Synthesis of cyclopentaquinolinone and cyclopentapyridinone from: Ortho-alkynyl-N-arylaldehyde via superbase-promoted C-N, C-O and C-C bond formation

Article abstract of DOI:10.1039/d0ob01281e

An environmentally benign, transition metal-free, superbase-mediated intramolecular annulation of o-alkynylaldehydes with primary amines forms highly functionalized amino-substituted cyclopentaquinolinones and cyclopentapyridinones via C-N, C-C, and CO bond formation. Contrary to the traditional approaches of ring closures, a different mode of annulation is disclosed. The protocol involves the in situ generations of imine intermediate followed by potassium hydroxide-promoted intramolecular cyclization and subsequent dimethyl sulfoxide induced dehydrogenation leads to the formation of N-heterocycles. X-ray crystallographic studies support the assigned structures of the amino-fused N-heterocycles.

Full text of DOI:10.1039/d0ob01281e

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DOI: 10.1039/D0OB01281E
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ARTICLE
Synthesis of Cyclopentaquinolinone and Cyclopentapyridinone
from ortho-alkynyl-N-arylaldehyde via Superbase-promoted C-N,
C-O and C-C Bonds Formation
Received 00th January 20xx,
Accepted 00th January 20xx
Kapil Mohan Saini,a Rakesh K. Saunthwal, a,b Sushmitaa and Akhilesh K. Vermaa*
DOI: 10.1039/x0xx00000x
www.rsc.org/
An environmentally benign, transition metal-free, superbase-mediated intramolecular annulation of o-alkynylaldehydes
with primary amines forms highly functionalized amino-subsituted cyclopentaquinolinones and cyclopentapyridinones via
C-N, C-C, and C=O bond formation. Contrary to the traditional approaches of ring closures, a different mode of annulation
is disclosed. The protocol involves the in-situ generations of imine intermediate followed by potassium hydroxide-
promoted intramolecular cyclization and subsequent dimethyl sulfoxide induced dehydrogenation leads to the formation
of N-heterocycles. X-ray crystallographic studies support the assigned structures of the amino-fused N-heterocycles.
Base-mediated nucleophilic addition reactions of alkynes4 are
essential devices for the assembly of a wide variety of natural
products,5 pharmaceuticals,6 and agrochemicals.7 The
Introduction
Superbase-mediated reactions have emerged as a potent tool
for the synthesis of heterocyclic compounds1 due to
fascinating selectivity and unique ability to activate π-systems,
especially carbon-carbon triple bonds, towards inter- and
intramolecular cyclization.2 Base-promoted intramolecular
cyclization3 of ortho-alkynyl-N-arylaldehyde derived (2-
cyclopenta-quinolinone and cyclopentapyridinone core
moieties have been found to exhibit medicinal activity, such as
cyclopenta[b]pyridin-7-one and 11H-indeno[1,2-b]quinolin-11-
one derivative, which have antimicrobial, antibacterial activity
respectively,8 as well as 7-azaindenoisoquinoline derivative
used as Topoisomerase I Inhibitors.9 Due to the medicinal
importance of these compounds, over the past decades,
significant effort has been made10 and are still demanding for
the developments of the efficient approach for the synthesis.
alkynyl)-arylaldimines having dual-functional groups is
a
significant challenge due to the chemoselectivity between
imines and alkyne functional groups. Despite the significant
achievements already accomplished, we have utilized the
KOH-DMSO chemistry for the synthesis of 3H-
cyclopentaquinolinone and 7H-cyclopentapyridinone via the
intermolecular nucleophilic hydroxylation onto alkyne
followed by intramolecular ring closure.
Previous work
a) Verma group
R2
R2
H2N
HN
O
O
KOH/DMSO
Ph
R
OCH3
O
O
O
N
N
N
b) This work
R2
HO
N
N
N
O2N
NH
O
11H-indeno[1,2-b]quinolin-11-one
Cyclopenta[b]pyridin-7-one derivative
7-Azaindenoisoquinoline derivative
Topoisomerase I Inhibitors
R1
R2
KOH
KOH
/DMSO
(Antibacterial Agent)
(Antimicrobial Agent)
(
)
NH
O
100 o
C
N
5a-g
7 examples
CHO
O
KOH
/DMSO
NH2
R
R1
Het
X
+
Fig 1. Biologically active compounds containing pyridinone and
100 o
C
R2
R2
N
quinolinone cores
R1
2
NH
1
,
4 6
,
3a-q
17 examples
/DMSO
R1
100 o
C
N
O
7a-e
5 examples
Mr. Kapil Mohan Saini, Dr. Rakesh K. Saunthwal, Sushmita, and Prof Akhilesh K.
Verma
Scheme 1 Synthetic approaches for utilizing ortho-alkynylaldehyde
aDepartment of Chemistry, University of Delhi, Delhi–110007, India
E-mail: averma@acbr.du.ac.in
In recent years, various research groups have reported the
metal-catalyzed synthesis of heterocycles.11-13 In 2016, the
Singh group reported the Pd-catalyzed synthesis of 3-
alkylsulfanyl-2- aryl-cyclopenta[b]quinolin-1-ones.14 Transition
bSchool of Chemistry, University of Bristol, Cantock’s Close Bristol, BS8 1TS UK
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
metal-free synthesis has
a
broad scope in synthetic
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chemistry;15,16 therefore, recently we have reported the group-bearing substrates 1bc, such as p-Me, Vpie-wEAtrtioclenOntlhinee
DOI: 10.1039/D0OB01281E
transition metal-free synthesis of amino-indinones via benzene ring of the alkyne, afforded the corresponding
intramolecular cyclization.17 In continuation of our ongoing products 3de in 8893% yield. Electron-withdrawing
metal-free research on tandem cyclization, herein, we report a substrates having substituents such as 2-fluoro and 4-fluoro
superbase-mediated tandem approach18 for the synthesis of provided the desired products 3f-g in good yield. A bulky group
3H-cyclopentaquinolinones and 7H-cyclopentapyridinones by such as 6-methoxynaphthalene-substituted aldehyde 1f
the reaction ortho-alkynyl-hetero-aldehydes with primary reacted smoothly with aniline 2a, and 8-aminoquinolene 2c,
amines.
and afforded the corresponding heterocycles 3h-i in 80% and
82% yields, respectively. It was interesting to note that under
the optimized reaction conditions, electron-deficient
heteroaromatic alkyne 1g provided the targeted product 3j in
86% yield.
Results and discussion
In preliminary experiments, a number of bases were examined
using 2-(phenylethynyl)quinoline-3-carbaldehyde 1a and
aniline 2a as model substrates (Table 1). The reaction of 1a
and 2a with K2CO3 and NaHCO3 at 100 °C for 4 h, did not give a
positive result (Table 1, entries 1 and 2). Instead of carbonate
bases, we next tried the hydroxide bases and gave fruitful
R2
NH
O
KOH
(2.0 equiv)
R2 NH2
R1
+
R
N
DMSO (2.0 mL)
100oC, 45 min
N
R1
O
1
2
3
o
H2N
results. KOH-DMSO at 120 C, provided 60% yield of desired
N
product 3a (entry 3). On increasing the amount of base from 1
equiv to 2 equiv, the yield of the desired cyclized product
increased from 60% to 90% (entry 4). When the reaction
NH
NH
O
NH
N
N
N
N
N
O
O
o
proceeds at 100 C for 45 min, the yield remains unchanged
3a
3c
, 87%
, 90%
3b
, 84%
(entry 5). It is noteworthy that no desired product 3a was
obtained in other polar organic solvents like DMF and THF
(entries 6 and 7). NaOH as the base also provided the desired
product 3a but in lower yield (entry 8). However, LiOH gave
only a trace amount of product (entry 9).
