Lewis acid-catalyzed selective synthesis of diversely substituted indolo-and pyrrolo[1,2-a]quinoxalines and quinoxalinones by modified pictet-spengler reaction

Article abstract of DOI:10.1002/ejoc.201101013

An efficient tandem process for the selective synthesis of 1,2-annulated α-fused quinoxalines using benzotriazole methodology by a modified Pictet-Spengler reaction is described. The approach involves the reaction of arylamines 4 with aromatic aldehydes 5 to furnish 6-endo-dig-cyclized products. Dihydroquinoxalines 6 were selectively obtained by using AlCl₃ in tetrahydrofuran (THF) at room temperature for two hours. However, after ten hours, quinoxalines 7 were obtained exclusively in excellent yields. A series of biologically important fluoro-and piperazenyl-substituted quinoxalines were also synthesized. This developed methodology also provides access to a novel tandem synthesis of quinoxalinones 9.

Full text of DOI:10.1002/ejoc.201101013

FULL PAPER
DOI: 10.1002/ejoc.201101013
Lewis Acid-Catalyzed Selective Synthesis of Diversely Substituted Indolo- and
Pyrrolo[1,2-a]quinoxalines and Quinoxalinones by Modified Pictet–Spengler
Reaction
Akhilesh K. Verma,*[a] Rajeev R. Jha,[a] V. Kasi Sankar,[a,b] Trapti Aggarwal,[a]
Rajendra P. Singh,[c] and Ramesh Chandra[a]
Keywords: Nitrogen heterocycles / Fused-ring systems / Polycycles / Cross-coupling / Cyclization / Lewis acids
An efficient tandem process for the selective synthesis of 1,2-
hours. However, after ten hours, quinoxalines 7 were ob-
annulated α-fused quinoxalines using benzotriazole method- tained exclusively in excellent yields. A series of biologically
ology by a modified Pictet–Spengler reaction is described.
The approach involves the reaction of arylamines 4 with aro-
matic aldehydes 5 to furnish 6-endo-dig-cyclized products.
Dihydroquinoxalines 6 were selectively obtained by using
AlCl3 in tetrahydrofuran (THF) at room temperature for two
important fluoro- and piperazenyl-substituted quinoxalines
were also synthesized. This developed methodology also pro-
vides access to a novel tandem synthesis of quinoxalinones
9.
formation of ring systems such as tetrahydroimidazo-pyr-
idines (THIPs), tetrahydroisoquinolines (THIQs), and
tetrahydro-β-carbolines (THBCs) (Figure 1).[7] From a syn-
thetic point of view, the opportunity to prepare complex
polycyclic molecules in a limited number steps is an exciting
goal for every modern organic chemist. Although a number
of methods are available for the synthesis of simple substi-
tuted quinoxalines,[8,9] only a limited amount of work has
been done on the synthesis of polycyclic quinoxalines, espe-
cially indoloquinoxalines.[10–11] Furthermore, to the best of
our knowledge, none of the reported procedures have de-
scribed the selective synthesis of dihydroquinoxalines or
quinoxalines. Reported syntheses of indolo- and pyrrolo-
fused quinoxalines involves the reaction of aryl amines with
Introduction
A wide variety of biologically active natural and syn-
thetic compounds are known to have substituted heterocy-
cles in their core. For instance, quinoxalines are an impor-
tant class of nitrogen-containing heterocycles[1] that possess
a broad spectrum of physiological and biological activities
and can act as anti-cancer[2] and anti-HIV[3a] agents, gluca-
gon receptor antagonists,[3b] and angiotensin receptor an-
tagonists.[3c] They have also been used as a template for the
synthesis of GABA benzodiazepines receptor agonists or
antagonists[4] and for other therapeutic applications.[5] Be-
sides these pharmaceutical applications, this class of com-
pounds has also been used as building blocks for the syn-
thesis of organic semiconductors, dyes, useful rigid subunits
in macrocyclic receptors, and chemically controllable swit-
ches.[1,6a] In comparison to α-fused angular polycyclic quin-
oxaline ring systems, compounds containing the β-fused
framework have been extensively studied because of their
wide range of pharmacological activities.[6b,6c] Therefore,
the development of a novel route that enables their synthe-
ses using efficient processes is an important area of re-
search.
Among the various C–C bond-forming reactions, the
Pictet–Spengler reaction[6d] has been widely used for the
[a] Department of Chemistry, University of Delhi,
Delhi 110007, India
E-mail: averma@acbr.du.ac.in
[b] Pharmaceutical Chemistry Division, VIT University,
Vellore 632014, Tamilnadu, India
[c] Centre for Fire, Explosive & Environment Safety,
Timarpur, Delhi 110054, India
Figure 1. (i) Typical base-catalyzed Pictet–Spengler reaction. (ii)
Typical acid-catalyzed Pictet–Spengler reaction.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101013.
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Synthesis of Ring-Fused Quinoxalinones
terminal alkynes in the presence of a ruthenium hydride available 2-fluoronitrobenzene (2a) and 2,4-difluronitro-
complex for 20–24 h.[11b]
benzene (2b) with N-heterocycles 1 using NaOH in di-
Kundu and co-workers reported the synthesis of imid- methyl sulfoxide (DMSO) at room temperature (see Table
azo-quinoxalines in 50–74% yields by using the Pictet– S1 in the Supporting Information).
Spengler reaction on solid phase at 80 °C for 48 h.[11c] Other
reported methods are multistep and required longer reac-
tion times, and high temperature.
In a continuation of our interest in the synthesis of fused
heterocycles by using benzotriazole[12] methodology[13] and
alkyne chemistry,[14] herein we report the selective synthesis
of 1,2-annulated α-fused dihydro-pyrrolo/indolo[1,2-a]quin-
oxalines 6 and pyrrolo/indolo[1,2-a]quinoxalines 7 in good
to excellent yields by using a modified Pictet–Spengler reac-
tion at 25 °C. The developed process is also successful for
the tandem synthesis of indolo/pyrrolo[2,1-a]quinoxalinone
9 (Scheme 1).
Scheme 2. Synthesis of N-heterocyclic amines.
To optimize the reaction conditions for the selective syn-
thesis of quinoxalines, various Lewis acids and organic sol-
vents were examined and the reaction time was varied; the
results are summarized in Table 1. We first allowed 4a
(0.5 mmol) to react with 1.0 equiv. of 5a, 10.0 mol-% of
AlCl3, and 1.0 equiv. of benzotriazole in 2.0 mL of CH2Cl2
at room temp. for 30 min, but found that 4,5-dihydropyr-
rolo[1,2-a]quinoxaline (6a) could be obtained in only 60%
yield (Table 1, entry 1). Increasing the reaction time to 1 h
and then to 2 h afforded the reduced product in 78 and 83%
yields respectively (Table 1, entries 2–3). When reaction was
stirred for 5 h, the desired product 6a was obtained in 68%
yield along with the oxidized form of quinoxaline 7a in 18%
yield (Table 1, entry 4). After 10 h, products 6a and 7a were
obtained in 45 and 50% yield, respectively (Table 1, entry
5). The same results were obtained when chloroform was
used (Table 1, entry 6). Using toluene as solvent, the prod-
uct 6a was obtained in 85% yield in 2 h (Table 1, entry 7).
When the reaction was continued for 10 h, products 6a and
7a were obtained in 13 and 70% yield, respectively (Table 1,
entry 8). When tetrahydrofuran (THF) was used, product
6a was obtained in 92% yield after 2 h, however it was com-
pletely oxidized after 10 h to compound 7a, which was se-
Scheme 1. Synthesis of reduced and oxidized forms of quinoxalines
6, 7, and polycyclic quinoxalinones 9.
Results and Discussion
In this study, we selected arylamines 4, which linked to lectively obtained in 90% yield (Table 1, entry 11). Lower
N-1 of indole and pyrrole 1, as possible substrates for the yield of product was obtained in the absence of benzotri-
synthesis of diversely-substituted indolo- and pyrrolo-quin- azole (Table 1, entry 12). When the catalyst loading was de-
oxalines. The arylamines 4 required for the reactions were creased from 10 to 5 mol-%, only 56% of product 6a was
obtained in quantitative yields by the reduction of the cor- obtained in 2 h (Table 1, entry 13). After 7 h, we obtained
responding nitro derivatives (Scheme 2). The nitro com- a mixture products 6a and 7a in 20 and 31% yield, respec-
pounds 3 were prepared by the reaction of commercially tively, along with 50% of starting material (Table 1, entry
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14). When the reaction was stirred under the same condi- dro-pyrrolo/indolo[1,2-a]quinoxalines 6a–r was synthesized
tions for 12 h, 50% yield of the oxidized product 7a was by reacting amines 4a–d with aldehydes 5a–l in the presence
obtained, along with starting material (Table 1, entry 15).
of AlCl3 in THF at room temp. for 2 h (Table 2). The pres-
ence of an electron-withdrawing group in the aldehyde af-
forded the cyclized products 6d–k and 6n–q in good yields
(Table 2, entries 4–11 and 14–17). However, aldehydes hav-
ing electron-releasing groups such as methoxy or 4-ethylfu-
ryl afforded the cyclized products 6b and 6c in 83 and 76%
yield, respectively (Table 2, entries 2 and 3). The reaction
proceeded well with π-deficient 2-bromonicotinaldehyde
(5i), providing the desired product in 82% yield (Table 2,
entry 11). However, the reaction with aliphatic aldehyde 5j,
afforded the desired product 6l in 65% yield (Table 2, entry
12). Reaction of 2-(3-methyl-1H-indol-1-yl)aniline (4c) and
4-fluoro-2-(3-methyl-1H-indol-1-yl)aniline (4d) provided
the expected products 6m–q in good to excellent yields
(Table 2, entries 11–15).
