Regioselective syntheses of 1-,2-,3-and 4-aminoindolo-[2,3-b]quinoxalines

Article abstract of DOI:10.3987/COM-08-11444

In view of the contradictory results published in the literature concerning the structure of the indoloquinoxalines obtained by condensation of isatin with an unsymmetrical benzene-1,2-diamine, regioselective syntheses of the 1-, 2-, 3-, and 4-aminoindolo

Full text of DOI:10.3987/COM-08-11444

HETEROCYCLES, Vol. 75, No. 11, 2008
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HETEROCYCLES, Vol. 75, No. 11, 2008, pp. 2745 - 2759. © The Japan Institute of Heterocyclic Chemistry
Received, 16th May, 2008, Accepted, 3rd July, 2008, Published online, 7th July, 2008. COM-08-11444
REGIOSELECTIVE SYNTHESES OF 1-, 2-, 3- AND 4-AMINOINDOLO-
[2,3-b]QUINOXALINES
Aurélie Jaouen, Philippe Helissey, Stéphanie Desbène-Finck, and
Sylviane Giorgi-Renault*
Laboratory of Therapeutic Chemistry, UMR CNRS N° 8638, University Paris
Descartes, Faculty of Pharmaceutical and Biological Sciences, 4 avenue de
l'Observatoire, 75270 Paris Cedex 06, France; sylviane.giorgi-renault@univ-
paris5.fr
Abstract – In view of the contradictory results published in the literature
concerning the structure of the indoloquinoxalines obtained by condensation of
isatin with an unsymmetrical benzene-1,2-diamine, regioselective syntheses of the
1-, 2-, 3-, and 4-aminoindolo[2,3-b]quinoxalines have been developed. With the
four derivatives in hand, isomers obtained by direct cyclocondensations starting
from amino or nitro substituted benzene-1,2-diamines could be unambiguously
identified. The results of these studies show, on the one hand, that some previous
findings need revision and, on the other hand, that the 1-amino isomer could be
prepared in one step and in 58% yield.
INTRODUCTION
As part of a program directed at developing new antitumor agents which target DNA, the biological
activity of indolo[2,3-b]quinoxalines prompted us to design new derivatives bearing aminoalkylamino
chains in various positions. A previous work has described the N,N’-dialkylation of the indolo[2,3-b]-
quinoxaline nucleus. The three possible regioisomers have been selectively synthesized and the structures
of the N,N’-dimethylated salts have been unambiguously determined by NMR correlation sequences
(NOESY 1H-1H, HMQC 1H-13C, HMBC 1H-13C).1 In order to introduce chains on the D-ring, we need to
have in hand the corresponding amino heterocycles.
The most classical pathway for the synthesis of indolo[2,3-b]quinoxalines consists in the
cyclocondensation of an indole-2,3-dione (1) (isatin) with a benzene-1,2-diamine. When unsymmetrical
diamines are used (3- or 4-substituted diamines 5 or 2), the condensation may obviously lead to the

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HETEROCYCLES, Vol. 75, No. 11, 2008
production of structural isomers i.e. a mixture of the 1- and 4-substituted indoloquinoxalines 6–7 in the
first case and of the 2- and 3-isomers in the later one 3–4 (cf. Table 1). Some authors claimed that the
results can be rationalized according to the mechanism of the cyclocondensation: the more nucleophilic
amino group of the phenylenediamine reacts with the more electrophilic 3-carbonyl group of isatin and a
subsequent dehydratation between the second amino group and the lactamic carbonyl affords the
tetracycle.2-4 However, several contradictory examples have been published in the literature.
Syntheses starting from benzene-1,2-diamines 2 substituted in the 4-position by various substituents, have
4
6
7
been claimed to give only the 2-substituted indoloquinoxalines (3, R = NO2 , Cl5 , F6 , CF3 , CH3 ), only
the 3-substituted isomer (4, R = Cl8, COOH8), one isomer whose structure was not specified (R = COOH9,
2
11
12
NO2 , F10, CF3 ) or a mixture of both derivatives (R = OCH3 , CN13, OEt9). Drushlyak et al. claimed to
have obtained only the 3-nitroindoloquinoxaline (4a) in a three step pathway: condensation of the
4-nitrobenzene-1,2-diamine (2a) with the N-acetylisatin to give the 3-(2-acetylaminophenyl)-7-
nitroquinoxalin-2-one, deacetylation and subsequent cyclization in boiling acetic acid.4
Under the same manner, from the corresponding 3-substituted benzene-1,2-diamines 5, the preparation of
indoloquinoxalines bearing a substituent in the 1-position 6 and in the 4-position 7 has been published
14
13
(R = halogen12 , OCH3 , COOH15, COOCH3 ).
Structural assignments, usually only based on elemental analyses and, in two cases, on melting points4,9
are not convincing. Furthermore, on most cases, when a mixture of isomers was known to be obtained,
they were not separable. As an exception, the 1- and 4-methyl esters have been isolated after flash column
chromatography on silica gel but have not been unambiguously identified.13 Regardless, it was not
13
possible to assign structures from 1H or C NMR spectra to the indoloquinoxalines substituted either on
the 2- or 3- position or on the 1- or 4-position. More recently, by condensation of 2,3-diaminobenzoic
acid (5, R = COOH) with isatin (1), Deady et al.15 have obtained indolo[2,3-b]quinoxaline-1- and
4-carboxylic acids respectively in a 1:4 ratio using indirect chemical proof in the structural elucidation.
According to these authors, treatment of the mixture with H2O2 in acetic acid afforded only the N-oxide
of the 4-substituted isomer.
In contrast to the reaction with C-substituted diamines, it is well known that the reaction of isatin with a
N-alkylated benzene-1,2-diamine led exclusively to the corresponding N5-alkylated heterocycle, the
primary amine reacting initially with the keto function of isatin (Scheme 1).1 In light of these results,
regioselective syntheses of the 1- and 4-hydroxyindolo[2,3-b]quinoxalines have been described in 1970
by Kidani et al. respectively from the N1-methyl- and N2-methyl-3-methoxybenzene-1,2-diamines.14
Treatment of the 1- or 4-methoxy-5-methyl intermediates by boiling hydrobromic acid in acetic acid
resulted in simultaneous N- and O-demethylations. According to this pathway, Bergman et al. have
patented the preparation of several indoloquinoxalines substituted in the 2 or 3-positions by methyl,

