Metal-Free Direct Oxidative C?N Bond Coupling of Quinoxalin-2(1H)-ones with Azoles under Mild Conditions

Article abstract of DOI:10.1002/ejoc.202100269

Direct C3?H amination of quinoxalin-2(1H)-ones with azoles under mild conditions promoted by PIFA has been achieved in good yield in a very fast manner. Mechanistic study revealed that the reaction proceeds through a radical process. In addition, this method could be applied to gram-scale reaction.

Full text of DOI:10.1002/ejoc.202100269

Full Papers
doi.org/10.1002/ejoc.202100269
Metal-Free Direct Oxidative CÀ N Bond Coupling of
Quinoxalin-2(1H)-ones with Azoles under Mild Conditions
Jingwen Guo, Lina Zhang, Xinyue Du, Liting Zhang, Yuepiao Cai,* and Qinqin Xia*
[a]
[a]
[a]
[a]
[a]
[a]
Direct C3À H amination of quinoxalin-2(1H)-ones with azoles
under mild conditions promoted by PIFA has been achieved in
good yield in a very fast manner. Mechanistic study revealed
that the reaction proceeds through a radical process. In
addition, this method could be applied to gram-scale reaction.
Introduction
Quinoxalin-2(1H)-ones are a crucial class of bioactive skeleton
[1]
widely found in natural products and pharmaceuticals, they
exhibit a wide spectrum of biological properties including
[2]
anticancer, antidiabetic, antimicrobial, and anti-inflammatory.
Recent years, numerous methods for the direct functionalisation
of the C3À H bonds of quinoxalin-2(1H)-ones have been
[3]
[4]
[5]
[6]
reported,
including alkylation,
arylation,
acylation,
[7]
[8]
alkoxylation and phosphonation. In particular, owing to the
presence of 3-N-substituted quinoxalin-2(1H)-ones in numerous
biologically active molecules, several approaches for their
syntheses have been established. For instance, Gulevskaya, Cui,
Phan and Jain group independently reported manganese,
copper, copper-organic framework or I catalytic systems for
2
[9]
direct amination of quinoxalinones. Wei and Zeng group
subsequently demonstrated the direct amination of quinoxali-
nones using a visible-light-catalyzed or electrochemical method
[
10]
(
Scheme 1a), respectively, While the direct CÀ H amidation of
Quinoxalin-2(1H)-ones have also been concurrently reported by
[11]
several groups (Scheme 1b). Other N-containing groups such
as sulfoximines and sulfonamides were also introduced into C3
position of quinoxalin-2(1H)-ones by Yotphan and Zhao groups,
[12]
respectively (Scheme 1c). Although these direct approaches
for the construction of 3-N-substituted quinoxalin-2(1H)-ones
have been developed, we noted that the introduction of azoles
at the C3 position of quinoxalin-2(1H)-ones through direct C3-H
functionalization remains rare and challenging.
Scheme 1. Synthesis of 3-N-substituted quinoxalin-2(1H)-one derivatives.
Azoles are an important class of compound that are widely
found in pharmaceutical agents, natural products, and func-
[13]
tional materials. Hence, the development of new synthetic
methods for the functionalization of azoles is of great interest
in organic synthesis, especially for the direct oxidative coupling
[15]
sulfinates. Very recently, Li and co-workers reported a visible-
light-promoted C-N coupling of quinoxaline-2(1H)-ones with
[14]
[16]
of CÀ H and NÀ H bonds. We recently reported the NBS or NIS
mediated direct N-sulfonylation of azoles with sodium
azoles (Scheme 1d). However, long reaction time (20 h) were
required and NH unprotected quinoxalin-2(1H)-ones were not
tolerated for this reaction. As a continuation of our previous
work, herein, we report a simple, efficient and convenient
method for the direct amination of quinoxalinones at their C3
[
a] J. Guo, L. Zhang, X. Du, L. Zhang, Prof. Y. Cai, Prof. Q. Xia
School of Pharmaceutical Sciences
Wenzhou Medical University
positions using PhI(OTFA) , which mediates oxidative CÀ N bond
2
Wenzhou 325035, P. R. China
E-mail: ypcai@126.com
coupling between the quinoxalin-2(1H)-one and azole.
zdxiaqinqin@163.com
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202100269
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Results and Discussion
Initially, we chose N-benzyl-quinoxalin-2(1H)-one (1a) and
pyrazole (2a) as the model compounds to optimize the reaction
conditions (Table 1). To our delight, the desired product 3a was
isolated in 34% yield in the presence of K S O at 70°C for 12 h
2
2
4
(
entry 1). Various oxidants, including Na S O , (NH) S O , I , tert-
2 2 8 2 2 8 2
butyl hydroperoxide (TBHP), N-iodosuccinimide (NIS), (diacetox-
yiodo)benzene (PIDA) and [bis(trifluoroacetoxy)iodo]benzene
(
(
PIFA) were tested, among which PIFA gave the best yield
35%) (entries 2–8). The effect of reaction temperature was also
investigated, and we found that the reaction could proceed
smoothly at room temperature (entries 9 and 10). Upon screen-
ing reactions in different solvents (entries 11–17), ethyl acetate
provided the highest yield and the reaction essentially
completed in 1 hour (entry 18). Finally, a survey of oxidant and
azole loading revealed that 2.0 equiv. of PIFA and pyrazole (2a)
was the most suitable (entry 19). Additionally, the result had no
obvious difference if the reaction was performed in a nitrogen
atmosphere (entry 20). In conclusion, the optimized conditions
were summarized as 1a (0.3 mmol), 2a (2 equiv), and PIFA
(2 equiv) in EtOAc at room temperature under air.
With the optimal reaction conditions in hand, the substrate
scope of the CÀ N coupling was subsequently explored by
employing various quinoxaline-2(1H)-ones (1) with pyrazole
(2a). The results are summarized in Scheme 2. To our delight, N-
benzyl functions with electron-rich groups (À CH , À Ph, À OCH )
3
3
and electron-poor groups (À F, À Cl, À Br, and À NO ) were
2
compatible with the reaction with good yields (3b–3j). When
[a]
Table 1. Optimization of Reaction Conditions.
Scheme 2. Substrate scope of quinoxalinones with pyrazole. Reaction
conditions: 1 (0.3 mmol), 2a (0.6 mmol), PIFA (0.6 mmol) in EtOAc (1.5 mL) at
room temperature for 1 h.
[
b]
Entry
Oxidant
T [°C]
Time
Solvent
Yield [%]
1
2
3
4
5
6
7
8
9
K
Na
2
S
2
2
O
4
70
70
70
70
70
70
70
70
50
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
1h
1 h
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
DCE
toluene
THF
1,4-dioxane
EtOAc
EtOAc
EtOAc
EtOAc
34
21
18
17
11
13
30
35
38
44
45
51
34
29
47
22
78
89
83
88
S
2
O
4
(NH
4 2 2 8
) S O
I
2
TBHP
NIS
we carried out the reaction of N-methyl quinoxalin-2(1H)-one
with pyrazole (2a), the corresponding product 3k was obtained
in 43% yield. However, other N-alkyl quinoxalin-2(1H)-ones
showed very good reactivity with pyrazole (2a) under the
optimal conditions to give the corresponding products (3l–3q)
in 77–88% yields. It is noteworthy that quinoxalin-2(1H)-ones
bearing the sensitive groups, including alkenyl and alkynyl
groups were well tolerated to provide the desired products in
moderate to excellent yields (3r, 3s and 3t). Other important
functional-groups including ester, ketone, naphthalene and
pyridine groups were also well tolerated (3u–3x). Afterward,
C6- or C7-substituted quinoxalin-2(1H)-ones were investigated.
