Microwave-assisted synthesis of fused tricyclic pyrazino[1,2-a]indole derivatives

Article abstract of DOI:10.1007/s00706-014-1216-7

A microwave-assisted expedient route for the synthesis of novel 3-phenylpyrazino[1,2-a]indol-1(2H)-one derivatives is reported. The method has advantages such as accelerated reaction rate, excellent yields, simplicity of operation, and is eco-friendly. Microwave heating of ammonium acetate generates the NH₃ nucleophile required for the cyclization reaction and acetic acid. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-014-1216-7

Monatsh Chem
DOI 10.1007/s00706-014-1216-7
ORIGINAL PAPER
Microwave-assisted synthesis of fused tricyclic
pyrazino[1,2-a]indole derivatives
•
Raghunath Toche Sunil Chavan Ravindra Janrao
•
Received: 15 July 2013 / Accepted: 25 March 2014
Ó Springer-Verlag Wien 2014
Abstract A microwave-assisted expedient route for the
synthesis of novel 3-phenylpyrazino[1,2-a]indol-1(2H)-one
derivatives is reported. The method has advantages such as
accelerated reaction rate, excellent yields, simplicity of
operation, and is eco-friendly. Microwave heating of
ammonium acetate generates the NH3 nucleophile required
for the cyclization reaction and acetic acid.
for the synthesis of series of pyrazino[1,2-a]indole
derivatives.
Pyrazino[1,2-a]indoles have a wide range of biological
activities, e.g., they are serotonin antagonists [12], throm-
bolytics [13], antidepressants and anxiolytics [14], central
nervous system depressants [15], anticonvulsants [16],
antihistamines [17, 18], protein kinase C inhibitors [19],
5-HT2A and 5-HT2C agonists [20, 21], selective imidazo-
line I2 receptor ligands [22], antifungals [23], antibacterials
[24], and cardiovascular agents [25]. Moreover, com-
pounds containing the pyrazino[1,2-a]indole nucleus were
identified as novel potent antiproliferative agents against
the human chronic myelogenous leukemia K562 cell line
[26]. Therefore, versatile and simple methods for the syn-
thesis of pyrazino[1,2-a]indoles are of considerable
interest.
Keywords 3-Phenylpyrazino[1,2-a]indol-1(2H)-one Á
Microwave-assisted synthesis Á Ammonium acetate
Introduction
The indole ring structure is a ubiquitous heterocycle in
nature. Owing to the vast structural assortment of biolog-
ically active indoles, it has become a key structural
component in many pharmaceutical agents [1–5]. Substi-
tuted indoles can act as ‘‘restricted structures’’ as they are
able to bind to receptors with high affinity [6, 7]. The
synthesis and derivatization of indole has been a key area
of focus for organic chemists and several synthetic meth-
ods for indole have been known for more than hundred
years [8–11]. The indole nucleus is a common molecular
fragment in natural products and pharmaceutically active
compounds and hence it is used as the initial building block
Existing procedures for the synthesis of pyrazino[1,2-
a]indol-1(2H)-ones [27–34] suffer from numerous practical
disadvantages, e.g., moderate yields, multistep syntheses,
requirement for expensive catalysts and difficulties
encountered in solvent recovery.
Microwave-assisted chemistry is a rapidly growing field
suited for organic synthesis [35] owing to merits of
increased yields, high purity products, and short reaction
times. The introduction of new equipment has a large
influence on the further development in this young research
field [36]. On the other hand, the pharmaceutical industries
need to synthesis large numbers of new chemical entities in
a short time. Microwave radiation provides an alternate
method to conventional heating using the ability of liquids
and solids to transform electromagnetic energy into heat.
Herein, we report an efficient and simplified procedure
for the synthesis of 3-phenylpyrazino[1,2-a]indole deriva-
tives in excellent yields with high purity and accelerated
reaction rates under microwave irradiation.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-014-1216-7) contains supplementary
material, which is available to authorized users.
