A catalyst-free, efficient green MCR protocol for access to functionalized γ-carbolines in water

Article abstract of DOI:10.1039/c5ra08422a

A general, mild, efficient and practical approach for the construction of functionalized γ-carboline derivatives has been successfully realized in water through a one-pot three-component reaction involving several aryl/hetero-aryl/alkyl/alkenyl/alkynyl/fe

Full text of DOI:10.1039/c5ra08422a

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Graphical Abstract
Catalystꢀfree, an efficient green MCR protocol for the access to
functionalized γꢀcarbolines in water
Anuradha Dagar, Soumen Biswas and Sampak Samanta*,a
a Indian Institute of Technology Indore, Department of Chemistry, Indore, 452017, MP, India
A facile, catalystꢀfree and green approach for the synthesis of functionalized γꢀcarbolines has been achieved in water with good to
excellent yields via oneꢀpot threeꢀcomponent heteroꢀannulation reaction of 3ꢀformyl indole derivatives, aldehydes with ammonium
acetate at room temperature under aerobic conditions.
62 examples
CHO
N
NH4OAc
X
X
R1CHO
N
H
R1
COR
H2O, rt, air
N
H
COR
R1 = alkyl, aryl, hetero-aryl,
ferrocenyl, alkenyl,
alkynyl
One-pot MCR
Catalyst-free
External-oxidant-free
Water
R = Ar, OMe
Room temperature
Open flask
Broad substrate scope
Excellent yield (≤91% )
Excellent FG tolerance

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Cite this: DOI: 10.1039/c0xx00000x
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PAPER
Catalyst-free, an efficient green MCR protocol for the access to
functionalized γ-carbolines in water
Anuradha Dagar, Soumen Biswas and Sampak Samanta*,a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
A general, mild, efficient and practical approach for the construction of functionalized γ-carboline
derivatives has been successfully realized in water through a one-pot three-component reaction involving
several aryl/hetero-aryl/alkyl/alkenyl/alkynyl/ferrocenyl aldehydes, 3-formyl indole derivatives and
ammonium acetate as a cheap N-source. The most important feature of current methodology is that this
hetero-annulation reaction of indole to γ-carboline can obtain in good to excellent yields with wider
substrate scope at room temperature in water, starting from simple inexpensive raw materials under
catalyst-free and oxidant-free conditions. Moreover, a facile access to pentacyclic quinolinone fused
carboline derivative has been achieved through our methodology.
Introduction
Multi-component reactions are unarguably one of the most 30 with alkynes for the preparation of γ-carbolines has been
practical, atom-economical and efficient synthetic techniques for
the rapid constructions of a wide range of pharmacologically
interesting frameworks from simple readily available raw
developed by Hua et al.5f Furthermore, an innovative route to N-
imino-γ-carboline ylides has been realized by Zhan et al. via
Ag(I) catalyzed imino-heteroannulation of propargyl alcohol
with 3-indolyl hydrazone derivative (Scheme 1c).5g Despite the
1
5
materials through a one-pot multiple bond forming process.
Thus, when such strategy is conducted in water at ambient 35 great advances,
many reported protocols entail several
temperature without using any external catalysts and
volatile/carcinogenic organic solvents, reaction conditions should
be considered nearly perfect in terms of safety, health, cost-
disadvantageous such as the use of toxic and expensive metals,
harmful and volatile organic solvents, excess amount of strong
oxidants, difficult operation, higher reaction temperature,
Other Work:
10 effectiveness, energy conservation and eco-sustainable points of
view.2 On the other hand, the highly efficient synthesis of multi-
functionalized γ-carboline derivatives has been subject of
growing interest in recent years since this tricyclic scaffold
played a crucial role in several biological processes and showed
15 broad spectrum of biological activities including anti-cancer,
antibiotic, antipsychotic, anti-Alzheimer etc.3 In order to evaluate
the biological activities, many synthetic and medicinal chemists
t-Bu
Larock'swork
N
N
cat. Pd (0) base
DMF, heating
40
R1
R2
(a)
N
R
R2
N
R
X
R1
R3
X= Br, I
X = t-Bu
Jiao'swork
cat. Pd (II), base
R3
X
N
4ÅMS, DMF, heating
N
N
R1
R2
(b)
(c)
Ru (II), base
MeOH, heating
X =OH, OMe
N
R
R2
N
R
H
H
R1
Jeganmohan's works
NTs
NNHTs
HO
R4
R3
cat. Ag (I)
R2
45
R3
THF, heating
Zhan's work
have developed several tools for the preparations of these
4,5
N
R
N
R2
R4
R
moieties.
Among them, one-shot hetero-annulation reactions
Two-step
Our previous work:
20 of indoles to γ-carbolines catalyzed by transition metal-salts have
been recognized tremendously as alternative powerful synthetic
CHO
(i) L-proline (25 mol%)
DMSO, rt, 2-3 days
N
+ R1CHO
(d)
N
H
R1
CO2Me
(ii) NH4OAc, DMSO
air, 12-16h
5a-c
Jiao5d
N
H
protocols in recent years. For instance, Larock et al.,
COR
and Jeganmohan5e groups have independently developed the one-
shot attractive synthetic protocols for the constructions of γ-
25 carboline scaffolds via iminoannulation reactions between
alkynes and 2-halo-3-iminoindoles or 3-iminoindoles using
Pd(0)/Pd(II)/Ru (II)-catalysts under heating conditions (Scheme
1a-b) . In 2012, Rh (III) catalyzed one-pot three-component
hetero-annulation reaction of 3-carbonyl indoles, NH2OH.HCl
Our present work:
50
CHO
N
Catalyst-free !
X
R1CHO
NH4OAc
+
X
+
(e)
COR
N
H
R1
H2O, rt, air
N
H
COR
Scheme 1 Various one-pot hetero-annulation approaches of
indoles to γ-carbolines
55

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unsatisfactory yields, poor atom-economy, specific substrate
14h, the expected γ-carboline 3aa was isolated in excellent yield
scope etc. Therefore, it would be highly meaningful to develop an 95 90%. The structure of product was ascertained by its
alternative one-pot, catalyst-free, efficient and environment
friendly protocol for the synthesis of pharmacologically
60 interesting γ-carboline scaffolds in water at room temperature by
utilizing cheap and easily available starting materials.
spectroscopic data (1H, 13C NMR and HRMS). This fascinating
result inspired us to examine this MCR in more detail. In this
context, we examined the reaction in various common solvents
such as DMF, DCM, toluene, MeCN, THF and 1,4-dioxane,
100 EtOH, MeOH and H2O. To our satisfaction, this reaction
proceeded very well not only in organic solvents but also in
water. Consequently, similar kinds of yields (84-89%, entries 2-
10) of γ-carboline 3aa were observed. However, it was witnessed
that the rate of the reaction in water was much slower than
As part of our continued research goal towards the newer
synthetic transformations for the access to biologically interesting
65 various N-heterocycles in a practical manner,6 we recently
reported on organocatalytic two-step synthetic method for the
preparation of substituted γ-carboline derivatives starting from 3- 105 organic solvents (14h vs 24h, entries 1-9 vs entry 10). In spite of,
formyl indoles in DMSO medium using L-proline as a catalyst
(Scheme 1d).6a Against these backgrounds, we envisioned that
70 this reaction may be conveniently performed in a one-pot manner
without using any catalyst in water medium, thereby enhancing
water was chosen as a best solvent for this hetero-annulation
reaction due to its unique beneficial features such as environment
friendly, extremely cheap, non-flammable, non-toxic, and most
abundant in nature. Next, we screened this reaction by
the substrate scope and structural complexity of final γ- 110 employing a variety of commercially available ammonium salts
carbolines. Here we wish to report a mild (room temperature),
easy, catalyst-free, green and efficient one-pot MCR technique
75 for the preparation of a wide range of functionalized γ-carbolines
by employing 2-substituted-3-formyl-1H-indoles, aldehydes and
as the N-sources in water. Results clearly addressed that the
NH4OAc, HCO2NH4 and NH4SCN offered superior yields (89%,
85% and 75% respectively, entries 10-12) than other basic
(NH4OH, NH4HCO3 and (NH4)2CO3) and acidic salts (NH4Cl
ammonium acetate as N-source in water at room temperature 115 and (NH4)2SO4,) tested for this annulation reaction (entries 13-
under aerobic conditions (Scheme 1e).
17). The probable reason is that ammonium salts (entries 10-12)
-
of weak acids (corresponding counteranion AcO-, HCO2 and
80 Table 1 Optimization of reaction conditionsa
SCN-) and weak base may easily dissociate into the ammonia in
reaction media as compared to the corresponding basic
-
CHO
120 (counteranion HO-, HCO3 and CO32-, entries 15-17) and acidic (
Ammonium salt
Conditions
N
Ph
+
PhCHO
counteranion Cl- and SO42-, entries 13-14) ammonium salts.7
Finally, NH4OAc being less expensive compared to NH4HCO2,
was opted as a best N-supplier.