HETEROCYCLES, Vol. 75, No. 11, 2008
2747
methoxy and carboxylic groups.16 Surprisingly contrary to the previous paper, methoxyindoloquinoxalines
have been obtained after hydrobromic acid-acetic acid treatment of the corresponding N5-methylated
analogues. However, such drastic experimental conditions of demethylation are not usable with unstable
groups such as amines.
N
C
N
A
O
R = H
B
N6
H
D
H2N
O +
N
H
HN
R
/
R = H
N
N
N5
R
Scheme 1 Classical syntheses of indolo[2,3-b]quinoxalines
In this paper, we report regioselective syntheses of the 1-, 2-, 3-, and 4-aminoindolo[2,3-b]quinoxalines
and we unambiguously determine the isomeric structures obtained by cyclocondensation of isatin with
substituted benzene-1,2-diamines.
RESULTS AND DISCUSSION
In view of the contradictory results published in the literature, we decided to study first the
cyclocondensation of isatin (1) with easily available amino- or nitro-benzene-1,2-diamines. By reaction of
the 4-nitro-1,2-diaminobenzene (2a) with isatin (1) in refluxing acetic acid, Drushlyak et al.4 claimed to
have isolated 72% of the 2-nitroisomer 3a (mp 338-340 °C). Previously, in the same conditions, Buu Hoï
et al.2 has observed that one of the isomers, which structure assignment was not undertaken, is
predominantly produced and seems to be isolated in the pure state after recrystallization from pyridine
(mp 340 °C, 80% yield).
In our hands, this reaction afforded, in 70% yield, a mixture of the 2- and 3-nitro isomers 3a-4a in a 1:2
1
ratio determined by H NMR (Table 1). The melting point of the crude mixture (337 °C) coincide with
the data published for a pure 2-nitro derivative.2,4 The two isomers could not be separated by
chromatography. Catalytic hydrogenation led also to a 1:2 inseparable mixture of the corresponding
amines 3b–4b. Similarly, an isomeric mixture of acetylamino derivatives 3c–4c (1:1 ratio) was obtained
starting from the 4-acetylaminobenzene-1,2-diamine17 (2c). Finally, reaction of the unstable benzene-
1,2,4-triamine18 (2b) gave a mixture of unidentified products.
In contrast, under similar conditions, the benzene-1,2,3-triamine19 (5b) led to a 97:3 mixture of the 1- and
4- isomers 6b–7b (60%) and the major isomer could be isolated in a pure state by washing the mixture

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HETEROCYCLES, Vol. 75, No. 11, 2008
with acetone. NMR spectra did not allow unambiguous assignment of the isomeric structure.
Table 1 Cyclocondensation of isatin (1) with substituted benzene-1,2-diamines 2 and 5
H2N
H2N
R
N
N
2
R
N
N
1
+
+
AcOH or
AcOH/EtOH
R
3
N
H
N
H
2
4
3
6
R
R
1
H2N
H2N
N
N
N
N
1
AcOH or
AcOH/EtOH
N
H
N
H
4
R
5
7
a
R = NO2
b
R = NH2
c
R = NHAc
Amine
Ratio
Yield (%)
70
3a - 4a 1:2
2a
b
3b - 4b 1:2a
c
2b
2c
5b
58
3c - 4c 1:1
60
58
6b - 7b 97:3a
d
6b
a Determined by comparison with the 1H NMR spectra of pure isomers. b Catalytic reduction. c Complex
mixture of unidentified products. d Washings with acetone.
In this light, we found it convenient to envisage regioselective syntheses of the four aminoindolo[2,3-b]-
quinoxalines 3b, 4b, 6b, 7b via the N5-benzyl heterocycles which can be deprotected in mild conditions
by catalytic hydrogenation.
Synthesis of the 5-benzyl-4-aminoindoloquinoxaline (11) could be envisaged by condensation of the
symmetrical N2-benzylbenzene-1,2,3-triamine (10) with isatin (1) (Scheme 2). Therefore, the
dinitrobenzylaniline 9 was prepared by nucleophilic aromatic substitution of the commercially available
2,6-dinitrochlorobenzene (8). Unfortunately, it was not possible to reduce the nitro groups of 9 without
concomitant N-debenzylation into 5b. On the contrary to the other syntheses (Scheme 4), catalytic
hydrogenation over Raney nickel afforded triamine 5b as a major product with a small amount of the
expected compound. Finally, compound 10 was obtained in 42% yield using a mixture of hydrazine
hydrate and Raney nickel as a reducing agent. Condensation of 10 with isatin (1) and subsequent catalytic
debenzylation (H2/Pd-C) afforded the 4-aminoindolo[2,3-b]quinoxaline (7b).

HETEROCYCLES, Vol. 75, No. 11, 2008
2749
H2N
O2N
O2N
Cl
i
ii
+
5b
87%
BnHN
20%
BnHN
NH2
NO2
NO2
9
10 42%
8
Bn : benzyl
N
N
iii
40%
iv
40%
10
N
N
H
N
N
Bn NH2
11
NH2
7b
Scheme 2 Reagents and conditions: i, BnNH2, AcONa, EtOH, reflux; ii, H2N-NH2.H2O, Raney Ni,
EtOH-ClCH2CH2Cl, 50 °C; iii, 1, EtOH-AcOH, reflux; iv, H2, Pd-C, EtOH, rt.
For the synthesis of the 1-amino isomer 6b, it was not possible to use the unsymmetrical N1-
benzylbenzene-1,2,3-triamine. We had envisioned a selective N-alkylation of the nitro-diamine 5a
(Scheme 3). Using benzyl bromide, 5a was regioselectively benzylated on the less hindered amino
function to give 12 (structure confirmed by NOESY correlations between CH2 of the benzyl group and 6-
H) but, whatever the conditions, the N,N-dibenzyl derivative 13 was also obtained. Total conversion of
NO2
NO2
H2N
H2N
i
5a
+
BnHN
Bn2N
13 30%
12 60%
ii
15%
NO2
NH2
N
N
iii
50%
N
N
Bn
14
N
N
H
6b
Scheme 3 Reagents and conditions: i, BnBr, K2CO3, DMF, rt; ii, 1, AcOH, AcONa, reflux; iii, H2,
Raney Ni, EtOH then H2, Pd-C.
5a was accomplished only when using 1.5 equivalent of the alkylating agent; under such conditions,
compound 12 could be isolated in 60% yield after flash chromatography. Reaction with isatin (1) afforded
a mixture of several products. In the best case, the expected benzylindoloquinoxaline 14 was obtained in
15% yield. The first attempt for the transformation of 14 into 6b by hydrogenation using Pd-C as a
catalyst was unsuccessful. Finally, compound 6b was obtained by two successive catalytic
hydrogenations without isolation of the intermediate. This pathway furnished the 1-
aminoindoloquinoxaline (6b) in three steps and in only 4.5% yield but without any doubt on the position