R. Toche (&) Á S. Chavan Á R. Janrao
Department of Chemistry, K. R. T. Arts, B. H. Commerce and
A. M. Science College, University of Pune (MS),
Gangapur Road, Nashik 422 002, India
e-mail: raghunath_toche@rediffmail.com
123

R. Toche et al.
Results and discussion
82 and 5 % yield respectively, whereas the same reaction
with DMF/POCl3 (1:1, v/v) yielded only product 4a in
79 % yield (entries 3 and 4). Thus by controlling the ratio
of DMF and POCl3, we have selectively synthesized
1-chloro-3-phenylpyrazino[1,2-a]indole-10-carbaldehyde
(4a) or 1,2-dihydro-1-oxo-3-phenylpyrazino[1,2-a]indole-
10-carbaldehyde (4). Furthermore, the chlorination of
compound 3 was achieved using POCl3 under microwave
irradiation at 90 °C in 5 min yielding compound 5 in
excellent yield (entry 5). On the other hand, N-methylation
of compound 3 using methyl iodide in the microwave
synthesizer was complete within 15 min to furnish N-
methylated product 6 in pure form and 86 % yield
(entry 6).
According to the literature, ethyl 1-(2-oxo-2-phenyl-
ethyl)-1H-indole-2-carboxylate (2) can be prepared in
75 % yield in 4 h by the conventional method [36],
whereas this reaction was complete in 10 min and fur-
nished 87 % yield under microwave irridiation
(Scheme 1; Table 1, entry 1). Compound
2
upon
intramolecular cyclization with ammonium acetate at
100 °C ( 5 °C) yields the new key intermediate
3-phenylpyrazino[1,2-a]indol-1(2H)-one (3) in 80 %
yield in 10 min under microwave irradiation (Scheme 1;
Table 1, entry 2). Ammonium acetate was used as the
key green reagent and solvent, which on heating
decomposes to acetic acid and the NH3 nucleophile that
induces the cyclization reaction.
The SNAr reaction of compound 5 was efficiently per-
formed with secondary amines 4-methylpiperazine and
morpholine and anilines in the presence of catalytic
amounts of p-toluenesulfonic acid (p-TSOH) in N-methyl-
2-pyrrolidone (NMP). The reaction was complete in
Vilsmeier–Haack reaction of compound 3 with DMF/
POCl3 (1:0.1, v/v) by microwave irradiation required
10 min and afforded a mixture of compounds 4 and 4a in
Scheme 1
O
H
CH3
Ph
O
N
O
OEt
Cl
N
N
N
H
6
N
1
DMF:POCl3
(1:1)
I
CH3
DMF, K
Ph
4a
MWI
2CO3
BrCH2COPh
DMF
MWI
MWI
K2
CO
KI
,
3
H
O
O
DMF:POCl3
(1:0.1)
O
O
NH4OAC
MWI
N
NH
Ph
4a
N
N
NH
Ph
OEt
O
3
MWI
4
2
Ph
X
POCl3
MWI
HN
X
N
R
p-TSOH, NMP
N
N
MWI
ArB(OH)2
7
Cl
Ph
Pd(PPh3)4
a
=
=
7
X
X
NCH3
O
,
,
N
N
N
N
7
b
K2CO3, DME
MWI
5
9
Ph
Ph
H2N
R
9a, R = H
9b, R = Cl
HN
N
R
N
p-TSOH, NMP
MWI
8
Ph
8a, R = H
8b, R = Cl
123

Microwave-assisted synthesis of fused tricyclic pyrazino[1,2-a]indole derivatives
Multiplicities are indicated by s (singlet), d (doublet), t
Table 1 Required reaction time, temperature, and yield of micro-
wave-assisted synthesis of compounds 2–9b
(triplet), q (quartet), and m (multiplet). Coupling constants,
J, are reported in Hertz. Mass spectral (MS) data were
obtained on a Bruker Daltonics spectrometer using an
electrospray ionization quadrupole time of flight (ESI-
QTOF) analyzer. All melting points were determined on a
manually operated Veego (VMP-1) melting point
apparatus.
Entry
Compound
Temp/°C
Time/min
Yield/%
1
2
3
2 [36]
3
80
105
100
10
10
10
87
80
82
5
4
4a
4a
5
4
5
6
7
100
90
10
5
79
82
86
78
72
73
77
86
76
Ethyl 1-(2-oxo-2-phenylethyl)-1H-indole-2-carboxylate (2)
mixture of 5.0 g ethyl 1H-indole-2-carboxylate
6
25
15
10
A
7a
7b
8a
8b
9a
9b
90
(0.264 mmol), 5.20 g phenacyl bromide (0.264 mmol),
7.30 g potassium carbonate (0.529 mmol), a catalytic
amount of potassium bromide, and 25 cm3 DMF was
irradiated in an 80-cm3 microwave vial at 80 °C ( 5 °C)
for 10 min in a microwave synthesizer. The reaction
mixture was allowed to cool at room temperature and was
stirred in 40 cm3 ice water, filtered, and washed with water
2–3 times to afford a colorless solid in 1.4 g (87 %) yield.