N
H
Ph
N
H
O
O
Ph
85
1a
2a
3aa
Entry Solvent
Salt
Time (h)
Yield (%)b
125 A mechanistic insight of this catalyst-free one-pot aqueous MCR
is proposed as depicted in Scheme 1. At first, benzaldehyde (2a)
may react with ammonium acetate to form iminium ion 2a' which
is subsequently nucleophilic attacked by keto-enol 1á to generate
Mannich adduct 4. Finally, γ-carboline 3aa is formed from
130 intermediate 4 via an intramolecular imination reaction, followed
by oxidation of tricyclic intermediate 5 under aerobic conditions
as follows in Path A. Alternatively, the intermediate 4 may be
possible to convert into the corresponding Knoevenagel
condensation product 4a6a by elimination of ammonium acetate
135 (Path B). Afterwards, the latter react with ammonium acetate to
form imine intermediate 4a' which upon intramolecular
cyclization and subsequent aerial oxidation lead to 3aa. However,
the detailed understanding the mode of reaction requires
additional efforts.
1
2
DMSO
DMF
NH4OAc
14
14
14
14
14
14
14
14
14
24
24
24
24
24
24
24
24
90
88
85
86
90
89
84
88
87
89
85
75
57
60
42
30
36
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
HCO2NH4
NH4SCN
(NH4)2CO3
NH4HCO3
NH4OH
3
4
5
6
DCM
toluene
MeCN
THF
7
8
1,4-dioxane
EtOH
9
MeOH
Water
Water
Water
Water
Water
Water
Water
Water
10
11
12
13
14
15
16
17
(NH4)2SO4
NH4Cl
aUnless otherwise to be noted, all the reactions were conducted with 2-(2-
oxo-2-phenylethyl)-1H-indole-3-carbaldehyde (1a, 0.2 mmol), PhCHO
(2a, 0.24 mmol) and ammonium salt (0.22 mmol) in specified solvent (0.5
mL) at room temperature under air. bIsolated yield after column
chromatography.
140
145
Results and Discussion
90 To access the desired γ-carboline, we have performed the model
reaction between 2-(2-oxo-2-phenylethyl)-1H-indole-3-
150
carbaldehyde (1a), benzaldehyde (2a) and ammonium acetate as
Scheme 2 Proposed mechanism for one-pot three-component
N-source in DMSO at room temperature under air. Indeed, after

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hetero-annulation reaction
210
Similarly, by this procedure, substituted indole derivatives 1b-c
also underwent spotless reactions with a variety of structurally
diverse aryl, hetero-aryl and alkyl aldehydes to furnish the
corresponding products in good to high yields (72-86%, 3ba-
With optimization reaction in hand, we thoroughly investigated
155 the scope and generality of this MCR by taking a variety of
aromatic/hetero-aromatic/aliphatic aldehydes (2a-r), 2-(2-oxo-2-
arylethyl)-1H-indole-3-carbaldehydes (1a-c) with ammonium 215 3cn).
acetate under our established reaction conditions. Results are
summarized in Table 2. Incorporation of several substituents
160 such as electron rich (Me, OMe, OBn) and electron poor (Br, Cl,
F, CF3, NO2, CN) at ortho-, meta- and para-positions on aryl
In order to explore the further possible substrate scope, we
decided to use other indole analogues such as 2-(3-formyl-1H-
indol-2-yl)acetates (1d-1e) under our standard conditions. As
can be seen from Table 3, the indole derivatives 1d-1e annulated
rings of aromatic aldehydes did not show any significant impact 220 not only with a benzaldehyde but also with several aromatic
on the rate of the reactions when substrate 1a was used.
Consequently, after 24h, all these reactions led to the
165 corresponding functionalized γ-carbolines in good to excellent
yields (3ab-3am, 79-89%). Furthermore, several challenging
aldehydes having a wide range of functional groups namely Me,
OMe, OBn, Cl, Br, NO2, NHBoc on the aromatic rings in a
practical manner, leading to the corresponding substituted γ-
carbolines (3da-3ds and 3ea) in high to excellent yields (81-
electrophiles like hetero-aryl, alkyl and ferrocenyl aldehydes also 225 91%). Similarly, several hetero-aromatic aldehydes (2-furyl, 2-
participated well with substrate 1a under identical conditions
(except 3ar, at 50 °C) to furnish the anticipated products in
170 satisfactory yields (66-76%, 3an-3ar).
thiophenyl and 3-indolyl) were found to be appropriate
electrophiles for this transformation. As a consequence, after 24h,
all these reactions produced the corresponding desired γ-
carbolines (3dn, 3eo and 3dt) in nearly perfect yields (81-85%).
230 It is noteworthy to mention that all the above γ-carbolines (3da-
3dt) had also been synthesized previously from same starting
material 1d by adopting two-step method involving L-proline as a
catalyst.6a However, the combined yields (60-80%, two-step) of
corresponding products are considerably (10-24%) lower than
235 those obtained (81-91%, Table 3) by this present procedure with
much shorter times (96h vs 24h). Therefore, the present
conditions are superior in terms of yields, times and green
chemistry point of view. Moreover, by this current one-shot
procedure, the substrates 1d-e were actively engaged with a
240 variety of 1°- and 2°-aliphatic aldehydes and resulted in good
to high yields (79-86%) of corresponding 3-alkylated γ-carboline
precursors (3dq-3dw & 3ev-3ex). Most importantly,
Table 2 The scope of the reaction between 2-(2-oxo-2-arylethyl)-1H-
indole-3-carbaldehydes (1a-c) and aldehydes (2a-r)
CHO
NH4OAc
N
R
O
R1CHO
+
H2O, air, rt
24-30h
N
H
R1
N
H
R
175
180
185
190
195
200
205
3aa-3cnO
2a-r
1a-c
1a: R = Ph
1b: R = 4-MeC6H4
1c: R = 4-MeOC6H4
OMe
N
O
N
O
N
O
N
O
N
N
H
N
H
N
H
H
OMe
Me
OMe
3aa: 89%
3ab: 87%
3ac: 84%
3ad: 81%
Cl
N
O
N
O
N
N
O
N
H
N
H
N
H
N
H
Cl
Br
OBn
O
OMe
3ah: 85%
3ae: 79%
3af: 88%
3ag: 89%
Table 3 The scope of the reaction between methyl 2-(3-formyl-1H-indol-
2-yl)acetate derivatives (1d-e) and aldehydes (2a-y)
N
O
NO2
N
O
N
N
O
N
H
N
H
N
H
N
H
NO2
CF3
O
F
245
3al: 82%
3aj: 88%
3ak: 84%
3ai: 85%
X
CHO
N
NH4OAc
N
N
O
N
O
N
RCHO
CO2Me
O
S
N
H
R
H2O, air, rt
24-36h
N
H
1d-e
N
H
N
H
N
H
N
H
CO2Me
2a-x
3da-3er
CN
O
O
1d: X = H
1e: X = Br
3an: 75%
3am: 84%
3ao: 76%
3ap: 73%
N
N
N
N
OMe
OBn
N
N
H
N
H
N
H
N
O
H
250
255
260
N
O
N
O
CO2Me
N
O
CO2Me
CO2Me
3dc: 84% (66%)a
CO2Me
3de: 82% (60%)a
Me
OMe
3da: 90% (80%)a
3db: 88% (73%)a
N
H
N
H
N
H
N
H
Fe
OMe
NO2
NHBoc
N
N
N
N
Me
Me
N
H
N
H
N
H
N
H
3aq: 73%
3ar: 66%b
3ba: 84%
3bc: 82%
CO2Me
CO2Me
CO2Me
CO2Me
Br
Cl
N
3df: 88% (78%)a
3dl: 87% (63%)a
3dg: 91% (80%)a
3ds: 78% (62%)a
N
O
N
O
N
N
H
N
H
N
H
N
H
N
N
N
N
CN
Me
O
NO2
Me
O
Br
O
N
H
N
H
N
H
N
H
Fe
NBoc
Me
CO2Me
CO2Me
Me
CO2Me
CO2Me
3bp: 72%
3bf: 84%
3bm: 86%
3bk: 83%
3dn: 84% (68%)a
3dt: 81% (71%)a
3dq: 83% (74%)a
3dr: 78%
Br
NHCbz
N
O
N
N
N
O
N
N
OMe
OMe
N
N
O
N
H
N
H
N
H
Ph
N
H
N
H
NHBoc
N
H
N
H
N
H
CO2Me
CO2Me
CO2Me
3dv: 79%
N
CO2Me
Me
OMe
MeO
O
3du: 86%(79%)a
3ea: 91%
3dw: 74%
MeO
MeO
MeO
Br
Br
Br
Br
N
N
N
3cd: 75%
3ca: 85%
3cb: 81%
3cc: 77%
N
H
N
H
N
H
N
H
NHBoc
N
O
Fe
N
O
N
O
S
CO2Me
CO2Me
CO2Me
3ev: 81%
aIn parantheses indicate the combined yields of two-step method starting from 1d as previously reported by us.
CO2Me
O
N
H
N
H
N
H
3ex: 85%
3eo: 85%
3er: 82%
NO2
MeO
Cl
MeO
MeO
3cn: 73%
3cg: 86%
3ck: 81%
ferrocenecaboxaldehyde also worked equally well with substrates
a All the reactions were carried out with compounds (1a-c, 0.2 mmol), aldehydes (2a-r, 0.24 mmol) and NH4OAc (0.22 mmol) in 0.5 mmol under air at room
temperature. b At 50 °C.
1d-e to afford the interesting ferrocenyl functionalized γ-

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265 carbolines in 78-82% yields
.