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HETEROCYCLES, Vol. 75, No. 11, 2008
of the amino group. This unambiguous regioselective synthesis allowed us to identify as the 1-amino
isomer 6b, the major product obtained in 58% yield by reaction of the triamine 5b with isatin (1) (Table
1).
For the syntheses of the 2-amino and 3-aminoindolo[2,3-b]quinoxalines (3b) and (4b) (Scheme 4), the
intermediate 2-amino-N-benzylanilines substituted either in the 4- or in the 5-position could be obtained
from the corresponding fluoronitroanilines. In order to introduce the benzylamino functions via a SNar, the
amino groups have to be protected first.
O2N
F
NHAc
O2N
NHAc
i
89%
N
N
R1
R2
BnHN
N
R1
R2
ii
iii
15
16
17
18
N
N
N
Bn
H
O2N
F
O2N
3c R1 = NHAc; R2 = H 76%
i
iv
iv
19 R1 = NHAc; R2 = H 74%
20 R1 = H; R2 = NHAc 83%
3b R1 = NH2; R2 = H 98%
86%
NHAc
BnHN
NHAc
4c R1 = H; R2 = NHAc 85%
4b R1 = H; R2 = NH2 85%
Scheme 4 Reagents and conditions: i, BnNH2, AcONa, EtOH, reflux; ii, H2, Raney Ni, EtOH then 1,
AcOH, reflux; iii, H2, Pd-C, EtOH; iv, HCl, EtOH, reflux.
Consequently, compounds 17 and 18 have been prepared by reaction of benzylamine on the fluoro
derivatives 1520 and 1621. The latter was synthesized by nitration of 3-fluoroacetanilide according to
Lynch21 but obtained only in 40% yield besides 20% of the 6-nitro isomer (lit.,21 ratio 6/4: 0.04, 52%
yield in pure 4-nitro). On the contrary to the previous series, the nitro groups of derivatives 17 and 18 can
be reduced by catalytic hydrogenation using Raney nickel as a catalyst without debenzylation. The
resulting unstable diamines were immediately condensed with isatin (1) to give the 5-benzylindolo[2,3-
b]quinoxalines 19 and 20 which structures were confirmed by NOESY correlations between CH2 and 4-H.
After hydrogenolysis (Pd-C) to give compounds 3c and 4c, the removal of the acetyl protective groups
were achieved by acid hydrolysis. According to these pathways, the 2-amino and the 3-aminoisomers 3b
and 4b were obtained from the fluoronitroacetanilide 15 and 16 in 4 steps with yields of 49% and 52%,
respectively.
CONCLUSION
In view of the contradictory results published in the literature concerning the structure of the
indoloquinoxalines obtained by condensation of isatin with an unsymmetrical benzene-1,2-diamine,
regioselective syntheses of the 1-, 2-, 3-, and 4-aminoindolo[2,3-b]quinoxalines have been developed.

HETEROCYCLES, Vol. 75, No. 11, 2008
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With the four isomers in hand, it is now possible to identify the products obtained by direct
cyclocondensations of substituted benzene-1,2-diamines with isatin. It is noteworthy that the major
derivative obtained starting from benzene-1,2-3-triamine is the 1-aminoisomer which could then be
prepared in one step and in 58% yield.
These results show that the structure of the obtained indoloquinoxalines cannot be rationalized in terms of
difference in nucleophilicity between the two functions of the benzene-1,2-diamine used as a starting
material. The more nucleophilic 2-amino function of 1,2,3-triaminobenzene (5b) reacted with the keto
function of isatin and furnished mixed yield 60% (ratio 6b:7b = 97:3). In contrast, the 3-nitro isomer 4a
was obtained as a major product using 4-nitrodiamine 2a by reaction of the amine para to the
electronwithdrawing nitro group and the reaction of the 4-acetylaminodiamine 2c afforded a 1:1 mixture
of both 2- and 3-isomers 3c–4c, indicating that previously reported structures need revisions.
The new synthetic pathways could be expanded to the preparation of different indolo[2,3-b]quinoxalines,
either mono or polysubstituted by aminoalkyl chains in various positions.
EXPERIMENTAL
Thin-layer chromatography was carried out on Merck GF 254 silica gel plates. Flash chromatography was
performed on Merck silica gel 70 (30-70 µm) or on Merck aluminum oxide 90 active, neutral. Melting
points were determined on a Maquenne apparatus and are uncorrected. Element analyses were performed
1
13
at the C.N.R.S. Analysis Laboratory, Gif-sur-Yvette. H and C NMR spectra were recorded on Bruker
AC 300 and COSY, HSQC, HMBC, NOESY spectra with AC 400 spectrometers. Multiplicities were
listed as s (singlet), d (doublet), t (triplet), and m (multiplet). Chemical shift values are given in ppm (δ),
using residual protic solvent as internal standard. IR spectra were obtained on Nicolet 510FT-IR.
Synthesis of the 4-aminoindolo[2,3-b]quinoxaline (7b)
N-Benzyl-2,6-dinitroaniline (9). A mixture of 2,6-dinitrochlorobenzene (8) (0.81 g, 4.00 mmol),
benzylamine (0.7 mL, 6.00 mmol), and anhydrous sodium acetate (0.66 g, 8.00 mmol) in EtOH (100 mL)
was refluxed for 3 h. After the solvent had been removed by evaporation, the solid residue was dissolved
in CH2Cl2 and washed with water. The organic layer was dried over Na2SO4 and evaporated. The oily
residue was triturated with MeOH (10 mL) and the resulting precipitate was filtered off to give a pure
yellow powder (0.95 g, 87%), which was used in the next step without further purification. An analytical
sample was prepared by flash chromatography (silica gel, CH2Cl2-MeOH, 100:0 to 95:5); mp 98 °C. IR
(KBr): ν = 3332, 1620, 1572, 1521, 1498, 1449, 1349, 1277, 1105, 916, 906, 747, 716, 698 cm-1. 1H NMR
(300 MHz, CDCl3): δ = 4.20 (s, 2H, CH2), 6.83 (t, J = 8 Hz, 1H, 4-H), 7.29 (m, 2H, 2 × ArH), 7.39 (m,
13
3H, 3 × ArH), 8.23 (d, J = 8 Hz, 2H, 3-H and 5-H), 8.63 (s, 1H, NH). C NMR (75 MHz, CDCl3): δ =