All the substituted substrates, whether the substituents are
electron-rich or electron-deficient, underwent smoothly to
provide the corresponding products in good yields (3y, 3z,
PIDA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
1
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
8
[
c]
9
0
[
d]
1 h
[
a] Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), oxidant (0.6 mmol),
solvent (1.5 mL), 1 h. [b] Yields of isolated product. [c] 2a (0.45 mmol), PIFA
0.45 mmol). [d] Under a N atmosphere.
(
2
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3
aa–3ac). Notably, N-unprotected quinoxalin-2(1H)-ones were
and NÀ H oxidative coupling reaction (4l and 4m). 1,2,4-Triazole
was very effective for this reaction and gave the corresponding
product 4n in 89% yield. Moreover, benzotriazole and tetrazole
were also suitable for this reaction, afforded the desired
products 4o and 4p in 38% and 50% yields, respectively.
Furthermore, a scale-up reaction was performed to demon-
strate the practicability of the developed protocol (5 mmol
scale). To our satisfaction, the reaction proceeded smoothly
under the optimized conditions to provide product 3a in 81%
yield (Scheme 4).
To gain insight into the mechanism, several control experi-
ments were performed (Scheme 5). When 2.0 equiv. of BHT (2,6-
Di-tert-butyl-4-methylphenol) was added into the reaction
system under the standard conditions, only 20% yield of
product 3a was observed, and 5a was detected by HRMS
(Scheme 5a). When 2.0 equiv. of hydroquinone was added to
the reaction, the yield of 3a was obtained in less than 5%, and
well compatible with present reaction conditions, furnishing the
desired products in satisfactory yields (3ad–3af).
After exploring the scope of quinoxaline-2(1H)-ones, we
expanded the range of azoles derivatives (Scheme 3). Both N-
benzyl quinoxaline-2(1H)-one and NÀ H free quinoxaline-2(1H)-
one showed a tolerance toward many azole coupling partners,
and the oxidative CÀ N bond coupling reactions can be achieved
without any difficulties (4a, 4b, 4e and 4f). The reaction of N-
benzyl quinoxaline-2(1H)-one and 3-halogen-substituted pyra-
zoles proceeded smoothly, affording the desired products in
excellent yields (4a, 4c and 4d). Pyrazoles with different 3-
substituents including tert-butyl, phenyl, ester, trifluoromethyl
and nitro groups on their rings could furnish the expected
products in moderate to good yields (4g–4k). Benzimidazole
and indazole were also effective substrates for this direct CÀ H
6
a was detected by HRMS (Scheme 5b) (see the Supporting
Information). These findings suggest the possible involvement
of a radical process in this transformation.
Based on the above-mentioned results and previous
[7b,d,17]
reports,
shown in Scheme 6. Initially, pyrazole (2a) is oxidized by PhI
OTFA) to furnish to form the corresponding N-centered radical
we proposed a possible reaction mechanism as
(
2
A. Then, the obtained radical then attacked substrate 1a to
produce nitrogen radical intermediate B. Next, intermediate B
underwent the 1,2-hydrogen shift to form carbon radical C.
Carbon radical C is further oxidized by PhI(OTFA) to form the
2
carbon cation intermediate D through a single electron transfer
(SET) process. Finally, the target product 3a was obtained
through a deprotonation process of carbon cation intermediate
D.
Scheme 4. Gram-Scale Reaction.
Scheme 3. Substrate scope of azoles. [a] Reaction conditions: 1 (0.3 mmol), 2
(
[
0.6 mmol), PIFA (0.6 mmol) in EtOAc (1.5 mL) at room temperature for 1 h.
b] Reaction for 3 h. [c] Stirred at 40°C, 12 h. [d] Stirred at 40°C, 3 h.
Scheme 5. Controlled experiments for mechanism study.
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by column chromatography on silica gel to give the product 3 or 4
using ethyl acetate/petroleum ether as an eluant.
Benzyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3a)
1
White solid (81 mg, 89% yield); M. p.=133.4–135.9°C. H NMR
(
1
7
500 MHz, CDCl ) δ 9.05 (d, J=2.7 Hz, 1H), 7.97 (dd, J=8.0, 1.3 Hz,
3
H), 7.84 (d, J=1.3 Hz, 1H), 7.40–7.35 (m, 1H), 7.28 (t, J=7.7 Hz, 1H),
13
.25–7.17 (m, 6H), 6.44 (dd, J=2.6, 1.7 Hz, 1H), 5.53 (s, 2H). C NMR
(
1
126 MHz, CDCl ) δ 150.8, 143.49, 142.69, 134.69, 133.31, 131.98,
31.56, 130.32, 130.11, 129.07, 127.94, 126.80, 124.66, 114.45,
3
1
08.35, 46.69. This is a known structure. These data are similar to
[16]
the reported one.
1
-(4-Methylbenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(
3b)
Scheme 6. Plausible mechanism.
1
White solid (84 mg, 88% yield); M. p.=146.0–148.7°C. H NMR
(
7
500 MHz, CDCl ) δ 9.13 (d, J=2.6 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H),
.92 (s, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.35 (dd, J=13.6, 7.9 Hz, 2H),
3
Conclusion
7.14 (dd, J=19.4, 8.0 Hz, 4H), 6.52 (d, J=1.6 Hz, 1H), 5.57 (s, 2H),
1
3
2
1
1
.30 (s, 3H). C NMR (126 MHz, CDCl ) δ 150.84, 143.46, 142.69,
37.73, 133.34, 132.02, 131.68, 131.56, 130.31, 130.09, 129.72,
3
In conclusion, we have developed a rapid, simple, convenient
and mild method for C3-amination of quinoxaline-2(1H)-ones
with azoles. Under the standard condition, a variety of versatile
functional groups were tolerated in this reaction to give the
desired products in good to excellent yields. In addition, this
method could be applied to gram-scale reaction. This method-
ology will exhibit promising potential for applications in
synthetic and medicinal chemistry.
26.83, 124.61, 114.48, 108.32, 46.50, 21.09. HRMS (ESI): Calculated
+
for C H N O [M+H] : 317.1402, Found: 317.1400.
1
9
17
4
1
-(3-Methylbenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(
3c)
1
White solid (90 mg, 95% yield); M. p.=116.2–117.0°C. H NMR
(500 MHz, CDCl ) δ 9.12 (d, J=2.7 Hz, 1H), 8.02 (dd, J=8.0, 1.4 Hz,
3
1
7
7
1
1
H), 7.90 (d, J=1.4 Hz, 1H), 7.42 (ddd, J=8.5, 7.4, 1.5 Hz, 1H), 7.35–
.31 (m, 1H), 7.28 (dd, J=8.4, 0.8 Hz, 1H), 7.18 (t, J=7.9 Hz, 1H),
.05 (d, J=7.7 Hz, 1H), 7.02 (d, J=6.0 Hz, 2H), 6.50 (dd, J=2.7,
Experimental Section
13
.6 Hz, 1H), 5.54 (s, 2H), 2.26 (s, 3H). C NMR (126 MHz, CDCl ) δ
3
50.82, 143.46, 142.66, 138.88, 134.62, 133.34, 132.02, 131.52,
General methods and materials
130.22, 130.11, 128.91, 128.70, 127.30, 124.61, 123.82, 114.52,
+
1
3
08.33, 46.67, 21.43. HRMS (ESI): Calculated for C H N O [M+H] :
17.1402, Found: 317.1394.
1
13
19 17 4
H and C NMR spectra were recorded on a Bruker 500 NMR
1
13
spectrometers (500 MHz for H, 126 MHz for C) in CDCl (with TMS
3
as internal standard). All chemical shifts were reported in δ units
with references to the residual solvent resonances of the
deuterated solvents for proton and carbon chemical shifts.