It is fruitful to mention that a large
Finally, the current one-pot hetero-annulation process can be
applied to the synthesis of biologically interesting quinolinone
fused heterocyclic scaffolds8 in 76-79% yields from the reaction
number of sensitive functional groups including Me, OMe, OBn,
Cl, Br, NO2, NHBoc, NHCbz, CO2Me, thiophene, furan, indole,
ferrocene etc remained unaltered in our mild conditions.
of indole derivatives 1d-1e,
aromatic aldehyde 2t and
320 ammonium acetate in DMSO at heating conditions as shown in
Scheme 4.
Table 4 One-pot synthesis of (E)-2-styryl-substituted γ-carboline
270 frameworks (3daa-3eaa)
CHO
X
X
CHO
CO2Me
N
NHBoc
NH4OAc
X
CHO
CO2Me
CHO
N
H
X
DMSO, air, 50 °C
24h
N
H
N
NH4OAc
325
N
H
H2O, air, rt
24h
O
N
Boc
N
H
R
R
1d-e
CO2Me
2t
2aa-2ah
1d-e
3daa-3eaa
1d: X = H
1e: X = Br
6: X = H; 76% yield
7: X = Br; 79% yield
1d: X = H
1e: X = Br
275
N
N
N
Scheme 4 One-pot synthesis of pentacyclic quinolinone fused γ-
N
H
N
H
N
H
CO2Me
CO2Me
CO2Me
Me
OMe
330 carbolines (6-7)
3dab: 85%
3daa: 82%
3dac: 81%
N
N
N
OMe
N
H
N
Experimental
N
H
H
CO2Me
CO2Me
CO2Me
CF3
Br
F
OBn
3dae: 84%
3dad: 78%
3daf: 87%
All reactions were carried out under air and monitored by TLC
335 using Merck 60 F254 pre coated silica gel plates (0.25 mm
thickness) and the products were visualized by UV detection.
Flash chromatography was carried out with silica-gel (200-300
mesh). 1H and 13C NMR spectra were recorded on a Bruker
Avance (III) 400 MHz spectrometer. Data for 1H NMR are
340 reported as a chemical shift (δ ppm), multiplicity (s = singlet, d
N
N
N
N
H
N
N
H
H
280
CO2Me
CO2Me
CO2Me
NO2
3dag: 82%
3dah: 75%
3eaa: 79%
Furthermore, this catalyst-free one-pot MCR was then applied to
the synthesis of synthetically challenging (E)-2-styryl-substituted
γ-carboline frameworks. In this regard,
we performed the
=
doublet, q = quartet, m = multiplet), coupling constant J (Hz),
reactions between several β-aryl/alkyl-substituted acroleins with
integration, and assignment, data for 13C are reported as a
chemical shift. High resolutions mass spectral analyses (HRMS)
were carried out using ESI-TOF-MS. All the starting materials
345 were either synthesized by literature procedure or purchased from
commercial sources.
285 diverse steric and stereoelectronic environments, NH4OAc and
indole derivatives (1d-1e) in our imposed conditions.
Surprisingly, instead of 1,4-addition products, we have isolated
exclusively (E)-2-styryl-substituted γ-carbolines (3daa-3eaa) in
highly satisfactory yields (75-87%, Table 4). Notably, this is the
290 first successful report for the one-pot synthesis of (E)-2-styryl-
substituted γ-carboline scaffolds in an efficient and eco-friendly
manner.
Representative experimental procedure for the synthesis of
phenyl(3-phenyl-5H-pyrido[4,3-b]indol-4-yl)methanone (3aa):
350 A heterogeneous mixture of 2-(2-oxo-2-phenylethyl)-1H-indole-
3-carbaldehyde (52.6 mg, 0.2 mmol, 1a), benzaldehyde (25.2 mg,
0.24 mmol, 2a) and ammonium acetate (16.97 mg; 0.22 mmol) in
water (0.5 mL) at room temperature was stirred for 24h under air.
After that, the reaction mixture was concentrated under vacuum
After successfully employing β-substituted acroleins as
electrophiles, we then inspired to substitute them with a more
295 complicated electrophile like β-arylpropargylaldehyde in the
reaction with indole derivatives 1d-e
under our present
conditions. To our pleasant surprise, the same (E)-2-styryl- 355 to leave the crude residue which was purified by column
substituted γ-carbolines (3da-3ea) were obtained in mediocre
yields (39-45%, Scheme 3) with a single isomer. Therefore, it is a
300 great opportunity for the construction of these heterocycles by
using either alkenyl aldehydes or alkynyl aldehydes as
electrophiles.
chromatography over silica-gel using ethyl acetate/hexane (1:10)
as an eluent to furnish the pure γ-carboline (3aa, 61.9 mg) in 89%
yield.
All the products in Table 2-4 and Scheme 3 were synthesized by
360 following procedure. All the unknown products were
characterized by its spectroscopic data (1H, 13C NMR and
HRMS).
CHO
X
X
CHO
CO2Me
N
NH4OAc
305
310
315
Phenyl(3-phenyl-5H-pyrido[4,3-b]indol-4-yl)methanone (3aa):
1
Yield 89%; H NMR (400 MHz, CDCl3) δ 9.48 (br s, 1H), 9.40
H2O, rt, 24h
N
H
R
N
H
R
CO2Me
1d-e
2aa-2ah
3da-3ea
365 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.45-7.48 (m, 5H ), 7.29-7.33
(m, 1H), 7.18-7.22 (m, 2H), 7.40-7.11 (m, 5H); 13C NMR (100
MHz, CDCl3) δ 198.2, 155.3, 144.8, 143.6, 140.3, 140.1, 137.9,
132.6, 130.4, 129.5, 128.5, 128.1, 128.0, 127.5, 121.5, 121.2,
120.9, 119.8, 115.3, 111.5; HRMS (ESI) m/z calcd. For
1d: X = H
1e: X = Br
3da: X = H, R = C6H5; 41% yield
3dc: X = H, R = 4-MeOC6H4; 45% yield
3ea: X = Br, R = C6H5; 39% yield
Scheme 3 One-pot hetero-annulation reaction of alkynyl aldehydes with 370 C24H16N2O[M+H]+: 349.1335; Found 349.1332.
indole derivatives (1d-1e)
Phenyl{3-(4-methylphenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3ab): Yield 87%; H NMR (400 MHz, CDCl3) δ
9.53 (br s, 1H), 9.45 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H), 7.50-7.55

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DOI: 10.1039/C5RA08422A
(m, 4H), 7.43 (d, J = 8.0 Hz, 2H), 7.34-7.39 (m, 1H), 7.27-7.31
375 (m, 1H), 7.12-7.16 (m, 2H), 6.95 (d, J = 7.6 Hz, 2H), 2.20 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 198.2, 155.3, 144.8, 143.5,
153.0, 144.4, 143.7, 140.2, 139.3, 138.4, 133.2, 132.8, 132.3,
129.6, 129.07, 127.7, 127.7,126.4, 121.6, 121.0, 121.0, 120.4,
116.6, 111.6; HRMS (ESI) m/z calcd. For C24H15ClN2O [M+H]+:
140.0, 138.4, 137.8, 137.5, 132.5, 130.3, 129.5, 128.8, 127.9, 435 383.0946; Found 383.0948.
127.3, 121.4, 121.3, 120.8, 119.5, 115.0, 111.5, 21.1; HRMS
(ESI) m/z calcd. For C25H18N2O[M+H]+:363.1498; Found
380 363.1492.
Phenyl{3-(4-fluorophenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3ai): Yield 85%; H NMR (400 MHz, CDCl3) δ
9.46 (br s, 1H), 9.38 (s, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.46-7.49
Phenyl{3-(4-methoxyphenyl)-5H-pyrido[4,3-b]indol-4-
(m, 6H ), 7.23-7.33 (m, 2H), 7.08-7.13 (m, 2H) 6.76-6.80 (m,
yl}methanone (3ac): Yield 84%; H NMR (400 MHz, CDCl3) δ 440 2H); 13C NMR (100 MHz, CDCl3) δ 198.0, 161.9, 154.0, 144.8,
1
9.59 (br s, 1H), 9.36 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.40-7.47
(m, 6H ), 7.06-7.28 (m, 4H), 6.60 (d, J = 7.2 Hz, 2H), 3.61 (s,
385 3H); 13C NMR (100 MHz, CDCl3) δ 198.2, 159.9, 154.8, 144.8,
143.5, 140.0, 137.8, 132.9, 132.6, 131.7, 129.5, 128.0, 127.3,
143.6, 140.1, 137.8, 136.6, 132.8, 132.2, 132.1, 129.4, 128.1,
127.6, 121.6, 121.2, 120.9, 119.9, 115.2, 115.0, 111.5; HRMS
(ESI) m/z calcd. For C24H15FN2O [M+H]+: 367.1250; Found
367.1241.
