.4. Electrophysiological recordings
The currents of calcium (ICa) were recorded using the reported
procedure.37 Fig. 3 shows the change rate of peak current
amplitude versus recording time in neurons treated with 0.22 μM
5a, 0.1 μM, 0.01 mM chlorantraniliprole and the control neurons.
Compared to chlorantraniliprole and control, the peak currents
were elevated to 106.3 ± 1.58 % (n = 9) after the neurons were

treated with 0.22 μM 5a. The peak currents decreased by 20 %
of the initial value by the end of 10-min recording. The
experimental results obtained from patch-clamp technique
indicated that compound 5a has weak effect on the voltage-gated
calcium channel. Fig. 4 shows the maximal value of calcium
currents (ICa) did not shift after the neurons were treated with 5a.
It is concluded that the voltage dependency of calcium do not
affact by 5a. The recorded peak currents of calcium channels
and I-V relationship curves of whole-cell calcium channels
recorded in 0.22 μM 5a-treated the third larvae neurons of S.
exigua indicated that the activation of voltage-gated channel by
compound 5a is weak.
results also indicated that the elevation of calcium concentration
by 5a is concentration independent.
chlorantraniliprole 1.6 M
5a 0.54 M
120
5a 2.2 M
5a 1.1M
control
100
3.00 3.05 3.10 3.15 3.20 3.25 3.30 3.35 3.40 3.45 3.50 3.55 3.60
Time (min)
110
105
100
95
90
Figure 5. 5a induced calcium elevation in isolated S. exigua in the presence
or absence of extracellular calcium. The central neurons of S. exigua third
larvae were dyed by loading with fluo-3 AM.
85
80
75
70
65
After the incubation of the primary cultured neurons with 2-
aminoethoxydiphenyl borate (2-APB, 50 μM, a chemical that
acts to inhibit both IP3R and TRP), there is no difference in the
elevation of calcium ion concentration.
60
55
Control
Chlorantraniliprole 0.01mM
5a 0.22M
50
45
40
chlorantraniliprole 0.1 M
Though the calcium imaging technique experiments
demonstrated that RyRs would be the possible action target of
this series of novel compounds, the whole-cell patch clamp also
indicated that these novel compounds have different effect on the
voltage-gated calcium channel compared with chlorantraniliprole.
In view of the complexity of calcium-signaling pathways, a
depolarization-induced limited calcium influx via voltage-gated
calcium channel by compound 5a may induce calcium release
from endoplasmic reticulum.
0
2
4
6
8
10
Time (min)
Figure 3. The change rates of peak current amplitude versus recording time
in the 5a, chlorantraniliprole treated and control neurons.
3. Conclusion
In summary, a series of compounds containing 2, 3-
dihydroquinazolinone moiety were synthesized, and their
1
structures were characterized and confirmed by H NMR and
HRMS. The bioassays showed that some compounds exhibited
favorable insecticidal activities against oriental armyworm. In
particular, compounds 5a and 5k against oriental armyworm
were 80 % at 5.0 mg/L. The preliminary structure-activity
relationship of the title compounds indicated that the small
substituents in dihydroquinazolinone were preferred.
The
calcium imaging technique experiments demonstrated that RyRs
would be the possible action target of this series of novel
compounds. To meet the requirements of future insect control,
RyRs is a promising targets for designing novel insecticides.
Figure 4. The current–voltage relationship curves of whole-cell calcium
channels recorded in 0.22 μM 5a-treated the third larvae neurons of S. exigua
at different times.
4. Experimental section
4.1. Chemistry
1H NMR spectra were recorded at 300 MHz using a Bruker
AC-P300 spectrometer or 400 MHz using a Bruker AV 400
spectrometer (Bruker Co., Switzerland) in CDCl3 or DMSO-d6
with tetramethylsilane as the internal standard, and chemical
shift values (δ) were given in ppm. High-resolution mass
spectrometry (HRMS) data were obtained on a Varian QFT-ESI
instrument. The melting points were determined on an X-4
binocular microscope melting point apparatus (Beijing Tech
2.5. Calcium imaging
Fig. 5 shows the change of [Ca2+]i vs. recording time when
the neurons were treated with 2.2 μM, 1.1 μM, 0.54 μM 5a in the
presence or absence of extracellular calcium. Application of 5a
to isolated S. exigua neurons caused an increase in the cytosolic
calcium concentration. The peaks of [Ca2+]i were 104.68 ± 2.26
% (n = 12), 111.91 ± 4.47 % (n = 6) 107.2 ± 2.6 % (n = 12) of
the initial value after the neurons were treated with 5a shorter
than 20 seconds respectively. In the absence of extracellular
calcium, the elevation of calcium ion concentration in the
neurons is due to release from internal stores. Our experimental
Instruments Co., Beijing, China) and uncorrected.
Flash
chromatography was performed with silica gel (200-300 mesh).
The whole-cell patch-clamp was performed using patch-clamp
amplifier (EPC-10, HEKA Electronik, Lambrecht, Germany).

3
Reagents were all analytically or chemically pure. All solvents
and liquid reagents were dried by standard methods in advance
and distilled before use. Chlorantraniliprole used in this work
was synthesized according to the literature38 as the control.