Coupling constants, J, are reported in hertz. Mass data were
measured with QTOF6600 mass spectrometer. Melting points (m.p.)
were determined on a capillary melting point apparatus and were
uncorrected. The crude products were purified by flash column
chromatography on silica gel and the reported yields are the actual
isolated yields of pure products. Thin-layer chromatography (TLC)
was performed using silica gel plates with fluorescence F254, and
visualized with short-wavelength UV light (254 nm). All other
chemicals were purchased from Chemical Co. and used as received
unless otherwise specified.
1
-(4-Methoxybenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(
3d)
1
White solid (90 mg, 90% yield); M. p.=132.6–133.6
(500 MHz, CDCl
7.89 (s, 1H), 7.44 (t, J=7.8 Hz, 1H), 7.35 (d, J=0.9 Hz, 1H), 7.34–7.31
(m, 1H), 7.20 (d, J=7.7 Hz, 2H), 6.8–6.78 (m, 2H), 6.50 (d, J=1.3 Hz,
1H), 5.51 (s, 2H), 3.72 (d, J=1.8 Hz, 3H). C NMR (126 MHz, CDCl ) δ
158.23, 149.77, 142.40, 141.67, 132.26, 130.94, 130.52, 129.25,
129.02, 127.32, 125.70, 123.54, 113.39, 107.26, 54.23, 45.13. HRMS
(ESI): Calculated for
333.1352.
°
C. H NMR
) δ 9.11 (d, J=2.4 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H),
3
1
3
3
+
C
H
N
17
O
2
[M+H] : 333.1352, Found:
19
4
General procedure for the amination of
quinoxalin-2(1H)-ones with azoles.
1-([1,1’-Biphenyl]-4-ylmethyl)-3-(1H-pyrazol-1-yl)
quinoxalin-2(1H)-one (3e)
1
White solid (106 mg, 93% yield); M. p.=157.0–158.2
°
C. H NMR
An overdried 15 mL pressure tube equipped with a magnetic stir
bar was charged with quinoxaline-2(1H)- one (0.3 mmol), pyrazoles
(500 MHz, CDCl
) δ 9.15 (d, J=2.7 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H),
7.93 (s, 1H), 7.54 (t, J=8.7 Hz, 4H), 7.50–7.46 (m, 1H), 7.38 (ddd, J=
10.5, 8.6, 6.2 Hz, 4H), 7.33 (t, J=8.3 Hz, 3H), 6.56–6.51 (m, 1H), 5.64
(s, 2H). C NMR (126 MHz, CDCl ) δ 150.86, 143.53, 142.71, 140.96,
140.35, 133.67, 133.34, 132.01, 131.60, 130.37, 130.18, 128.83,
127.78, 127.52, 127.31, 127.04, 124.72, 114.46, 108.40, 46.47. HRMS
ESI): Calculated for C H N O [M+H] : 379.1559, Found: 379.1559.
3
(0.6 mmol), PIFA (0.6 mmol), and EtOAc (1.5 mL). The mixture was
stirred at room temperature for 1 h under air. After completion of
1
3
the reaction, diluted with 10 mL of H O, and extracted with EtOAc
3
2
(
2×10 mL). The combined organic extracts were dried over Na SO ,
2
4
filtered, and concentrated under vacuum. The residue was purified
+
(
2
4
19
4
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1
-(4-Nitrobenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3f)
1-Methyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3k)
1
1
White solid (71 mg, 68% yield); M. p.=177.8–178.9°C. H NMR
White solid (29 mg, 43% yield); M. p.=150.2–151.8°C. H NMR
(
8
500 MHz, CDCl3) δ 9.05 (d, J=2.6 Hz, 1H), 8.16 (d, J=8.7 Hz, 2H),
.04 (d, J=8.0 Hz, 1H), 7.90 (s, 1H), 7.48–7.37 (m, 4H), 7.18 (d, J=
.4 Hz, 1H), 6.55–6.48 (m, 1H), 5.68 (s, 2H). C NMR (126 MHz, CDCl3)
(500 MHz, CDCl ) δ 9.10 (d, J=2.7 Hz, 1H), 8.04 (dd, J=8.0, 1.3 Hz,
1H), 7.90 (d, J=1.2 Hz, 1H), 7.61–7.56 (m, 1H), 7.43–7.39 (m, 1H),
7.37 (d, J=8.4 Hz, 1H), 6.52 (dd, J=2.6, 1.7 Hz, 1H), 3.83 (s, 3H).
3
13
13
8
C
δ 149.68, 146.62, 142.68, 141.53, 140.99, 132.14, 130.54, 130.51,
29.56, 129.35, 126.70, 124.08, 123.29, 112.83, 107.57, 45.10. HRMS
NMR (126 MHz, CDCl ) δ 150.70, 143.39, 142.62, 133.20, 132.59,
3
1
131.32, 130.25, 130.10, 124.61, 113.65, 108.27, 29.92. This is a known
+
[16]
(
ESI): Calculated for C H N O [M+H] : 348.1097, Found:
structure. These data are similar to the reported one.
18
14
5
3
348.1097.
1
-Ethyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3l)
1
-(3-Nitrobenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
1
White solid (63 mg, 88% yield). M. p.=105.5–107.8°C. H NMR
(3g)
(500 MHz, CDCl ) δ 9.08 (d, J=2.7 Hz, 1H), 8.02 (d, J=8.1 Hz, 1H),
3
1
White solid (77 mg, 74% yield); M. p.=165.1–167.0°C. H NMR
7.87 (d, J=0.9 Hz, 1H), 7.55 (dd, J=11.6, 4.1 Hz, 1H), 7.36 (t, J=
8.5 Hz, 2H), 6.51–6.47 (m, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.41 (t, J=
(
(
500 MHz, CDCl ) δ 9.05 (d, J=2.4 Hz, 1H), 8.20–8.09 (m, 2H), 8.04
d, J=7.9 Hz, 1H), 7.90 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.52–7.44 (m,
3
1
3
7.2 Hz, 3H). C NMR (126 MHz, CDCl ) δ 150.14, 143.31, 142.58,
3
2
H), 7.38 (t, J=7.6 Hz, 1H), 7.23 (d, J=8.3 Hz, 1H), 6.51 (s, 1H), 5.66
133.18, 131.60, 131.50, 130.46, 130.07, 124.39, 113.48, 108.20, 38.29,
12.39. This is a known structure. These data are similar to the
reported one.
13
(
s, 2H). C NMR (126 MHz, CDCl ) δ 150.75, 148.63, 143.68, 142.58,
36.92, 133.18, 132.90, 131.57, 131.54, 130.59, 130.39, 130.24,
3
[16]
1
1
25.07, 123.13, 122.10, 113.81, 108.55, 46.02. HRMS (ESI): Calculated
+
for C H N O [M+H] : 348.1097, Found: 348.1096.
18
14
5
3
1
-Propyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3m)
1
White solid (61 mg, 80% yield); M. p.=84.5–86.5°C. H NMR
1
-(4-Fluorobenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(
1
500 MHz, CDCl ) δ 9.08 (d, J=2.7 Hz, 1H), 8.02 (dd, J=8.0, 1.2 Hz,
H), 7.87 (d, J=1.2 Hz, 1H), 7.56–7.51 (m, 1H), 7.36 (dd, J=11.2,
3
(3h)
1
White solid (66 mg, 69% yield); M. p.=162.2–163.9°C. H NMR
4.1 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 4.33–4.28 (m, 2H), 1.83 (dt, J=
13
(
1
500 MHz, CDCl3) δ 9.11 (d, J=2.7 Hz, 1H), 8.06 (dd, J=8.0, 1.3 Hz,
H), 7.93 (d, J=1.0 Hz, 1H), 7.52–7.47 (m, 1H), 7.42–7.37 (m, 1H),
15.0, 7.5 Hz, 2H), 1.06 (t, J=7.4 Hz, 3H). C NMR (126 MHz, CDCl ) δ
3
150.40, 143.31, 142.60, 133.19, 131.77, 131.55, 130.43, 130.00,
7
.34–7.26 (m, 3H), 7.05–7.00 (m, 2H), 6.57–6.50 (m, 1H), 5.59 (s, 2H).
