Naphtho- and benzo[g]quinoxalino-fused oxazocinoquinolinones and their diaryl and alkynyl analogues from quinolin-8-ols: A library of novel polynuclear heteroaromatics

Article abstract of DOI:10.1055/s-0030-1257974

The efficient syntheses of 6,6,8,6,6-pentacyclic naphtho-fused oxazocinoquinolinones and 6,6,8,6,6,6-hexacyclic benzo[g]quinoxalino-fused oxazocinoquinolinones were achieved in one-pot sequences. The generation of libraries of their diaryl- and alkynyl-su

Full text of DOI:10.1055/s-0030-1257974

3520
PAPER
Naphtho- and Benzo[g]quinoxalino-Fused Oxazocinoquinolinones and Their
Diaryl and Alkynyl Analogues from Quinolin-8-ols: A Library of Novel
Polynuclear Heteroaromatics
P
olycyclic
O
xazo
u
cinoquinolin
p
ones and
T
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a
eir
D
iaryl
a
n
nd
A
lkynyl
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k
nalogues ar Paira, Arindam Maity, Subhendu Naskar, Shyamal Mondal, Priyankar Paira, Abhijit Hazra,
Krishnendu B. Sahu, Pritam Saha, Sukdeb Banerjee, Nirup B. Mondal*
Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research,
4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India
Fax +91(33)24735197; E-mail: nirup@iicb.res.in
Received 15 June 2010
We were also interested in functionalizing the synthesized
Abstract: The efficient syntheses of 6,6,8,6,6-pentacyclic naphtho-
fused oxazocinoquinolinones and 6,6,8,6,6,6-hexacyclic ben-
zo[g]quinoxalino-fused oxazocinoquinolinones were achieved in
one-pot sequences. The generation of libraries of their diaryl- and
quinolinones by forming their diaryl- and alkynyl-substi-
tuted analogues because of the neuroprotective properties
of diarylquinolinones,13 the antiviral activity of alkynylu-
alkynyl-substituted analogues via Suzuki–Miyaura and Sonogash- racil nucleosides,14a and the antiproliferative activity of 4-
alkynylpyrones.14b Biaryl motifs also occur in a range of
ira cross-coupling reactions, respectively, were also achieved.
pharmaceuticals, herbicides, and natural products,15 and
Key words: fused-ring systems, oxazocinoquinolinones, diaryla-
tions, alkynylations, cross-coupling
alkynyl moieties exist in several bioactive compounds,
e.g. b-D-4¢-C-ethynyl-2¢-3¢-dideoxycytidine (a substrate
for HIV reverse transcriptase),16a SKS-927 (inhibits Src
kinase activity),16b and in a series of nonterpenoid C15-me-
tabolites known as lauroxanes16c and in several substituted
flavones (3-alkynyl-substituted flavone)16d with antican-
cer potential. We, therefore, attempted to apply the two
most versatile and widely used reactions, the Suzuki–
Miyaura17 and Sonogashira18 cross-coupling reactions, for
the selective incorporation of aryl and alkynyl groups onto
the heteroaromatic compounds, i.e. polycyclic oxazocino-
quinolinones that possess halo substituents ready to act as
handles for aryl or alkynyl insertion (Scheme 1).
Nitrogen- and oxygen-containing heterocycles are omni-
present substructures in a myriad of biologically active
natural products and small-molecule pharmaceuticals.1,2
The compounds inhibit enzyme function by binding to the
catalytic intermediate enzyme–DNA complex,3–6 exhibit
high binding affinity to the glycine site of the N-methyl-
D-aspartate receptor, and are highly promising antagonists
for the treatment of several central nervous system disor-
ders.7 The intercalative binding of these drugs to DNA is
due to the presence of a linearly fused cyclic system.8
Moreover, tri-, tetra-, penta-, and hexacyclic compounds
containing one or two heterocyclic rings fused to a quino-
line ring in a linear fashion, derived from natural sources
or of synthetic origin, are reported to have antitumor and
anticancer activities.9 Because quinolinone-containing
natural products express such a wide array of bioactivi-
ties, the synthesis and derivatization of this family of com-
pounds are increasingly gaining importance. Great
efforts, therefore, have been made to discover and opti-
mize new reactions and methodologies to facilitate the
construction of these heterocycles.10 Phase-transfer catal-
ysis has long been recognized as a versatile methodology
for organic synthesis in industry, academia, and process
chemistry.11 As a part of our ongoing endeavor to use
phase-transfer catalysis for the construction of structural-
ly unique N-heteroaromatics,12 we contemplated applying
this tool to the syntheses of novel naphtho- and ben-
zo[g]quinoxalino-fused oxazocinoquinolinones, contain-
ing a quinolinone moiety in their core structure, in one-pot
sequences (Scheme 1).
In this paper, we wish to report in detail the syntheses of
novel penta- and hexacyclic heteroaromatics and their di-
arylated and alkynylated derivatives, along with a plausi-
ble pathway for their formation.
For the synthesis of our initial target compounds, naph-
tho- and benzo[g]quinoxalino-fused oxazocinoquinolino-
nes, the reagents chosen as the key building blocks were
well-known quinolin-8-ol derivatives and 2,3-bis(bro-
momethyl)naphthalene or 2,3-bis(bromomethyl)ben-
zo[g]quinoxaline, both very easily synthesized from 2,3-
dimethylnaphthalene or naphthalene-2,3-diamine, respec-
tively (Scheme 2).
First, quinolin-8-ol (1a) and 2,3-bis(bromomethyl)naph-
thalene (2a) were reacted in a 1:3 molar ratio under phase
transfer catalysis (PTC) conditions.12a During the reac-
tion, thin-layer chromatography was performed every two
hours to monitor progress and showed that complete con-
version of alcohol 1a into product 3a occurred after 12
hours. Usual workup followed by chromatographic sepa-
ration gave the product in 86% yield (Table 1, entry 1).
The characterization of the product as a fused pentacyclic
quinolinone was accomplished by spectral analysis. The
success of the synthesis of unsubstituted derivative 3a
from alcohol 1a and dibromo compound 2a led to the syn-
SYNTHESIS 2010, No. 20, pp 3520–3535
Advanced online publication: 04.08.2010
DOI: 10.1055/s-0030-1257974; Art ID: P09310SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

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Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3521
Cl
Cl
N
O
O
Ar
O
N
n
O
Ar
Cl
O
O
N
N
N
N
N
I
N
O
Cl
O
n
I
O
N
N
O
N
N
N
N
R1
Ar1
O
R1
O
Ar2
R2
R2
N
OH
O
O
N
N
O
Ar1
R1
O
N
O
Ar2
R2
Cl
O
Cl
I
Cl
O
N
O
Ar
N
O
Ar
O
Scheme 1
theses of a variety of naphtho-fused oxazocinoquinolino- After the successful construction of the naphtho- and ben-
nes by the cyclization of quinolin-8-ol derivatives 1b–e zo[g]quinoxalino-fused oxazocinoquinolinones, attempts
with 2,3-bis(bromomethyl)naphthalene (2a); the corre- were made at the synthesis of their diarylated derivatives
sponding quinolinones were isolated in excellent yields using the well-known Suzuki–Miyaura cross-coupling re-
(78–88%) (entries 2–5, respectively).
action. The journey to the target polycyclic diarylquinoli-
nones began with the reaction of benzo[g]quinoxalino-
fused dibromooxazocinoquinolinone 3i and phenylboron-
ic acid (4a) as model reaction partners. When the Suzuki–
Miyaura cross-coupling reaction was carried out using
Amberlite IRA 402(OH) resin mediated conditions in wa-
ter,12e the corresponding product was obtained in only
moderate yield (up to 51%, Table 3, entries 1–3), possibly
because of the poor solubility of quinolinone 3i in aque-
ous media. However, use of the N,N-dimethylformamide–
water (2:3) solvent system removed the solubility prob-
lem, and carrying out the reaction at 100 °C for 8 hours us-
ing Amberlite IRA 402(OH) as the base and 0.5 mol% of
tetrakis(triphenylphosphine)palladium(0) as the catalyst
gave diarylated product 5a in high yield (86%) (entry 5).
A change in the ratio of the solvent system severely low-
ered the yield of the product (entries 4–6).
NBS
Br
Br
CCl4, 4 h
2a
2b
NH2
NH2
O
O
N
N
CH2Cl2, r.t.
4 h
Br
Br
Br
Br
+
Scheme 2
To explore the scope of this methodology with a more
complex ring system, dibromo compound 2a was replaced
with 2,3-bis(bromomethyl)benzo[g]quinoxaline (2b),
which was allowed to react with quinolin-8-ol (1a)
(Table 2, entry 1) and its substituted derivatives 1b–e (en-
tries 2–5, respectively) under similar reaction conditions
to those above. The reactions appeared to be complete
within 14 hours and the corresponding products 3f–j were
isolated in high yields (75–86%).