M.p.: 120–122 °C (Ref. [36] 119–120 °C); 1H NMR
spectrum was found to be identical with the one described
in Ref. [36].
8
9
90
10
15
100
10 min and yielded compounds 7 and 8 in excellent yields
at 90 °C (entries 7 and 8).
The palladium-catalyzed C–C bond Suzuki cross-cou-
pling of compound
5 with the weak nucleophile
1,2-Dihydro-1-oxo-3-phenylpyrazino[1,2-a]indole
arylboronic acid in the presence of Pd(PPh3)4 catalyst,
K2CO3 in DME under conventional heating afforded
compounds 9a and 9b in 63–66 % yield in 4 h. The same
reaction under microwave irradiation using the aforemen-
tioned reagents was complete within 15 min and afforded
76–86 % yields (entry 9).
A mixture of 0.200 g compound 2 (0.651 mmol) and
0.502 g ammonium acetate (6.51 mmol) was irradiated at
105 °C ( 5 °C) for 10 min in a microwave synthesizer.
The reaction mixture was allowed to cool to room
temperature. The residue was treated with 20 cm3 ice-cold
water and neutralized with saturated sodium bicarbonate
solution to afford an off-white solid in 0.135 g (80 %)
yield. M.p.: 210–212 °C; Rf = 0.33 (MeOH/CHCl3 1:9,
Table 1 summarizes the isolated yields of pure products
using the microwave synthesizer at the 300-W power level,
temperature recorded using an IR sensor, and irradiation
time in minutes. All new compounds were characterized by
analytical and spectral methods and the spectral data are
given in the ‘‘Experimental’’ section.
1
v/v); H NMR (300 MHz, DMSO-d6): d = 11.11 (bs, 1H,
NH), 8.27 (s, 1H), 8.24 (d, J = 8.7 Hz, 1H, ArH), 7.82 (t,
J = 7.5 Hz, 3H, ArH), 7.52–7.43 (m, 4H, ArH), 7.34–7.29
(m, 2H, ArH) ppm; 13C NMR (75 MHz, DMSO-d6):
d = 94.99, 110.94, 117.67, 122.05, 123.72, 127.63, 127.63,
128.87, 128.87, 129.04, 129.11, 141.34, 147.17,
151.02 ppm; MS: m/z = 261.1 ([M ? 1]?), 259.1 ([M -
1]?).
Experimental
All reagents were of commercial quality and reagent
quality solvents were used without further purification. All
the microwave irradiation experiments were performed in a
CEM Explorer microwave system and reaction tempera-
tures were monitored by an IR sensor. All reactions were
monitored by thin-layer chromatography (TLC), carried
out on 0.2-mm silica gel 60 F254 (Merck) plates using UV
1,2-Dihydro-1-oxo-3-phenylpyrazino[1,2-a]indole-9-
carbaldehyde (4, C18H12N2O2)
To the stirring solution of 0.200 g compound
3
(0.768 mmol) in 1.0 cm3 dry DMF in a 10-cm3 microwave
vial was added 0.1 cm3 POCl3 at 0–5 °C dropwise and the
mixture was irradiated at 100 °C ( 5 °C) for 10 min in a
microwave synthesizer. Thereafter, POCl3 was removed
under vacuum and the residue obtained was poured into
ice-cold water and neutralized with sodium bicarbonate.
The product was extracted with EtOAc (2 9 15 cm3). The
combined organic extracts were washed with water
(2 9 25 cm3), dried over anhydrous sodium sulfate, and
1
light (254 and 366 nm) for detection. H NMR and 13C
NMR spectra were recorded on a Bruker spectrometer
operating at 300 and 75 MHz for 1H and 13C, respectively,
using either CDCl3 or DMSO-d6 as the solvent. Chemical
shifts, d, are reported in parts per million (ppm) relative to
solvent resonance: CDCl3, d 7.26 (1H NMR) and 77.3 (13C
NMR); DMSO-d6, d 2.50 (1H NMR) and 40.2 (13C NMR).
