One-pot synthesis of spiropyrroloquinoline-isoindolinone and their aza-analogs via the Ugi-4CR/metal-free intramolecular bis-annulation process

Article abstract of DOI:10.1039/c5ob01095k

This presentation discloses a one-pot synthesis of a series of spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds. The reaction proceeds by the combination of a Ugi four-component reaction (4CR) and two intramolecular cyclizations under metal-free conditions. The proof of the structures relies on analytical investigation and X-ray crystallography.

Full text of DOI:10.1039/c5ob01095k

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Page 1 of 11
Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
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DOI: 10.1039/C5OB01095K
Journal Name
ARTICLE
One-pot synthesis of spiropyrroloquinoline-isoindolinone and
their aza-analogs via Ugi-4CR/ metal-free intramolecular bis-
annulation process†
A
Received 00th January 20xx,
Accepted 00th January 20xx
*
Mehdi Ghandi, Nahid Zarezadeh and Alireza Abbasi
DOI: 10.1039/x0xx00000x
This presentation discloses
a one-pot synthesis of a series of spiropyrroloquinoline isoindolinone and
www.rsc.org/
spiropyrroloquinoline aza-isoindolinone scaffolds. The reaction proceeds by combination of an Ugi four-component
reaction (4CR) and two intramolecular cyclizations under metal-free conditions. The proof of the structures relies on
analytical investigation and X-ray crystallography.
of 3a,8a-dihydroxyindeno[2,1-d]imidazole-2,8-dione using lead(IV)
15c
acetate, Rh(III)-catalyzed C-H activation of N-benzoylsulfonamide
Introduction
15d
with cyclic olefins,
compound with O-pivaloyl benzhydroxamic acids, and a domino
dehydration/condensation/cyclization reaction of cyclic
enaminones with 3-hydroxy-3-ethoxycarbonylisoindolin-1-one
or C–H activation reaction of cyclic diazo
15e
Multicomponent reactions (MCRs) have extensively been used as
powerful synthetic strategies for the construction of biological
interesting compounds. The isocyanide-based multicomponent
reactions (IMCRs) have emerged particularly as efficient tools in this
area based on their high efficiency, rich diversity, and easy
15f
derivatives using (±)-CSA as a Brønsted acid catalyst. However,
one has to use either expensive transition metal catalysts or
multistep procedures in these methods. Therefore, alternative
catalyst-free protocols using mild conditions, low cost, and simple
1
operation. Recently, there have been efforts on the synthesis of
2
more complex structures with the tandem Ugi/post-Ugi reactions.
The
spirocyclic
nitrogen-containing
heterocycles
like operation are desirable.
spiroisoindoline, spiroisoindolinone and spirooxindole are present
in many pharmaceuticals and biolologically active natural
compounds (Fig. 1a). Isoindolinones can be regarded as valuable
(a)
O
R
O
O
N
R
Cl
NH
O
H
F
O
NH
O
3
H
O
N
O2N
NMe
O
NH
O
N
building blocks in view of the presence of this core structure in
N
N
H
O
O
4
4a
N
many natural and pharmaceutical compounds like Lennoxamine,
O
O
Cl
N
H
H
4b
4c
4d
R = pyridyl
AChE inhibitor
R = 4-carbamoyl-2-methoxyphenyl
RO2468
Taliscanine, as well as Zopiclone and Pazinaclone (Fig. 1b). In
addition, isoindolinone and their analogs show a wide spectrum of
considerable biological activities such as antiviral, anti HIV-1,
Spirotryprostatin A
Anticancer Drug
Aldolase Inhibitor
AChE = acetylcholinesterase
p53-MDM2 Inhibitor
5
5a
5b
(b)
O
O
O
O
N
O
NH
5c
5d
5e
O
O
N
N
N
antihypertensive, antileukemic, and anesthetic. Therefore, a
variety of synthetic methods have been developed for the
N
N
Cl
O
O
N
O
N
5d,6
N
N
N
O
Cl
generation of isoindolinones including Diels-Alder
and Wittig
O
O
7
8
9
O
O
reactions, electrophilic and radical cyclization, lithiation
O
1
0
11
Lennoxamine
Taliscanine
Zopiclone
Pazinaclone
Sedative Drug
approaches,
based-mediated procedures,
metal-catalyzed
Isoindolobenzazepine
Alkaloid
Antiparkinson Alkaloid Drug Treatment of Insomnia
12
12a,b
12c,d
12e
12f,g
12h
12i,j
12k
processes (Ru,
Rh,
Re, Cu,
Co, Ni,
Pt and
12l,m
(c)
O
O
Pd
), as well as tandem aldol(Henry)/heterocyclization reactions
of suitable carbon nucleophiles with 2-formylbenzonitriles using
OH
HN
N
N
1
3
14
chemical or electrochemical methods.
N
N
Nonetheless,
spiroisoindolinones have been reported.
limited methodologies for construction of
15
In this context,
PGP-4008
P-gp-specific MDR modulator
Bebbistatin
Myosin II Inhibitor
palladium-catalyzed heterocyclization of 2-iodobenzoyl chloride
1
5a
Fig. 1 Example of pharmaceuticals and bioactive natural compounds contain
with ketimines,
silver-catalyzed spirolactonization of 3-(2-
15b
spiroisoindolinone,
spirooxindoles,
pyrrolo[2,3-b]quinoline
and
propynyl)isoindoline-1-one-3-carboxylic acids, oxidative cleavage
isoindolinone fragments.
On the other hand, pyrroloquinoline core is widely present in
1
6
School of Chemistry, College of Science, University of Tehran, Tehran, P.O. Box
various biological active natural products and pharmaceutics such
16a 16b 16c
1
4155 6455, Iran.
E-mail: Ghandi@khayam.ut.ac.ir
Electronic Supplementary Information (ESI) available: Copies of H NMR,
NMR, MS and IR of all the compounds, and crystallographic data for 8a and 10j
CIF). See DOI: 10.1039/x0xx00000x
as Ammosamide B,
Mycenarubin A,
Marinoquinoline A-F,
16d
1
13
Martinelline and Martinellic acid. Particularly significant are PGP-
008 and blebbistatin which contain pyrrolo[2,3-b]quinoline
scaffolds (Fig. 1c). Most synthetic approaches toward pyrrolo[2,3-
†
C
16e
16f
4
(
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Page 2 of 11
ARTICLE
Journal Name
a
b]quinolines involved multiplestep synthetic methods and harsh Table 1 Optimization of reaction conditions
View Article Online
DOI: 10.1039/C5OB01095K
17
18
conditions, or metal-catalyzed processes. For example, Yum has
reported a palladium-catalyzed heteroannulation of 2-amino-3-
iodoquinoline derivatives with 1-trimethylsilyl internal alkynes to
18a
access pyrrolo[2,3-b]quinolones in 2003. Moreover, a Pauson-
Khand-type reaction of N-[2-(2-alkyn-1- yl)phenyl]carbodiimides has
been described for the synthesis of pyrrolo[2,3-b]quinolines using
18b
Rh(I) catalyst by Saito in 2010 and Cu-catalyzed heteroannulation
of 1,2-haloaldehydes with alkylisocyanoacetates has been also
developed for the synthesis of pyrrolo[2,3-b]quinolones by
1
8c
Nagarajan in 2015. Consequently, development of milder and
metal-free routes for the preparation of pyrrolo[2,3-b]quinolines is
still highly desirable.
b
Entry Solvent
Base
Cs CO
T (ºC)
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
120
Time (h)
24
24
24
24
24
24
24
24
24
24
24
10
2
Yield
23%
21%
NR
1
2
3
4
5
6
7
8
9
10
Toluene
Dioxane
MeOH
DCE
2
3
3
3
3
3
Inspired by the known properties of isoindolinone derivatives
along with the documented biological activities of pyrrolo[2,3-
b]quinolones, we undertook a study of the synthesis of heterocyclic
scaffolds containing both motifs into one molecule in a spiro
manner. In continuation of our investigation in searching for new
heterocyclic scaffolds via Ugi reactions, in addition to some
drawbacks in some of the reported methods for these compounds,
we disclose a sequential Ugi/post-Ugi intramolecular bis-annulation
approach for the synthesis of spiropyrroloquinoline-isoindolinone
and their aza-analogs. Similar C–C cyclizations were found in
literature in which the Ugi product prepared with electron-deficient
aldehydes readily cyclizied to 3-oxoisoindoline scaffolds under basic
Cs CO
2
Cs CO
2
Cs CO
2
NR
MeCN
Toluene
Dioxane
MeOH
DCE
Cs CO
2
NR
19
K2CO3
trace
trace
NR
K CO
2 3
K2CO3
K2CO3
NR
MeCN
DMF
K
CO
2
NR
3
20
condition. On the other hand, N-C cyclization were expected to be
carried out easily using Buchwald-Hartwig protocols.