With the optimal set of reaction conditions thus selected,
the study was further extended by coupling dibromoquin-
olinones 3d and 3i with various aryl- and heteroarylboron-
ic acids 4a–e, and the corresponding diarylated products
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3522
R. Paira et al.
PAPER
Table 1 Construction of Naphtho-Fused Oxazocinoquinolinones 3a–e from Quinolin-8-ol Derivativesa
Entry
1
Quinolin-8-ol derivative
Alkylating agent
Time (h)
12
Product
Yieldb (%)
O
N
Br
Br
86
N
OH
O
2a
2a
1a
3a
Cl
O
N
2
3
12
10
81
87
N
Cl
O
OH
1b
3b
O
N
Cl
2a
2a
2a
Cl
I
N
O
OH
I
1c
3c
O
N
Br
4
5
12
14
88
78
Br
Br
N
O
OH
Br
1d
3d
O
I
N
I
I
N
O
OH
I
1e
3e
a All reactions were carried out using PTC under the conditions reported previously.12a
b Isolated yield.
5a–g were obtained in excellent yields (81–94%) h) gave monoarylated quinolinone 5h along with some of
(Table 4, entries 1–7). As expected, the rate-accelerating diarylated product 5g (entry 8). This evidence unambigu-
effect of a para-methoxy group relative to the boronic ously proves that the diarylation protocol is actually the
acid functionality, as in compound 4b, was well indicated sum of two consecutive monoarylation reactions and not
by the achieved yields (94%) of the corresponding prod- the result of two parallel monoarylations.
ucts and shortest reaction time (4 h) required (entries 2
We next focused our attention towards the possibility of
and 7) compared with the other examples. The reactions
applying the Sonogashira cross-coupling reaction to poly-
of two structural isomers, boronic acids 4c and 4e, dem-
cyclic N,O-heterocycle-fused 5-chloro-7-iodoquinoli-
onstrated interesting results. Although both substrates
nones, which contain an iodo substituent suitable for
produced the corresponding diarylated quinolinones 5e
undergoing alkynyl substitution, for the synthesis of alky-
nylquinolinones. At the outset, we chose pentacyclic 5-
chloro-7-iodoquinolinone 3c and phenylacetylene (6a) as
model reaction partners for the development of the opti-
and 5f in high yields in the reaction with dibromo com-
pound 3d (entries 5 and 6, respectively), higher steric
crowding in 5f compared with that in 5e decelerated the
reaction. This meant the synthesis of the latter compound
mum reaction conditions (Table 5). After thorough
required a longer reaction time (entry 6).
screening of palladium catalysts, solvents, bases, and re-
Regarding the mechanistic course, it is expected that the action parameters (time and temperature), we found that
reaction follows the same pathway as palladium-cata- carrying out the reaction at room temperature for six hours
lyzed Suzuki–Miyaura cross-coupling reactions using in N,N-dimethylformamide, using triethylamine as a base,
Amberlite resin as the base.12e The two arylation steps oc- 0.2 mol% of palladium(II) acetate as a catalyst, and 0.2
cur at different rates, and carrying out the reaction of com- mol% of copper(I) iodide as co-catalyst, produced product
pound 3d and boronic acid 4b for a shorter duration (1.5 7a in the best yield (78%) (entry 9). Alteration of any one
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Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3523
Table 2 Construction of Benzo[g]quinoxalino-Fused Oxazocinoquinolinones 3f–j from Quinolin-8-ol Derivativesa
Entry
1
Quinolin-8-ol derivativeAlkylating agent
Time (h)
14
Product
Yieldb (%)
O
N
N
N
Br
Br
80
86
82
N
N
N
OH
2b
O
1a
3f
Cl
O
N
N
2
3
2b
14
12
N
N
N
N
Cl
OH
O
1b
3g
Cl
O
N
N
2b
I
N
Cl
OH
Br
O
1c
3h
O
N
N
4
5
2b
2b
12
14
75
79
Br
N
Br
O
OH
Br
1d
3i
O
I
N
N
N
I
N
I
O
OH
I
1e
3j
a All reactions were carried out using PTC under the conditions reported previously.12a
b Isolated yield.
of the above conditions decelerated the coupling and se- because of the electron-withdrawing properties of the sub-
verely lowered the yield of the product (entries 1–8 and stituents. The study was further extended using presynthe-
10).
sized tetra- and pentacyclic quinolinones12b–d as
substrates. A gradual decrease in the yields of the corre-
sponding products 11 and 13 (entries 9–14), compared
with those of compounds 9, was observed which might be
due to an increase in steric crowding and the structural
complexity of the systems. Indeed, attempts to alkynylate
hexacyclic 5-chloro-7-iodoquinolinone 3h were unsuc-
cessful. We presume that the greater structural complexity
of fused 6,6,8,6,6,6-ring systems might be partly respon-
sible for the reluctant nature of compound 3h towards the
Sonogashira reaction.
The scope of this methodology was investigated for the
preparation of our target alkynylquinolinones by treating
dihaloquinolinone 3c with aryl- and heteroarylalkynes
6b–d (Table 6, entries 2–4). In further pursuit of this ob-
jective, presynthesized tricyclic dihaloquinolinones 8a–c
were also treated with various aryl-, heteroaryl-, and cy-
clopropylalkynes under the optimal set of reaction condi-
tions to synthesize the corresponding alkynylquinolinones
(Table 7, entries 1–8). The results summarized in Tables 6
and 7 reveal that the reactions generally proceed with
good to excellent yields. However, the presence of an The mechanistic course of the alkynylation is expected
electron-withdrawing group, such as 4-fluorophenyl or 2- to follow the usual profile of palladium-catalyzed
pyridyl, marginally lowers the yield (e.g., Table 7, entries Sonogashira cross-coupling reactions.19 In all cases, the
2, 3, 5, and 8) and the cyclopropyl group drastically low- carbon–chloride bond remained intact and the coupling
ers it (e.g., entry 6). These results are attributed to the low- reaction only involved the carbon–iodide bond; thus,
er activity of the intermediate copper acetylide species complete regioselectivity occurred in every case.
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3524
R. Paira et al.
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Table 3 Optimization of the Reaction Conditions for the Suzuki–Miyaura Cross-Coupling Reaction of Benzo[g]quinoxalino-Fused Dibro-
mooxazocinoquinolinone 3i and Phenylboronic Acid (4a)
O
O
N
N
N
N
PhB(OH)2 (4a)
catalyst (0.5 mol%)
N
N
O
Br
O
3i
5a
Br
Entry
Solvent/base
Catalyst
Time (h)
Temp (°C)
110
Yielda (%)
1
2
3
4
5
6
7
H2O/Amberlite resin
PdCl2/Ph3P
12
14
12
12
8
43
37
51
63
86
72
58
H2O/Amberlite resin
Pd(OAc)2/Ph3P
Pd(PPh3)4
110
H2O/Amberlite resin
110
DMF–H2O (1:4)/Amberlite resin
DMF–H2O (2:3)/Amberlite resin
DMF–H2O (3:2)/Amberlite resin
DMF–H2O (2:3)/Amberlite resin
Pd(PPh3)4
110
Pd(PPh3)4
100
Pd(PPh3)4
14
14
110
b
Pd(PPh3)4
110
a Isolated yield.
b Using 0.1 mol% Pd catalyst.
Table 4 Construction of Polycyclic Diarylquinolinones 5a–g Using the Suzuki–Miyaura Cross-Coupling Reactiona
Entry Quinolinone derivative
Boronic acidTime (h) Product
Yieldb
(%)
O
O
N
N
N
N
N
1
N
8
86
O
B
Br
O
HO
OH
4a
Br
3i
5a
MeO
O
N
N
N
MeO
O
2
3i
4
94
B
HO
OH
4b
MeO
5b
O
N
N
N
3
3i
9
81
O
B
HO
OH
4c
5c
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PAPER
Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3525
Table 4 Construction of Polycyclic Diarylquinolinones 5a–g Using the Suzuki–Miyaura Cross-Coupling Reactiona (continued)
Entry Quinolinone derivative
Boronic acidTime (h) Product
Yieldb
(%)
O
N
N
N
S
S
4
3i
10
83
O
B
HO
OH
S
4d
5d
O
O
N
N
5
9
87
O
Br
O
B
HO
OH
Br
4c
3d
5e
O
N
6
7
8
3d
3d
3d
12
84
B
O
HO
OH
4e
5f
MeO
O
MeO
N
O
4
94
B
HO
OH
4b
OMe
5g
MeO
O
MeO
O
MeO
N
N
O
1.5
31 + 43
O
B
Br
HO
OH
4b
OMe
5g + 5h
a All reactions were carried out under the optimal set of reaction conditions (see above).
b Isolated yield.
All the products were characterized by NMR spectrosco- construction of novel diaryl- and alkynyl-substituted
py and mass spectrometry. Single-crystal X-ray crystallo- polynuclear heteroaromatics using Suzuki–Miyaura and
graphic analysis of quinolinone 3a20 and alkynyl Sonogashira cross-coupling reactions, respectively, has
derivative 11a21 was carried out for the unambiguous de- also been disclosed. The novelty of these versatile meth-
termination of their structures (Figure 1 and Figure 2, re- odologies lies in their operational simplicity, mild reac-
spectively).
tion conditions, and use of readily available starting
materials. We presume that the structural similarities of
these molecules to several natural and synthetic bioactive
compounds may lead to the identification of new biologi-
cally active molecules.
In summary, we have demonstrated the efficient one-pot
synthesis of a novel class of penta- and hexacyclic het-
eroaromatics containing a fused oxazocinoquinolinone
ring system. The application of these molecules for the
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R. Paira et al.
