Three-component tandem-intramolecular hydroamination reactions in one pot involving indoles, 2-aminobenzyl alcohols, and 2-alkynylbenzaldehydes: Consecutive 7-endo-trig and electrophilic 6-endo-dig cyclizations

Article abstract of DOI:10.1002/ejoc.201300100

A one-pot protocol for the synthesis of indole-based annulated polyheterocycles involving consecutive 7-endo-trig and electrophilic 6-endo-dig cyclizations is described. The reaction proceeds initially through annulation of 5-methoxyindole, 2-amino benzyl

Full text of DOI:10.1002/ejoc.201300100

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FULL PAPER
Tandem Reactions
S. Samala, M. Saifuddin,
A. K. Mandadapu, B. Kundu* ......... 1–11
Three-Component Tandem-Intramolecular
Hydroamination Reactions in One Pot In-
volving Indoles, 2-Aminobenzyl Alcohols,
and 2-Alkynylbenzaldehydes: Consecutive
7-endo-trig and Electrophilic 6-endo-dig
Cyclizations
A one-pot three-component tandem reac-
tion with a subsequent intramolecular hy-
droamination reaction was applied to gen-
erate libraries of benzazepino-indole and
isoquinolino-benzazepino-indole deriva-
tives.
Keywords: Multicomponent reactions
Nitrogen heterocycles Cyclization
Hydroamination / Polycycles
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Date: 18-04-13 16:26:03
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S. Samala, M. Saifuddin, A. K. Mandadapu, B. Kundu
FULL PAPER
DOI: 10.1002/ejoc.201300100
Three-Component Tandem-Intramolecular Hydroamination Reactions in One
Pot Involving Indoles, 2-Aminobenzyl Alcohols, and 2-Alkynylbenzaldehydes:
Consecutive 7-endo-trig and Electrophilic 6-endo-dig Cyclizations[‡]
Srinivas Samala,[a] Mohammad Saifuddin,[a] Anil K. Mandadapu,[a] and Bijoy Kundu*[a]
Keywords: Multicomponent reactions / Nitrogen heterocycles / Cyclization / Hydroamination / Polycycles
A one-pot protocol for the synthesis of indole-based annu-
lated polyheterocycles involving consecutive 7-endo-trig and
electrophilic 6-endo-dig cyclizations is described. The reac-
tion proceeds initially through annulation of 5-methoxy-
indole, 2-amino benzyl alcohol and 2-alkynylbenzaldehyde
in a three-component tandem manner to form benzazepino-
indole, which then undergoes a second consecutive ring clo-
sure through intramolecular hydroamination to yield isoquin-
olino-benzazepino-indoles hitherto not reported in the litera-
ture.
in situ second consecutive intramolecular annulation in-
volving the alkyne moiety and the secondary amine as a
post-multicomponent transformation. In recent years,
multicomponent strategies have been combined with post-
multicomponent transformation reactions either as one-pot
or tandem processes by us[9] and others[10] with the view to
generate annulated polyheterocycles with increased archi-
tectural complexity. Herein, we report fast and versatile
one-pot three component tandem-intramolecular hydro-
amination[11] reactions to furnish annulated pentacyclic in-
dole-based polyheterocycles in good yields.[12]
Introduction
Indole-based annulated polyheterocycles are ubiquitous
structures isolated from plants, fungi and marine organ-
isms.[1] These annulated polyheterocycles feature structur-
ally diverse frameworks arising from the combination of
privileged heterocycles fused to an indole moiety.[2] In the
literature, both synthetic and naturally occurring indole-
based annulated polyheterocycles are reported to be associ-
ated with a wide range of biological activities[3] and there-
fore remain inspiration for new indole-based polyhetero-
cyclic chemical entities for chemical biology research. As
part of our continuing effort on the development of
multistep[4]/three-component reactions[5] for the synthesis of
indole-based annulated polyheterocycles, we embarked on
the combination of a multi-component reaction with a
post-multicomponent transformation of the resulting prod-
uct in a one-pot strategy. We envisaged that by introducing
ring-forming reactions in both steps in one pot, a new
method for indole-based annulated polyheterocycles with
enhanced architectural complexity and diversity[6] could be
accomplished. To achieve this, we proposed an intermo-
lecular annulation[7] by treating indole with 2-aminobenzyl
alcohol and 2-alkynylbenzaldehyde in a three-component
reaction with a view to generating a seven-membered ring
annulated to the indole at C-3 and C-2 through a modified
Pictet–Spengler cyclization route.[8] Next, we proposed an
Results and Discussion
Our studies commenced with development of a method-
ology for the annulation of 5-methoxyindole (1a), 2-amino-
benzyl alcohol (2a), and 4-chlorobenzaldehyde (3a) in a
three-component reaction to give benzazepinoindole 5aaa.
Initial attempts at a three-component annulation reaction
failed, which prompted us to carry out the annulation as
a three-component tandem reaction by first allowing the
condensation of 5-methoxyindole (1a) with 2-aminobenz-
ylalcohol (2a) in the presence of trifluoroacetic acid (TFA)
followed by the addition of 4-chlorobenzaldehyde (3a) as
the third component. The conditions for the tandem reac-
tion were optimized by monitoring the progress of the reac-
tion for both steps involving C-3 alkylation of indole 1a
followed by 7-endo-trig cyclization (the modified Pictet–
Spengler cyclization reaction) by TLC/HPLC and the re-
sults are summarized in Table 1. We treated 1a with 2a in
the presence of TFA (10%) in 1,2-dichloroethene (DCE)
at 50 °C for 12 h followed by addition of 3a. Under these
conditions, C-3 alkylated product of the indole derivative
4aa as an intermediate was formed in 54% yield based on
HPLC data. The in situ conversion to annulated benzazep-
[‡] CDRI Communication No. 8415
[a] Medicinal & Process Chemistry Division, Central Drug
Research Institute, CSIR,
Lucknow 226001, India
Fax: +91-522-2623405
E-mail: bijoy_kundu@yahoo.com
b_kundu@cdri.res.in
Homepage: www.cdriindia.org/bjoykundu.htm
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300100.
2
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One-Pot Tandem-Intramolecular Hydroamination Reactions
inoindole 5aaa in the presence of 3a was obtained in 35% (3,4-OCH2O-) and electron-withdrawing group (5-Cl). The
isolated yield. In an attempt to increase the yield, we in- R3 group on the aromatic aldehydes was substituted with
creased the concentration of TFA to 30% and carried out both electron-donating groups (mono, di and tri-OMe) and
the first step (C-3 alkylation) at 80 °C and the second step electron-withdrawing groups (Br and NO2). For the three-
(7-endo cyclization) at room temperature. These changes led component tandem reactions, a TFA (30%)/DCE mixture
to a moderate increase in the isolated yields of 4aa and 5aaa at 80 °C was used for the C-3 alkylation reaction followed
(Table 1, Entries 1–6). Switching the solvent from DCE to by the application of the modified Pictet–Spengler cycliza-
acetonitrile (ACN), toluene and tetrahydrofuran (THF) tion at room temperature. In all cases the three-component
failed to furnish intermediate 4aa (Table 1, Entries 7–9) tandem reaction led to the formation of benzazepinoindoles
whereas in CH2Cl2, formation of 4aa and final product 5 in 50–75% isolated yields (Table 2). Aromatic aldehydes
5aaa occurred in reduced yields (Table 1, Entry 10). The use with an electron-withdrawing and electron-donating group
of DCE was selected as the solvent of choice. The conden- had no adverse effect on the rate of cyclization; the slight
sation of 1a with 2a in the presence of TFA (30%) at 80 °C variation in the yield observed may be attributed to the
for 1.5 h followed by in situ 7-endo cyclization in the pres- presence of the 5-OMe and 5-Br group on the indole. Ali-
ence of 3a at room temperature for 30 min furnished 5aaa phatic aldehydes failed to furnish endo cyclized products 5.
in 75% isolated yield (Table 1, Entry 11). Replacing TFA
After successfully optimizing the three-component tan-
with other Brønsted and Lewis acids failed to yield interme- dem reaction for the synthesis of benzazepinoindoles, we
diate 4aa (Table 1, Entries 12–15).
turned our attention to extending the utility of one-pot
three-component tandem reactions to enhance structural
diversity by exploiting the nucleophilicity of the NH group
present in the seven membered azepine ring of benzazepino-
indole. To achieve this, we replaced the aldehyde partner
with bi-functional 2-alkynylbenzaldehydes 6. We envisaged
that benzazepinoindoles 7 derived from 6 may undergo a
second consecutive cyclization following either the 5-exo or
6-endo-dig hydroamination reaction by involving the NH
(nucleophile) and the alkyne (electrophile).
Table 1. Optimization of the three-component tandem reaction to
yield 5aaa.
In the first instance, we treated 1a with 2-aminobenz-
ylalcohol (2a) and TFA (30%) in DCE at 80 °C followed
by the addition of 2-alkynylbenzaldehyde 6a (Table 3). The
progress of the reaction was monitored by TLC that showed
formation of benzazepinoindole 7aaa through the modified
Pictet–Spengler cyclization with complete consumption of
the starting materials within 2 h. However, under these con-
ditions a new fluorescent spot with a lower Rf value by TLC
appeared. After extending the reaction time at 80 °C, par-
tial conversion of 7aaa into the compound resulting in the
fluorescent spot was evident by TLC and it remained un-
changed even after 24 h stirring (Table 3, Entry 2). After
purification, a mixture of tetracyclic benzazepinoindole
7aaa and pentacyclic isoquinolinobenzazepinoindole 8aaa
was isolated in 52 and 20% yields, respectively. The finding
clearly suggests that the three-component tandem-post
multicomponent transformation involves the formation of
Pictet–Spengler product 7aaa through 7-endo-trig cycliza-
tion followed by an in situ 6-endo-dig hydroamination reac-
tion to furnish pentacyclic compound 8aaa. To further in-
crease the yield of 8aaa during the hydroamination reac-
tion, we employed a series of alkyne activating metal cata-
lysts and the results are summarized in Table 3. We started
Entry Tandem reaction
conditions
Reaction
temp. [°C] time [h]
for steps
(i)/(ii)
Reaction
Yield [%]
of 4aa/5aaa
for steps
(i)/(ii)
1
2
3
4
5
6
7
8
10% TFA, DCE
10% TFA, DCE
20% TFA, DCE
30% TFA, DCE
30% TFA, DCE
30% TFA, DCE
30% TFA, ACN
30% TFA, toluene
30% TFA, THF
30% TFA, Cl2
30% TFA, DCE
30% Triflic acid, DCE
30 mol-% pTsOH, DCE
30 mol-% Sc(OTf)3, DCE 80/–
30 mol-% Yb(OTf)3, DCE 80/–
50/50
50/r.t.