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HETEROCYCLES, Vol. 75, No. 11, 2008
50.9 (CH2), 114.6 (C-4), 127.9 (2 × CH), 128.5 (CH), 129.2 (2 × CH), 132.4 (C-3 and C-5), 136.5 (2 × C-
q), 138.1 (C-q), 139.7 (C-q). Anal. Calcd for C13H11N3O4.1/4H2O: C, 56.22; H, 4.17; N, 15.13. Found: C,
56.18; H, 3.92; N, 15.09.
N2-Benzylbenzene-1,2,3-triamine 10 and benzene-1,2,3-triamine (5b). Hydrazine hydrate (0.73 mL,
15.00 mmol) was added dropwise over a 30 min period to a suspension of N-benzyl-2,6-dinitroaniline (9)
(0.82 g, 3.00 mmol) and Raney nickel (0.40 g) in a 1:1 EtOH/1,2-dichloroethane mixture (40 mL). After
heating for 15 min at 50 °C, the catalyst was filtered off, and the solvents were eliminated in vacuo. The
resulting brown oil was purified by flash chromatography (silica gel, CH2Cl2) to give 10 (0.27 g, 42%)
and then 5b (0.07 g, 20%) as brown oils. The unstable amine 10 was used immediately in the next step.
10: 1H NMR (300 MHz, CDCl3): δ = 3.32 (br s, 4H, 2 × NH2), 4.16 (s, 2H, CH2), 6.20 (d, J = 8 Hz, 2H,
4-H and 6-H), 6.80 (t, J = 8, 1H, 5-H), 7.35 (m, 6H, 5 × ArH and NH). 5b19: 1H NMR (300 MHz, CDCl3):
δ = 3.24 (br s, 6H, 3 × NH2), 6.34 (d, J = 8 Hz, 2H, 4-H and 6-H), 6.63 (t, J = 8 Hz, 1H, 5-H).
4-Amino-5-benzyl-5H-indolo[2,3-b]quinoxaline (11). A solution of isatin (1) (0.10 g, 0.68 mmol) in
AcOH (10 mL) was added to a solution of triamine 10 (0.19 g, 0.88 mmol) in EtOH (10 mL) and the
mixture was refluxed for 30 min. The solvents were eliminated under reduced pressure and MeOH was
added to give a precipitate which was filtered off, washed with water and purified by flash
chromatography (aluminum oxide, CH2Cl2-MeOH, 98:2) to give a red solid (0.09 g, 40%); mp 194 °C. IR
(KBr): ν = 3429, 3277, 1627, 1577, 1565, 1531, 1440, 1419, 1365, 1307, 1265, 1217, 1195, 1116, 1012,
952, 870, 832, 758, 738, 723, 690 cm-1 1H NMR (300 MHz, DMSO-d6): δ = 5.16 (s, 2H, NH2), 6.42 (s,
.
2H, CH2), 7.13 (d, J = 7 Hz, 2H, 2 × ArH), 7.22 (m, 5H, 1-H or 3-H, 9-H and 3 × ArH), 7.28 (t, J = 9 Hz,
1H, 2-H), 7.52 (d, J = 8 Hz, 1H, 7-H), 7.61 (t, J = 8 Hz, 1H, 8-H), 7.65 (d, J = 9 Hz, 1H, 1-H or 3-H),
13
8.14 (d, J = 8 Hz, 1H, 10-H). C NMR (75 MHz; DMSO-d6): δ = 51.2 (CH2), 118.6 (C-7), 120.1 (C-q),
120.3 (C-1 or C-3), 121.3 (C-9), 121.5 (C-1 or C-3), 122.8 (C-10), 123.4 (C-q), 124.7 (C-2), 126.6 (2 ×
CH), 127.8 (CH), 129.2 (2 × CH), 133.0 (C-8), 137.3 (C-q), 137.9 (C-q), 138.6 (C-q), 148.8 (C-q), 152.7
(C-q), 159.1 (C-q). Anal. Calcd for C21H16N4: C, 77.76; H, 4.97; N, 17.27. Found: C, 78.02; H, 5.23; N,
17.25.
4-Amino-6H-indolo[2,3-b]quinoxaline (7b). A suspension of N-benzylated derivative 11 (0.10 g, 0.3
mmol) in EtOH (20 mL) was hydrogenated for 1 h at rt under a 5 bar pressure in the presence of 10%
palladium on charcoal (0.05 g). After filtration of the catalyst, the solution was concentrated under
reduced pressure. The resulting precipitate was filtered off and purified by flash chromatography
(aluminum oxide, CH2Cl2) to give 7b as a yellow solid (0.03 g, 40%); mp 312 °C. IR (KBr): ν = 3413,
3284, 1636, 1602, 1515, 1480, 1460, 1397, 1347, 1322, 1285, 1242, 1204, 1173, 1102, 1084, 887, 853,