H), 7.31 (d, 1H, J = 4.4 Hz, Ar-H), 7.22 (s, 1H, Ar-H), 6.99 (d,
1H, 3J = 4.8 Hz, Ar-H), 5.77 (s, 2H, NH2), 2.20 (s, 3H, CH3).
2-Amino-5-chloro-N-ethyl-3-methylbenzamide (4h) White
1
solid; yield, 52 %; mp 109-110 ℃. H NMR (400 MHz, CDCl3):
δ 7.17 (d, 1H, 4J = 2.4 Hz, Ar-H), 7.10 (d, 1H, J = 1.8 Hz, Ar-
4
H), 5.95 (br s, 1H, NH), 5.53 (s, 2H, NH2), 3.49-3.40 (m, 2H,
CH2), 2.14 (s, 3H, Ar-CH3), 1.25 (t, 3H, 3J = 7.5 Hz, CH3).
2-Amino-5-chloro-N-isopropylbenzamide (4j) White solid;
yield, 40 %; mp 165-166 ℃. 1H NMR (300 MHz, CDCl3): δ
4
4
3
7.24 (d, 1H, J = 2.4 Hz, Ar-H), 7.14 (dd, 1H, J = 2.4 Hz, J =
3
8.7 Hz, Ar-H), 6.62 (d, 1H, J = 8.7 Hz, Ar-H), 5.78 (br s, 1H,
NH), 5.47 (s, 2H, NH2), 4.28-4.16 (m,1H, CH), 1.26 (d, 6H, J =
3
6.3 Hz, CH3).
2-Amino-5-chloro-N-propylbenzamide (4k) White solid;
Scheme 1
Scheme 2
yield, 55 %; mp 120-122 ℃. 1H NMR (300 MHz, CDCl3): δ
4
3
7.26 (in CDCl3, 1H, Ar-H), 7.15 (dd, 1H, J = 2.4 Hz, J = 8.7
3
Hz, Ar-H), 6.62 (d, 1H, J = 8.7 Hz, Ar-H), 6.01 (br s, 1H, NH),
3
5.47 (s, 2H, NH2), 3.37 (q, 2H, J = 6.9 Hz, NHCH2), 1.69-1.57
(m, 2H, CH2), 0.99 (t, 3H, 3J = 7.5 Hz, CH3).
2-Amino-5-chloro-N-cyclohexylbenzamide (4l) White solid;
yield, 60 %; mp 176-177 ℃. 1H NMR (300 MHz, CDCl3): δ
4
4
3
7.24 (d, 1H, J = 2.4 Hz, Ar-H), 7.14 (dd, 1H, J = 2.4 Hz, J =
3
8.7 Hz, Ar-H), 6.62 (d, 1H, J = 8.7 Hz, Ar-H), 5.82 (br s, 1H,
NH), 5.47 (s, 2H, NH2), 3.97-3.84 (m, 1H, CH), 2.04-1.99 (m,
2H, cyclohexyl), 1.80-1.74 (m, 2H, cyclohexyl), 1.68-1.61 (m,
1H, cyclohexyl), 1.50-1.35 (m, 2H, cyclohexyl),1.29-1.15 (m,
3H, cyclohexyl).
Scheme 3
2-Amino-5-bromo-N-cyclopropyl-3-methylbenzamide (4m)
White solid; yield, 65 %; mp 150-151 ℃. 1H NMR (300 MHz,
CDCl3): δ 7.23 (s, 2H, Ar-H), 6.10 (s, 1H, NH), 5.63 (s, 2H,
NH2), 2.88-2.79 (m,1H, CH), 2.14 (s, 3H, Ar-CH3), 0.90-0.84 (m,
2H, cyclopropyl), 0.64-0.58 (m, 2H, cyclopropyl).
4.1.2. General synthetic procedure for compounds 2a-b
To a 0℃ solution of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxylate (1a) (0.33 g, 1.0 mmol) in 15 mL of
tetrahydrofuran, lithium aluminum hydride (0.038 g, 1.0 mmol)
was added in small portions. The reaction was maintained at
0 ℃ and monitored with TLC. After agitation for 1 h, excessive
dosage of sodium sulfate was added with vigorous stirring for 20
min. The precipitation was filtered and the filtrate was
evaporated. The residue was applied to a flash column
chromatography by eluting with petroleum ether/ethyl acetate
(3:1) to give the compound 2a as a white solid; yield, 89 %; mp
Scheme 4
3
109-111 ℃. 1H NMR (400 MHz, CDCl3): δ 8.41 (dd, 1H, J =
Scheme 5
4.8 Hz, 4J = 1.6 Hz, Ar-H), 8.01 (dd, 1H, 3J = 8.2 Hz, 4J = 1.4 Hz,
Ar-H), 7.39 (dd, 1H, 3J = 4.8 Hz, 3J = 8.0 Hz, Ar-H), 6.49 (s, 1H,
3
3
Ar-H), 4.51 (d, 2H, J = 6.8 Hz, CH2), 4.29 (t, 2H, J = 6.8 Hz,
OH).