50/r.t.
50/r.t.
70/r.t.
80/r.t.
80/–
80/–
80/–
50/r.t.
80/r.t.
80/–
12/2
12/2
12/2
12/2
5/2
54/35
54/39
60/44
63/46
66/56
70/60
n.r.
2/2
24/–
24/–
24/–
4/1
1.5/0.5
24/–
24/–
24/–
24/–
n.r.
n.r.
9
10
11
12
13
14
15
38/25[a]
72/75
n.r.
80/–
n.r.
n.r.
n.r.
[a] Yield based on HPLC data; n.r.: no reaction.
The scope and limitation of the strategy was established by treating 1a with 2-aminobenzylalcohol (2a) in the pres-
by synthesizing benzazepinoindoles 5 by using a variety of ence of TFA (30%) in DCE at 80 °C for 2 h followed by the
indoles, 2-aminobenzylalcohols and a series of aromatic al- addition of the third component (6a). After stirring at 80 °C
dehydes bearing electron-donating and withdrawing groups. for 2 h, the reaction was cooled to room temperature and
The R1 group on the phenyl ring of the indole was substi- Cu(OAc)2 (10 mol-%) was added as catalyst to activate the
tuted with an electron-donating group (OCH3) and elec- alkyne moiety. The progress of the reaction was monitored
tron-withdrawing group (Br) at position 5 whereas R2 in the by TLC and HPLC. After 16 h the formation of 7aaa (55%
2-aminobenzyl alcohol included an electron-donating group yield) was seen, whereas its conversion to 8aaa was poor
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S. Samala, M. Saifuddin, A. K. Mandadapu, B. Kundu
Table 2. Synthesis of benzazepinoindoles 5 from indoles 1, benzyl alcohols 2 and benzaldehydes 3 in a three-component tandem reaction.
FULL PAPER
[a] All reactions were carried out with 1 (1 mmol), 2 (2 mmol), 3 (1.5 mmol) and TFA (30%).
(35% based on HPLC data; Table 3, Entry 3). The highest placing R4 and R5 in 6 with H/OCH3 and 4-C(CH3)3-Ph,
isolated yield of 8aaa was obtained when CuI (10 mol-%) respectively, increased the yield of final products to 80–82%
was employed as catalyst and heated for 1.5 h (Table 3, En- (Table 4, 8aac and 8aag). However, for substrates in which
try 4). Replacing CuI with other metal catalysts such as R1 in 1 was replaced with H/OCH3/Br, R2 in 2 with Cl
Yb(OTf)3, AuCl3, AgSbF6, and AuCl3/AgOTf either failed and R4 and R5 with H/F and Ph/4-MePh/4-C(CH3)3-Ph,
or furnished 8aaa in diminished yields (Table 3, Entries 5– respectively, corresponding products 8abb, 8aba, 8abi, 8abc,
9).
8cbb, 8bba, 8bbb were isolated in moderate yields. Similarly,
The scope and limitation of the optimized reaction was the three-component tandem-hydroamination reactions
established by synthesizing a series of pentacyclic isoquinol- also tolerated substrates with R1 in 1 as H, R2 in 2 as H,
inobenzazepinoindoles 8 by using a variety of 2-alkynyl- R4 and R5 as H/F/OMe and Ph/4-CH3-Ph/4-C(CH3)3-Ph/
benzaldehydes bearing R4 and R5 substituents. In all cases cyclohexenyl in 6 to furnish annulated products 8bae, 8baa,
the substrates underwent three-component tandem reac- 8bac, 8bah, 8bag, 8baf, and 8bad in satisfactory yields. In
tions followed by in situ intramolecular hydroamination re- general, the presence of electron-donating substituents at
actions to afford 8 in moderate to good yields (50–82%; position R1 furnished final products in good yields, whereas
Table 4). In the substrates when R1 in indole 1 is substituted the presence of electron-withdrawing groups at position R1
with OCH3, R2 in 2 with H, R4 and R5 in 6 with H and gave only moderate yields. The variation of yields may be
Ph/4-MePh, respectively, corresponding products 8 were attributed to the increase/decrease of nucleophilicity at C-2
obtained in moderate yields (Table 4, 8aaa and 8aab). Re- of the indole ring.
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One-Pot Tandem-Intramolecular Hydroamination Reactions
Table 3. Optimization table for the three-component tandem post-
multicomponent transformation.
Experimental Section
General Information: All reagents and solvents were purchased
from commercial sources and used without purification. NMR
1
spectra were recorded with a 200 or 300 MHz spectrometer for H
NMR, 50, 75 or 100 MHz for 13C NMR spectroscopy. Chemical
shifts are reported relative to the residual signals of tetramethylsil-
1
ane in CDCl3 or deuterated solvent CDCl3/[D6]DMSO for H and
13C NMR spectroscopy. Multiplicities are reported as follows: sing-
let (s), doublet (d), doublet of doublets (dd), doublet of triplets
(dt), triplet (t), quartet (q), multiplet (m). HRMS were recorded
with a 3000 mass spectrometer, by using Waters Agilent 6520-Q-
TofMS/MS system and JEOL-AccuTOF JMS-T100LC. Column
chromatography was performed with silica gel 60 Thomas Baker
(100–200 mesh) as the stationary phase. All reactions were moni-
tored by using TLC. The purity and characterization of compounds
were further established by using HRMS (EI). Melting points were
determined with a Büchi B-545 apparatus.
General Procedure for the Synthesis of Compounds 5: To a stirred
solution of indole 1a–c (1 mmol) in DCE (5 mL) was added 2-
aminobezyl alcohol 2a–c (1.2 mmol) and TFA (30%). After that
the reaction mixture was allowed to stir under a nitrogen atmo-
sphere at 80 °C for 1.5 h. The reaction was monitored by TLC and
the reaction mixture was cooled to room temperature followed by
addition of aldehydes 3a–g (1.5 mmol). The reaction was again
monitored by TLC to establish completion and the reaction mix-
ture was quenched with NaHCO3 solution and the aqueous layer
was extracted with EtOAc (3ϫ 20 mL) and the organic layer was
dried with anhydrous sodium sulfate and the solvents evaporated
to dryness under reduced pressure. The crude product obtained was
purified by column chromatography (EtOAc/Hexane) to afford 5.
Entry Tandem reaction
conditions in one pot
Reaction
time [h]
Yield [%][a]
of 7aaa/
8aaa
(i) C-3 Alkylation/Pictet–Spengler for steps
cyclization
(ii) Hydroamination
(i)/(ii)
1
2
3
(i)/(ii) 30% TFA, DCE, 80 °C
(i)/(ii) 30% TFA, DCE, 80 °C
30 TFA, DCE, 80 °C
10 mol-% Cu(OAc)2
2
24
2/16
68/trace
52/20[b]
55/35
General Procedure for the Synthesis of Compounds 8: To a stirred
solution of indole 1a–c (1 mmol) in DCE (5 mL) was added 2-
aminobezyl alcohol 2a–b (1.2 mmol) and TFA (30%). The reaction
mixture was allowed to stir under a nitrogen atmosphere at 80 °C
for 1.5 h. The reaction was monitored by TLC to establish comple-
tion and the reaction mixture was cooled to room temperature fol-
lowed by addition of 2-alkynylaldehydes 6a–g (1.5 mmol). The re-
action mixture was monitored by TLC to establish completion of
the cationic π-cyclization followed by addition of CuI (10 mol-%)
to perform the hydroamination reaction in one pot at 80 °C. The
reaction mixture was monitored by TLC. After completion of the
reaction it was quenched with NaHCO3 solution and the aqueous
layer was extracted with EtOAc (3ϫ 20 mL). The organic layer was
dried with anhydrous sodium sulfate and the solvents evaporated
to dryness under reduced pressure. The crude product obtained was
purified by column chromatography (EtOAc/Hexane) to afford 8.
4
5
6
7
30% TFA, DCE, 80 °C
10 mol-% CuI
30% TFA, DCE, 80 °C
10 mol-% Yb(OTf)3
30% TFA, DCE, 80 °C
10 mol-% AuCl3/10 mol-% CuI
30% TFA, DCE, 80 °C
10 mol-% AuCl3/10 mol-%
AgSbF6
2/1.5
2/16
2/16
2/16
trace/65[b]
67/trace
34/40
54/trace
8
9
30% TFA, DCE, 80 °C
10 mol-% AuCl3
30% TFA, DCE, 80 °C
10 mol-% AuCl3/AgOTf
2/16
2/16
58/25
55/35
[a] Calculated yield based on HPLC data. [b] Based on isolated
yield.