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Table 5 Optimization of the Reaction Conditions for the Sonogashira Cross-Coupling Reaction Using Pentacyclic 5-Chloro-7-iodoquinoli-
none 3c and Phenylacetylene (6a)
Cl
O
Ph
(6a)
O
N
N
catalyst (0.2 mol%)
CuI (0.2 mol%)
O
Cl
O
7a
I
3c
Entry
Solvent, base
Catalysta
Time (h)
Temp (°C)
Yielda (%)
1
2
MeCN, K2CO3
MeCN, Et3N
toluene, Cs2CO3
toluene, Et3N
DMSO, Et3N
DMSO, Et3N
DMF, Na2CO3
DMF, Et3N
PdCl2/Ph3P/CuI
PdCl2/Ph3P/CuI
Pd(PPh3)4/CuI
14
14
8
r.t.
r.t.
r.t.
r.t.
r.t.
80
r.t.
r.t.
r.t.
80
25
38
20
27
35
35
43
58
78
62b
3
4
Pd(OAc)2/Ph3P/CuI
Pd(OAc)2/Ph3P/CuI
Pd(OAc)2/Ph3P/CuI
PdCl2/Ph3P/CuI
6
5
12
12
8
6
7
8
PdCl2/Ph3P/CuI
8
9
DMF, Et3N
Pd(OAc)2/Ph3P/CuI
Pd(OAc)2/Ph3P/CuI
6
10
DMF, Et3N
10
a Isolated yield.
b Using 0.1 mol% Pd catalyst and 0.1 mol% CuI.
Table 6 Construction of Naphtho-Fused Alkynyloxazocinoquinolinones 7a–d Using the Sonogashira Cross-Coupling Reactiona
Entry
Quinolinone derivative
Arylacetylene
Time (h)
Product
Yieldb (%)
Cl
N
O
N
O
1
6
78
O
Cl
O
I
6a
3c
7a
Cl
F
O
N
2
3c
8
O
73
F
6b
7b
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Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3527
Table 6 Construction of Naphtho-Fused Alkynyloxazocinoquinolinones 7a–d Using the Sonogashira Cross-Coupling Reactiona (continued)
Entry
Quinolinone derivative
Arylacetylene
Time (h)
Product
Yieldb (%)
Cl
N
Cl
O
3
3c
8
74
O
Cl
6c
7c
Cl
N
O
N
4
3c
8
O
70
N
6d
7d
a All reactions were carried out under the optimal set of reaction conditions (see above).
b Isolated yield.
Table 7 Construction of Tri-, Tetra-, and Other Pentacyclic N,O-Heterocycle-Fused Alkynylquinolinones Using the Sonogashira Cross-
Coupling Reactiona
Entry
Quinolinone derivative
Arylacetylene
Time (h)
Product
Yieldb (%)
Cl
N
Cl
I
1
6
93
O
N
O
O
O
6a
8a
9a
Cl
F
2
3
4
8a
8a
8
8
6
88
86
91
O
N
O
F
9b
6b
Cl
N
N
O
N
O
6d
9c
Cl
Cl
I
O
O
N
N
O
O
6a
8
9d
Cl
F
5
8b
8
88
O
N
O
F
9e
6b
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R. Paira et al.
PAPER
Table 7 Construction of Tri-, Tetra-, and Other Pentacyclic N,O-Heterocycle-Fused Alkynylquinolinones Using the Sonogashira Cross-
Coupling Reactiona (continued)
Entry
Quinolinone derivative
Arylacetylene
Time (h)
11
Product
Yieldb (%)
Cl
N
6
8b
47
O
O
6e
9f
Cl
Cl
I
7
8
6
8
92
85
O
O
N
N
O
O
6a
8c
9g
Cl
F
8c
O
N
O
F
6b
9h
Cl
N
Cl
I
O
O
9
10
11
12
6
87
83
67
52
N
O
O
6a
10
11a
Cl
N
F
O
10
10
10
8
O
F
6b
11b
Cl
N
N
O
8
N
O
6d
11c
Cl
N
O
12
O
6e
11d
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Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3529
Table 7 Construction of Tri-, Tetra-, and Other Pentacyclic N,O-Heterocycle-Fused Alkynylquinolinones Using the Sonogashira Cross-
Coupling Reactiona (continued)
Entry
Quinolinone derivative
Arylacetylene
Time (h)
Product
Yieldb (%)
Cl
N
Cl
I
O
O
N
13
8
86
O
O
N
N
N
N
6a
12
12
13a
Cl
F
O
N
14
8
80
O
N
N
F
6b
13b
a All reactions were carried out under the optimal set of reaction conditions (see above).
b Isolated yield.
Figure 2 ORTEP representation of compound 11a, the displace-
ment ellipsoid is drawn at a probability of 50%
Figure 1 ORTEP representation of compound 3a (not labeled for
simplification); the displacement ellipsoid is drawn at a probability of
50%
Penta- and Hexacyclic Quinolinones 3a–j; General Procedure
Polycyclic oxazocinoquinolinones 3a–j were synthesized using the
same protocol reported previously by us.12a
Melting points were determined with a capillary melting point ap-
paratus and are uncorrected. Mass spectrometry (ESI, positive) was
conducted using an LC-ESI-Q-TOF micro mass spectrometer. H
1
8,15-Dihydronaphtho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-
1-one (3a)
Yellow needles. Yield: 86%; mp 236–238 °C; Rf = 0.35 (30%
EtOAc–petroleum ether).
1H NMR (600 MHz, CDCl3): d = 5.33 (d, J = 14.4 Hz, 1 H), 5.97
(m, 2 H), 6.55 (d, J = 13.8 Hz, 1 H), 6.70 (d, J = 9.0 Hz, 1 H), 7.12
(t, J = 7.8 Hz, 1 H), 7.23 (m, 1 H), 7.40 (m, 3 H), 7.50 (m, 2 H), 7.68
(m, 1 H), 7.79 (m, 1 H), 8.05 (s, 1 H).
13C NMR (150 MHz, CDCl3): d = 45.5 (CH2), 78.5 (CH2), 122.1
(CH), 123.0 (CH), 123.2 (C), 125.1 (CH), 125.2 (CH), 125.5 (CH),
126.2 (CH), 126.7 (CH), 127.1 (CH), 128.0 (CH), 131.7 (CH),
and 13C NMR spectra were recorded on a Bruker 300/600 MHz
DPX spectrometer using TMS as an internal standard. The quinolin-
8-ol and naphthalene derivatives, 1,4-dibromobutane-2,3-dione,
NBS, boronic acids, alkynes, catalysts, and PTC (TBAB) were pur-
chased from Aldrich Chemical Company Ltd (USA). The organic
solvents used for the chemical syntheses and chromatography were
acquired from E. Merck (India) and were of analytical grade. All
chromatographic purification was performed using silica gel (100–
200 mesh) obtained from SRL (India). Thin-layer chromatography
was performed on precoated silica gel 60 F254 aluminum sheets (E.
Merck, Germany) and the spots were developed using Liebermann–
Burchard solution.
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

3530
R. Paira et al.
PAPER
132.6 (C), 133.1 (2 C), 133.6 (2 C), 138.8 (CH), 146.5 (C), 162.6
(C).
132.7 (C), 133.2 (C), 134.1 (C), 142.3 (CH), 142.7 (CH), 147.1 (C),
162.3 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C21H15NO2Na: 336.0995;
HRMS (ESI): m/z [M + Na]+ calcd for C21H13I2NO2Na: 587.8928;
found: 336.1006.
found: 587.8917.
4-Chloro-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-
ij]quinolin-1-one (3b)
Yellow needles. Yield: 81%; mp 242–246 °C; Rf = 0.33 (30%
8,17-Dihydrobenzo[g]quinazolino[8¢,8a¢,1¢:2,3,4][1,4]oxazoci-
no[6,7-b]quinoxalin-1-one (3f)
Yellow solid. Yield: 80%; mp 221–223 °C; Rf = 0.35 (40% EtOAc–
EtOAc–petroleum ether).
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.30 (d, J = 14.7 Hz, 1 H), 5.95
(m, 2 H), 6.54 (d, J = 13.5 Hz, 1 H), 6.78 (d, J = 9.9 Hz, 1 H), 7.17
(d, J = 8.4 Hz, 1 H), 7.29 (m, 1 H), 7.43 (m, 2 H), 7.50 (s, 1 H), 7.68
(m, 1 H), 7.78 (m, 1 H), 7.99 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 45.8 (CH2), 78.4 (CH2), 120.4 (C),
123.0 (CH), 123.5 (CH), 125.2 (CH), 125.3 (CH), 126.3 (CH),
126.8 (CH), 127.1 (CH), 128.0 (CH), 128.8 (C), 131.8 (CH), 132.7
(2 C), 133.2 (C), 134.9 (CH), 135.0 (2 C), 145.4 (C), 162.1 (C).
1H NMR (600 MHz, CDCl3): d = 5.39 (d, J = 16.2 Hz, 1 H), 5.93 (d,
J = 16.2 Hz, 1 H), 6.17 (d, J = 13.8 Hz, 1 H), 6.64 (d, J = 13.2 Hz,
1 H), 6.75 (d, J = 9.0 Hz, 1 H), 7.20 (m, 1 H), 7.30 (m, 1 H), 7.48
(m, 1 H), 7.58 (m, 2 H), 8.11 (m, 2 H), 8.52 (s, 1 H), 8.64 (s, 1 H),
8.78 (s, 1 H).