Compound 2b was synthesized according to the procedure of
2a, except for duplation of the amount of lithium aluminum
hydride. White solid; yield, 70 %; mp 72-73 ℃. 1H NMR (400
MHz, CDCl3): δ 8.42 (dd, 3J = 5.0, 4J = 1.0 Hz, 1H, Ar-H), 8.00
3
Scheme 6
(d, J = 8.4 Hz, 1H, Ar-H), 7.94 - 7.88 (m, 1H, Ar-H), 7.33 -
7.27 (m, 1H, Ar-H), 6.34 (s, 1H, Ar-H), 5.82 (t, 3J = 7.5 Hz, 1H,
OH), 4.68 (d, 3J = 7.4 Hz, 2H, CH2).
4.1.1. General synthetic procedure for compounds 4a-n, 4o
and 4p
4.1.3. General synthetic procedure for compounds 3a-b
Compounds 4a-f, 4i and 4n were prepared in moderate yield
by the method reported9, 24-29, 38 respectively. Compounds 4o and
4p were prepared according to Hanusek39 and Cheng40
respectively. The 1H NMR and melting point data were
consistent with the literature.
To the suspension of PCC (0.43 g, 2 mmol) in 15 mL of
dichloromethane, a solution of (3-bromo-1-(3-chloropyridin-2-
yl)-1H-pyrazol-5-yl)methanol (2a) (0.287 g, 1.0 mmol) in 15 mL
of dichloromethane was added in one portion at room
temperature. The reaction was monitored with TLC. After
agitation for 10 h, 1 g of silica gel was added and stirred for
another 30 min. The solvent was evaporated, and the residue
2-Amino-5-chloro-3-methyl-N-(thiazol-2-yl)benzamide (4g)
Yellow solid; yield, 45 %; mp 250-252 ℃. 1H NMR (400 MHz,
4
CDCl3): δ 11.05 (s, 1H, CONH), 7.48 (d, 1H, J = 1.6 Hz, Ar-

was applied to a flash column chromatography by eluting with
ethyl acetate to give the compound 3a as a yellow solid; yield,
78 %; mp 104-105 ℃. 1H NMR (400 MHz, CDCl3): δ 9.81 (s,
Ar-H), 8.06 (dd, 1H, 4J = 1.2 Hz, 3J = 4.6 Hz, Ar-H), 7.84 (d, 1H,
4J = 2.0 Hz, Ar-H), 7.49 (dd, 1H, 3J = 4.6 Hz, 3J = 8.2 Hz, Ar-H),
4
7.14 (d, 1H, J = 2.0 Hz, Ar-H), 6.32 (s, 1H, Ar-H), 5.98 (d, 1H,
4
3
3
1H, CHO), 8.53 (dd, 1H, J = 2.0 Hz, J = 6.0 Hz, Ar-H), 7.99
3J = 2.0, NH), 5.71 (d, 1H, J = 2.4 Hz, CH), 2.70-2.65 (m, 1H,
4
3
(dd, 1H, J = 2.0 Hz, 3J = 10.8 Hz, Ar-H), 7.49 (dd, 1H, J = 6.0
NCH), 2.08 (s, 3H, Ar-CH3), 1.12-1.04 (m, 1H, CH), 0.89-0.82
(m, 1H, CH), 0.69-0.61 (m, 1H, CH), 0.52-0.45 (m, 1H, CH).
HRMS calcd for C20H16BrCl2N5O ([M-H]-): 489.9843, found:
489.9835.
Hz, 3J = 10.8 Hz, Ar-H), 7.12 (s, 1H, Ar-H).
(3-Chloro-1-(pyridin-2-yl)-1H-pyrazol-5-yl)methanol (3b)
yellow solid; yield, 80 %; mp 70-71 ℃. 1H NMR (400 MHz,
3
CDCl3): δ 10.71 (s, 1H, CHO), 8.46 (d, J = 4.3 Hz, 1H, Ar-H),
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-8-methyl-3-propyl-2,3-dihydroquinazolin-4(1H)-one
(5f) White solid; yield, 87 %; mp 198-200 ℃. 1H NMR (400
7.92 (q, 2H, Ar-H), 7.33 (t, 1H, Ar-H), 6.97 (s, 1H, Ar-H).