6-(4-Chlorophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]benzazepin-2-
yl Methyl Ether (5aaa): White solid, yield 61% (0.38 g). Rf = 0.58
(20:80 ethyl acetate/hexane), m.p. 102 °C. FTIR (KBr): ν = 3398,
˜
Conclusions
2942, 1714, 1591, 1477, 1219, 1100 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 10.22 (s, 1 H), 7.29 (d, J = 8.2 Hz, 2 H), 7.23–7.12 (m,
4 H), 7.04 (d, J = 8.5 Hz, 1 H), 6.94 (t, J = 7.5 Hz, 1 H), 6.82 (t,
J = 7.1 Hz, 1 H), 6.72 (d, J = 7.6 Hz, 1 H), 6.63 (d, J = 8.7 Hz, 1
H), 5.50 (s, 1 H), 5.29 (s, 1 H), 4.08 (d, J = 15.6 Hz, 1 H), 3.94 (d,
J = 15.4 Hz, 1 H), 3.79 (s, 3 H) ppm. 13C NMR (50 MHz, [D6]-
In conclusion we have described a one-pot three-compo-
nent tandem intramolecular hydroamination reaction in-
volving indole, 2-aminobenzyl alcohols and 2-alkynylbenz-
aldehydes. The salient feature of the strategy involves se-
quential 7-endo-trig and electrophilic 6-endo-dig sequential DMSO): δ = 153.2, 146.3, 142.4, 136.8, 135.4, 131.6, 130.5, 129.8,
128.2, 127.9, 127.3, 126.6, 124.2, 123.4, 122.0, 111.4, 110.6, 108.9,
59.5, 55.5, 30.4 ppm. HRMS (ESI): calcd. for C23H20ClN2O [M +
H] 375.1264; found 375.1245.
cyclization reactions in one pot. Further studies involving
the application of 2-alkynylbenzaldehydes in a one-pot
multicomponent tandem reaction for the synthesis of new
indole-based annulated polyheterocycles is in progress and
results will be published in due course.
6-(3,4,5-Triimethoxyphenyl)-5,6,7,12-tetrahydroindolo[2,3c][1]-
benzazepin-2-yl Methyl Ether (5aac): Yellow solid, yield 75 %
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FULL PAPER
Table 4. Three-component tandem-intramolecular hydroamination reaction for the synthesis of pentacyclic isoquinolinobenzazepinoin-
doles 8.
[a] All reactions were carried out with 1 (1 mmol), 2 (2 mmol), 6 (1.5 mmol), TFA (30%) and CuI (10 mol-%).
(0.51 g). Rf = 0.30 (20:80 ethyl acetate/hexane), m.p. 137–139 °C.
128.1, 127.2, 123.7, 111.6, 111.4, 110.3, 105.2, 100.5, 62.8, 60.9,
56.2, 29.8, 29.0 ppm. HRMS (ESI): calcd. for C26H27N2O4 [M +
H] 431.1970; found 431.1972.
1
FTIR (KBr): ν = 3322, 2930, 1593, 1468, 1322, 1221 cm–1. H
˜
NMR (300 MHz, [D6]DMSO): δ = 10.13 (s, 1 H), 7.24 (d, J =
6.9 Hz, 1 H), 7.13–7.06 (m, 2 H), 7.00 (t, J = 7.1 Hz, 1 H), 6.88–
6.82 (m, 2 H), 6.65–6.63 (m, 1 H), 6.57 (s, 2 H), 5.40 (s, 1 H), 5.16
(s, 1 H), 4.14 (d, J = 15.4 Hz, 1 H), 3.93 (d, J = 15.6 Hz, 1 H),
3.80 (s, 3 H), 3.64 (s, 3 H), 3.61 (s, 6 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 154.1, 153.5, 146.2, 137.8, 137.5, 135.4, 130.8, 129.0,
2-Methoxy-6-(3,4-dimethoxyphenyl)-5,6,7,12-tetrahydroindolo-
[2,3-c][1]benzazepine (5aae): Red solid, yield 71% (0.48 g). Rf = 0.41
(20:80 ethyl acetate/hexane), m.p. 152–154 °C. FTIR (KBr): ν =
˜
3338, 2925, 1595, 1462, 1262, 1140 cm–1 1H NMR (300 MHz,
.
6
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One-Pot Tandem-Intramolecular Hydroamination Reactions
CDCl3): δ = 10.13 (s, 1 H), 7.22 (d, J = 7.2 Hz, 1 H), 7.11 (s, 1 H),
7.05 (d, J = 8.6 Hz, 1 H), 6.97 (t, J = 7.4 Hz, 1 H), 6.84–6.77 (m,
4 H), 6.64 (t, J = 8.5 Hz, 2 H), 5.42 (s, 1 H), 5.13 (br. s, 1 H), 4.10
(d, J = 15.1 Hz, 1 H), 3.94 (d, J = 15.5 Hz, 1 H), 3.79 (s, 3 H),
(KBr): ν = 3398, 2925, 1602, 1461, 1246, 1172 cm–1 1H NMR
.
˜
(300 MHz, [D6]DMSO): δ = 10.32 (s, 1 H), 7.59 (s, 1 H), 7.20 (d,
J = 6.7 Hz, 1 H), 7.12 (d, J = 8.5 Hz, 3 H), 6.96 (t, J = 6.63 Hz, 3
H), 6.80 (t, J = 8.1 Hz, 4 H), 5.44 (s, 1 H), 5.13 (s, 1 H), 4.13 (d,
3.69 (s, 3 H), 3.61 (s, 3 H) ppm. 13C NMR (50 MHz, [D6]DMSO): J = 15.0 Hz, 1 H), 3.80 (d, J = 15.5 Hz, 1 H), 3.7 (s, 3 H) ppm.
δ = 153.0, 148.2, 147.9, 146.7, 136.8, 136.1, 136.0, 133.2, 132.7,
131.5, 130.4, 126.4, 123.4, 121.8, 120.0, 114.9, 111.9, 111.2, 108.3,
60.1, 55.4, 28.2 ppm. HRMS (ESI): calcd. for C25H25N2O3 [M +
H] 401.1865; found 401.1860.
13C NMR (75 MHz, [D6]DMSO): δ = 158.5, 146.8, 137.0, 135.7,
135.5, 135.4, 129.2, 128.0, 127.0, 126.6, 123.4, 122.0, 120.6, 118.2,
117.6, 113.4, 110.7, 108.8, 59.9, 55.1, 28.2 ppm. HRMS (ESI):
calcd. for C23H21N2O [M + H] 341.1653; found 341.1652.
10-Chloro-6-(4-chlorophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]- 6-(4-Chlorophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]benzazepine
benzazepin-2-yl Methyl Ether (5aba): Yellow solid, yield 62 %
(0.43 g). Rf = 0.52 (20:80 ethyl acetate/hexane), m.p. 138–140 °C.
(5baa): white solid, yield 68% (0.49 g). Rf = 0.62 (20:80 ethyl acet-
ate/hexane), m.p. 170–172 °C [Lit.[4c] 176–178 °C]. FTIR (KBr): ν
˜
FTIR (KBr): ν = 3347, 2926, 1591, 1477, 1215, 1096, 1024 cm–1.
= 3413, 3173, 2926, 1913, 1588, 1467, 1244 cm–1
.
1H NMR
˜
1H NMR (300 MHz, [D6]DMSO): δ = 10.30 (s, 1 H), 7.33 (d, J = (300 MHz, [D6]DMSO): δ = 10.40 (s, 1 H), 7.62 (t, J = 4.2 Hz, 1
8.1 Hz, 3 H), 7.16 (d, J = 8.6 Hz, 3 H), 7.08–6.99 (m, 2 H), 6.73
(d, J = 8.3 Hz, 1 H), 6.65 (d, J = 8.7 Hz, 1 H), 5.51 (d, J = 6.9 Hz,
2 H), 4.09 (d, J = 15.2 Hz, 1 H), 3.96 (d, J = 15.4 Hz, 1 H), 3.93
(s, 3 H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ = 153.2, 145.4,
142.2, 138.8, 135.0, 133.0, 131.7, 131.2, 130.4, 129.7, 128.5, 127.1,
H), 7.32 (d, J = 8.3 Hz, 2 H), 7.19 (t, J = 8.4 Hz, 4 H), 7.00 (d, J
= 4.9 Hz, 3 H), 6.83 (t, J = 7.3 Hz, 1 H), 6.74 (d, J = 7.5 Hz, 1 H),
5.53 (s, 1 H), 5.28 (s, 1 H), 4.12 (d, J = 15.2 Hz, 1 H), 3.97 (d, J =
15.2 Hz, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 146.3,
142.9, 136.8, 135.4, 134.5, 131.7, 129.9, 128.1, 127.8, 126.9, 126.5,
125.5, 124.7, 111.4, 110.8, 108.3, 99.9, 59.2, 55.4, 27.7 ppm. HRMS 123.4, 122.0, 120.7, 118.2, 117.6, 110.7, 109.0, 59.5, 28.1 ppm.
(ESI): calcd. for C23H19Cl2N2O [M + H] 409.0874; found 409.0872. HRMS (ESI): calcd. for C22H18N2Cl [M + H] 345.1158; found
345.1151.
6-(3,4,5-Triimethoxyphenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]-
benzazepine (5bac): Yellow solid, yield 70 % (0.59 g). Rf = 0.30 6-(3,4-Dimethoxyphenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]benz-
(20:80 ethyl acetate/hexane), m.p. 184–186 °C. FTIR (KBr): ν = azepine (5bae): Red solid, yield 71% (0.56 g). Rf = 0.40 (20:80 ethyl
˜
3379, 2927, 1592, 1461, 1321, 1232 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 10.30 (s, 1 H), 7.60 (t, J = 4.7 Hz, 1 H), 7.24–7.17 1596, 1458, 1238, 1132, 1024 cm–1
acetate/hexane), m.p. 157–159 °C. FTIR (KBr): ν = 3348, 2926,
˜
.