NH
NH
NH
O
Et
Me
N
N
O
O
F
3d
, 93%
3e
3f
, 86%
, 88%
Table 1. Optimization of the reaction conditionsa
Ph
N
NH
NH
O
O
NH
O
base, solvent
temp., time
NH
Ph
Ph NH2
2a
+
N
F
N
OMe
N
Ph
O
OMe
N
O
1a
3a
yield (%)b
3a
3g,
85%
3h,
3i
, 82%
80%
entry
base (equiv)
solvent
time
4 h
NH
1
2
3c
4c
5
6
7
8
9
K2CO3 (1.0)
NaHCO3 (1.0)
KOH (1.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
NaOH (2.0)
LiOH (2.0)
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
THF
DMSO
DMSO
00
NH
NH
Me
Me
4 h
00
60
Et
N
N
N
N
O
Me
O
30 min
30 min
45 min
45 min
45 min
4 h
O
90
3j
3k
, 88%
, 86%
3l
, 87%
90
00
NH
NH
00
Me
Me
nBu
F
42
trace
N
N
O
O
4 h
aUnless otherwise noted all reactions were carried out using 2-
(phenylethynyl)quinoline-3-carbaldehyde 1a (0.50 mmol), aniline 2a
(0.50 mmol), and KOH (2.0 equiv) in 2 mL solvent at 100 oC,
bIsolated yield, c 120 oC.
3n
, 82%
3m
, 90%
3n
Cl
NH
N
N
Cl
Me
NH
NH
Me
Me
Me
F
CF3
CF3
N
N
N
O
O
With optimized conditions in hand, we explored the scope
and generality of the developed reaction by using a variety of
o-alkynylquinolinaldehyde 1a-l and various aryl and heteroaryl
amines 2a-e (Scheme 2). The reaction of substrate 1a, with
aniline 2a, provided the desired product 3a in 90% yield. 4-
aminoaniline 2b and 8-aminoquinolene 2c performed well in
the reaction, providing the cyclized product 3b-c in 84% and
87% yield, respectively. The reaction of electron-donating
O
3o
3p
3q
, 85%
, 86%
, 84%
Scheme 2. Scope of o-alkynylquinolinaldehyde and primary amines.
We further extended the scope of the developed protocol with
electron-rich substitution on the quinoline ring 1h-l. 6-Methyl
2 | J. Name., 2012, 00, 1-3
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R2
substituted quinoline 1h-1l provided the desired products 3k-
3q in good yields with electron-donating and electron-
View Article Online
DOI: 10.103N9H/D0OB01281E
O
R1
KOH
/DMSO
N
R2
NH2
2
N
withdrawing
group
substituted
aryl-alkynes.
The
100 oC, 45 min
R1
O
regioselectivity of the products was clearly assigned by X-ray
crystallographic study19 of compound 3n.
6
7
F
N
R2
NH
NH
NH
NH
Me
O
N
N
KOH
/DMSO
N
R2 NH2
R1
+
O
N
O
O
100oC, 45 min
N
R1
O
2
7a
7b
7c
, 81%
, 86%
, 83%
4
5
F
N
NH
O
NH
NH
NH
NH
N
F
N
Me
N
N
F
N
O
O
O
O
7d
7e
, 82%
, 83%
5a
5b
5c
, 86%
, 84%
, 82%
Me
Scheme 4. Scope of Isonicotinaldehyde
N
N
NH
NH
NH
To further check the generality of the developed protocol,
we extended the chemistry on substrates ortho-alkynyl
S
Me
N
N
N
O
O
benzo[b]thiophen-2-carbaldehyde
and
ortho-alkynyl
O
, 81%
5d
5e
5f
, 83%
, 80%
benzo[b]furan-2-carbaldehyde 8a–b; both of the substrates
failed to provide the desired products 9a-b (Scheme 5).
N
S
NH
MeO
Ph
O
O
N
KOH
Ph
R2
/DMSO
R2 NH2
+
O
5g
, 78%
100oC, 45 min
X
X
HN
9
2
8
Scheme 3. Scope of o-alkynylpyridinaldhyde
a
9a
9b
, X = O; 0 %
a
, X = S; 0 %
Encouraged by the above results, we explored the scope of
ortho-alkynylnicotinaldehydes for the synthesis of
Scheme 5. Scope of O/S heterocycles; a reaction decomposed.
cyclopentapyridinone derivatives (Scheme 3). The reaction of
2-(phenylethynyl)nicotinaldehyde 4a, with aniline 2a or
electron-withdrawing 4-fluoroaniline 2f, provided the desired
products 5a-b in good yields. Electron donating group-bearing
aryl alkyne 4b gave the desired products 5c-d in 86% and 83%
yields, respectively. It is worth noting that the reaction of
substrate 4c having an electron-rich thiophene-substituted
alkyne provided the desired product 5e in 80% yield. Notably,
the heterocyclic amine such as 6-methylpyridin-2-amine 2h
and 6-methoxybenzo[d]thiazol-2-amine 2i effectively gave the
corresponding cyclopenta[b]pyridin-7-ones 5f-g in good yields.
Based on the literature reports,20 a plausible reaction pathway
has been proposed in Scheme 6. The mechanism starts with
the aldehyde-amine reaction, which results in the formation of
species A. Regioselective intramolecular annulation promoted
by hydroxide would produce species C. Nucleophilic attack of
the enol C on dimethyl sulfoxide and subsequent proton
transfer would generate the species D. Finally base-mediated
elimination of dimethyl sulfide produces the desired products.
O
CHO
KOH/DMSO
R
Het
1
Het
The scope of this base-mediated intramolecular annulation
HN
R
R'
3 5, 7
,
was
further
investigated
by
using
ortho-alkynyl
H2O
Me2S
R'
isonicotinaldehyde 6a-c (Scheme 4). Reaction of 3-
(phenylethynyl)isonicotinaldehyde 6a with aniline 2a and 2f
were successful and provided the cyclized amino-fused
products 7a-b in 86% and 83% yields respectively.
Interestingly, electron-rich and electron-poor alkyne-
substituted aldehydes 6b and 6c afforded the desired products
7c-e in 81-84% yields.
2
H2N
R'
R'
N
N
R'
R'
O
S
KN
OH
NK
H
KOH
OH
R
Het
B
Het
S
Het
Het
R
OH
R
R
A
O
OH
C
D
K
Scheme 6. Plausible reaction pathway
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130.7, 130.6, 129.6, 128.7, 128.5, 128.45, 127.5, 126.5, 125.4,
Conclusions
View Article Online
125.2, 124.2, 114.5; HRMS (ESI) [M+H]+ Calcd for [C24H16N2O]
DOI: 10.1039/D0OB01281E
349.1341, found 349.1333.