124.37, 113.67, 108.19, 44.67, 20.66, 11.35. HRMS (ESI): Calculated
1
3
+
C NMR (126 MHz, CDCl ) δ 162.33 (d, J=248.22 Hz), 150.78,
for C14
H
15
N
4
O [M+H] : 255.1246, Found: 255.1248.
3
1
43.53, 142.67, 133.23, 131.81, 131.57, 130.47 (d, J=3.78 Hz), 130.29
(
d, J=31.5 Hz), 128.74 (d, J=8.82 Hz), 124.76, 116.12, 115.95,
14.20, 108.40, 46.02. F NMR (376 MHz, CDCl ) δ À 113.839. HRMS
19
1
- Butyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3n)
1
3
+
(ESI): Calculated for C H FN O [M+H] : 321.1152, Found:
1
18
14
4
Yellow oil (66 mg, 82% yield); H NMR (500 MHz, CDCl3) δ 9.09 (d,
J=2.7 Hz, 1H), 8.04 (dd, J=8.0, 1.3 Hz, 1H), 7.89 (d, J=1.3 Hz, 1H),
321.1163.
7
4
7
1
.58–7.55 (m, 1H), 7.41–7.34 (m, 2H), 6.50 (dd, J=2.7, 1.6 Hz, 1H),
.42–4.32 (m, 2H), 1.83–1.77 (m, 2H), 1.56–1.48 (m, 2H), 1.02 (t, J=
1
-(4-Chlorobenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
1
3
.4 Hz, 3H). C NMR (126 MHz, CDCl ) δ 150.39, 143.33, 142.60,
3
(3i)
33.20, 131.79, 131.60, 130.47, 130.02, 124.39, 113.65, 108.20, 43.06,
1
+
White solid (75 mg, 74% yield); M. p.=164.8–166.6°C. H NMR
29.31, 20.29, 13.76. HRMS (ESI): Calculated for C15
269.1402, Found: 269.1402.
H
17
N
4
O [M+H] :
(
500 MHz, CDCl ) δ 9.05 (d, J=2.7 Hz, 1H), 8.00 (dd, J=8.0, 1.3 Hz,
H), 7.88 (s, 1H), 7.45–7.39 (m, 1H), 7.33 (dd, J=10.9, 4.4 Hz, 1H),
.23 (dd, J=9.4, 6.2 Hz, 3H), 7.17 (d, J=8.4 Hz, 2H), 6.48 (dd, J=2.6,
.6 Hz, 1H), 5.52 (s, 2H). C NMR (126 MHz, CDCl ) δ 150.75, 143.56,
42.63, 133.88, 133.22, 133.23, 131.76, 131.55, 130.42, 130.18,
29.25, 128.31, 124.81, 114.17, 108.43, 46.07. HRMS (ESI): Calculated
3
1
7
1
1
1
13
1
-Isobutyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3o)
3
1
Yellow oil (66 mg, 82% yield); H NMR (500 MHz, CDCl ) δ 9.07 (d,
J=2.7 Hz, 1H), 8.02 (dd, J=8.0, 1.4 Hz, 1H), 7.88 (d, J=1.3 Hz, 1H),
7
4
3
+
for C H ClN O [M+H] : 337.0856, Found: 337.0856.
18
14
4
.54–7.51 (m, 1H), 7.3–7.32 (m, 2H), 6.49 (dd, J=2.6, 1.7 Hz, 1H),
13
.24 (d, J=7.5 Hz, 2H), 2.35–2.26 (m, 1H), 1.02 (d, J=6.7 Hz, 6H).
C
NMR (126 MHz, CDCl ) δ 150.83, 143.32, 142.67, 133.25, 132.08,
3
1
-(4-Bromobenzyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
1
31.52, 130.46, 129.86, 124.36, 114.08, 108.17, 49.77, 27.32, 20.19.
(3j)
+
HRMS (ESI): Calculated for C H N O [M+H] : 269.1402, Found:
1
5
17
4
1
White solid (97 mg, 85% yield); M. p.=166.2–167.6°C. H NMR
269.1424
(
1
500 MHz, CDCl3) δ 9.09 (d, J=2.7 Hz, 1H), 8.04 (dd, J=8.0, 1.3 Hz,
H), 7.91 (d, J=1.2 Hz, 1H), 7.48–7.43 (m, 3H), 7.39–7.35 (m, 1H),
13
1-Hexyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3p)
7.24 (s, 1H), 7.14 (d, J=8.4 Hz, 2H), 6.52 (dd, 1H), 5.54 (s, 2H).
C
NMR (126 MHz, CDCl ) δ 149.73, 142.54, 141.60, 132.72, 132.20,
1
3
Yellow oil (68 mg, 77% yield); H NMR (500 MHz, CDCl ) δ 9.08 (d,
3
1
31.18, 130.72, 130.53, 129.41, 129.16, 127.59, 123.79, 120.91,
J=2.7 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.88 (s, 1H), 7.55 (dd, J=11.5,
.2 Hz, 1H), 7.37 (t, J=7.7 Hz, 1H), 7.34 (d, J=8.5 Hz, 1H), 6.49 (dd,
J=2.5, 1.6 Hz, 1H), 4.38–4.31 (m, 2H), 1.83–1.76 (m, 2H), 1.48 (dd,
J=14.6, 7.4 Hz, 2H), 1.39–1.30 (m, 4H), 0.89 (t, J=6.9 Hz, 3H).
113.14, 107.41, 45.10. HRMS (ESI): Calculated for C H BrN O [M+
18
14
4
4
+
H] : 381.0351, Found: 381.0352.
1
3
C
NMR (126 MHz, CDCl ) δ 150.35, 143.31, 142.60, 133.19, 131.77,
3
131.58, 130.44, 130.01, 124.36, 113.64, 108.18, 43.29, 31.42, 27.24,
Eur. J. Org. Chem. 2021, 2230–2238
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Full Papers
doi.org/10.1002/ejoc.202100269
+
2
2
6.66, 22.52, 13.97. HRMS (ESI): Calculated for C H N O [M+H] :
97.1715, Found: 297.1715.
1-(2-Oxo-2-phenylethyl)-3-(1H-pyrazol-1-yl)quinoxalin-
2(1H)-one (3v)
17
21
4
1
White solid (72 mg, 73% yield); M. p.=215.2–216.2°C. H NMR
(
1
4
500 MHz, CDCl ) δ 9.02 (d, J=2.7 Hz, 1H), 8.10–8.03 (m, 3H), 7.90 (s,
H), 7.68 (t, J=7.5 Hz, 1H), 7.55 (t, J=7.7 Hz, 2H), 7.45 (dd, J=11.4,
1
-(Cyclohexylmethyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
3
(3q)
.2 Hz, 1H), 7.37 (t, J=7.6 Hz, 1H), 6.99 (d, J=8.3 Hz, 1H), 6.52–6.47
1
13
White solid (78 mg, 84% yield); M. p.=125.2–127.9°C. H NMR
(m, 1H), 5.82 (s, 2H). C NMR (126 MHz, CDCl ) δ 190.47, 150.55,
3
(
500 MHz, CDCl ) δ 9.09 (d, J=2.7 Hz, 1H), 8.04 (dd, J=8.0, 1.3 Hz,
H), 7.89 (d, J=1.3 Hz, 1H), 7.58–7.53 (m, 1H), 7.41–7.35 (m, 2H),
.51 (dd, J=2.6, 1.7 Hz, 1H), 4.26 (d, J=7.1 Hz, 2H), 1.96 (dd, J=
0.1, 7.2 Hz, 1H), 1.76–1.69 (m, 4H), 1.32–1.12 (m, 6H). C NMR
143.47, 142.38, 134.53, 134.37, 133.19, 132.04, 131.45, 130.40,
130.16, 129.15, 128.19, 124.72, 113.47, 108.34, 49.17. This is a known
3
1
6
1
[16]
structure. These data are similar to the reported one.