1H NMR (300 MHz, [D6]-
(m, 2 H), 6.98 (t, J = 4.7 Hz, 3 H), 6.86 (t, J = 6.4 Hz, 2 H), 6.58
(s, 2 H), 5.42 (s, 1 H), 5.17 (s, 1 H), 4.17 (d, J = 15.1 Hz, 1 H),
DMSO): δ = 10.30 (s, 1 H), 7.21–7.10 (m, 3 H), 6.96 (d, J = 6.5 Hz,
3 H), 6.85–6.76 (m, 4 H), 6.64 (d, J = 8.5 Hz, 1 H), 5.42 (s, 1 H),
3.95 (d, J = 15.1 Hz, 1 H), 3.64 (s, 6 H), 3.61 (s, 3 H) ppm. 13C 5.13 (s, 1 H), 4.12 (d, J = 15.3 Hz, 1 H), 3.94 (d, J = 15.2 Hz, 1 H),
NMR (50 MHz, CDCl3): δ = 153.6, 146.2, 137.9, 137.8, 137.6, 3.67 (s, 3 H), 3.59 (s, 3 H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ
135.6, 134.4, 129.0, 127.8, 127.2, 123.7, 121.8, 119.4, 118.2, 110.7,
110.6, 105.2, 62.8, 61.0, 56.2, 29.9, 29.0 ppm. HRMS (ESI): calcd.
for C25H25N2O3 [M + H] 401.1865; found 401.1864.
= 148.3, 148.0, 146.7, 136.9, 135.9, 135.4, 135.3, 128.0, 126.4, 123.4,
121.8, 120.5, 120.1, 118.0, 117.5, 112.1, 111.4, 110.7, 108.5, 60.1,
55.5, 55.3, 28.2 ppm. HRMS (ESI): calcd. for C24H23N2O2 [M +
H] 371.1759; found 371.1758.
6-(4-Chlorophenyl)-5,6,7,13-tetrahydro[1,3]dioxolo[4,5-h]indolo-
[2,3-c][1]benzazepine (5bca): White solid, yield 65% (0.53 g). Rf =
2-Bromo-6-(4-chlorophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]-
benzazepine (5caa): Yellow solid, yield 65 % (0.35 g). Rf = 0.51
0.57 (20:80 ethyl acetate/hexane), m.p. 108 °C. FTIR (KBr): ν =
˜
3401, 2927, 1478, 1170, 1037, 851 cm–1. 1H NMR (300 MHz, [D6]-
(20:80 ethyl acetate/hexane), m.p. 157–159 °C. FTIR (KBr): ν =
˜
DMSO): δ = 10.36 (s, 1 H), 7.58 (t, J = 3.1 Hz, 1 H), 7.34 (d, J =
3195, 2924, 1588, 1461, 1244, 1089 cm–1. 1H NMR (300 MHz, [D6]-
8.2 Hz, 2 H), 7.18 (d, J = 8.3 Hz, 3 H), 6.99 (d, J = 3.8 Hz, 2 H), DMSO): δ = 10.64 (s, 1 H), 7.82 (s, 1 H), 7.31 (d, J = 8.2 Hz, 2
6.86 (s, 1 H), 6.38 (s, 1 H), 5.85 (d, J = 12.3 Hz, 2 H), 5.45 (s, 1
H), 5.06 (d, J = 2.5 Hz, 1 H), 4.05 (d, J = 14.9 Hz, 1 H), 3.89 (d,
J = 15.1 Hz, 1 H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ =
145.0, 142.1, 140.0, 135.3, 134.7, 131.7, 130.7, 130.0, 127.8, 126.8,
120.6, 118.1, 117.5, 110.7, 109.4, 108.3, 105.3, 100.4, 59.7,
H), 7.24 (d, J = 6.7 Hz, 1 H), 7.17–7.12 (m, 4 H), 6.96 (t, J =
6.3 Hz, 1 H), 6.84 (t, J = 7.0 Hz, 1 H), 6.73 (d, J = 7.9 Hz, 1 H),
5.53 (s, 1 H), 5.30 (s, 1 H), 4.11 (d, J = 15.5 Hz, 1 H), 3.96 (d, J =
15.3 Hz, 1 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 145.6, 140.1,
137.4, 135.1, 134.0, 129.6, 129.1, 128.8, 127.2, 124.6, 123.9, 123.5,
27.7 ppm. HRMS (ESI): calcd. for C23H18ClN2O [M + H] 120.9, 112.7, 111.9, 110.9, 31.9, 28.5 ppm. HRMS (ESI): calcd. for
389.1057; found 389.1030.
C22H17N2BrCl [M + H] 423.0236; found 423.0229.
Methyl 4-(5,6,7,13-Tetrahydro[1,3]dioxolo[4,5-h]indolo[2,3-c][1]-
benzazepin-6-yl)phenyl Ether (5bcb): White solid, yield 59 %
(0.48 g). Rf = 0.50 (20:80 ethyl acetate/hexane), m.p. 173–175 °C.
2-Bromo-6-(3,4,5-triimethoxyphenyl)-5,6,7,12-tetrahydroindolo-
[2,3-c][1]benzazepine (5cac): Gray solid, yield 62% (0.37 g). Rf =
0.31 (20:80 ethyl acetate/hexane), m.p. 170–172 °C. FTIR (KBr): ν
˜
FTIR (KBr): ν = 3388, 2921, 1609, 1475, 1247, 1175, 1028, = 3291, 2924, 1592, 1460, 1322, 1228 cm–1. 1H NMR (300 MHz,
˜
834 cm–1. 1H NMR (300 MHz, [D6]DMSO): δ = 10.28 (s, 1 H), [D6]DMSO): δ = 10.53 (s, 1 H), 7.80 (s, 1 H), 7.25 (d, J = 6.3 Hz,
7.56 (t, J = 5.6 Hz, 1 H), 7.13 (t, J = 3.9 Hz, 3 H), 6.98–6.95 (m, 1 H), 7.16–7.08 (m, 2 H), 7.00 (t, J = 6.8 Hz, 1 H), 6.88–6.81 (m,
2 H), 6.86–6.83 (m, 3 H), 6.44 (s, 1 H), 5.85 (d, J = 12.7 Hz, 2 H),
2 H), 6.54 (s, 2 H), 5.42 (s, 1 H), 5.18 (s, 1 H), 4.14 (d, J = 15.4 Hz,
5.36 (s, 1 H), 4.91 (s, 1 H), 4.07 (d, J = 15.3 Hz, 1 H), 3.86 (d, J = 1 H), 3.95 (d, J = 15.4 Hz, 1 H), 3.62 (s, 3 H), 3.60 (s, 6 H) ppm.
15.2 Hz, 1 H), 3.72 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO):
δ = 158.5, 145.0, 141.9, 140.5, 135.4, 135.5, 135.3, 130.8, 129.3,
126.9, 120.4, 118.0, 117.4, 113.3, 110.6, 109.1, 108.2, 105.3, 100.3,
60.1, 55.0, 27.7 ppm. HRMS (ESI): calcd. for C24H21N2O3 [M +
H] 385.1552; found 385.1554.
13C NMR (50 MHz, CDCl3): δ = ; δ 153.6, 146.1, 137.5, 137.2,
136.0, 134.2, 129.6, 129.0, 127.4, 124.5, 123.9, 123.7, 121.0, 112.6,
112.2, 110.4, 105.2, 62.7, 61.0, 56.2, 29.9, 28.8 ppm. HRMS (ESI):
calcd. for C25H24BrN2O3 [M + H] 479.0970; found 479.0964.
2-Bromo-6-(4-nitrophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]benz-
azepine (5cad): White solid, yield 50% (0.27 g). Rf = 0.38 (20:80
Methyl 4-(5,6,7,12-Tetrahydroindolo[2,3-c][1]benzazepine-6-yl)-
phenyl Ether (5bab): Red solid, yield 62% (0.45 g). Rf = 0.52 (20:80
ethyl acetate/hexane), m.p. 162–164 °C [Lit.[4c] 169–171 °C]. FTIR
ethyl acetate/hexane), m.p. 165–167 °C. FTIR (KBr): ν = 3413,
˜
2925, 1667, 1595, 1511, 1340 cm–1 1H NMR (300 MHz, [D6]-
.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O30100
/KAP1
Date: 18-04-13 16:26:03
Pages: 11
S. Samala, M. Saifuddin, A. K. Mandadapu, B. Kundu
FULL PAPER
DMSO): δ = 10.75 (s, 1 H), 8.14 (d, J = 8.6 Hz, 2 H), 7.84 (s, 1
H), 7.37 (d, J = 8.5 Hz, 2 H), 7.25 (d, J = 7.1 Hz, 1 H), 7.16 (s, 2
H), 6.95 (t, J = 6.51 Hz, 1 H), 6.85 (t, J = 6.9 Hz, 1 H), 6.68 (d, J
= 7.3 Hz, 1 H), 5.70 (s, 1 H), 5.50 (d, J = 3.3 Hz, 1 H), 4.12 (d, J
= 15.3 Hz, 1 H), 4.00 (d, J = 15.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = . δ = 148.7, 147.9, 144.6, 137.7, 134.4,
134.0, 129.3, 129.2, 129.1, 127.5, 125.1, 124.4, 124.2, 124.0, 121.2,
113.0, 112.2, 111.6, 29.8, 28.6 ppm. HRMS (ESI): calcd. for
C22H17BrN2O3 [M + H] 434.0504; found 434.0476.
8-Methoxy-16-(4-terbutylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]-
isoquino[2,1-a][1]benzazepine (8aac): Blue solid, yield 82% (0.55 g).
Rf = 0.51 (20:80 ethyl acetate/hexane), m.p. 220–222 °C. FTIR
(KBr): ν = 3398, 2954, 1588, 1462, 1288, 1219 cm–1 1H NMR
.
˜
(300 MHz, [D6]DMSO): δ = 10.69 (s, 1 H), 7.65 (s, 3 H), 7.32–7.25
(m, 3 H), 7.14 (t, J = 7.3 Hz, 1 H), 6.99–6.87 (m, 3 H), 6.83 (d, J
= 6.8 Hz, 2 H), 6.70 (d, J = 8.5 Hz, 1 H), 6.62–6.58 (m, 1 H), 6.47
(d, J = 7.7 Hz, 1 H), 6.06 (d, J = 10.5 Hz, 2 H), 3.63 (d, J =
15.6 Hz, 1 H), 3.46 (s, 3 H), 3.41 (s, 1 H), 1.41 (s, 9 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 150.3, 143.8, 142.8, 138.3, 137.0,
136.0, 135.3, 134.4, 130.5, 127.9, 127.0, 126.5, 125.4, 125.3, 123.1,
120.6, 119.5, 118.6, 114.6, 113.1, 112.1, 111.0, 100.1, 59.9, 55.1,
46.5, 34.4, 31.2 ppm. HRMS (ESI): calcd. for C35H33N2O [M + H]
497.2592; found 497.2592.