4
3
4.1.4. General synthetic procedure for compounds 5a-r
MHz, CDCl3): δ 8.52 (dd, 1H, J = 1.6 Hz, J = 4.6 Hz, Ar-H),
4
3
4
8.06 (dd, 1H, J = 1.4 Hz, J = 8.2 Hz, Ar-H), 7.83 (d, 1H, J =
2-Amino-5-chloro-N, 3-dimethylbenzamide (4a) (0.099 g, 0.5
mmol) and 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carbaldehyde (3a) (0.143 g, 0.5 mmol) were dissolved in 20 mL
of toluene, followed by a catalytic amount of p-toluenesulfonic
acid monohydrate. The resulting mixture was refluxed for 1 h
and then evaporated. The residue was dissolved in ethyl acetate
(40 mL), and washed with saturated sodium bicarbonate solution
(2 × 20 mL). The organic layer was dried over with sodium
sulfate and evaporated to obtain the crude product, which was
further purified with flash column chromatography by eluting
with petroleum ether/ethyl acetate (2:1) to afford the compound
5a as a white solid; yield, 92 %; mp 247-249 ℃. 1H NMR (400
3
3
2.4 Hz, Ar-H), 7.48 (dd, 1H, J = 4.6 Hz, J = 8.2 Hz, Ar-H),
4
7.13 (d, 1H, J = 2.0 Hz, Ar-H), 6.26 (s, 1H, Ar-H), 5.95 (d, 1H,
3J = 2.0, NH), 5.69 (d, 1H, 3J = 2.4 Hz, CH), 4.05 (m, 1H, NCH),
2.80 (m, 1H, NCH), 2.07 (s, 3H, Ar-CH3), 1.58 (m, 2H,
3
CH2CH3), 0.91 (t, 3H, J = 7.2 Hz, CH3). HRMS calcd for
C20H18BrCl2N5O ([M+H]+): 494.0145, found: 494.0140.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-8-methyl-3-(thiazol-2-yl)-2,3-dihydroquinazolin-
4(1H)-one (5g) White solid; yield, 80 %; mp 260-262 ℃. 1H
3
NMR (400 MHz, CDCl3): δ 8.54 (d, 1H, J = 3.6 Hz, Ar-H),
8.08 (d, 1H, 3J = 8.0 Hz, Ar-H), 7.94 (s, 1H, Ar-H), 7.49 (dd, 1H,
3J = 4.4 Hz, 3J = 8.2 Hz, Ar-H), 7.41 (d, 1H, 4J = 2.8 Hz, Ar-H),
4
3
MHz, CDCl3): δ 8.50 (dd, 1H, J = 1.4 Hz, J = 4.6 Hz, Ar-H),
3
4
3
4
7.36 (d, 1H, J = 3.6 Hz, Ar-H), 7.24 (s, 1H, Ar-H), 7.04 (d, 1H,
8.05 (dd, 1H, J = 1.6 Hz, J = 8.0 Hz, Ar-H), 7.82 (d, 1H, J =
3
3
3J = 3.6 Hz, Ar-H), 6.14 (s, 1H, NH), 6.10 (s, 1H, CH), 2.14 (s,
3H, Ar-CH3). HRMS calcd for C20H13BrCl2N6OS ([M+H]+):
534.9505, found: 534.9501.
2.4 Hz, Ar-H), 7.46 (dd, 1H, J = 4.8 Hz, J = 8.0 Hz, Ar-H),
7.14 (d, 1H, 4J = 2.4 Hz, Ar-H), 6.26 (s, 1H, Ar-H), 5.95 (d, 1H,
3J = 1.6 Hz, NH), 5.71 (d, 1H, J = 3.6 Hz, CH), 3.07 (s, 3H,
3
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-3-ethyl-8-methyl-2,3-dihydroquinazolin-4(1H)-one (5h)
White solid; yield, 65 %; mp 222-224 ℃. 1H NMR (300 MHz,
NCH3), 2.09 (s, 3H, Ar-CH3). HRMS calcd for C18H14BrCl2N5O
([M-H]-): 463.9686, found: 463.9682.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-3-methoxy-8-methyl-2,3-dihydroquinazolin-4(1H)-one
(5b) White solid; yield, 89 %; mp 200-202 ℃. 1H NMR (400
4
3
CDCl3): δ 8.52 (dd, 1H, J = 1.7 Hz, J = 4.7 Hz, Ar-H), 8.06
(dd, 1H, 4J = 1.5 Hz, 3J = 8.1 Hz, Ar-H), 7.83 (d, 1H, 4J = 2.1 Hz,
Ar-H), 7.48 (dd, 1H, 3J = 4.8 Hz, 3J = 8.1 Hz, Ar-H), 7.13 (d, 1H,
4
3
MHz, CDCl3): δ 8.48 (dd, 1H, J = 1.6 Hz, J = 4.8 Hz, Ar-H),
3
4
3
4
4J = 2.4 Hz, Ar-H), 6.26 (s, 1H, Ar-H), 5.99 (d, 1H, J = 1.8 Hz,
8.04 (dd, 1H, J = 1.4 Hz, J = 8.2 Hz, Ar-H), 7.84 (d, 1H, J =
3
3
3
NH), 5.72 (d, 1H, J = 2.4 Hz, CH), 4.12-4.00 (m, 1H, NCH),
2.4 Hz, Ar-H), 7.45 (dd, 1H, J = 4.8 Hz, J = 8.0 Hz, Ar-H),
3
4
3.07-2.95 (m, 1H, NCH), 2.08 (s, 3H, Ar-CH3), 1.18 (t, 3H, J =
7.18 (d, 1H, J = 2.0 Hz, Ar-H), 6.44 (s, 1H, Ar-H), 6.07 (br s,
7.2 Hz, CH3). HRMS calcd for C19H16BrCl2N5O ([M+Na]+):
501.9813, found: 501.9800.