121.4, 120.7; 119.4, 114.8, 113.6, 111.5, 55.2; HRMS (ESI) m/z 445 Phenyl{3-(4-trifluoromethylphenyl)-5H-pyrido[4,3-b]indol-4-
1
calcd. For C25H18N2O2[M+H]+:379.1441; Found 379.1444.
yl}methanone (3aj): Yield 89%; H NMR (400 MHz, CDCl3) δ
9.57 (br s, 1H), 9.48 (s, 1H), 8.22 (d, J = 7.6 Hz, 1H), 7.64-7.66
(m, 2H ), 7.50-7.54 (m, 4H), 7.39-7.41 (m, 3H) 7.29-7.30 (m,
1H), 7.14-7.17 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 197.8,
Phenyl{3-(2,5-dimethoxyphenyl)-5H-pyrido[4,3-b]indol-4-
1
390 yl}methanone (3ad): Yield 81%; H NMR (400 MHz, CDCl3) δ
9.65 (br s, 1H), 9.47 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H), 7.51-7.57
(m, 4H ), 7.28-7.38 (m, 3H), 7.15-7.19 (m, 2H), 6.62 (d, J = 7.6 450 153.6, 144.6, 143.7, 140.2, 137.7, 133.0, 130.6, 130.3, 130.0,
Hz, 1H), 6.36 (d, J = 8.8 Hz, 1H), 3.79 (s, 3H), 3.52 (s, 3H); 13
C
129.4, 128.6, 128.2, 127.8, 124.9 (m), 122.5, 121.7, 121.0, 120.4,
115.7, 111.6; HRMS (ESI) m/z calcd. For C25H15F3N2O [M+H]+:
417.1208; Found 417.1209.
NMR (100 MHz, CDCl3) δ 197.1, 153.6, 151.3, 150.2, 144.4,
395 143.8, 140.1, 137.6, 132.2, 130.1, 129.2, 127.5, 127.4, 121.3,
121,1, 120.8, 120.1, 116.8, 116.0, 111.4, 111.2, 55.9, 54.9;
Phenyl{3-(4-nitrophenyl)-5H-pyrido[4,3-b]indol-4-
HRMS (ESI) m/z calcd. For C26H20N2O3 [M+H]+: 409.1552; 455 yl}methanone (3ak): Yield 85%; H NMR (400 MHz, CDCl3) δ
1
Found 409. 1559.
9.57 (br s, 1H), 9.49 (s, 1H), 8.24 (d, J = 7.2 Hz, 1H), 8.02 (d, J =
7.6Hz, 2H ), 7.72 (d, J = 7.6 Hz, 2H), 7.53-7.56 (m, 4H), 7.31-
7.44 (m, 2H), 7.16-7.19 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
197.4, 152.3, 147.3, 146.6, 143.7, 140.3, 139.4, 137.7, 133.3,
Phenyl{3-(3-methoxy-4-benzyloxyphenyl)-5H-pyrido[4,3-
1
400 b]indol-4-yl}methanone (3ae): Yield 79%; H NMR (400 MHz,
1
CDCl3) δ H NMR (400 MHz, CDCl3) δ 9.50 (br s, 1H), 9.41 (s,
1H), 8.19 (d, J = 7.6 Hz, 1H), 7.50-7.54 (m, 4H), 7.38-7.42 (m, 460 131.1, 129.5, 128.3, 128.1, 123.2, 121.9, 121.1, 120.9, 120.7,
2H), 7.31-7.37 (m, 5H), 7.11-7.19 (m, 3H), 6.95-6.98 (m, 1H),
6.62 (d, J = 7.6 Hz, 1H), 5.04 (s, 2H), 3.85 (s, 3H); 13C NMR
405 (100 MHz, CDCl3) δ 198.2, 154.8, 149.3, 148.6, 144.9, 143.3,
140.1, 137.9, 136.8, 133.7, 132.5, 129.3, 128.5, 128.0, 127.8,
115.9, 111.7; HRMS (ESI) m/z calcd. For C24H15N3O3 [M+H]+:
394.1186; Found 394.1189.
Phenyl{3-(2-nitrophenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3al): Yield 82%; H NMR (400 MHz, CDCl3) δ
127.4, 127.1, 123.8, 121.5, 121.3, 120.8, 119.5, 115.0, 113.6, 465 9.64 (br s, 1H), 9.36 (s, 1H), 8.20 (d, J = 7.2 Hz, 1H), 7.78-7.80
113.5, 111.5, 70.8, 56.0; HRMS (ESI) m/z calculated For
C32H24N2O3 [M+H]+: 485.1869; Found 485.1860.
(m, 2H ), 7.41-7.56 (m, 2H), 7.30-7.40 (m, 1H),7.17-7.26 (m,
7H); 13C NMR (100 MHz, CDCl3) δ 197.5, 151.5, 148.8, 144.6,
143.8, 140.1, 138.4, 135.4, 133.4, 132.8, 131.7, 129.2, 129.0,
128.1, 127.8, 124.6, 121.7, 121.0, 120.9, 120.4, 116.0, 111.6;
410 Phenyl{3-(4-bromophenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3af): Yield 88%; H NMR (400 MHz, CDCl3) δ
9.49 (br s, 1H), 9.45 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.53-7.60 470 HRMS (ESI) m/z calcd. For C24H15N3O3 [M+Na]+ 416.1006;
(m, 4H ), 7.28-7.43 (m, 6H), 7.14-7.21 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 197.9, 153.8, 144.7, 143.6, 140.1, 139.4, 137.7,
415 132.9, 131.8, 131.2, 129.5, 128.2, 127.7, 123.1, 121.6, 121.1,
120.9, 120.0, 115.3, 111.6; HRMS (ESI) m/z calcd. For
C24H15BrN2O [M+H]+: 427.0441, 429.0421; Found 427.0441;
429.0426.
Found 416.1009.
Phenyl{3-(4-cyanophenyl)-5H-pyrido[4,3-b]indol-4-
yl}methanone (3am): Yield 84%; 1H NMR (400 MHz, CDCl3) δ
9.54 (br s, 1H), 9.48 (s, 1H), 8.23 (d, J = 7.6 Hz,1H), 7.65-7.67
475 (m, 2H ), 7.53-7.59 (m, 4H), 7.40-7.46 (m, 3H), 7.33-7.37 (m,
1H), 7.16-7.20 (m, 2H); 13C NMR (100 MHz, CDCl3) δ; 197.4,
152.8, 144.7, 144.5, 143.7, 140.3, 137.6, 133.2, 131.8, 130.9,
129.5, 128.3, 128.0, 121.8, 121.1, 120.9, 120.6, 118.6, 115.8,
111.9, 111.7; HRMS (ESI) m/z calcd. For C25H15N3O [M+H]+
Phenyl{3-(4-chlorophenyl)-5H-pyrido[4,3-b]indol-4-
1
420 yl}methanone (3ag): Yield 88%; H NMR (400 MHz, CDCl3) δ
9.56 (br s, 1H), 9.46 (s, 1H), 8.21 (d, J = 4.8 Hz, 1H), 7.47-7.53
(m, 6H), 7.34-7.31 (m, 2H), 7.13-7.18 (m, 4H); 13C NMR (100 480 374.1293; Found 374.1282.
MHz, CDCl3) δ 197.9, 153.7, 144.7, 143.5, 140.1, 138.7, 137.7,
134.7, 132.9, 131.5, 129.5, 128.3, 128.2, 127.7, 121.6, 121.1,
425 120.1, 120.0, 115.3, 111.6; HRMS (ESI) m/z calcd. For
C24H15ClN2O [M+H]+: 383.0946; Found 383.0947.
Phenyl{3-(2-furyl)-5H-pyrido[4,3-b]indol-4-yl}methanone
1
(3an): Yield 75%; H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H),
9.30 (br s, 1H), 8.18 (d, J = 7.2 Hz, 1H), 7.73-7.71 (m, 2H), 7.28-
7.51 (m, 6H ), 7.17-7.13 (s, 1H), 6.92 (s, 1H), 6.29 (s, 1H); 13C
485 NMR (100 MHz, CDCl3) δ 196.8, 152.9, 144.0, 143.9, 143.7,
143.6, 140.1, 138.1, 132.9, 128.7, 128.4, 127.5, 121.8, 121.3,
120.8, 119.7, 113.6, 112.1, 111.7, 111.5; HRMS (ESI) m/z calcd.
For C22H14N2O2[M+H]+ 339.1134; Found 339.1140
Phenyl{3-(2-chlorophenyl)-5H-pyrido[4,3-b]indol-4-
yl}methanone (3ah): Yield 84%; 1H NMR (400 MHz, CDCl3) δ
9.75 (br s, 1H), 9.49 (s, 1H), 8.23 (d, J = 7.2 Hz, 1H), 7.52-7.56
430 (m, 4H ), 7.27-7.42 (m, 3H), 7.15-7.19 (m, 2H), 7.08-7.11 (m,
2H), 7.00-7.03 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 198.0,

Page 7 of 11
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DOI: 10.1039/C5RA08422A
Phenyl{3-(2-thiophenyl)-5H-pyrido[4,3-b]indol-4-
490 yl}methanone (3ao): Yield 76%; 1H NMR (400 MHz, DMSO-
C25H17BrN2O [M+H]+ 441.0603, 443.0582; Found 441.0610,
443.0588
d6) δ 11.80 (br s, 1H), 9.45 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H) 7.75
4-Methylphenyl{3-(4-nitrophenyl)-5H-pyrido[4,3-b]indol-4-
(d, J = 7.6 Hz, 2H), 7.28-7.62 (m, 7H), 6.88-6.96 (m, 2H); 13C 550 yl}methanone (3bk): Yield 83%; 1H NMR (400 MHz, CDCl3) δ
NMR (100 MHz, DMSO-d6) δ 196.0, 144.0, 143.7, 143.1, 142.1,
140.8, 136.3, 134.3, 129.3, 129.1, 128.7, 127.9, 127.2, 127.0,
495 120.8, 120.8, 120.3, 118.7, 115.0, 112.0; HRMS (ESI) m/z calcd.