2-Bromo-6-(3-nitrophenyl)-5,6,7,12-tetrahydroindolo[2,3-c][1]benz-
azepine (5caf): Red solid, yield = 60% (0.33 g). Rf = 0.41 (20:80
ethyl acetate/hexane), m.p. 120–122 °C. FTIR (KBr): ν = 3405,
˜
2924, 1718, 1595, 1526, 1465, 1347 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 10.76 (s, 1 H), 8.09 (t, J = 7.5 Hz, 2 H), 7.85 (s, 1 H),
7.56–7.47 (m, 2 H), 7.28 (d, J = 6.5 Hz, 1 H), 7.13 (s, 2 H), 6.98–
6.84 (m, 2 H), 6.69 (d, J = 7.3 Hz, 1 H), 5.75 (s, 1 H), 5.48 (d, J =
2.9 Hz, 1 H), 4.15 (d, J = 16.1 Hz, 1 H), 4.04 (t, J = 7.1 Hz, 1
H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ = 147.4, 145.8, 145.0,
136.7, 135.7, 134.6, 134.1, 129.4, 128.7, 128.3, 126.7, 123.5, 123.3,
122.7, 122.4, 122.2, 120.2, 112.7, 111.0, 109.4, 59.2, 27.7 ppm.
HRMS (ESI): calcd. for C22H17BrN3O2 [M + H] 434.0504; found
434.0503.
3,8-Dimethoxy-16-(4-terbutylphenyl)-5,10-dihydro-4bH-indolo-
[2,3-c]isoquino[2,1-a][1]benzazepine (8aag): Blue solid, yield 80%
(0.57 g). Rf = 0.42 (20:80 ethyl acetate/hexane), m.p. 195–197 °C.
1
FTIR (KBr): ν = 3369, 2951, 1606, 1466, 1277, 1035 cm–1. H
˜
NMR (300 MHz, [D6]DMSO): δ = 10.66 (s, 1 H), 7.60 (s, 3 H),
7.29 (t, J = 6.9 Hz, 2 H), 6.98–6.84 (m, 4 H), 6.74 (s, 1 H), 6.66 (d,
J = 8.4 Hz, 1 H), 6.57–6.53 (m, 2 H), 6.40 (d, J = 8.5 Hz, 1 H),
6.04 (d, J = 6.2 Hz, 2 H), 3.78 (d, J = 12.9 Hz,1 H), 3.66 (s, 3 H),
3.57 (d, J = 15.6 Hz, 1 H), 3.45 (s, 3 H), 1.40 (s, 9 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 159.6, 151.5, 150.1, 145.0, 144.1,
136.8, 136.0, 135.2, 134.6, 131.0, 129.2, 128.0, 127.0, 126.4, 125.7,
124.0, 120.6, 119.5, 118.6, 114.5, 113.1, 112.4, 111.8, 110.9, 110.4,
100.0, 60.3, 55.1, 46.7, 34.4, 31.2 ppm. HRMS (ESI): calcd. for
C36H35N2O2 [M + H] 527.2698; found 527.2698.
2-Bromo-6-phenyl-5,6,7,12-tetrahydroindolo[2,3-c][1]benzazepine
(5cag): Yellow solid, yield 65% (0.32 g). Rf = 0.60 (20:80 ethyl acet-
ate/hexane), m.p. 106–108 °C. FTIR (KBr): ν = 3405, 3202, 2924,
˜
1
1725, 1584, 1458, 1241 cm–1. H NMR (300 MHz, [D6]DMSO): δ
= 10.62 (s, 1 H), 7.81 (s, 1 H), 7.24 (d, J = 8.6 Hz, 6 H), 7.15–7.08
(m, 2 H), 6.96 (t, J = 6.7 Hz, 1 H), 6.86–6.77 (m, 2 H), 5.51 (s, 1
H), 5.25 (s, 1 H), 4.14 (d, J = 15.3 Hz, 1 H), 3.96 (d, J = 15.3 Hz,
1 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 146.1, 141.8, 137.4,
135.9, 134.1, 129.5, 129.1, 128.9, 128.8, 128.5, 127.4, 124.5, 123.9,
123.6, 120.9, 112.7, 112.1, 110.7, 29.9, 28.8 ppm. HRMS (ESI):
calcd. for C22H18BrN2 [M + H] 389.0653; found 389.0630.
3,8-Dimethoxy-16-(1-cyclohexenyl)-5,10-dihydro-4bH-indolo[2,3-c]-
isoquino[2,1-a][1]benzazepine (8aad): Blue solid, yield 82% (0.45 g).
Rf = 0.55 (20:80 ethyl acetate/hexane), m.p. 195–197 °C. FTIR
(KBr): ν = 3376, 2926, 1602, 1464, 1277, 1031 cm–1 1H NMR
.
˜
(300 MHz, [D6]DMSO): δ = 10.60 (s, 1 H), 7.81 (s, 1 H), 7.28–7.21
(m, 2 H), 6.94–6.82 (m, 4 H), 6.60–6.56 (m, 4 H), 6.04–5.90 (m, 2
H), 3.89 (d, J = 13.9 Hz, 1 H), 3.72 (s, 3 H), 3.59 (s, 3 H), 3.49 (s,
1 H), 2.36–2.27 (m, 2 H), 1.90–1.77 (m, 6 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 159.5, 151.7, 144.7, 144.2, 136.9, 136.0,
134.1, 133.0, 131.2, 130.1, 128.3, 127.0, 124.3, 120.5, 119.4, 118.5,
114.7, 113.6, 112.8, 110.9, 110.3, 109.9, 100.0, 59.9, 55.1, 55.0, 46.7,
30.3, 24.9, 22.6, 21.8 ppm. HRMS (ESI): calcd. for C32H31N2O2
[M + H] 475.2385; found 475.2383.
16-(4-Methylphenyl)-8-methoxy-5,10-dihydro-4bH-indolo[2,3-c]-
isoquino[2,1-a][1]benzazepine (8aaa): Green solid, yield 65 %
(0.40 g). Rf = 0.51 (20:80 ethyl acetate/hexane), m.p. 197–198 °C.
FTIR (KBr): ν = 3369, 2918, 1725, 1601, 1454, 1284, 1217 cm–1.
˜
1H NMR (300 MHz, [D6]DMSO): δ = 10.72 (s, 1 H), 7.62 (s, 1 H),
7.52 (s, 1 H), 7.32–7.26 (m, 4 H), 7.13 (t, J = 7.05 Hz, 1 H), 6.97
(t, J = 7.3 Hz, 3 H), 6.87–6.82 (m, 2 H), 6.68 (d, J = 8.6 Hz,1 H),
6.61–6.53 (m, 2 H), 6.07 (d, J = 4.6 Hz, 2 H), 3.63 (d, J = 15.5 Hz,
1 H), 3.45 (s, 3 H), 3.40 (s, 1 H), 2.47 (s, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 152.1, 144.4, 143.4, 138.9, 137.6, 136.6,
135.7, 134.9, 131.2, 130.1, 128.5, 127.6, 127.1, 126.0, 125.9, 123.7,
121.2, 120.1, 119.2, 115.3, 114.1, 112.2, 111.5, 100.7, 60.5, 55.7,
47.1, 21.5 ppm. HRMS (ESI): calcd. for C32H27N2O [M + H]
455.2123; found 455.2149.
12-Chloro-8-methoxy-16-phenyl-5,10-dihydro-4bH-indolo[2,3-c]-
isoquino[2,1-a][1]benzazepine (8abb): White solid, yield 62 %
(0.39 g). Rf = 0.48 (20:80 ethyl acetate/hexane), m.p. 204–206 °C.
FTIR (KBr): ν = 3407, 2934, 1577, 1485, 1300, 1219, 1046 cm–1.
˜
1H NMR (300 MHz, [D6]DMSO): δ = 10.91 (s, 1 H), 7.73 (s, 2 H),
7.55 (s, 2 H), 7.35–7.27 (m, 3 H), 7.14 (t, J = 7.1 Hz, 1 H), 7.06 (s,
1 H), 6.94 (t, J = 7.8 Hz, 3 H), 6.71 (d, J = 8.2 Hz, 1 H), 6.61 (t,
J = 6.7 Hz, 1 H), 6.44 (d, J = 7.7 Hz, 1 H), 6.10 (s, 2 H), 3.66 (s,
1 H), 3.61 (s, 1 H), 3.46 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 151.6, 145.9, 142.8, 138.1, 137.4, 136.9, 135.0, 134.5,
131.3, 130.7, 129.5, 129.0, 128.3, 128.1, 128.0, 126.7, 125.6, 125.0,
123.2, 120.6, 118.8, 114.9, 113.7, 112.6, 111.5, 99.9, 59.9, 55.1,
46.5 ppm. HRMS (ESI): calcd. for C31H24ClN2O [M + H]
475.1577; found 475.1577.