123

R. Toche et al.
1
the solvent was evaporated under vacuum to furnish a
crude solid, which according to TLC was a mixture of two
products. These two products were separated on a silica gel
column (MeOH/CHCl3 0.5:9.5, v/v) to afford 0.181 g
(82 %) of 4 and 0.011 g (5 %) of 4a. IR (KBr): m = 2,710,
1,710, 1,695 cm-1; m.p.: 189–193 °C; Rf = 0.50 (MeOH/
CHCl3 1:9, v/v); 1H NMR (300 MHz, DMSO-d6):
d = 11.97 (bs, 1H, NH), 10.95 (s, 1H, CHO), 9.76 (s,
1H), 8.71 (d, J = 7.8 Hz, 1H, ArH), 8.61 (d, J = 7.5 Hz,
1H, ArH), 6.18 (d, J = 7.2 Hz, 2H, ArH), 7.68–7.46 (m,
5H, ArH) ppm; 13C NMR (75 MHz, DMSO-d6):
d = 97.24, 106.84, 113.49, 116.26, 117.45, 123.35,
125.02, 129.13, 131.21, 131.44, 132.37, 148.05, 154.77,
192.55 ppm; MS: m/z = 289.1 ([M ? 1]?).
(EtOAc/n-hexane 1:1, v/v); H NMR (300 MHz, DMSO-
d6): d = 9.53 (s, 1H, ArH), 8.56 (d, J = 7.8 Hz, 1H, ArH),
8.10 (d, J = 7.5 Hz, 2H, ArH), 7.93 (d, J = 6.9 Hz, 1H,
ArH), 7.53–7.36 (m, 5H, ArH), 7.24 (s, 1H, ArH) ppm; 13
C
NMR (75 MHz, DMSO-d6): d = 102.54, 116.76, 122.53,
125.23, 127.79, 128.74, 128.87, 131.38, 132.29, 142.33,
146.98, 152.31 ppm; MS: m/z = 279.1 ([M ? 1]?).
2-Methyl-3-phenylpyrazino[1,2-a]indol-1(2H)-one
(6, C18H14N2O)
To a solution of 0.100 g compound 3 (0.384 mmol) in
3.0 cm3 dry DMF containing 0.159 g K2CO3
(1.153 mmol), 0.57 g methyl iodide (0.403 mmol) was
added dropwise. After complete addition, the reaction
mixture was irradiated in a microwave synthesizer for
15 min at room temperature. The reaction mixture was
then diluted with 15 cm3 water, the product was extracted
in EtOAc (2 9 15 cm3), and the combined extracts were
washed with saturated Na2CO3 solution. The solvent was
evaporated under vacuum and the product was recrystal-
lized from ethanol to afford a colorless solid in 0.090 g
(86 %) yield. M.p.: 180–183 °C; Rf = 0.92 (MeOH/CHCl3
1-Chloro-3-phenylpyrazino[1,2-a]indole-10-carbaldehyde
(4a, C18H11ClN2O)
A solution of 0.200 g compound 3 (0.768 mmol) in
3.0 cm3 dry DMF and 3.0 cm3 POCl3 at 0–5 °C was
irradiated at 100 °C ( 5 °C) for 10 min in a microwave
synthesizer. The reaction mixture was allowed to cool to
room temperature. Thereafter POCl3 was removed under
vacuum and the residue obtained was poured into ice-cold
water and neutralized with sodium bicarbonate. The
product was extracted with EtOAc (2 9 15 cm3) and the
combined extract was washed with water (2 9 25 cm3),
dried over anhydrous sodium sulfate, and concentrated
under vacuum. The residue was recrystallized from EtOAc/
n-hexane (90:10, v/v) to afford a yellowish solid 4a in
0.185 g (79 %) yield. M.p.: 215–217 °C; Rf = 0.78
(MeOH/CHCl3 1:9, v/v); IR (KBr): m = 1,710,
1
1:8, v/v); H NMR (300 MHz, DMSO-d6): d = 9.16 (s,
1H, ArH), 8.45 (d, J = 7.5 Hz, 1H, ArH), 8.17 (d,
J = 7.5 Hz, 2H, ArH), 7.89 (d, J = 7.2 Hz, 1H, ArH),
7.52–7.33 (m, 5H, ArH), 7.06 (s, 1H, ArH), 4.20 (s, 3H,
CH3) ppm; 13C NMR (75 MHz, DMSO-d6): d = 30.04,
97.45, 117.34, 123.28, 123.47, 124.02, 127.17, 128.39,
129.00, 129.12, 129.71, 130.39, 136.02, 138.33, 145.40,
147.85, 159.93 ppm; MS: m/z = 275.1 ([M ? 1]?).