11
12
13
14
15
NEt3
NR
21
DMF
NaOMe
KOtBu
K2CO3
120
75%
81%
88%
93%
DMF
120
DMF
120
3
Results and discussion
DMF
Cs CO
2
120
2
3
Initially, 2-chloroquinoline-3-carbaldehydes 3a-c were prepared
using the previously reported procedure (Scheme 1). To probe the
proposed strategy, the Ugi product 7a, obtained via the reaction of
a
22
Reacction conditions: (i) 3a (1 mmol), 4a (1 mmol), 5 (1 mmol), 6a (1 mmol)
in MeOH (5 ml) at rt for 10 h. (ii) all reactions were carried out with 7a
b
(1mmol), base (2 equiv), and 3 mL of solvent. Isolated yields, NR = No
electron-deficient
2-chloroquinoline-3-carbaldehyde
(3a), reaction.
benzylamine (4a), 2-chloronicotinic acid (5) and cyclohexyl
isocyanide (6a) (Table 1), was characterized and served for our early
exploration to study the effect of various bases and solvents for the
next step. To our surprise, spiro compound 8a was identified as the
sole product when the solution of 7a in toluene containing two
equivalents of cesium carbonate was heated at reflux for 24 h
To explore the generality and the substrate scope of the
developed condensation, we replaced 5 with 2-bromobenzoic acid
. The corresponding products 10a-l were obtained in excellent
9
yields (Table 3). Compounds 8a-o and 10a-l were characterized by
1
13
elemental analysis, MS, IR, and H and C NMR spectroscopy.
Unambiguous evidence for the proposed structures of 8a and 10j
was finally obtained by single crystal X-ray-diffraction analysis (Fig.
2 and Fig. 3).
(
entry 1, Table 1). Further efforts to increase the yield by varying
the reaction time, solvent or temperature were found to be
successful (Table 1). The best conditions were concluded to be
º
Cs CO and DMF at 120 C (entry 15, Table 1).
2
3
This new method was then applied to a domino reaction of
As indicated in Tables 1 and 2, whereas products 8j, 8k and 10i
aldehydes 3a-c, amines 4a-e, 2-chloronicotinic acid
5
and were obtained in moderate yields using aromatic amines, utilization
isocyanides 6a-c in MeOH and then in DMF under the optimized of aliphatic amines afforded the corresponding products in rather
conditions, to afford the bis-annulated products 8a-o in moderate higher yields (Tables 2 and 3). Such behavior is expected perhaps
to high yields (Table 2).
due to the the rather lower elctrophilicity of the in situ generated
imines from aromatic amines. Ready cyclization of sterically
hindered amides such as 2,4,4-trimethylpentyl amides to the
corresponding products indicated that the reaction is not sensitive
to steric hindrance around the amide (entries 2, 5, 8, 13, 15, Table
2) and (entries 2, 4, 8, 11, Table 3). On the other hand, although
unsubstituted aldehyde or substituted with modest electron-
donating methyl group produced the products in satisfactory
yields, those bearing stronger electron-donating methoxy group
afforded product 8f (Table 2) and 10f (Table 3) in 61% and 65%
Scheme 1 Preparation of 2-Chloroquinoline-3-Carbaldehydes 3a-c.
yields, repectively. This behavior is in accord with the S Ar reaction
N
2
| J. Name., 2012, 00, 1-3
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Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Journal Name
ARTICLE
a
a
Table 2 Synthesis of spiropyrroloquinoline aza-isoindolinones
Table 3 Synthesis of spiropyrroloquinoline-isoindolinones
View Article Online
DOI: 10.1039/C5OB01095K
1
2
3
b
Entry
1
R
R
R
Product Yield
1
2
3
b
Entry
R
R
R
Product Yield
H
Bn
Bn
Bn
Bn
Bn
Cy
10a
10b
10c
10d
10e
10f
10g
10h
10i
91%
89%
90%
87%
90%
65%
86%
88%
73%
90%
88%
87%
1
2
3
4
5
6
7
8
9
H
Bn
Bn
Bn
Bn
Bn
Cy
8a
8b
8c
8d
8e
8f
91%
87%
90%
89%
85%
61%
93%
89%
91%
71%
77%
92%
89%
91%
88%
2
H
tBuCH CMe
2
2
H
tBuCH CMe
3
Me
Me
Me
Cy
2
2
2
2
H
tBu
4
tBuCH CMe
2
2
Me
Me
Cy
5
tBu
Cy
tBuCH CMe
6
OMe Bn
2
OMe Bn
Cy
Cy
7
Me
Me
H
4-MeBn
Cy
H
4-MeBn
8g
8h
8i
8
4-MeBn
tBuCH CMe
2
2
H
4-MeBn
tBuCH CMe
9
4-MePh
Cy
Cy
2
c
c
c
H
4-MeBn
tBu
10
11
12
H
Tryptamine
Tryptamine
Tryptamine
10j
10
11
12
13
14
15
Me
H
4-MePh
Cy
8j
H
tBuCH CMe
10k
10l
2
2
3,4-diMePh
tBuCH CMe
8k
8l
H
tBu
2
2
2
2
c
a
b
c
2
H
Tryptamine
Tryptamine
Tryptamine
Tryptamine
Cy
2
Reaction conditions: See Table 2. Isolated yields. R NH .
c
c
c
H
tBuCH CMe
8m
8n
8o
2
Me
Me
Cy
tBuCH CMe
2
a
Reacction conditions: 2-chloroquinoline-3-carbaldehyde (1 mmol), amine (1
mmol), acid (1 mmol), and isocyanide (1 mmol) in MeOH (5 mL) at rt for 10
h, followed by treatment with DMF (3 ml) and Cs
except for tryptamine (3 equiv)) at 120 ºC for 2 h. Isolated yields.
2
CO
3
(2 equiv for all amines
b
c
2
R NH
2
.
Fig. 3 ORTEP diagram of spiro compound 10j (CCDC 1053522).
It has been postulated that the ugi reaction involved a sequence
of imine formation, protonation of the imine by acid thus strongly
increasing the electrophilicity of the C=N bond, α-addition of the
electrophilic iminium cation, the nucleophilic carboxylate anion
attack to isocyanide and finally intramolecular acyl-transfer
Fig. 2 ORTEP diagram of spiro compound 8a (CCDC 1010288).
(
Mumm’s rearrangement) (Scheme 2). The generated α-
acylaminoamides were subsequently bis-annulated under basic
in which the presence of methoxy group makes the 2- condition, affording the desired spyrocyclic products .
chloroquinoline a weaker electrophile. Due to obtaining even lower
product yields with aldehyde 3c in other experiments that were
carried out, we decided not to employ it anymore even though the Conclusions
diversity of aldehyde precursor was limited to two elements.
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ARTICLE
Journal Name
In summary, we have developed a method for the synthesis of General procedure for synthesis of compound 8a-o and 10a-l
View Article Online
highly functionalized spirocyclic scaffolds by modification of Ugi-
CR followed by two consecutive post condensation intramolecular
C–C and N-C cyclizations, respectively. These reactions are
particularly interesting in terms of molecular diversity, simplicity,
and atom economy along with using readily available starting
DOI: 10.1039/C5OB01095K
To a stirring solution of aldehyde (1 mmol) in MeOH (5 ml) were
added amine (1 mmol), acid (1 mmol), and isocyanide (1 mmol),
and the reaction mixture was stirred at rt for 10 h. After completion
of this step as indicated by TLC, the solvent was removed under
reduced pressure, then DMF (3 ml) and Cs CO (2 equiv for all
4
2
3
materials.
A
novel route to
a
variety of spiro[pyrrolo[2,3-
and
amines except for tryptamine (3 equiv)) were added to the residue.
The reaction mixture was heated at 120 °C for 2 h. The progress of
the reaction was monitored by TLC. On completion, the reaction
b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione
spiro[isoindoline-1,3'-pyrrolo[2,3-b]quinoline]-2',3(1'H)-diones was
disclosed. These reactions were designed to initially generate in situ
mixture was cooled to rt, and then H O (10 mL) was added and the
2
mixture was extracted with EtOAc (3 × 10 ml). The combined
organic phase was dried over Na SO , filtered, and evaporated in
vacuo. The residue was purified by column chromatography (SiO2,
O
R2
2
4
O
N
OH
NH2
R2
eluent: 5:1, n-hexane/ EtOAc for all compounds except 3:1, n-
hexane/ EtOAc for 8l-o and 10j-l) to afford the desired products.