Table 1. Optimization of the reaction conditions.[a]
Entry
Solvent
Catalyst / mol-%
t [h]
Yield [%][b]
6a
7a
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
toluene
toluene
THF
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 10
AlCl3 / 05
AlCl3 / 05
AlCl3 / 05
TsOH / 10
TsOH / 10
TsOH / 10
FeCl3 / 10
FeCl3 / 10
FeCl3 / 10
ZnCl2 / 10
ZnCl2 / 10
–
0.5
1.0
2.0
60
78
83
68
45
40
85
13
92
39
00
00
50
20
00
80
45
17
59
70
81
45
67
–
00
00
00
18
50
54
00
70
00
60
90
60[c]
00
31
50
00
30
70
00
00
00
00
00
10
5.0
The formation of the desired cyclized products were con-
10.0
10.0
2.0
10.0
2.0
5.0
10.0
10.0
2.0
7.0
12.0
2.0
5.0
10.0
2.0
5.0
10.0
2.0
1
firmed by H NMR and 13C NMR spectroscopic analysis.
Furthermore, the formation of dihydro-quinoxalines was
confirmed by the disappearance of the NH proton in the
NMR spectra of compound 6d measured in D2O (see the
Supporting Information).
Reaction of terephthaldehyde (5m) with 2.0 equiv. of
amine 4a using AlCl3 in THF afforded 1,4-bis(4,5-dihy-
dropyrrolo[1,2-a]quinoxalin-4-yl)benzene (6r) in 78% yield
(Scheme 3).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
10.0
24.0
Scheme 3. Synthesis of bis-dihydroquinoxaline.
[a] Reagents and conditions: aldehyde 5a (0.6 mmol), benzotriazole
(0.5 mmol), catalyst (5.0/10 mol-%), amine 4a (0.5 mmol), solvent
(2.0 mL), 25 °C unless otherwise noted. [b] Isolated yield. [c] Reac-
tion performed without benzotriazole.
Using the optimized reaction conditions for the oxidized
form of quinoxalines, a second library of quinoxalines 7a–
r was synthesized in good to excellent yields by reacting
We then examined the effect of a range of Lewis acids amines 4a–h with substituted aldehydes 5a–p (Table 3). It
on the reaction. Use of TsOH in the reaction afforded the was noticed that the effect on the reaction of different sub-
products 6a and 7a with slightly lower yield than with AlCl3 stituents on the aldehyde was the same as observed in the
(Table 1, entries 16–18). FeCl3 afforded the reduced product synthesis of dihydroquinoxaline. The reaction of 2-(3-
in 5 h and no oxidized product 7a was observed even after methyl-1H-indol-1-yl)anilines 4c–d, bearing an electron-re-
10 h (Table 1, entries 19–21). ZnCl2 afforded only the re- leasing methyl group at the 3-position of the indole, af-
duced product in 67% yield after 10 h (Table 1, entries 22– forded quinoxalines 7f–p in 85 to 96% yield (Table 3, entries
23). When the reaction was performed in the absence of 6–13). However, amine 4e and 4f, without a methyl group
AlCl3, only 10% of the reduced form 6a was obtained in at the 3-position of the indole nucleus, afforded the desired
5 h, which was further oxidized to 7a in 24 h. No further products 7n–p in 58–66% yields (Table 3, entries 9–11).
conversion of 4a into the product 6a was observed (Table 1,
The scope of the reaction was further extended for the
entry 24). Among the different solvent systems and Lewis synthesis of another important class of fused imidazo[1,5-a]-
acids examined, THF with AlCl3 was found to be most ef- quinoxalines (Table 3, entries 17–18). Reaction of electron-
fective for the selective formation of the desired products deficient 2-(1H-imidazol-1-yl)aniline 4g failed to afford the
6a and 7a in good to excellent yields (Table 1, entries 9 and desired cyclized product 7q under the standardized condi-
11).
tions (Table 3, entry 17). However, reaction of 2-(4-methyl-
The scope and limitations of the optimized reaction con- 1H-imidazol-1-yl)aniline 4h, having an electron-releasing
ditions were then examined by employing various substi- methyl group at the 4-position, afforded the cyclized prod-
tuted aldehydes and amines. First, a diverse library of dihy- uct 7r in 74% yield (Table 3, entry 18).
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Synthesis of Ring-Fused Quinoxalinones
Table 2. Selective synthesis of 4,5-dihydropyrrolo[1,2-a]quinoxalines 6a–l and 5,6-dihydroindolo[1,2-a]quinoxalines 6m–q.[a]
[a] Reagents and conditions: aldehyde 5 (0.6 mmol), benzotriazole (1.0 equiv.), AlCl3 (10 mol-%), amine 4 (0.5 mmol), THF (2.0 mL),
room temp., 1–2 h, unless otherwise noted. [b] Isolated yield.
Higher yields observed for the reaction with 3-methyl- C-2 position of indole and the C-5 position of imidazole to
indole amine were presumably due to the formation of a afford the cyclized products (Figure 2).
more stable transient tertiary carbocation, which then in-
creases the efficiency of the cyclization (Figure 2).
Piperazine scaffolds are commonly found in biologically
active compounds across a number of different therapeutic
The presence of an electron-releasing methyl group at the areas.[15] Therefore, a novel series of piperazine fused
3-position of indole-arylamine 4a, and at the 4-position of indolo[1,2-a]quinoxalines were synthesized to further ex-
imidazole-arylamine 4h, increases the nucleophilicity of the tend the scope of this reaction. Reaction of arylamines 4i–
ring system, which facilitates intramolecular attack of the j with aldehydes 5d–f, 5k, and m-nitobenzaldehyde (5q) af-
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Table 3. Selective synthesis of pyrrolo, indolo-quinoxalines 7a–p and imidazo-quinoxaline 7q–r.[a]
[a] Reagents and conditions: 5 (0.6 mmol), benzotriazole (1.0 equiv.), AlCl3 (10 mol-%), 4 (0.5 mmol), THF (2.0 mL), room temp., 8–
10 h; unless otherwise noted. [b] Isolated yield.
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Synthesis of Ring-Fused Quinoxalinones
Figure 2. Effect of substituents on intramolecular cyclization.
forded the piperazine-substituted cyclized products 7s–x in
72–82% yields under the standardized reaction conditions
(Table 4).
Table 4. Synthesis of piperazinyl-substituted quinoxalines.
Scheme 4. Possible mechanism for the selective synthesis of quin-
oxalines.
The strategy was further extended to the tandem synthe-
sis of polycyclic quinoxalinones 9a–d by the condensation
of amines 4a and 4c with 2-formylbenzoic acid (8a) and 2-
acetylbenzoic acid (8b) in the presence of benzotriazole in
toluene using a Dean–Stark apparatus at 110 °C for 2–4 h
(Table 5).
Table 5. Synthesis of quinoxalinones 9a–d.[a]
With these results, we have proposed a plausible mecha-
nism for the selective formation of quinoxalines. The sug-
gested reaction mechanism involves the formation of inter-
mediate A in the presence of a Lewis acid and benzotri-
azole. This intermediate forms the true iminium ion B by
facile removal of benzotriazole.[12] The latter intermediate
B undergoes intramolecular C–C bond formation by 6-
endo-dig attack at C-2 of the N-heterocycle to furnish the
dihydroquinoxalines 6 (Scheme 4). These dihydroquin-
oxalines were oxidized in the presence of air after 8–10 h to
yield the oxidized form of quinoxalines 7.
Entry
Product
R1
R6
Yield [%][b]
1
2
3
4
9a
9b
9c
9d
H
H
Me
Me
H
Me
H
91
88
84
73
Me
[a] Reagents and conditions: carboxy-benzoic acid 8 (0.6 mmol),
TsOH (5.0 mol-%), 4 (0.5 mmol), benzotriazole (0.5 mmol), toluene
(2.0 mL), Dean–Stark apparatus at 110 °C for 2–4 h. [b] Isolated
yield.
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and dried with Na2SO4. The solvent was evaporated in vacuo and
the solid obtained was purified by column chromatography (hex-
ane/ethyl acetate) to afford the desired product in good yields.
Quinoxaline 7c, containing a bromo handle, could be
further functionalized through palladium-catalyzed cou-
pling reactions such as Suzuki[16] and Heck[17] reactions to
afford the corresponding coupling products 10, 11, 12, and 3-Methyl-1-[2-nitro-5-(4-phenylpiperazin-1-yl)phenyl]-1H-indole
(3i): The product was obtained as a yellow solid; m.p. 174–176 °C.
1H NMR (300 MHz, CDCl3): δ = 8.15 (d, J = 9.3 Hz, 1 H), 7.66–
7.54 (m, 1 H), 7.31–7.28 (m, 3 H), 7.20–7.13 (m, 3 H), 6.97–6.84
(m, 5 H), 3.59–3.56 (m, 4 H), 3.36–3.33 (m, 4 H), 2.39 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 154.1, 150.5, 136.7, 135.8, 135.2,
129.5, 129.3, 128.5, 125.5, 122.7, 120.5, 120.0, 119.3, 116.3, 113.7,
113.2, 111.5, 109.6, 48.8, 47.00, 9.7 ppm. HRMS (ESI): calcd. for
C25H24N4O2 [M + H]+ 412.1899; found 412.1901.
13 in 85, 81, 72, and 74% yields, respectively (Scheme 5).
