Unprecedented access to functionalized pyrrolo[2,1-a]isoquinolines from the domino reaction of isoquinolinium ylides and electrophilic benzannulated heterocycles

Article abstract of DOI:10.1039/d1ob00005e

We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methylides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield the products in good yields. We also observed the f

Full text of DOI:10.1039/d1ob00005e

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Unprecedented access to functionalized pyrrolo
[2,1-a]isoquinolines from the domino reaction of
isoquinolinium ylides and electrophilic
benzannulated heterocycles†
Cite this: Org. Biomol. Chem., 2021,
19, 1807
Sheba Ann Babu,a,b Rajalekshmi A. R.,a Nitha P. R.,a,b Vishnu K. Omanakuttan,a,b
a,b
Rahul P.,a,b Sunil Varughese
*
a,b and Jubi John
*
Received 2nd January 2021,
Accepted 25th January 2021
We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methyl-
ides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield
the products in good yields. We also observed the formation of S–S-bridged bis-pyrrolo[2,1-a]isoquino-
lines from the reaction of 3-nitro benzothiophene and isoquinolinium methylides.
DOI: 10.1039/d1ob00005e
rsc.li/obc
us devise dipolar cycloaddition reactions towards novel hetero-
acenes (Scheme 1d).
Introduction
Electrophilic benzannulated heterocycles, which exhibit
Heteroaromatic N-ylides are a class of dipoles which have
unusual reactivity can be generated by installing electron-with- been comprehensively studied for the generation of highly
drawing substituents at precise positions.1 In this way, an functionalized carbocycles and heterocycles.8 In particular,
indole moiety can be made electrophilic by placing electron- isoquinolinium methylides have been utilized in dipolar
withdrawing groups on the N-atom and C-2 or C-3 carbon cycloaddition reactions with several dipolarophiles, such as
atoms. The chemistry of electrophilic indoles was extensively electron-deficient alkenes and alkynes to access fused
investigated by several groups for the synthesis of functiona-
lized (or fused) indoline/indole moieties.2 Dipolar cyclo-
addition utilizing an electrophilic indole as the dipolarophile
towards annulated heterocycles has been reported by different
groups. The first of these reports came from Gribble’s group in
1998 in which they synthesized pyrrolo[3,4-b]indoles via the
dipolar cycloaddition of münchnones with an electrophilic
indole (Scheme 1a).3 Later, the same group also reported the
reaction of azomethine ylides with electrophilic indoles, fur-
nishing hexahydropyrrolo[3,4-b]indoles.4 The asymmetric
version of azomethine ylide addition to an electrophilic indole
was independently reported by Arai and Stanley (Scheme 1b).5
In 2017, Wang and co-workers reported the synthesis of five-
ring-fused tetrahydroisoquinolines from azomethine imines
and electrophilic indoles (Scheme 1c).6 Our interest in the
chemistry of electrophilic benzannulated heterocycles7 made
aChemical Sciences and Technology Division, CSIR-National Institute for
Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram
695019, India. E-mail: jubijohn@niist.res.in, s.varughese@niist.res.in
bAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
†Electronic supplementary information (ESI) available. CCDC 2042168 and
2042169. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/d1ob00005e
Scheme 1 Dipolar cycloadditions involving electrophilic benzannulated
heterocycles.
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N-heterocyclic scaffolds.9 The 1,3-dipolar cycloaddition of iso- developing different metal cation and organic sensors.16 Two
quinolinium methylides to nitrostyrenes has been reported well-known strategies to access pyrrolo[2,1-a]isoquinolines are
previously. The first work in this line was published in 1990 the annulation of appropriate rings to a substituted pyrrole or
when 1-nitro-2-phenyl-3-R-2,3-dihydrobenzo[g]indolizine was an N-functionalized isoquinoline.13,15a,17 In 2019, Dong and
synthesized via the reaction between β-nitrostyrene and isoqui- Huang reported the synthesis of substituted indolizines from
nolinium methylide.10 Later, Kucukdisli and Opatz reported the reaction of chromones and pyridinium salts.18 This reac-
the reaction of different heteroaromatic N-ylides (including tion proceeded via a 1,3-dipolar cycloaddition-ring opening
isoquinolinium methylides) with β-nitrostyrene and found that and aromatization cascade.
aromatized products were obtained after the elimination of
Intrigued by the unexpected synthesis of the substituted
HNO2.11 In 2014, the dipolar cycloaddition of isoquinolinium pyrrolo[2,1-a]isoquinoline moiety, we went on with the optim-
methylides to 3-nitrochromenes was reported to furnish azadi- ization of the reaction conditions with 1a and 2a as substrates.
benzo[a,g]fluorene derivatives.12 Inspired by these reports on Screening of different bases, such as BuOK, BuONa, NaOMe,
the dipolar cycloaddition of isoquinolinium methylides to Cs2CO3, K2CO3, Na2CO3, KOH, NaOH, LiOH, NaH and DIPEA
nitrostyrenes, we hypothesized that the reactions of these het- (Table 1, entries 1–11) revealed that KOH was the most suitable
eroaromatic N-ylides with electrophilic benzannulated hetero- base, furnishing the product in 54% yield. Then, we focused
cycles would result in the development of novel heteroacenes on the effect of different solvents on the reaction outcome
t
t
(Scheme 1d).
(Table 1, entries 12–16). Among the screened solvents, DMF
was found to be the most effective, giving the product in 54%
yield. The yield of the reaction was found to decrease when the
amount of base was decreased to 2.0 equivalents. In this case,
the starting material was found to remain unreacted and no
by-product was observed (Table 1, entry 19). Finally, we turned
our attention towards the effect of substrate concentration on
the reaction. To our delight, the use of 1.5 equivalents of 2a
increased the yield of 3a to 88% (Table 1, entry 18).
Results and discussion
We commenced our studies by selecting N-tosyl-3-nitro indole
1a and 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a as
model substrates. Initially, 1a (1.0 equiv.) and 2a (1.1 equiv.)
were treated in the presence of potassium t-butoxide (tBuOK,
4.0 equiv.) in dimethylformamide (DMF) at room temperature
for 1 h. Contrary to our expectation of the formation of a pen-
tacene, as depicted in Scheme 1d, the 1,3-dipolar cycloaddition
reaction between 1a and 2a resulted in the formation of func-
tionalized pyrrolo[2,1-a]isoquinoline 3a in 48% yield
(Scheme 2). The structure of 3a established by various spectro-
scopic analyses was further confirmed from X-ray crystallo-
graphic data.
With the optimized conditions in hand (1.0 equiv. of 1a, 1.5
equiv. of 2a, 4.0 equiv. of KOH, DMF, rt), we then explored the
scope of the 1,3-dipolar cycloaddition of isoquinolinium
Table 1 Optimization studiesa
Pyrrolo[2,1-a]isoquinoline moieties13 are important fused
N-heterocycles that are found in plenty of core structures of
natural products, such as crispine A and B, trolline, lamellar-
ins, and erythrina alkaloids, which are found to show interest-
ing anticancer, antiviral and antibacterial activities.14
Synthetic pyrrolo[2,1-a]isoquinolines have also been found to
exhibit a plethora of biological properties, such as anticancer
effects, multidrug resistance (MDR) reversal, estrogen receptor
modulation, deoxyribonucleic acid (DNA) chelation, and anti-
microbial, antiplatelet and anti-inflammatory effects.15 In
addition, these fused N-heterocycles have been utilized in
Entry
Base
Solvent
Time (h)
Yield of 3a (%)
1
2
3
4
5
6
7
8
tBuOK
tBuONa
NaOMe
Cs2CO3
K2CO3
Na2CO3
KOH
NaOH
LiOH
NaH
DIPEA
KOH
KOH
KOH
KOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1,4-Dioxane
EtOH
CH3CN
EtOAc
THF
DMF
DMF
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
12
1
1
48
21
—
37
16
Trace
54
49
43
38
—
16
—
26
—
9
10
11
12
13
14
15
16
17
18b
19c
KOH
KOH
KOH
KOH
22
61
88
10
DMF
a Reaction conditions: 1a (1.0 equiv., 0.16 mmol), 2a (1.1 equiv.), base
(4.0 equiv.), solvent (1.0 mL), rt. b 2a (1.5 equiv.). c Base (2.0 equiv.).
Scheme 2 1,3-Dipolar cycloaddition of an isoquinolinium methylide
with an electrophilic indole.
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Table 2 Generalization of 1,3-dipolar cycloaddition of isoquinolinium
methylides with substituted electrophilic indolesa
Table 3 Generalization of 1,3-dipolar cycloaddition reaction with
various isoquinolinium bromidesa
a Reaction conditions: 1 (1.0 equiv., 100 mg), 2a (1.5 equiv.), KOH (4.0
equiv.), DMF (0.16 M), rt, 1 h.