13C NMR (150 MHz, CDCl3): d = 49.1 (CH2), 79.0 (CH2), 122.6
(C), 123.4 (CH), 125.0 (C), 125.7 (C), 126.6 (C), 126.9 (C), 127.0
(CH), 127.2 (CH), 127.5 (CH), 128.4 (C), 128.5 (2 CH), 128.7
(CH), 134.0 (CH), 137.4 (CH), 137.6 (CH), 139.0 (CH), 150.5 (C),
152.6 (2 C), 162.7 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C21H14ClNO2Na: 370.0605;
found: 370.0632.
HRMS (ESI): m/z [M + Na]+ calcd for C23H15N3O2Na: 388.1056;
4-Chloro-6-iodo-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazoci-
no[2,3,4-ij]quinolin-1-one (3c)
Brown needles. Yield: 87%; mp 250–252 °C; Rf = 0.25 (25%
EtOAc–petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.53 (d, J = 14.7 Hz, 1 H), 5.87
(m, 2 H), 6.37 (d, J = 13.5 Hz, 1 H), 6.78 (d, J = 9.6 Hz, 1 H), 7.45
(m, 2 H), 7.57 (s, 1 H), 7.68 (s, 1 H), 7.72 (m, 1 H), 7.82 (m, 1 H),
7.95 (d, J = 9.9 Hz, 1 H), 8.08 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 46.8 (CH2), 77.0 (CH2), 95.2 (C),
120.5 (C), 123.3 (CH), 125.2 (CH), 126.4 (CH), 126.8 (CH), 127.2
(CH), 128.0 (CH), 129.2 (C), 131.5 (CH), 132.4 (C), 132.5 (C),
132.6 (CH), 132.7 (C), 133.2 (C), 134.8 (CH), 135.0 (C), 145.2 (C),
162.1 (C).
found: 388.1039.
4-Chloro-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (3g)
Yellow solid. Yield: 86%; mp 236–238 °C; Rf = 0.35 (30% EtOAc–
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.31 (d, J = 16.5 Hz, 1 H), 5.89 (d,
J = 16.5 Hz, 1 H), 6.04 (d, J = 14.4 Hz, 1 H), 6.36 (d, J = 13.8 Hz,
1 H), 6.83 (d, J = 9.6 Hz, 1 H), 7.61 (m, 3 H), 7.77 (s, 1 H), 8.06 (m,
3 H), 8.56 (s, 1 H), 8.82 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C23H14ClN3O2Na: 422.0667;
found: 422.0679.
4-Chloro-6-iodo-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (3h)
Yellow solid. Yield: 82%; mp 245–247 °C; Rf = 0.35 (30% EtOAc–
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.32 (m, 1 H), 5.89 (d, J = 16.2
Hz, 1 H), 6.04 (d, J = 14.1 Hz, 1 H), 6.36 (d, J = 14.1 Hz, 1 H), 6.83
(d, J = 9.9 Hz, 1 H), 7.60 (m, 2 H), 7.77 (s, 1 H), 8.06 (m, 3 H), 8.60
(m, 1 H), 8.82 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H13ClINO2Na: 495.9572;
found: 495.9561.
4,6-Dibromo-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazoci-
no[2,3,4-ij]quinolin-1-one (3d)
Brown needles. Yield: 88%; mp 238–240 °C; Rf = 0.23 (25%
EtOAc–petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.63 (d, J = 14.8 Hz, 1 H), 5.88
(m, 2 H), 6.51 (d, J = 13.5 Hz, 1 H), 6.77 (d, J = 9.6 Hz, 1 H), 7.44
(m, 2 H), 7.57 (s, 1 H), 7.63 (s, 1 H), 7.71 (m, 1 H), 7.80 (m, 1 H),
7.91 (d, J = 9.6 Hz, 1 H), 8.02 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C23H13ClIN3O2Na:
547.9633; found: 547.9668.
4,6-Dibromo-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (3i)
Yellow solid. Yield: 75%; mp 242–244 °C; Rf = 0.33 (30% EtOAc–
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.49 (d, J = 16.2 Hz, 1 H), 5.91 (d,
J = 16.2 Hz, 1 H), 6.09 (d, J = 13.5 Hz, 1 H), 6.54 (d, J = 13.5 Hz,
1 H), 6.82 (d, J = 9.9 Hz, 1 H), 7.59 (m, 2 H), 7.74 (s, 1 H), 7.99 (d,
J = 9.9 Hz, 1 H), 8.05 (m, 2 H), 8.56 (s, 1 H), 8.80 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 46.2 (CH2), 76.0 (CH2), 118.9 (C),
121.0 (C), 121.1 (C), 123.2 (CH), 125.4 (CH), 126.4 (CH), 126.9
(CH), 127.2 (CH), 127.9 (CH), 130.2 (CH), 131.4 (CH), 132.5 (C),
132.6 (2 C), 133.2 (C), 136.2 (C), 137.4 (CH), 142.7 (C), 162.1 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C21H13Br2NO2Na: 491.9205;
found: 491.9202.
4,6-Diiodo-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-
ij]quinolin-1-one (3e)
HRMS (ESI): m/z [M + Na]+ calcd for C23H13Br2N3O2Na:
Yellow needles. Yield: 78%; mp 246–248 °C; Rf = 0.30 (25%
EtOAc–petroleum ether).
543.9267; found: 543.9285.
4,6-Diiodo-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (3j)
Yellow solid. Yield: 79%; mp 247–249 °C; Rf = 0.30 (30% EtOAc–
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.25 (d, J = 16.9 Hz, 1 H), 5.92
(m, 2 H), 6.27 (d, J = 14.1 Hz, 1 H), 6.76 (d, J = 9.6 Hz, 1 H), 7.59
(m, 2 H), 7.87 (d, J = 9.6 Hz, 1 H), 8.09 (m, 2 H), 8.23 (s, 1 H), 8.55
(s, 1 H), 8.80 (s, 1 H).
1H NMR (300 MHz, CDCl3): d = 5.51 (d, J = 14.4 Hz, 1 H), 5.87
(m, 2 H), 6.32 (d, J = 13.8 Hz, 1 H), 6.73 (d, J = 9.9 Hz, 1 H), 7.47
(m, 2 H), 7.57 (s, 1 H), 7.68 (m, 1 H), 7.81 (m, 2 H), 8.00 (m, 1 H),
8.06 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 47.4 (CH2), 76.8 (CH2), 94.8 (C),
96.3 (C), 123.9 (CH), 124.4 (C), 125.2 (CH), 126.4 (CH), 126.9
(CH), 127.3 (CH), 128.0 (CH), 131.5 (CH), 131.8 (C), 132.4 (C),
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

PAPER
Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3531
13C NMR (75 MHz, CDCl3): d = 51.7 (CH2), 78.0 (CH2), 94.8 (C),
95.9 (C), 124.2 (CH), 124.7 (C), 126.8 (CH), 127.0 (CH), 127.2
(CH), 128.4 (2 CH), 128.7 (CH), 134.0 (C), 134.3 (C), 134.4 (C),
137.4 (C), 137.9 (C), 142.4 (CH), 143.0 (CH), 149.7 (2 C), 150.9
(C), 162.7 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C23H13I2N3O2Na: 639.8989;
found: 639.8972.
HRMS (ESI): m/z [M + Na]+ calcd for C37H27N3O4Na: 600.1894;
found: 600.1902.
4,6-Di-2-naphthyl-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (5c)
Brown solid. Yield: 81%; mp 254–256 °C; Rf = 0.28 (30% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 5.02 (d, J = 16.2 Hz, 1 H), 5.53 (d,
J = 15.6 Hz, 1 H), 6.21 (d, J = 13.8 Hz, 1 H), 6.55 (d, J = 13.8 Hz,
1 H), 6.69 (d, J = 9.6 Hz, 1 H), 7.45 (s, 1 H), 7.49 (m, 1 H), 7.54 (m,
7 H), 7.74 (m, 1 H), 7.87 (m, 2 H), 7.91 (m, 1 H), 7.93 (m, 3 H), 7.99
(m, 1 H), 8.02 (m, 1 H), 8.08 (m, 1 H), 8.16 (s, 1 H), 8.46 (s, 1 H),
8.78 (s, 1 H).
13C NMR (150 MHz, CDCl3): d = 51.1 (CH2), 77.5 (CH2), 120.7
(C), 122.0 (CH), 126.3 (CH), 126.5 (CH), 126.6 (3 CH), 126.7
(CH), 126.9 (CH), 127.1 (2 CH), 127.3 (CH), 127.7 (CH), 127.8
(CH), 128.0 (CH), 128.1 (CH), 128.2 (CH), 128.3 (2 CH), 128.4
(CH), 128.6 (CH), 128.7 (CH), 129.0 (CH), 132.7 (C), 132.9 (C),
133.1 (C), 133.4 (C), 133.9 (C), 134.1 (C), 134.5 (C), 134.9 (C),
136.0 (C), 137.2 (C), 137.4 (CH), 137.5 (C), 138.1 (C), 138.2 (C),
144.3 (C), 150.8 (C), 152.2 (C), 163.3 (C).