1-(5-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-nitrophenyl)-3-
methyl-1H-indole (3j): The product was obtained as a yellow solid;
m.p. 166–168 °C. 1H NMR (300 MHz, CDCl3): δ = 8.10 (d, J =
9 Hz, 1 H), 7.60–7.57 (m, 1 H), 7.37–7.33 (m, 4 H), 7.18–7.09 (m,
3 H), 7.08–6.94 (m, 4 H), 6.89 (d, J = 9 Hz, 1 H), 6.81–6.75 (m, 2
H), 4.25 (s, 1 H), 3.38 (t, J = 5.1 Hz, 4 H), 2.50 (t, J = 4.9 Hz, 4
H), 2.35 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 163.5,
160.3, 154.2, 137.5, 136.5, 135.7, 134.9, 129.5, 129.1, 129.0, 128.4,
125.4, 122.6, 120.0, 119.3, 115.7, 115.5, 113.7, 113.0, 111.3, 109.6,
74.2, 51.1, 47.1, 9.6 ppm. HRMS (ESI): calcd. for C32H28F2N4O2
[M + H]+ 538.2180; found 538.2188.
Typical Procedure for the Synthesis of 2,4-Di(pyrrol-1-yl)phenyl-
amine (4b): To a well-stirred solution of alkyl-substituted
1-(2-nitrophenyl)-1H-indole or 1-(2-nitrophenyl)-1H-imidazole
(5.0 mmol) in absolute ethanol (25 mL), 10% Pd/C (20 mol-%) was
added. The reaction mixture was stirred for 2–3 h at room tempera-
ture under a hydrogen atmosphere at 45 psi. The reaction mixture
was filtered through Celite and the filtrate was evaporated in vacuo
to obtain the desired amines.
Scheme 5. Palladium-catalyzed diversification.
2,4-Di(pyrrol-1-yl)phenylamine (4b): The product was obtained as a
white solid; m.p. 96–98 °C. 1H NMR (300 MHz, CDCl3): δ = 7.27–
7.22 (m, 2 H), 7.00 (t, J = 1.8 Hz, 2 H), 6.90–6.81 (m, 3 H), 6.40–
6.32 (m, 4 H), 3.77 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 139.9, 132.6, 127.6, 121.5, 121.1, 119.9, 119.5, 116.6, 109.8,
109.7 ppm. HRMS (ESI): calcd. for C14H13N3 [M + H]+ 223.1109;
found 223.1113.
Conclusions
We have demonstrated for the first time a simple and
efficient method for the selective synthesis of oxidized and
reduced forms of indolo/pyrrolo[1,2-a]quinoxalines, in good
to excellent yields, by applying a modified Pictet–Spengler
reaction under mild conditions. The reaction was facilitated
by Lewis acids as a catalyst and benzotriazole as an addi-
tive. The results show that benzotriazole can be used for
various types of transformation due to its unique proper-
ties. A novel series of piperazine-substituted quinoxalines
were also synthesized because of their importance in medic-
inal chemistry. We have also extended our strategy to the
tandem synthesis of indolo/pyrrolo quinoxalinones in one
pot without isolating the benzotriazole intermediate. Fur-
ther investigations that are focused on expanding the reac-
tion scope are ongoing and will be reported in due course.
General Procedure for the Synthesis of 4,5-Dihydropyrrolo[1,2-a]-
quinoxalines 6a–l and 6r and 5,6-Dihydroindolo[1,2-a]quinoxalines
6m–q: To a well-stirred solution of aldehyde 5 (0.6 mmol), benzotri-
azole (1.0 equiv.), and 10 mol-% AlCl3 in THF, 1-(2-aminophenyl)-
pyrrole or 2-(3-methylindol-1-yl)phenylamine (4; 0.5 mmol) was
added. The reaction was stirred at room temperature for 1–2 h,
then the reaction mixture was extracted with ethyl acetate and
water. The organic layer was washed with NaOH, brine, and dried
with Na2SO4. The solvent was evaporated in vacuo and the solid
obtained was purified by column chromatography (hexane/ethyl
acetate) to afford the desired product in good yields.
4-Phenyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (6a): The product
was obtained as a pale-yellow solid; m.p. 98–99 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.47–7.45 (m, 2 H), 7.37–7.32 (m, 4 H),
7.21–7.19 (m, 1 H), 6.96 (t, J = 7.5 Hz, 1 H), 6.84 (d, J = 7.8 Hz,
1 H), 6.72 (d, J = 7.8 Hz, 1 H), 6.24 (t, J = 3 Hz, 1 H), 5.57–5.52
(m, 2 H), 4.13 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
141.4, 136.1, 130.0, 128.6, 128.2, 127.9, 125.4, 119.3, 115.3, 114.7,
114.3, 110.1, 105.8, 56.2 ppm. HRMS (ESI): calcd. for C17H14N2
[M + H]+ 246.1157; found 246.1161.
Experimental Section
General Procedure for the Synthesis of Piperazinyl-Substituted 3-
Methyl-1-(2-nitrophenyl)-1H-indoles 3i and 3j: To a well-stirred
solution of N-heterocycle (1.0 mmol) in DMSO (1.0 mL), NaOH
(1.0 equiv.) and aryl halide (1.0 mmol) were added slowly. The reac-
tion mixture was stirred vigorously for 1–1.5 h at room temperature
until no more starting material was detectable by TLC analysis.
The reaction mixture was extracted with ethyl acetate and water
4-(4-Methoxyphenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6b): The
1
product was obtained as a light-yellow solid; m.p. 108–110 °C. H
NMR (300 MHz, CDCl3): δ = 7.32–6.76 (m, 9 H), 6.25 (s, 1 H),
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Eur. J. Org. Chem. 2011, 6998–7010

Synthesis of Ring-Fused Quinoxalinones
5.62 (s, 1 H), 5.52 (s, 1 H), 4.17 (br. s, 1 H), 3.79 (s, 3 H) ppm. 13C 1.2 Hz, 1 H), 7.52–7.46 (m, 3 H), 7.22–7.20 (m, 1 H), 6.96 (td, J =
NMR (75 MHz, CDCl3): δ = 159.5, 136.2, 133.4, 130.2, 129.1, 7.8, 1.4 Hz, 1 H), 6.90–6.88 (m, 1 H), 6.78–6.50 (m, 1 H), 6.50 (dd,
125.4, 124.5, 119.2, 115.2, 114.6, 114.2, 113.9, 110.0, 105.7, 55.5,
55.2 ppm. HRMS (ESI): calcd. for C18H16N2O [M + H]+ 276.1263;
found 276.1269.
J = 1.2, 7.8 Hz, 1 H), 6.32 (t, J = 3.3 Hz, 1 H), 6.12 (d, J = 3.3 Hz,
1 H), 6.06 (d, J = 2.7 Hz, 1 H), 5.73 (s, 1 H), 4.4 (br. s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 155.1, 151.2, 134.6, 132.9, 130.9,
130.6, 130.5, 127.5, 125.9, 125.5, 124.8, 123.4, 122.8, 119.8, 115.8,
114.7, 110.3, 109.2, 107.2, 105.8, 49.3 ppm. HRMS (ESI): calcd.
for C21H14Cl2N2O [M + H]+ 380.0483; found 380.0489.
4-(5-Ethylfuran-2-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6c): The
1
product was obtained as a semi-solid; m.p. 208–210 °C. H NMR
(300 MHz, CDCl3): δ = 7.29 (d, J = 7.8 Hz, 1 H), 7.18–7.13 (m, 1
H), 7.94 (t, J = 7.5 Hz, 1 H), 6.84–6.78 (m, 1 H), 6.72 (d, J =
7.8 Hz, 1 H), 6.33–6.30 (m, 1 H), 6.00–5.96 (m, 2 H), 5.85 (d, J =
2.7 Hz, 1 H), 5.63 (s, 1 H), 4.33 (br. s, 1 H), 2.61 (q, J = 7.5 Hz, 2
H), 1.2 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 157.7, 152.2, 135.0, 126.2, 125.4, 124.6, 119.5, 115.7, 114.6, 116.4,
110.0, 109.3, 107.7, 105.6, 104.5, 49.3, 21.3, 12.0 ppm. HRMS
(ESI): calcd. for C17H16N2O [M + H]+ 264.1263; found 264.1267.
4-(4-Fluorophenyl)-8-pyrrol-1-yl-4,5-dihydropyrrolo[1,2-a]quin-
oxaline (6i): The product was obtained as a colourless solid; m.p.
150–152 °C. 1H NMR (300 MHz, CDCl3): δ = 7.42–7.47 (m, 2 H),
7.34 (d, J = 2.4 Hz, 1 H), 7.17–7.19 (m, 1 H), 6.98–7.10 (m, 5 H),
6.78 (d, J = 8.4 Hz, 1 H), 6.34 (t, J = 2.1 Hz, 2 H), 6.27 (t, J =
3.1 Hz, 1 H), 5.56–5.58 (m, 1 H), 5.53 (s, 1 H), 4.17 (br. s, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 136.8, 134.0, 133.7,
129.9, 129.7, 129.5, 125.8, 119.7, 117.6, 115.8, 115.7, 115.4, 114.5,
110.7, 109.9, 108.4, 106.4, 55.5 ppm. HRMS (ESI): calcd. for
C21H16FN3 [M + H]+ 329.1328; found 329.1333.