Reaction conditions: a 1 (1.0 equiv., 100 mg), 2a (1.5 equiv.), KOH (4.0
equiv.), DMF (0.16 M), rt, 1 h. b 4 h.
methylides using different substituted electrophilic indoles,
the results of which are summarized in Table 2. In this way,
the generalization of different 3-nitro-indoles 1 with the model
substrate 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a was
studied. Reactions with halogens (Br, F, Cl)-substituted
nitroindoles proceeded well, affording products 3b, 3c and 3d
in good yields. The dipolar cycloaddition of 2a with 3-nitro-1-
tosyl-1H-indole-5-carbonitrile afforded the corresponding sub-
stituted pyrrolo[2,1-a]isoquinoline 3e in 52% yield. With an
electron-releasing OMe-substituent (5-methoxy-3-nitro-1-tosyl-
1H-indole), even after heating to reflux in DMF for a prolonged
period of time, the reaction failed, which might be due to the
reduced electrophilicity (3f). Next, the electron-withdrawing
substituent on the N-atom of the indole was changed to Boc,
in which case the expected product 3g was isolated in 75%
yield. The reactions with electrophilic indole substrates with
SO2Me and SO2Ph on the N-atom afforded 3h and 3i in 52%
and 61% yields. Finally, other sulfonyl substituents on the
N-atom of the indole were found to influence the outcome of
the reaction from which products 3j to 3m were obtained in
moderate to excellent yields.
pyrrolo[2,1-a]isoquinoline 3r in 62% yield. Finally, isoquinoli-
nium bromides 2f–2i prepared from 4-bromo isoquinoline and
5-bromo isoquinoline were tested for reactivity in the present
transformation and products 3s–3v were isolated from the
reactions in satisfactory yields. N-Methyl-3-nitroindole led to
the formation of pyrrolo[2,1-a] isoquinoline 3w, wherein we
observed the elimination of the N-methyl group.
We also attempted a gram-scale synthesis (starting from
1.0 g of 1a) of pyrrolo[2,1-a]isoquinoline 3a, and the com-
pound was obtained in 72% yield (Scheme 3). Compound 3a
was then subjected to Ts-deprotection by treating it with con-
centrated H2SO4 for 2 hours, which furnished pyrrolo[2,1-a]iso-
quinoline 4. In compound 4 not only was the Ts-group
removed but the CN-moiety was also converted to the corres-
ponding amide.
Based on our observations and on the reported
literature,10–12 we propose a plausible mechanism for the
present domino dipolar cycloaddition-ring opening process
that takes place during the reaction of electrophilic indole and
Further investigations were focused on evaluating the reac-
tivity of different isoquinolinium bromides in the present
dipolar cycloaddition with electrophilic indoles (Table 3). The
reactions with isoquinolinium methylides 2b–2d (with
different substituents on the para-position of the phenyl ring)
afforded the products 3n–3p in good yields. The isoquinoli-
nium methylides 2e with an ethoxycarbonyl-group as the elec-
Scheme 3 Gram-scale reaction of 1a with 2a and N-Ts deprotection of
tron-withdrawing moiety also afforded the corresponding pyrrolo[2,1-a]isoquinoline 3a.
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Table 4 Optimization studiesa
Scheme 4 Plausible mechanism for the synthesis of pyrrolo[2,1-a]iso-
quinoline 3.
Temp. Yield of 6a
Entry Base
Solvent
(°C)
(%)
isoquinolinium methylide (Scheme 4). The first step is the
deprotonation of the activated methylene group of the isoqui-
nolinium salt by KOH to generate the corresponding N-ylide.
This dipole then participates in a 1,3-dipolar cycloaddition
with the dipolarophile, N-tosyl-3-nitroindole 1a to generate the
corresponding cycloadduct A (Scheme 4). Subsequent elimin-
ation of HNO2 from A generates intermediate B, which upon
aromatization results in a strain-induced cleavage of the C–N
bond, furnishing the final product pyrrolo[2,1-a]isoquinoline
3a.
The unexpected domino transformation observed from the
reaction of electrophilic indoles and isoquinolinium methyl-
ides prompted us to check the reactivity of electrophilic ben-
zothiophenes. The initial experiment was performed by react-
ing 3-nitro benzothiophene 5a with 2-(2-oxo-2-phenylethyl)iso-
quinolin-2-ium-bromide 2b in the presence of KOH (2.0 equiv.)
in DMF at room temperature. After 24 h, a bis-pyrrolo[2,1-a]iso-
quinoline 6a linked with an S–S bond was isolated in 12%
yield (Scheme 5). The structure of 6a was established by
various spectroscopic analyses and confirmed from X-ray crys-
tallographic data.
1
KOH
KOH
KOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
EtOH
THF
1,4-Dioxane 60
CH3CN
DMA
DMSO
DMF
rt
rt
rt
12
10
10
14
14
10
29
14
—
12
—
—
—
80
14
20
2b
3c
4
KOH
60
60
60
60
60
60
60
60
60
5
6
7
8
tBuOK
NaOH
K3PO4
K2CO3
Na2CO3
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4, Cu(OAc)2·H2O
9
10
11
12
13
14
15
16
17
18d
19e
60
60
60
60
60
60
Trace
Trace
20
2,6-Lutidine, Cu(OAc)2·H2O DMF
K3PO4 CH3CN
a Reaction conditions: 5a (1.0 equiv., 0.28 mmol), 2b (1.5 equiv.), base
(2.0 equiv.), solvent (1.0 mL), rt, 24 h. b Base (4.0 equiv.). c 2b (3.0
equiv.). d Base (5.0 equiv.); Cu(OAc)2·H2O (1.5 equiv.). e Under an argon
atmosphere.
The poor yield obtained for the synthesis of bis-pyrrolo[2,1-
a]isoquinoline 6a prompted us to optimize the reaction con-
ditions with 5a and 2b as substrates. Increasing the equiva-
lents of base and 2b was found not to have a positive outcome
on the reaction yield (Table 4, entries 2 and 3). A slight
increase in the yield of 6a was noted by carrying out the reac-
tion at 60 °C (Table 4, entry 4). Screening of different bases,
such as K2CO3, K3PO4, Na2CO3, Cs2CO3, NaOH, KOH and
KOtBu (Table 4, entries 4–10), revealed that K3PO4 was more
efficient. Further screening of solvents showed that CH3CN
gave better results in comparison to other solvents, such as
DMF, THF, EtOH, DMA, 1,4-dioxane or DMSO (Table 4, entries
7, 11–16). Also, performing the reaction in the presence of an
oxidant, Cu(OAc)2·H2O, was found to be less efficient (Table 4,
entries 17 and 18). Finally, we carried out the reaction under
an inert atmosphere to see whether the oxidation of intermedi-
ate thiol to an S–S bond bridged bis-pyrrolo[2,1-a]isoquinoline
could be prevented (Table 4, entry 19). From this reaction, 6a
was isolated in low yield and we were not able to isolate the
thiol or any other intermediates. Complete consumption of
3-nitrobenzothiophene 5a was not observed in any of the reac-
tions mentioned above.
Table 5 Generalization of 1,3-dipolar cycloaddition reaction of various
isoquinolinium methylides with 3-nitro benzothiophenea
a Reaction conditions: 5 (1.0 equiv., 100 mg), 2 (1.5 equiv.), K3PO4 (2.0
equiv.), CH3CN (0.28 M), 60 °C, 24 h.
Scheme 5 Synthesis of bis-pyrrolo[2,1-a]isoquinoline 6a from 3-nitro
benzothiophene and 2b.
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With the optimized conditions in hand [1.0 equiv. of 5a, 1.5 (Hz) and multiplicities are indicated as follows s (singlet), d
equiv. of 2b, 2.0 equiv. of K3PO4, CH3CN (1 ml), 60 °C], the (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of
scope of the reaction for the synthesis of bis-pyrrolo[2,1-a]iso- doublets). Mass spectra were recorded with a ThermoFinnigan
quinoline was investigated (Table 5). The presence of a phenyl- MAT95XL, a ThermoFisher Scientific LTQ Orbitrap Velos, and
ethanone substitution on the isoquinolinium N-atom resulted an Agilent 6890 gas chromatograph with a JMS-T100GC
in a better reaction, furnishing the corresponding S–S-bridged spectrometer or with an ESI/HRMS at 60 000 resolution using
bis-pyrrolo[2,1-a]isoquinolines 6a–6c in good to excellent a Thermo Scientific Exactive mass spectrometer with orbitrap
yields. Reactions of isoquinolinium methylides 2e with an analyzer. Gas chromatographic analysis was performed using
ethoxycarbonyl group as the electron-withdrawing substituent GCMS-TQ8030 SHIMADZU.
afforded the corresponding products 6d and 6e in satisfactory
yields. In all the reactions mentioned above, unreacted 3-nitro-
benzothiophene 5a was recovered.
