Efficient synthesis of novel benzo[b][1,8]naphthyridin-4(1H)-ones and pyrido[2,3-b]quinoxalin-4(1H)-ones from alkynones and primary amines

Article abstract of DOI:10.1016/j.tet.2013.01.008

An efficient palladium-catalyzed cyclization of o-chlorohetaryl ynones with aliphatic and aromatic primary amines represents a simple access to a wide range of benzo[b][1,8]naphthyridin-4(1H)-one and pyrido[2,3-b]quinoxalin-4(1H)- one derivatives in good to excellent yields.

Full text of DOI:10.1016/j.tet.2013.01.008

Tetrahedron 69 (2013) 2309e2318
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of novel benzo[b][1,8]naphthyridin-4(1H)-ones
and pyrido[2,3-b]quinoxalin-4(1H)-ones from alkynones and
primary amines
,
b
,
a
a
Viktor O. Iaroshenko a , Muhammad Zahid , Satenik Mkrtchyan ,
*
Ashot Gevorgyan a, Kai Altenburger a, Ingo Knepper a, Alexander Villinger a,
Vyacheslav Ya. Sosnovskikh c, Peter Langer a
,
d
a
€
€
Institut fur Chemie, Universitat Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
b National Taras Shevchenko University, 62 Volodymyrska Str., 01033 Kyiv, Ukraine
c Department of Chemistry, Ural Federal University, 51 Lenina Ave., 620083 Ekaterinburg, Russia
d
€
€
Leibniz-Institut fur Katalyse an der Universitat Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient palladium-catalyzed cyclization of o-chlorohetaryl ynones with aliphatic and aromatic pri-
mary amines represents a simple access to a wide range of benzo[b][1,8]naphthyridin-4(1H)-one and
pyrido[2,3-b]quinoxalin-4(1H)-one derivatives in good to excellent yields.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 17 November 2012
Accepted 4 January 2013
Available online 10 January 2013
Keywords:
o-Chlorohetaryl ynones
Amines
Palladium-catalyzed cyclization
Benzo[b][1,8]naphthyridin-4(1H)-ones
Pyrido[2,3-b]quinoxalin-4(1H)-ones
1. Introduction
O
F
CO2H
O
Of the six isomeric pyridopyridines (diazanaphthalenes), 1,8-
naphthyridines are the most studied subclass because their
skeleton is present in many compounds, which have been iso-
lated from natural substances and exhibit various biological ac-
tivities. They represent important lead structures in medicinal
chemistry (treatment of various human diseases) and agricultural
chemistry (use as pesticides). Among 1,8-naphthyridine de-
rivatives, 6-fluoro-1,8-naphthyridin-4-ones, which are azaanalogs
of fluoroquinolones, have attracted the most attention in the last
30 years.1 There are a number of drugs with 4-pyridone ring, such
as enoxacin,2 a fluoronaphthyridone antibacterial agent showing
the most broad and potent in vitro antibacterial activity, an ex-
cellent in vivo efficacy on systemic infections, and a weak acute
toxicity, and trovafloxacin,3 which is a broad spectrum antibiotic
and inhibits the uncoiling of supercoiled DNA in various bacteria
by blocking the activity of DNA gyrase and topoisomerase IV
(Fig. 1). Its spectrum of activity includes aerobic gram-positive
F
CO2H
H
N
N
N
F
N
N
N
HN
Et
H
H2N
Enoxacin
Trovafloxacin
F
Fig. 1. Important 1,8-naphthyridin-4(1H)-ones.
and gram-negative organisms as well as anaerobic pathogens,
however, it was withdrawn from the market due to the risk of
hepatotoxicity.
Given the broad utility of 1,8-naphthyridines in medicinal
chemistry1 and continuing our research on the efficient synthesis of
drug-like heteroannulated pyridines,4 we were interested in de-
veloping novel approaches, which would allow access to these in-
teresting heterocyclic compounds. In previous study dealing
with the domino amination/conjugate addition reaction of 1-(2-
chloropyridin-3-yl)prop-2-yn-1-ones with amines, Iaroshenko’s
* Corresponding author. Tel.: þ49 381 4986410; fax: þ49 381 49864112; e-mail
addresses: viktor.iaroshenko@uni-rostock.de, iva108@googlemail.com (V.O.
Iaroshenko).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.008