HETEROCYCLES, Vol. 75, No. 11, 2008
2753
820, 788, 749, 732 cm-1. 1H NMR (300 MHz; DMSO-d6): δ = 5.84 (s, 2H, NH2), 6.96 (t, J = 6 Hz, 1H, 2-
H), 7.34 (t, J = 8 Hz, 1H, 9-H), 7.42 (m, 2H, 1-H and 3-H), 7.56 (d, J = 8 Hz, 1H, 7-H), 7.68 (t, J = 8 Hz,
1H, 8-H), 8.32 (d, J = 8 Hz, 1H, 10-H), 11.93 (s, 1H, NH). 13C NMR (75 MHz; DMSO-d6): δ = 108.7 (C-
2), 112.4 (C-7), 115.9 (C-1 or C-3), 119.5 (C-q), 120.9 (C-9), 122.5 (C-10), 127.1 (C-1 or C-3), 130.0 (C-
q), 131.3 (C-8), 139.7 (C-q), 139.9 (C-q), 144.2 (C-q), 144.3 (C-q), 144.7 (C-q). Anal. Calcd for
C14H10N4.1/2H2O: C, 69.12; H, 4.56; N, 23.03. Found: C, 69.15; H, 4.39; N, 23.31.
Synthesis of the 1-aminoindolo[2,3-b]quinoxaline (6b)
N1-Benzyl-3-nitrobenzene-1,2-diamine (12) and N1,N1-dibenzyl-3-nitrobenzene-1,2-diamine (13). To
a suspension of diamine 5a (0.61 g, 4.00 mmol) and dried potassium carbonate (0.61 g, 4.40 mmol) in
DMF (20 mL) was added benzyl bromide (0.52 mL, 4.40 mmol). The mixture was stirred at rt for 72 h
and then a second amount of benzyl bromide (0.19 mL, 1.60 mmol) was added. Two days later, after
elimination of the solvent, the residue was extracted with CH2Cl2. The organic layers were washed with
water, dried over Na2SO4 and evaporated. The oily residue was purified by flash chromatography (silica
gel, CH2Cl2-cyclohexane, 50:50 to 80:20) to give compound 13 as a yellow oil (0.40 g, 30%) and then the
expected derivative 12 as a purple solid (0.58 g, 60%). 13: IR: ν = 3490, 3367, 1617, 1575, 1517, 1497,
1453, 1358, 1322, 1265, 1182, 1078, 1028, 876, 738, 699 cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.06 (s,
4H, 2 × CH2), 6.55 (dd, J = 7 and 8 Hz, 1H, 5-H), 6.84 (br s, 1H, NH2), 7.04 (dd, J = 1 and 7 Hz, 1H, 6-
13
H), 7.22 (m, 4H, 4 × ArH), 7.29 (m, 6H, 6 × ArH), 7.91 (dd, J = 1 and 8 Hz, 1H, 4-H). C NMR (75
MHz; CDCl3): δ = 56.8 (2 × CH2), 114.8 (C-5), 122.2 (C-4), 127.6 (2 × CH), 128.2 (4 × CH), 128.8 (4 ×
CH), 129.7 (C-6), 132.4 (C-q), 136.9 (2 × C-q), 139.0 (C-q), 142.1 (C-q). Anal. Calcd for C20H19N3O2: C,
72.05; H, 5.74; N, 12.60. Found: C, 72.16; H, 5.91; N, 12.28. 12: mp 95 °C. IR (KBr): ν = 3459, 3377,
1
3353, 1624, 1593, 1523, 1465, 1426, 1381, 1353, 1331, 1269, 1254, 1223, 754, 733, 721, 701 cm-1. H
NMR (300 MHz, CDCl3): δ = 4.37 (s, 2H, CH2), 6.00 (s, 2H, NH2), 6.70 (dd, J = 7 and 9 Hz, 1H, 5-H),
6.92 (dd, J = 1 and 7 Hz, 1H, 6-H), 7.37 (m, 5H, 5 × ArH), 7.74 (dd, J =1 and 9 Hz, 1H, 4-H), 8.63 (s, 1H,
13
NH). C NMR (75 MHz; CDCl3): δ = 49.8 (CH2), 116.9 (C-5), 118.1 (C-4), 119.6 (C-6), 128.1 (CH),
128.3 (2 × CH), 128.8 (2 × CH and C-q), 133.5 (C-q), 136.8 (2 × C-q). Anal. Calcd for C13H13N3O2: C,
64.19; H, 5.39; N, 17.27. Found: C, 64.29; H, 5.11; N, 17.19.
5-Benzyl-1-nitro-5H-indolo[2,3-b]quinoxaline (14). A mixture of isatin (1) (0.27 g, 1.85 mmol),
diamine 12 (0.58 g, 2.40 mmol), and anhydrous sodium acetate (0.39 g, 4.81 mmol) in AcOH (50 mL)
was refluxed for 24 h. After evaporation of the solvent under reduced pressure, addition of CH2Cl2, the
organic layer was washed with water, dried over Na2SO4 and evaporated. The oily residue was purified
by flash chromatography (silica gel, CH2Cl2-MeOH, 100:0 to 95:5) to give indoloquinoxaline 14 as a red

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HETEROCYCLES, Vol. 75, No. 11, 2008
solid (0.10 g, 15%); mp 241 °C. IR (KBr): ν = 1580, 1568, 1528, 1482, 1438, 1375, 1283, 1199, 1184,
1
1104, 869, 800, 746, 701 cm-1. H NMR (300 MHz; DMSO-d6): δ = 6.15 (s, 2H, CH2), 7.32 (m, 6H, 5 ×
ArH and 9-H), 7.64 (d, J = 8 Hz, 1H, 7-H), 7.74 (t, J = 8 Hz, 1H, 8-H), 7.89 (t, J = 9 Hz, 1H, 3-H), 8.03
(dd, J = 2 and 9 Hz, 1H, 2-H), 8.13 (dd, J = 2 and 9 Hz, 1H, 4-H), 8.20 (d, J = 8 Hz, 1H, 10-H). 13C NMR
(75 MHz; DMSO-d6): δ = 49.2 (CH2), 117.2 (C-4), 119.1 (C-2), 119.3 (C-7), 122.2 (C-9), 122.9 (C-q),
123.8 (C-10), 126.1 (C-q), 127.4 (2 × CH), 128.2 (CH), 129.3 (2 × CH), 130.0 (C-3), 130.2 (C-q), 134.5
(C-8), 135.5 (C-q), 147.0 (C-q), 149.3 (C-q), 155.4 (C-q), 159.8 (C-q). Anal. Calcd for
C21H14N4O2.1/2H2O: C, 69.41; H, 4.16; N, 15.42. Found: C, 69.41; H, 4.17; N, 15.11.
1-Amino-6H-indolo[2,3-b]quinoxaline (6b). A suspension of 14 (0.06 g, 0.17 mmol) in EtOH (10 mL)
was first hydrogenated for 3 h at rt under a 5 bar pressure in the presence of Raney nickel (0.05 g). After
filtration of the catalyst, 10% palladium on charcoal (0.05 g) was added and a second hydrogenation was
performed for 16 h at rt under a 5 bar pressure. The crude product, obtained after filtration of the catalyst
and elimination of the solvent, was purified by flash chromatography (aluminum oxide, CH2Cl2) to give
6b as a yellow solid (0.02 g, 50%); mp 330 °C. IR (KBr): ν = 3415, 3320, 1612, 1524, 1491, 1480, 1459,
1
1407, 1339, 1328, 1245, 1211, 1196, 1101, 1077, 1028, 1005, 877, 814, 750, 727 cm-1. H NMR (300
MHz; DMSO-d6): δ = 6.16 (s, 2H, NH2), 6.82 (d, J = 9 Hz, 1H, 2-H or 4-H), 7.17 (d, J = 9 Hz, 1H, 2-H or
4-H), 7.35 (t, J = 8 Hz, 1H, 9-H), 7.47 (t, J = 9 Hz, 1H, 3-H), 7.55 (d, J = 8 Hz, 1H, 7-H), 7.66 (t, J = 8
13
Hz, 1H, 8-H), 8.31 (d, J = 8 Hz, 1H, 10-H), 11.87 (s, 1H, NH). C NMR (75 MHz; [D6]DMSO): δ =
106.1 (C-2 or C-4), 112.3 (C-7), 113.8 (C-2 or C-4), 119.8 (C-q), 120.9 (C-9), 122.1 (C-10), 128.9 (C-q),
130.4 (C-3), 130.9 (C-8), 136.7 (C-q), 141.5 (C-q), 143.9 (C-q), 146.4 (C-q), 146.6 (C-q). Anal. Calcd for
C14H10N4.H2O: C, 66.65; H, 4.79; N, 22.21. Found: C, 66.34; H, 4.49; N, 21.91.
Synthesis of the 2 and 3-aminoindolo[2,3-b]quinoxalines (3b) and (4b)
N-(4-Benzylamino-3-nitrophenyl)acetamide (17). Compound 17 was prepared by using the same
procedure as described above for 9 starting from the fluorobenzene 1520 (11.26 g, 56.87 mmol) in EtOH
(100 mL); reflux: 22 h. Crude 17 was isolated as a pure red solid (14.44 g, 89%) that was used without
further purification for the next step. An analytical sample was prepared by flash chromatography (silica
gel, CH2Cl2-MeOH, 100:0 to 95:5); mp 178 °C. IR (KBr): ν = 3353, 1666, 1639, 1594, 1520, 1491, 1455,
1402, 1354, 1312, 1263, 1222, 1148, 1060, 985, 910, 877, 808, 763, 750, 701 cm-1. 1H NMR (300 MHz;
DMSO-d6): δ = 2.49 (s, 3H, Me), 4.60 (d, J = 6 Hz, 2H, CH2), 6.90 (d, J = 9 Hz, 1H, 5-H), 7.24 (m, 1H, 1
× ArH), 7.36 (m, 4H, 4 × ArH), 7.53 (dd, J = 2 and 9 Hz, 1H, 6-H), 8.47 (d, J = 2 Hz, 1H, 2-H), 8,56 (t, J
13
= 6 Hz, 1H, NHCH2), 9.92 (s, 1H, NHCO). C NMR (75 MHz; DMSO-d6): δ = 24.2 (Me), 46.2 (CH2),
115.6 (C-5), 115.7 (C-6), 127.4 (2 × CH), 127.5 (CH), 128.5 (C-q), 129.0 (2 × CH), 129.7 (C-2), 130.7