1
3
(
1
2
126 MHz, CDCl ) δ 150.84, 143.30, 142.65, 133.25, 132.21, 131.53,
3
30.45, 129.87, 124.33, 114.14, 108.15, 48.87, 36.64, 30.92, 26.11,
1-(Naphthalen-2-ylmethyl)-3-(1H-pyrazol-1-yl)
quinoxalin-2(1H)-one (3w)
+
5.76. HRMS (ESI): Calculated for C H N O [M+H] : 309.1715,
18
21
4
Found: 309.1715.
1
White solid (62 mg, 59% yield); M. p.=209.7–210.5°C. H NMR
(
500 MHz, CDCl3) δ 9.15 (d, J=2.6 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H),
.94 (d, J=0.9 Hz, 1H), 7.81 (d, J=8.5 Hz, 1H), 7.79-7.78 (m, 1H),
.73–7.71 (m, 1H), 7.62 (s, 1H), 7.45–7.42 (m, 2H), 7.42–7.37 (m, 2H),
.34 (t, J=7.8 Hz, 2H), 6.55–6.51 (m, 1H), 5.74 (s, 2H). C NMR
7
7
7
1
-Allyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3r)
1
Yellow solid (70 mg, 92% yield); M. p.=93.0–94.3°C. H NMR
13
(
1
7
1
500 MHz, CDCl3) δ 9.07 (d, J=2.7 Hz, 1H), 8.01 (dd, J=8.0, 1.3 Hz,
(
126 MHz, CDCl ) δ 149.85, 142.49, 141.66, 132.31, 132.26, 131.80,
31.06, 130.95, 130.54, 129.27, 129.11, 128.04, 126.70, 126.68,
3
H), 7.87 (d, J=1.2 Hz, 1H), 7.53–7.48 (m, 1H), 7.38–7.34 (m, 1H),
.30 (d, J=8.3 Hz, 1H), 6.48 (dd, J=2.6, 1.7 Hz, 1H), 5.98–5.91 (m,
H), 5.28 (d, J=10.4 Hz, 1H), 5.17 (d, J=17.2 Hz, 1H), 4.99 (dd, J=
1
1
25.52, 125.23, 124.49, 123.66, 123.48, 113.48, 107.35, 45.82. HRMS
+
(
ESI): Calculated for C H N O [M+H] : 353.1402, Found: 353.1402.
2
2
17
4
13
3
.4, 1.7 Hz, 2H). C NMR (126 MHz, CDCl ) δ 150.26, 143.39, 142.56,
3
1
33.23, 131.79, 131.43, 130.26, 130.08,130.02, 124.56, 118.49,
1
14.18, 108.28, 45.27. This is a known structure. These data are
similar to the reported one.
3-(1H-Pyrazol-1-yl)-1-(pyridin-2-ylmethyl)
quinoxalin-2(1H)-one (3x)
[
16]
1
White solid (81 mg, 89% yield); M. p.=159.5–160.9°C. H NMR
(
(
500 MHz, CDCl ) δ 9.11 (d, J=2.7 Hz, 1H), 8.59–8.54 (m, 1H), 8.02
dd, J=8.0, 1.2 Hz, 1H), 7.90 (d, J=1.3 Hz, 1H), 7.62 (td, J=7.7,
1
-(3-Methylbut-2-en-1-yl)-3-(1H-pyrazol-1-yl)
3
quinoxalin-2(1H)-one (3s)
.7 Hz, 1H), 7.52–7.44 (m, 2H), 7.38–7.34 (m, 1H), 7.25 (d, J=7.9 Hz,
H), 7.20 (dd, J=7.1, 5.2 Hz, 1H), 6.52 (dd, J=2.6, 1.7 Hz, 1H), 5.72
1
White solid (75 mg, 89% yield); M. p.=126.1–127.6°C. H NMR
1
3
(
500 MHz, CDCl3) δ 9.07 (d, J=2.7 Hz, 1H), 8.00 (dd, J=8.0, 1.2 Hz,
H), 7.86 (d, J=1.2 Hz, 1H), 7.55–7.46 (m, 1H), 7.35 (t, J=7.6 Hz, 1H),
.30 (d, J=8.4 Hz, 1H), 6.47 (dd, J=2.5, 1.7 Hz, 1H), 5.20–5.12 (m,
H), 4.96 (d, J=6.1 Hz, 2H), 1.90 (s, 3H), 1.72 (s, 3H). C NMR
3
1
7
1
1
41.65, 136.24, 132.19, 131.10, 130.50, 129.15, 129.16, 123.70,
121.98, 120.96, 113.86, 107.31, 47.57. HRMS (ESI): Calculated for
1
3
+
C H N O [M+H] : 304.1198, Found: 304.1198.
1
7
14
5
(126 MHz, CDCl ) δ 149.26, 142.24, 141.59, 136.90, 132.19, 130.85,
3
1
30.47, 129.22, 128.93, 123.34, 116.39, 113.03, 107.11, 40.54, 24.62,
+
17.45. HRMS (ESI): Calculated for C H N O [M+H] : 281.1402,
1,6,7-Trimethyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)- one (3y)
16
17
4
Found: 281.1402.
1
Yellow solid (68 mg, 89% yield); M. p.=205.4–206.1°C. H NMR
(
500 MHz, CDCl3) δ 9.03 (d, J=2.6 Hz, 1H), 7.84 (d, J=0.8 Hz, 1H),
7
2
1
.70 (s, 1H), 7.02 (s, 1H), 6.48–6.44 (m, 1H), 3.72 (s, 3H), 2.31 (d, J=
1
-(Prop-2-yn-1-yl)-3-(1H-pyrazol-1-yl)quinoxalin- 2(1H)-one
1
3
2.9 Hz, 6H). C NMR (126 MHz, CDCl ) δ149.52, 141.93, 140.76,
(3t)
3
39.51, 132.59, 131.97, 129.53, 129.03, 128.40, 113.15, 106.8, 28.72,
1
White solid (42 mg, 56% yield); M. p.=185.5–188.2°C. H NMR
19.51, 18.25. This is a known structure. These data are similar to the
[16]
(
1
500 MHz, CDCl3) δ 9.07 (d, J=2.7 Hz, 1H), 8.04 (dd, J=8.1, 1.3 Hz,
H), 7.89 (d, J=1.3 Hz, 1H), 7.62–7.59 (m, 1H), 7.55–7.48 (m, 1H),
reported one.
7
.46–7.38 (m, 1H), 6.51 (dd, J=2.7, 1.6 Hz, 1H), 5.16 (d, J=2.5 Hz,
13
2H), 2.33 (t, J=2.5 Hz, 1H). C NMR (126 MHz, CDCl ) δ 148.87,
6,7-Dichloro-1-methyl-3-(1H-pyrazol-1-yl)quinoxalin-
2(1H)-one (3z)
3
1
42.53, 141.35, 132.19, 130.46, 130.08, 129.32, 129.19, 123.95,
1
13.09, 107.43, 75.25, 72.68, 31.31. This is a known structure. These
data are similar to the reported one.