Experimental procedure for the reaction between 3-nitro-N-
tosyl indole and isoquinolinium salt
A mixture of 3-nitro-N-tosyl indole (1.0 equiv., 100 mg), isoqui-
nolinium salt (1.5 equiv.) and KOH (4.0 equiv.) was weighed
into a dry reaction tube. Dry DMF was added and the reaction
Conclusions
mixture was stirred at room temperature. After completion of
In short, we have developed a domino reaction involving a 1,3- the reaction as indicated from the TLC, water was added and
dipolar cycloaddition and a ring-opening between isoquinoli- the aqueous layer was extracted three times with ethyl acetate.
nium ylides and electrophilic benzannulated heterocycles. The organic layer was dried over anhydrous Na2SO4 and the
This hitherto unknown methodology gives easy access to a solvent was removed under vacuum. The residue was then pur-
series of highly functionalized pyrrolo[2,1-a] isoquinolines ified by column chromatography (neutral alumina, eluent:
starting from different isoquinolinium methylides and mixtures of ethyl acetate/hexanes) to afford the corresponding
3-nitroindoles. In addition, we observed the formation of S–S- products.
bridged bis-pyrrolo[2,1-a]isoquinolines from the reaction of
3-nitro benzothiophene and isoquinolinium methylides. We
have also demonstrated the applicability of this cycloaddition
Synthesis and characterization of pyrrolo[2,1-a]isoquinolines
(3a–3v)
reaction for the generation of pyrrolo[2,1-a] isoquinolines on
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-4-methyl-
the gram scale. Presently, we are currently looking at ways to benzenesulfonamide (3a). The general procedure was followed
synthesize pentacenes and dibenzazepines via site-selective C– using 3-nitro-N-tosyl indole 1a (100 mg, 0.32 mmol), 2-(cyano-
H activation from the above obtained pyrrolo[2,1-a]isoquino- methyl)isoquinolin-2-ium-bromide 2a (118 mg, 0.47 mmol)
lines, the details of which will be reported in due course.
and KOH (71 mg, 1.26 mmol) at rt for 1 h. Chromatography
(eluent: 20% ethyl acetate in hexane) afforded the desired
product 3a as a pale yellow solid (122 mg, 88%). Mp:
147–150 °C. IR (neat) νmax: 3884, 3822, 3732, 3485, 3010, 2356,
Experimental
General experimental methods
1546, 1493, 1452, 1334, 1161, 1091, 903, 762 cm−1 1H NMR
.
(500 MHz, CDCl3, TMS): δ 8.09 (d, J = 7 Hz, 1H), 7.84 (d, J = 8.5
All chemicals were of the best grade commercially available Hz, 1H), 7.68 (d, J = 7.5 Hz, 1H), 7.50–7.44 (m, 2H), 7.38 (d, J =
and were used without further purification. All solvents were 8.5 Hz, 2H), 7.25–7.21 (m, 2H), 7.17–7.13 (m, 3H), 7.10 (d, J = 8
purified according to the standard procedures; dry solvents Hz, 2H), 6.44 (s, 1H), 6.38 (s, 1H), 2.37 (s, 3H) ppm. 13C{1H}
were obtained according to the methods in the literature and NMR (125 MHz, CDCl3): δ 144.0, 136.2, 135.6, 131.6, 130.1,
stored over molecular sieves. Analytical thin-layer chromato- 129.7, 129.6, 128.6, 128.4, 128.1, 127.5, 127.0, 126.8, 125.4,
graphy was performed on polyester sheets pre-coated with 124.9, 122.8, 122.7, 122.5, 121.7, 114.6, 113.0, 112.9, 98.0,
silica gel containing a fluorescent indicator (POLYGRAMSIL G/ 21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for
UV254). Gravity column chromatography was performed using C26H19N3NaO2S 460.10902, found 460.11007.
neutral alumina, and mixtures of ethyl acetate hexanes were
used for elution melting points which were determined using 4-methylbenzenesulfonamide (3b). The general procedure was
calibrated digital melting point apparatus (Büchi followed using 5-bromo-3-nitro-N-tosyl indole 1b (100 mg,
N-(4-Bromo-2-(3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
a
530 melting point apparatus). Infrared spectra were recorded 0.25 mmol), 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a
on a Bruker FT-IR spectrometer. Nuclear magnetic resonance (95 mg, 0.38 mmol) and KOH (57 mg, 1.01 mmol) at rt for 1 h.
(NMR) spectra were recorded using a Bruker Avance-300 Chromatography (eluent: 25% ethyl acetate in hexane)
1
(300 MHz for H NMR, 75 MHz for 13C{1H} NMR) and Bruker afforded the desired product 3b as a brown solid (98 mg,
AMX-500 (500 MHz for 1H NMR, 125 MHz for 13C{1H} NMR) 75%). Mp: 208–210 °C. IR (neat) νmax: 3837, 3747, 3534, 3463,
instruments. All spectra were measured at 300 K, unless other- 3273, 2959, 2205, 1721, 1451, 1269, 1116, 1069, 885, 740 cm−1
.
wise specified. The chemical shifts δ are given in ppm and 1H NMR (500 MHz, (CD3)2CO, TMS): δ 8.20 (d, J = 7.5 Hz, 1H),
referenced to the external standard TMS or internal solvent 8.13 (s, 1H), 7.85 (d, J = 8 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.71
standard. 1H NMR coupling constants (J) are reported in Hertz (dd, J1 = 9 Hz, J2 = 1.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.51 (d, J
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= 1.5 Hz, 1H), 7.44 (d, J = 8 Hz, 2H), 7.35 (d, J = 7.5 Hz, 1H), 1H), 2.40 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ
7.29–7.24 (m, 2H), 7.17 (d, J = 7.5 Hz, 2H), 6.73 (s, 1H), 2.36 (s, 144.8, 140.2, 135.6, 135.5, 133.6, 130.3, 129.9, 128.8, 128.6,
3H) ppm. 13C{1H} NMR (125 MHz, (CD3)2CO): δ 143.7, 137.3, 128.4, 127.8, 127.1, 126.4, 124.5, 124.1, 122.6, 122.6, 122.4,
136.1, 134.4, 132.2, 130.5, 130.4, 129.4, 128.6, 128.2, 127.9, 122.0, 120.7, 119.8, 119.3, 118.0, 115.1, 112.4, 111.0, 110.0,
127.6, 126.8, 125.1, 124.9, 123.2, 122.8, 122.6, 117.5, 114.3, 108.0, 102.7, 99.0, 21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M +
112.6, 112.5, 97.8, 20.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for C27H18N4NaO2S 485.10427, found 485.10656.
Na)+ calcd for C26H18BrN3NaO2S 538.01953, found 538.02063.
tert-Butyl(2-(3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)
N-(4-Chloro-2-(3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)- carbamate (3g). The general procedure was followed using
4-methylbenzenesulfonamide (3c). The general procedure was 3-nitro-N-Boc indole 1g (100 mg, 0.38 mmol), 2-(cyanomethyl)
followed using 5-chloro-3-nitro-N-tosyl indole 1c (100 mg, isoquinolin-2-ium-bromide 2a (143 mg, 0.57 mmol) and KOH
0.28 mmol), 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a (85 mg, 1.53 mmol) at rt for 1 h. Chromatography (eluent: 10%
(106 mg, 0.42 mmol) and KOH (64 mg, 1.14 mmol) at rt for ethyl acetate in hexane) afforded the desired product 3g as a
1 h. Chromatography (eluent: 20% ethyl acetate in hexane) colourless solid (110 mg, 75%). Mp: 157–160 °C. IR (neat) νmax
afforded the desired product 3c as a yellow solid (96 mg, 72%). 3804, 3586, 3533, 3506, 3365, 2992, 2359, 2326, 2206, 1717,
Mp: 190–192 °C. IR (neat) νmax: 3839, 3751, 3570, 3481, 3265, 1513, 1452, 1151, 1021, 829, 763, 739, 702 cm−1 1H NMR
:
.
3239, 3142, 3048, 2952, 2207, 1595, 1490, 1327, 1160, 1087, (500 MHz, CDCl3, TMS): δ 8.14 (d, J = 8 Hz, 1H), 8.07(d, J = 7.5
890, 778, 674 cm−1. 1H NMR (500 MHz, CDCl3, TMS): δ 8.02 (d, Hz, 1H), 7.61 (d, J = 8 Hz, 1H), 7.47 (d, J = 8.5 Hz, 1H),
J = 7.5 Hz, 1H), 7.72 (d, J = 9 Hz, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.42–7.39 (m, 2H), 7.26–7.22 (m, 2H), 7.19 (s, 1H), 7.17 (s, 1H),
7.42–7.37 (m, 2H), 7.29 (d, J = 8 Hz, 2H), 7.16–7.05 (m, 6H), 7.10–7.07 (m, 2H), 6.22 (s, 1H), 1.23 (s, 9H) ppm. 13C{1H} NMR
6.32 (s, 1H), 6.25 (s, 1H), 2.32 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 152.7, 137.1, 131.3, 130.1, 129.4, 128.6,
(125 MHz, CDCl3): δ 144.4, 135.9, 134.3, 131.4, 130.7, 130.1, 128.4, 128.0, 127.2, 125.4, 124.2, 123.5, 123.4, 123.2, 122.7,
129.8, 129.7, 128.8, 128.6, 128.5, 128.3, 127.7, 127.0, 124.7, 119.8, 114.5, 114.3, 113.3, 98.2, 80.6, 28.1 ppm. HRMS
123.1, 122.7, 122.5, 114.8, 112.6, 111.6, 98.3, 21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M
(ESI-Orbitrap) m/z: (M + Na)+ calcd for C26H18ClN3NaO2S 406.15260, found 406.15397.