16-Phenyl-8-methoxy-5,10-dihydro-4bH-indolo[2,3-c]isoquino[2,1-a]-
[1]benzazepine (8aab): Yellow solid, yield 60% (0.36 g). Rf = 0.51
(20:80 ethyl acetate/hexane), m.p. 161–163 °C. FTIR (KBr): ν =
˜
3369, 2927, 1602, 1456, 1281, 1219 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 10.71 (s, 1 H), 7.72 (s, 2 H), 7.53 (s, 2 H), 7.31–7.25
(m, 3 H), 7.11 (t, J = 7.1 Hz, 1 H), 7.03 (s, 1 H), 6.98–6.91 (m, 2
H), 6.86 (t, J = 6.3 Hz, 2 H), 6.68 (d, J = 8.5 Hz, 1 H), 6.60–6.58
(m, 1 H), 6.43 (d, J = 7.7 Hz, 1 H), 6.06 (s, 2 H), 3.63 (d, J =
15.7 Hz, 1 H), 3.45 (s, 1 H), 3.43 (s, 3 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 151.5, 143.8, 142.9, 138.2, 137.5, 137.1, 136.1, 135.2,
130.7, 128.1, 127.9, 127.1, 126.6, 125.6, 125.1, 123.2, 120.7, 119.6,
12-Chloro-8-methoxy-16-(4-methylphenyl)-5,10-dihydro-4bH-
indolo[2,3-c]isoquino[2,1-a][1]benzazepine (8aba): Red solid, yield
61 % (0.40 g). Rf = 0.52 (20:80 ethyl acetate/hexane), m.p. 230–
232 °C. FTIR (KBr): ν = 3413, 2934, 1725, 1573, 1461, 1299,
˜
118.7, 114.8, 113.7, 111.6, 111.0, 100.2, 59.9, 55.1, 46.6 ppm. 1056 cm–1. 1H NMR (300 MHz, [D6]DMSO): δ = 10.90 (s, 1 H),
HRMS (ESI): calcd. for C31H25N2O [M + H] 441.1966; found 7.61 (s, 1 H), 7.51 (s, 1 H), 7.35–7.26 (m, 4 H), 7.14 (t, J = 7.3 Hz,
441.1966.
1 H), 6.97 (t, J = 6.8 Hz, 3 H), 6.87 (s, 1 H), 6.69 (d, J = 8.7 Hz,
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O30100
/KAP1
Date: 18-04-13 16:26:03
Pages: 11
One-Pot Tandem-Intramolecular Hydroamination Reactions
1 H), 6.61 (t, J = 2.4 Hz, 1 H), 6.54 (d, J = 7.8 Hz, 1 H), 6.09 (s, 16-(4-Terbutylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]isoquino-
2 H), 3.67 (d, J = 11.9 Hz, 1 H), 3.59 (s, 1 H), 3.45 (s, 3 H), 2.47
(s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 151.6, 146.0,
142.8, 138.2, 137.1, 137.0, 135.0, 134.5, 134.4, 130.8, 128.3, 128.1,
126.7, 125.5, 125.3, 123.2, 120.6, 118.8, 114.8, 113.7, 112.5, 111.7,
99.9, 59.9, 55.2, 46.5, 21.0 ppm. HRMS (ESI): calcd. for
C32H26ClN2O [M + H] 489.1733; found 489.1734.
[2,1-a][1]benzazepine (8bac): Gray solid, yield 76% (0.60 g). Rf =
0.65 (20:80 ethyl acetate/hexane), m.p. 205–207 °C. FTIR (KBr): ν
˜
= 3403, 3050, 2954, 1725, 1598, 1461, 1281 cm–1
.
1H NMR
(300 MHz, [D6]DMSO): δ = 10.67 (s, 1 H), 7.71 (s, 3 H), 7.43 (d,
J = 8.3 Hz, 1 H), 7.33–7.25 (m, 3 H), 7.15 (t, J = 8.3 Hz, 2 H),
6.99–6.83 (m, 4 H), 6.73 (d, J = 7.7 Hz, 1 H), 6.55–6.44 (m, 3 H),
6.08 (s, 1 H), 3.67 (d, J = 15.4 Hz, 1 H), 3.46 (d, J = 16.0 Hz, 1
H), 1.41 (s, 9 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 150.2,
143.8, 142.8, 142.4, 138.4, 136.0, 134.5, 133.9, 130.8, 128.3, 127.9,
127.0, 126.5, 126.1, 125.9, 125.4, 124.1, 123.0, 120.7, 119.6, 118.7,
117.3, 114.0, 111.0, 100.1, 59.6, 46.5, 31.2, 30.6 ppm. HRMS (ESI):
calcd. for C34H31N2 [M + H] 467.2487; found 467.2487.
12-Chloro-3-fluoro-8-methoxy-16-phenyl-5,10-dihydro-4bH-
indolo[2,3-c]isoquino[2,1-a][1]benzazepine (8abi): Green solid, yield
60 % (0.40 g). Rf = 0.53 (20:80 ethyl acetate/hexane), m.p. 216–
218 °C. FTIR (KBr): ν = 3381, 2934, 1594, 1468, 1222, 1035 cm–1.
˜
1H NMR (300 MHz, [D6]DMSO): δ = 10.89 (s, 1 H), 7.71 (s, 2 H),
7.55 (s, 2 H), 7.34 (t, J = 6.8 Hz, 2 H), 7.15 (d, J = 8.9 Hz, 1 H),
7.04 (s, 1 H), 6.97 (d, J = 9.8 Hz, 1 H), 6.91 (s, 1 H), 6.85 (d, J = 3-Flouro-16-(4-terbutylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]-
10.6 Hz, 1 H), 6.71 (d, J = 8.3 Hz, 1 H), 6.64 (dd, J1 = 2.9, J2 =
8.5 Hz, 1 H), 6.41 (t, J = 6.0 Hz, 1 H), 6.09 (d, J = 11.2 Hz, 2 H),
isoquino[2,1-a][1]benzazepine (8bah): White solid, yield 72 %
(0.59 g). Rf = 0.61 (20:80 ethyl acetate/hexane), m.p. 242–244 °C.
3.63 (d, J = 16.1 Hz, 1 H), 3.45 (s, 1 H), 3.34 (s, 3 H) ppm. 13C FTIR (KBr): ν = 3391, 2949, 1606, 1468, 1270, 746 cm–1. 1H NMR
˜
NMR (75 MHz, [D6]DMSO): δ = 160.5, 151.6, 145.6, 145.5, 137.1,
136.7, 134.6, 133.7, 130.4, 128.3, 128.1, 124.9, 124.6, 124.4, 123.3,
120.7, 118.8, 114.9, 114.1, 113.8, 112.8, 112.6, 112.5, 111.5, 99.9,
60.3, 55.1, 46.5 ppm. HRMS (ESI): calcd. for C31H23ClFN2O [M
+ H] 493.1482; found 493.1481.
(300 MHz, [D6]DMSO): δ = 10.66 (s, 1 H), 7.65 (s, 3 H), 7.33 (t, J
= 7.5 Hz, 2 H), 7.14 (t, J = 5.4 Hz, 2 H), 7.00–6.72 (m, 6 H), 6.54–
6.40 (m, 3 H), 6.09 (s, 1 H), 3.67 (d, J = 16.0 Hz, 1 H), 3.46 (d, J
= 16.0 Hz, 1 H), 1.40 (s, 9 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 160.3, 150.3, 145.2, 145.1, 143.5, 142.7, 136.1, 134.9,
134.2, 132.7, 130.4, 127.9, 127.0, 125.8, 124.3, 124.0, 120.8, 119.6,
118.7, 117.4, 114.1, 113.7, 112.6, 112.3, 111.1, 100.1, 60.0, 46.6,
34.4, 31.2 ppm. HRMS (ESI): calcd. for C34H30FN2 [M + H]
485.2393; found 485.2390.
12-Chloro-8-methoxy-16-(4-terbutylphenyl)-5,10-dihydro-4bH-
indolo[2,3-c]isoquino[2,1-a][1]benzazepine (8abc): Yellow solid, yield
58 % (0.41 g). Rf = 0.61 (20:80 ethyl acetate/hexane), m.p. 227–
229 °C. FTIR (KBr): ν = 3413, 2935, 1459, 1289, 1212, 1049 cm–1.
˜
1H NMR (300 MHz, [D6]DMSO): δ = 10.92 (s, 1 H), 7.63 (s, 3 H),
3-Methoxy-16-(4-terbutylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]iso-
7.34–7.26 (m, 3 H), 7.13 (t, J = 7.1 Hz, 1 H), 6.97 (t, J = 1.8 Hz, quino[2,1-a][1]benzazepine (8bag): White solid, yield 80% (0.67 g).
3 H), 6.87 (s, 1 H), 6.70 (d, J = 8.4 Hz, 1 H), 6.62 (t, J = 2.5 Hz, Rf = 0.58 (20:80 ethyl acetate/hexane), m.p. 214–216 °C. FTIR
1
1 H), 6.46 (d, J = 7.7 Hz, 1 H), 6.07 (s, 2 H), 3.62 (d, J = 15.8 Hz,
(KBr): ν = 3426, 3376, 2957, 1608, 1466, 1279, 1104 cm–1. H
˜
1 H), 3.46 (s, 3 H), 3.41 (s, 1 H), 1.41 (s, 9 H) ppm. 13C NMR NMR (300 MHz, [D6]DMSO): δ = 10.65 (s, 1 H), 7.71–7.61 (m, 3
(75 MHz, [D6]DMSO): δ = 150.3, 145.9, 142.8, 138.2, 137.0, 135.1,
134.5, 134.3, 130.6, 128.3, 128.1, 128.0, 126.6, 125.5, 125.3, 123.2,
123.1, 120.5, 118.7, 114.7, 113.2, 112.5, 112.1, 99.9, 59.9, 55.1, 46.5,
34.4, 31.2 ppm. HRMS (ESI): calcd. for C35H32ClN2O [M + H]
531.2203; found 531.2201.
H), 7.30 (t, J = 7.2 Hz, 2 H), 7.13–6.83 (m, 6 H), 6.71 (d, J =
7.65 Hz, 1 H), 6.54–6.37 (m, 4 H), 6.07 (s, 1 H), 3.85 (d, J =
10.7 Hz, 1 H), 3.66 (s, 3 H), 3.41 (d, J = 15.6 Hz, 1 H), 1.40 (s, 9
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 159.5, 150.0, 144.6,
144.0, 142.6, 136.0, 134.7, 133.8, 131.1, 129.1, 128.3, 127.3, 127.0,
125.4, 124.4, 123.9, 120.6, 119.5, 118.6, 117.3, 114.0, 113.1, 111.0,
110.4, 99.9, 60.0, 55.1, 46.8, 34.4, 31.2 ppm. HRMS (ESI): calcd.
for C35H33N2O [M + H] 497.2592; found 497.2592.