HETEROCYCLES, Vol. 75, No. 11, 2008
2755
(C-q), 139.1 (C-q), 142.1 (C-q), 168.6 (CO). Anal. Calcd for C15H15N3O3: C, 63.15; H, 5.30; N, 14.73.
Found: C, 63.48; H, 5.50; N, 14.82.
N-(3-Benzylamino-4-nitrophenyl)acetamide (18). Compound 18 was prepared by using the same
procedure as described above for 9 starting from the fluorobenzene 1621 (3.76 g, 19 mmol) in EtOH (50
mL), reflux: 72 h. Crude 18 was obtained as a pure red solid (4.62 g, 86%) that was used without further
purification for the next step. An analytical sample was prepared by flash chromatography (silica gel,
CH2Cl2-MeOH, 100:0 to 95:5); mp 112 °C. IR (KBr): ν = 3392, 1680, 1634, 1555, 1482, 1455, 1418,
1328, 1289, 1245, 1209, 1159, 1054, 859, 843, 818, 758, 736, 696 cm-1. 1H NMR (300 MHz; CDCl3): δ =
2.19 (s, 3H, Me), 4.55 (d, J = 6 Hz, 2H, CH2), 6.53 (dd, J = 2 and 9 Hz, 1H, 6-H), 7.34 (m, 5H, 5 × ArH),
13
7.50 (d, J = 2 Hz, 1H, 2-H), 8.17 (d, J = 9 Hz, 1H, 5-H), 8.65 (t, J = 6 Hz, 1H, NHCH2). C NMR (75
MHz; CDCl3): δ = 25.0 (Me), 47.2 (CH2), 102.2 (C-2), 107.4 (C-6), 127.4 (2 × CH), 127.7 (CH), 128.1
(C-q), 128.4 (C-5), 128.9 (2 × CH), 137.1 (C-q), 144.8 (C-q), 146.8 (C-q), 168.7 (CO). Anal. Calcd for
C15H15N3O3.1/2H2O: C, 61.22; H, 5.48; N, 14.28. Found: C, 61.15; H, 5.15; N, 14.04.
2-Acetylamino-5-benzyl-5H-indolo[2,3-b]quinoxaline (19). A suspension of nitro derivative 17 (4.79 g,
16.80 mmol) in EtOH (150 mL) was hydrogenated for 12 h at rt under a 3 bar pressure in the presence of
Raney nickel (1.00 g). After filtration of the catalyst, isatin (1) (1.90 g, 12.90 mmol) in AcOH (80 mL)
was added to the resulting solution and the mixture was refluxed for 1.5 h. The solvents were eliminated
under reduced pressure, the residue was triturated with MeOH. The resulting precipitate was filtered off,
washed with water and purified by flash chromatography (silica gel, CH2Cl2-MeOH, 99:1 to 90:10) to
give a red solid (3.49 g, 74%); mp 278 °C. IR (KBr): ν = 3294, 1681, 1578, 1556, 1493, 1470, 1428, 1371,
1
1341, 1293, 1191, 1139, 1101, 1063, 1027, 882, 811, 763, 748, 702 cm-1. H NMR (400 MHz; DMSO-
d6): δ = 2.09 (s, 3H, Me), 6.07 (s, 2H, CH2), 7.27 (m, 6H, 9-H and 5 × ArH), 7.55 (d, J = 8 Hz, 1H, 7-H),
7.63 (t, J = 8 Hz, 1H, 8-H), 7.81 (dd, J = 2 and 9 Hz, 1H, 3-H), 7.86 (d, J = 9 Hz, 1H, 4-H), 8.20 (d, J = 8
Hz, 1H, 10-H), 8.62 (d, J = 2 Hz, 1H, 1-H), 10.28 (s, 1H, NH). 13C NMR (75 MHz; DMSO-d6): δ = 25.1
(Me), 49.2 (CH2), 116.6 (C-3 or C-4), 119.3 (C-7), 119.8 (C-1), 121.8 (C-9), 123.4 (C-3 or C-4), 123.6
(C-10), 125.8 (C-q), 128.1 (2 × CH), 128.7 (CH), 129.8 (2 × CH), 133.8 (C-8), 135.7 (C-q), 136.4 (C-q),
136.5 (2 x C-q), 147.3 (C-q), 154.3 (C-q), 160.0 (C-q), 169.6 (CO). Anal. Calcd for C23H18N4O.2H2O: C,
68.64; H, 5.51; N, 13.92. Found: C, 68.31; H, 5.16; N, 13.90.
3-Acetylamino-5-benzyl-5H-indolo[2,3-b]quinoxaline (20). A suspension of nitro derivative 18 (4.56 g,
16.00 mmol) in EtOH (400 mL) was hydrogenated for 18 h at rt under a 3 bar pressure in the presence of
Raney nickel (1.00 g). After filtration of the catalyst, isatin (1) (1.81 g, 12.3 mmol) in AcOH (150 mL)
was added to the resulting solution and the mixture was refluxed for 1 h. The solvents were eliminated