In summary, we have demonstrated the transition metal-
free, superbase-promoted intramolecular cyclization of readily
accessible ortho-alkynyl-hetero-aldehydes with a wide range of
1-((4-Aminophenyl)amino)-2-phenyl-3H-cyclopenta[b]quinolin-3-
one (3b). The product was obtained as a red needles, mp: 160–162
1
oC (152.4 mg, 84%); H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H),
anilines
for
the
synthesis
of
substituted
cyclopentaquinolinones and cyclopentapyridinones with good 8.04 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 3.9 Hz, 1H), 7.73–7.69 (m, 1H),
yields. A wide variety of readily available ortho-alkynyl-hetero-
aldehydes were utilised including electron-withdrawing and
electron-donating alkynyl-aldehydes. We expect that the
protocol will be useful for the synthesis of highly-substituted
cyclopentanone-fused quinoline and pyridine derivatives,
which could find application in the synthesis of
pharmaceutically active compounds.
7.60–7.56 (m, 1H), 7.18–6.99 (m, 6H), 6.66 (d, J = 5.5 Hz, 2H), 6.35–
6.26 (m, 2H), 5.04 (br s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 187.7,
156.6, 148.4, 147.3, 132.5, 130.6, 130.5, 129.8, 129.6, 128.5, 128.3,
127.5, 126.8, 125.9, 125.4, 116.1, 113.6; HRMS (ESI) [M+H]+ Calcd
for [C24H17N3O] 364.1450, found 364.1471.
2-Phenyl-1-(quinolin-8-ylamino)-3H-cyclopenta[b]quinolin-3-one
o
(3c). The product was obtained as a red needles, mp: 175–177 C
1
(173.5 mg, 87%); H NMR (400 MHz, CDCl3) δ 9.31 (br s, 1H), 8.94
(dd, J = 4.2, 1.6 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.23 (dd, J = 8.4, 1.6
Hz, 1H), 7.89 (s, 1H), 7.77 (dd, J = 8.0, 1.2 Hz, 1H), 7.73–7.68 (m,
1H), 7.59–7.53 (m, 2H), 7.50 (dd, J = 8.3, 1.0 Hz, 1H), 7.43–7.41 (m,
2H), 7.29–7.23 (m, 3H), 7.19-7.15 (m, 1H), 6.82 (dd, J = 7.6, 0.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 189.9, 154.9, 153.2, 149.3, 148.7,
139.9, 136.6, 133.6, 131.4, 130.6, 130.2, 129.6, 128.7, 128.4,
128.34, 128.2, 127.5, 126.0, 124.6, 122.6, 122.2, 119.8, 118.7;
HRMS (ESI) [M+H]+ Calcd for [C27H17N3O] 400.1450, found
400.1464.
Experimental Section
General Procedure for the Synthesis of Starting Substrate
1, 4, 6 and 9: To a solution of substituted 2-halo-aldehyde (1.0
mmol) in MeCN (5 mL), 3 mol% of Pd(PPh3)2Cl2 was added. The
reaction vial was then sealed and flushed with nitrogen. Then,
1.5 equiv of Et3N and 1.05 mmol of alkyne were added to the
reaction mixture. Afterwards the reaction was stirred at 70 °C
until TLC revealed complete conversion of the starting
material. After complete of the reaction, the reaction mixture
was allowed to cool, diluted with H2O, and finally extracted
with EtOAc (3 × 10 mL). The combined organic layers were
dried over Na2SO4, concentrated under vacuum, and purified
by column chromatography using 100−200 mesh sized silica
gel (hexane: ethyl acetate) to afford the corresponding
product. The structure and purity of known starting materials
1, 4, 6 and 9 were confirmed by comparison of their physical
and NMR-spectral data (1H NMR and 13C NMR) with those
reported in the literature.21
1-(phenylamino)-2-(p-tolyl)-3H-cyclopenta[b]quinolin-3-one (3d).
o
The product was obtained as a red needles, mp: 278–280 C (168.3
1
mg, 93%); H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.2 Hz, 1H), 7.67
(s, 1H), 7.65–7.59 (m, 1H), 7.46–7.43 (m, 2H), 7.42–7.32 (m, 5H),
7.24 (d, J = 7.0 Hz, 2H), 7.20 (d, J = 7.8 Hz, 2H), 7.01 (s, 1H), 2.33 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 188.4, 157.1, 156.0, 148.3, 137.8,
137.5, 131.0, 130.1, 129.7, 129.4, 128.9, 128.5, 128.0, 127.7, 127.1,
126.9, 125.8, 117.9, 21.4; HRMS (ESI) [M+H]+ Calcd for [C25H18N2O]
363.1497, found 363.1500.
2-(4-Ethylphenyl)-1-(phenylamino)-3H-cyclopenta[b]quinolin-3-
one (3e). The product was obtained as a red needles, mp: 258–260
1
oC (165.4 mg, 88%); H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.2 Hz,
General experimental procedure for the synthesis of
cyclopenta[b]quinolin-3-one, cyclopenta[b]pyridin-7-one 3,
5, 7: To a solution of ortho-alkynylaldehyde (0.5 mmol), amine
2 (0.5 mmol) in DMSO (2.0 mL), 2.0 equiv of KOH was added.
1H), 8.08 (br s, 1H), 7.62–7.58 (m, 1H), 7.45–7.39 (m, 2H), 7.33–7.24
(m, 5H), 7.18–7.16 (m, 3H), 7.11 (d, J = 7.8 Hz, 2H), 2.55 (q, J = 7.5
Hz, 2H), 1.16 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 188.7,
157.2, 156.1, 148.3, 143.7, 137.8, 130.9, 130.1, 129.1, 129.0, 128.9,
128.8, 128.3, 128.1, 127.9, 126.8, 126.6, 125.6, 117.5, 28.8, 15.7;
HRMS (ESI) [M+H]+ Calcd for [C26H20N2O] 377.1654, found
377.1649.
o
The reaction was then stirred at 100 C temperature until TLC
revealed a complete conversion of the starting material. The
reaction mixture was allowed to cool, diluted with H2O, and
finally extracted with EtOAc (2 × 10 mL). The combined organic
layers were dried over Na2SO4, concentrated under vacuum,
and purified by column chromatography using 100−200 mesh
size silica gels (hexane: ethyl acetate) to afford the
corresponding product.
2-(2-Fluorophenyl)-1-(phenylamino)-3H-cyclopenta[b]quinolin-3-
one (3f). The product was obtained as a yellow needles, mp: 221–
o
1
223 C (157.3 mg, 86%); H NMR (400 MHz, DMSO-d6) δ 10.49 (s,
1H), 8.49 (s, 1H), 8.12 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H),
7.80–7.76 (m, 1H), 7.69–7.65 (m, 1H), 7.17–7.08 (m, 2H), 7.03–6.92
(m, 6H), 6.74–6.69 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 188.0,
159.2 (d, JC-F = 244.7 Hz), 156.5, 155.8, 148.5, 137.5, 132.0, 130.8,
129.8, 129.5, 129.4, 128.8, 128.3, 128.2, 125.7, 125.6, 124.4, 124.0,
121.1 (d, JC-F = 16.4 Hz), 114.9 (d, JC-F = 22.2 Hz), 108.4; HRMS (ESI)
[M+H]+ Calcd for [C24H15FN2O] 367.1247, found 367.1257.
2-Phenyl-1-(phenylamino)-3H-cyclopenta[b]quinolin-3-one (3a).