1H, NH), 6.03 (d, 1H, 3J = 2.4, CH), 3.83 (s, 3H, OCH3), 2.11 (s,
3H, Ar-CH3). HRMS calcd for C18H14BrCl2N5O2 ([M+H]+):
481.9781, found: 481.9785.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-3-
methyl-2,3-dihydroquinazolin-4(1H)-one (5i) White solid;
yield, 70 %; mp 233-235 ℃. 1H NMR (400 MHz, CDCl3): δ
8.52 (dd, 1H, 4J = 1.6 Hz, 3J = 4.4 Hz, Ar-H), 8.04 (dd, 1H, 4J =
1.2 Hz, 3J = 8.0 Hz, Ar-H), 7.98 (d, 1H, 3J = 7.6 Hz, Ar-H), 7.46
(dd, 1H, 3J = 4.8 Hz, 3J = 8.0 Hz, Ar-H), 7.30 (t, 1H, 3J = 8.0 Hz,
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-3-isopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-
one (5c) White solid; yield, 88 %; mp 222-224 ℃. 1H NMR
4
3
(400 MHz, CDCl3): δ 8.55 (dd, 1H, J = 1.4 Hz, J = 4.6 Hz,
Ar-H), 8.08 (dd, 1H, 4J = 1.6 Hz, 3J = 8.2 Hz, Ar-H), 7.84 (d, 1H,
4J = 2.4 Hz, Ar-H), 7.51 (dd, 1H, 3J = 4.4 Hz, 3J = 8.0 Hz, Ar-H),
3
3
Ar-H), 6.90 (t, 1H, J = 7.6 Hz, Ar-H), 6.62 (d, 1H, J = 7.6 Hz,
3
4
Ar-H), 6.28 (s, 1H, Ar-H), 5.74 (s, 1H, NH), 5.64 (d, 1H, J =
7.13 (d, 1H, J = 2.0 Hz, Ar-H), 6.27 (s, 1H, Ar-H), 5.88 (d, 1H,
3J = 2.0, NH), 5.67 (d, 1H, 3J = 2.4 Hz, CH), 4.97 (m, 1H, NCH),
2.09 (s, 3H, Ar-CH3), 1.18 (d, 3H, 3J = 6.8 Hz, CH3), 1.01 (d, 3H,
3J = 6.8 Hz, CH3). HRMS calcd for C20H18BrCl2N5O ([M+H]+):
494.0145, found: 494.0146.
2.0 Hz, CH), 3.05 (s, 3H, NCH3).
HRMS calcd for
C17H13BrClN5O ([M+Na]+): 439.9890, found: 439.9897.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-3,8-
dimethyl-2,3-dihydroquinazolin-4(1H)-one (5j) White solid;
yield, 80 %; mp 265-267 ℃. 1H NMR (300 MHz, CDCl3): δ
8.51 (dd, 1H, 4J = 1.4 Hz, 3J = 4.7 Hz, Ar-H), 8.05 (dd, 1H, 4J =
1.2 Hz, 3J = 8.1 Hz, Ar-H), 7.86 (d, 1H, 3J = 7.8 Hz, Ar-H), 7.47
(dd, 1H, 3J = 4.8 Hz, 3J = 8.1 Hz, Ar-H), 7.17 (d, 1H, 3J = 7.2 Hz,
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-3-
tert-butyl-6-chloro-8-methyl-2,3-dihydroquinazolin-4(1H)-
one (5d) White solid; yield, 85 %; mp 168-170 ℃. 1H NMR
4
3
(400 MHz, CDCl3): δ 8.53 (dd, 1H, J = 1.2 Hz, J = 4.8 Hz,
Ar-H), 8.06 (dd, 1H, 4J = 1.0 Hz, 3J = 8.0 Hz, Ar-H), 7.83 (d, 1H,
4J = 1.6 Hz, Ar-H), 7.49 (dd, 1H, 3J = 4.8 Hz, 3J = 8.0 Hz, Ar-H),
3
Ar-H), 6.82 (t, 1H, J = 7.7 Hz, Ar-H), 6.28 (s, 1H, Ar-H), 5.92
3
(s, 1H, NH), 5.72 (d, 1H, J = 2.1 Hz, CH), 3.08 (s, 3H, NCH3),
3
2.11 (s, 1H, Ar-CH3). HRMS calcd for C18H15BrClN5O
7.11 (s, 1H, Ar-H), 6.32 (s, 1H, Ar-H), 6.00 (d, 1H, J = 3.2,
([M+Na]+): 454.0046, found: 454.0047.
NH), 5.74 (d, 1H, 3J = 2.0 Hz, CH), 2.06 (s, 3H, Ar-CH3), 1.47 (s,
HRMS calcd for C21H20BrCl2N5O ([M+H]+):
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-8-methyl-2,3-dihydroquinazolin-4(1H)-one (5k) White
9H, CH3).
508.0301, found: 508.0302.