+
Na)+ calcd for C24H21N3NaO2
494.07004, found 494.07205.
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)-4-fluorophenyl)-
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)methane-
sulfonamide (3h). The general procedure was followed using 1-
4-methylbenzenesulfonamide (3d). The general procedure was (methylsulfonyl)-3-nitro-1H-indole 1h (100 mg, 0.42 mmol), 2-
followed using 5-flouro-3-nitro-N-tosyl-indole 1d (100 mg, (cyanomethyl)isoquinolin-2-ium-bromide 2a (155 mg,
0.29 mmol), 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a 0.62 mmol) and KOH (93 mg, 1.66 mmol) at rt for 1 h.
(111 mg, 0.44 mmol) and KOH (67 mg, 1.19 mmol) at rt for Chromatography (eluent: 20% ethyl acetate in hexane)
1 h. Chromatography (eluent: 20% ethyl acetate in hexane) afforded the desired product 3h as a colourless solid (78 mg,
afforded the desired product 3d as a brown solid (97 mg, 52%). Mp: 167–169 °C. IR (neat) νmax: 3884, 3769, 3688, 3546,
71%). Mp: 172–174 °C. IR (neat) νmax: 3869, 3805, 3714, 3622, 3478, 3269, 2903, 2206, 1569, 1485, 1385, 1326, 1157, 1101,
1
3479, 3326, 3190, 2214, 1546, 1453, 1324, 1154, 1087, 784, 969, 768 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 8.08 (d, J =
662 cm−1. 1H NMR (500 MHz, CDCl3, TMS): δ 8.07 (d, J = 7 Hz, 7.5 Hz, 1H), 7.72 (d, J = 8.5 Hz, 1H), 7.64 (d, J = 8 Hz, 1H), 7.47
1H), 7.85–7.82 (m, 1H), 7.69 (d, J = 8 Hz, 1H), 7.48 (t, J = 7.5 (t, J = 8 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.35 (d, J = 8 Hz, 1H),
Hz, 1H), 7.30 (d, J = 8 Hz, 2H), 7.25–7.17 (m, 3H), 7.15 (d, J = 7.31 (d, J = 7.5 Hz, 1H), 7.24–7.19 (m, 2H), 7.12–7.10 (m, 2H),
7.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 2H), 6.94 (d, J = 8 Hz, 1H), 6.27 6.22 (s, 1H), 2.78 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3):
(s, 1H), 6.26 (s, 1H), 2.38 (s, 3H) ppm. 13C{1H} NMR (125 MHz, δ 136.0, 132.2, 130.2, 128.7, 128.6, 128.4, 127.8, 125.4, 125.0,
CDCl3): δ 161.0, 159.1, 144.2, 135.9, 131.6, 131.6, 129.9, 129.7, 124.9, 122.9, 122.7, 122.7, 118.8, 114.9, 112.9, 112.8, 98.6,
129.6, 128.8, 128.5, 128.3, 127.7, 127.0, 125.0, 124.9, 124.6, 39.9 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for
122.6, 122.5, 122.4, 118.3, 118.1, 116.8, 116.6, 114.8, 112.7, C20H15N3NaO2S 384.07772, found 384.07822.
112.0, 98.1, 21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+
calcd for C26H18FN3NaO2S 478.09960, found 478.10168.
N-(4-Cyano-2-(3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)benzene-
sulfonamide (3i). The general procedure was followed using
3-nitro-1-(phenylsulfonyl)-1H-indole 1i (100 mg, 0.33 mmol),
4-methylbenzenesulfonamide (3e). The general procedure was 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a (124 mg,
followed using 5-cyano-3-nitro-N-tosyl-indole 1e (100 mg, 0.50 mmol) and KOH (74 mg, 1.32 mmol) at rt for 1 h.
0.29 mmol), 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a Chromatography (eluent: 20% ethyl acetate in hexane)
(110 mg, 0.44 mmol) and KOH (66 mg, 1.17 mmol) at rt for afforded the desired product 3i as a colourless solid (85 mg,
1 h. Chromatography (eluent: 25% ethyl acetate in hexane) 61%). Mp: 203–205 °C. IR (neat) νmax: 3870, 3848, 3726, 3675,
afforded the desired product 3e as a yellow solid (71 mg, 52%). 3536, 3451, 3301, 3260, 2876, 2355, 2196, 1576, 1487, 1445,
1
Mp: 217–220 °C. IR (neat) νmax: 3920, 3870, 3815, 3750, 3674, 1386, 1329, 1159, 1092, 896 cm−1. H NMR (500 MHz, CDCl3,
1
3535, 3463, 2906, 2209, 1523, 1490, 1334, 1163, 901 cm−1. H TMS): δ 8.02 (d, J = 7 Hz, 1H), 7.77 (d, J = 8 Hz, 1H), 7.61 (d, J =
NMR (500 MHz, CDCl3, TMS): δ 8.13 (d, J = 7.5 Hz, 1H), 7.88 8 Hz, 1H), 7.45–7.38 (m, 5H), 7.28–7.25 (m, 1H), 7.19–7.11 (m,
(d, J = 9 Hz, 1H), 7.72 (t, J = 7 Hz, 2H), 7.53–7.46 (m, 4H), 5H), 7.08 (d, J = 8 Hz, 1H), 6.31 (s, 2H) ppm. 13C{1H} NMR
7.22–7.15 (m, 4H), 7.06 (d, J = 8.5 Hz, 1H), 6.76 (s, 1H), 6.69 (s, (125 MHz, CDCl3): δ 139.0, 135.4, 133.1, 131.7, 130.1, 129.8,
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129.0, 128.7, 128.4, 128.2, 127.6, 127.0, 126.9, 125.5, 124.9, 129.8, 129.0, 128.6, 128.5, 128.0, 127.7, 126.9, 125.5, 125.1,
122.8, 122.6, 122.5, 121.7, 114.7, 112.9, 98.1 ppm. HRMS 124.9, 122.5, 122.2, 114.6, 113.5, 112.8 ppm. HRMS
(ESI-Orbitrap) m/z: (M
+ +
Na)+ calcd for C25H17N3NaO2S (ESI-Orbitrap) m/z: (M Na)+ calcd for C25H16N4NaO4S
446.09337, found 446.09430.
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-2,4,6-tri-
491.07845, found 491.07918.
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-4-nitro-
methylbenzenesulfonamide (3j). The general procedure was benzenesulfonamide (3m). The general procedure was fol-
followed using 1-(mesitylsulfonyl)-3-nitro-1H-indole 1j lowed using 3-nitro-1-((4-nitrophenyl)sulfonyl)-1H-indole 1m
(100 mg, 0.29 mmol), 2-(cyanomethyl)isoquinolin-2-ium- (100 mg, 0.29 mmol), 2-(cyanomethyl)isoquinolin-2-ium-
bromide 2a (109 mg, 0.44 mmol) and KOH (65 mg, bromide 2a (108 mg, 0.43 mmol) and KOH (65 mg,
1.16 mmol) at rt for 1 h. Chromatography (eluent: 20% ethyl 1.15 mmol) at rt for 1 h. Chromatography (eluent: 25% ethyl
acetate in hexane) afforded the desired product 3j as a colour- acetate in hexane) afforded the desired product 3m as a yellow
less solid (77 mg, 57%). Mp: 213–215 °C. IR (neat) νmax: 3895, solid (54 mg, 40%). Mp: 209–212 °C. IR (neat) νmax: 3825, 3711,
3788, 3669, 3636, 3531, 3436, 3300, 3123, 2922, 2794, 2340, 3630, 3484, 3187, 2364, 1562, 1520, 1338, 1156, 862, 754,
1
1
2207, 1573, 1485, 1441, 1330, 1258, 1156, 1011, 791 cm−1. H 679 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 8.03 (d, J = 7.5
NMR (500 MHz, CDCl3, TMS): δ 8.02 (d, J = 7 Hz, 1H), 7.66 (d, J Hz, 1H), 7.80–7.76 (m, 3H), 7.55 (d, J = 7.5 Hz, 1H), 7.49–7.44
= 8.5 Hz, 1H), 7.61 (d, J = 8 Hz, 1H), 7.41–7.38 (m, 2H), (m, 3H), 7.31 (t, J = 7.5 Hz, 1H), 7.24–7.19 (m, 2H), 7.05 (d, J =
7.19–7.18 (m, 2H), 7.15–7.13 (m, 2H), 7.07 (d, J = 7 Hz, 1H), 7.5 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H),
6.59 (s, 1H), 6.57 (s, 2H), 6.45 (s, 1H), 2.11 (s, 3H), 2.04 (s, 6H) 6.82 (s, 1H), 6.64 (s, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3):
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 142.4, 138.8, 135.3, δ 149.8, 144.8, 134.5, 132.0, 130.1, 130.0, 128.3, 128.2, 128.2,
133.9, 131.8, 131.6, 129.9, 129.5, 128.6, 128.4, 128.2, 128.0, 127.9, 127.7, 127.3, 126.3, 124.7, 123.8, 122.6, 122.4, 122.3,
127.5, 125.9, 124.9, 123.8, 122.9, 122.6, 122.4, 114.6, 113.7, 122.2, 114.8, 112.8, 112.6, 98.5 ppm. HRMS (ESI-Orbitrap) m/z:
112.9, 98.1, 22.8, 21.0 ppm. HRMS (ESI-Orbitrap) m/z: (M + (M
+
Na)+ calcd for C25H16N4NaO4S 491.07845, found
Na)+ calcd for C28H23N3NaO2S 488.14032, found 488.14207.