Penta- and Hexacyclic Diarylquinolinones 5a–g; General Pro-
cedure
Dibromoquinolinone 3d or 3i (0.5 mmol) was taken up in DMF–
H2O (2:3, 20 mL) in a 100-mL round-bottomed flask under an inert
atmosphere. Amberlite IRA 402(OH) (400 mg) was added, and the
mixture was stirred at 45–50 °C until the substrate had dissolved.
Then, 0.5 mol% Pd(PPh3)4 and one of the aryl- or heteroarylboronic
acids 4a–f (1.1 mmol) were added to the solution and the stirring
was continued for the appropriate time period, as given in Table 4,
at 100 °C. After completion of the reaction, the resin was recovered
by simple filtration, thoroughly washed with EtOH (20 mL) fol-
lowed by NaOH soln (20 mL), and then dried at 80 °C under re-
duced pressure for use in subsequent runs. The filtrate was
transferred to a separating funnel and extracted with EtOAc
(75 mL). The organic layer was washed thoroughly with H2O until
free from alkali, dried (anhyd Na2SO4), and evaporated to dryness
in a rotary evaporator under reduced pressure. The residue was pu-
rified by chromatography (silica gel, EtOAc–petroleum ether) to
give the corresponding fused diarylquinolinone.
HRMS (ESI): m/z [M + Na]+ calcd for C43H27N3O2Na: 640.1995;
found: 640.1978.
4,6-Di-2-thienyl-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (5d)
Yellow solid. Yield: 83%; mp 240–242 °C; Rf = 0.25 (30% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 5.07 (m, 1 H), 5.64 (m, 1 H), 6.14
(m, 1 H), 6.45 (m, 1 H), 6.68 (d, J = 9.6 Hz, 1 H), 7.40 (s, 1 H), 7.47
(m, 2 H), 7.56 (m, 4 H), 7.77 (m, 1 H), 7.81 (m, 1 H), 8.11 (m, 2 H),
8.51 (s, 1 H), 8.64 (s, 1 H), 8.81 (s, 1 H).
4,6-Diphenyl-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (5a)
Yellow solid. Yield: 86%; mp 250–252 °C; Rf = 0.30 (30% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 5.01 (d, J = 16.2 Hz, 1 H), 5.54 (d,
J = 15.6 Hz, 1 H), 6.15 (d, J = 14.4 Hz, 1 H), 6.48 (d, J = 14.4 Hz,
1 H), 6.67 (d, J = 9.6 Hz, 1 H), 7.24 (s, 1 H), 7.36 (m, 2 H), 7.44 (m,
4 H), 7.55 (m, 4 H), 7.70 (m, 3 H), 8.09 (m, 2 H), 8.49 (s, 1 H), 8.80
(s, 1 H).
13C NMR (150 MHz, CDCl3): d = 38.7 (CH2), 68.1 (CH2), 121.9
(CH), 126.6 (CH), 126.8 (CH), 127.1 (CH), 127.2 (CH), 128.1
(CH), 128.3 (CH), 128.4 (CH), 128. 5 (2 CH), 128.6 (CH), 128.7
(CH), 128.8 (2 CH), 129.3 (CH), 129.9 (CH), 130.9 (2 CH), 132.4
(2 C), 133.9 (C), 134.2 (C), 134.9 (C), 137.0 (C), 137.1 (C), 137.3
(CH), 137.5 (C), 138.2 (C), 138.6 (C), 144.2 (C), 150.8 (C), 152.2
(C), 163.3 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C31H19N3O2S2Na: 552.0811;
found: 552.0816.
4,6-Di-2-naphthyl-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazoci-
no[2,3,4-ij]quinolin-1-one (5e)
Brown solid. Yield: 87%; mp 244–246 °C; Rf = 0.21 (25% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 4.77 (d, J = 14.4 Hz, 1 H), 5.48 (d,
J = 14.4 Hz, 1 H), 6.09 (d, J = 13.8 Hz, 1 H), 6.61 (d, J = 13.8 Hz,
1 H), 6.65 (d, J = 10.2 Hz, 1 H), 7.28 (s, 1 H), 7.32 (s, 1 H), 7.43 (m,
2 H), 7.45 (m, 1 H), 7.51 (m, 2 H), 7.57 (m, 2 H), 7.64 (m, 2 H), 7.81
(m, 3 H), 7.89 (m, 3 H), 7.95 (m, 2 H), 8.01 (m, 1 H), 8.06 (s, 1 H),
8.14 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C35H23N3O2Na: 540.1682;
found: 540.1693.
13C NMR (150 MHz, CDCl3): d = 46.8 (CH2), 75.8 (CH2), 120.6
(C), 121.7 (CH), 125.0 (CH), 126.2 (CH), 126.4 (2 CH), 126.5
(CH), 126.6 (2 CH), 127.0 (CH), 127.2 (CH), 127.4 (CH), 127.7
(CH), 127.8 (CH), 127.9 (CH), 128.0 (4 CH), 128.3 (2 CH), 128.9
(CH), 131.5 (CH), 132.6 (C), 132.7 (C), 132.8 (C), 133.1 (C), 133.2
(C), 133.4 (2 C), 133.9 (C), 134.9 (C), 135.3 (C), 136.4 (C), 136.9
(CH), 137.3 (C), 137.8 (C), 143.0 (C), 163.0 (C).
4,6-Bis(4-methoxyphenyl)-8,17-dihydrobenzo[g]quinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (5b)
Yellow solid. Yield: 94%; mp 248–250 °C; Rf = 0.25 (30% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 3.86 (s, 3 H), 3.90 (s, 3 H), 5.00
(d, J = 16.2 Hz, 1 H), 5.53 (d, J = 16.2 Hz, 1 H), 6.15 (d, J = 13.8
Hz, 1 H), 6.47 (d, J = 13.8 Hz, 1 H), 6.65 (d, J = 10.2 Hz, 1 H), 6.98
(m, 2 H), 7.05 (m, 2 H), 7.21 (s, 1 H), 7.28 (m, 2 H), 7.56 (m, 2 H),
7.65 (m, 2 H), 7.70 (m, 1 H), 8.07 (m, 2 H), 8.49 (s, 1 H), 8.80 (s, 1
H).
13C NMR (150 MHz, CDCl3): d = 51.3 (CH2), 55.4 (2 CH3), 77.4
(CH2), 113.9 (2 CH), 114.0 (2 CH), 120.3 (C), 121.4 (CH), 126.5
(CH), 126.6 (CH), 126.8 (CH), 127.1 (CH), 128.3 (2 CH), 128.7
(CH), 129.2 (C), 130.7 (2 CH), 130.9 (C), 131.0 (2 CH), 133.9 (C),
134.1 (C), 134.9 (C), 136.8 (C), 137.5 (CH), 137.5 (C), 137.7 (C),
138.1 (C), 143.9 (C), 150.9 (C), 152.3 (C), 159.4 (C), 159.6 (C),
163.5 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C41H27NO2Na: 588.1934;
found: 588.1923.
4,6-Di-1-naphthyl-8,15-dihydronaphtho[2¢,3¢:6,7][1,4]oxazoci-
no[2,3,4-ij]quinolin-1-one (5f)
Brown solid. Yield: 84%; mp 248–250 °C; Rf = 0.23 (25% EtOAc–
petroleum ether).
1H NMR (300 MHz, CDCl3): d = 4.75 (m, 1 H), 5.28 (d, J = 14.1
Hz, 1 H), 6.03 (m, 2 H), 6.59 (m, 2 H), 7.36 (m, 3 H), 7.45 (m, 5 H),
7.60 (m, 5 H), 7.71 (m, 1 H), 7.84 (m, 4 H), 7.97 (m, 2 H), 8.09 (m,
1 H).
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

3532
R. Paira et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 46.3 (CH2), 78.4 (CH2), 121.7 (C),
121.8 (CH), 125.1 (CH), 125.4 (CH), 125.9 (CH), 126.0 (CH),
126.2 (CH), 126.5 (2 CH), 126.7 (CH), 127.2 (CH), 127.8 (CH),
127.9 (CH), 128.0 (2 CH), 128.1 (CH), 128.2 (2 CH), 128.3 (2 CH),
128.4 (2 CH), 131.3 (CH), 131.9 (C), 132.7 (C), 133.1 (C), 133.4
(C), 133.5 (C), 133.8 (2 C), 134.1 (C), 134.4 (C), 135.2 (C), 136.2
(C), 136.5 (C), 137.0 (C), 137.1 (CH), 143.0 (C), 162.9 (C).
4-Chloro-6-(phenylethynyl)-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (7a)
Brown crystalline solid. Yield: 78%; mp 263–265 °C; Rf = 0.23
(25% EtOAc–petroleum ether).
IR (KBr): 3455, 1653, 1587 cm–1.
1H NMR (600 MHz, CDCl3): d = 5.83 (d, J = 14.4 Hz, 1 H), 5.97
(m, 2 H), 6.62 (d, J = 13.8 Hz, 1 H), 6.78 (d, J = 9.6 Hz, 1 H), 7.36
(s, 1 H), 7.42 (m, 2 H), 7.45 (m, 3 H), 7.57 (s, 1 H), 7.68 (m, 3 H),
7.78 (m, 1 H), 7.95 (m, 1 H), 8.01 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C41H27NO2Na: 588.1934;
found: 588.1931.