ForC22H14N2OS [M+H]+ 355.0905; Found 355.0899.
9.47 (br s, 2H), 8.22 (d, J = 6.0 Hz, 1H), 8.02-8.05 (m, 2H), 7.73-
7.76 (m, 2H), 7.41-7.54 (m, 5H ), 6.97-6.99 (m, 2H), 2.25 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 196.7, 151.7, 147.3, 146.6,
144.6, 144.3, 143.5, 140.2, 134.8, 131.0, 129.7, 129.1, 128.0,
555 123.2, 121.8, 121.1, 120.9, 120.6, 116.2, 111.65, 21.6; HRMS
(ESI) m/z calcd For C25H17N3O3 [M+H]+: 408.1343; Found
408.1347.
Phenyl{3-(4-butyl)-5H-pyrido[4,3-b]indol-4-yl}methanone
(3ap): Yield 73%; 1H NMR (400 MHz, CDCl3) δ 9.31 (br s, 1H),
8.90 (s, 1H), 8.14 (d, J = 7.8 Hz,1H), 7.82-7.84 (m, 2H), 7.62-
500 7.66 (m, 1H), 7.41-7.52 (m, 4H ), 7.32-7.36 (m, 1H), 2.73 (t, J =
8.0 Hz, 2H), 1.60-1.68 (m, 2H), 1.10-1.19 (m, 2H), 0.75 (t, J =
4-Methylphenyl{3-(4-cyanophenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3bl): Yield 86%; H NMR (400 MHz, CDCl3) δ
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 197.7, 156.9, 143.8, 560 9.46 (br s, 2H), 8.21 (d, J = 7.92 Hz, 1H), 7.68 (d, J = 7.8 Hz,
143.5, 139.6, 138.6, 133.7, 129.4, 128.9, 127.1, 121.3, 121.20,
120.6, 118.9, 116.3, 111.3, 37.0, 32.7, 22.5, 13.7; HRMS (ESI)
505 m/z calcd. For C22H20N2O [M+H]+ 329.1648; Found 329.1645.
2H), 7.38-7.57 (m, 7H), 6.98 (d, J = 7.76 Hz, 2H), 2.28 (s, 3H);
3C NMR (100 MHz, CDCl3) δ 196.8, 152.4, 144.9, 144.5, 144.4,
143.6, 140.3, 134.9, 131.8, 130.8, 129.8, 129.1, 128.0, 121.8,
121.0, 121.0, 120.5, 118.7, 116.1, 111.8, 111.7, 21.7; HRMS
Phenyl{3-(3-propyl)-5H-pyrido[4,3-b]indol-4-yl}methanone
1
(3aq): Yield 73%; H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 565 (ESI) m/z calcd. ForC26H17N3O[M+H]+ : 388.1445; Found
8.92 (s, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.82-7.83 (m, 2H), 7.62-
7.65 (m, 1H ), 7.41-7.51 (m, 4H), 7.32-7.35 (m, 1H), 2.72 (t, J =
510 7.6 Hz, 2H), 1.67-1.71 (m, 2H), 0.76 (t, J = 6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 197.7, 156.7, 143.7, 143.6, 139.6,
388.1444.
4-Methylphenyl
(3-butyl-5H-pyrido[4,3-b]indol-4-
yl)methanone (3bp): Yield 72%; 1H NMR (400 MHz, CDCl3) δ
9.22 (br s, 1H), 8.81 (s, 1H), 8.06 (d, J = 7.9 Hz, 1H), 7.65-7.67
138.6, 133.7, 129.4, 128.9, 127.1, 121.3, 120.6, 119.0, 116.4, 570 (d, J = 7.2 Hz, 2H), 7.33-7.41 (m, 2H ), 7.20-7.28 (m, 3H), 2.69
111.3, 39.3, 23.8, 13.9; HRMS (ESI) m/z calculated For
C21H18N2O [M+H]+ 315.1492; Found 315.1485.
(t, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.55-1.59 (m, 2H), 1.07-1.12 (m,
2H), 0.69 (t, J = 7.2 Hz, 3H).; 13C NMR (100 MHz, CDCl3) δ
197.0, 156.5, 144.9, 143.6, 143.2, 139.6, 135.8, 129.7, 127.1,
123.1, 121.3, 120.6, 118.9 116.6, 111.3, 36.8, 32.7, 22.5, 21.8,
515 Phenyl(3-ferrocenyl-5H-pyrido[4,3-b]indol-4-yl)methanone
1
(3ar): Yield 66%; H NMR (400 MHz, CDCl3) δ 9.36 (s, 1H),
9.16 (br s, 1H), 8.16 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 7.2 Hz, 2H), 575 13.75; HRMS (ESI) m/z calcd. For C23H22N2O [M+H]+
7.47-7.50 (m, 2H), 7.33-7.41 (m, 2H), 7.22-7.24 (m, 2H), 4.61
(s, 2H), 4.11 (s, 2H), 4.01 (s, 5H); HRMS (ESI) m/z calcd. For
520 C28H20FeN2O [M+H]+: 457.1003; Found 457.1051.
343.1810, Found 343.1787.
4-Methoxyphenyl(3-phenyl-5H-pyrido[4,3-b]indol-4-
1
yl)methanone (3ca): Yield 85%; H NMR (400 MHz, CDCl3) δ
9.59 (br s, 1H), 9.36 (s, 1H), 8.10 (d, J = 7.04 Hz, 1H), 7.40-7.47
4-Methylphenyl(3-phenyl-5H-pyrido[4,3-b]indol-4-
yl)methanone (3ba): Yield 84%; 1H NMR (400 MHz, CDCl3) δ 580 (m, 6H), 7.19-7.28 (m, 2H), 7.05-7.08 (m, 2H), 6.60 (d, J =
9.46 (br s, 1H), 9.39 (s, 1H), 8.21 (d, J = 7.9 Hz, 2H), 7.46-7.57
(m, 6H), 7.36-7.39 (m, 1H ), 7.14-7.20 (m, 3H), 6.94-6.96 (d, J =
525 7.76 Hz, 2H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
197.7, 156.3, 144.8, 143.5, 140.0, 138.4, 137.9, 137.5, 132.5,
7.2Hz, 2H), 3.61(s, 3H); 13C NMR (100 MHz, CDCl3) δ 13C
NMR (100 MHz, CDCl3) δ 196.2, 163.3, 154.2, 144.5, 143.2,
140.3, 140.1, 132.0, 130.4, 130.2, 128.4, 128.2, 127.4, 121.3,
121.2, 120.8, 119.7, 115.9, 113.4, 111.5, 55.3; HRMS (ESI) m/z
130.3, 129.5, 128.8, 128.0, 127.3, 121.4, 120.8, 119.5, 115.0, 585 calcd. For C25H18N2O2 [M+H]+ 379.1442; Found 379.1441.
111.5, 21.7; HRMS (ESI) m/z calcd. For C25H18N2O[M+H]+
4-Methoxyphenyl{3-(4-methylphenyl-5H-pyrido[4,3-b]indol-
1
4-yl)methanone (3cb): Yield 81%; H NMR (400 MHz, CDCl3)
363.1492; Found 363.1496.
530 4-Methylphenyl{3-(4-methoxyphenyl)-5H-pyrido[4,3-b]indol-
4-yl}methanone (3bc): Yield 82%; 1H NMR (400 MHz, acetone-
δ 9.42 (br s, 1H), 9.37 (s, 1H), 8.17 (d, J = 7.8 Hz, 2H), 7.58-7.60
(d, J = 7.8 Hz, 2H), 7.45-7.50 (m, 4H ), 7.33-7.37 (m, 1H), 6.99
d6) δ 11.22 (br s, 1H), 9.60 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H), 7.69 590 (d, J = 7.8 Hz, 2H), 6.65 (d, J = 8.28 Hz, 2H), 3.74 (s, 3H), 2.23
(d, J = 8.04 Hz, 1H), 7.54-7.60 (m, 5H), 7.39-7.43 (m, 1H), 7.10
(d, J = 7.5 Hz, 2H), 6.80 (d, J = 7.3 Hz, 2H), 3.71 (s, 3H), 2.26
535 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 195.4, 161.5, 150.6,
145.3, 142.2, 141.2, 135.4, 132.4, 130.6, 130.5, 129.9, 129.0,
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.3, 163.3, 154.3,
154.3, 144.6, 143.2, 140.0, 138.4, 132.1, 130.4, 128.9, 127.3,
121.4, 120.8, 119.5 115.6, 113.4, 111.4, 55.4, 21.2; HRMS (ESI)
m/z calcd. For C26H20N2O2 [M+H]+: 393.1598; Found 393.1594.