1
solid; yield, 75 %; mp 222-224 ℃. H NMR (400 MHz, CDCl3):
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-3-cyclopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-
one (5e) White solid; yield, 91 %; mp 267-269 ℃. 1H NMR
δ 8.47 (dd, 1H, 4J = 1.0 Hz, 3J = 4.6 Hz, Ar-H), 8.03 (dd, 1H, 4J
3
4
= 1.2 Hz, J = 8.0 Hz, Ar-H), 7.79 (d, 1H, J = 2.0 Hz, Ar-H),
3
3
4
4
3
7.45 (dd, 1H, J = 4.8 Hz, J = 8.0 Hz, Ar-H), 7.20 (d, 1H, J =
(400 MHz, CDCl3): δ 8.52 (dd, 1H, J = 1.4 Hz, J = 4.6 Hz,

1.6 Hz, Ar-H), 6.57 (s, 1H, Ar-H), 6.41 (s, 1H, CONH), 5.86 (s,
1H, NH), 5.65 (s, 1H, CH), 2.16 (s, 3H, CH3). HRMS calcd for
C17H12BrCl2N5O ([M+Na]+): 473.9500, found: 473.9501.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
7.39-7.31 (m, 1H, Ar-H), 7.08 (s, 1H, Ar-H), 6.77 (s, 1H, Ar-H),
6.20 (s, 1H, NH), 6.16 (s, 1H, CH), 3.14 (s, 3H, NCH3), 1.96 (s,
3H, Ar-CH3). HRMS calcd for C18H15Cl2N5O ([M+Na]+):
410.0551, found: 410.0616.
chloro-3-isopropyl-2,3-dihydroquinazolin-4(1H)-one
(5l)
2-(3-bromo-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-6-chloro-3-
cyclopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-one (5r)
White solid; yield, 79 %; mp 173-174 ℃. 1H NMR (400 MHz,
CDCl3): δ 8.53 (d, 3J = 4.2 Hz, 1H, Ar-H), 8.03 (d, 3J = 8.3 Hz,
White solid; yield, 72 %; mp 220-222 ℃. 1H NMR (400 MHz,
4
3
CDCl3): δ 8.58 (dd, 1H, J = 1.2 Hz, J = 4.8 Hz, Ar-H), 8.09
(dd, 1H, 4J = 1.6 Hz, 3J = 8.0 Hz, Ar-H), 7.99 (d, 1H, 4J = 2.4 Hz,
3
3
3
Ar-H), 7.53 (dd, 1H, J = 4.8 Hz, J = 8.0 Hz, Ar-H), 7.26 (dd,
1H, Ar-H), 7.94 (t, J = 7.5 Hz, 1H, Ar-H), 7.83 (s, 1H, Ar-H),
1H, 4J = 2.4 Hz, 3J = 8.4 Hz, Ar-H), 6.61 (d, 1H, 3J = 8.8 Hz, Ar-
7.39-7.32 (m, 1H, Ar-H), 7.07 (s, 1H, Ar-H), 6.88 (s, 1H, Ar-H),
6.28 (s, 1H, CH), 6.18 (s, 1H, NH), 2.69 (s, 1H, cyclopropyl),
1.94 (s, 3H, Ar-CH3), 0.97-0.82 (m, 2H, cyclopropyl), 0.68 (m,
2H, cyclopropyl). HRMS calcd for C20H17Cl2N5O ([M+Na]+):
436.0708, found: 436.0634.
3
H), 6.29 (s, 1H, Ar-H), 5.79 (d, 1H, J = 1.2 Hz, NH), 5.61 (d,
1H, 3J = 2.0 Hz, CH), 5.01-4.94 (m, 1H, NCH), 1.17 (d, 3H , 3J =
3
6.8 Hz, CH3), 0.99 (d, 3H, J = 6.8 Hz, CH3). HRMS calcd for
C19H16BrCl2N5O ([M+Na]+): 501.9813, found: 501.9807.
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
chloro-3-propyl-2,3-dihydroquinazolin-4(1H)-one
(5m)
chloro-3,8-dimethylquinazolin-4(3H)-one (5s)
2-Amino-5-
White solid; yield, 86 %; mp 203-205 ℃. 1H NMR (400 MHz,
chloro-N,3-dimethylbenzamide (4a) (0.099 g, 0.5 mmol) and 3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbaldehyde (3a)
(0.143 g, 0.5 mmol) were added to 20 mL of ethanol, then
refluxed and monitored with TLC. After 1 h, the reaction was
completed, the solution was evaporated, and the residue was
applied to a flash column chromatography by eluting with
petroleum ether/ethyl acetate (2:1) to give the compound 5s as a
white solid; yield, 30 %; mp 214-216 ℃. 1H NMR (400 MHz,
DMSO-d6): δ 8.44 (d, 1H, 3J = 4.4 Hz, Ar-H), 8.21 (d, 1H, 3J =
8.0 Hz, Ar-H), 7.90 (s, 1H, Ar-H), 7.65 (s, 1H, Ar-H), 7.58 (dd,
4
3
CDCl3): δ 8.54 (dd, 1H, J = 1.4 Hz, J = 4.6 Hz, Ar-H), 8.07
(dd, 1H, 4J = 1.2 Hz, 3J = 8.0 Hz, Ar-H), 7.96 (d, 1H, 4J = 2.4 Hz,
3
3
Ar-H), 7.50 (dd, 1H, J = 4.8 Hz, J = 8.0 Hz, Ar-H), 7.26 (dd,
1H, 4J = 2.4 Hz, 3J = 8.8 Hz, Ar-H), 6.59 (d, 1H, 3J = 8.4 Hz, Ar-
3
H), 6.28 (s, 1H, Ar-H), 6.85 (s, 1H, NH), 5.63 (d, 1H, J = 2.0
Hz, CH), 4.04-3.97 (m, 1H, NCH), 2.87-2.80 (m, 1H, NCH),
3
1.61-1.53 (m, 2H, CH2), 0.92 (t, 3H, J = 7.4 Hz, CH3). HRMS
calcd for C19H16BrCl2N5O ([M+Na]+): 501.9813, found:
501.9806.