1
[
16]
White solid (58 mg, 66% yield); M. p.=212.1–213.0°C.. H NMR
(
6
500 MHz, CDCl ) δ 9.02 (s, 1H), 8.02 (s, 1H), 7.86 (s, 1H), 7.38 (s, 1H),
3
1
3
.48 (s, 1H), 3.72 (s, 3H). C NMR (126 MHz, CDCl ) δ 150.03, 143.94,
3
1
1
43.10, 134.06, 133.35, 131.75, 130.60, 130.33, 128.48, 115.17,
Ethyl 2-(2-oxo-3-(1H-pyrazol-1-yl)quinoxalin-1(2H)- yl)acetate
3u)
08.81, 30.18. This is a known structure. These data are similar to
(
[16]
the reported one.
1
White solid (75 mg, 84% yield); M. p.=167.7–168.9°C. H NMR
(
1
500 MHz, CDCl3) δ 9.04 (d, J=2.7 Hz, 1H), 8.05 (dd, J=8.0, 1.2 Hz,
H), 7.90 (d, J=1.1 Hz, 1H), 7.55–7.51 (m, 1H), 7.42–7.39 (m, 1H),
.13 (d, J=8.4 Hz, 1H), 6.51 (dd, J=2.5, 1.6 Hz, 1H), 5.12 (s, 2H), 4.26
7-Bromo-1-methyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(3aa)
7
13
(q, J=7.1 Hz, 2H), 1.27 (t, J=7.1 Hz, 3H). C NMR (126 MHz, CDCl3)
1
Yellow solid (58 mg, 63% yield); M. p.=182.4–184.6°C. H NMR
δ 166.63, 150.45, 143.52, 142.40, 133.15, 131.77, 131.36, 130.46,
(
500 MHz, CDCl ) δ 9.06 (d, J=2.6 Hz, 1H), 7.89–7.82 (m, 2H), 7.52–
3
13
1
30.24, 124.86, 113.08, 108.40, 62.29, 44.24, 14.09. This is a known
[16]
7.46 (m, 2H), 6.50 (s, 1H), 3.77 (s, 3H). C NMR (126 MHz, CDCl ) δ
3
structure. These data are similar to the reported one.
Eur. J. Org. Chem. 2021, 2230–2238
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Full Papers
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1
3
1
49.32, 142.65, 141.57, 132.43, 132.24, 130.25, 129.11, 126.92,
23.07, 115.74, 107.54, 29.03. HRMS (ESI): Calculated for C H BrN O
2H). C NMR (126 MHz, CDCl ) δ 150.59, 142.04, 141.88, 134.53,
3
1
132.12, 131.32, 130.95, 130.54, 130.38, 129.10, 128.04, 126.84,
124.84, 114.53, 113.15, 46.76. HRMS (ESI): Calculated for C H ClN O
M+H] : 337.0856, Found: 337.0856.
12
10
4
+
[
M+H] : 305.0038, Found: 305.0038.
18
14
4
+
[
1
-Methyl-6-nitro-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(3ab)
3-(4-Chloro-1H-pyrazol-1-yl)quinoxalin-2(1H)-one (4b)
1
1
White solid (71 mg, 87% yield); M. p.=236.6–238.5°C. H NMR
White solid (67 mg, 91% yield); M. p.=273.2–274.0°C. H NMR
(
8
500 MHz, DMSO) δ 8.91 (d, J=2.7 Hz, 1H), 8.54 (d, J=2.6 Hz, 1H),
.43 (dd, J=9.2, 2.6 Hz, 1H), 7.95 (d, J=1.0 Hz, 1H), 7.84 (d, J=
.3 Hz, 1H), 6.65–6.63 (m, 1H), 3.77 (s, 3H). C NMR (126 MHz, CDCl3)
(500 MHz, DMSO) δ 13.02 (s, 1H), 9.00 (s, 1H), 8.02 (s, 1H), 7.79 (d,
1
3
J=8.0 Hz, 1H), 7.58 (t, J=7.6 Hz, 1H), 7.41–7.35 (m, 2H). C NMR
(126 MHz, DMSO) δ 150.58, 143.11, 140.58, 131.77, 130.51, 130.22,
13
9
δ 150.36, 144.39, 144.14, 143.96, 136.83, 133.41, 130.73, 125.58,
24.30, 114.37, 109.22, 30.57. HRMS (ESI): Calculated for C H N O
3
130.16, 128.19, 124.01, 115.31, 110.66. HRMS (ESI): Calculated for
+
1
C
11
H
ClN
8
4
O [M+H] : 247.0387, Found: 247.0387.
1
2
10
5
+
[M+H] : 272.0784, Found: 272.0784.
1
(4c)
-Benzyl-3-(4-bromo-1H-pyrazol-1-yl)quinoxalin-2(1H)-one
1
-Methyl-3-(1H-pyrazol-1-yl)benzo[g]quinoxalin-2(1H)-one
(
3ac)
1
White solid (104 mg, 91% yield); M. p.=156.0–158.9°C. H NMR
1
Yellow solid (64 mg, 77% yield); M. p.=194.3–196.6°C. H NMR
(500 MHz, CDCl ) δ 9.20 (s, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.86 (s, 1H),
3
13
(500 MHz, CDCl ) δ 9.02 (s, 1H), 8.40 (s, 1H), 7.89 (s, 1H), 7.87 (d, J=
7.49 (t, J=7.8 Hz, 1H), 7.41–7.26 (m, 7H), 5.61 (s, 2H). C NMR
3
8
7
.1 Hz, 1H), 7.79 (d, J=8.1 Hz, 1H), 7.50–7.44 (m, 2H), 7.41 (t, J=
.4 Hz, 1H), 6.49 (s, 1H), 3.72 (d, J=5.0 Hz, 3H). C NMR (126 MHz,
(126 MHz, CDCl
3
) δ 150.61, 143.92, 141.81, 134.53, 133.16, 132.12,
131.32, 130.57, 130.42, 129.12, 128.05, 126.85, 124.86, 114.54, 96.70,
13
+
CDCl ) δ 149.68, 142.51, 141.46, 132.34, 132.31, 129.83, 129.30,
46.78. HRMS (ESI): Calculated for C18
H14BrN O [M+H] : 381.0351,
4
3
1
29.12, 128.16, 127.39, 126.89, 126.17, 124.57, 109.15, 107.42, 28.77.
Found: 381.0349.
+
HRMS (ESI): Calculated for C H N O [M+H] : 277.1089, Found:
16
13
4
277.1089.
1
-Benzyl-3-(4-iodo-1H-pyrazol-1-yl)quinoxalin-2(1H)-one (4d)
1
White solid (121 mg, 94% yield); M. p.=171.9–173.9°C. H NMR
3
-(1H-Pyrazol-1-yl)quinoxalin-2(1H)-one (3ad)
(
500 MHz, CDCl ) δ 9.20 (s, 1H), 8.00 (dd, J=8.0, 0.9 Hz, 1H), 7.86 (s,
3
1
White solid (54 mg, 85% yield); M. p.=234.3–237.4°C. H NMR
1H), 7.47–7.43 (m, 1H), 7.36–7.28 (m, 4H), 7.23 (t, J=6.1 Hz, 3H),
13
(
1
500 MHz, CDCl3) δ 12.90 (s, 1H), 8.87 (d, J=2.5 Hz, 1H), 7.83 (d, J=
.2 Hz, 1H), 7.74 (dd, J=8.0, 0.7 Hz, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.35–
5.57 (s, 2H). C NMR (126 MHz, CDCl ) δ 150.63, 147.97, 141.67,
3
137.46, 134.54, 132.10, 131.28, 130.58, 130.41, 129.11, 128.05,
13
7
.35 (m, 2H), 6.53 (dd, J=2.6, 1.7 Hz, 1H). C NMR (126 MHz, CDCl3)
126.85, 124.86, 114.53, 60.53, 46.78. HRMS (ESI): Calculated for
+
δ 150.74, 143.72, 142.28, 132.81, 131.57, 130.38, 129.81, 128.05,
C
18
H
14IN
4
O [M+H] : 429.0212, Found: 429.0208.