128.8, 122.6, 122.0, 121.9, 120.3, 117.5, 114.5, 113.2, 55.6, 21.5; 595 4-Methoxyphenyl{3-(4-methoxyphenyl-5H-pyrido[4,3-
1
HRMS (ESI) m/z calcd. For C26H20N2O2 [M+H]+: 393.1598;
Found 393.1594.
b]indol-4-yl)methanone (3cc): Yield 77%; H NMR (400 MHz,
CDCl3) δ 9.41 (br s, 1H), 9.38 (s, 1H), 8.17 (d, J = 7.8 Hz, 2H),
7.53-7.60 (m, 4H), 7.45-7.49 (m, 2H), 7.33-7.37 (m, 1H), 6.72 (d,
J = 8.04 Hz, 2H), 6.65 (d, J = 8.2 Hz, 2H), 3.74 (s, 3H), 3.72 (s,
540 4-Methylphenyl{3-(4-bromophenyl)-5H-pyrido[4,3-b]indol-4-
1
yl}methanone (3bf): Yield 84%; H NMR (400 MHz, CDCl3) δ
9.39 (br s, 2H), 8.14 (d, J = 3.6 Hz, 1H), 7.32-7.53 (m, 7H), 7.20- 600 3H); 13C NMR (100 MHz, CDCl3) δ 196.3, 163.3, 159.9, 153.9,
7.26 (m, 2H), 6.92-6.94 (m, 2H), 2.22 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 196.0, 151.9, 143.6, 143.2, 142.1, 139.1, 137.7,
545 133.7, 130.7, 130.3, 128.7, 128.1, 128.0, 126.7, 122.2, 120.6,
120.0, 118.9, 114.6, 110.6, 20.6; HRMS (ESI) m/z calcd. For
144.6, 143.2, 140.0, 133.0, 132.0, 131.5, 130.3, 127.2, 121.3,
120.7, 119.3 115.3, 113.9, 113.4, 111.4, 55.3, 55.2; HRMS (ESI)
m/z calcd. For C26H20N2O3[M+H]+ 409.1547; Found 409.1578.
4-Methoxyphenyl{3-(2,5-dimethoxyphenyl-5H-pyrido[4,3-

RSC Advances
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DOI: 10.1039/C5RA08422A
605 b]indol-4-yl)methanone (3cd): Yield 75%; 1H NMR (400 MHz,
CDCl3) δ 9.52 (br s, 1H), 9.45 (s, 1H), 8.18 (d, J = 7.8 Hz, 2H),
7.59-7.62 (d, J = 8.52 Hz, 2H), 7.47-7.55 (m, 2H ), 7.34-7.37 (m, 665 9.27 (s, 1H), 8.12 (d, J = 7.76 Hz, 1H) 7.50 (m, 2H), 7.34 (m,
Methyl
3-ferrocenyl-5H-pyrido[4,3-b]indole-4-carboxylate
(3dr): Yield 78%; 1H NMR (400 MHz, CDCl3) δ 9.45 (br s, 1H),
1H), 7.26-7.28 (m, 1H), 6.65-6.67 (m, 3H), 6.43 (d, J = 9.0 Hz,
2H), 3.79 (s, 3H), 3.76 (s, 3H), 3.51 (s, 3H); 13C NMR (100
610 MHz, CDCl3) δ 195.3, 163.0, 153.7, 150.8, 150.3, 144.3, 143.5,
140.2, 131.8, 130.2, 130.1, 127.4, 121.3, 120.8, 120.8120.2,
1H), 4.83 (s, 2H ), 4.41 (s, 2H), 4.07 (s, 5H), 3.86 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 169.1, 155.6, 144.4, 143.1, 139.7,
126.9, 121.3, 120.4, 117.9, 111.3, 107.6, 85.7, 70.3, 70.0, 69.1,
52.0; HRMS (ESI) m/z calcd For C23H18FeN2O2 [M+H]+:
120.0, 117.0, 116.6, 116.0, 115.7, 113.0, 112.9, 111.4, 111.3, 670 411.0796; Found 411.0790.
56.0, 55.4, 55.0; HRMS (ESI) m/z calcd. For C27H22N2O4
[M+H]+: 439.1652; Found 439.1666.
Methyl 3-propyl-5H-pyrido[4,3-b]indole-4-carboxylate (3dq)
6a: Yield 83%.
615 4-Methoxyphenyl{3-(4-chlorophenyl)-5H-pyrido[4,3-b]indol-
1
4-yl}methanone (3cg): Yield 86%; H NMR (400 MHz, CDCl3)
Methyl
3-(2-phenylethyl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3du)6a: Yield 86%.
δ 9.43 (s, 1H), 9.27 (br s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.50-7.58 675 Methyl
3-{2-(tert-butoxycarbonyl)amino)ethyl}-5H-
1
(m, 6H), 7.36-7.40 (m, 1H), 7.18 (d, J = 8.0 Hz, 2H), 6.68 (d, J =
8.4 Hz, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 195.9,
620 163.6, 152.7, 144.4, 143.2, 140.1, 138.8, 138.7, 134.7, 132.1,
131.4, 130.1, 128.4, 127.6, 127.5, 121.6, 120.9, 119.9, 113.6,
pyrido[4,3-b]indole-4-carboxylate (3dv): Yield 79%; H NMR
(400 MHz, CDCl3) δ 10.03 (br s, 1H), 9.24 (s, 1H), 8.10 (d, J =
7.6 Hz, 1H), 7.48-7.52 (m, 2H), 7.32-7.36 (m, 1H), 5.37 (br s,
1H), 4.07 (s, 3H), 3.64-3.66 (m, 2H), 3.52-3.53 (m, 2H), 1.40 (s,
111.5, 55.5; (ESI) m/z calcd. For C25H17N2O2Cl [M+H]+: 680 9H); 13C NMR (100 MHz, CDCl3) δ 167.9, 157.5, 156.0, 145.5,
413.1053; Found 413.1051.
143.9, 139.6, 127.3, 121.4, 120.9, 120.6, 119.7, 111.4, 107.7,
78.8, 52.4, 39.9, 37.6, 28.4; HRMS (ESI) m/z calcd. For
C20H23N3O4 [M+H]+: 370.1767; Found 370.1760.
4-Methoxyphenyl{3-(4-nitrophenyl)-5H-pyrido[4,3-b]indol-4-
1
625 yl}methanone (3ck): Yield 81%; H NMR (400 MHz, CDCl3) δ
9.45 (br s, 2H), 8.21 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 8.0 Hz, 2H),
Methyl
3-{1-(benzyloxycarbonyl)amino)methyl}-5H-
7.76-7.78 (m, 2H), 7.49-7.57 (m, 4H), 7.37-7.41 (m, 1H), 6.66 (d, 685 pyrido[4,3-b]indole-4-carboxylate (3dw): Yield 74%; 1H NMR
J = 7.6 Hz, 2H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
195.3, 163.9, 151.3, 147.4, 146.6, 144.1, 143.4, 140.3, 132.1,
630 130.9, 130.0, 127.9, 123.3, 121.7, 121.0, 120.9, 120.5, 116.5,
113.7, 111.6, 55.4; HRMS (ESI) m/z calcd. For C25H17N3O4
[M+H]+: 424.1291; Found 424.1292.
(400 MHz, CDCl3) δ 10.12 (br s, 1H), 9.20 (s, 1H), 8.10 (d, J =
7.6Hz, 1H), 7.51-7.55 (m, 2H), 7.31-7.43 (m, 6H), 6.85 (br s,
1H), 5.19 (s, 2H), 4.99 (d, J = 4.8Hz, 2H), 4.06 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.4, 156.5, 153.1, 145.6, 143.3, 139.8,
690 136.8, 128.5, 128.1, 128.0, 127.7, 121.5, 120.8, 120.7, 120.6,
111.5, 106.04, 66.7, 52.5, 45.8; HRMS (ESI) m/z calcd. For
C22H19N3O4 [M+H]+: 390.1448; Found 390.1447.
4-Methoxyphenyl{3-(2-furyl)-5H-pyrido[4,3-b]indol-4-
yl)methanone (3cn): Yield 73%; 1H NMR (400 MHz, CDCl3) δ
635 9.28 (br s, 1H), 9.16 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.66 (d, J =
8.04 Hz, 2H), 7.36-7.47 (m, 2H), 7.26-7.28 (m, 1H), 7.13 (s, 1H),
Methyl
8-bromo-3-phenyl-5H-pyrido[4,3-b]indole-4-
1
carboxylate (3ea): Yield 91%; H NMR (400 MHz, CDCl3) δ
6.85 (s, 1H), 6.70 (d, J = 8.0 Hz, 2H), 6.25 (s, 1H), 3.72 (s, 3H); 695 9.92 (br s, 1H), 9.33 (s, 1H), 8.29 (s, 1H), 7.62 (d, J = 8.4 Hz, 1H
13C NMR (100 MHz, CDCl3) δ 193.9, 162.5, 151.9, 142.7,
142.6, 142.3, 142.1, 139.0, 130.3, 129.7, 126.4, 120.4,
640 120.3,119.7, 118.5, 113.1, 112.7, 111.0, 110.4, 54.4; HRMS
(ESI) m/z calcd. For C23H16N2O3[M+H]+ 369.1286; Found:
369.1239.
), 7.56 (d, J = 6.4 Hz, 2H), 7.42-7.44 (m, 4H), 3.70 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 168.3, 157.5, 145.5, 144.0, 141.5,
138.5, 130.3, 129.1, 128.3, 127.9, 123.7, 122.9, 118.8, 114.4,
112.9, 107.8, 52.0; HRMS (ESI) m/z calcd. For C19H13BrN2O2
700 [M+H]+: 381.0239, 383.0218; Found 381.0233, 383.0215.