4-(4-Nitrophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6d): The
1
product was obtained as a light-yellow solid; m.p. 106–108 °C. H
NMR (400 MHz, CDCl3): δ = 8.21–8.20 (m, 2 H), 7.63–7.60 (m, 2
H), 7.3 (d, J = 7.3 Hz, 1 H), 7.21–7.20 (m, 1 H), 7.0 (td, J = 8.0,
1.4 Hz, 1 H), 6.8 (t, J = 8 Hz, 1 H), 6.7 (m, 1 H), 6.24 (m, 1 H),
5.6 (m, 1 H), 5.6 (s, 1 H), 4.2 (br. s, 1 H) ppm. 13C (100 MHz,
CDCl3): δ = 148.7, 147.7, 135.1, 128.6, 127.9, 125.2, 124.9, 123.9,
119.9, 115.5, 114.8, 110.3, 106.2, 55.4 ppm. HRMS (ESI): calcd.
for C17H13N3O2 [M + H]+ 291.1008; found 291.1010.
4-(4-Nitrophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6d): 1H
NMR (400 MHz, D2O): δ = 8.20 (d, J = 8.8 Hz, 2 H), 7.60 (d, J
= 8.8 Hz, 2 H), 7.5 (d, J = 9.4 Hz, 1 H), 7.4 (d, J = 1.4 Hz, 1 H),
6.99–6.92 (m, 2 H), 6.8 (t, J = 5.1 Hz, 1 H), 6.24 (t, J = 3.3 Hz, 1
H), 5.79 (d, J = 2.9 Hz, 1 H), 5.76 (s, 1 H) ppm.
4-(2,4-Dichlorophenyl)-8-(1H-pyrrol-1-yl)-4,5-dihydropyrrolo[1,2-a]-
quinoxaline (6j): The product was obtained as a light-yellow solid;
1
m.p. 188–189 °C. H NMR (300 MHz, CDCl3): δ = 7.43 (s, 1 H),
7.36 (s, 1 H), 7.26–7.24 (m, 2 H), 7.15 (q, J = 8.7 Hz, 2 H), 7.02–
6.97 (m, 2 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.34 (m, 3 H), 6.06 (s, 1 H),
5.86 (s, 1 H), 4.43 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 137.9, 134.3, 133.8, 133.2, 132.8, 130.1, 129.3, 127.7, 126.9, 125.6,
119.7, 117.7, 116.1, 114.6, 111.0, 109.9, 108.3, 106.6, 51.5 ppm.
HRMS (ESI): calcd. for C21H15Cl2N3 [M + H]+ 379.0643; found
379.0645.
4-(2-Bromopyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6k):
The product was obtained as a light-yellow solid; m.p. 145–148 °C.
1H NMR (400 MHz, CDCl3): δ = 8.25 (t, J = 2.9 Hz, 1 H), 7.36–
7.35 (m, 2 H), 7.26–7.25 (m, 1 H), 7.16–7.15 (m, 1 H), 6.99–6.98
(m, 1 H), 6.88–6.81 (m, 1 H), 6.73–6.72 (m, 1 H), 6.33 (t, J =
3.3 Hz, 1 H), 6.1 (s, 1 H), 5.89–5.88 (m, 1 H), 4.57 (br. s, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 149.3, 142.3, 138.6, 137.8, 134.3,
126.2, 125.2, 124.9, 123.3, 119.7, 115.8, 114.6, 110.5, 106.3,
53.6 ppm. HRMS (ESI): calcd. for C16H12BrN3 [M + H]+
326.1906; found 326.1909.
4-(4-Bromophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6e): The
1
product was obtained as a light-yellow solid; m.p. 116–118 °C. H
NMR (300 MHz, CDCl3): δ = 7.5 (d, J = 8.1 Hz, 2 H), 7.33 (d, J
= 8.4 Hz, 3 H), 7.21–7.19 (m, 1 H), 6.97 (t, J = 7.5 Hz, 1 H), 6.88
(t, J = 7.8 Hz, 1 H), 6.74 (d, J = 7.8 Hz, 1 H), 6.24–6.23 (m, 1 H),
5.55–5.48 (m, 2 H), 4.11 (br. s, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 140.4, 135.8, 131.8, 129.6, 125.4, 124.7, 122.2, 119.6,
115.4, 114.7, 114.5, 110.2, 105.9, 55.6 ppm. HRMS (ESI): calcd.
for C17H13BrN2 [M + H]+ 324.0262; found 324.0268.
4-Ethyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (6l): The product was
obtained as a light-yellow oil. 1H NMR (400 MHz, CDCl3): δ =
7.20–7.17 (m, 1 H), 7.06–7.05 (m, 1 H), 6.85 (td, J = 7.8, 1.4 Hz,
1 H), 6.71 (td, J = 8.0, 1.4 Hz, 2 H), 6.65 (dd, J = 7.8, 0.9 Hz, 1
H), 6.22–6.20 (m, 1 H), 5.91–5.90 (m, 1 H), 4.29 (q, J = 1.8 Hz, 2
H), 3.2 (br. s, 1 H), 0.95 (t, J = 7.8 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 136.2, 129.7, 125.6, 124.7, 119.1, 115.7,
114.8, 114.2, 110.1, 104.0, 52.2, 27.1, 9.8 ppm. HRMS (ESI): calcd.
for C13H14N2 [M + H]+ 198.2637; found 198.2639.
4-(4-Fluorophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6f): The
product was obtained as a light-yellow solid; m.p. 112–114 °C. H
1
NMR (300 MHz, CDCl3): δ = 7.46–7.41 (m, 2 H), 7.33 (d, J =
7.8 Hz, 1 H), 7.19–7.18 (m, 1 H), 7.12–7.10 (m, 2 H), 6.97 (td, J =
1.2, 7.5 Hz, 1 H), 6.85 (td, J = 1.2, 7.8 Hz, 1 H), 6.74 (dd, J = 1.2,
7.8 Hz, 1 H), 6.27–6.23 (m, 1 H), 5.54–5.50 (m, 2 H), 4.10 (br. s, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.3, 161.0, 137.2,
137.1, 136.0, 129.8, 129.7, 129.6, 125.5, 124.7, 119.5, 115.6, 115.3,
114.7, 114.4, 110.2, 105.8, 55.5 ppm. HRMS (ESI): calcd. for
C17H13FN2 [M + H]+ 264.1063; found 264.1066.
7-Methyl-6-phenyl-5,6-dihydroindolo[1,2-a]quinoxaline (6m): The
1
product was obtained as a light-yellow solid; m.p. 148–150 °C. H
4-(2,4-Dichlorophenyl)-4,5-dihydropyrrolo[1,2-a]quinoxaline (6g):
1
NMR (300 MHz, CDCl3): δ = 8.01 (d, J = 8.2 Hz, 1 H), 7.90 (t, J
= 4.3 Hz, 1 H), 7.56 (d, J = 7.7 Hz, 1 H), 7.31–7.17 (m, 7 H), 6.95
(t, J = 4.3 Hz, 2 H), 6.75 (t, J = 4.5 Hz, 1 H), 5.60 (s, 1 H), 4.22
(br. s, 1 H), 2.03 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
141.7, 135.6, 133.3, 132.5, 130.6, 128.7, 127.8, 127.1, 123.6, 122.4,
120.3, 119.7, 118.8, 116.3, 116.1, 114.3, 111.7, 107.3, 55.0, 8.3 ppm.
HRMS (ESI): calcd. for C22H18N2 [M + H]+ 310.1470; found
310.1479.
The product was obtained as a yellow solid; m.p. 240–242 °C. H
NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 1.5 Hz, 1 H), 7.36 (d,
J = 7.8 Hz, 1 H), 7.26–7.24 (m, 1 H), 7.16–7.10 (m, 2 H), 6.96 (td,
J = 1.5, 7.8 Hz, 1 H), 6.86 (td, J = 1.2, 7.8 Hz, 1 H), 6.73 (dd, J =
0.6, 2.7 Hz, 1 H), 6.32 (t, J = 3.2 Hz, 1 H), 6.05 (s, 1 H), 5.83 (d,
J = 2.72 Hz, 1 H), 4.38 (br. s, 1 H) ppm. 13C (75 MHz, CDCl3):
138.2, 134.8, 134.1, 133.2, 130.1, 129.2, 127.6, 126.8, 125.2, 124.8,
119.6, 115.7, 114.7, 114.5, 110.4, 106.0, 51.4 ppm. HRMS (ESI):
calcd. for C17H12Cl2N2 [M + H]+ 314.0378; found 314.0380.
6-(4-Fluorophenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinoxaline
4-[5-(3,4-Dichlorophenyl)furan-2-yl]-4,5-dihydropyrrolo[1,2-a]- (6n): The product was obtained as a light-yellow solid; m.p. 218–
quinoxaline (6h): The product was obtained as a light-yellow solid;
220 °C. 1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 7.9 Hz, 1
H), 7.91 (d, J = 3.8 Hz, 1 H), 7.57 (d, J = 6.8 Hz, 1 H), 7.30–7.22
m.p. 220–222 °C. 1H NMR (300 MHz, CDCl3): δ = 7.60 (d, J =
Eur. J. Org. Chem. 2011, 6998–7010
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7005

A. K. Verma et al.
FULL PAPER
(m, 4 H), 6.97 (d, J = 4.6 Hz, 4 H), 6.78 (s, 1 H), 5.68 (s, 1 H), 2.9 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 154.4, 138.4,
4.20 (br. s, 1 H), 2.03 (d, J = 2.7 Hz, 3 H) ppm. 13C NMR (75 MHz, 136.2, 130.2, 129.8, 128.5, 127.4, 127.1, 125.3, 125.2, 114.5, 113.9,
CDCl3): δ = 158.3, 135.8, 134.3, 130.5, 128.9, 128.2, 126.8, 124.1,
121.8, 121.3, 120.5, 119.6, 118.5, 116.7, 114.8, 111.5, 108.4, 54.8,
7.9 ppm. HRMS (ESI): calcd. for C22H17FN2 [M + H]+ 328.1376;
found 328.1380.