The product was obtained as a red needles, mp: 171–173 C (156.6
mg, 90%); 1H NMR (400 MHz, DMSO-d6) δ 10.29 (s, 1H), 8.33 (s, 1H),
8.07 (d, J = 8.2 Hz, 1H), 7.90–7.87 (m, 1H), 7.74–7.70 (m, 1H), 7.62–
7.58 (m, 1H), 7.02–6.93 (m, 8H), 6.92–6.88 (m, 2H); 13C NMR (100
MHz, DMSO-d6) δ 188.8, 155.8, 155.5, 148.5, 138.3, 132.3, 131.2,
o
4 | J. Name., 2012, 00, 1-3
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o
1
2-(4-Fluorophenyl)-1-(phenylamino)-3H-cyclopenta[b]quinolin-3-
red needles, mp: 153–155 C (169.6 mg, 87%); H NMR (400 MHz,
View Article Online
DOI: 10.1039/D0OB01281E
one (3g). The product was obtained as a yellow needles, mp: 282– CDCl3) δ 8.15 (br s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.41 (d, J = 8.2 Hz,
o
1
284 C (155.3 mg, 85%); H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 7.29–7.23 (m, 5H), 7.20 (s, 1H), 7.16–7.13 (m, 3H), 7.07 (d, J =
1H), 8.38 (s, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.93–7.89 (m, 1H), 7.75– 7.3 Hz, 2H), 2.54 (q, J = 7.5 Hz, 2H), 2.40 (s, 3H), 1.15 (t, J = 7.6 Hz,
7.70 (m, 1H), 7.63–7.59 (m, 1H), 7.06–6.95 (m, 5H), 6.91-6.86 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 189.0, 157.1, 155.2, 146.7, 143.5,
2H), 6.83–6.78 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ 188.8, 138.1, 137.8, 132.0, 130.6, 129.0, 128.3, 128.2, 128.17, 126.6,
161.0 (d, JC-F = 243.7 Hz), 155.8, 155.7, 148.5, 138.2, 131.4 (d, JC-F
=
126.2, 125.4, 117.1, 28.8, 21.5, 15.7; HRMS (ESI) [M+H]+ Calcd for
7.7 Hz), 131.1, 130.8, 130.7, 129.7, 128.8, 128.6, 128.5, 125.4 (d, JC-F [C27H22N2O] 391.1810, found 391.1786.
= 21.2 Hz), 124.4, 114.3 (d, JC-F = 21.2 Hz), 113.4; HRMS (ESI) [M+H]+
Calcd for [C24H15FN2O] 367.1247, found 367.1251.
2-(6-Methoxynaphthalen-2-yl)-1-(phenylamino)-3H-cyclopenta[b]
2-(4-Butylphenyl)-7-methyl-1-(phenylamino)-3H-
cyclopenta[b]quinolin-3-one (3m). The product was obtained as a
o
1
red needles, mp: 251–253 C (188.1 mg, 90%); H NMR (400 MHz,
quinolin-3-one (3h). The product was obtained as a yellow needles, CDCl3) δ 8.13 (br s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.42 (dd, J = 8.5, 1.6
o
1
mp: 217–219 C (171.1 mg, 80%); H NMR (400 MHz, DMSO-d6) δ Hz, 1H), 7.29–7.23 (m, 5H), 7.20 (s, 1H), 7.17–7.13 (m, 3H), 7.06 (d, J
10.36 (s, 1H), 8.34 (s, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.91 (d, J = 7.8 Hz, = 8.1 Hz, 2H), 2.49 (t, J = 7.6 Hz, 2H), 2.39 (s, 3H), 1.54–1.46 (m, 2H),
1H), 7.77–7.73 (m, 1H), 7.65–7.61 (m, 1H), 7.56–7.52 (m, 2H), 7.44 1.34–1.25 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
(d, J = 8.2 Hz, 1H), 7.14–7.12 (m, 2H), 7.03 (d, J = 8.2 Hz, 1H), 6.97– δ 189.0, 157.0, 155.2, 146.7, 142.1, 138.1, 137.8, 132.0, 130.6,
6.93 (m, 4H), 6.85–6.83 (m, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, 129.0, 128.9, 128.7, 128.3, 128.2, 128.17, 126.6, 126.1, 125.4,
DMSO-d6) δ 189.0, 157.6, 155.9, 155.5, 148.5, 138.4, 133.1, 131.3, 117.0, 35.5, 33.6, 22.3, 21.5, 14.0; HRMS (ESI) [M+H]+ Calcd for
130.8, 130.6, 129.9, 129.6, 128.7, 128.5, 128.3, 128.1, 127.4, 125.6, [C29H26N2O] 419.2123, found 419.2148.
125.3, 125.1, 124.2, 118.7, 114.6, 106.1, 55.6; HRMS (ESI) [M+H]+
Calcd for [C29H20N2O2] 429.1603, found 429.1596.
2-(6-Methoxynaphthalen-2-yl)-1-(quinolin-8-ylamino)-3H-
2-(4-Fluorophenyl)-7-methyl-1-(phenylamino)-3H-cyclopenta[b]
quinolin-3-one (3n). The product was obtained as a red needles,
mp: 155–157 C (155.9 mg, 82%); H NMR (400 MHz, DMSO-d6) δ
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1
cyclopenta[b]quinolin-3-one (3i). The product was obtained as a 10.29 (s, 1H), 8.23 (s, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.63 (s, 1H), 7.53
o
1
red needles, mp: 265–267 C (196.1 mg, 82%); H NMR (400 MHz, (dd, J = 8.5, 1.8 Hz, 1H), 7.05–7.02 (m, 2H), 6.99–6.93 (m, 3H), 6.90–
DMSO-d6) δ 10.59 (s, 1H), 8.96–8.95 (m, 1H), 8.56 (s, 1H), 8.19–8.17 6.88 (m, 2H), 6.83–6.77 (m, 2H), 2.45 (s, 3H); 13C NMR (100 MHz,
(m, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.76–7.72 DMSO-d6) δ 188.9, 161.0 (d, JC-F = 242.8 Hz), 155.6, 154.9, 146.9,
(m, 1H), 7.64–7.60 (m, 1H), 7.54–7.51 (m, 1H), 7.42 (d, J = 8.2 Hz, 138.6, 138.2, 132.5, 131.4 (d, JC-F = 7.7 Hz), 131.2, 130.5, 128.7,
1H), 7.22–7.15 (m, 4H), 7.01–6.96 (m, 2H), 6.91–6.87 (m, 2H), 3.76 128.6, 128.4, 125.5, 124.8, 124.4, 114.3 (d, JC-F = 21.2 Hz), 113.1,
(s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 189.0, 157.5, 157.3, 156.2, 21.6; HRMS (ESI) [M+H]+ Calcd for [C25H17FN2O] 381.1403, found
150.6, 148.5, 142.5, 136.7, 135.4, 132.9, 131.4, 130.8, 130.6, 129.7, 381.1403.