491.08002.
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-4-meth-
N-(2-(3-Benzoylpyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-4-methyl-
oxybenzenesulfonamide (3k). The general procedure was fol- benzenesulfonamide (3n). The general procedure was followed
lowed using 1-((4-methoxyphenyl)sulfonyl)-3-nitro-1H-indole using 3-nitro-N-tosyl indole 1a (100 mg, 0.32 mmol), 2-(2-oxo-
1k (100 mg, 0.30 mmol), 2-(cyanomethyl)isoquinolin-2-ium- 2-phenylethyl)isoquinolin-2-ium-bromide
2b
(156
mg,
bromide 2a (112 mg, 0.45 mmol) and KOH (68 mg, 0.47 mmol) and KOH (71 mg, 1.26 mmol) at rt for 4 h.
1.20 mmol) at rt for 1 h. Chromatography (eluent: 25% ethyl Chromatography (eluent: 20% ethyl acetate in hexane)
acetate in hexane) afforded the desired product 3k as a brown afforded the desired product 3n as a yellow solid (111 mg,
solid (125 mg, 91%). Mp: 183–185 °C. IR (neat) νmax: 3838, 68%). Mp: 223–226 °C. IR (neat) νmax: 3843, 3741, 3633, 3438,
3728, 3675, 3644, 3459, 3217, 2319, 1700, 1543, 1402, 1324, 3251, 2371, 1608, 1487, 1436, 1334, 1231, 1159, 905, 871,
1
1
1153, 1091, 1019, 892, 836, 785, 660 cm−1. H NMR (500 MHz, 807 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 9.59 (d, J = 7.5
CDCl3, TMS): δ 8.02 (d, J = 7.5 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), Hz, 1H), 7.78–7.76 (m, 3H), 7.64 (d, J = 8 Hz, 1H), 7.54–7.52
7.60 (d, J = 8 Hz, 1H), 7.43–7.34 (m, 4H), 7.17–7.15 (m, 2H), (m, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.42–7.36 (m, 2H), 7.24 (s, 1H),
7.10–7.06 (m, 3H), 6.68 (d, J = 8.5 Hz, 2H), 6.43 (s, 1H), 6.30 (s, 7.21–7.19 (m, 2H), 7.15–7.11 (m, 3H), 7.04 (t, J = 7.5 Hz, 1H),
1H), 3.75 (s, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 6.73 (d, J = 8 Hz, 2H), 6.65 (s, 1H), 6.46 (s, 1H), 2.07 (s, 3H)
163.2, 135.6, 131.6, 130.6, 129.8, 129.2, 128.6, 128.4, 128.1, ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 185.4, 143.7, 140.2,
127.5, 126.7, 125.3, 124.9, 122.9, 122.7, 122.5, 121.5, 114.7, 136.0, 135.7, 132.7, 131.7, 131.5, 129.6, 129.5, 129.3, 129.2,
114.1, 113.0, 55.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ 128.4, 128.0, 127.8, 127.2, 127.0, 127.0, 126.8, 125.5, 125.0,
calcd for C26H19N3NaO3S 476.10393, found 476.10366.
124.6, 124.0, 123.4, 120.5, 114.3, 113.1, 21.4 ppm. HRMS
N-(2-(3-Cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-2-nitro- (ESI-Orbitrap) m/z: (M + H)+ calcd for C32H25N2O3S 517.15804,
benzenesulfonamide (3l). The general procedure was followed found 517.15996.
using 3-nitro-1-((2-nitrophenyl)sulfonyl)-1H-indole 1l (100 mg,
N-(2-(3-(4-Chlorobenzoyl)pyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
0.29 mmol), 2-(cyanomethyl)isoquinolin-2-ium-bromide 2a 4-methylbenzenesulfonamide (3o). The general procedure was
(108 mg, 0.43 mmol) and KOH (64 mg, 1.15 mmol) at rt for followed using 3-nitro-N-tosyl indole 1a (100 mg, 0.32 mmol),
1 h. Chromatography (eluent: 25% ethyl acetate in hexane) 2-(2-(4-chlorophenyl)-2-oxoethyl)isoquinolin-2-ium bromide 2c
afforded the desired product 3l as a yellow solid (66 mg, 49%). (172 mg, 0.47 mmol) and KOH (71 mg, 1.26 mmol) at rt for
Mp: 132–135 °C. IR (neat) νmax: 3865, 3803, 3680, 3605, 3453, 1 h. Chromatography (eluent: 20% ethyl acetate in hexane)
3112, 2203, 1635, 1582, 1532, 1400, 1349, 1173, 1121, 898, 850, afforded the desired product 3o as a yellow solid (127 mg,
1
777, 733 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 7.94 (d, J = 73%). Mp: 215–218 °C. IR (neat) νmax: 3837, 3750, 3478, 3247,
7 Hz, 1H), 7.84 (d, J = 8 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.58 2360, 1606, 1433, 1365, 1331, 1155, 1084, 900, 804 cm−1 1H
.
(d, J = 8 Hz, 1H), 7.50 (t, J = 7.5 Hz, 1H), 7.45–7.38 (m, 3H), NMR (500 MHz, CDCl3, TMS): δ 9.54 (d, J = 7.5 Hz, 1H), 7.76
7.36–7.33 (m, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.23–7.19 (m, 2H), (d, J = 8.5 Hz, 1H), 7.71 (d, J = 8.5 Hz, 2H), 7.64 (d, J = 8 Hz,
7.04–7.00 (m, 3H), 6.42 (s, 1H) ppm. 13C{1H} NMR (125 MHz, 1H), 7.43–7.36 (m, 4H), 7.26 (d, J = 8 Hz, 2H), 7.20–7.12 (m,
CDCl3): δ 147.1, 135.0, 133.7, 132.9, 132.4, 131.5, 130.5, 130.2, 4H), 7.05 (t, J = 7.5 Hz, 1H), 6.74 (d, J = 7.5 Hz, 2H), 6.60 (s,
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1H), 6.44 (s, 1H), 2.11 (s, 3H) ppm. 13C{1H} NMR (125 MHz, 3267, 2837, 1684, 1544, 1493, 1447, 1380, 1332, 1290, 1203,
CDCl3): δ 183.9, 143.8, 138.5, 137.8, 136.0, 135.7, 133.0, 131.7, 1158, 1079, 954, 902, 790, 742 cm−1 1H NMR (500 MHz,
.
130.5, 129.6, 129.3, 128.7, 128.2, 127.9, 127.1, 127.0, 126.7, CDCl3, TMS): δ 9.23 (d, J = 7.5 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H),
125.4, 125.0, 124.5, 123.7, 123.4, 120.5, 114.5, 113.3, 21.4 ppm. 7.56 (d, J = 8 Hz, 1H), 7.38–7.30 (m, 2H), 7.27 (d, J = 8 Hz, 2H),
HRMS (ESI-Orbitrap) m/z: (M
+
Na)+ calcd for 7.18–7.10 (m, 2H), 7.04 (d, J = 8 Hz, 1H), 7.00–6.95 (m, 2H),
C32H33ClN2NaO3S 573.10101, found 573.10307.
4-Methyl-N-(2-(3-(4-nitrobenzoyl)pyrrolo[2,1-a]isoquinolin-1-
6.87–6.86 (m, 3H), 6.54 (s, 1H), 4.35 (q, J = 7 Hz, 2H,), 2.19 (s,
3H), 1.37 (t, J = 7 Hz, 3H) ppm. 13C{1H} NMR (125 MHz,
yl)phenyl)benzenesulfonamide (3p). The general procedure CDCl3): δ 161.1, 143.6, 136.0, 135.5, 131.7, 131.1, 130.3, 129.4,
was followed using 3-nitro-N-tosyl indole 1a (100 mg, 129.3, 128.5, 127.7, 127.6, 127.4, 127.0, 127.0, 127.0, 125.0,
0.32 mmol), 2-(2-(4-nitrophenyl)-2-oxoethyl)isoquinolin-2-ium 125.0, 124.6, 122.9, 122.0, 120.8, 116.3, 113.5, 112.3, 60.3, 21.6,
bromide 2d (177 mg, 0.47 mmol) and KOH (71 mg, 14.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for
1.26 mmol) at rt for 1 h. Chromatography (eluent: 20% ethyl C28H24N2NaO4S 507.13490, found 507.13644.
acetate in hexane) afforded the desired product 3p as a bright
yellow solid (134 mg, 75%). Mp: 199–203 °C. IR (neat) νmax
N-(2-(7-Bromo-3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
4-methylbenzenesulfonamide (3s). The general procedure
:
3876, 3831, 3798, 3717, 3573, 3463, 3404, 3229, 2348, 1740, was followed using 3-nitro-N-tosyl indole 1a (100 mg,
1650, 1587, 1523, 1440, 1333, 1161, 1086, 798, 704 cm−1 1H 0.32
mmol), 5-bromo-2-(cyanomethyl)isoquinolin-2-ium-
.