113.6, 108.8 ppm. HRMS (ESI): calcd. for C17H12N2 [M + H]+
244.1000; found 244.1002.
4-(4-Fluorophenyl)pyrrolo[1,2-a]quinoxaline (7b): The product was
obtained as a light-yellow solid; m.p. 108–110 °C. 1H NMR
(300 MHz, CHCl3): δ = 8.01 (d, J = 13.9 Hz, 4 H), 7.90 (d, J =
7.2 Hz, 1 H), 7.53–7.44 (m, 2 H), 7.25–7.20 (m, 2 H), 6.95–6.90 (m,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.9, 153.2, 136.2,
134.6, 130.6, 130.2, 127.5, 127.1, 125.3, 115.5, 115.3, 114.7, 113.6,
108.5 ppm. HRMS (ESI): calcd. for C17H11FN2 [M + H]+
262.0906; found 262.0912.
6-(4-Chlorophenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinoxaline
(6o): The product was obtained as a light-yellow solid; m.p. 190–
192 °C. 1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.2 Hz, 1
H), 7.91–7.89 (m, 1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.32 (td, J = 6.8,
1.3 Hz, 1 H), 7.24–7.21 (m, 3 H), 7.15 (d, J = 8.2 Hz, 2 H), 6.98–
6.95 (m, 2 H), 6.77–6.74 (m, 1 H), 5.60 (s, 1 H), 2.06 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 140.4, 135.4, 133.9, 133.6, 132.3,
130.7, 129.1, 128.7, 127.5, 124.0, 122.9, 120.7, 120.7, 120.2, 119.1,
116.6, 116.5, 112.0, 107.4, 54.2, 8.3 ppm. HRMS (ESI): calcd. for
C22H17ClN2 [M + H]+ 344.1080; found 344.1087.
4-(4-Bromophenyl)pyrrolo[1,2-a]quinoxaline (7c): The product was
1
obtained as a white solid; m.p. 104–106 °C. H NMR (400 MHz,
CDCl3): δ = 8.00–7.90 (m, 2 H), 7.90–7.80 (m, 3 H), 7.70–7.60 (m,
2 H), 7.50 (td, J = 8.7, 1.5 Hz, 1 H), 7.50 (td, J = 8.0, 1.4 Hz, 1
H), 6.94 (t, J = 3 Hz, 1 H), 6.93 (t, J = 2.9 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 153.0, 137.2, 136.0, 131.7, 130.2,
127.7, 127.0, 125.3, 124.9, 124.1, 114.8, 114.1, 113.6, 108.5 ppm.
HRMS (ESI): calcd. for C17H11BrN2 [M + H]+ 322.0106; found
322.0108.
6-(3-Chlorophenyl)-7-methyl-5,6-dihydroindolo[1,2-a]quinoxaline
(6p): The product was obtained as a light-yellow solid; m.p. 168–
170 °C. 1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 8.1 Hz, 1
H), 7.91–7.88 (m, 1 H), 7.59 (d, J = 7.5 Hz, 1 H), 7.33–7.15 (m, 5
H), 7.08 (d, J = 6.9 Hz, 1 H), 6.98–6.94 (m, 2 H), 6.77 (t, J =
4.5 Hz, 1 H), 5.66 (s, 1 H), 4.31 (br. s, 1 H), 2.07 (s, 3 H) ppm. 13
C
4-(4-Chlorophenyl)pyrrolo[1,2-a]quinoxaline (7d): The product was
obtained as a pale-yellow solid; m.p. 110–112 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.03 (d, J = 7.2 Hz, 2 H), 7.96 (d, J =
8.4 Hz, 2 H), 7.89 (d, J = 8.1 Hz, 1 H), 7.56–7.44 (m, 4 H), 6.97–
6.90 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.1, 136.8,
136.1, 135.8, 130.2, 129.9, 128.8, 127.7, 125.4, 125.0, 114.8, 114.1,
113.6, 108.4 ppm. HRMS (ESI): calcd. for C17H11ClN2 [M + H]+
278.0611; found 278.0616.
NMR (75 MHz, CDCl3): δ = 143.7, 135.1, 134.6, 133.5, 131.8,
130.6, 130.1, 128.1, 127.3, 125.3, 123.8, 122.7, 120.5, 120.1, 119.0,
116.5, 116.3, 111.8, 107.6, 54.4, 8.4 ppm. HRMS (ESI): calcd. for
C22H17ClN2 [M + H]+ 344.0924; found 344.0928.
6-(4-Chlorophenyl)-2-fluoro-7-methyl-5,6-dihydroindolo[1,2-a]-
quinoxaline (6q): The product was obtained as a yellow solid; m.p.
190–192 °C. 1H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 8.4 Hz,
1 H), 7.64–7.57 (m, 2 H), 7.33 (td, J = 1.2, 7.2 Hz, 1 H), 7.25–7.21
(m, 3 H), 7.15–7.12 (m, 2 H), 6.67 (dd, J = 1.2, 6.6 Hz, 2 H), 5.63
(s, 1 H), 4.19 (br. s, 1 H), 2.04 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 155.4, 139.8, 133.8, 131.9, 130.7, 129.0, 128.5, 127.9,
123.1, 120.9, 119.2, 116.7, 111.5, 109.9, 109.6, 108.1, 104.4, 104.0,
54.3, 8.3 ppm. HRMS (ESI): calcd. for C22H16ClFN2 [M + H]+
362.0986; found 362.0996.
8-(1H-Pyrrol-1-yl)-4-p-tolylpyrrolo[1,2-a]quinoxaline (7e): The
product was obtained as a light-yellow crystals; m.p. 174–176 °C.
1H NMR (300 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.96 (s, 1 H), 7.86
(d, J = 7.5 Hz, 2 H), 7.77–7.75 (m, 1 H), 7.44 (d, J = 8.4 Hz, 1 H),
7.30 (d, J = 7.8 Hz, 1 H), 7.17 (d, J = 6.6 Hz, 3 H), 7.03 (s, 1 H),
6.91 (s, 1 H), 6.37 (m, 2 H), 2.4 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.8, 140.0, 139.5, 135.5, 134.2, 131.4, 129.3, 128.5,
127.7, 125.5, 119.6, 117.8, 114.5, 114.4, 111.2, 109.0, 105.1,
21.5 ppm. HRMS (ESI): calcd. for C22H17N3 [M + H]+ 323.1422;
found 323.1426.
1,4-Bis(4,5-dihydropyrrolo[1,2-a]quinoxalin-4-yl)benzene (6r): The
product was obtained as a yellow solid; m.p. 190–192 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.6 (d, J = 8.3 Hz, 1 H), 7.48–7.46 (m, 3
H), 7.33–7.31 (m, 2 H), 7.21–7.18 (m, 2 H), 6.95 (td, J = 8.7,
1.3 Hz, 2 H), 6.8 (td, J = 7.8, 0.9 Hz, 2 H), 6.73–6.71 (m, 2 H),
6.3–6.2 (m, 2 H), 5.56–5.53 (m, 2 H), 5.5 (s,2 H), 4.13 (br. s, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.5, 136.0, 129.6,
128.1, 125.4, 124.6, 119.3, 115.3, 114.7, 114.3, 110.1, 105.8,
55.7 ppm. HRMS (ESI): calcd. for C28H22N4 [M + H]+ 414.1844;
found 414.1848.
7-Methyl-6-phenylindolo[1,2-a]quinoxaline (7f): The product was
obtained as a yellow solid; m.p. 94–96 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.48 (d, J = 8.2 Hz, 2 H), 8.01 (d, J = 7.8 Hz, 1 H),
7.90 (d, J = 8.1 Hz, 1 H), 7.25–7.63 (m, 9 H), 2.05 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 157.6, 139.8, 136.2, 135.9, 133.1,
132.5, 131.2, 130.1, 130.0, 129.6, 128.8, 128.3, 128.1, 125.3, 124.5,
123.6, 122.0, 121.7, 120.5, 114.2, 110.7, 11.2 ppm. HRMS (ESI):
calcd. for C22H16N2 [M + H]+ 308.1313; found 308.1323.
General Procedure for the Synthesis of Pyrrolo/Indolo-quinoxalines
7a–e, 7f–p and 7s–x and Imidazoquinoxalines 7q–r: To a well-stirred
solution of aldehyde 5 (0.6 mmol), benzotriazole (1.0 equiv.) and
10 mol-% AlCl3 in THF, 1-(2-aminophenyl)pyrrole or 2-(3-meth-
ylindol-1-yl)phenylamine (4; 0.5 mmol) was added. The reaction
was stirred at room temperature for 8–10 h. The reaction mixture
was extracted with ethyl acetate and water and the organic layer
was washed with NaOH, brine, and dried with Na2SO4. The sol-
vent was evaporated in vacuo and the solid obtained was purified
by column chromatography (hexane/ethyl acetate) to afford the de-
sired product in good yields.
6-(4-Fluorophenyl)-7-methylindolo[1,2-a]quinoxaline (7g): The prod-
uct was obtained as a greenish-yellow solid; m.p. 112–114 °C. 1H
NMR (300 MHz, CDCl3): δ = 8.49 (d, J = 7.7 Hz, 2 H), 7.99 (d,
J = 7.6 Hz, 1 H), 7.91 (d, J = 7.9 Hz, 1 H), 7.21–7.66 (m, 8 H),
2.09 (t, J = 19.8 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
156.5, 135.6, 131.6, 130.5, 130.1, 128.4, 127.7, 126.5, 125.8, 124.8,
123.8, 123.6, 122.1, 121.1, 120.4, 115.6, 115.4, 114.4, 110.5,
11.3 ppm. HRMS (ESI): calcd. for C22H15FN2 [M + H]+ 326.1219;
found 326.1226.