129.4, 128.7, 127.9, 127.7, 127.4, 126.0, 125.9, 125.6, 125.4, 125.2,
1-((2, 5-Dichlorophenyl)amino)-2-(4-fluorophenyl)-7-methyl-3H-
122.5, 118.6, 115.2, 105.9, 55.6; HRMS (ESI) [M+H]+ Calcd for cyclopenta[b]quinolin-3-one (3o). The product was obtained as a
[C32H21N3O2] 480.1712, found 480.1703.
yellow needles, mp: 321–323 oC (192.6 mg, 86%); 1H NMR (400
1-(Phenylamino)-2-(pyridin-2-yl)-3H-cyclopenta[b]quinolin-3-one
MHz, DMSO-d6) δ 10.24 (s, 1H), 8.36 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H),
o
(3j). The product was obtained as a red needles, mp: 284–286 C 7.71 (s, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.30 (d, J = 8.7 Hz, 1H), 7.17-
(149.9 mg, 86%); H NMR (400 MHz, CDCl3) δ 13.39 (br s, 1H), 8.90 7.11 (m, 2H), 6.93–6.83 (m, 4H), 2.48 (s, 3H); 13C NMR (100 MHz,
1
(d, J = 8.3 Hz, 1H), 8.43 (d, J = 4.2 Hz, 1H), 8.20 (d, J = 8.3 Hz, 1H), DMSO-d6) δ 189.2, 161.1 (d, JC-F = 243.7 Hz), 156.5, 154.7, 146.8,
7.77–7.73 (m, 1H), 7.63–7.60 (m, 1H), 7.56–7.47 (m, 5H), 7.43–7.36 138.8, 137.0, 132.6, 132.0, 131.3 (d, JC-F = 7.7 Hz), 131.1, 130.8,
(m, 2H), 7.08–7.05 (m, 1H), 6.88 (s, 1H); 13C NMR (100 MHz, CDCl3) 130.6, 128.8, 128.4, 128.1 (d, JC-F = 6.7 Hz), 124.9, 116.6, 116.2,
δ 186.5, 163.0, 157.2, 154.7, 148.9, 146.4, 138.1, 136.9, 130.9, 114.4 (d, JC-F = 21.2 Hz), 114.3, 21.6; HRMS (ESI) [M+H]+ Calcd for
130.6, 129.6, 129.2, 129.1, 128.1, 127.9, 127.8, 127.0, 122.2, 120.2, [C25H15Cl2FN2O] 449.0624, found 449.0620.
109.0; HRMS (ESI) [M+H]+ Calcd for [C23H15N3O] 350.1293, found
350.1302.
7-Methyl-1-((4-methylpyridin-2-yl)amino)-2-(4-(trifluoromethyl)
phenyl)-3H-cyclopenta[b]quinolin-3-one (3p). The product was
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1
7-Methyl-1-(phenylamino)-2-(o-tolyl)-3H-cyclopenta[b]quinolin-3- obtained as a yellow needles, mp: 148–150 C (186.9 mg, 84%); H
one (3k). The product was obtained as a red needles, mp: 268–270 NMR (400 MHz, DMSO-d6) δ 10.80 (br s, 1H), 8.40 (s, 1H), 7.96 (d, J
1
oC (165.4 mg, 88%); H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.4 Hz, = 8.4 Hz, 1H), 7.90 (d, J = 5.1 Hz, 1H), 7.69 (s, 1H), 7.57 (dd, J = 8.5,
1H), 7.47 (dd, J = 8.5, 1.8 Hz, 1H), 7.36–7.30 (m, 3H), 7.26 (s, 2H), 1.8 Hz, 1H), 7.38 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 7.8 Hz, 2H), 6.76 (d, J
7.23–7.15 (m, 6H), 7.05 (s, 1H), 2.45 (s, 3H), 2.29 (s, 3H); 13C NMR = 4.9 Hz, 1H), 6.59 (s, 1H), 2.47 (s, 3H), 1.94 (s, 3H); 13C NMR (100
(100 MHz, CDCl3) δ 188.3, 157.9, 155.4, 146.7, 138.2, 138.1, 137.5, MHz, DMSO-d6) δ 189.2, 156.0, 154.2, 151.1, 148.7, 147.8, 146.9,
132.2, 130.8, 130.75, 130.5, 130.1, 129.2, 128.5, 128.4, 128.3, 138.9, 137.6, 132.8, 131.1, 130.6, 129.5, 128.9, 128.5, 126.8 (q, JC-F
=
128.0, 127.0, 126.3, 126.2, 125.7, 118.4, 116.3, 21.6, 20.5; HRMS 31.8 Hz), 125.9, 124.8 (q, JC-F = 271.7 Hz), 124.4 (q, JC-F = 2.9 Hz),
(ESI) [M+H]+ Calcd for [C26H20N2O] 377.1654, found 377.1655.
2-(4-Ethylphenyl)-7-methyl-1-(phenylamino)-3H-
121.3, 119.0, 114.4, 21.6, 20.5; HRMS (ESI) [M+H]+ Calcd for
[C26H18F3N3O] 446.1480, found 446.1506.
cyclopenta[b]quinolin-3-one (3l). The product was obtained as a
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J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
Page 6 of 9
ARTICLE
Journal Name
7-Methyl-1-(quinolin-8-ylamino)-2-(4-(trifluoromethyl)phenyl)-
8.45–8.43 (m, 1H), 7.84–7.82 (m, 1H), 7.33 (dd, J = 7.V5i,ew5.A2rtiHclez,O1nHlin)e,
DOI: 10.1039/D0OB01281E
3H-cyclopenta[b]quinolin-3-one (3q). The product was obtained as 7.16–7.14 (m, 1H), 7.12–7.08 (m, 2H), 7.04–7.00 (m, 1H), 6.97–6.96
a yellow needles, mp: 149–151 C (204.1 mg, 85%); H NMR (400 (m, 1H), 6.94–6.91 (m, 2H), 6.73–6.71 (m, 1H); 13C NMR (100 MHz,
MHz, DMSO-d6) δ 10.80 (s, 1H), 8.84–8.83 (m, 1H), 8.48 (s, 1H), 8.20 DMSO-d6) δ 190.5, 154.4, 154.2, 150.0, 138.4, 135.7, 132.0, 128.7,
(dd, J = 8.4, 1.6 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.70 (s, 1H), 7.63 126.7, 125.4, 125.3, 124.1, 124.0, 123.2, 104.8; HRMS (ESI) [M+H]+
(dd, J = 8.2, 1.0 Hz, 1H), 7.58 (dd, J = 8.5, 1.8 Hz, 1H), 7.48–7.45 (m, Calcd for [C18H12N2OS] 305.0749, found 305.0739.
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1
1H), 7.36–7.34 (m, 1H), 7.24 (t, J = 7.8 Hz, 1H), 6.95 (d, J = 8.2 Hz,
5-((6-Methylpyridin-2-yl)amino)-6-phenyl-7H-
2H), 6.79 (d, J = 8.1 Hz, 2H), 2.48 (s, 3H); 13C NMR (100 MHz, DMSO- cyclopenta[b]pyridin-7-one (5f). The product was obtained as a red
d6) δ 188.3, 158.5, 155.2, 150.7, 147.0, 142.4, 138.7, 136.7, 136.6, needles, mp: 258–260 oC (126.7 mg, 81%); 1H NMR (400 MHz,
135.5, 132.7, 130.9, 130.5, 129.4, 128.9, 128.8, 128.5, 126.9, 126.4, DMSO-d6) δ 10.45 (br s, 1H), 8.47–8.46 (m, 1H), 8.01–7.99 (m, 1H),
126.1, 126.07, 125.5, 123.3 (q, JC-F = 2.9 Hz), 122.5, 113.4, 21.6; 7.38 (dd, J = 7.5, 5.2 Hz, 1H), 7.33–7.29 (m, 1H), 7.21–7.18 (m, 1H),
HRMS (ESI) [M+H]+ Calcd for [C29H18F3N3O] 482.1480, found 7.07–7.01 (m, 2H), 6.98–6.95 (m, 2H), 6.71 (d, J = 7.4 Hz, 1H), 6.67
482.1473.