NMR (500 MHz, CDCl3, TMS): δ 9.61 (d, J = 7.5 Hz, 1H), 8.30 bromide 2f (156 mg, 0.47 mmol) and KOH (71 mg, 1.26 mmol)
(d, J = 8.5 Hz, 2H), 7.91 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 8 Hz, at rt for 1 h. Chromatography (eluent: 10% ethyl acetate in
1H), 7.68 (d, J = 8 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.37 (t, J = hexane) afforded the desired product 3s as a colourless solid
7.5 Hz, 1H), 7.29 (d, J = 8 Hz, 2H), 7.20–7.19 (m, 2H), 7.16–7.11 (96 mg, 59%). Mp: 74–76 °C. 1H NMR (500 MHz, CDCl3, TMS):
(m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 8 Hz, 2H), 6.73 (s, δ 8.13 (d, J = 7.5 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.69 (d, J = 8
1H), 6.45 (s, 1H), 2.12 (s, 3H) ppm. 13C{1H} NMR (125 MHz, Hz, 1H), 7.56 (d, J = 7.5 Hz, 1H), 7.50–7.46 (m, 1H), 7.36 (d, J =
CDCl3): δ 182.7, 149.3, 145.6, 143.8, 136.1, 135.7, 133.7, 131.7, 8 Hz, 2H), 7.24–7.14 (m, 3H), 7.08 (d, J = 8 Hz, 2H), 6.98 (t, J =
129.9, 129.8, 129.4, 128.5, 128.1, 127.3, 127.2, 127.0, 126.5, 8 Hz, 1H), 6.50 (s, 1H), 6.40 (s, 1H), 2.37 (s, 3H) ppm. 13C{1H}
125.4, 124.9, 124.4, 124.6, 123.6, 123.2, 120.1, 115.1, 114.0, NMR (125 MHz, CDCl3): δ 144.1, 136.1, 135.5, 131.9, 131.5,
21.4 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for 130.0, 129.6, 129.3, 129.0, 127.6, 127.0, 126.5, 126.4, 125.5,
C32H23N3NaO5S 584.12506, found 584.12785.
N-(4-Bromo-2-(3-(4-nitrobenzoyl)pyrrolo[2,1-a]isoquinolin-1-
123.7, 123.4, 122.5, 122.1, 121.8, 113.8, 113.2, 112.5, 98.3,
21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for
yl)phenyl)-4 methylbenzene sulfonamide (3q). The general C26H18BrN3NaO2S 538.01953, found 538.02089.
procedure was followed using 5-bromo-3-nitro-N-tosyl indole
N-(2-(3-Benzoyl-7-bromopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
1b (100 mg, 0.25 mmol), 2-(2-(4-nitrophenyl)-2-oxoethyl)isoqui- 4-methylbenzenesulfonamide (3t). The general procedure was
nolin-2-ium bromide 2d (142 mg, 0.38 mmol) and KOH followed using 3 -nitro-N-tosyl indole 1a (100 mg, 0.32 mmol),
(57 mg, 1.01 mmol) at rt for 1 h. Chromatography (eluent: 20% 5-bromo-2-(2-oxo-2-phenylethyl)isoquinolin-2-ium bromide 2g
ethyl acetate in hexane) afforded the desired product 3q as a (192 mg, 0.47 mmol) and KOH (71 mg, 1.26 mmol) at rt for
yellow solid (115 mg, 71%). Mp: 250–252 °C. IR (neat) νmax
:
4 h. Chromatography (eluent: 20% ethyl acetate in hexane)
3937, 3870, 3792, 3726, 3597, 3560, 3527, 3396, 3337, 3238, afforded the desired product 3t as a yellow solid (98 mg, 52%).
3043, 2927, 1729, 1694, 1589, 1518, 1468, 1435, 1334, 1163, Mp: 243–247 °C. IR (neat) νmax: 3916, 3877, 3804, 3670, 3529,
1
802, 702 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 9.59 (d, J = 3444, 2957, 2450, 1727, 1673, 1618, 1334, 1162, 911, 867,
1
7.5 Hz, 1H), 8.31 (d, J = 8.5 Hz, 2H), 7.90 (d, J = 8 Hz, 2H), 7.69 787 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 9.62 (d, J = 7.5
(d, J = 7.5 Hz, 1H), 7.60 (d, J = 9 Hz, 1H), 7.49–7.46 (m, 2H), Hz, 1H), 7.79–7.75 (m, 3H), 7.64 (d, J = 7.5 Hz, 1H), 7.55–7.53
7.34 (s, 1H), 7.28 (s, 1H), 7.21–7.19 (m, 2H), 7.16–7.10 (m, 2H), (m, 2H), 7.46 (t, J = 7.5 Hz, 2H), 7.40–7.37 (m,1H), 7.25 (d, J = 8
6.81 (d, J = 7.5 Hz, 2H), 6.69 (s, 1H), 6.42 (s, 1H), 2.14 (s, 3H) Hz, 2H), 7.17–7.11 (m, 3H), 6.86 (t, J = 8 Hz, 1H), 6.74 (d, J = 8
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 182.8, 149.4, 145.4, Hz, 2H), 6.71 (s, 1H), 6.42 (s, 1H), 2.08 (s, 3H) ppm. 13C{1H}
144.0, 135.9, 135.0, 134.3, 133.5, 132.7, 129.9, 129.8, 129.5, NMR (125 MHz, CDCl3): δ 185.5, 143.8, 139.9, 136.0, 135.6,
128.7, 128.5, 128.3, 127.3, 127.1, 127.0, 125.4, 124.1, 123.6, 131.8, 131.8, 131.7, 131.6, 129.7, 129.3, 129.2, 128.6, 128.4,
123.5, 123.4, 121.5, 117.6, 115.2, 112.4, 21.4 ppm. HRMS 128.2, 127.0, 127.0, 126.7, 126.1, 125.1, 124.0, 122.8, 122.0,
(ESI-Orbitrap) m/z: (M + Na)+ calcd for C32H22BrN3NaO5S 120.8, 113.7, 112.8, 21.4 ppm. HRMS (ESI-Orbitrap) m/z: (M +
662.03558, found 662.03709.
H)+ calcd for 617.05050, found 617.05084.
Ethyl 1-(2-(4-methylphenylsulfonamido)phenyl)pyrrolo[2,1-
N-(2-(6-Bromo-3-cyanopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)-
a]isoquinoline-3-carboxylate (3r). The general procedure was 4-methylbenzenesulfonamide (3u). The general procedure
followed using 3-nitro-N-tosyl indole 1a (100 mg, 0.32 mmol), was followed using 3-nitro-N-tosyl indole 1a (100 mg,
2-(2-ethoxy-2-oxoethyl)isoquinolin-2-ium-bromide 2e (140 mg, 0.32
mmol),
4-bromo-2-(cyanomethyl)isoquinolin-2-ium-
0.47 mmol) and KOH (71 mg, 1.26 mmol) at rt for 1 h. bromide 2h (156 mg, 0.47 mmol) and KOH (70 mg,
Chromatography (eluent: 20% ethyl acetate in hexane) 1.26 mmol) at rt for 1 h. Chromatography (eluent: 10% ethyl
afforded the desired product 3r as a colourless solid (95 mg, acetate in hexane) afforded the desired product 3u as a yellow
62%). Mp: 125–126 °C. IR (neat) νmax: 3904, 3831, 3700, 3437, solid (88 mg, 54%). Mp: 167–170 °C. IR (neat) νmax: 3917, 3847,
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3803, 3619, 3448, 3227, 2204, 1591, 1489, 1434, 1331, 1159, under vacuum. The residue was then purified by column
1
1086, 915, 811 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 8.37 chromatography (50% ethyl acetate in hexane) to afford the
(s, 1H), 8.04 (d, J = 8 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.56–7.53 pyrrolo[2,1-a]isoquinoline 4 as a brown solid (49 mg, 71%).