6-(3-Chlorophenyl)-7-methylindolo[1,2-a]quinoxaline (7h): The prod-
4-Phenylpyrrolo[1,2-a]quinoxaline (7a): The product was obtained
uct was obtained as a pale-yellow solid; m.p. 114–116 °C. 1H NMR
1
as a light-yellow solid; m.p. 118–120 °C. H (400 MHz, CDCl3): δ (400 MHz, CDCl3): δ = 8.43–8.41 (m, 2 H), 7.99 (dd, J = 7.7,
= 8.13 (d, J = 8 Hz, 1 H), 7.99–7.97 (m, 3 H), 7.80 (d, J = 7.3 Hz,
1.3 Hz, 1 H), 7.88 (dd, J = 8.2, 0.9 Hz, 1 H), 7.64 (t, J = 1.4 Hz, 1
1 H), 7.50–7.40 (m, 5 H), 6.90 (t, J = 3 Hz, 1 H), 6.80 (t, J = H), 7.57–7.56 (m, 3 H), 7.52–7.50 (m, 2 H), 7.48–7.44 (m, 1 H),
7006
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Eur. J. Org. Chem. 2011, 6998–7010

Synthesis of Ring-Fused Quinoxalinones
7.39 (td, J = 5.9, 0.9 Hz, 1 H), 2.08 (s, 3 H) ppm. 13C NMR 9-Methoxy-6-[4-(trifluoromethyl)phenyl]indolo[1,2-a]quinoxaline
(100 MHz, CDCl3): δ = 155.9, 141.1, 135.4, 134.4, 131.9, 130.4, (7o): The product was obtained as a pale-yellow solid; m.p. 200–
1
130.1, 129.7, 129.3, 128.8, 128.5, 126.8, 125.2, 124.8, 123.8, 122.1,
120.7, 114.34, 114.32, 110.6, 11.2 ppm. HRMS (ESI): calcd. for
C22H15ClN2 [M + H]+ 342.0924; found 342.0928.
205 °C. H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 8 Hz, 1 H),
8.30 (d, J = 9.4 Hz, 1 H), 8.10 (d, J = 8.1 Hz, 2 H), 8.01 (d, J =
7.4 Hz, 1 H), 7.70 (d, J = 8.1 Hz, 2 H), 7.60 (td, J = 7.4, 1.4 Hz, 1
H), 7.40 (t, J = 7.1 Hz, 1 H), 7.20 (d, J = 2 Hz, 1 H), 7.20 (d, J =
14.7 Hz, 1 H), 7.05 (s, 1 H), 3.8 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 155.8, 154.1, 141.9, 136.0, 131.6, 131.1, 130.7, 130.2,
129.9, 129.2, 129.0, 128.8, 125.6, 125.6, 124.2, 116.1, 115.6, 114.3,
102.2, 101.5, 55.5 ppm. HRMS (ESI): calcd. for C23H15F3N2O [M
+ H]+ 392.1136; found 392.1140.
7-Methyl-6-p-tolylindolo[1,2-a]quinoxaline (7i): The product was
obtained as a pale-yellow solid; m.p. 118–120 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.48 (d, J = 8.4 Hz, 2 H), 8.00 (dd, J =
7.8, 1.5 Hz, 1 H), 7.90 (d, J = 8.1 Hz, 1 H), 7.60–7.51 (m, 4 H),
7.47–7.41 (m, 2 H), 7.39–7.32 (m, 2 H), 2.47 (s, 3 H), 2.1 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.8, 139.2, 136.8,
135.8, 132.0, 130.5, 130.3, 130.1, 129.1, 128.5, 128.1, 125.9, 124.6,
123.1, 122.0,120.7, 114.4, 114.3, 110.8, 21.5, 11.3 ppm. HRMS
(ESI): calcd. for C23H18N2 [M + H]+ 322.1470; found 322.1470.
6-(3-Chlorophenyl)-9-methoxyindolo[1,2-a]quinoxaline (7p): The
product was obtained as a yellow solid; m.p. 190–192 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.40 (d, J = 7.4 Hz, 1 H), 8.36 (d, J =
8.7 Hz, 1 H), 8.04 (d, J = 8 Hz, 1 H), 7.9 (d, J = 1.3 Hz, 1 H), 7.8
(dt, J = 7.4, 2 Hz, 1 H), 7.6 (td, J = 7.1, 1.3 Hz, 1 H), 7.51–7.48
(m, 2 H), 7.44–7.40 (m, 1 H), 7.2 (d, J = 2.7 Hz, 1 H), 7.2 (d, J =
8.7 Hz, 1 H), 7.12 (s, 1 H), 3.9 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 155.7, 154.5, 140.0, 135.6, 134.2, 130.6, 130.4, 130.2,
130.0, 129.9, 129.8,129.3, 128.7, 128.4, 126.7, 124.1, 115.9, 115.5,
114.3, 102.2, 101.6, 55.6 ppm. HRMS (ESI): calcd. for
C22H15ClN2O [M + H]+ 358.0873; found 358.0876.
6-(3-Bromophenyl)-7-methylindolo[1,2-a]quinoxaline (7j): The prod-
uct was obtained as a pale-yellow solid; m.p. 102–104 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.49 (dd, J = 3.4, 8.4 Hz, 2 H), 7.99 (d, J
= 7.5 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.81 (s, 1 H), 7.69–7.58
(m, 4 H), 7.49–7.39 (m, 3 H), 2.11 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 156.0, 141.4, 135.5, 132.0, 131.7, 130.6,
130.2, 130.0, 128.6, 12.7.3, 125.5, 125.0, 123.9, 122.5, 122.2, 120.8,
114.4, 110.7, 11.3 ppm. HRMS (ESI): calcd. for C22H15BrN2 [M +
H]+ 386.0419; found 386.0427.
3-Methyl-4-(4-nitrophenyl)imidazo[1,5-a]quinoxaline (7r): The prod-
uct was obtained as a pale-yellow solid; m.p. 126–128 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.60 (s, 1 H), 8.31 (d, J = 8.3 Hz, 2 H),
8.00 (d, J = 8.7 Hz, 2 H), 7.67–7.65 (m, 1 H), 7.45–7.39 (m, 1 H),
7.27–7.22 (m, 1 H), 6.96 (s, 1 H), 2.29 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 158.6, 149.5, 144.0, 140.9, 138.2, 137.5,
131.8, 129.7, 128.4, 127.9, 125.0, 124.1, 119.2, 116.8, 13.6 ppm.
HRMS (ESI): calcd. for C17H12N4O2 [M + H]+ 304.0960; found
304.0960.
7-Methyl-6-[4-(trifluoromethyl)phenyl]indolo[1,2-a]quinoxaline (7k):
The product was obtained as a white solid; m.p. 220–224 °C. 1H
NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 6 Hz, 2 H), 7.90 (d, J
= 8.1 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 1 H), 7.70 (d, J = 8hz, 4 H),
7.54–7.52 (m, 2 H), 7.40 (t, J = 7.4 Hz, 1 H), 7.36 (t, J = 7.4 Hz,
1 H), 2.00 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 155.9,
142.9, 135.4, 134.7, 132.1, 130.5, 130.2, 130.2, 129.1, 128.7, 125.5,
125.4, 125.0, 123.9, 122.3, 120.8, 114.4, 114.4, 110.6, 11.3 ppm.
HRMS (ESI): calcd. for C23H15F3N2 [M + H]+ 376.1187; found
376.1187.
7-Methyl-6-(3-nitrophenyl)-2-(4-phenylpiperazin-1-yl)indolo[1,2-a]-
quinoxaline (7s): The product was obtained as a orange solid; m.p.
1
248–250 °C. H NMR (300 MHz, CDCl3): δ = 8.55 (t, J = 2 Hz, 1
6-(4-Bromophenyl)-7-methylindolo[1,2-a]quinoxaline (7l): The prod-
uct was obtained as a yellow solid; m.p. 200–202 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.48 (dd, J = 3.4, 7.7 Hz, 2 H), 7.99 (dd,
J = 1.1, 7.8 Hz, 1 H), 7.91 (d, J = 8 Hz, 1 H), 7.69 (d, J = 8.3 Hz,
2 H), 7.60 (t, J = 7.4 Hz, 2 H), 7.54 (d, J = 8.2 Hz, 2 H), 7.49 (t,
J = 7.6 Hz, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 2.12 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 156.6, 138.7, 135.8, 132.3, 131.8,
130.7, 130.5, 130.4, 130.3, 128.7, 125.6, 125.1, 124.1, 123.8, 122.4,
121.0, 114.6, 110.3, 11.7 ppm. HRMS (ESI): calcd. for C22H15BrN2
[M + H]+ 386.0419; found 386.0425.
H), 8.45–8.37 (m, 2 H), 8.03–7.98 (m, 2 H), 7.93–7.88 (m, 2 H),
7.75–7.50 (m, 1 H), 7.64–7.62 (m, 1 H), 7.52–7.47 (m, 1 H), 7.35–
7.34 (m, 2 H), 7.09–7.03 (m, 3 H), 6.97–6.94 (m, 1 H), 3.64 (t, J =
5 Hz, 4 H), 3.49–3.46 (m, 4 H), 2.10 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 151.7, 150.9, 148.1, 141.4, 134.9, 131.8,
131.6, 130.9, 130.5, 129.4, 129.3, 128.9, 125.4, 124.5, 124.2, 123.8,
122.3, 120.7, 120.3, 116.4, 114.2, 112.8, 112.2, 109.2, 100.3, 49.3,
48.9, 11.6 ppm. HRMS (ESI): calcd. for C32H27N5O2 [M + H]+
513.2165; found 513.2168.