(d, J = 8.1 Hz, 1H), 2.02 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
191.4, 159.6, 156.9, 153.9, 150.9, 150.0, 138.0, 136.2, 133.2, 129.0,
(5a). 127.6, 127.1, 126.3, 118.9, 114.2, 111.3, 105.5, 23.7; HRMS (ESI)
6-Phenyl-5-(phenylamino)-7H-cyclopenta[b]pyridin-7-one
The product was obtained as a yellow needles, mp: 164–166 oC [M+H]+ Calcd for [C20H15N3O] 314.1293, found 314.1294.
(124.9 mg, 84%); 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H), 8.48 5-((6-Methoxybenzo[d]thiazol-2-yl)amino)-6-phenyl-7H-
(dd, J = 5.1, 1.2 Hz, 1H), 7.97 (d, J = 6.9 Hz, 1H), 7.38 (dd, J = 7.5, 5.2 cyclopenta[b]pyridin-7-one (5g). The product was obtained as a
Hz, 1H), 7.02–6.90 (m, 8H), 6.88–6.86 (m, 2H); 13C NMR (100 MHz, yellow needles, mp: 180–182 oC (150.1 mg, 78%); 1H NMR (400
DMSO-d6) δ 190.4, 154.8, 154.2, 150.1, 138.2, 135.5, 132.3, 129.6, MHz, DMSO-d6) δ 11.36 (br s, 1H), 8.52 (d, J = 4.7 Hz, 1H), 7.77 (d, J
128.4, 127.4, 126.5, 126.1, 125.2, 124.1, 108.3; HRMS (ESI) [M+H]+ = 7.1 Hz, 1H), 7.59–7.50 (m, 1H), 7.43–7.32 (m, 2H), 7.21–7.01 (m,
Calcd for [C20H14N2O] 299.1184, found 299.1186.
5-((4-Fluorophenyl)amino)-6-phenyl-7H-cyclopenta[b]pyridin-7-
4H), 6.99–6.94 (m, 1H), 6.82 (dd, J = 8.8, 2.5 Hz, 1H), 3.70 (s, 3H); 13
NMR (100 MHz, DMSO-d6) δ 191.8, 169.7, 161.5, 156.6, 156.5,
C
one (5b). The product was obtained as a red needles, mp: 153–155 151.5, 143.1, 132.7, 129.2, 128.6, 127.6, 127.0, 124.9, 121.6, 115.3,
oC (129.5 mg, 82%); H NMR (400 MHz, CDCl3) δ 10.12 (s, 1H), 8.48 114.8, 105.2, 56.1; HRMS (ESI) [M+H]+ Calcd for [C22H15N3O2S]
1
(dd, J = 5.2, 1.1 Hz, 1H), 7.98 (d, J = 7.3 Hz, 1H), 7.39–7.36 (m, 1H), 386.0963, found 386.0959.
6.98 (dd, J = 6.0, 3.6 Hz, 3H), 6.91–6.87 (m, 4H), 6.82–6.78 (m, 2H);
6-Phenyl-5-(phenylamino)-7H-cyclopenta[c]pyridin-7-one
(7a).
o
13C NMR (100 MHz, DMSO-d6) δ 190.4, 159.8 (d, J = 242.8 Hz, 1C), The product was obtained as a red needles, mp: 265–267 C (128.1
155.2, 154.3, 150.2, 135.4, 134.7, 132.3, 129.8, 127.5, 126.4, 126.3, mg, 86%); 1H NMR (400 MHz, DMSO-d6) δ 10.08 (s, 1H), 8.75 (d, J =
126.2 (d, J = 4.8 Hz, 1C), 125.3, 115.1 (d, J = 23.1 Hz, 1C), 108.1; 4.8 Hz, 1H), 8.50 (s, 1H), 7.72 (d, J = 4.7 Hz, 1H), 6.99–6.95 (m, 5H),
HRMS (ESI) [M+H]+ Calcd for [C20H13FN2O] 317.1090, found 6.92–6.88 (m, 3H), 6.83–6.81 (m, 2H); 13C NMR (100 MHz, DMSO-d6)
317.1086.
δ 191.7, 155.0, 154.1, 148.7, 140.3, 138.2, 132.1, 129.7, 128.4,
5-(Phenylamino)-6-(p-tolyl)-7H-cyclopenta[b]pyridin-7-one (5c). 127.5, 127.3, 126.4, 125.1, 123.8, 114.8, 108.5; HRMS (ESI) [M+H]+
o
The product was obtained as a red needles, mp: 170–172 C (134.1 Calcd for [C20H14N2O] 299.1184, found 299.1185.
mg, 86%); H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.46–8.44
1
5-((4-Fluorophenyl)amino)-6-phenyl-7H-cyclopenta[c]pyridin-7-
(m, 1H), 7.90–7.88 (m, 1H), 7.35 (dd, J = 7.5, 5.2 Hz, 1H), 7.04–7.00 one (7b). The product was obtained as a red needles, mp: 267–269
1
(m, 2H), 6.96–6.92 (m, 1H), 6.89–6.87 (m, 2H), 6.84–6.79 (m, 4H), oC (131.1 mg, 83%); H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H),
2.13 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 190.6, 154.6, 154.2, 8.78 (d, J = 4.9 Hz, 1H), 8.52 (s, 1H), 7.74 (d, J = 4.9 Hz, 1H), 7.62–
150.0, 138.4, 135.6, 135.2, 129.5, 129.4, 128.5, 128.1, 126.5, 125.3, 7.53 (m, 1H), 7.02–7.01 (m, 2H), 6.88–6.78 (m, 6H); 13C NMR (100
125.2, 124.2, 108.6, 21.3; HRMS (ESI) [M+H]+ Calcd for [C21H16N2O] MHz, DMSO-d6) δ 191.3, 159. 2 (d, JC-F = 242.5 Hz), 154.6, 154.1,
313.1341, found 313.1321.
5-((2-(1H-pyrrol-1-yl)phenyl)amino)-6-(p-tolyl)-7H-
cyclopenta[b]pyridin-7-one (5d). The product was obtained as a 107.8; HRMS (ESI) [M+H]+ Calcd for [C20H13FN2O] 317.1090, found
yellow needles, mp: 163–165 oC (156.4 mg, 83%); 1H NMR (400 317.1093.
148.2, 139.9, 139.8, 134.2 (d, JC-F = 1.9 Hz), 131.6, 129.5, 127.1,
126.9, 126.1, 125.5 (d, JC-F = 7.7 Hz), 114.7 (d, JC-F = 23.0 Hz), 114.3,
MHz, CDCl3) δ 8.35–8.34 (m, 1H), 7.65 (s, 1H), 7.31–7.28 (m, 1H),
5-((2-(1H-pyrrol-1-yl)phenyl)amino)-6-(p-tolyl)-7H-
7.26–7.22 (m, 1H), 7.15–7.11 (m, 1H), 7.09–7.06 (m, 2H), 7.04–6.97 cyclopenta[c]pyridin-7-one (7c). The product was obtained as a red
(m, 5H), 6.81–6.80 (m, 2H), 6.31–6.30 (m, 2H), 2.25 (s, 3H); 13C NMR needles, mp: 226–228 oC (152.6 mg, 81%); 1H NMR (400 MHz,
(100 MHz, CDCl3) δ 190.2, 155.2, 154.3, 149.6, 136.9, 135.5, 133.8, CDCl3) δ 8.60 (s, 1H), 8.50 (d, J = 4.9 Hz, 1H), 7.35 (dd, J = 7.8, 1.5 Hz,
132.4, 129.2, 128.8, 127.5, 127.3, 127.2, 126.5, 124.3, 121.7, 112.6, 1H), 7.25–7.21 (m, 1H), 7.14–7.06 (m, 6H), 6.94 (dd, J = 8.0, 1.2 Hz,
110.6, 21.4; HRMS (ESI) [M+H]+ Calcd for [C25H19N3O] 378.1606, 1H), 6.84–6.83 (m, 2H), 6.66–6.65 (m, 1H), 6.36–6.35 (m, 2H), 2.29
found 378.1600.