(m, 1H), 7.50 (t, J = 7.5 Hz, 1H), 7.37 (d, J = 7.5 Hz, 2H), Analytical data of 4: Mp: 118–120 °C. 1H NMR (500 MHz,
7.28–7.21 (m, 4H), 7.09 (d, J = 7.5 Hz, 2H), 6.46 (s, 2H), 2.38 (s, (CD3)2CO, TMS): δ 9.45 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 8 Hz,
3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 144.0, 136.2, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.24 (s,
135.6, 131.5, 129.9, 129.5, 129.4, 128.6, 127.3, 127.2, 127.0, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 7.02 (d, J =
126.4, 125.4, 125.0, 123.6, 123.1, 122.9, 121.8, 113.6, 112.4, 7.5 Hz, 1H), 6.95 (d, J = 8 Hz, 1H), 6.75 (d, J = 8 Hz, 1H), 6.60
110.8, 98.0, 21.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + Na)+ (t, J = 7 Hz, 1H), 4.28 (s, 2H) ppm. 13C{1H} NMR (125 MHz,
calcd for C26H18BrN3NaO2S 538.01953, found 538.02112.
(CD3)2CO): δ 163.3, 146.7, 131.2, 129.0, 128.7, 128.1, 127.0,
N-(2-(3-Benzoyl-6-bromopyrrolo[2,1-a]isoquinolin-1-yl)phenyl)- 126.6, 126.5, 126.0, 125.2, 123.4, 121.3, 118.7, 118.5, 116.8,
4-methylbenzenesulfonamide (3v). The general procedure was 115.7, 115.1, 114.6, 112.0 ppm. HRMS (ESI-Orbitrap) m/z: (M +
followed using 3-nitro-N-tosyl indole 1a (100 mg, 0.32 mmol), H)+ calcd for C19H16N3O 302.12879, found 302.12991.
4-bromo-2-(2-oxo-2-phenylethyl)isoquinolin-2-ium bromide 2i
Experimental procedure for the reaction between
3-nitrobenzothiophene and isoquinolinium salt
(192 mg, 0.47 mmol) and KOH (71 mg, 1.26 mmol) at rt for
4 h. Chromatography (eluent: 20% ethyl acetate in hexane)
afforded the desired product 3v as a yellow solid (90 mg, 48%). A mixture of 3-nitrobenzothiophene (1.0 equiv., 100 mg), iso-
Mp: 230–234 °C. IR (neat) νmax: 3878, 3744, 3638, 3557, 3492, quinolinium salt (1.5 equiv.) and K3PO4 (2.0 equiv.) was
3264, 3059, 1744, 1708, 1649, 1613, 1428, 1335, 1160, 1089, weighed into a dry reaction tube. Dry CH3CN was added and
980, 903, 814, 762, 727 cm−1. 1H NMR (500 MHz, CDCl3, TMS): allowed to stir at 60 °C for 24 h. After completion of the reac-
δ 9.92 (s, 1H), 8.02 (d, J = 8 Hz, 1H), 7.77–7.74 (m, 3H), 7.53 (t, tion, the solvent was removed under vacuum. The residue was
J = 7 Hz, 1H), 7.50–7.43 (m, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.24 then purified by column chromatography (silica gel, eluent:
(d, J = 8 Hz, 2H), 7.19–7.12 (m, 3H), 7.08 (t, J = 7.5 Hz, 1H), mixtures of ethyl acetate/hexanes) to afford the corresponding
6.72 (d, J = 8 Hz, 2H), 6.67 (s, 1H), 6.43 (s, 1H), 2.07 (s, 3H) products.
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 185.4, 143.8, 139.8,
136.0, 135.6, 131.8, 131.7, 131.6, 129.7, 129.3, 129.2, 128.7,
Synthesis and characterization of bis-pyrrolo[2,1-a]
isoquinolines (6a–6e)
128.5, 128.2, 126.9, 126.9, 126.9, 126.6, 126.6, 125.2, 124.5,
123.8, 123.5, 120.9, 113.5, 110.6, 21.5 ppm. HRMS
(1,1′-(Disulfanediylbis(2,1-phenylene))bis(pyrrolo[2,1-a]iso-
(ESI-Orbitrap) m/z: (M
+
H)+ calcd forC32H23BrN2NaOsS quinoline-3,1-diyl))bis(phenylmethanone) (6a). The general
procedure was followed using 3-nitrobenzo[b]thiophene 5a
617.05050, found 617.05255.
Phenyl(1-phenylpyrrolo[2,1-a]isoquinolin-3-yl)methanone (3w). (100 mg, 0.56 mmol), 2-(2-oxo-2-phenylethyl)isoquinolin-2-
The general procedure was followed using 3-nitro-N-methyl ium-bromide 2b (275 mg, 0.84 mmol) and K3PO4 (237 mg,
indole 1n (100 mg, 0.57 mmol), 2-(2-oxo-2-phenylethyl)isoqui- 1.12 mmol) at 60 °C for 24 h. Chromatography (eluent: 20%
nolin-2-ium-bromide 2b (279 mg, 0.85 mmol) and KOH ethyl acetate in hexane) afforded the desired product 6a as a
(128 mg, 2.28 mmol) at rt for 1 h. Chromatography (eluent: 5% yellow solid (169 mg, 80%). Mp: 249–252 °C. IR (neat) νmax
ethyl acetate in hexane) afforded the desired product 3w as a 3945, 3846, 3779, 3682, 3538, 2961, 2363, 1728, 1613, 1414,
yellow solid (65 mg, 33%). Mp: 183–185 °C. IR (neat) νmax 1331, 1227, 1168, 1121, 1072, 1031, 965, 932, 871, 791, 756,
:
:
1
3700, 3643, 3531, 3557, 3358, 2328, 1911, 1764, 1730, 1598, 727, 688 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 9.61 (dd, J1
1566, 1443, 1393, 1364, 1331, 1282, 1195, 902, 790, 747, = 7.5 Hz, J2 = 1 Hz, 2H), 7.80–7.77 (m, 4H), 7.63 (t, J = 7 Hz,
718 cm−1. 1H NMR (500 MHz, CDCl3, TMS): δ 9.30 (d, J = 8 Hz, 2H), 7.47–7.42 (m, 5H), 7.41–7.37 (m, 7H), 7.25–7.20 (m, 3H),
1H), 8.19 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H), 7.59–7.55 7.17–7.14 (m, 3H), 7.12–7.05 (m, 6H) ppm. 13C{1H} NMR
(m, 2H), 7.52 (d, J = 8 Hz, 2H), 7.19 (t, J = 7 Hz, 1H), 7.15–7.13 (125 MHz, CDCl3): δ 185.6, 185.5, 140.5, 140.4, 137.1, 137.1,
(m, 3H), 7.09–7.04 (m, 6H) ppm. 13C{1H} NMR (125 MHz, 134.4, 134.4, 132.8, 132.7, 131.3, 131.3, 129.7, 129.6, 129.2,
CDCl3): δ 187.6, 139.7, 138.1, 135.8, 134.8, 131.2, 130.1, 129.8, 128.9, 128.9, 128.2, 127.9, 127.8, 127.8, 127.6, 127.5, 127.0,
128.9, 127.9, 127.7, 127.7, 127.5, 126.9, 126.6, 125.3, 124.7, 126.9, 126.5, 126.4, 125.7, 125.7, 125.5, 125.4, 125.2, 125.1,
123.4, 122.0, 113.0, 103.6 ppm. HRMS (ESI-Orbitrap) m/z: (M + 124.0, 123.7, 123.7, 116.4, 114.0 ppm. HRMS (ESI-Orbitrap) m/
H)+ calcd forC25H18NO 348.13829, found 348.13923.
z: (M
757.20007.
(1,1′-(Disulfanediylbis(2,1-phenylene))bis(pyrrolo[2,1-a]iso-
+
H)+ calcd for C50H33N2O2S2 757.19780, found
Synthesis and characterization of 4
The compound 3a (100 mg, 0.23 mmol) was treated with con- quinoline-3,1-diyl))bis((4-nitrophenyl)methanone) (6b). The
centrated H2SO4 (2.0 equiv.) at room temperature for 2 hours. general procedure was followed using 3-nitrobenzo[b]thio-
After completion of the reaction as indicated from the TLC, phene 5a (100 mg, 0.56 mmol), 2-(2-(4-nitrophenyl)-2-oxoethyl)
the reaction mixture was cooled and quenched by drop-wise isoquinolin-2-ium-bromide 2d (312 mg, 0.84 mmol) and K3PO4
addition of saturated NaHCO3 solution and the aqueous layer (237 mg, 1.12 mmol) at 60 °C for 24 h. Chromatography
extracted three times with ethyl acetate. The organic layer was (eluent: 20% ethyl acetate in hexane) afforded the desired
dried over anhydrous Na2SO4 and the solvent was removed product 6b as a yellow solid (145 mg, 61%). Mp: 290–292 °C.