2,710 cm-1
;
1H
NMR
(300 MHz,
DMSO-d6):
1-(4-Methylpiperazin-1-yl)-3-phenylpyrazino[1,2-a]indole
(7a, C22H22N4)
d = 7.09–7.14 (m, 2H, ArH), 7.30 (t, 1H, J = 7.2 Hz,
ArH), 7.37–7.44 (m, 5H, ArH), 7.52 (d, 1H, J = 8.4 Hz,
ArH), 7.67 (s, 1H, ArH), 11.22 (s, 1H, CHO) ppm; 13C
NMR (75 MHz, DMSO-d6): d = 109.04, 113.90, 116.25,
123.20, 125.33, 126.13 (2), 127.26, 128.55, 129.44 (2),
130.12, 131.46, 134.95, 142.89, 185.18 ppm; MS: m/
z = 307.1 ([M ? 1]?), 308.1 ([M ? 2]?).
To a solution of 0.100 g compound 5 (0.359 mmol) and
0.040 g 4-methylpiperazine (0.395 mmol) in 2 cm3 NMP
was added a catalytic amount of p-TSOH in a 10-cm3
microwave tube which was then irradiated at 90 °C ( 5 °C)
for 10 min in a microwave synthesizer. The reaction
mixture was allowed to cool to room temperature. To this
reaction mixture 15 cm3 Na2CO3 solution (10 %) was
added and the precipitated product was filtered and washed
with chilled diethyl ether to afford a yellow solid in 0.095 g
yield. M.p.: 222–225 °C; Rf = 0.55 (MeOH/CHCl3 1:8,
1-Chloro-3-phenylpyrazino[1,2-a]indole
(5, C17H11ClN2)
A mixture of 0.200 g compound 3 (0.768 mmol) and
3.0 cm3 phosphorus oxychloride was irradiated in a
microwave synthesizer at 100 °C ( 5 °C) for 10 min.
The progress of the reaction was monitored by TLC.
Thereafter, POCl3 was removed under vacuum and the
residue obtained was poured into ice-cold water and
neutralized with sodium bicarbonate. The precipitated
solid was filtered, washed with water, and recrystallized
from chilled EtOAc to afford a yellow crystalline product
in 0.175 g (82 %) yield. M.p.: 178–181 °C; Rf = 0.60
1
v/v); H NMR (300 MHz, DMSO-d6): d = 8.27 (s, 1H,
ArH), 8.24 (d, J = 8.7 Hz, 1H, ArH), 7.85–7.80 (m 3H,
ArH), 7.52–7.43 (m, 4H, ArH), 7.34–7.29 (m, 2H, ArH),
3.31–2.25 (m, 8H), 2.18 (s, 3H, CH3) ppm; 13C NMR
(75 MHz, DMSO-d6): d = 46.14, 53.08, 54.90, 105.93,
111.29, 119.10, 120.98, 122.61, 124.89, 127.19, 129.13,
129.71, 136.74, 139.88, 155.23 ppm; MS: m/z = 343.2
([M ? 1]?), 341.0 ([M – 1]?).
123

Microwave-assisted synthesis of fused tricyclic pyrazino[1,2-a]indole derivatives
1-Morpholino-3-phenylpyrazino[1,2-a]indole
the temperature being ramped from room temperature to
(7b,C21H19N3O)
the desired 105 °C ( 5 °C). The reaction mixture was
stirred continuously at this temperature. After completion
of the reaction, the solid catalyst was filtered and washed
with diethyl ether. The aqueous solution was then extracted
with diethyl ether (3 9 15 cm3). The ether layer was dried
over anhydrous sodium sulfate and then evaporated under
reduced pressure; the residue was chromatographed over
silica gel column (MeOH/CHCl3 9.5:0.5, v/v). Colorless
solid; yield 0.042 g; m.p.: 206–208 °C; Rf = 0.83 (MeOH/
CHCl3 1:8, v/v); 1H NMR (300 MHz, DMSO-d6):
d = 9.02 (s, 1H, ArH), 8.19 (d, 1H, J = 8.2 Hz, ArH),
7.83–7.65 (m, 5H, ArH), 7.57–7.41 (m, 8H, ArH), 6.97 (s,
1H, indole) ppm; 13C NMR (75 MHz, DMSO-d6):
d = 106.07, 118.08, 119.86, 123.46, 124.29, 127.36,
127.56, 128.42, 129.07, 129.20, 129.75, 130.47, 130.63,
137.10, 137.74, 138.24, 145.59, 148.11, 158.43,
159.86 ppm; MS: m/z = 321.1 ([M ? 1]?), 319.0
([M - 1]?).