+
123.91, 115.21, 107.67. HRMS (ESI): Calculated for C H N O [M+H]
11 9 4
:
213.0776, Found: 213.0776.
1
-Benzyl-3-(3-methyl-1H-pyrazol-1-yl)quinoxalin-2(1H)-one
(
4e)
7
-(tert-Butyl)-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3ae)
1
White solid (58 mg, 61% yield); M. p.=132.1–133.9°C. H NMR
1
Yellow solid (64 mg, 80% yield); M. p.=215.7–217.9°C. H NMR
(500 MHz, CDCl ) δ 9.04 (s, 1H), 8.03 (d, J=7.9 Hz, 1H), 7.38 (dd, J=
11.0, 4.4 Hz, 1H), 7.34–7.27 (m, 3H), 7.26–7.18 (m, 4H), 6.30 (s, 1H),
3
(
(
(
500 MHz, CDCl ) δ 12.71 (s, 1H), 9.16 (d, J=2.1 Hz, 1H), 7.97–7.95
m, 1H), 7.92 (s, 1H), 7.58–7.55 (m, 1H), 7.36 (d, J=8.5 Hz, 1H), 6.54
d, J=0.6 Hz, 1H), 1.33–1.31 (m, 9H). C NMR (126 MHz, CDCl ) δ
3
1
3
5.57 (s, 2H), 2.45 (s, 3H). C NMR (126 MHz, CDCl ) δ 153.50, 150.85,
3
13
142.46, 134.75, 134.26, 131.72, 131.63, 130.21, 129.65, 129.03,
127.87, 126.75, 124.49, 114.35, 109.08, 46.62, 14.15. HRMS (ESI):
3
1
51.98, 148.76, 143.34, 142.52, 132.82, 131.30, 128.24, 125.53,
15.06, 108.38, 34.78, 31.29. HRMS (ESI): Calculated for C H N O
+
1
Calculated for C H N O [M+H] : 317.1402, Found: 317.1392.
1
5
17
4
19 17
4
+
[M+H] : 269.1402, Found: 269.1402.
3
-(3-Methyl-1H-pyrazol-1-yl)quinoxalin-2(1H)-one (4f)
6
,7-Dimethyl-3-(1H-pyrazol-1-yl)quinoxalin-2(1H)-one (3af)
1
White solid (32 mg, 47% yield); M. p.=252.2–253.9°C. H NMR
(500 MHz, DMSO) δ 12.84 (s, 1H), 8.83 (d, J=2.5 Hz, 1H), 7.73 (d, J=
8.0 Hz, 1H), 7.50–7.47 (m, 1H), 7.33–7.29 (m, 2H), 6.34 (d, J=2.5 Hz,
1
Yellow solid (34 mg, 47% yield); M. p.=243.6–245.1°C. H NMR
(
7
500 MHz, DMSO) δ 12.80 (s, 1H), 8.85 (d, J=2.3 Hz, 1H), 7.83 (s, 1H),
.53 (s, 1H), 7.11 (s, 1H), 6.54 (s, 1H), 2.30 (d, J=11.2 Hz, 6H).
1
3
13
C
1H), 2.28 (s, 3H). C NMR (126 MHz, DMSO) δ 151.33, 150.69,
NMR (126 MHz, DMSO)
δ
150.70, 142.98, 141.97, 139.55,
143.35, 133.59, 131.28, 130.53, 129.38, 127.85, 123.86, 115.13,
+
1
32.71,132.59, 129.62, 128.73, 127.87, 115.20, 107.42, 19.74, 18.96.
HRMS (ESI): Calculated for C H N O [M+H] : 241.1089, Found:
108.14, 13.50. HRMS (ESI): Calculated for C H N O [M+H] :
1
2
11
4
+
227.0933, Found: 227.0933.
15
17
4
241.1089.
1
-Benzyl-3-(4-(tert-butyl)-1H-pyrazol-1-yl)
1
-Benzyl-3-(4-chloro-1H-pyrazol-1-yl)quinoxalin-2(1H)-one
quinoxalin-2(1H)-one (4g)
(4a)
1
White solid (66 mg, 61% yield); M. p.=161.7–163.8°C. H NMR
1
White solid (98 mg, 97% yield); M. p.=150.5–153.1°C. H NMR
(500 MHz, CDCl ) δ 8.99 (d, J=2.8 Hz, 1H), 8.04 (dd, J=7.9, 1.1 Hz,
3
(
7
500 MHz, CDCl ) δ 9.11 (s, 1H), 8.00 (d, J=7.9 Hz, 1H), 7.80 (s, 1H),
.47–7.43 (m, 1H), 7.37–7.28 (m, 4H), 7.23 (t, J=6.6 Hz, 3H), 5.57 (s,
1H), 7.44–7.41 (m, 1H), 7.39–7.26 (m, 6H), 7.25 (s, 1H), 6.45 (d, J=
3
1
3
2.8 Hz, 1H), 5.62 (s, 2H), 1.46 (s, 9H). C NMR (126 MHz, CDCl ) δ
3
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1
66.08, 151.07, 142.90, 134.79, 133.97, 131.79, 131.74, 130.43,
143.04, 134.63, 132.61, 131.49, 131.35, 130.04, 129.41, 129.11,
128.04, 126.88, 124.72, 124.64, 124.40, 120.34, 116.03, 114.64, 46.82.
1
29.64, 129.03, 127.86, 126.74, 124.35, 114.30, 105.98, 46.60, 32.70,
0.18. HRMS (ESI): Calculated for C H N O [M+H] : 359.1872,
+
+
3
HRMS (ESI): Calculated for C H N O [M+H] : 353.1402, Found:
22
23
4
22 17
4
Found: 359.1874.
353.1400.
1
-Benzyl-3-(3-phenyl-1H-pyrazol-1-yl)quinoxalin-2(1H)-one
1-Benzyl-3-(1H-indazol-1-yl)quinoxalin-2(1H)-one (4m)
(
4h)
1
White solid (53 mg, 50% yield); M. p.=137.5–138.2°C. H NMR
1
White solid (81 mg, 71% yield); M. p.=180.5–182.5°C. H NMR
(500 MHz, CDCl ) δ 8.37 (s, 1H), 8.23 (d, J=8.5 Hz, 1H), 7.91 (d, J=
3
7.9 Hz, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.45 (t, J=
7.7 Hz, 1H), 7.38–7.30 (m, 7H), 7.28 (d, J=7.1 Hz, 1H), 5.63 (s, 2H).
C NMR (126 MHz, CDCl ) δ 151.37, 145.34, 140.35, 138.62, 135.13,
132.49, 131.43, 130.02, 129.65, 128.98, 127.94, 127.86, 127.27,
(500 MHz, CDCl ) δ 9.13 (d, J=2.5 Hz, 1H), 8.02 (dd, J=24.8, 7.7 Hz,
3
3
H), 7.42 (t, J=7.5 Hz, 3H), 7.35 (dd, J=12.7, 7.0 Hz, 2H), 7.29 (dd,
1
3
J=13.4, 6.9 Hz, 3H), 7.23 (d, J=7.4 Hz, 3H), 6.83 (d, J=2.5 Hz, 1H),
3
13
5
1
1
.60 (s, 2H). C NMR (126 MHz, CDCl ) δ 155.18, 150.97, 142.65,
34.86, 134.73, 132.20, 131.95, 131.70, 130.48, 130.01, 129.09,
28.86, 128.60, 127.94, 126.79, 126.75, 124.58, 114.43, 106.31, 46.71.