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HETEROCYCLES, Vol. 75, No. 11, 2008
under reduced pressure, the residue was triturated with MeOH. The resulting precipitate was filtered off,
washed with water and purified by flash chromatography (silica gel, CH2Cl2-MeOH, 99:1 to 90:10) to
give a red solid (3.76 g, 83%); mp 289 °C. IR (KBr): ν = 3254, 1691, 1584, 1497, 1432, 1370, 1259, 1201,
1
1149, 1101, 1073, 821, 786, 765, 746, 697 cm-1. H NMR (400 MHz; DMSO-d6): δ = 2.11 (s, 3H, Me),
5.98 (s, 2H, CH2), 7.27 (m, 4H, 9-H and 3 × ArH), 7.37 (m, 2H, 2 × ArH), 7.60 (m, 2H, 7-H and 8-H),
7.65 (dd, J = 2 and 8 Hz, 1H, 2-H), 8.19 (m, 2H, 10-H and 1-H), 8.44 (d, J = 2 Hz, 1H, 4-H), 10.50 (s, 1H,
NH). 13C NMR (75 MHz; DMSO-d6): δ = 24.7 (Me), 49.0 (CH2), 103.7 (C-4), 116.0 (C-2), 118.8 (C-7 or
C-8), 121.4 (C-9), 122.5 (C-1 or C-10), 123.6 (C-q), 127.7 (2 × CH), 128.2 (CH), 129.2 (2 × CH), 130.3
(C-q), 131.2 (C-q), 131.5 (C-1 or C-10), 132.5 (C-7 or C-8), 135.5 (C-q), 141.7 (C-q), 147.1 (C-q), 151.1
(C-q), 158.4 (C-q), 169.7 (CO). Anal. Calcd for C23H18N4O.5/4H2O: C, 71.03; H, 5.31; N, 14.40. Found:
C, 71.26; H, 5.06; N, 14.51.
2-Acetylamino-6H-indolo[2,3-b]quinoxaline (3c). Compound 19 (12.40 g, 33.88 mmol) in EtOH (500
mL) was debenzylated according to the same procedure as described for 7b using 10% palladium on
charcoal (1.00g), time reaction: 12 h. After work up, 3c was purified by flash chromatography (silica gel,
CH2Cl2-MeOH, 99:1 to 70:30 and then CH2Cl2-MeOH -Et3N 69:30:1) to give a yellow solid (7.09 g,
76%); mp 389 °C. IR (KBr): ν = 3271, 1663, 1621, 1543, 1492, 1464, 1406, 1339, 1266, 1196, 1128,
1108, 1031, 1005, 884, 857, 828, 754 cm-1. 1H NMR (300 MHz; DMSO-d6): δ = 2.14 (s, 3H, Me), 7.33 (t,
J = 8 Hz, 1H, 9-H), 7.54 (d, J = 8 Hz, 1H, 7-H), 7.67 (t, J = 8 Hz, 1H, 8-H), 7.85 (dd, J = 2 and 9 Hz, 1H,
3-H), 7.98 (d, J = 9 Hz, 1H, 4-H), 8.32 (d, J = 8 Hz, 1H, 10-H), 8.64 (d, J = 2 Hz, 1H, 1-H), 10.33 (s, 1H,
13
NHCO), 11.92 (s, 1H, NH). C NMR (75 MHz; DMSO-d6): δ = 24.6 (CH3), 112.4 (C-7), 116.4 (C-1),
119.3 (C-q), 121.0 (C-9), 122.7 (C-10), 122.9 (C-3), 128.0 (C-4), 131.6 (C-8), 137.2 (C-q), 137.6 (C-q),
139.5 (C-q), 140.2 (C-q), 144.3 (C-q), 145.7 (C-q), 169.2 (CO). Anal. Calcd for C16H12N4O: C, 69.55; H,
4.38; N, 20.28. Found: C, 69.64; H, 4.39; N, 19.93.
3-Acetylamino-6H-indolo[2,3-b]quinoxaline (4c). Compound 20 (3.77 g, 10.30 mmol) in EtOH (150
mL) was debenzylated using to the same procedure as described for 7b using 10% palladium on charcoal
(1.00g), time reaction: 18 h. After work up, 4c was purified by flash chromatography (silica gel, CH2Cl2-
MeOH, 99:1 to 70:30 and then CH2Cl2-MeOH -Et3N 69:30:1) to give a yellow solid (2.42 g, 85%); mp
362 °C. IR (KBr): ν = 3491, 3146, 1679, 1621, 1607, 1588, 1548, 1496, 1461, 1401, 1369, 1342, 1274,
1205, 1146, 1111, 1035, 1015, 873, 848, 833, 799, 757 cm-1. 1H NMR (300 MHz; DMSO-d6): δ = 2.16 (s,
3H, Me), 7.34 (t, J = 8 Hz, 1H, 9-H), 7.55 (d, J = 8 Hz, 1H, 7-H), 7.67 (t, J = 8 Hz, 1H, 8-H), 7.78 (dd, J
= 2 and 9 Hz, 1H, 2-H), 8.15 (d, J = 9 Hz, 1H, 1-H), 8.29 (d, J = 8 Hz, 1H, 10-H), 8.48 (s, 1H, 4-H),
13
10.39 (s, 1H, NHCO), 11,96 (s, 1H, NH). C NMR (75 MHz; DMSO-d6): δ = 24.7 (Me), 112.3 (C-7),
114.6 (C-4), 119.7 (C-q), 120.0 (C-2), 121.1 (C-9), 122.3 (C-10), 129.7 (C-1), 131.2 (C-8), 135.8 (C-q),