Synthesized by the procedure reported in 7a, starting from
compound 0.100 g 5 (0.359 mmol) and of 0.031 g mor-
pholine (0.359 mmol). The desired product was obtained as
an off-white solid and recrystallized from chilled EtOAc to
afford 0.085 g (72 %) yield. M.p.: 170–172 °C; Rf = 0.42
1
(MeOH/CHCl3 1:8, v/v); H NMR (300 MHz, DMSO-d6):
d = 8.22 (s, 1H, ArH), 7.68 (d, 2H, J = 8.6 Hz, ArH),
7.53 (d, J = 7.5 Hz, 1H, ArH), 7.44–7.09 (m, 7H, ArH),
2.55–2.43 (m, 8H, morpholine) ppm; 13C NMR (75 MHz,
DMSO-d6): d = 53.80, 66.77, 105.05, 111.09, 114.45,
120.81, 122.44, 124.41, 127.16, 129.69, 129.90, 136.54,
156.03 ppm; MS: m/z = 330.1 ([M ? 1]?), 328.1
([M – 1]?).
N,3-Diphenylpyrazino[1,2-a]indol-1-amine
(8a, C23H17N3)
Synthesized by the procedure reported for 7a, starting from
0.100 g compound 5 (0.359 mmol) and 0.035 g aniline
(0.377 mmol). The desired product was obtained as a
colorless solid after recrystallization from chilled EtOAc in
0.087 g (73 %) yield. M.p.: 255–258 °C; Rf = 0.35
(MeOH/CHCl3 1:8, v/v); 1H NMR (300 MHz, DMSO-
d6): d = 9.23 (s, 1H, ArH), 8.46–8.31 (m, 4H, ArH), 8.15
(d, J = 8.12 Hz, 1H, ArH), 7.94–7.76 (m, 4H, ArH),
7.63–7.58 (m, 6H, ArH), 5.38 (bs, 1H, NH) ppm; 13C NMR
(75 MHz, DMSO-d6): d = 118.45, 123.27, 124.32, 125.95,
127.19, 128.27, 128.39, 128.95, 129.11, 129.68, 130.11,
130.69, 131.80, 133.35, 134.12, 138.44, 139.81, 145.17,
146.98, 154.78, 159.62 ppm; MS: m/z = 336.1
([M ? 1]?), 334.1 ([M – 1]?).
1-(4-Chlorophenyl)-3-phenylpyrazino[1,2-a]indole
(9b, C23H15ClN2)
Synthesized by using the procedure reported for 9a,
starting from 0.050 g of compound 5 (0.179 mmol),
0.062 g K2CO3 (0.449 mmol), 0.010 g Pd(PPh3)4
(8.99 mmol), and 0.042 g 4-chlorophenylboronic acid
(0.269 mmol). Yield 0.048 g; white solid. M.p.:
230–232 °C; Rf = 0.79 (MeOH/CHCl3 1:8, v/v); 1H
NMR (300 MHz, DMSO-d6): d = 9.22 (s, 1H, ArH),
8.15–8.09 (m, 2H, ArH), 7.89–7.74 (m, 5H, ArH),
7.62–7.44 (m, 5H, ArH), 7.37–7.35 (m, 2H, ArH) ppm;
MS: m/z = 355.2 ([M ? 1]?), 356.2 ([M ? 2]?).
N-(4-Chlorophenyl)-3-phenylpyrazino[1,2-a]indol-1-
amine (8b, C23H16ClN3)
Acknowledgments The authors thank Council for Scientific and
Industrial Research (CSIR) New Delhi for financial assistance for this
work and the Principal, K. T. H. M. College, Nashik - 422 002 for
facilities.
Synthesized by the procedure reported for 7a, starting from
0.100 g compound 5 (0.359 mmol) and 0.048 g 4-chloro-
aniline (0.377 mmol). The desired product obtained was
recrystallized from ethanol to yield 0.102 g (77 %) 8b.
References
1
M.p.: 199–201 °C; Rf = 0.43 (MeOH/CHCl3 1:9, v/v); H
1. Sundberg RJ (1970) The chemistry of indoles, vol 18. Academic
Press, New York
2. Sundberg RJ (1984) Pyrroles and their benzoderivatives: syn-
thesis and applications. In: Katritzky AR, Rees CW (eds)
Comprehensive heterocyclic chemistry, vol 4. Pergamon, Oxford,
p 313
NMR (300 MHz, DMSO-d6): d = 9.21 (s, 1H, ArH),
8.45–8.40 (m, 3H, ArH), 8.30 (d, J = 8.7 Hz, 1H, ArH),
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