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IR (neat) νmax: 3900, 3822, 3722, 3650, 3430, 2959, 2918, 2336, phene 5b (100 mg, 0.39 mmol), 2-(2-ethoxy-2-oxoethyl)isoqui-
1727, 1616, 1519, 1334, 1282, 1119, 1072, 853, 798, 729, nolin-2-ium-bromide 2e (172 mg, 0.58 mmol) and K3PO4
1
697 cm−1. H NMR (500 MHz, CDCl3, TMS): δ 9.62 (d, J = 7.5 (165 mg, 0.78 mmol) at 60 °C for 24 h. Chromatography
Hz, 2H), 8.26–8.24 (m, 4H), 7.93–7.90 (m, 4H), 7.69 (t, J = 7 Hz, (eluent: 10% ethyl acetate in hexane) afforded the desired
2H), 7.50–7.36 (m, 7H), 7.27–7.23 (m, 3H), 7.17–7.06 (m, 8H) product 6e as a colourless solid (66 mg, 40%). Mp: 237–240 °C.
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ 182.8, 182.7, 149.2, IR (neat) νmax: 3911, 3840, 3754, 3681, 3603, 3564, 3263, 3130,
145.9, 145.9, 137.0, 137.0, 134.0, 133.9, 133.8, 133.7, 131.3, 2361, 1691, 1457, 1375, 1340, 1214, 1077, 801, 745, 691,
129.9, 129.1, 129.1, 128.5, 128.4, 127.9, 127.9, 127.8, 127.8, 638 cm−1. 1H NMR (500 MHz, CDCl3, TMS): δ 9.26 (dd, J1 = 7.5
127.2, 127.1, 126.7, 126.7, 125.6, 125.5, 125.0, 124.9, 124.1, Hz, J2 = 1.5 Hz, 2H), 7.64–7.60 (m, 2H), 7.43–7.38 (m, 4H),
123.5, 123.1, 123.0, 117.2, 117.2, 114.7 ppm. HRMS 7.34–7.31 (m, 2H), 7.28–7.27 (m, 2H), 7.22–7.14 (m, 6H),
(ESI-Orbitrap) m/z: (M + H)+ calcd for C25H15N2O3S 847.16795, 7.03–7.00 (m, 2H), 4.37–4.29 (m, 4H),1.36–1.32 (m, 6H) ppm.
found 847.16754.
13C{1H} NMR (125 MHz, CDCl3): δ 161.3, 161.2, 136.7, 136.3,
(1,1′-(Disulfanediylbis(3-bromo-6,1phenylene))bis(pyrrolo 136.3, 133.9, 133.9, 131.8, 131.7, 131.1, 130.9, 128.6, 128.6,
[2,1-a]isoquinoline-3,1 diyl))bis(phenylmethanone) (6c). 127.6, 127.6, 127.5, 127.5, 127.4, 127.1, 127.0, 125.3, 125.2,
The general procedure was followed using 5-bromo-3-nitro- 124.8, 124.8, 123.2, 122.4, 122.3, 120.3, 120.3, 116.2, 116.1,
benzo[b]thiophene 5b (100 mg, 0.39 mmol), 2-(2-oxo-2-pheny- 114.2, 114.1, 113.4, 113.4, 60.3, 60.3, 14.5, 14.5 ppm. HRMS
lethyl)isoquinolin-2-ium-bromide 2b (191 mg, 0.58 mmol) and (ESI-Orbitrap) m/z: (M + Na)+ calcd for C42H30Br2N2NaO4S2
K3PO4 (165 mg, 0.78 mmol) at 60 °C for 24 h. Chromatography 872.98855, found 872.98987.
(eluent: 10% ethyl acetate in hexane) afforded the desired
product 6c as a light yellow solid (117 mg, 66%). Mp:
230–232 °C. IR (neat) νmax: 3952, 3803, 3390, 3072, 2958, 2922, Conflicts of interest
2357, 1722, 1606, 1572, 1457, 1328, 1279, 1118, 1070, 938, 868,
There are no conflicts to declare.
791, 742, 687 cm−1. 1H NMR (500 MHz, CDCl3, TMS): δ 9.60 (d,
J = 7.5 Hz, 2H), 7.78 (t, J = 7 Hz, 4H), 7.70–7.66 (m, 2H),
7.50–7.46 (m, 3H), 7.44–7.39 (m, 8H), 7.33 (d, J = 8 Hz, 1H),
7.26–7.22 (m, 2H), 7.18–7.05 (m, 8H) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ 185.6, 185.6, 140.3, 140.2, 136.4, 136.4,
136.3, 133.9, 132.6, 132.4, 131.9, 131.8, 131.5, 129.7, 129.6,
129.2, 128.3, 128.3, 128.2, 128.2, 127.7, 127.6, 127.5, 127.5,
127.4, 127.3, 127.2, 127.1, 125.7, 125.6, 124.9, 124.8, 123.9,
123.8, 123.7, 120.4, 120.4, 114.9, 114.9, 114.2, 114.2 ppm.
HRMS (ESI-Orbitrap) m/z: (M + H)+ calcd for C50H31Br2N2O2S2
915.01677, found 915.01770.
Acknowledgements
SAB, NPR, VKO and RP thank CSIR and UGC for research fel-
lowship. JJ thanks CSIR (HCP-029) for financial assistance.
The authors thank Prof. Mahesh Hariharan and Mr Alex
Andrews of IISER-Thiruvananthapuram for single-crystal X-ray
analysis. The authors also thank Mrs Saumini Mathew and
Mrs Viji S. of CSIR-NIIST for recording the NMR and mass
spectra, respectively.
Diethyl1,1′-(disulfanediylbis(2,1-phenylene))bis(pyrrolo[2,1-
a]isoquinoline-3-carboxylate)(6d). The general procedure was
followed using 3-nitrobenzo[b]thiophene 5a (100 mg,
0.56 mmol), 2-(2-ethoxy-2-oxoethyl)isoquinolin-2-ium-bromide
2e (248 mg, 0.84 mmol) and K3PO4 (237 mg, 1.12 mmol) at
60 °C for 24 h. Chromatography (eluent: 5% ethyl acetate in
hexane) afforded the desired product 6d as a colourless solid
(93 mg, 48%). Mp: 248–250 °C. IR (neat) νmax: 3898, 3841,
3732, 3598, 3357, 2917, 2846, 2312, 1738, 1477, 1444, 1374,
Notes and references
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ences cited therein.
2 (a) E. T. Pelkey, L. Chang and G. W. Gribble, Chem.
Commun., 1996, 1909; (b) E. T. Pelkey and G. W. Gribble,
Chem. Commun., 1997, 1873; (c) B. Biolatto, M. Kneeteman
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(d) I. Chataigner, E. Hess, L. Toupet and S. R. Piettre, Org.
Lett., 2001, 3, 525; (e) B. Biolatto, M. Kneeteman, E. Paredes
and P. M. E. Mancini, J. Org. Chem., 2001, 66, 3906;
(f) T. L. S. Kishbaugh and G. W. Gribble, Tetrahedron Lett.,
2001, 42, 4783; (g) A. Chrtien, I. Chataigner, N. L.′. Helias
and S. R. Piettre, J. Org. Chem., 2003, 68, 7990; (h) S. Roy,
T. L. S. Kishbaugh, J. P. Jasinski and G. W. Gribble,
Tetrahedron Lett., 2007, 48, 1313; (i) S. Lee, S. Diab,
P. Queval, M. Sebban, I. Chataigner and S. R. Piettre,
Chem. – Eur. J., 2013, 19, 7181; ( j) C. Beemelmanns,
S. Gross and H.-U. Reissig, Chem. – Eur. J., 2013, 19, 17801;
(k) B. M. Trost, V. Ehmke, B. M. O’Keffe and D. A. Bringely,
J. Am. Chem. Soc., 2014, 136, 8213; (l) J.-Q. Zhao,
1331, 1203, 1074, 693, 665 cm−1 1H NMR (500 MHz, CDCl3,
.
TMS): δ 9.26 (d, J = 7.5 Hz, 2H), 7.60–7.58 (m, 2H), 7.48–7.46
(m, 1H), 7.42 (dd, J1 = 8 Hz, J2 = 1 Hz, 1H), 7.39–7.32 (m, 6H),
7.23–7.20 (m, 2H), 7.18–7.10 (m, 6H), 6.99 (d, J = 7.5 Hz, 2H),
4.36–4.29 (m, 4H), 1.36–1.32 (m, 6H) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ 161.4, 161.4, 137.1, 137.0, 134.6, 131.3,
131.2, 131.1, 128.8, 128.7, 128.6, 128.5, 127.5, 127.4, 127.2,
126.9, 126.8, 126.3, 126.3, 125.6, 125.6, 125.3, 125.2, 124.8,
124.8, 123.5, 122.6, 115.9, 115.9, 115.6, 115.6, 60.2, 14.5 ppm.
HRMS (ESI-Orbitrap) m/z: (M + Na)+ calcd for C42H32N2NaO4S2
715.16957, found 715.17230.
Diethyl
1,1′-(disulfanediylbis(3-bromo-6,1-phenylene))bis
(pyrrolo[2,1-a]isoquinoline-3-carboxylate) (6e). The general
procedure was followed using 5-bromo-3-nitrobenzo[b]thio-
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