13C NMR (150 MHz, CDCl3): d = 45.8 (CH2), 76.1 (CH2), 84.3 (C),
97.2 (C), 120.4 (C), 121.3 (C), 122.4 (C), 123.2 (CH), 125.4 (CH),
126.4 (CH), 126.6 (CH), 126.8 (CH), 127.2 (CH), 128.0 (CH),
128.5 (C), 128.6 (2 CH), 129.2 (CH), 131.6 (CH), 131.8 (2 CH),
132.7 (C), 132.8 (C), 133.2 (2 C), 134.7 (CH), 135.3 (C), 145.5 (C),
162.2 (C).
4,6-Bis(4-methoxyphenyl)-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (5g)
Yellow solid. Yield: 94%; mp 243–245 °C; Rf = 0.18 (25% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 3.85 (s, 3 H), 3.92 (s, 3 H), 4.78
(d, J = 14.4 Hz, 1 H), 5.48 (d, J = 15.0 Hz, 1 H), 6.03 (d, J = 13.2
Hz, 1 H), 6.53 (d, J = 13.8 Hz, 1 H), 6.62 (d, J = 9.6 Hz, 1 H), 6.94
(m, 2 H), 7.07 (m, 3 H), 7.22 (m, 2 H), 7.33 (s, 1 H), 7.42 (m, 2 H),
7.60 (s, 1 H), 7.62 (m, 2 H), 7.66 (m, 1 H), 7.81 (m, 1 H), 8.04 (s, 1
H).
13C NMR (150 MHz, CDCl3): d = 46.9 (CH2), 55.3 (2 CH3), 75.6
(CH2), 113.8 (2 CH), 113.9 (2 CH), 120.1 (C), 121.1 (CH), 125.0
(CH), 126.1 (CH), 126.5 (CH), 126.6 (CH), 127.1 (CH), 128.0
(CH), 129.9 (C), 130.5 (2 CH), 131.0 (2 CH), 131.3 (C), 131.4
(CH), 132.6 (C), 133.1 (C), 133.4 (C), 134.0 (C), 134.8 (C), 136.9
(C), 137.0 (CH), 137.4 (C), 142.5 (C), 159.2 (C), 159.3 (C), 163.1
(C).
HRMS (ESI): m/z [M + Na]+ calcd for C29H18ClNO2Na: 470.0918;
found: 470.0941.
4-Chloro-6-[(4-fluorophenyl)ethynyl]-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (7b)
Gray crystalline solid. Yield: 73%; mp 256–258 °C; Rf = 0.21 (25%
EtOAc–petroleum ether).
IR (KBr): 3450, 1668, 1586 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.79 (d, J = 14.7 Hz, 1 H), 5.97
(m, 2 H), 6.61 (d, J = 13.5 Hz, 1 H), 6.79 (d, J = 9.9 Hz, 1 H), 7.15
(m, 2 H), 7.35 (m, 1 H), 7.43 (m, 2 H), 7.57 (s, 1 H), 7.67 (m, 3 H),
7.79 (m, 1 H), 7.95 (m, 1 H), 8.02 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C35H27NO4Na: 548.1832;
13C NMR (150 MHz, CDCl3): d = 45.9 (CH2), 76.2 (CH2), 84.0 (C),
96.0 (C), 115.9 (CH), 116.1 (CH), 118.5 (C), 118.6 (C), 120.4 (C),
121.1 (C), 123.2 (CH), 125.4 (CH), 126.4 (CH), 126.6 (CH), 126.9
(CH), 127.2 (CH), 128.0 (CH), 128.5 (C), 131.6 (CH), 132.7 (C),
132.8 (C), 133.1 (C), 133.2 (C), 133.7 (CH), 133.8 (CH), 134.7
(CH), 135.3 (C), 145.6 (C), 162.1 (C), 162.2 (C).
found: 548.1811.
6-Bromo-4-(4-methoxyphenyl)-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (5h)
Yellow solid. Yield: 43%; mp 241–243 °C; Rf = 0.20 (25% EtOAc–
petroleum ether).
1H NMR (600 MHz, CDCl3): d = 3.92 (s, 3 H), 4.69 (d, J = 14.4 Hz,
1 H), 5.43 (d, J = 14.4 Hz, 1 H), 5.97 (d, J = 13.8 Hz, 1 H), 6.48 (d,
J = 13.8 Hz, 1 H), 6.77 (d, J = 9.6 Hz, 1 H), 7.06 (m, 2 H), 7.20 (s,
1 H), 7.29 (s, 1 H), 7.41 (m, 2 H), 7.58 (m, 2 H), 7.63 (m, 1 H), 7.78
(m, 1 H), 7.98 (m, 2 H).
13C NMR (150 MHz, CDCl3): d = 30.9 (CH3), 46.8 (CH2), 75.6
(CH2), 114.1 (2 CH), 119.3 (C), 122.5 (CH), 125.0 (CH), 125.3
(CH), 126.2 (CH), 126.6 (CH), 127.1 (CH), 127.9 (CH), 128.3 (C),
128.8 (C), 130.4 (2 CH), 131.4 (CH), 132.6 (C), 132.9 (C), 133.1
(C), 133.4 (C), 134.9 (CH), 135.7 (C), 138.0 (C), 142.2 (C), 159.6
(C), 162.8 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C29H17ClFNO2Na: 488.0824;
found: 488.0859.
4-Chloro-6-[(3-chlorophenyl)ethynyl]-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (7c)
Brown crystalline solid. Yield: 74%; mp 258–260 °C; Rf = 0.24
(25% EtOAc–petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.77 (d, J = 14.4 Hz, 1 H), 5.97
(m, 2 H), 6.61 (d, J = 13.8 Hz, 1 H), 6.80 (d, J = 9.6 Hz, 1 H), 7.35
(s, 1 H), 7.42 (m, 4 H), 7.56 (m, 2 H), 7.65 (s, 1 H), 7.70 (m, 1 H),
7.79 (m, 1 H), 7.96 (m, 1 H), 8.02 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.9 (CH2), 76.3 (CH2), 85.4 (C),
95.4 (C), 120.6 (C), 120.7 (C), 123.4 (CH), 124.2 (C), 125.4 (CH),
126.4 (CH), 126.6 (CH), 126.9 (CH), 127.2 (CH), 128.0 (CH),
128.5 (C), 129.5 (CH), 129.9 (2 CH), 131.6 (CH), 131.7 (CH),
132.7 (2 C), 133.1 (C), 133.3 (C), 134.5 (C), 134.6 (CH), 135.4 (C),
145.8 (C), 162.1 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C28H20BrNO3Na: 520.0519;
found: 520.0554.
Polycyclic Alkynylquinolinones 7a–d, 9a–h, 11a–d, 13a, and
13b; General Procedure
One of the arylacetylenes 6a–e (1.1 mmol), Et3N (1.1 mmol), and
CuI (0.2 mmol) were added to DMF (10 mL) in a 25-mL round-bot-
tom flask, and the mixture was stirred for 30 min at r.t. under an
argon atmosphere. The fused dihaloquinolinone 3c, 8a–c, 10 or 12
(1.0 mmol), Pd(OAc)2 (0.2 mol%) and Ph3P (1 mol%) were then
added to the mixture and the stirring was continued for the appro-
priate time period, as given in Tables 6 and 7; TLC was performed
every 2 h to monitor the progress of the reaction. After completion
of the reaction, the mixture was extracted with EtOAc (3 × 50 mL).
The organic layers were combined, washed thoroughly with brine
(25 mL), dried (Na2SO4), and evaporated to dryness in a rotary
evaporator under reduced pressure. The residue was purified by
chromatography (silica gel, EtOAc–petroleum ether) to give the
corresponding fused alkynylquinolinone.
HRMS (ESI): m/z [M + Na]+ calcd for C29H17Cl2NO2Na: 504.0529;
found: 504.0498.
4-Chloro-6-(2-pyridylethynyl)-8,15-dihydronaph-
tho[2¢,3¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (7d)
Yellowish crystalline solid. Yield: 70%; mp 248–250 °C; Rf = 0.21
(25% EtOAc–petroleum ether).
1H NMR (300 MHz, CDCl3): d = 5.84 (d, J = 14.4 Hz, 1 H), 5.99
(m, 2 H), 6.61 (d, J = 13.5 Hz, 1 H), 6.81 (d, J = 9.6 Hz, 1 H), 7.36
(m, 1 H), 7.44 (m, 3 H), 7.60 (s, 1 H), 7.69 (m, 2 H), 7.79 (m, 2 H),
7.97 (m, 1 H), 8.01 (s, 1 H), 8.73 (m, 1 H).
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

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Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
3533
13C NMR (75 MHz, CDCl3): d = 45.9 (CH2), 76.4 (CH2), 83.7 (C),
95.8 (C), 120.3 (C), 120.9 (C), 123.5 (CH), 123.6 (CH), 125.5 (CH),
126.4 (CH), 126.8 (CH), 126.9 (CH), 127.2 (CH), 127.6 (CH),
127.9 (CH), 128.5 (C), 131.5 (CH), 132.7 (2 C), 133.1 (C), 133.2
(C), 134.6 (CH), 135.3 (C), 136.4 (CH), 142.7 (C), 146.2 (C), 150.4
(CH), 162.0 (C).