6-(4-Fluorophenyl)-7-methyl-2-(4-phenylpiperazin-1-yl)indolo-
6-(4-Chlorophenyl)-2-fluoro-7-methylindolo[1,2-a]quinoxaline (7m):
The product was obtained as a pale-yellow solid; m.p. 220–222 °C.
1H NMR (300 MHz, CDCl3): δ = 8.37 (d, J = 8.7 Hz, 1 H), 8.16
(dd, J = 2.4, 8.1 Hz, 1 H), 7.96–7.89 (m, 2 H), 7.64–7.46 (m, 6 H),
7.10 (td, J = 2.7, 5.7 Hz, 1 H), 2.09 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 155.3, 137.6, 135.3, 132.0, 131.8, 131.5,
131.3, 130.2, 125.0, 124.8, 122.4, 120.7, 113.9, 111.6, 110.9, 110.7,
101.7, 101.4, 11.2 ppm. HRMS (ESI): calcd. for C22H14ClFN2 [M
+ H]+ 360.0830; found 360.0839.
[1,2-a]quinoxaline (7t): The product was obtained as a yellowish
1
orange crystals; m.p. 254–256 °C. H NMR (300 MHz, CDCl3): δ
= 8.44 (d, J = 8.7 Hz, 1 H), 8.00 (d, J = 2.4 Hz, 1 H), 7.94–7.90
(m, 2 H), 7.66–7.59 (m, 2 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.39–7.33
(m, 2 H), 7.28–7.21 (m, 3 H), 7.10–7.05 (m, 3 H), 6.96 (t, J =
7.2 Hz, 1 H), 3.63 (t, J = 2.7 Hz, 4 H), 3.48 (t, J = 4.5 Hz, 4 H),
2.10 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.0, 151.4,
151.1, 138.2, 135.1, 131.7, 131.5, 130.7, 130.6, 129.3, 129.2, 126.0,
124.3, 122.05, 120.6, 120.3, 116.4, 115.6, 115.3, 114.2, 112.2, 109.7,
100.6, 49.4, 49.1, 11.3 ppm. HRMS (ESI): calcd. for C32H27FN4
[M + H]+ 486.2220; found 486.2226.
6-[4-(Trifluoromethyl)phenyl]indolo[1,2-a]quinoxaline (7n): The
1
product was obtained as a pale-yellow solid; m.p. 140–142 °C. H
NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 8 Hz, 2 H), 8.10 (d, J
= 8.1 Hz, 2 H), 8.03 (d, J = 8.1 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 1 6-(4-Chlorophenyl)-7-methyl-2-(4-phenylpiperazin-1-yl) indolo[1,2-
H), 7.78 (d, J = 8 Hz, 2 H), 7.60 (td, J = 8.7 Hz, 1 H), 7.50 (td, J
= 8.1 Hz, 1 H), 7.40 (td, J = 3.7 Hz, 2 H), 7.20 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 154.6, 139.8, 135.9, 134.6, 133.0,
130.5, 130.1, 130.0, 129.9, 129.5, 129.0, 128.7, 128.6, 126.7, 124.5,
124.2, 122.7, 122.7, 114.6, 114.5, 102.2 ppm. HRMS (ESI): calcd.
for C22H13F3N2 [M + H]+ 362.1031; found 362.1036.
a]quinoxaline (7u): The product was obtained as a yellow solid; m.p.
272–275 °C. 1H NMR (300 MHz, CDCl3): δ = 8.43 (d, J = 8.7 Hz,
1 H), 7.99 (d, J = 1.2 Hz, 1 H), 7.94–7.89 (m, 2 H), 7.64–7.58 (m,
3 H), 7.54–7.47 (m, 3 H), 7.35 (t, J = 7.8 Hz, 2 H), 7.09–7.05 (m,
3 H), 6.95 (t, J = 7.2 Hz, 1 H), 3.63 (t, J = 4.6 Hz, 4 H), 3.48 (t, J
= 5.1 Hz, 4 H), 2.11 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
Eur. J. Org. Chem. 2011, 6998–7010
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7007

A. K. Verma et al.
FULL PAPER
= 152.8, 151.4, 151.1, 138.3, 135.0, 131.7, 131.5, 130.8, 130.6, 130.2,
129.3, 129.1, 128.6, 125.8, 124.3, 122.1, 120.6, 120.3, 116.4, 114.2,
112.2, 109.6, 100.6, 49.4, 49.1, 11.4 ppm. HRMS (ESI): calcd. for
C32H27ClN4 [M + H]+ 502.1924; found 502.1928.
7.8 Hz, 1 H), 7.76 (d, J = 7.8 Hz, 1 H), 7.63 (t, J = 7.2 Hz, 1 H),
7.49–7.41 (m, 2 H), 7.24–7.16 (m, 2 H), 7.10–7.09 (m, 1 H), 6.19
(t, J = 3.3 Hz, 1 H), 6.11–6.10 (m, 1 H), 1.51 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 165.6, 147.1, 132.8, 130.6, 130.0,
128.9, 128.8, 125.9, 124.8, 124.7, 124.5, 124.1, 122.2, 116.0, 115.0,
110.6, 104.0, 61.6, 28.0 ppm. HRMS (ESI): calcd. for C19H14N2O
[M + H]+ 286.1106; found 286.1109.
2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-6-(4-bromophenyl)-
7-methylindolo[1,2-a]quinoxaline (7v): The product was obtained as
a yellow solid; m.p. 264–266 °C. 1H NMR (300 MHz, CDCl3): δ =
8.33 (d, J = 8.4 Hz, 1 H), 7.89–7.83 (m, 3 H), 7.65 (d, J = 8.4 Hz, 16-Methylindolo[1,2-a]isoindolo[1,2-c]quinoxalin-11(15bH)-one (9c):
2 H), 7.55–7.40 (m, 8 H), 7.05–6.99 (m, 5 H), 4.31 (s, 1 H), 3.46 (s, The product was obtained as a pale-yellow solid; m.p. 140–142 °C.
4 H), 2.65 (s, 4 H), 2.10 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): 1H NMR (400 MHz, CDCl3): δ = 8.12 (dd, J = 1.3, 7.8 Hz, 1 H),
δ = 153.3, 131.7, 131.6, 130.7, 130.5, 129.3, 129.2, 129.1, 128.7,
8.06–7.97 (m, 4 H), 7.72 (td, J = 1.4, 6.4 Hz, 1 H), 7.64–7.57 (m,
2 H), 7.38 (td, J = 1.3, 7.8 Hz, 1 H), 7.31–7.28 (m, 2 H), 7.27–7.22
128.1, 127.8, 125.9, 125.8, 124.0, 123.4, 122.1, 115.7, 115.5, 114.9,
114.1, 111.8, 109.5, 100.0, 51.7, 48.9, 29.7, 11.4 ppm. HRMS (ESI): (m, 1 H), 5.9 (s, 1 H), 2.39 (s, 3 H) ppm. 13C NMR (100 MHz): δ
calcd. for C39H31BrF2N4 [M + H]+ 672.1700; found 672.1708.
= 164.7, 138.6, 133.7, 133.1, 131.3, 130.7, 130.2, 129.3, 127.9, 127.2,
126.3, 125.6, 124.7, 123.9, 123.6, 122.5, 120.9, 119.3, 117.5, 111.1,
108.5, 58.2, 9.8 ppm. HRMS (ESI): calcd. for C23H16N2O [M +
H]+ 336.1263; found 336.1267.
2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-7-methyl-6-(4-
nitrophenyl)indolo[1,2-a]quinoxaline (7w): The product was ob-
tained as a pale-yellow solid; m.p. 269–271 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.33 (d, J = 8.4 Hz, 1 H), 7.88–7.83 (m, 3
H), 7.58–7.41 (m, 10 H), 7.05–6.96 (m, 5 H), 4.31 (s, 1 H), 3.46 (s,
15b,16-Dimethylindolo[1,2-a]isoindolo[1,2-c]quinoxalin-11(15bH)-
one (9d): The product was obtained as a yellow solid; m.p. 192–
4 H), 2.65 (s, 4 H), 2.08 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): 194 °C. 1H NMR (400 MHz, CDCl3): δ = 8.04–7.95 (m, 5 H), 7.72
δ = 167.0, 161.0, 152.6, 151.4, 137.9, 135.0, 131.7, 130.7, 130.2,
129.3, 128.8, 128.6, 125.8, 124.2, 122.0, 120.6, 115.7, 115.4, 114.1,
111.8, 109.5, 99.9, 78.0, 51.7, 48.9, 29.7, 11.4 ppm. HRMS (ESI):
calcd. for C39H31F2N5O2 [M + H]+ 639.2417; found 639.2420.
(t, J = 7.8 Hz, 1 H), 7.58 (t, J = 7.3 Hz, 1 H), 7.54 (d, J = 5.6 Hz,
1 H), 7.40 (t, J = 6.8 Hz, 1 H), 7.30–7.26 (m, 2 H), 7.18 (t, J =
7 Hz, 1 H), 2.35 (s, 3 H), 1.65 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.6, 144.5, 133.3, 132.6, 131.8, 131.5, 130.6, 130.5,
129.1, 126.0, 125.6, 125.0, 124.7, 124.4, 123.9, 123.5, 120.9, 119.1,
117.1, 111.1, 107.2, 63.6, 25.7, 10.1 ppm. HRMS (ESI): calcd. for
C24H18N2O [M + H]+ 350.4125; found 350.1479.