3
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-
1H, J = 4.4 Hz, 3J = 8.0 Hz, Ar-H), 7.48 (s, 1H, Ar-H), 3.71 (s,
chloro-3-cyclohexyl-2,3-dihydroquinazolin-4(1H)-one
(5n)
3H, NCH3), 1.91 (s, 3H, Ar-CH3).
HRMS calcd for
White solid; yield, 84 %; mp 293-295 ℃. 1H NMR (400 MHz,
C18H13BrCl2N5O ([M+H]+): 463.9675, found: 463.9672.
4
3
CDCl3): δ 8.56 (dd, 1H, J = 1.5 Hz, J = 4.8 Hz, Ar-H), 8.08
(dd, 1H, 4J = 1.5 Hz, 3J = 8.1 Hz, Ar-H), 7.96 (d, 1H, 4J = 2.4 Hz,
4.1.5. 6-chloro-2,2,3,8-tetramethyl-2,3-dihydroquinazolin-
4(1H)-one 6.
3
3
Ar-H), 7.51 (dd, 1H, J = 4.8 Hz, J = 8.1 Hz, Ar-H), 7.24 (dd,
1H, 4J = 2.4 Hz, 3J = 8.4 Hz, Ar-H), 6.58 (d, 1H, 3J = 8.4 Hz, Ar-
2-Amino-5-chloro-N, 3-dimethylbenzamide (4a) (0.198 g, 1
mmol) was dissolved in 5 mL of acetone, followed by a catalytic
amount of p-toluenesulfonic acid monohydrate. The mixture
was refluxed for 1 h and the solvent was evaporated. The 20 mL
of ethyl acetate was added and the solution was washed with
saturated sodium bicarbonate, and brine. The ethyl acetate
solution was dried and evaporated to afford title compound as a
white solid; yield, 95 %; mp 154-156 ℃. 1H NMR (400 MHz,
3
H), 6.26 (s, 1H, Ar-H), 5.72 (d, 1H, J = 1.8 Hz, NH), 5.61 (d,
3
1H, J = 2.4 Hz, CH), 4.61-4.51 (m, 1H, NCH), 1.76-1.64 (m,
5H, cyclohexyl), 1.47-1.17 (m, 3H, cyclohexyl), 1.02-0.79 (m,
2H, cyclohexyl). HRMS calcd for C22H20BrCl2N5O ([M+Na]+):
542.0126, found: 542.0111.
6-bromo-2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-
5-yl)-3-cyclopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-
one (5o) White solid; yield, 80 %; mp 272-274 ℃. 1H NMR
(400 MHz, CDCl3): δ 8.52 (d, 1H, 3J = 3.6 Hz, Ar-H), 8.06 (dd,
1H, 4J = 0.8 Hz, 3J = 8.0 Hz, Ar-H), 7.99 (s, 1H, Ar-H), 7.49 (dd,
4
CDCl3): δ 7.79 (d, 1H, J = 2.0 Hz, Ar-H), 7.15 (s, 1H, Ar-H),
3.88 (s, 1H, NH), 3.07 (s, 3H, NCH3), 2.14 (s, 3H, Ar-CH3), 1.56
(s, 6H, C(CH3)2).
3
1H, J = 4.6 Hz, 3J = 8.2 Hz, Ar-H), 7.28 (s, 1H, Ar-H), 6.32 (s,
3
1H, Ar-H), 6.03 (s, 1H, NH), 5.70 (d ,1H, J = 2.4 Hz, CH),
4.2. Biological Assay.
2.69-2.64 (m, 1H, NCH), 2.08 (s, 3H, Ar-CH3), 1.12-1.05 (m, 1H,
cyclopropyl), 0.90-0.83 (m, 1H, cyclopropyl), 0.68-0.61 (m, 1H,
cyclopropyl), 0.51-0.45 (m, 1H, cyclopropyl). HRMS calcd for
C20H16Br2ClN5O ([M+Na]+): 557.9308, found: 557.9290.