1H NMR (300 MHz, CDCl3): d = 2.36 (m, 2 H), 4.43 (m, 2 H), 4.63
(m, 2 H), 6.75 (d, J = 9.6 Hz, 1 H), 7.37 (m, 4 H), 7.56 (m, 2 H),
8.03 (d, J = 9.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 27.6 (CH2), 42.3 (CH2), 71.4
(CH2), 84.2 (C), 96.4 (C), 118.1 (C), 120.1 (C), 122.6 (C), 123.0
(CH), 126.1 (C), 126.6 (CH), 128.4 (2 CH), 128.9 (CH), 131.8 (2
CH), 134.9 (C), 135.2 (CH), 148.6 (C), 162.0 (CO).
HRMS (ESI): m/z [M + Na]+ calcd for C28H17ClN2O2Na: 471.0871;
found: 471.0883.
HRMS (ESI): m/z [M + Na]+ calcd for C20H14ClNO2Na: 358.0605;
found: 358.0618.
8-Chloro-10-(phenylethynyl)-2,3-dihydro[1,4]oxazino[2,3,4-
ij]quinolin-5-one (9a)
Yellowish crystalline solid. Yield: 93%; mp 163–164 °C; Rf = 0.55
(40% EtOAc–petroleum ether).
9-Chloro-11-[(4-fluorophenyl)ethynyl]-3,4-dihydro[1,4]oxaze-
pino[2,3,4-ij]quinolin-6(2H)-one (9e)
Brown crystalline solid. Yield: 88%; mp 177–178 °C; Rf = 0.55
(40% EtOAc–petroleum ether).
IR (KBr): 3460, 1663, 1590 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.30 (m, 2 H), 4.49 (m, 2 H), 6.79
(d, J = 9.9 Hz, 1 H), 7.38 (m, 4 H), 7.67 (m, 2 H), 8.09 (d, J = 9.6
Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 39.8 (CH2), 64.1 (CH2), 83.6 (C),
96.9 (C), 112.9 (C), 118.2 (C), 122.5 (C), 122.6 (CH), 123.8 (C),
126.0 (CH), 127.8 (C), 128.4 (2 CH), 128.9 (CH), 131.8 (2 CH),
135.4 (CH), 142.9 (C), 159.6 (CO).
IR (KBr): 3440, 1673, 1585 cm–1
1H NMR (200 MHz, CDCl3): d = 2.36 (m, 2 H), 4.21 (m, 2 H), 4.62
(m, 2 H), 6.75 (d, J = 9.8 Hz, 1 H), 7.06 (m, 2 H), 7.34 (s, 1 H), 7.54
(m, 2 H), 8.02 (d, J = 9.8 Hz, 1 H).
13C NMR (400 MHz, CDCl3): d = 27.6 (CH2), 42.3 (CH2), 71.5
(CH2), 83.9 (C), 95.2 (C), 115.6 (CH), 116.0 (CH), 117.9 (C), 118.8
(C), 120.2 (C), 123.1 (CH), 126.2 (CH), 128.8 (C), 133.7 (CH),
133.9 (CH), 135.0 (C), 135.2 (CH), 148.6 (C), 160.5 (C), 162.0 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C19H12ClNO2Na: 344.0449;
found: 344.0461.
HRMS (ESI): m/z [M + Na]+ calcd for C20H13ClFNO2Na: 376.0517;
found: 376.0561.
8-Chloro-10-[(4-fluorophenyl)ethynyl]-2,3-dihydro[1,4]oxazi-
no[2,3,4-ij]quinolin-5-one (9b)
White crystalline solid. Yield: 88%; mp 151–153 °C; Rf = 0.50
(40% EtOAc–petroleum ether).
9-Chloro-11-(cyclopropylethynyl)-3,4-dihydro[1,4]oxazepi-
no[2,3,4-ij]quinolin-6(2H)-one (9f)
Yellowish crystalline solid. Yield: 47%; mp 183–185 °C; Rf = 0.61
IR (KBr): 3460, 1669, 1588 cm–1.
(40% EtOAc–petroleum ether).
1H NMR (600 MHz, CDCl3): d = 4.29 (m, 2 H), 4.49 (m, 2 H), 6.78
(d, J = 10.2 Hz, 1 H), 7.07 (m, 2 H), 7.35 (s, 1 H), 7.56 (m, 2 H),
8.08 (d, J = 10.2 Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 39.8 (CH2), 64.2 (CH2), 83.3 (C),
95.8 (C), 112.7 (C), 115.7 (CH), 115.9 (CH), 118.3 (C), 118.6 (C),
122.6 (CH), 123.9 (C), 125.9 (CH), 127.8 (C), 133.7 (CH), 133.8
(CH), 135.4 (CH), 142.8 (C), 159.6 (CO), 162.0 (C), 163.7 (C).
IR (KBr): 3467, 1651, 1564 cm–1
1H NMR (300 MHz, CDCl3): d = 0.91 (m, 4 H), 1.53 (m, 1 H), 2.33
(m, 2 H), 4.32 (m, 2 H), 4.59 (m, 2 H), 6.71 (d, J = 9.3 Hz, 1 H),
7.20 (s, 1 H), 7.98 (d, J = 9.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 0.6 (CH), 9.1 (2 CH2), 27.7 (CH2),
42.1 (CH2), 70.7 (C), 71.2 (CH2), 101.4 (C), 118.8 (C), 119.5 (C),
122.6 (CH), 125.9 (C), 126.9 (CH), 134.8 (C), 135.2 (CH), 148.7
(C), 162.1 (CO).
HRMS (ESI): m/z [M + Na]+ calcd for C19H11ClFNO2Na: 362.0355;
found: 362.0343
HRMS (ESI): m/z [M + Na]+ calcd for C17H14ClNO2Na: 322.0605;
found: 322.0590.
8-Chloro-10-(2-pyridylethynyl)-2,3-dihydro[1,4]oxazino[2,3,4-
ij]quinolin-5-one (9c)
White crystalline solid. Yield: 86%; mp 199–200 °C; Rf = 0.14
(40% EtOAc–petroleum ether).
IR (KBr): 3455, 1663, 1590 cm–1.
10-Chloro-12-(phenylethynyl)-2,3,4,5-tetrahydro[1,4]oxazoci-
no[2,3,4-ij]quinolin-7-one (9g)
Yellow crystalline solid. Yield: 92%; mp 119–120 °C; Rf = 0.75
(40% EtOAc–petroleum ether).
1H NMR (300 MHz, CDCl3): d = 4.30 (m, 2 H), 4.50 (t, J = 4.5 Hz,
2 H), 6.80 (d, J = 9.9 Hz, 1 H), 7.29 (m, 1 H), 7.43 (s, 1 H), 7.58 (d,
J = 4.8 Hz, 1 H), 7.73 (m, 1 H), 8.09 (d, J = 9.9 Hz, 1 H), 8.66 (d,
J = 4.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 39.7 (CH2), 64.2 (CH2), 83.1 (C),
95.6 (C), 111.8 (C), 118.7 (C), 122.9 (CH), 123.2 (CH), 123.8 (C),
126.1 (CH), 127.4 (CH), 127.8 (C), 135.3 (CH), 136.2 (CH), 142.7
(C), 143.5 (C), 150.2 (CH), 159.5 (CO).
IR (KBr): 3457, 1667, 1577 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.63 (m, 2 H), 2.07 (m, 2 H), 4.45
(m, 2 H), 4.95 (m, 2 H), 6.79 (d, J = 9.6 Hz, 1 H), 7.39 (m, 4 H),
7.55 (m, 2 H), 8.12 (d, J = 9.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.2 (CH2), 26.8 (CH2), 44.1
(CH2), 76.2 (CH2), 84.3 (C), 96.2 (C), 119.4 (C), 122.0 (C), 122.5
(C), 123.0 (CH), 126.4 (CH), 128.2 (C), 128.4 (2 CH), 128.9 (CH),
131.7 (2 CH), 135.1 (CH), 138.0 (C), 144.5 (C), 162.2 (CO).
HRMS (ESI): m/z [M + Na]+ calcd for C18H11ClN2O2Na: 345.0407;
found: 345.0407
HRMS (ESI): m/z [M + Na]+ calcd for C21H16ClNO2Na: 372.0767;
found: 372.0804.
9-Chloro-11-(phenylethynyl)-3,4-dihydro[1,4]oxazepino[2,3,4-
ij]quinolin-6(2H)-one (9d)
White crystalline solid. Yield: 91%; mp 171–173 °C; Rf = 0.62
(40% EtOAc–petroleum ether).
IR (KBr): 3448, 1661, 1580 cm–1.
10-Chloro-12-[(4-fluorophenyl)ethynyl]-2,3,4,5-tetrahy-
dro[1,4]oxazocino[2,3,4-ij]quinolin-7-one (9h)
Brown crystalline solid. Yield: 85%; mp 139–140 °C; Rf = 0.69
(40% EtOAc–petroleum ether).
IR (KBr): 3450, 1663, 1584 cm–1
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

3534
R. Paira et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 1.61 (m, 2 H), 2.08 (m, 2 H), 4.42
(m, 2 H), 4.92 (m, 2 H), 6.79 (d, J = 9.3 Hz, 1 H), 7.08 (m, 2 H),
7.41 (s, 1 H), 7.55 (m, 2 H), 8.12 (d, J = 9.6 Hz, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C24H15ClN2O2Na: 421.0714;
found: 421.0720.
4-Chloro-6-(cyclopropylethynyl)-8,13-dihydroben-
zo[1¢,2¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (11d)
Yellowish crystalline solid. Yield: 52%; mp 216–218 °C; Rf = 0.77
(40% EtOAc–petroleum ether).