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 191.7, 154.3, 153.2, 147.4,
5-(Phenylamino)-6-(thiophen-3-yl)-7H-cyclopenta[b]pyridin-7-one 141.2, 137.5, 134.7, 132.8, 129.3, 128.9, 127.5, 127.4, 126.9, 126.7,
(5e). The product was obtained as a red needles, mp: 171–173 C 126.6, 126.1, 121.8, 114.3, 113.9, 110.8; HRMS (ESI) [M+H]+ Calcd
o
(121.5 mg, 80%); 1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), for [C25H19N3O] 378.1606, found 378.1615.
6 | J. Name., 2012, 00, 1-3
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Page 7 of 9
Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
6-(4-Fluorophenyl)-5-(phenylamino)-7H-cyclopenta[c]pyridin-7-
Pan, Z. Li, T. Ding, X. Fang, W. Zhang, H. Xu and Y. Xu, J.
View Article Online
Org. Chem., 2017, 82, 10043–1005D0O. I: 10.1039/D0OB01281E
J. B. Bharate, R. A. Vishwakarma and S. B. Bharate, RSC
Adv., 2015, 5, 42020–42053.
(a) X. P. Peng, Y. Wang, P. P. Liu, K. Hong, H. Chen, X. Yin
and W. M. Zhu, Arch. Pharm. Res., 2011, 34, 907–912. (b)
G. C. Muscia, G. Y. Buldain and S. E. Asís, Eur. J. Med.
Chem., 2014, 73, 243–249. (c) K. Mishra, A. K. Pandey, J.
B. Singh and R. M. Singh, Org. Biomol. Chem., 2016, 14,
6328–6336.
one (7d). The product was obtained as a red needles, mp: 243–245
7
8
1
oC (131.1 mg, 83%); H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H),
8.79 (d, J = 4.6 Hz, 1H), 8.53 (s, 1H), 7.77 (d, J = 4.6 Hz, 1H), 7.05–
7.01 (m, 2H), 6.99–6.95 (m, 1H), 6.93–6.89 (m, 2H), 6.85–6.79 (m,
4H); 13C NMR (100 MHz, DMSO-d6) δ 191.6, 161.0 (d, JC-F = 243.7
Hz), 155.0, 154.2, 148.6, 140.3, 138.1, 131.5 (d, JC-F = 8.7 Hz), 128.5,
127.2, 125.3, 124.0, 114.7, 114.3 (d, JC-F = 21.2 Hz), 107.4; HRMS
(ESI) [M+H]+ Calcd for [C20H13FN2O] 317.1090, found 317.1091.
6-(4-Fluorophenyl)-5-(quinolin-8-ylamino)-7H-
cyclopenta[c]pyridin-7-one (7e). The product was obtained as a red
needles, mp: 257–259 oC (150.4 mg, 82%); 1H NMR (400 MHz,
DMSO-d6) δ 10.37 (s, 1H), 8.88-8.86 (m, 1H), 8.76 (s, 1H), 8.51 (s,
1H), 8.27–8.25 (m, 1H), 7.89 (d, J = 4.7 Hz, 1H), 7.64–7.62 (m, 1H),
7.51–7.48 (m, 1H), 7.20–7.12 (m, 2H), 6.65–6.60 (m, 2H), 6.55–6.49
(m, 2H); 13C NMR (100 MHz, DMSO-d6) δ 191.6, 160.7 (d, JC-F = 243.7
Hz), 156.1, 155.1, 150.5, 148.6, 142.2, 140.2, 136.8, 135.3, 130.9 (d,
JC-F = 7.7 Hz), 128.7, 128.3, 127.4, 126.1 (d, JC-F = 9.0 Hz), 125.5,
122.5, 116.2, 115.0, 113.8 (d, JC-F = 21.2 Hz), 108.2; HRMS (ESI)
[M+H]+ Calcd for [C23H14FN3O] 368.1199, found 368.1199.
9
E. Kiselev, D. Sooryakumar, K. Agama, M. Cushman and Y.
Pommier, J. Med. Chem., 2014, 57, 1289–1298.
10 (a) S. A. Patil, R. Patil and S. A. Patil, Eur. J. Med. Chem.,
2017, 138, 182–198. (b) D. J. Kerr, E. Hamel, M. K. Jung
and B. L. Flynn, Bioorganic Med. Chem., 2007, 15, 3290–
3298. (c) M. Turek, D. Szczesna, M. Koprowski and P.
Bałczewski, Beilstein J. Org. Chem., 2017, 13, 451–494. (d)
A. Das, A. G. K. Reddy, J. Krishna and G. Satyanarayana,
RSC Adv., 2014, 4, 26662–26666.
11 (a) G. Sartori and R. Maggi, Advances in Friedel-Crafts
acylation reactions: Catalytic and green processes, 2009.
(b) M. Rostami, A. R. Khosropour, V. Mirkhani, M.
Moghadam, S. Tangestaninejad and I. Mohammadpoor-
Baltork, Tetrahedron Lett., 2011, 52, 7149–7152. (c) E.
Fillion and D. Fishlock, J. Am. Chem. Soc., 2005, 127,
13144–13145. (d) N. Wu, A. Messinis, A. S. Batsanov, Z.
Yang, A. Whiting and T. B. Marder, Chem. Commun., 2012,
48, 9986–9988. (e) B. Zhou, H. Yang, H. Jin and Y. Liu, J.
Org. Chem., 2019, 84, 2169–2177.
Conflicts of interest
There are no conflicts of interest to declare.
12 (a) A. N. Butkevich, B. Ranieri, L. Meerpoel, I. Stansfield, P.
Angibaud, A. Corbu and J. Cossy, Org. Biomol. Chem.,
2014, 12, 728–731. (b) A. A. Pletnev, Q. Tian and R. C.
Larock, J. Org. Chem., 2002, 67, 9276–9287. (c) K. Gao and
N. Yoshikai, Chem. Commun., 2012, 48, 4305–4307. (d) X.
Chen, Q. He, Y. Xie and C. Yang, Org. Biomol. Chem., 2013,
11, 2582–2585.
Acknowledgements
We gratefully acknowledge the SERB for financial support and
USIC, the University of Delhi for providing instrumentation
facilities. K.M.S. and S. is thankful to CSIR and UGC for the
fellowship respectively.
13 (a) T. Miura and M. Murakami, Org. Lett., 2005, 7, 3339–
3341. (b) H. Tsukamoto and Y. Kondo, Org. Lett., 2007, 9,
4227–4230. (c) C. C. Liu, R. P. Korivi and C. H. Cheng,
Chem. - A Eur. J., 2008, 14, 9503–9506. (d) T. Morimoto,
K. Yamasaki, A. Hirano, K. Tsutsumi, N. Kagawa, K.
Kakiuchi, Y. Harada, Y. Fukumoto, N. Chatani and T.