Methyl
(3da)6a: Yield 90%.
3-(4-methylphenyl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3db)6a: Yield 88%.
Methyl
carboxylate (3dc)6a: Yield 84%.
3-phenyl-5H-pyrido[4,3-b]indole-4-carboxylate
Methyl
8-bromo-3-(2-tert-butoxycarbonylaminoethyl)-5H-
1
pyrido[4,3-b]indole-4-carboxylate (3ev): Yield 81%; H NMR
(400 MHz, DMSO-d6) δ 11.65 (br s, 1H), 9.39 (s, 1H), 8.48 (s,
1H), 7.59-7.65 (m, 2H), 6.78 (br s, 1H), 3.99 (s, 3H), 3.34 (s,
645 Methyl
3-(4-methoxyphenyl)-5H-pyrido[4,3-b]indole-4- 705 4H), 1.32 (s, 9H); 13C NMR (100 MHz, DMSO-d6) δ 166.3,
156.9, 155.4, 144.8, 143.6, 138.9, 129.4, 123.1, 122.3, 118.0,
114.1, 112.8, 118.5, 77.3, 52.3, 52.2, 37.0, 28.2; HRMS (ESI)
m/z calcd. For C20H22BrN3O4 [M+H]+: 448.0872, 450.0851;
Found 448.0865, 450.0850.
Methyl
3-(3-methoxy-4-benzyloxyphenyl)-5H-pyrido[4,3-
650 b]indole-4-carboxylate (3de)6a: Yield 82%.
Methyl
3-(4-bromophenyl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3df)6a: Yield 88%.
710 Methyl
8-bromo-3-isopropyl-5H-pyrido[4,3-b]indole-4-
1
Methyl
3-(4-chlorophenyl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3ex): Yield 85%; H NMR (400 MHz, CDCl3) δ
carboxylate (3dg)6a: Yield 91%.
9.93 (br s, 1H), 9.29 (s, 1H), 8.22 (s, 1H), 7.58 (d, J = 8.4 Hz,
1H), 7.40 (d, J = 8.4Hz, 1H), 4.12-4.19 (m, 1H), 4.08 (s, 3H),
1.40 (s, 3H), 1.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.0,
655 Methyl
3-(2-nitrophenyl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3dl)6a: Yield 87%.
Methyl
pyrido[4,3-b]indole-4-carboxylate (3ds)6a: Yield 78%.
Methyl 3-(2-furyl)-5H-pyrido[4,3-b]indole-4-carboxylate
660 (3dn)6a: Yield 84%.
3-{2-(tetr-butoxycarbonyl)amino)phenyl}-5H- 715 145.6, 144.4, 138.1, 129.9, 123.3, 123.0, 118.0, 114.2, 112.7,
107.0, 52.4, 32.8, 22.8; HRMS (ESI) m/z calcd. For
C16H15BrN2O2 [M+H]+: 347.0390, 349.0370; Found 347.0395,
347.0374.
Methyl
3-{1-(tetr-butoxycarbonyl)-1H-indol-3yl}-5H-
Methyl 8-bromo-3-(2-thiophenyl)-5H-pyrido[4,3-b]indole-4-
1
720 carboxylate (3eo): Yield 85%; H NMR (400 MHz, DMSO-d6)
pyrido[4,3-b]indole-4-carboxylate (3dt)6a: Yield 81%.

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DOI: 10.1039/C5RA08422A
δ 11.97 (br s, 1H), 9.41 (s, 1H), 8.52 (s, 1H), 7.57-7.68 (m, 3H),
7.31 (d, J = 3.6 Hz, 1H), 7.13-7.15 (m, 1H), 3.95 (s, 3H); 13C 780 144.9, 144.4, 140.8, 139.6, 134.0, 129.1, 127.4, 127.4, 125.6 (m),
1H), 4.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.5, 151.8,
NMR (100 MHz, DMSO-d6) δ 167.1, 145.4, 144.1, 143.4, 142.7,
139.4, 129.7, 128.9, 128.1, 126.8, 123.5, 122.4, 117.9, 114.0,
725 113.0, 108.4, 52.9; HRMS (ESI) m/z calcd. For C17H11BrN2O2S
[M+H]+: 386.9791, 388.9772; Found 386.9797, 388.9777.
121.5, 121.0, 120.6, 119.9, 111.4, 106.7, 52.5; HRMS (ESI) m/z
calcd. For C22H15F3N2O2 [M+H]+: 397.1164; Found 397.1170.
(E)-Methyl
3-(4-fluorostyryl)-5H-pyrido[4,3-b]indole-4-
carboxylate (3daf): Yield 87%; 1H NMR (400 MHz, CDCl3) δ
Methyl
8-bromo-3-ferrocenyl-5H-pyrido[4,3-b]indole-4- 785 9.95 (br s, 1H), 9.31 (s, 1H), 8.26 (d, J = 16.0 Hz, 1H), 8.13 (d, J
1
carboxylate (3er): Yield 82%; H NMR (400 MHz, CDCl3) δ
9.48 (br s, 1H), 9.21 (s, 1H), 8.23 (s, 1H), 7.57 (d, J = 7.2 Hz,
730 1H), 7.37 (d, J = 7.2 Hz, 1H), 4.82 (s, 2H), 4.42 (s, 2H), 4.06 (s,
5H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.9, 156.6,
= 7.6 Hz, 1H), 7.97 (d, J = 16.0 Hz, 1H), 7.61-7.65 (m, 2H), 7.48-
7.54 (m, 2H), 7.33-7.36 (m, 1H), 7.06-7.11 (m, 2H), 4.14 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 167.5, 162.7 (d, J = 240Hz),
152.4, 144.9, 144.2, 139.5, 134.5, 133.5, 129.0, 127.1, 126.4,
144.8, 143.4, 138.3, 129.6, 123.4, 123.2, 116.9, 114.2, 112.7, 790 121.1, 120.4, 119.5, 115.7, 115.5, 111.3, 106.1, 52.4; HRMS
107.6, 85.5, 70.4, 70.1, 69.3, 51.9; HRMS (ESI) m/z calcd. For
C23H17BrFeN2O2 [M+H]+: 488.9901, 490.9881; Found 488.9982,
735 490.9821.
(ESI) m/z calcd. For C21H15FN2O2 [M+H]+: 347.1190. Found
347.1196.
(E)-methyl
carboxylate: (3dag): Yield 82%; H NMR (400 MHz, DMSO-
(3daa): Yield 82%; H NMR (400 MHz, CDCl3) δ 9.97 (br s, 795 d6)δ 11.67 (br s, 1H), 9.50 (s, 1H), 8.40 (d, J = 16.0 Hz, 1H),
3-(4-nitrostyryl)-5H-pyrido[4,3-b]indole-4-
1
(E)-Methyl
3-styryl-5H-pyrido[4,3-b]indole-4-carboxylate
1
1H), 9.32 (s, 1H), 8.34 (d, J = 16.0 Hz, 1H), 8.12 (d, J = 7.6 Hz,
1H), 8.00 (d, J = 16.0 Hz, 1H), 7.66-7.68 (m, 2H), 7.48-7.51 (m,
740 2H), 7.32-7.41 (m, 4H), 4.13 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.7, 152.5, 145.1, 144.3, 139.5, 137.2, 135.8, 128.7,
8.25-8.29 (m, 3H), 8.05 (d, J = 16.0 Hz, 1H), 7.93 (d, J = 7.6 Hz,
2H), 7.72 (d, J = 8.0 Hz, 1H), 7.50-7.55 (m, 1H), 7.30-7.34 (m,
1H), 4.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.2, 149.6,
146.7, 144.5, 143.5, 142.9, 140.6, 131.9, 130.7, 128.0, 127.4,
128.3, 127.5, 127.2, 126.7, 121.4, 121.2, 120.5, 119.5, 111.3, 800 124.2, 121.0, 120.7, 120.4, 119.8, 112.3, 108.5, 52.7; HRMS
106.3, 52.5; HRMS (ESI) m/z calcd. For C21H16N2O2 [M+H]+:
(ESI) m/z calcd. For C21H15N3O4 [M+H]+: 374.1141; Found
329.1285; Found 329.1287.
374.1148.