3-Methoxy-16-phenyl-5,10-dihydro-4bH-indolo[2,3-c]isoquino-
[2,1-a][1]benzazepine (8bae): Green solid, yield 76% (0.54 g). Rf =
0.40 (20:80 ethyl acetate/hexane), m.p. 230–232 °C. FTIR (KBr): ν
˜
= 3420, 3420, 2927, 1602, 1467, 1261 cm–1. 1H NMR (300 MHz,
3-Flouro-16-(4-methylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]iso-
quino[2,1-a][1]benzazepine (8baf): Green solid, yield 76% (0.57 g).
[D6]DMSO): δ = 10.64 (s, 1 H), 7.69 (s, 2 H), 7.52 (s, 1 H), 7.32 (t,
J = 6.3 Hz, 2 H), 7.12–6.86 (m, 7 H), 6.72 (d, J = 7.9 Hz, 1 H), Rf = 0.48 (20:80 ethyl acetate/hexane), m.p. 231–233 °C. FTIR
6.56–6.45 (m, 3 H), 6.35 (d, J = 8.5 Hz, 1 H), 6.10 (s, 1 H), 3.83 (KBr): ν = 3471, 3363, 2925, 1598, 1466, 1249 cm–1 1H NMR
.
˜
(d, J = 9.0 Hz, 1 H), 3.66 (s, 3 H), 3.42 (d, J = 16.3 Hz, 1 H) ppm. (300 MHz, [D6]DMSO): δ = 10.65 (s, 1 H), 7.60 (s, 1 H), 7.51 (s, 1
13C NMR (75 MHz, [D6]DMSO): δ = 159.6, 144.6, 143.9, 142.6, H), 7.31 (d, J = 6.9 Hz, 3 H), 7.16 (d, J = 13.0 Hz, 2 H), 6.97–6.84
137.7, 136.0, 133.8, 131.0, 128.4, 127.7, 127.4, 127.0, 126.4, 125.4,
124.3, 124.0, 120.8, 120.7, 119.6, 118.7, 117.4, 114.0, 113.3, 111.0,
110.3, 99.9, 60.0, 55.1, 46.8 ppm. HRMS (ESI): calcd. for
C31H25N2O [M + H] 441.1966; found 441.1965.
(m, 5 H), 6.73 (d, J = 7.8 Hz, 1 H), 6.53–6.48 (m, 3 H), 6.10 (s, 1
H), 3.67 (d, J = 15.9 Hz, 1 H), 3.46 (d, J = 15.8 Hz, 1 H), 2.46 (s,
3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 164.1, 160.9,
145.8 (d, J = 9.0 Hz), 144.1, 143.2, 137.6, 136.6, 135.4, 134.8, 133.1,
131.0, 128.5, 127.6, 126.4, 125.0 (d, J = 9.0 Hz), 124.6, 121.3, 120.2,
119.3, 117.9, 114.6 (d, J = 27.0 Hz), 113.2 (d, J = 90 Hz) 111.6,
100.6, 60.5, 47.1, 21.5 ppm. HRMS (ESI): calcd. for C31H24FN2
[M + H] 443.1923; found 443.1927.
16-(4-Methylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]isoquino-
[2,1-a][1]benzazepine (8baa): Green solid, yield 50% (0.36 g). Rf =
0.55 (20:80 ethyl acetate/hexane), m.p. 224–226 °C. FTIR (KBr): ν
˜
1
= 3449, 3374, 3052, 2923, 1596, 1459, 1282, 1219 cm–1. H NMR
(300 MHz, [D6]DMSO): δ = 10.69 (s, 1 H), 7.62 (s, 1 H), 7.52 (s, 1
H), 7.33–7.26 (m, 4 H), 7.17–7.10 (m, 2 H), 6.99–6.83 (m, 4 H),
16-Cyclohexenyl-3-methoxy-5,10-dihydro-4bH-indolo[2,3-c]iso-
quino[2,1-a][1]benzazepine (8bad): Gray solid, yield 78% (0.59 g). Rf
6.73 (d, J = 7.7 Hz, 1 H), 6.54–6.48 (m, 3 H), 6.10 (s, 1 H), 5.76 = 0.62 (20:80 ethyl acetate/hexane), m.p. 155–157 °C. FTIR (KBr):
1
(s, 1 H), 3.68 (d, J = 15.8 Hz, 1 H), 3.45 (d, J = 15.8 Hz, 1 H),
ν = 3394, 2920, 1613, 1465, 1273 cm–1. H NMR (300 MHz, [D ]-
˜
6
2.47 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 144.5, 142.6, DMSO): δ = 10.57 (s, 1 H), 7.80 (s, 1 H), 7.29–7.22 (m, 2 H), 7.06
142.4, 138.5, 137.6, 135.8, 134.73, 134.4, 131.4, 129.1, 128.8, 128.5,
127.8, 127.4, 127.3, 125.3, 124.7, 124.2, 121.8, 120.4, 119.8, 119.1,
114.2, 110.9, 98.9, 60.7, 47.4, 21.6 ppm. HRMS (ESI): calcd. for
C31H25N2 [M + H] 425.2017; found 425.2018.
(d, J = 6.8 Hz, 1 H), 6.96–6.79 (m, 6 H), 6.67–6.56 (m, 2 H), 6.04
(s, 1 H), 5.93 (s, 1 H), 3.86 (d, J = 9.9 Hz, 1 H), 3.73 (s, 3 H), 3.55
(d, J = 15.9 Hz, 1 H), 2.34–2.26 (m, 2 H), 1.90–1.77 (m, 6 H) ppm.
13C NMR (50 MHz, [D6]DMSO): δ = 159.5, 144.4, 144.2, 142.9,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O30100
/KAP1
Date: 18-04-13 16:26:03
Pages: 11
S. Samala, M. Saifuddin, A. K. Mandadapu, B. Kundu
FULL PAPER
136.0, 134.1, 131.8, 131.4, 130.4, 128.3, 127.3, 127.0, 124.4, 122.4,
120.7, 119.5, 118.7, 117.6, 114.1, 113.6, 111.0, 110.4, 99.9, 59.6,
55.2, 46.8, 27.1, 25.0, 22.6, 21.8 ppm. HRMS (ESI): calcd. for
C31H29N2O [M + H] 445.2279; found 445.2279.
1041 cm–1. 1H NMR (300 MHz, [D6]DMSO): δ = 10.65 (s, 1 H),
7.23 (d, J = 8.7 Hz, 1 H), 7.07 (s, 1 H), 6.88 (d, J = 9.5 Hz, 3 H),
6.70 (d, J = 8.5 Hz, 1 H), 6.62 (d, J = 7.5 Hz, 1 H), 6.46 (t, J =
7.1 Hz, 1 H), 4.80 (s, 2 H), 3.81 (s, 2 H), 3.69 (s, 3 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 153.3, 146.5, 132.1, 129.7, 128.1,
126.9, 125, 124.5, 116.6, 115.1, 112.4, 111.3, 101.2, 55.7, 27.3 ppm.
HRMS (ESI): calcd. for C16H17N2O [M + H] 253.1340; found
253.1336.
12-Chloro-16-(4-methylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]iso-
quino[2,1a][1]benzazepine (8bba): Yellow solid, yield 52% (0.40 g).
Rf = 0.51 (20:80 ethyl acetate/hexane), m.p. 201–203 °C. FTIR
(KBr): ν = 3434, 2925, 1598, 1460, 1306, 753 cm–1 1H NMR
.
˜
(300 MHz, [D6]DMSO): δ = 10.88 (s, 1 H), 7.62 (s, 1 H), 7.51 (s, 1
H), 7.36–7.27 (m, 4 H), 7.19 (s, 1 H), 7.13 (t, J = 7.0 Hz, 1 H), 6.96
(d, J = 8.4 Hz, 4 H), 6.73 (d, J = 7.8 Hz, 1 H), 6.54 (t, J = 7.7 Hz,
3 H), 6.12 (s, 1 H) 3.66 (d, J = 15.7 Hz, 1 H), 3.46 (d, J = 15.6 Hz,
1 H), 2.46 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 145.9,
142.8, 142.4, 138.4, 137.0, 134.6, 134.5, 133.6, 131.1, 131.0, 128.3,
128.0, 127.9, 126.7, 126.0, 125.5, 124.1, 123.3, 123.1, 120.6, 118.8,
117.5, 114.1, 112.7, 99.9, 59.6, 46.5, 21.0 ppm. HRMS (ESI): calcd.
for C31H24ClN2 [M + H] 459.1628; found 459.1629.
2-Methoxy-6-(2-p-tolylethynyl-phenyl)-5,6,7,12-tetrahydrobenzo-
[2,3]azepino[6,5-b]indole (7aaa): Red solid, yield 70% (0.31 g). Rf =
0.78 (20:80 ethyl acetate/hexane), m.p. 154–156 °C. FTIR (KBr): ν
˜
= 3398, 2927, 1703, 1595, 1477, 1214, 1031 cm–1 1H NMR
.
(300 MHz, [D6]DMSO): δ = 10.27 (s, 1 H), 7.64 (t, J = 8.0 Hz, 2
H), 7.45 (s, 3 H), 7.30 (t, J = 14.6 Hz, 2 H), 7.16 (s, 2 H), 7.06 (d,
J = 8.6 Hz, 1 H), 6.98–6.86 (m, 1 H), 6.76–6.64 (m, 3 H), 6.07 (s,
1 H), 4.95 (s, 1 H), 4.16 (d, J = 15.4 Hz, 1 H), 4.03 (d, J = 6.9 Hz,
1 H), 3.82 (s, 3 H), 2.00 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 153.1, 146.3, 137.5, 134.9, 131.9, 131.4, 130.6, 128.8,
128.7, 128.4, 128.0, 127.4, 127.1, 126.5, 123.7, 122.6, 122.4, 121.5,
111.4, 110.6, 109.6, 99.9, 93.5, 57.7, 58.4, 55.4, 31.5, 28.2 ppm.