13C NMR (75 MHz, CDCl3): d = 22.3 (CH2), 26.8 (CH2), 44.1
(CH2), 76.3 (CH2), 84.1 (C), 95.0 (C), 115.7 (CH), 116.0 (CH),
118.7 (C), 119.5 (C), 121.8 (C), 123.1 (CH), 126.3 (CH), 128.2 (C),
133.7 (CH), 133.8 (CH), 135.1 (CH), 138.0 (C), 144.5 (C), 161.2
(CO), 162.2 (C), 164.5 (C).
IR (KBr): 3463, 1656, 1567 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C21H15ClFNO2Na: 390.0673;
found: 390.0721.
1H NMR (300 MHz, CDCl3): d = 0.94 (m, 4 H), 1.66 (m, 1 H), 5.46
(d, J = 15.0 Hz, 1 H), 5.81 (m, 2 H), 6.34 (m, 1 H), 6.75 (m, 1 H),
7.03 (m, 1 H), 7.24 (m, 3 H), 7.51 (m, 1 H), 7.96 (m, 1 H).
4-Chloro-6-(phenylethynyl)-8,13-dihydroben-
zo[1¢,2¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (11a)
Yellowish crystalline solid. Yield: 87%; mp 202–204 °C; Rf = 0.83
(40% EtOAc–petroleum ether).
HRMS (ESI): m/z [M + Na]+ calcd for C22H16ClNO2Na: 384.0762;
found: 384.0744.
4-Chloro-6-(phenylethynyl)-8,15-dihydroquinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (13a)
Brown crystalline solid. Yield: 86%; mp 259–260 °C; Rf = 0.63
(40% EtOAc–petroleum ether).
IR (KBr): 3453, 1655, 1579 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.58 (d, J = 14.7 Hz, 1 H), 5.87
(m, 2 H), 6.39 (d, J = 13.5 Hz, 1 H), 6.77 (d, J = 9.9 Hz, 1 H), 7.06
(m, 1 H), 7.23 (m, 2 H), 7.38 (s, 1 H), 7.43 (m, 3 H), 7.53 (m, 1 H),
7.63 (m, 2 H), 7.97 (d, J = 9.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.2 (CH2), 76.5 (CH2), 84.2 (C),
97.1 (C), 120.3 (C), 121.3 (C), 122.4 (C), 123.0 (CH), 126.0 (CH),
126.6 (CH), 128.4 (CH), 128.51 (CH), 128.53 (C), 128.6 (2 CH),
129.2 (CH), 131.8 (2 CH), 132.5 (CH), 134.5 (C), 134.6 (CH),
135.1 (C), 136.0 (C), 145.8 (C), 162.0 (CO).
IR (KBr): 3453, 1667, 1580 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.79 (d, J = 16.2 Hz, 1 H), 5.97 (d,
J = 16.2 Hz, 1 H), 6.19 (d, J = 13.2 Hz, 1 H), 6.73 (d, J = 13.5 Hz,
1 H), 6.83 (d, J = 9.9 Hz, 1 H), 7.43 (m, 4 H), 7.65 (m, 2 H), 7.74
(m, 2 H), 7.99 (m, 2 H), 8.16 (m, 1 H).
13C NMR (300 MHz, CDCl3): d = 48.5 (CH2), 76.8 (CH2), 83.7 (C),
98.1 (C), 120.4 (C), 121.3 (C), 122.2 (C), 123.5 (CH), 127.0 (CH),
128.3 (CH), 128.6 (2 CH), 129.0 (C), 129.3 (CH), 129.8 (CH),
130.1 (CH), 130.8 (CH), 131.7 (C), 131.9 (2 CH), 134.9 (CH),
141.1 (C), 141.9 (C), 145.9 (C), 149.3 (C), 151.4 (C), 162.0 (CO).
HRMS (ESI): m/z [M + Na]+ calcd for C25H16ClNO2Na: 420.0767;
found: 420.0804.
4-Chloro-6-[(4-fluorophenyl)ethynyl]-8,13-dihydroben-
zo[1¢,2¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (11b)
Yellowish crystalline solid. Yield: 83%; mp 249 °C; Rf = 0.81 (40%
EtOAc–petroleum ether).
HRMS (ESI): m/z [M + Na]+ calcd for C27H16ClN3O2Na: 472.0823;
found: 472.0830.
4-Chloro-6-[(4-fluorophenyl)ethynyl]-8,15-dihydroquinazoli-
no[8¢,8a¢,1¢:2,3,4][1,4]oxazocino[6,7-b]quinoxalin-1-one (13b)
White crystalline solid. Yield: 80%; mp 257–258 °C; Rf = 0.67
(40% EtOAc–petroleum ether).
IR (KBr): 3427, 1660, 1581 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.55 (d, J = 14.7 Hz, 1 H), 5.87
(m, 2 H), 6.38 (d, J = 13.5 Hz, 1 H), 6.77 (d, J = 9.6 Hz, 1 H), 7.12
(m, 3 H), 7.24 (m, 2 H), 7.37 (s, 1 H), 7.53 (m, 1 H), 7.62 (m, 2 H),
7.98 (d, J = 9.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.2 (CH2), 76.5 (CH2), 84.0 (C),
95.9 (C), 115.8 (CH), 116.1 (CH), 118.5 (C), 118.6 (C), 120.4 (C),
121.1 (C), 123.1 (CH), 125.9 (CH), 126.5 (CH), 128.4 (CH), 128.5
(CH), 132.5 (CH), 133.7 (CH), 133.8 (CH), 134.5 (C), 134.6 (CH),
135.1 (C), 135.8 (C), 145.8 (C), 161.3 (C), 162.0 (C), 164.7 (CO).
IR (KBr): 3438, 1673, 1580 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.75 (d, J = 16.2 Hz, 1 H), 5.96 (d,
J = 16.2 Hz, 1 H), 6.17 (d, J = 16.2 Hz, 1 H), 6.72 (d, J = 13.5 Hz,
1 H), 6.83 (d, J = 12.6 Hz, 1 H), 7.13 (m, 2 H), 7.40 (s, 1 H), 7.64
(m, 2 H), 7.75 (m, 2 H), 7.99 (m, 2 H), 8.17 (m, 1 H).
13C NMR (300 MHz, CDCl3): d = 48.5 (CH2), 76.9 (CH2), 83.5 (C),
96.9 (C), 115.8 (CH), 116.1 (CH), 118.3 (C), 120.4 (C), 121.0 (C),
123.6 (CH), 126.9 (CH), 128.2 (CH), 129.0 (C), 129.8 (CH), 130.2
(CH), 130.9 (CH), 133.8 (CH), 133.9 (CH), 134.8 (CH), 134.9 (C),
141.1 (C), 141.9 (C), 145.9 (C), 149.3 (C), 151.3 (C), 161.4 (CO),
161.9 (C), 164.8 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C25H15ClFNO2Na: 438.0668;
found: 438.0665.
4-Chloro-6-(2-pyridylethynyl)-8,13-dihydroben-
zo[1¢,2¢:6,7][1,4]oxazocino[2,3,4-ij]quinolin-1-one (11c)
Brown crystalline solid. Yield: 67%; mp 109–110 °C; Rf = 0.36
(40% EtOAc–petroleum ether).
HRMS (ESI): m/z [M + Na]+ calcd for C27H15ClFN3O2Na:
490.0729; found: 490.0737.
IR (KBr): 3408, 1659, 1581 cm–1.
Acknowledgment
1H NMR (200 MHz, CDCl3): d = 5.57 (d, J = 15.0 Hz, 1 H), 5.84
(m, 2 H), 6.34 (d, J = 13.6 Hz, 1 H), 6.75 (d, J = 9.8 Hz, 1 H), 7.08
(m, 1 H), 7.23 (m, 3 H), 7.40 (s, 1 H), 7.49 (m, 1 H), 7.66 (m, 2 H),
7.94 (d, J = 9.8 Hz, 1 H), 8.59 (d, J = 4.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.3 (CH2), 76.9 (CH2), 83.8 (C),
95.8 (C), 120.4 (C), 120.9 (C), 123.5 (CH), 123.8 (CH), 126.1 (C),
127.6 (CH), 128.4 (CH), 128.5 (CH), 130.9 (C), 132.5 (CH), 134.5
(C), 134.6 (C), 135.9 (CH), 136.2 (CH), 136.4 (CH), 142.7 (C),
146.6 (C), 150.4 (CH), 161.9 (CO).
We thank the Council of Scientific and Industrial Research (CSIR)
for fellowships to R. Paira, A. Maity, S. Naskar, S. Mondal, P. Paira,
A. Hazra, K. B. Sahu, and P. Saha; Mr. E. Padmanaban and Mr. K.
K. Sarkar for NMR spectroscopic and HRMS analysis; and Mr.
Rajendra Mahato for a helping hand. We are also thankful to Dr. B.
Achari, Emeritus Scientist, CSIR, for valuable suggestions and en-
couragement.
synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York

PAPER
Polycyclic Oxazocinoquinolinones and Their Diaryl and Alkynyl Analogues
Mondal, S.; Maity, A.; Banerjee, S.; Mondal, N. B.
3535
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synthesis 2010, No. 20, 3520–3535 © Thieme Stuttgart · New York