Nishioka, Org. Lett., 2009, 11, 1777–1780. (e) B. J. Li, H. Y.
Wang, Q. L. Zhu and Z. J. Shi, Angew. Chemie Int. Ed.,
2012, 51, 3948–3952. (f) S. Chen, J. Yu, Y. Jiang, F. Chen
and J. Cheng, Org. Lett., 2013, 15, 4754–4757. (g) Z. Qi, M.
Wang and X. Li, Org. Lett., 2013, 15, 5440–5443. (h) Y.
Kuninobu, T. Matsuki and K. Takai, Org. Lett., 2010, 12,
2948–2950.
Notes and references
1
B. A. Trofimov and E. Y. Schmidt, Acc. Chem. Res., 2018,
51, 1117–1130.
2
(a) E. Y. Schmidt, B. A. Trofimov, I. A. Bidusenko, N. A.
Cherimichkina, I. A. Ushakov, N. I. Protzuk and Y. V.
Gatilov, Org. Lett., 2014, 16, 4040–4043. (b) E. Y. Schmidt,
I. A. Bidusenko, N. A. Cherimichkina, I. A. Ushakov, T. N.
Borodina, V. I. Smirnov and B. A. Trofimov, Chem. - A Eur.
J., 2015, 21, 15944–15946. (c) Andrew Morrell, Michael
Placzek, Seth Parmley, Brian Grella, Smitha Antony, and
Yves
Pommier and
Mark
Cushman,
DOI:10.1021/JM070307.
14 R. M. Singh, R. Kumar, K. C. Bharadwaj and T. Gupta, Org.
3
4
(a) D. Grandjean, P. Pale and J. Chuche, Tetrahedron Lett.,
1992, 33, 4905–4908. (b) Y. Liu, T. Lu, W. F. Tang and J.
Gao, RSC Adv., 2018, 8, 28637–28641.
(a) A. K. Verma, M. Joshi and V. P. Singh, Org. Lett., 2011,
13, 1630–1633. (b) R. Muruganantham, S. M. Mobin and I.
N. N. Namboothiri, Org. Lett., 2007, 9, 1125–1128. (c) M.
Yamagishi, J. Okazaki, K. Nishigai, T. Hata and H. Urabe,
Org. Lett., 2012, 14, 34–37.
X. F. Wu, S. Oschatz, A. Block, A. Spannenberg and P.
Langer, Org. Biomol. Chem., 2014, 12, 1865–1870.
(a) S. Nayak, P. Panda, B. P. Raiguru, S. Mohapatra and C.
S. Purohit, Org. Biomol. Chem., 2019, 17, 74–82. (b) L.
Chem. Front., 2016, 3, 1100–1104.
15 (a) C. Pan, B. Huang, W. Hu, X. Feng and J. T. Yu, J. Org.
Chem., 2016, 81, 2087–2093. (b) Y. K. Song, P. C. Qian, F.
Chen, C. L. Deng and X. G. Zhang, Tetrahedron, 2016, 72,
7589–7593. (c) S. B. Nagode, A. K. Chaturvedi and N.
Rastogi, Asian J. Org. Chem., 2017, 6, 453–457. (d) S. K.
Pagire, P. Kreitmeier and O. Reiser, Angew. Chemie Int.
Ed., 2017, 56, 10928–10932. (e) B. Banerji, L. Majumder
and S. Adhikary, ChemistrySelect, 2018, 3, 1381–1384.
16 (a) C. Wang, J. Yang, X. Cheng, E. Li and Y. Li, Tetrahedron
Lett., 2012, 53, 4402–4404. (b) S. Zhang, X. T. Bai, D. Y.
Chen, P. Chen, Q. Q. Zhang and Y. B. Wang, RSC Adv.,
5
6
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Organic & Biomolecular Chemistry
Page 8 of 9
ARTICLE
Journal Name
2017, 7, 31142–31147. (c) P. Zhao, Y. Liu and C. Xi, Org.
View Article Online
Lett., 2015, 17, 4388–4391. (d) X. Yan, S. Zou, P. Zhao and
C. Xi, Chem. Commun., 2014, 50, 2775–2777.
DOI: 10.1039/D0OB01281E
17 K. M. Saini, R. K. saunthwal, S., and A. K. Verma, Chem. – A
Eur. J., 2020, 26, 1017–1021.
18 (a) R. K. Saunthwal, M. Patel and A. K. Verma, Org. Lett.,
2016, 18, 2200–2203. (b) K. M. Saini, R. K. Saunthwal, S.
Kumar and A. K. Verma, J. Org. Chem., 2019, 84, 2689–
2698. (c) S. Kumar, R. K. Saunthwal, K. M. Saini and A. K.
Verma, Chem. Commun., 2019, 55, 10721–10724. (d) K.
M. Saini, R. K. Saunthwal, S. Kumar, and A. K. Verma, Org.
Biomol. Chem., 2019, 17, 2657-2662.
19 Crystallographic data for the compound 3n has been
deposited with the Cambridge Crystallographic Data
Centre. CCDC deposit number for compound 3n is
1972359, contains all crystallographic details of this
publication and is available free of charge at
www.ccdc.cam.ac.uk
20 M. Rehan, G. Hazra and P. Ghorai, Org. Lett., 2015, 17,
1668–1671.
21 (a) R. Kumar, A. Chandra, B. A. Mir, and G. Shukla, J. Org.
Chem., 2019, 84, 10710−10723. (b) K. Mishra, J. B. Singh,
T. Gupta and R. M. Singh, Org. Chem. Front., 2017, 4,
1926–1930. (c) A. K. Verma, D. Choudhary, R. K.
Saunthwal, V. Rustagi, M. Patel, and R. K. Tiwari, J. Org.
Chem., 2013, 78, 6657−6669. (d) A. K. Verma, V. Rustagi,
T. Aggarwal, and A. P. Singh, J. Org. Chem., 2010, 75,
7691–7703. (e) N. Sharma, M. Asthana, D. Nandini, R. P.
Singh, R. M. Singh, Tetrahedron, 2013, 69, 1822–1829. (f)
V. Rustagi, R. Tiwari, and A. K. Verma, Eur. J. Org. Chem.,
2012, 4590–4602. (g) S., T. Aggarwal, N. Shibata, and A. K.
Verma, Chem. Eur. J. 2019, 25, 16063 – 16067. (h) P.
Kumar, T. Aggarwal, and A. K. Verma, J. Org. Chem., 2017,
82, 6388−6397. (h) M. Asthana, J. B. Singh, R. M. Singh,
Tetrahedron Lett., 2016, 57, 615–618. (i) S. Kumar, C.
Cruz, S. Pal, R. K. Saunthwal, R. K. Tiwari, E. Juaristi, and A.
K. Verma, J. Org. Chem. 2015, 80, 10548–10560
8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/D0OB01281E
Graphical Abstract
R2
NH
O
R1
R2
KOH
/DMSO
/DMSO
100 oC
NH
N
CHO
KOH
/DMSO
NH2
R2
R1
7 examples
R
Het
X
+
100 oC
R2
N
R1
O
NH
17 examples
KOH
R1
100 oC
N
O
5 examples