HRMS (ESI): calcd. for C32H26N2O [M + H] 455.2123; found
455.2112.
12-Chloro-16-phenyl-5,10-dihydro-4bH-indolo[2,3-c]isoquino-
[2,1-a][1]benzazepine (8bbb): Red solid, yield 60% (0.45 g). Rf =
0.51 (20:80 ethyl acetate/hexane), m.p. 207–209 °C. FTIR (KBr): ν
˜
= 3442, 2923, 1588, 1458, 1304, 1125, 916 cm–1 1H NMR
.
(300 MHz, [D6]DMSO): δ = 10.89 (s, 1 H), 7.73 (s, 2 H), 7.54 (s, 2
H), 7.36–7.27 (m, 3 H), 7.22 (s, 1 H), 7.13 (t, J = 6.8 Hz, 1 H), 6.95
(t, J = 8.5 Hz, 4 H), 6.75 (d, J = 7.7 Hz, 1 H), 6.51 (d, J = 6.7 Hz,
2 H), 6.43 (d, J = 7.5 Hz, 1 H), 6.13 (s, 1 H), 3.67 (d, J = 16.0 Hz,
1 H), 3.47 (d, J = 15.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 146.3, 143.3, 142.9, 138.7, 137.9, 135.0, 134.1, 131.5,
131.0, 130.0, 129.4, 128.8, 128.4, 127.1, 126.4, 126.0, 124.4, 123.7,
123.6, 121.1, 119.3, 118.0, 114.6, 113.1, 100.3, 46.9, 29.4 ppm.
HRMS (ESI): calcd. for C30H22ClN2 [M + H] 445.1471; found
445.1472.
(6-Aminobenzo[1,3]dioxol-5-yl)methanol (2c): White solid, yield
85 % (0.18 g). Rf = 0.35 (20:80 ethyl acetate/hexane), m.p. 121–
123 °C. FTIR (KBr): ν = 3386, 3174, 2927, 1604, 1460, 1214,
˜
1041 cm–1. 1H NMR (300 MHz, [D6]DMSO): δ = 6.58 (s, 1 H),
6.24 (s, 1 H), 5.73 (s, 2 H), 4.85 (s, 1 H), 4.58 (s, 2 H), 4.21 (d, J =
2.5 Hz, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 146.5,
141.3, 137.9, 117.7, 108.2, 99.8, 96.9, 60.7 ppm. HRMS (ESI):
calcd. for C8H10NO3 [M + H] 168.0661; found 168.0642.
8-Bromo-16-(4-terbutylphenyl)-5,10-dihydro-4bH-indolo[2,3-c]-
isoquino[2,1-a][1]benzazepine (8cac): Red solid, yield 60% (0.33 g).
Rf = 0.53 (20:80 ethyl acetate/hexane), m.p. 212–214 °C. FTIR
2-(Cyclohex-1-en-1-ylethynyl)-5-methoxybenzaldehyde (6d): Yellow
solid, yield 87% (0.24 g), m.p. 40–42 °C. Rf = 0.62 (1:19 ethyl acet-
1
ate/hexane). FTIR (KBr): ν = 3441, 2935, 2198, 1688 cm–1. H
˜
(KBr): ν = 3384, 2953, 1718, 1602, 1466, 1270 cm–1 1H NMR
.
˜
NMR (300 MHz, CDCl3): δ = 10.49 (s, 1 H), 7.44 (d, J = 8.5 Hz,
1 H), 7.37 (d, J = 2.8 Hz, 1 H), 7.08 (dd, J1 = 2.8, J2 = 8.5 Hz, 1
H), 6.26–6.24 (m, 1 H), 3.85 (s, 3 H), 2.24–2.13 (m, 4 H), 1.71–1.61
(m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 191.9, 159.4,
137.0, 136.1, 134.4, 121.7, 120.5, 120.4, 109.7, 96.9, 82.3, 55.6, 29.1,
25.9, 22.3, 21.5 ppm. HRMS (ESI): calcd. for C16H17O2 [M + H]
241.1229; found 241.1215.
(300 MHz, [D6]DMSO): δ = 10.62 (s, 1 H), 7.71–7.52 (m, 4 H),
7.40 (s, 1 H), 7.33–7.26 (m, 2 H), 7.16–7.06 (m, 3 H), 6.99 (t, J =
7.2 Hz, 1 H), 6.89–6.78 (m, 2 H), 6.72 (d, J = 8.6 Hz, 1 H), 6.59
(s, 1 H), 6.38–6.33 (m, 1 H), 6.11 (s, 1 H), 3.72 (d, J = 16.4 Hz, 1
H), 3.47 (d, J = 15.5 Hz, 1 H), 1.41 (s, 9 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 150.7, 145.5, 142.9, 141.9, 136.2, 134.4,
134.1, 133.5, 130.2, 129.1, 127.6, 127.0, 126.7, 126.1, 125.3, 124.7,
123.4, 120.9, 119.7, 118.8, 116.1, 111.2, 108.4, 100.2, 60.4, 34.4,
31.2, 30.8 ppm. HRMS (ESI): calcd. for C34H30BrN2 [M + H]
545.1592; found 545.1562.
2-{[4-(tert-Butyl)phenyl]ethynyl}-5-methoxybenzaldehyde (6 g):
White solid, yield 91% (0.31 g), m.p. 83–85 °C. Rf = 0.51 (1:19 ethyl
acetate/hexane). FTIR (KBr): ν = 3434, 2963, 2132, 1686 cm–1. 1H
˜
NMR (300 MHz, CDCl3): δ = 10.61 (s, 1 H), 7.57–7.53 (m, 1 H),
7.49–7.46 (m, 2 H), 7.42–7.37 (m, 3 H), 7.14–7.11 (m, 1 H), 3.88
(s, 3 H), 1.33 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 191.8,
159.8, 152.3, 137.3, 134.6, 131.4, 125.6, 121.8, 120.0, 119.7, 109.9,
95.23, 84.3, 55.7, 34.9, 31.2 ppm. HRMS (ESI): calcd. for
C20H21O2 [M + H] 293.1542; found 293.1528.
8-Bromo-12-chloro-16-phenyl-5,10-dihydro-4bH-indolo[2,3-c]iso-
quino[2,1-a][1]benzazepine (8cbb): Red solid, yield 59% (0.31 g). Rf
= 0.46 (20:80 ethyl acetate/hexane), m.p. 197–199 °C. FTIR (KBr):
1
ν = 3402, 2923, 1723, 1459, 1274, 696 cm–1. H NMR (300 MHz,
˜
[D6]DMSO): δ = 10.85 (s, 1 H), 7.74 (s, 2 H), 7.57 (s, 2 H), 7.47 (s,
1 H), 7.38–7.30 (m, 3 H), 7.17 (t, J = 7.7 Hz, 1 H), 7.09 (d, J =
8.5 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H), 6.73 (d, J = 8.4 Hz, 1 H),
6.57 (s, 1 H), 6.40 (d, J = 5.9 Hz, 1 H), 6.16 (s, 1 H), 3.73 (d, J =
15.3 Hz, 1 H), 3.48 (d, J = 15.6 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 145.6, 143.1, 142.4, 138.2, 137.2, 135.4,
135.0, 130.8, 130.1, 129.7, 129.0, 128.7, 128.1, 127.3, 126.4, 126.1,
124.6, 123.8, 121.3, 119.4, 116.7, 113.2, 108.8, 100.4, 60.2, 46.6,
29.4 ppm. HRMS (ESI): calcd. for C30H21BrClN2 [M + H]
523.0576; found 523.0571.
2-{[4-(tert-Butyl)phenyl]ethynyl}-5-fluorobenzaldehyde (6h): Yellow
solid, yield 81% (0.28 g), m.p. 63–65 °C. Rf = 0.61 (1:19 ethyl acet-
1
ate/hexane). FTIR (KBr): ν = 3437, 2963, 2215, 1694 cm–1. H
˜
NMR (300 MHz, CDCl3): δ = 10.59 (d, J = 2.9 Hz, 1 H), 7.65–
7.59 (m, 2 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.40 (d, J = 8.2 Hz, 2 H),
7.32–7.28 (m, 1 H), 1.33 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 190.6 (d, J = 1.5 Hz), 162.4 (d, J = 251.2 Hz), 152.8, 137.8 (d,
J = 6.7 Hz), 135.3 (d, J = 8.2 Hz), 131.5, 125.7, 123.4 (d, J = 3 Hz),
121.6, 121.3, 119.2, 113.7 (d, J = 22.5 Hz), 96.4 (d, J = 1.5 Hz),
83.4, 35.0, 31.2 ppm. HRMS (ESI): calcd. for C19H18FO [M + H]
281.1342; found 281.1331.
2-(5-Methoxy-1H-indol-3-ylmethyl)phenylamine (4aa): White solid,
yield 77% (0.33 g). Rf = 0.51 (20:80 ethyl acetate/hexane), m.p.
137–139 °C. FTIR (KBr): ν = 3386, 3174, 2927, 1604, 1460, 1214,
˜
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O30100
/KAP1
Date: 18-04-13 16:26:03
Pages: 11
One-Pot Tandem-Intramolecular Hydroamination Reactions
2011, 13, 3162–3165; c) S. K. Sharma, S. Gupta, M. Saifuddin,
Supporting Information (see footnote on the first page of this arti-
cle): The 1H NMR and 13C NMR spectroscopic data for represen-
tative compounds is provided
A. K. Mandadapu, P. K. Agarwal, H. M. Gauniyal, B. Kundu,
Tetrahedron Lett. 2011, 52, 65–68; d) S. K. Sharma, A. K.
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Acknowledgments
S. S., M. S. and A. K. M are thankful to Council of Scientific and
Industrial Research (CSIR), New Delhi for fellowships. The au-
thors would like to thank SAIF, CDRI, India for providing analyti-
cal data.
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