-
H2O
Y
X
+
N
Cl
N
Cl
MeOH
R3
N
H
C
Ugi-4CR
6'-Benzyl-1-cyclohexylspiro[pyrrolo[2,3-b]quinoline-3,7'-
pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8a). White crystal (431
H
R2
R2
-1
N
O
O
N
R3
N
mg, 91%); mp 187-189 °C; IR (KBr) νmax 1713 cm ; R
f
(20%
1
EtOAc/hexane) 0.23; H NMR (300 MHz, DMSO-d ) δ 1.13-2.35 (m,
6
C
O
10H), 4.30-4.38 (m, 1H), 4.56 (s, 2H), 7.04 (s, 5H), 7.41 (t, J = 7.4 Hz,
N
Cl
X
Y
N
Cl
Y
N
R3
1H), 7.59-7.71 (m, 3H), 7.86 (s, 1H), 7.90 (d, J = 8.3 Hz, 1H), 8.37 (d, J
O
13
=
7.1 Hz, 1H), 8.65 (d, J = 3.8 Hz, 1H) ppm; C NMR (75 MHz, DMSO-
Y
d6) δ 24.8, 25.3 (2C), 28.2, 28.4, 44.0, 52.1, 70.5, 118.9, 124.8, 125.0
X
O
(2C), 125.4, 127.4 (2C), 128.1 (2C), 128.4 (2C), 128.6, 130.6, 132.6,
R2
133.7, 135.5, 146.8, 153.8, 155.6, 163.3, 166.9, 170.7 ppm; m/z (EI,
O
C-C cyclization
R2
N
N
N
+
7
0 eV) 474 (13, M ) 392 (39), 301 (100), 287 (11), 258 (5), 230 (9),
H
Y
O
N
DMF, Cs2CO3
R3
91 (40%); Anal. Calcd for C H N O : C, 75.93; H, 5.52, N, 11.81.
30 26 4 2
N
Mumms
rearrangment
metal-free
intramolecular
bis-annulation
O
R3
Found: C, 75.91; H, 5.39; N, 11.80%.
'-Benzyl-1-(2,4,4-trimethylpentan-2-yl)spiro[pyrrolo[2,3-
N
Cl
6
N-C cyclization
spirocyclic compounds
b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8b).
X = C, N
Y = Br, Cl
-
White crystal (439 mg, 87%); mp 150-152 °C; IR (KBr) ν 1706 cm
max
1
1
;
R (20% EtOAc/hexane) 0.30; H NMR (300 MHz, DMSO-d ) δ 0.91
f
6
(
1
s, 9H), 1.70 and 1.76 (2s, 6H), 2.04 (d, J = 14.4 Hz, 1H), 2.46 (d, J =
4.4 Hz, 1H), 4.55 (s, 2H), 7.08 (s, 5H), 7.39 (br t, J = 6.5 Hz, 1H),
7.60-7.66 (m, 3H), 7.80 (s, 1H), 7.87 (br d, J = 7.8 Hz, 1H), 8.36 (br d,
Scheme 2 Suggested mechanism for the formation of spirocyclic
products.
13
J = 7.0 Hz, 1H), 8.62 (br s, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ
6
2
1
1
7
9
9.1, 29.5, 31.0, 31.3, 43.9, 49.3, 63.2, 71.1, 118.8, 124.76 (2C),
24.84, 125.1, 127.2, 127.8 (3C), 128.0 (2C), 128.3, 130.5, 132.3,
33.2, 135.9, 146.6, 153.5, 157.9, 163.7, 167.1, 171.8 ppm; m/z (EI,
a Ugi product containing four active centers in order to accomplish
two bis-annulation post-Ugi processes. These new structures
broaden the scaffolds that are accessible through Ugi/post-Ugi
reactions and many of them may represent interesting
pharmacophores.
+
0 eV) 505 (28, M +1) 393 (72), 301 (100), 287 (10), 258 (5), 230 (9),
1 (43%); Anal. Calcd for C H N O : C, 76.16; H, 6.39, N, 11.10.
32 32 4 2
Found: C, 76.17; H, 6.42; N, 11.11%.
'-Benzyl-1-tert-butylspiro[pyrrolo[2,3-b]quinoline-3,7'-
pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8c). White crystal (403
mg, 90%); mp 158-160 °C; IR (KBr) ν
EtOAc/hexane) 0.25; H NMR (300 MHz, DMSO-d ) δ 1.68 (s, 9H),
6
-1
1731, 1694 cm ; R (20%
max
f
Experimental
1
6
General information
4.42 (d, J = 15.3 Hz, 1H), 4.72 (d, J = 15.3 Hz, 1H), 7.05-7.08 (m, 5H),
7
.41 (t, J = 7.4 Hz, 1H), 7.59-7.71 (m, 3H), 7.86-7.88 (m, 2H), 8.35
13
All commercially available chemicals and reagents were purchased (dd, J = 7.6, 1.3 Hz, 1H), 8.64 (dd, J = 4.8, 1.3 Hz, 1H) ppm; C NMR
from Merck Chemical Company and used without further (75 MHz, DMSO-d ) δ 28.1, 43.8, 59.4, 70.8, 118.9, 124.8, 124.8,
6
purification. Melting points were determined with an 124.9, 125.1, 127.4, 127.8, 128.0 (2C), 128.3, 128.5 (2C), 130.4,
Electrothermal model 9100 apparatus and are uncorrected. IR 132.4, 133.0, 135.5, 146.6, 153.6, 157.4, 163.7, 166.9, 171.2 ppm;
+
spectra were recorded on a Shimadzu 4300 spectrophotometer, in m/z (EI, 70 eV) 448 (9, M ) 392 (51), 301 (100), 287 (10), 258 (8),
-
1
1
13
cm . H and C NMR spectra were recorded on a Bruker DRX-500- 230 (20), 91 (74%); Anal. Calcd for C28H N O : C, 74.98; H, 5.39, N,
24 4 2
1
13
AVANCE spectrometer at 300 ( H) and 75 MHz ( C) using DMSO-d
as solvent. Mass spectra of the products were obtained with an HP
Agilent technologies) 5937 Mass Selective Detector. Elemental
analyses were carried out by a CHN-Rapid Heraeus elemental
analyzer (Wellesley, MA).
12.49. Found: C, 75.01; H, 5.40; N, 12.53%.
'-Benzyl-1-cyclohexyl-6-methylspiro[pyrrolo[2,3-b]quinoline-
,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8d). White crystal
6
6
(
3
-1
(
(
(
434 mg, 89%); mp 218-220 °C; IR (KBr) ν
1733, 1706 cm ; R
max f
1
20% EtOAc/hexane) 0.25; H NMR (300 MHz, DMSO-d ) δ 1.26-2.31
6
m, 10H), 2.39 (s, 3H), 4.26-4.34 (m, 1H), 4.50 (d, J = 15.3 Hz, 1H),
4
.60 (d, J = 15.3 Hz, 1H), 7.03-7.08 (m, 5H), 7.41 (s, 1H), 7.51 (dd, J =
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 11
Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Journal Name
ARTICLE
1
3
8
(
(
.6, 1.3 Hz, 1H), 7.62 (dd, J = 7.6, 4.9 Hz, 1H), 7.78-7.80 (m, 2H), 8.35 1H), 8.61 (d, J = 7.1 Hz, 1H), 8.62 (d, J = 4.8 Hz, 1H) ppm; C NMR
View Article Online
13
dd, J = 7.6, 1.2 Hz, 1H), 8.63 (dd, J = 4.8, 1.2 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 20.4, 29.1, 29.5, 31.1D,O3I1: .130,.14033.96/,C45O9.B40,16039.52K,
75 MHz, DMSO-d ) δ 20.8, 24.9, 25.3 (2C), 28.2, 28.4, 44.0, 52.1, 71.0, 118.9, 124.76 (2C), 124.84, 125.0, 127.7, 127.9 (2C), 128.2,
6
6
7
1
1
0.6, 118.9, 124.8, 125.0, 125.3, 127.2, 127.4, 127.5, 128.1 (2C), 128.5 (2C), 130.3, 132.3, 132.8, 133.0, 136.5, 146.5, 153.5, 157.8,
+
28.4 (2C), 132.45, 132.53, 133.1, 134.3, 135.4, 145.2, 153.7, 155.0, 163.6, 167.0, 171.8 ppm; m/z (EI, 70 eV) 520 (20, M +2), 406 (60),
+
63.4, 167.0, 170.7 ppm; m/z (EI, 70 eV) 488 (25, M ), 406 (76), 391 301 (100), 287 (22), 230 (9), 105 (54%); Anal. Calcd for C H N O :
33
34
4
2
(
20), 315 (100), 301 (18), 272 (9), 244 (15), 91 (72%); Anal. Calcd for C, 76.42; H, 6.61, N, 10.80. Found: C, 76.41; H, 6.60; N, 10.77%.
C H N O : C, 76.21; H, 5.78, N, 11.47. Found: C, 76.20; H, 5.81; N,
31
28
4
2
1-tert-Butyl-6'-(4-methylbenzyl)spiro[pyrrolo[2,3-b]quinoline-
1
1.56%.