Insecticidal activity against oriental armyworms was
performed on test organisms reared in a greenhouse. The
bioassay was replicated at 25 ± 1 ℃ according to statistical
requirements. Assessments were made on a dead/alive basis,
and mortality rates were corrected applying Abbott’s formula.41
Evaluation was based on a percentage scale of 0-100, where 0
equals no activity, and 100 equals total kill. Error of the
2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-3-
cyclopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-one (5p)
White solid; yield, 86 %; mp 217-219 ℃. 1H NMR (400 MHz,
4
3
CDCl3): δ 8.54 (dd, 1H, J = 1.4 Hz, J = 3.6 Hz, Ar-H), 8.06
(d, 1H, 3J = 8.0 Hz, Ar-H), 7.89 (d, 1H, 3J = 7.6 Hz, Ar-H), 7.48
(dd, 1H, 3J = 4.8 Hz, 3J = 8.0 Hz, Ar-H), 7.18 (d, 1H, 3J = 7.6 Hz,
experiments was
5
%.
For comparative purposes,
chlorantraniliprole was tested as reference under the same
conditions. The insecticidal activity was summarized in Table 2.
The larvicidal activity of compounds 5a-s and
chlorantraniliprole were evaluated using the reported
3
Ar-H), 6.82 (t, 1H, J = 7.6 Hz, Ar-H), 6.34 (s, 1H, Ar-H), 5.93
3
(s, 1H, NH), 5.72 (d ,1H, J = 2.4 Hz, CH), 2.70-2.65 (m, 1H,
NCH), 2.10 (s, 3H, Ar-CH3), 1.12-1.04 (m, 1H, cyclopropyl),
0.90-0.83 (m, 1H, cyclopropyl), 0.66-0.59 (m, 1H, cyclopropyl),
procedure.23
The insecticidal activity against oriental
armyworms was tested by foliar application; individual corn
(Tangyu 10, Zeamays L.) leaves were placed on moistened
pieces of filter paper in Petri dishes. The leaves were then
sprayed with the test solution and allowed to dry. The dishes
were infested with 10 fourth-instar oriental armyworm larvae.
Percentage mortalities were evaluated 2 days after treatment.
0.51-0.45 (m, 1H, cyclopropyl).
HRMS calcd for
C20H17BrClN5O ([M+Na]+): 480.0203, found: 480.0201.
6-chloro-2-(3-chloro-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-3-
cyclopropyl-8-methyl-2,3-dihydroquinazolin-4(1H)-one (5q)
White solid; yield, 82 %; mp 208-209 ℃. 1H NMR (400 MHz,
CDCl3): δ 8.52 (d, 3J = 4.1 Hz, 1H, Ar-H), 8.01 (d, 3J = 8.3 Hz,
3
Each
treatment
was
replicated
three
times.
1H, Ar-H), 7.94 (t, J = 7.6 Hz, 1H, Ar-H), 7.81 (s, 1H, Ar-H),

Table 2. Insecticidal activities of compounds 5a-s and chlorantraniliprole against oriental armyworms
Larvicidal activity (%)
at a concentration of (mg/L)
Comp.
5a
5b
5c
R1
CH3
OCH3
i-Pr
R2
X
Y
50
25
100
30
0
10
100
20
5
80
0
6-Cl, 8-CH3 Br Cl 100
6-Cl, 8-CH3 Br Cl
6-Cl, 8-CH3 Br Cl
6-Cl, 8-CH3 Br Cl
50
10
0
5d
5e
t-Bu
Cyclopropyl 6-Cl, 8-CH3 Br Cl
40
50
20
0
10
0
5f
n-Pr
2-thiazolyl
CH2CH3
CH3
6-Cl, 8-CH3 Br Cl
6-Cl, 8-CH3 Br Cl
0
0
0
5g
5h
5i
6-Cl, 8-CH3 Br Cl 100
50
H
Br Cl
20a
5j
CH3
8-CH3
Br Cl 100
70
100
100
0
20
100
60
0
80
0
5k
5l
H
6-Cl, 8-CH3 Br Cl 100
i-Pr
6-Cl
6-Cl
6-Cl
Br Cl 100
5m
5n
5o
5p
5q
5r
n-Pr
Br Cl
Br Cl
70
Cyclohexyl
20a
Cyclopropyl 6-Br,8-CH3 Br Cl 100
60
0
Cyclopropyl
CH3
8-CH3
8-CH3
8-CH3
Br Cl
40b
60a
10a
20a
Cl
Cl
H
H
Cyclopropyl
5s
Chlorantraniliprole
100
a 200 mg/L b 100 mg/L
3. David, B. S.; Daniel, C.; Timothy, R. C. Invert Neurosci. 2008, 8,
107-119.
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Acknowledgments
The project was supported by the National Basic Research
Program of China (973 project 2010CB126106), Natural Science
Foundation of China (No. 31000861) and the National Key
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Graphical Abstract
5a induced calcium elevation in isolated S.
exigua in the presence or absence of
extracellular calcium.
Synthesis and insecticidal activities of
2,3-dihydroquinazolin-4(1H)-one derivatives
targeting calcium channel
Yunyun Zhoua §, Qi Fengb §, Fengjuan Dia, Qiaoxiao Liua, Duoyi Wanga, Youwei Chena, Lixia Xionga, Haibin
Songa, Yuxin Lia*, Zhengming Lia*
a State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, PR China.
b Zhejiang Base of National Southern Pesticide Research Centre, Zhejiang Research Institute of Chemical
Industry, Hangzhou 310023, PR China.
§ These authors contributed equally to the work.