745 (E)-Methyl
3-(4-methylstyryl)-5H-pyrido[4,3-b]indole-4-
(E)-Methyl 3-pentenyl-5H-pyrido[4,3-b]indole-4-carboxylate
carboxylate (3dab): Yield 85%; 1H NMR (400 MHz, CDCl3) δ
9.97 (br s, 1H), 9.31 (s, 1H), 8.30 (d, J = 15.8 Hz, 1H), 8.12 (d, J 805 1H), 9.26 (s, 1H), 8.10 (d, J = 8 .0 Hz, 1H), 7.47-7.54 (m, 3H),
(3dah): Yield 75%; H NMR (400 MHz, CDCl3) δ 9.94 (br s,
1
= 7.6 Hz, 1H), 7.98 (d, J = 15.8 Hz, 1H), 7.47-7.57 (m, 4H), 7.32-
7.36 (m, 1H), 7.20 (d, J = 7.8 Hz, 2H), 4.13 (s, 3H), 2.38 (s, 3H);
750 13C NMR (100 MHz, CDCl3) δ 167.8, 152.8, 145.2, 144.4,
139.5, 138.4, 135.8, 134.5, 229.4, 127.4, 127.0, 125.8, 121.3,
7.30-7.34 (m, 1H), 7.10-7.14 (m, 1H), 4.08 (s, 3H), 2.32-2.37 (m,
2H), 1.58-1.65 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 167.9, 153.0, 145.2, 144.3, 139.3, 128.5, 126.9,
121.3, 121.2, 120.4, 119.2, 111.2, 111.3, 105.6, 52.2, 35.4, 22.2,
121.2, 120.4, 119.3, 111.3, 106.1, 52.4, 21.4; HRMS (ESI) m/z 810 13.9; HRMS (ESI) m/z calcd. For C18H18N2O2[M+H]+: 295.1447.
calcd. For C22H18N2O2 [M+H]+: 343.1441; Found 343.1442.
Found 295.1443.
(E)-Methyl 3-(4-methoxystyryl)-5H-pyrido[4,3-b]indole-4-
755 carboxylate (3dac): Yield 81%; 1H NMR (400 MHz, CDCl3) δ
9.96 (br s, 1H), 9.33 (s, 1H), 8.42 (d, J = 15.8 Hz, 1H), 8.14 (d, J
(E)-Methyl
8-bromo-3-styryl-5H-pyrido[4,3-b]indole-4-
1
carboxylate (3eaa): Yield 79%; H NMR (400 MHz, CDCl3) δ
10.02 (br s, 1H), 9.26 (s, 1H), 8.33 (d, J = 15.8 Hz, 1H), 8.26 (s,
= 7.6 Hz, 1H), 8.00 (d, J = 15.8Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 815 1H), 8.03 (d, J = 15.8 Hz, 1H), 7.58-7.68 (m, 3H), 7.30-7.42 (m,
7.64 (d, J = 8.0 Hz, 2H), 7.49-7.55 (m, 2H), 7.34-7.38 (m, 1H),
4.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.8, 159.9, 153.0,
760 145.2, 144.4, 139.6, 135.5, 130.6, 130.2, 128.9, 127.0, 124.6,
121.3, 121.3, 120.4, 119.2, 114.1, 111.3, 55.3, 52.4; HRMS (ESI)
m/z calcd. For C22H18N2O3 [M+H]+: 359.1390; Found 359.1398.
(E)-Methyl 3-(3-methoxy-4-benzyloxystyryl)-5H-pyrido[4,3-
b]indole-4-carboxylate (3dad): Yield 78%; 1H NMR (400
765 MHz, DMSO-d6) δ 9.96 (br s, 1H), 9.30 (s, 1H), 8.21 (d, J =
15.8Hz, 1H), 8.12 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 15.8 Hz, 1H),
4H), 4.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.7, 145.6,
144.8, 138.2, 137.2, 136.5, 130.0, 128.7, 128.5, 128.4, 127.6,
126.5, 123.3, 123.0, 118.6, 114.8, 112.8, 106.4, 52.6; HRMS
(ESI) m/z calcd. For C21H15BrN2O2 [M+H]+: 407.2679,
820 409.0375; Found 407.2671, 409.0384.
tert-Butyl 1-oxo-1H-benzo[h]indolo[3,2-c][1,6]naphthyridine-
2(13H)-carboxylate (6): Yield 76%; 1H NMR (400 MHz,
CDCl3) δ 10.63 (br s,1H), 9.58 (s, 1H), 8.97 (d, J = 8.04 Hz,
1H), 8.19 (d, J = 7.76 Hz, 1H), 7.50-7.61 (m, 3H), 7.41-7.46 (m,
7.44-7.53 (m, 4H), 7.29-7.40 (m, 4H), 7.18-7.21 (m, 2H), 6.90 (d, 825 1H), 7.35-7.39 (m, 1H), 7.23-7.25 (m, 1H), 1.78 (s, 9H) ; 13C
J = 8.0 Hz, 1H), 5.20 (s, 2H), 4.12 (s, 3H), 3.97 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.7, 152.8, 149.6, 148.7, 145.1,
770 144.3, 139.5, 136.9, 135.6, 130.9, 128.5, 127.8, 127.2, 127.0,
125.0, 121.3, 121.2, 120.6, 120.4, 119.2, 113.8, 111.3, 110.7,
NMR (100 MHz, CDCl3) δ 161.0, 150.7, 147.7, 146.8, 143.0,
139.7, 135.1, 130.7, 127.2, 125.9, 123.9, 121.7, 121.0, 120.6,
119.4, 114.1, 111.9, 105.4, 87.0, 27.7; HRMS (ESI) m/z calcd.
For C23H19N3O3 [M+H]+: 386.1505; Found 386.1499.
105.9, 70.9, 55.9, 52.3; HRMS (ESI) m/z calcd. For C29H24N2O4 830 tert-Butyl
[M+H]+: 465.1809; Found 465.1814.
(E)-Methyl 3-(4-trifluorostyryl)-5H-pyrido[4,3-b]indole-4-
10-bromo-1-oxo-1H-benzo[h]indolo[3,2-
c][1,6]naphthyridine-2(13H)-carboxylate (7): Yield 79%;
Yield 79%; 1H NMR (400 MHz, CDCl3) δ 10.68 (br s, 1H), 9.57
(s, 1H), 8.99 (d, J = 8.0 Hz, 1H), 8.35 (s, 1H), 7.60-7.65 (m, 2H),
7.45-7.49 (m, 2H), 7.25 (s, 1H), 1.77 (s, 9H); HRMS (ESI) m/z
1
775 carboxylate (3dae): Yield 84%; H NMR (400 MHz, CDCl3) δ
9.96 (br s, 1H), 9.33 (s, 1H), 8.42 (d, J = 15.8 Hz, 1H), 8.14 (d, J
= 7.6 Hz, 1H), 8.00 (d, J = 15.8 Hz, 1H), 7.74 (d, J = 8.0 Hz, 835 calcd. For C23H18BrN3O3 [M+H]+: 464.0604, 466.0585; Found
2H), 7.64 (d, J = 8.0 Hz, 2H), 7.49-7.55 (m, 2H), 7.34-7.38 (m, 464.0560, 466.0564.

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DOI: 10.1039/C5RA08422A
M. N. Sabbagh and H. A. Shill, Curr. Opin. Invest. Drugs, 2010, 11,
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J. Med. Chem., 1987, 30, 1818.
Conclusions
900
905
910
915
920
925
930
935
940
In summary, we have developed a general, catalyst-free, simple,
840 mild, convenient and green method for the synthesis of
biologically interesting functionalized γ-carboline derivatives
4. γ-Carboline synthesis, see (a) H. Dong, R. T. Latka and T. G. Driver,
Org. Lett., 2011, 13, 2726; (b) Chen, W. Chen and Y. Hu, Synlett,
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via
between
aromatic/alkyl/alkenyl/alkynyl/ferrocenyl
845 ammonium acetate as an inexpensive N-supplier in water at room
temperature under aerobic conditions. Our current MCR
a
one-pot three-component hetero-annulation reaction
3-formyl indoles, aromatic/hetero-
aldehydes and
technique provides good to excellent yields of title compounds,
thus it ensures a broad substrate scope and allows a wide range of
synthetically useful functional groups. Very interestingly, this
850 chemistry could be applied for the synthesis of same (E)-2-styryl-
substituted γ-carboline derivatives by employing either alkenyl
aldehydes or alkynyl aldehydes. In addition, the quinolinone
fused γ-carboline derivatives have been achieved in a practical
manner through our methodology. Further exploration into the
855 potential substrates scope and test their biological activities are in
progress in our laboratory which will be documented in due
course
Acknowledgements
6. (a) S. Biswas, P. K. Jaiswal, S. Singh, S. M. Mobin and S. Samanta,
Org. Biomol. Chem., 2013, 11, 7084; (b) S. Biswas, D. Majee, A.
Dagar and S. Samanta, Synlett, 2014, 25, 2115; (c) P. K. Jaiswal, S.
Biswas, S. Singh and S. Samanta, Org. Biomol. Chem., 2013, 11,
8410; (d) P. K. Jaiswal, S. Biswas, S. Singh, B. Pathak, S. M. Mobin,
S. Samanta, RSC Adv. 2013, 3, 10644‒106449; (e) S. Singh, A.
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Singh, A. Srivastava, S. M. Mobin and S. Samanta, RSC Adv., 2015,
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Samanta, RSC Adv., 2015, 5, 26891.
The authors thank the DST, Govt. of India research grant (Project
860 No. SB/S1/OC-19/2013). S. Biswas is thankful to his UGC
fellowship. Authors are also thankful to Mr. K. Pandey for
recording the NMR spectra.
Notes and references
a Indian Institute of Technology, Department of Technology,
865 Indore, Madhya Pradesh, India. Fax: 917312364182; Tel: 91 731
2438742; E-mail: sampaks@iiti.ac.in
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G. Abbiati, Org. Biomol. Chem., 2014, 12, 8019.
† Electronic Supplementary Information (ESI) available: [copies
of all unknown compounds 1H and 13C NMR spectra are attached.
See DOI: 10.1039/b000000x/
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