'-Benzyl-6-methyl-1-(2,4,4-trimethylpentan-2-
yl)spiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
3
,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8i). White crystal
-1
6
(420 mg, 91%); mp 179-181 °C; IR (KBr) ν
(20% EtOAc/hexane) 0.26; H NMR (300 MHz, DMSO-d ) δ 1.70 (s,
1733, 1706 cm ; R
max f
1
6
2
,5'(1H,6'H)-dione (8e). White crystal (440 mg, 85%); mp 128-130 9H), 1.99 (s, 3H), 4.49 (d, J = 15.0 Hz, 1H), 4.57 (d, J = 15.0 Hz, 1H),
-
1
1
°C; IR (KBr) νmax 1701 cm ; R (20% EtOAc/hexane) 0.34; H NMR 6.80 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 7.9 Hz, 2H), 7.42 (t, J = 7.4 Hz,
f
(
300 MHz, DMSO-d ) δ 0.89 (s, 9H), 1.67 and 1.72 (2s, 6H), 2.02 (d, J 1H), 7.59-7.63 (m, 2H), 7.68 (t, J = 7.7 Hz, 1H), 7.75 (s, 1H), 7.87 (d, J
6
=
7
14.8 Hz, 1H), 2.36 (s, 3H), 2.43 (d, J = 14.8 Hz, 1H), 4.50 (s, 2H), = 8.3 Hz, 1H), 8.34 (d, J = 7.4 Hz, 1H), 8.63 (d, J = 4.5 Hz, 1H) ppm;
13
.04-7.13 (m, 5H), 7.37 (s, 1H), 7.50 (dd, J = 8.5, 1.5 Hz, 1H), 7.60
C NMR (75 MHz, DMSO-d ) δ 20.4, 28.1, 43.6, 59.3, 70.7, 119.0,
6
(
(
(
dd, J = 7.7, 4.9 Hz, 1H), 7.71 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 8.33 124.76, 124.82, 124.9, 125.0, 127.8, 128.2, 128.57 (2C), 128.60 (2C),
dd, J = 7.7, 1.3 Hz, 1H), 8.61 (dd, J = 4.8, 1.3 Hz, 1H) ppm; C NMR 130.3, 132.2, 132.4, 132.8, 136.8, 146.4, 153.6, 157.3, 163.6, 166.8,
75 MHz, DMSO-d ) δ 20.8, 29.2, 29.5, 31.1, 31.3, 43.9, 49.4, 63.1, 171.2 ppm; m/z (EI, 70 eV) 462 (6, M ), 406 (39), 343 (11), 301
13
+
6
7
1.2, 118.8, 124.8 (2C), 124.9, 127.2, 127.3, 127.6, 127.8 (2C), 128.0 (100), 287 (20), 230 (17), 105 (81%); Anal. Calcd for C H N O : C,
29 26 4 2
(
2C), 132.3, 132.4, 132.6, 134.5, 135.9, 145.1, 153.5, 157.4, 163.8, 75.30; H, 5.67, N, 12.11. Found: C, 75.31; H, 5.62; N, 11.98%.
+
1
3
7
67.2, 171.7 ppm; m/z (EI, 70 eV) 518 (1, M ), 407 (77), 315 (100),
01 (13), 272 (8), 244 (14), 91 (46%); Anal. Calcd for C H N O : C,
1
-Cyclohexyl-6-methyl-6'-p-tolylspiro[pyrrolo[2,3-b]quinoline-
33 34 4 2
3,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8j). White crystal
346 mg, 71%); mp 242-245 °C; IR (KBr) ν
EtOAc/hexane) 0.23; H NMR (300 MHz, DMSO-d ) δ 1.15-1.82 (m,
-1
6.42; H, 6.61, N, 10.80. Found: C, 76.57; H, 6.71; N, 10.97%.
'-Benzyl-1-cyclohexyl-6-methoxyspiro[pyrrolo[2,3-b]quinoline-
,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8f). White crystal 8H), 2.14 (s, 3H), 2.24-2.40 [5H, consisting s, 3H (2.36) and m, 2H],
(
1720 cm ; R (20%
max f
1
6
6
3
-1
(
(
307 mg, 61%); mp 221-223 °C; IR (KBr) νmax 1729, 1706 cm ; R 4.38-4.46 (m, 1H), 7.11 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H),
20% EtOAc/hexane) 0.21; H NMR (300 MHz, DMSO-d ) δ 1.13-2.27 7.50-7.52 (m, 2H), 7.68 (dd, J = 7.6, 5.0 Hz, 1H), 7.77 (d, J = 9.0 Hz,
f
1
6
(
m, 10H), 3.78 (s, 3H), 4.24-4.32 (m, 1H), 4.50 (d, J = 15.2 Hz, 1H), 1H), 8.25 (s, 1H), 8.41 (d, J = 7.6 Hz, 1H), 8.72 (d, J = 4.7 Hz, 1H)
13
4
1
1
.60 (d, J = 15.2 Hz, 1H), 7.03-7.09 (m, 6H), 7.35 (dd, J = 8.9, 2.3 Hz, ppm; C NMR (75 MHz, DMSO-d ) δ 20.4, 20.7, 24.8, 25.3 (2C), 28.3
6
H), 7.62 (dd, J = 7.5, 4.9 Hz, 1H), 7.74 (s, 1H), 7.81 (d, J = 9.1 Hz, (2C), 52.2, 72.5, 119.6, 125.0, 125.2, 125.4, 126.4 (2C), 127.3, 127.6,
13
H), 8.35 (d, J = 7.7 Hz, 1H), 8.64 (d, J = 4.8 Hz, 1H) ppm; C NMR 129.8 (2C), 132.6, 132.7, 132.9, 133.3, 134.7, 137.4, 145.2, 154.1,
+
(
75 MHz, DMSO-d ) δ 24.8, 25.3 (2C), 28.2, 28.4, 44.0, 52.1, 55.4, 155.0, 162.8, 166.3, 171.6 ppm; m/z (EI, 70 eV) 488 (80, M ), 406
6
7
1
1
0.6, 107.7, 119.2, 121.6, 124.7, 125.0, 126.2, 127.4, 128.0 (2C), (100), 377 (17), 363 (13), 349 (7), 334 (24), 316 (5), 301 (6), 272
28.4 (2C), 128.7, 132.5, 132.6, 135.4, 142.1, 153.7, 153.9, 156.1, (19), 244 (18), 55 (17%); Anal. Calcd for C H N O : C, 76.21; H,
63.4, 166.9, 170.4 ppm; m/z (EI, 70 eV) 504 (28, M ), 422 (27), 331 5.78, N, 11.47. Found: C, 76.12; H, 5.85; N, 11.36%.
31 28 4 2
+
(
100), 317 (8), 288 (6), 91 (31%); Anal. Calcd for C H N O : C,
31 28 4 3
6'-(3,4-Dimethylphenyl)-1-(2,4,4-trimethylpentan-2-
7
3.79; H, 5.59, N, 11.10. Found: C, 73.74; H, 5.56; N, 11.08%.
-Cyclohexyl-6'-(4-methylbenzyl)spiro[pyrrolo[2,3-b]quinoline-
,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione (8g). White crystal °C; IR (KBr) νmax 1727, 1712 cm ; R (20% EtOAc/hexane) 0.27; H
f
-1
yl)spiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
2,5'(1H,6'H)-dione (8k). White crystal (398 mg, 77%); mp 116-118
1
-1
1
3
(
(
(
454 mg, 93%); mp 190-192 °C; IR (KBr) νmax 1732, 1707 cm ; R NMR (300 MHz, DMSO-d ) δ .77 (s, 9H), 1.73 (s, 3H), 1.87 (s, 3H),
20% EtOAc/hexane) 0.25; H NMR (300 MHz, DMSO-d ) δ 1.14-1.82 2.07 (s, 6H), 2.16 (d, J = 14.9 Hz, 1H), 2.34 (d, J = 14.9 Hz, 1H), 6.95
m, 8H), 1.95 (s, 3H), 2.14-2.32 (m, 2H), 4.27-4.35 (m, 1H), 4.47 (d, J (dd, J = 8.0, 1.7 Hz, 1H), 7.02-7.04 (m, 2H), 7.44 (t, J = 7.5 Hz, 1H),
f
6
1
6
=
15.0 Hz, 1H), 4.59 (d, J = 15.0 Hz, 1H), 6.77 (d, J = 7.9 Hz, 2H), 6.84 7.63-7.70 (m, 2H), 7.78 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H),
(
d, J = 7.9 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H), 7.57-7.63 (m, 2H), 7.68 (t, 8.32 (s, 1H), 8.37 (dd, J = 7.7, 1.4 Hz, 1H), 8.69 (dd, J = 4.8, 1.4 Hz,
1
3
J = 7.2 Hz, 1H), 7.76 (s, 1H), 7.88 (d, J = 8.3 Hz, 1H), 8.34 (d, J = 7.7 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 18.8, 19.3, 29.5, 29.8, 30.8,
Hz, 1H), 8.62 (d, J = 4.9 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 31.1, 49.3, 63.1, 73.1, 119.8, 124.86, 124.91, 125.1, 125.3, 125.4,
6
13
6
2
1
1
0.3, 24.8, 25.3, 25.4 (2C), 28.2, 28.4, 43.7, 52.1, 70.4, 118.9, 124.8, 127.8, 128.4, 128.5, 130.0, 130.6, 132.65, 132.69, 133.0, 136.5,
24.9, 125.0, 125.3, 127.4, 128.5 (3C), 128.6 (2C), 130.4, 132.1, 137.1, 146.6, 153.9, 158.0, 163.2, 166.4, 172.4 ppm; m/z (EI, 70 eV)
+
32.5, 133.4, 136.8, 146.6, 153.7, 155.5, 163.3, 166.7, 170.7 ppm; 519 (8, M +1), 406 (100), 363 (12), 349 (6), 334 (10), 258 (9), 230
+
m/z (EI, 70 eV) 488 (4, M ), 406 (16), 369 (19), 301 (100), 287 (23), (8), 57 (32%); Anal. Calcd for C H N O : C, 76.42; H, 6.61, N, 10.80.