3
125.70, 124.28, 123.12, 121.08, 114.60, 114.25, 46.85. HRMS (ESI):
+
Calculated for C22
H
N
O [M+H] : 353.1402, Found: 353.1398.
17
4
+
HRMS (ESI): Calculated for C H N O [M+H] : 379.1559, Found:
28
15
4
379.1560.
1
-Benzyl-3-(1H-1,2,4-triazol-1-yl)quinoxalin-2(1H)-one (4n)
1
White solid (81 mg, 89% yield); M. p.=164.2–165.3°C. H NMR
Ethyl
-(4-benzyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-1H-pyrazole-3--
carboxylate (4i)
(
7
500 MHz, CDCl ) δ 9.74 (s, 1H), 8.13 (s, 1H), 7.98 (d, J=8.0 Hz, 1H),
.45 (t, J=7.8 Hz, 1H), 7.36–7.27 (m, 2H), 7.25–7.13 (m, 5H), 5.54 (s,
3
1
13
2
H). C NMR (126 MHz, CDCl ) δ 152.71, 150.39, 146.77, 141.18,
3
1
White solid (88 mg, 78% yield); M. p.=120.5-122.3°C. H NMR
134.26, 132.07, 131.32, 131.16, 130.70, 129.15, 128.13, 126.79,
+
(
7
500 MHz, CDCl ) δ 8.99 (d, J=2.7 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H),
.51–7.46 (m, 1H), 7.37 (t, J=7.7 Hz, 1H), 7.34–7.29 (m, 3H), 7.25 (dd,
125.08, 114.69, 46.85. HRMS (ESI): Calculated for C17
304.1198, Found: 304.1198.
H
N
14
5
O [M+H] :
3
J=13.4, 7.7 Hz, 3H), 7.01 (d, J=2.7 Hz, 1H), 5.60 (s, 2H), 4.45 (q, J=
13
7
.1 Hz, 2H), 1.42 (t, J=7.1 Hz, 3H). C NMR (126 MHz, CDCl ) δ
3
3
-(1H-Benzo[d][1,2,3]
1
1
1
62.04, 150.78, 146.97, 142.47, 134.51, 134.5, 132.41, 131.29, 130.99,
triazol-1-yl)-1-benzylquinoxalin-2(1H)-one (4o)
30.86, 129.10, 128.02, 126.81, 124.78, 114.57, 110.09, 61.46, 46.77,
+
4.34. HRMS (ESI): Calculated for C H N O [M+H] : 375.1457,
1
21
19
4
3
White solid (40 mg, 38% yield); M. p.=177.5–180.3°C. H NMR
Found: 375.1454.
(
7
7
500 MHz, CDCl ) δ 8.18 (d, J=8.2 Hz, 1H), 8.05 (d, J=8.3 Hz, 1H),
3
.98 (d, J=7.9 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.56 (t, J=7.8 Hz, 1H),
13
.47 (t, J=7.6 Hz, 1H), 7.44–7.28 (m, 7H), 5.66 (s, 2H). C NMR
1
-Benzyl-3-(3-(trifluoromethyl)-1H-pyrazol-1-yl)
(
1
126 MHz, CDCl ) δ 150.96, 145.85, 143.67, 134.66, 132.95, 132.83,
31.59, 131.24, 130.53, 129.09, 128.86, 128.07, 127.18, 125.00,
3
quinoxalin-2(1H)-one (4j)
1
White solid (102 mg, 92% yield); M. p.=148.2–150.1°C. H NMR
124.73, 120.22, 114.85, 113.38, 46.99. HRMS (ESI): Calculated for
C H N O [M+H] : 354.1355, Found: 354.1355.
21 16 5
+
(
1
8
500 MHz, CDCl ) δ 9.08 (dd, J=1.7, 0.7 Hz, 1H), 8.08 (d, J=8.0 Hz,
H), 7.54–7.51 (m, 1H), 7.41 (t, J=7.6 Hz, 1H), 7.35 (dd, J=15.1,
.0 Hz, 3H), 7.30 (t, J=4.9 Hz, 1H), 7.27 (d, J=4.0 Hz, 2H), 6.77 (d,
3
13
1-Benzyl-3-(2H-tetrazol-2-yl)quinoxalin-2(1H)-one (4p)
J=2.7 Hz, 1H), 5.63 (s, 2H). C NMR (126 MHz, CDCl ) δ 150.71,
3
1
1
1
45.91 (q, J=41.58 Hz), 142.23, 134.87, 134.41, 132.43, 131.19,
1
White solid (46 mg, 50% yield); M. p.=258.3–259.5°C. H NMR
30.89, 129.14, 128.08, 126.81, 124.86, 118.83 (q, J=276.36 Hz),
(
7
500 MHz, CDCl ) δ 8.80 (s, 1H), 8.02 (dd, J=8.0, 1.1 Hz, 1H), 7.66–
.62 (m, 1H), 7.47–7.43 (m, 2H), 7.34–7.28 (m, 5H), 5.63 (s, 2H).
NMR (126 MHz, CDCl ) δ 152.96, 150.36, 142.33, 134.25, 133.93,
33.26, 131.52, 130.67, 129.16, 128.23, 127.18, 125.09, 115.02, 47.16.
19
3
14.59, 106.02, 106.01 (q, J=5.04 Hz), 46.85. F NMR (376 MHz,
13
C
CDCl ) δ À 137.80 (s, 3F). HRMS (ESI): Calculated for C H F N O [M
3
19 14
3
4
+
3
+
H] : 371.1120, Found: 371.1118.
1
+
HRMS (ESI): Calculated for C H N O [M+H] : 305.1151, Found:
1
6
13
6
305.1146.
1
-Benzyl-3-(3-nitro-1H-pyrazol-1-yl)quinoxalin-2(1H)-one (4k)
1
Yellow solid (52 mg, 50% yield); M. p.=190.3–193.0°C. H NMR
(
500 MHz, CDCl ) δ 9.09–8.98 (m, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.56 (t,
3
Acknowledgements
J=7.8 Hz, 1H), 7.41 (dd, J=17.6, 8.3 Hz, 2H), 7.35–7.32 (m, 2H), 7.29
(
d, J=6.4 Hz, 1H), 7.27 (s, 1H), 7.26 (s, 1H), 7.07 (d, J=2.6 Hz, 1H),
13
5
1
1
.62 (s, 2H). C NMR (126 MHz, CDCl ) δ 158.12, 150.59, 141.63,
We are grateful for the financial support from the National
Natural Science Foundation of China (21602159, 21877085).
3
36.04, 134.25, 132.70, 131.89, 131.05, 131.00, 129.18, 128.18,
26.85, 125.14, 114.78, 103.75, 46.92. HRMS (ESI): Calculated for
+
C H N O [M+H] : 348.1097, Found: 348.1097.
1
8
14
5
3
Conflict of Interest
3
-(1H-Benzo[d]imidazol-1-yl)-1-benzylquinoxalin-2(1H)-one
(4l)
The authors declare no conflict of interest.
1
White solid (76 mg, 72% yield); M. p.=158.8–160.2°C. H NMR
(
7
500 MHz, CDCl ) δ 9.51 (s, 1H), 8.51 (d, J=7.8 Hz, 1H), 7.80 (d, J=
.9 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.36–7.27 (m, 3H), 7.24–7.20 (m,
Keywords: Azoles · [Bis(trifluoroacetoxy)iodo]benzene · CÀ N
coupling · Quinoxalin-2(1H)-ones · Radicals
3
13
7
H), 5.48 (s, 2H). C NMR (126 MHz, CDCl ) δ 151.23, 143.61, 143.40,
3
Eur. J. Org. Chem. 2021, 2230–2238
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