HETEROCYCLES, Vol. 75, No. 11, 2008
2757
138.7 (C-q), 140.0 (C-q), 141.4 (C-q), 143.8 (C-q), 146.6 (C-q), 169.4 (CO). Anal. Calcd for
C16H12N4O.5/4H2O: C, 64.31; H, 4.89; N, 18.75. Found: C, 64.37; H, 4.54; N, 18.43.
General procedure for the preparation of the 2- and 3-amino-6H-indolo[2,3-b]quinoxalines (3b) and
(4b)
A suspension of acetamide derivative 3c or 4c (0.28 g, 1.00 mmol) in EtOH (30 mL) and a 0.5 M
aqueous solution of HCl (20 mL) was refluxed for 3 h. After the solvents had been removed by
evaporation, a saturated aqueous solution of Na2CO3 was added until a pH 8-9 was reached to give a
precipitate that was filtered off, washed with water and purified by flash chromatography (silica gel,
CH2Cl2-MeOH, 99:1 to 70:30 and then CH2Cl2-MeOH -Et3N 69:30:1) to give a yellow solid.
2-amino-6H-indolo[2,3-b]quinoxalines (3b): Yield: 0.23 g (98%); mp 386 °C. IR (KBr): ν = 3439, 3302,
1644, 1625, 1579, 1519, 1494, 1473, 1460, 1407, 1341, 1323, 1270, 1248, 1194, 1135, 1104, 1030, 1004,
859, 823, 752 cm-1. 1H NMR (300 MHz; DMSO-d6): δ = 5.65 (s, 2H, NH2), 7.17 (d, J = 2 Hz, 1H, 1-H),
7.25 (dd, J = 2 and 9 Hz, 1H, 3-H), 7.28 (t, J = 8 Hz, 1H, 9-H), 7.51 (d, J = 8 Hz, 1H, 7-H), 7.61 (t, J = 8
Hz, 1H, 8-H), 7.76 (d, J = 9 Hz, 1H, 4-H), 8.26 (d, J = 8 Hz, 1H, 10-H), 11.65 (s, 1H, NH). 13C NMR (75
MHz; DMSO-d6): δ = 106.7 (C-1), 112.1 (C-7), 119.5 (C-q), 120.3 (C-9), 121.9 (C-3), 122.3 (C-10),
128.2 (C-4), 130.7 (C-8), 134.3 (C-q), 139.0 (C-q), 141.4 (C-q), 143.7 (C-q), 144,1 (C-q), 147.8 (C-q).
Anal. Calcd for C14H10N4.1/2H2O: C, 69.12; H, 4.56; N, 23.03. Found: C, 69.15; H, 4.18; N, 22.88.
3-amino-6H-indolo[2,3-b]quinoxalines (4b): Yield: 0.20 g (85%); mp 365 °C. IR (KBr): ν = 3446, 3311,
1645, 1600, 1581, 1559, 1515, 1495, 1459, 1404, 1341, 1287, 1256, 1223, 1141, 1106, 1033, 1009, 833,
820, 749, 720 cm-1. 1H NMR (300 MHz; DMSO-d6): δ = 5.95 (s, 2H, NH2), 6.94 (d, J = 2 Hz, 1H, 4-H),
7.12 (dd, J = 2 and 9 Hz, 1H, 2-H), 7.27 (t, J = 8 Hz, 1H, 9-H), 7.47 (d, J = 8 Hz, 1H, 7-H), 7.56 (t, J = 8
Hz, 1H, 8-H), 7.86 (d, J = 9 Hz, 1H, 1-H), 8.17 (d, J = 8 Hz, 1H, 10-H), 11.63 (s, 1H, NH). 13C NMR (75
MHz; DMSO-d6): δ = 104.9 (C-4), 112.0 (C-7), 119.0 (C-q), 120.4 (C-2), 120.6 (C-9), 121.3 (C-10),
129.6 (C-8), 130.1 (C-1), 133.4 (C-q), 135.1 (C-q), 142.6 (C-q), 143.4 (C-q), 146.8 (C-q), 150.4 (C-q).
Anal. Calcd for C14H10N4.1/4H2O: C, 70.43; H, 4.43; N, 23.47. Found: C, 70.79; H, 4.32; N, 23.73.
Reaction of isatin (1) with 4-nitrobenzene-1,2-diamine (2a)
A mixture of isatin (1) (1.47 g, 10 mmol), 2a (1.99 g, 13 mmol) in AcOH (80 mL) was refluxed for 2 h.
After elimination of the solvent under reduced pressure and trituration of the residue with MeOH, the
1
resulting precipitate was washed with water, dried and identified by H NMR as a 1:2 mixture of 2- and
3-nitro-6H-indolo[2,3-b]quinoxalines (3a) and (4a) (1.86 g, 70%; mp 337 °C). After catalytic reduction, a
1
crude 1:2 mixture of amines 3b and 4b was obtained (90%). Comparison with the H NMR spectra of

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HETEROCYCLES, Vol. 75, No. 11, 2008
pure 3b and 4b identified 4b as the major product.
Reaction of isatin (1) with 4-acetylaminobenzene-1,2-diamine17 (2c)
A solution of isatin (1) (0.15 g, 1.0 mmol) in AcOH (10 mL) was added to a solution of 2c (obtained by
reduction of the N-(4-amino-3-nitrophenyl)acetamide)17 (0.21 g, 1.3 mmol) in AcOH (10 mL) was
1
refluxed for 1.5 h. After work up, the crude solid was washed with water, dried and identified by H
NMR as a 1:1 mixture (0.16 g, 58%) of 2- and 3-acetylaminoquinoxalines (3c) and (4c).
Reaction of isatin (1) with benzene-1,2,3-triamine19 (5b)
The same procedure as described above was used starting from 3-nitrobenzene-1,2-diamine (0.46 g, 3.00
mmol), time reaction: 3 h. After elimination of the solvents, the residue was washed with water, dried and
1
identified by H NMR as a mixture of 6b:7b (97:3). The 1-amino-6H-indolo[2,3-b]quinoxaline (6b)
(0.31 g, 58%; mp 330 °C) was isolated in a pure state by washing the crude precipitate with acetone (5 x
5 mL).
ACKNOWLEDGEMENTS
A. Jaouen was supported by a fellowship from MNSER.
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