33 34 4 2
2
5
30 (11), 213 (7), 105 (63%); Anal. Calcd for C H N O : C, 76.21; H, Found: C, 76.38; H, 6.52; N, 10.77%.
31 28 4 2
.78, N, 11.47. Found: C, 76.22; H, 5.81; N, 11.49%.
'-(4-Methylbenzyl)-1-(2,4,4-trimethylpentan-2-
yl)spiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
6
'-(2-(1H-Indol-3-yl)ethyl)-1-cyclohexylspiro[pyrrolo[2,3-
6
b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-2,5'(1H,6'H)-dione
White crystal (485 mg, 92%); mp 232-235 °C; IR (KBr) ν
(8l).
3332,
max
-1
1
2
,5'(1H,6'H)-dione (8h). White crystal (462 mg, 89%); mp 175-177 1727, 1695 cm ; R (33% EtOAc/hexane) 0.21; H NMR (300 MHz,
f
-1 1
°
C; IR (KBr) νmax 1738, 1704 cm ; R (20% EtOAc/hexane) 0.28;
H
DMSO-d ) δ 1.13-2.45 (m, 10H), 2.90 (t, J = 8.0 Hz, 2H), 3.43-3.53
6
f
NMR (300 MHz, DMSO-d ) δ 0.92 (s, 9H), 1.73 and 1.78 (2s, 6H), (m, 1H), 3.57-3.67 (m, 1H), 4.49-4.57 (m, 1H), 6.70 (t, J = 7.4 Hz, 1H),
6
2
2
2
.00-2.05 [4H, consisting s, 3H (2.02) and d, J = 14.6 Hz, 1H (2.03)], 6.92-6.99 (m, 2H), 7.11 (s, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.45 (t, J =
.49 (d, J = 14.6 Hz, 1H), 6.82 (d, J = 7.7 Hz, 2H), 6.92 (d, J = 7.8 Hz, 7.5 Hz, 1H), 7.63 (dd, J = 7.7, 4.9 Hz, 1H), 7.72-7.76 (m, 2H), 7.98 (d,
H), 7.40 (t, J = 7.4 Hz, 1H), 7.56-7.67 (m, 4H), 7.86 (d, J = 8.3 Hz, J = 8.7 Hz, 1H), 8.06 (s, 1H), 8.34 (dd, J = 7.7, 1.2 Hz, 1H), 8.67 (dd, J
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Page 6 of 11
ARTICLE
Journal Name
2-Benzyl-1'-cyclohexylspiro[isoindoline-1,3'-pyrrolo[2,3-
1
3
=
2
1
1
1
4.8, 1.3 Hz, 1H), 10.78 (s, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ
6
4.1, 24.8, 25.3 (2C), 28.4, 28.5, 41.8, 52.4, 71.0, 110.3, 111.5, b]quinoline]-2',3(1'H)-dione (10a). White crDysOtIa:l1(04.130039m/Cg,5O91B%01)0;9m5pK
17.3, 118.1, 119.3, 120.9, 122.9, 125.1, 125.2, 125.3, 125.5, 126.6, 198-200 °C; IR (KBr ) ν 1728, 1696 cm ; R (20% EtOAc/hexane)
27.5, 128.8, 130.9, 132.3, 133.7, 136.1, 147.1, 153.6, 155.9, 163.1, 0.34; H NMR (300 MHz, DMSO-d ) δ 1.13-2.89 (m, 10H), 4.30-4.40
View Article Online
-1
max
f
1
6
+
66.9, 171.7 ppm; m/z (EI, 70 eV) 527 (9, M ), 385 (28), 369 (8), 303 (m, 1H), 4.42 (d, J = 15.3 Hz, 1H), 4.54 (d, J = 15.0 Hz, 1H), 6.99 (s,
(
11), 287 (45), 143 (100), 130 (87), 55 (24%); Anal. Calcd for 5H), 7.14 (d, J = 7.4 Hz, 1H), 7.39 (t, J = 7.3 Hz, 1H), 7.53 (t, J = 7.1
C H N O : C, 75.12; H, 5.54, N, 13.27. Found: C, 75.16; H, 5.47; N, Hz, 1H), 7.59-7.71 (m, 3H), 7.75 (s, 1H), 7.89 (d, J = 8.6 Hz, 1H), 7.93
3
3 29 5 2
1
3
1
3.22%.
'-(2-(1H-Indol-3-yl)ethyl)-1-(2,4,4-trimethylpentan-2-
yl)spiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
,5'(1H,6'H)-dione (8m). Yellowish crystal (496 mg, 89%); mp 182-
84 °C; IR (KBr ) νmax 3322, 1725, 1693 cm ; R (33% EtOAc/hexane)
.26; H NMR (300 MHz, DMSO-d ) δ 0.93 (s, 9H), 1.86 and 1.92 (2s,
H), 2.27 (d, J = 15.0 Hz, 1H), 2.44 (d, J = 15.0 Hz, 1H), 2.90-3.05 (m,
H), 3.43-3.61 (m, 2H), 6.72 (t, J = 7.4 Hz, 1H), 6.96 (t, J = 7.5 Hz,
(d, J = 7.5 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 24.9, 25.3
6
(
2C), 28.1, 28.4, 44.0, 52.1, 69.4, 119.9, 121.5, 123.7, 124.9, 125.5,
27.3, 127.4, 128.0 (2C), 128.3 (2C), 128.6, 129.8, 130.6, 130.8,
33.1, 133.5, 135.7, 143.9, 146.8, 155.2, 168.4, 171.6 ppm; m/z (EI,
0 eV) 473 (3, M ), 391 (19), 300 (100), 286 (31), 257 (5), 229 (14),
1 (95%); Anal. Calcd for C H N O : C, 78.62; H, 5.75, N, 8.87.
Found: C, 78.69; H, 5.75; N, 8.92%.
6
1
1
7
9
2
1
0
6
2
1
+
-1
f
1
31 27 3 2
6
2-Benzyl-1'-(2,4,4-trimethylpentan-2-yl)spiro[isoindoline-1,3'-
H), 7.03 (d, J = 7.9 Hz, 1H), 7.07 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.44 pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10b). White crystal (448
-1
(
t, J = 7.4 Hz, 1H), 7.61 (dd, J = 7.6, 5.0 Hz, 1H), 7.70-7.74 (m, 2H), mg, 89%); mp 179-181 °C; IR (KBr ) νmax 1721, 1639 cm ; R (20%
f
1
7
=
2
1
1
1
3
.94 (d, J = 8.6 Hz, 1H), 7.99 (s, 1H), 8.32 (d, J = 7.4 Hz, 1H), 8.65 (d, J EtOAc/hexane) 0.41; H NMR (300 MHz, DMSO-d ) δ 0.91 (s, 9H),
6
13
4.2 Hz, 1H), 10.79 (s, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 1.75 (s, 6H), 2.04 (d, J = 14.8 Hz, 1H), 2.49 (d, J = 14.8 Hz, 1H), 3.32
6
4.2, 29.6, 29.9, 31.0, 31.4, 42.0, 49.3, 63.4, 71.7, 110.4, 111.5, (d, J = 15.8 Hz, 1H), 4.58 (d, J = 15.8 Hz, 1H), 7.03 (s, 6H), 7.38 (t, J =
17.5, 118.1, 119.5, 120.9, 122.7, 124.9 (2C), 125.1, 125.4, 126.7, 7.4 Hz, 1H), 2.52-6.70 [5H, consisting m, 4H and s, 1H (7.67)], 7.86
27.9, 128.5, 130.7, 132.2, 132.9, 136.1, 146.8, 153.5, 158.1, 163.4, (d, J = 8.3 Hz, 1H), 7.94 (d, J = 7.2 Hz, 1H) ppm; C NMR (75 MHz,
67.1, 172.7 ppm; m/z (EI, 70 eV) 557 (20, M ), 445 (11), 415 (6), DMSO-d ) δ 29.1, 29.5, 31.0, 31.4, 43.9, 49.2, 63.2, 70.0, 119.7,
13
+
6
15 (16), 303 (51), 287 (54), 143 (100), 130 (70), 57 (66%); Anal. 121.3, 123.7, 124.9, 125.1, 127.1, 127.6 (2C), 127.8, 127.9 (2C),
Calcd for C H N O : C, 75.38; H, 6.33, N, 12.56. Found: C, 75.43; H, 128.3, 129.7, 130.5, 130.9, 133.0, 133.3, 136.2, 144.1, 146.6, 157.5,
3
5 35 5 2
+
6
.36; N, 12.60%.