2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-6-(4-fluorophenyl)-
7-methylindolo[1,2-a]quinoxaline (7x): The product was obtained as
a yellow solid; m.p. 258–260 °C. 1H NMR (300 MHz, CDCl3): δ =
8.34 (d, J = 8.4 Hz, 1 H), 7.87 (t, J = 9.3 Hz, 3 H), 7.60 (d, J =
General Procedure for the Synthesis of Compounds 10–11: To a
8.4 Hz, 2 H), 7.5 (t, J = 7.5 Hz, 1 H), 7.47–7.41 (m, 4 H), 7.21 (t, vial was added 4-(4-bromophenyl)pyrrolo[1,2-a]quinoxaline
J = 8.7 Hz, 3 H), 7.05–6.96 (m, 5 H), 4.32 (s, 1 H), 3.47 (t, J = (1.0 mmol), boronic acid (1.2 equiv.), [Pd(PPh3)2Cl2] (10 mol-%),
4.5 Hz, 4 H), 2.66 (t, J = 4.5 Hz, 4 H), 2.09 (s, 3 H) ppm. 13C NMR
K2CO3 (2.5 equiv.), and DMF/H2O (4:1, 2.0 mL). The solution was
(75 MHz, CDCl3): δ = 165.2, 159.7, 148.7, 146.3, 145.1, 138.3, flushed with argon and then heated to 80 °C for 1 h until TLC
137.6, 135.4, 131.7, 130.7, 129.3, 124.8, 120.5, 115.7, 115.4, 115.2,
114.8, 112.7, 111.8, 109.5, 105.1, 100.4, 80.2, 51.7, 48.9, 29.7,
11.6 ppm. HRMS (ESI): calcd. for C39H31F3N4 [M + H]+
612.2501; found 612.2507.
revealed complete conversion of the starting material. The solution
was allowed to cool and diluted with H2O and then extracted with
EtOAc. The combined organic layers were dried with Na2SO4, con-
centrated, and purified by column chromatography to afford the
corresponding product.
General Procedure for the Synthesis of Indolo- and Pyrrolo[1,2-
a]quinoxalinones (9a–d): To a well-stirred solution of 1-(2-ami-
nophenyl) pyrrole or 2-(3-methylindol-1-yl)phenylamine
(1.0 mmol) in toluene (2.0 mL), benzotriazole (1.0 equiv.) and 2-
carboxybenzaldehyde (1.0 equiv.) were added followed by addition
of a catalytic amount of TsOH (10 mol-%). The reaction was
heated to reflux in a Dean–Stark apparatus for 2–4 h until no more
starting material was detectable by TLC analysis. The reaction mix-
ture was extracted with ethyl acetate and water and the organic
layer was washed with brine and dried with Na2SO4. The solvent
was removed in vacuo and the crude material was purified by col-
umn chromatography (hexane/ethyl acetate) using silica mesh (100–
200). The desired product was recrystallied from diethyl ether.
4-(4Ј-Methoxybiphenyl-4-yl)pyrrolo[1,2-a]quinoxaline (10): The
product was obtained as a white solid; m.p. 187–190 °C. H NMR
1
(300 MHz, CDCl3): δ = 8.06 (d, J = 7.5 Hz, 4 H), 7.90 (d, J =
8.1 Hz, 1 H), 7.73 (d, J = 7.8 Hz, 2 H), 7.60 (d, J = 8.4 Hz, 2 H),
7.50–7.40 (m, 2 H), 7.07–7.01 (m, 3 H), 6.90 (s, 1 H), 3.90 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.3, 154.0, 142.2,
136.7, 136.2, 133.0, 130.1, 129.0, 128.2, 127.0, 126.8, 125.3, 125.2,
114.6, 114.3, 114.0, 113.6, 108.6, 55.3 ppm. HRMS (ESI): calcd.
for C24H18N2O [M + H]+ 350.1419; found 350.1421.
4-[4Ј-(Methylthio)biphenyl-4-yl]pyrrolo[1,2-a]quinoxaline (11): The
product was obtained as a off-white solid; m.p. 173–175 °C. 1H
NMR (400 MHz, CDCl3): δ = 8.10–8.00 (m, 3 H), 7.99–7.98 (m, 1
H), 7.88–7.86 (m, 1 H), 7.73 (d, J = 8 Hz, 2 H), 7.60 (d, J = 8 Hz,
2 H), 7.51–7.45 (m, 2 H), 7.34 (d, J = 8.8 Hz, 2 H), 7.04 (m, 1 H),
6.90 (t, J = 3.3 Hz, 1 H), 2.53 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 153.8, 141.8, 138.1, 137.2, 136.2, 130.2, 129.1, 127.4,
127.1, 127.0, 126.9, 126.8, 125.2, 114.6, 113.9, 113.6, 108.5,
15.7 ppm. HRMS (ESI): calcd. for C24H18N2S [M + H]+ 366.1191;
found 366.1193.
Isoindolo[1,2-c]pyrrolo[1,2-a]quinoxalin-10(14bH)-one (9a): The
1
product was obtained as a pale-yellow solid; m.p. 220–224 °C. H
NMR (300 MHz, CDCl3): δ = 8.20–8.17 (m, 1 H), 7.98 (d, J =
7.5 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1 H), 7.72 (t, J = 7.5 Hz, 1 H),
7.59 (t, J = 7.5 Hz, 1 H), 7.53–7.50 (m, 1 H), 7.30–7.25 (m, 3 H),
6.35–6.30 (m, 2 H), 5.81 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 168.7, 145.0, 136.1, 134.3, 130.8, 128.6, 128.4, 128.3, 127.1,
125.5, 123.5, 101.0, 71.5 ppm. HRMS (ESI): calcd. for C18H12N2O
[M + H]+ 272.0950; found 272.0954.
General Procedure for the Synthesis of Compounds 12 and 13: To a
vial was added 4-(4-bromophenyl)pyrrolo[1,2-a]quinoxalin
14b-Methylisoindolo[1,2-c]pyrrolo[1,2-a]quinoxalin-10(14bH)-one (1.0 mmol), acrylate (1.2 equiv.), [Pd(PPh3)2Cl2] (10 mol-%),
(9b): The product was obtained as a yellow solid; m.p. 228–230 °C. K3PO4 (2.5 equiv.), and DMF (2.0 mL). The solution was flushed
1H NMR (300 MHz, CDCl3): δ = 8.04–8.01 (m, 1 H), 7.86 (d, J = with argon, and then heated to 120 °C for 4 h until TLC revealed
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Eur. J. Org. Chem. 2011, 6998–7010

Synthesis of Ring-Fused Quinoxalinones
G. Campiani, V. Nacci, F. Corelli, M. Anzini, Synth. Commun.
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complete conversion of the starting material. The solution was al-
lowed to cool and diluted with H2O and then extracted with
EtOAc. The combined organic layers were dried with Na2SO4, con-
centrated, and purified by column chromatography to afford the
corresponding product.
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Ethyl (E)-3-[4-(Pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]acrylate (12):
The product was obtained as a white solid; m.p. 89–91 °C. 1H
NMR (400 MHz, CDCl3): δ = 8.05–8.01 (m, 4 H), 7.90 (d, J =
8 Hz, 1 H), 7.80 (d, J = 16.1 Hz, 1 H), 7.70 (d, J = 8 Hz, 2 H),
7.50 (td, J = 8 Hz, 1 H), 7.49 (td, J = 9.5 Hz, 1 H), 7.01–6.99 (m,
1 H), 6.90 (t, J = 3 Hz, 1 H), 6.53 (d, J = 16.1 Hz, 1 H), 4.29 (q,
J = 8 Hz, 2 H), 1.35 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 166.8, 153.3, 143.8, 140.0, 136.1, 135.7, 130.2, 129.1,
128.2, 127.7, 127.1, 125.3, 125.1, 119.1, 114.7, 114.1, 113.6, 108.4,
60.6, 14.3 ppm. HRMS (ESI): calcd. for C22H18N2O2 [M + H]+
342.1368; found 342.1371.
Methyl (E)-3-[4-(Pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]acrylate (13):
The product was obtained as a pale-yellow solid; m.p. 102–104 °C.
1H NMR (300 MHz, CDCl3): δ = 8.04 (d, J = 7.8 Hz, 4 H), 7.90
(d, J = 7.8 Hz, 1 H), 7.80–7.70 (m, 3 H), 7.50–7.40 (m, 2 H), 7.03
(d, J = 18.3 Hz, 2 H), 6.50 (d, J = 15.9 Hz, 1 H), 3.80 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 167.3, 153.3, 144.2, 140.2, 136.1,
135.7, 130.3, 129.2, 128.3, 127.8, 127.2, 125.4, 125.1, 119.7, 114.8,
114.1, 113.7, 108.5, 51.8 ppm. HRMS (ESI): calcd. for C21H16N2O2
[M + H]+ 328.1212; found 328.1212.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra of all new compounds.
[9]
Acknowledgments
We thank the Defence Research & Development Organization
(DRDO), the Department of Science and Technology (DST), the
University Grants Commission (UGC), and the University of
Delhi (DU-DST PURSE) for financial support, and USIC for in-
strumentation facilities. R. R. J and T. A. are thankful to the DU-
DST for a PURSE grant and the DST for Fellowships.
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Received: July 12, 2011
Published Online: October 10, 2011
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