'-(2-(1H-Indol-3-yl)ethyl)-1-cyclohexyl-6-
methylspiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
,5'(1H,6'H)-dione (8n). Yellowish crystal (492 mg, 91%); mp 227-
29 °C; IR (KBr ) νmax 3351, 1726, 1693 cm ; R (33% EtOAc/hexane)
168.5, 172.8 ppm; m/z (EI, 70 eV) 504 (12, M +1), 391 (76), 300
(
100), 286 (15), 257 (3), 229 (8), 91 (56%); Anal. Calcd for
C H N O : C, 78.70; H, 6.60, N, 8.34. Found: C, 78.74; H, 6.72; N,
6
33 33
3 2
8
.38%.
2
2
0
[
3
-1
2-Benzyl-1'-cyclohexyl-6'-methylspiro[isoindoline-1,3'-
f
1
.23; H NMR (300 MHz, DMSO-d ) δ 1.13-1.80 (m, 8H), 2.38-2.45 pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10c). White crystal (438
6
-1
5H, consisting s, 3H (2.38) and m, 2H], 2.91 (t, J = 8.0 Hz, 2H), 3.46- mg, 90%); mp 258-260 °C; IR (KBr ) νmax 1734, 1698 cm ; R (20%
f
1
.65 (m, 2H), 4.48-4.56 (m, 1H), 6.70 (t, J = 7.4 Hz, 1H), 6.93-6.98 EtOAc/hexane) 0.34; H NMR (300 MHz, DMSO-d ) δ 1.13-2.67 (m,
6
(
7
m, 2H), 7.12 (s, J = 1.1 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.45 (s, 1H), 10H), 2.38 (s, 3H), 4.27-4.35 (m, 1H), 4.46 (AB-q, J = 15.4 Hz, 2H),
.55 (d, J = 8.6 Hz, 1H), 7.63 (dd, J = 7.7, 4.9 Hz, 1H), 7.88 (d, J = 8.6 6.69-7.05 (m, 5H), 7.09 (d, J = 7.4 Hz, 1H), 7.40 (s, 1H), 7.50-7.64
Hz, 1H), 7.90 (s, 1H), 8.34 (dd, J = 7.6, 1.2 Hz, 1H), 8.67 (dd, J = 4.9, [4H, consisting m, 3H and s, 1H (7.64)], 7.78 (d, J = 8.5 Hz, 1H), 7.91
13
13
1
2
1
1
1
.2 Hz, 1H), 10.81 (s, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 20.8, (d, J = 7.4 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 20.8, 24.9,
6
6
4.1, 24.9, 25.3 (2C), 28.5, 28.6, 41.7, 52.3, 71.1, 110.3, 111.5, 25.3 (2C), 28.1, 28.4, 44.0, 52.0, 69.5, 119.9, 121.4, 123.6, 125.5,
17.3, 118.2, 119.2, 120.9, 122.9, 125.0, 125.2, 125.5, 126.6, 127.3, 127.2, 127.3, 127.6, 128.0 (2C), 128.3 (2C), 129.7, 130.8, 132.4,
27.7, 132.3, 132.7, 133.2, 134.6, 136.1, 145.4, 153.6, 155.3, 163.1, 132.9, 133.1, 134.2, 135.7, 144.0, 145.2, 154.6, 168.5, 171.5 ppm;
+
+
67.0, 171.7 ppm; m/z (EI, 70 eV) 541 (6, M ), 412 (2), 399 (26), 383 m/z (EI, 70 eV) 487 (4, M ), 473 (47), 405 (9), 391 (100), 349 (25),
(
5), 316 (13), 301 (29), 143 (100), 130 (93), 55 (29%); Anal. Calcd for 334 (20), 314 (51), 300 (20), 286 (9), 271 (6), 257 (17), 243 (10), 229
C H N O : C, 75.39; H, 5.77, N, 12.93. Found: C, 75.48; H, 5.78; N, (48), 91 (91%); Anal. Calcd for C H N O : C, 78.82; H, 5.99, N, 8.62.
34
31
5
2
32 29 3 2
1
2.89%.
'-(2-(1H-Indol-3-yl)ethyl)-6-methyl-1-(2,4,4-trimethylpentan-2-
yl)spiro[pyrrolo[2,3-b]quinoline-3,7'-pyrrolo[3,4-b]pyridine]-
Found: C, 78.83; H, 6.10; N, 8.75%.
6
2-Benzyl-6'-methyl-1'-(2,4,4-trimethylpentan-2-
yl)spiro[isoindoline-1,3'-pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione
2
,5'(1H,6'H)-dione (8o). White crystal (503 mg, 88%); mp 208-210 (10d). White crystal (451 mg, 87%); mp 175-177 °C; IR (KBr ) ν
max
-1 -1 1
°C; IR (KBr ) ν
3298, 1728, 1686 cm ; R (33% EtOAc/hexane) 1720, 1694 cm ; R (20% EtOAc/hexane) 0.41; H NMR (300 MHz,
max f f
1
0
6
2
7
7
2
.28; H NMR (300 MHz, DMSO-d ) δ 0.93 (s, 9H), 1.85 and 1.91 (2s, DMSO-d ) δ 0.90 (s, 9H), 1.73 (s, 6H), 2.03 (d, J = 14.8 Hz, 1H), 2.35
6
6
H), 2.56 (d, J = 15.0 Hz, 1H), 2.38 (s, 3H), 2.43 (d, J = 15.0 Hz, 1H), (s, 3H), 2.45 (d, J = 14.8 Hz, 1H), 4.33 (d, J = 15.9 Hz, 1H), 4.53 (d, J =
.90-3.04 (m, 2H), 3.43-3.48 (m, 1H), 3.54-3.64 (m, 1H), 6.71 (t, J = 15.9 Hz, 1H), 6.96-7.08 (m, 6H), 7.34 (s, 1H), 7.48-7.63 [4H,
.4 Hz, 1H), 6.93-7.00 (m, 2H), 7.06 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), consisting m, 3H and s, 1H (7.56)], 7.76 (d, J = 8.5 Hz, 1H), 7.93 (d, J
13
.42 (s, 1H), 7.54 (d, J = 8.6 Hz, 1H), 7.59-7.63 (m, 1H), 7.83-7.84 (m, = 7.2 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 20.8, 29.1, 29.5,
6
H), 8.31 (d, J = 7.7 Hz, 1H), 8.64 (d, J = 4.8 Hz, 1H), 10.80 (s, 1H) 30.9, 31.3, 43.9, 49.2, 63.1, 70.1, 119.6, 121.2, 123.6, 124.8, 127.1,
13
ppm; C NMR (75 MHz, DMSO-d ) δ 20.8, 24.2, 29.6, 29.9, 31.0, 127.2, 127.6 (3C), 127.9 (2C), 129.7, 131.0, 132.4, 132.6, 132.9,
6
3
1
1
1.4, 41.9, 49.3, 63.3, 71.8, 110.4, 111.4, 117.5, 118.1, 119.4, 120.9, 134.5, 136.2, 144.2, 145.1, 156.9, 168.6, 172.7 ppm; m/z (EI, 70 eV)
22.7, 124.87, 124.94, 125.1, 126.6, 127.4, 127.6, 132.2, 132.3, 518 (31, M +1), 405 (100), 314 (91), 300 (29), 271 (5), 243 (9), 91
+
32.5, 134.7, 136.1, 145.2, 153.5, 157.5, 163.4, 167.1, 172.6 ppm; (91%); Anal. Calcd for C H N O : C, 78.89; H, 6.81, N, 8.12. Found:
34 35 3 2
+
m/z (EI, 70 eV) 572 (27, M +1), 459 (23), 429 (9), 317 (68), 301 (57), C, 78.90; H, 6.77; N, 8.10%.
1
43 (100), 130 (55), 57 (45%); Anal. Calcd for C H N O : C, 75.63;
36 37 5 2
2-Benzyl-1'-tert-butyl-6'-methylspiro[isoindoline-1,3'-
pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10e). White crystal (415
H, 6.52, N, 12.25. Found: C, 75.67; H, 6.56; N, 12.34%.
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 11
Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Journal Name
ARTICLE
-1
mg, 90%); mp 192-194 °C; IR (KBr ) νmax 1730, 1694 cm ; R (20% 2.38 (m, 2H), 4.39-4.47 (m, 1H), 4.09 (s, 4H), 7.30 (d, JV=iew7A.1rtiHclez,O1nHlin)e,
f
1
EtOAc/hexane) 0.36; H NMR (300 MHz, DMSO-d ) δ 1.68 (s, 9H), 7.44 (t, J = 7.4 Hz, 1H), 7.60-7.72 (m, 3H), 7D.O7I9: 1(0d.1,0J3=9/C7.59OHB0z1,019H5)K,
6
13
2
7
(
(
1
1
.37 (s, 3H), 4.37 (d, J = 15.3 Hz, 1H), 4.57 (d, J = 15.3 Hz, 1H), 6.96- 7.88 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 6.8 Hz, 1H), 8.27 (s, 1H) ppm;
.04 (m, 6H), 7.36 (s, 1H), 7.48-7.91 [4H, consisting m, 3H and s, 1H NMR (75 MHz, DMSO-d ) δ 20.4, 24.8, 25.3 (2C), 28.1, 28.2, 52.1,
7.56)], 7.77 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 7.4 Hz, 1H) ppm; C NMR 71.2, 120.8, 121.8, 123.9, 125.2, 125.6, 126.3 (2C), 127.5, 128.7,
75 MHz, DMSO-d ) δ 20.8, 28.1, 43.9, 59.2, 69.8, 119.9, 121.2, 129.7 (2C), 129.9, 130.8, 130.9, 133.0, 133.4, 133.5, 137.1, 143.3,
23.6, 124.9, 127.3 (2C), 127.6, 128.0 (2C), 128.4 (2C), 129.6, 130.8, 146.8, 155.3, 167.7, 172.4 ppm; m/z (EI, 70 eV) 473 (80, M ), 391
32.2, 132.3, 133.0, 134.4, 135.7, 144.4, 145.0, 156.4, 168.5, 172.1 (100), 362 (21), 349 (28), 334 (19), 319 (17), 300 (8), 286 (9), 257
ppm; m/z (EI, 70 eV) 461 (5, M ), 404 (43), 314 (79), 300 (19), 243 (17), 244 (9), 229 (37), 174 (21), 91 (39%); Anal. Calcd for
C
6
1
3
6
+
+
(
9), 91 (100%); Anal. Calcd for C H N O : C, 78.07; H, 5.90, N, 9.10. C H N O : C, 78.62; H, 5.75, N, 8.87. Found: C, 78.63; H, 5.79; N,
30 27 3 2 31 27 3 2
Found: C, 78.09; H, 5.91; N, 9.06%.
-Benzyl-1'-cyclohexyl-6'-methoxyspiro[isoindoline-1,3'-
pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10f). White crystal (327 pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10j). White crystal (473
8.97%.
2
2-(2-(1H-Indol-3-yl)ethyl)-1'-cyclohexylspiro[isoindoline-1,3'-
-
1
-1
mg, 65%); mp 243-245 °C; IR (KBr ) νmax 1731, 1695 cm ; R (20% mg, 90%); mp 187-189 °C; IR (KBr ) ν 3333, 1728, 1689 cm ; R
f
max
f
1
1
EtOAc/hexane) 0.30; H NMR (300 MHz, DMSO-d ) δ 1.13-2.28 (m, (33% EtOAc/hexane) 0.28; H NMR (300 MHz, DMSO-d ) δ 1.38-2.44
6
6
1
6
1
0H), 3.77 (s, 3H), 4.26-4.34 (m, 1H), 4.47 (AB-q, J = 15.3 Hz, 2H), (m, 10H), 2.86 (t, J = 8.4 Hz, 2H), 3.39-3.58 (m, 2H), 4.51-4.59 (m,
.96-7.06 (m, 7H), 7.33 (dd, J = 9.1, 2.8 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 6.69 (t, J = 7.4 Hz, 1H), 6.92-6.96 (m, 2H), 7.09 (s, 1H), 7.24 (m,
H), 7.56 (s, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.81 (d, J = 9.1 Hz, 1H), 7.92 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.54-7.64 (m, 2H), 7.75 (m, 2H), 7.91 (d,
13
13
(
(
d, J = 7.4 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 24.9, 25.3 J = 7.2 Hz, 1H), 7.99-8.01 (m, 2H), 10.77 (s, 1H) ppm; C NMR (75
2C), 28.1, 28.3, 44.0, 51.9, 55.4, 69.5, 107.7, 120.1, 121.4, 121.6, MHz, DMSO-d ) δ 24.0, 24.9, 25.3 (2C), 28.3, 28.5, 41.7, 52.3, 69.8,
6
6
1
1
23.6, 126.4, 127.3, 128.0 (2C), 128.3 (2C), 128.7, 129.7, 130.7, 110.4, 111.4, 117.3, 118.1, 120.3, 120.9, 121.6, 122.8, 123.4, 125.1,
32.4, 133.0, 135.7, 142.1, 144.0, 153.5, 156.1, 168.4, 171.3 ppm; 125.7, 126.6, 127.5, 128.8, 129.7, 130.8, 131.3, 132.9, 133.4, 136.1,
+
+
m/z (EI, 70 eV) 503 (19, M ), 420 (9), 398 (13), 330 (100), 316 (19), 143.6, 147.1, 155.6, 168.4, 172.6 ppm; m/z (EI, 70 eV) 526 (27, M ),
3
7
01 (11), 286 (6), 143 (29), 91 (88%); Anal. Calcd for C H N O : C, 443 (2), 396 (6), 384 (24), 368 (23), 300 (13), 286 (66), 143 (100),
32 29 3 3
6.32; H, 5.80, N, 8.34. Found: C, 76.33; H, 5.77; N, 8.34%.
'-Cyclohexyl-6'-methyl-2-(4-methylbenzyl)spiro[isoindoline-
,3'-pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10g). White crystal
130 (76), 55 (24%); Anal. Calcd for C H N O : C, 77.54; H, 5.74, N,
34 30 4 2
1
0.64. Found: C, 77.63; H, 5.70; N, 10.71%.
1
1
2-(2-(1H-Indol-3-yl)ethyl)-1'-(2,4,4-trimethylpentan-2-
-1
(
(
(
431 mg, 86%); mp 220-222 °C; IR (KBr ) νmax 1735, 1670 cm ; R yl)spiro[isoindoline-1,3'-pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione
f
1
20% EtOAc/hexane) 0.29; H NMR (300 MHz, DMSO-d ) δ 1.14-1.83 (10k). White crystal (490 mg, 88%); mp 201-202 °C; IR (KBr ) ν
6
max
-1
1
m, 8H), 1.93 (s, 3H), 2.12-2.29 (m, 2H), 2.38 (s, 3H), 4.28-4.33 [2H, 3242, 1733, 1658 cm ; R (20% EtOAc/hexane) 0.33; H NMR (300
f
consisting d, J = 15.0 Hz, 1H (2.30) and m, 1H], 4.56 (d, J = 15.0 Hz, MHz, DMSO-d ) δ 0.92 (s, 9H), 1.84 and 1.96 (2s, 6H), 2.36 (AB-q, J =
6
1
H), 6.72 (d, J = 7.9 Hz, 2H), 6.77 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 7.5 14.9 Hz, 2H), 2.88-3.07 (m, 2H), 3.37-3.45 (m, 1H), 3.54-3.64 (m,
Hz, 1H), 7.32 (s, 1H), 7.42 (s, 1H), 7.47-7.52 (m, 2H), 7.52 (t, J = 7.5 1H), 6.72 (t, J = 7.4 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 7.03-7.11 (m,
1
3
Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 7.4 Hz, 1H) ppm;
C
3H), 7.27 (d, J = 8.1 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.52-7.62 (m,
13
NMR (75 MHz, DMSO-d ) δ 20.2, 20.7, 24.9, 25.3 (2C), 28.1, 28.4, 2H), 7.67-7.72 (m, 2H), 7.92-7.97 (m, 3H), 10.80 (s, 1H) ppm;
C
6
4
1
1
4
3.7, 52.0, 69.3, 119.8, 121.3, 123.6, 125.4, 127.2, 127.5, 128.3 (2C), NMR (75 MHz, DMSO-d ) δ 24.2, 29.6, 29.9, 30.9, 31.4, 42.1, 49.3,
6
28.5 (2C), 129.6, 130.8, 132.2, 132.5, 132.6, 132.9, 134.1, 136.7, 63.3, 70.6, 110.6, 111.4, 117.6, 118.1, 120.4, 120.9, 121.2, 122.6,
+
43.9, 145.0, 154.5, 168.2, 171.5 ppm; m/z (EI, 70 eV) 501 (7, M ), 123.5, 125.1, 125.3, 126.7, 127.9, 128.5, 129.7, 130.6, 131.4, 132.8,
19 (12), 382 (83), 314 (100), 300 (62), 243 (12), 105 (81), 55 (35%); 132.9, 136.2, 143.9, 146.9, 157.7, 168.6, 173.6 ppm; m/z (EI, 70 eV)
+
Anal. Calcd for C H N O : C, 79.01; H, 6.23, N, 8.38. Found: C, 557 (23, M +1), 443 (6), 414 (3), 314 (20), 302 (27), 286 (61), 143
33 31 3 2
7
8.98; H, 6.25; N, 8.45%.
'-Methyl-2-(4-methylbenzyl)-1'-(2,4,4-trimethylpentan-2-
yl)spiro[isoindoline-1,3'-pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione
(100), 130 (41), 57 (51%); Anal. Calcd for C H N O : C, 77.67; H,
36 36 4 2
6
.52, N, 10.06. Found: C, 77.63; H, 6.57; N, 10.15%.
2-(2-(1H-Indol-3-yl)ethyl)-1'-tert-butylspiro[isoindoline-1,3'-
pyrrolo[2,3-b]quinoline]-2',3(1'H)-dione (10l). White crystal (435
6
(10h). White crystal (467 mg, 88%); mp 163-165 °C; IR (KBr ) ν
max
-1
1
-1
1
728, 1709 cm ; R (20% EtOAc/hexane) 0.36; H NMR (300 MHz, mg, 87%); mp 185-187 °C; IR (KBr ) ν 3261, 1725, 1690 cm ; R
f max f
1
DMSO-d ) δ .92 (s, 9H), 1.76 and 1.99 (2s, 6H), 2.00-2.06 (singlet (33% EtOAc/hexane) 0.31; H NMR (300 MHz, DMSO-d ) δ 1.87 (s,
6
6
overlapped with a doublet, 4H), 2.36 (s, 3H), 2.49 (d, J = 14.3 Hz, 9H), 2.87-2.96 (m, 2H), 3.46 (t, J = 8.1 Hz, 2H), 6.68 (t, J = 7.4 Hz,
H), 6.77 (d, J = 7.8 Hz, 2H), 6.90 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 7.4 1H), 6.88-6.96 (m, 2H), 7.10 (s, 1H), 7.24 (m, 2H), 7.45 (t, J = 7.4 Hz,
Hz, 1H), 7.27 (s, 1H), 7.38 (s, 1H), 7.47-7.62 (m, 3H), 7.75 (d, J = 8.5 1H), 7.54-7.63 (m, 2H), 7.71-7.76 (m, 2H), 7.89 (d, J = 6.9 Hz, 1H),
1
13
13
Hz, 1H), 7.91 (d, J = 7.2 Hz, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ 7.94-7.97 (m, 2H), 10.77 (s, 1H) ppm; C NMR (75 MHz, DMSO-d ) δ
6
6
2
1
1
1
0.3, 20.7, 29.1, 29.5, 31.0, 31.3, 43.6, 49.3, 63.2, 70.0, 119.6, 24.1, 28.4, 41.8, 59.6, 70.3, 110.5, 111.4, 117.3, 118.1, 120.5, 120.9,
21.2, 123.6, 124.8, 127.2, 127.5, 127.6 (2C), 128.5 (2C), 129.6, 121.4, 122.9, 123.4, 125.1, 125.3, 126.6, 127.9, 128.5, 129.7, 130.6,
31.0, 132.2, 132.5, 132.9, 133.3, 134.4, 136.3, 144.0, 144.9, 156.7, 131.2, 132.8, 132.9, 136.1, 143.8, 146.8, 157.4, 168.5, 173.3 ppm;
+
+
68.4, 172.7 ppm; m/z (EI, 70 eV) 533 (6, M +2), 419 (69), 314 m/z (EI, 70 eV) 500 (17, M ), 443 (2), 314 (13), 301 (27), 286 (64),
(
100), 300 (31), 243 (8), 105 (65), 57 (42%); Anal. Calcd for 143 (100), 130 (58), 57 (49%); Anal. Calcd for C H N O : C, 76.78;
32 28 4 2
C H N O : C, 79.06; H, 7.01, N, 7.90. Found: C, 79.05; H, 7.05; N, H, 5.64, N, 11.19. Found: C, 76.80; H, 5.65; N, 11.19%.
35 37 3 2
7
.90%.
'-Cyclohexyl-2-p-tolylspiro[isoindoline-1,3'-pyrrolo[2,3-
b]quinoline]-2',3(1'H)-dione (10i). White crystal (345 mg, 73%); mp
1
Acknowledgements
-1
1
241-243 °C; IR (KBr ) νmax 1719 cm ; R (20% EtOAc/hexane) 0.45; H
f
We acknowledge the University of Tehran for financial support of
this research.
NMR (300 MHz, DMSO-d ) δ 1.17-1.84 (m, 8H), 2.15 (s, 3H), 2.21-
6
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Page 8 of 11
ARTICLE
Journal Name
9
(a) L. Benati, R. Leardini, M. Minozzi, D. Nanni,ViPew. SArptiaclgenOonllione,
Notes and references
S. Strazzari and G. Zanardi, Org. Lett., 2002, 4, 3079; (b) G.
DOI: 10.1039/C5OB01095K
1
For reviews on multicomponent reactions, see: (a) A.
Dömling and I. Ugi, Angew. Chem., Int. Ed., 2000, 39, 3168;
López-Valdez, S. Olguín-Uribe, A. Millan-Ortíz, R. Gamez-
Montaño and L. D. Miranda, Tetrahedron, 2011, 67, 2693.
(
b) R. V. A. Orru and M. de Greef, Synthesis, 2003, 1471; (c) J. 10 (a) H. Watanabe, C.-L. Mao, I. T. Barnish and C. R. Hauser, J.
ꢀ
hu and ꢁ. ꢂꢃenaꢄmꢅ, Multicomponent Reactions; Wiley-
Org. Chem., 1969, 34, 919; (b) K. Smith, G. A. El-Hiti and A. S.
Hegazy, Chem. Commun., 2010, 46, 2790.
VCH: Weinheim, 2005; (d) A. Dömling, Chem. Rev., 2006,
1
06, 17; (e) J. D. Sunderhaus and S. F. Martin, Chem. Eur. J., 11 B. S. Bhakuni, A. Yadav, S. Kumar, S. Patel, S. Sharma and S.
2
009, 15, 1300; (f) E, Ruijter, R, Scheffelaar and R. V. A. Orru,
Kumar, J. Org. Chem., 2014, 79, 2944.
Angew. Chem., Int. Ed., 2011, 50, 6234; (g) A. Dömling, W. 12 For examples on synthesis of isoindolinones via metal-
Wang and K. Wang, Chem. Rev., 2012, 112, 3083; (h) T. J. J.
Müller, Multicomponent Reactions, Science of Synthesis;
Georg Thieme: Stuttgart, Germany, 2014.
For examples on post-Ugi transformations, see: (a) X. Huang
and J. Xu, J. Org. Chem., 2009, 74, 8859; (b) C. Che, S. Li, X.
Jiang, J. Quan, S. Lin and Z. Yang, Org. Lett., 2010, 12, 4682;
catalyzed processes, see: (a) M. C. Reddy and M.
Jeganmohan, Org. Lett., 2014, 16, 4866; (b) R. Manoharan,
and M. Jeganmohan, Chem. Commun., 2015, 51, 2929; (c) F.
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Page 10 of 11
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5OB01095K
Table of contents
Abstract ....................................................................................................................................................... 1
Introduction................................................................................................................................................. 1
Results and discussion ..............................................................................................................................2-3
Conclusions.................................................................................................................................................. 4
Experimental................................................................................................................................................ 4
General information .................................................................................................................................... 4
General procedure for synthesis of compound 8a-o and 10a-l................................................................4-7
Acknowledgments ....................................................................................................................................... 7
Notes and references ...............................................................................................................................7-9
Graphical abstract
One-pot synthesis of spiropyrroloquinoline-isoindolinone and their aza-analogs
via Ugi-4CR/ metal-free intramolecular bis-annulation process†
*
Mehdi Ghandi, Nahid Zarezadeh and Alireza Abbasi
catalyst-free one-pot process
O
O
1
O
R
HOOC
COOH
Cl
2
R
2
1
N
1
R N
R
R
N
Cl
Br
N
N
O
O
+
N
N
N
1. MeOH, rt
1. MeOH, rt
2 3
2. DMF, Cs CO , 120 °C
N
3
R
NH
2
CN
3
2
. DMF, Cs
2
CO
3
, 120 °C
2
R
R
3
R
Spiropyrroloquinoline-
isoindolinones
Spiropyrroloquinoline-
aza-isoindolinones
12 examples
15 examples
1
0 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5OB01095K
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