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V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
group described the synthesis of 1,8-naphthyridin-4(1H)-ones.5
Though this method of preparation of 1,8-naphthyridine core
seems to be satisfactory, new routes starting from different mate-
rials are desirable for efficient structure modifications of
these molecules. In connection with this, we decided to prepare
benzo[b][1,8]naphthyridin-4(1H)-one and pyrido[2,3-b]quinox-
alin-4(1H)-one derivatives, commencing with quinoline and
quinoxaline-based substrates. Earlier 2,5-diarylbenzo[b][1,8]naph-
thyridin-4(1H)-ones have been constructed from 3-acetyl-4-
arylquinolin-2(1H)-ones via the intermediates 3-cinnamoyl-4-
arylquinolin-2(1H)-ones,6 while pyrido[2,3-b]quinoxalin-4(1H)-
ones represent a novel heterocyclic system.
In this paper we report the successful realization of our goal
with an efficient palladium-catalyzed tandem amination approach,
which was developed in one pot to afford pyridoannulated quino-
lines and quinoxalines from easily accessible o-chlorohetaryl
acetylenic ketones and primary amines.
naphthyridin-4(1H)-ones 3ael from aliphatic amines. In the case of
less nucleophilic aromatic amines, compounds 3meu were ob-
tained with Pd(PPh3)4 (5 mol %), Cs2CO3 (1.2 equiv) in toluene
(90 ꢀC, 6 h) in variable yields (29e77%). When allylamine was used,
product 3g was obtained in 90% yield as a result of cleavage of the
allyl group under the reaction conditions employed.
The progress of the reaction was monitored by TLC, and the
results are summarized in Table 1. It is important that a wide range
of aromatic and aliphatic amines can effectively participate in the
reaction with acetylenic ketone 2, providing a variety of benzofused
1,8-naphthyridines 3 with high purity after column chromatogra-
phy. It can be observed that the process tolerates only electron-
donating substituents (alkyl, alkoxy, diethylamino) on the
aromatic amines. This is a palladium-catalyzed tandem reaction
consisting of a sequential double CeN bond formation to give benzo
[b][1,8]naphthyridin-4(1H)-ones 3 from quinolinyl acetylenic ke-
tone 2 and primary amines via intermediates A5,10 (Scheme 1). The
structures of all products 3 were characterized by IR, 1H, 13C NMR
spectral data as well as HRMS analysis. Furthermore, the structure
of compound 3f was established by X-ray crystallographic analysis
(Fig. 2).11
2. Results and discussion
Based on previous experience of the Iaroshenko’s group
related to the development of new coupling reactions of pyridinyl
alkynones5 and alkynyl thiophenes,7 we envisaged that 1-(2-
chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one (2), which can be
prepared by allowing a lithium acetylide to react with 2-chloro-3-
formylquinoline, followed by oxidation of the resulting 1-(2-
chloroquinolin-3-yl)-3-phenylprop-2-yn-1-ol (1)8 is suitable sub-
strate for the synthesis of benzo[b][1,8]naphthyridin-4(1H)-one
derivatives 3 (Scheme 1). The requisite starting material, 2-chloro-
3-formylquinoline, was obtained by treatment of acetanilide with
the Vilsmeier reagent (DMF/POCl3) according to the described
procedure.9
Table 1
1-Substituted 2-phenylbenzo[b][1,8]naphthyridin-4(1H)-ones 3aeu
3
R
Yield (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Cyclohexyl
Benzyl
p-Methoxybenzyl
Phenethyl
n-Heptyl
Cyclopropyl
H
3-(4-Morpholino)propyl
HOCH2CH2
3-Methoxybenzyl
2-Chlorobenzyl
N-(3-Propyl)imidazole
4-Methoxyphenyl
3,4-Dimethoxyphenyl
3,5-Dimethoxyphenyl
3,4,5-Trimethoxyphenyl
3,5-Dimethylphenyl
2,4-Dimethoxyphenyl
4-(Diethylamino)phenyl
4-Ethylphenyl
72
85
64
46
65
57
90
87
72
52
86
70
73
76
64
77
58
53
77
50
29
O
OH
n-BuLi, Ph
THF, -78 o
H
C
Ph
N
Cl
N
Cl
1 (98%)
s
t
u
3 h,
MnO2/CH2Cl2
2-Fluorophenyl
O
NHR
O
R-NH2
Ph
i
Ph
N
Cl
N
Cl
A
2 (91%)
O
N
N
Ph
R
3a-u
Scheme 1. Reaction conditions: (i) Pd(PPh3)4, K2CO3, DMF, 170 ꢀC, 3 h (for 3ael);
Pd(PPh3)4, Cs2CO3, toluene, 90 ꢀC, 6 h (for 3meu).
Fig. 2. Molecular structure of compound 3f.
Next, we have obtained a series of 1-(3-chloroquinoxalin-2-yl)
prop-2-yn-1-ones5 by Sonogashira couplingof3-chloroquinoxaline-
2-carbonyl chloride (4), obtained from 3-chloroquinoxaline-2-
carboxylic acid and thionyl chloride,12 with terminal alkynes
(R0¼Ph, 4-t-BuC6H4, n-C8H17) using PdCl2(PPh3)2 in THF to give ke-
tones 5aec in 35e58% yield. Reactions of these compounds with
Then we examined the reactions of alkynone 2 with a range of
commercially available aliphatic and aromatic amines. After the
optimization of the reaction conditions with regard to the type of
catalyst and solvent, we have found that the use of Pd(PPh3)4
(5 mol %), 2 equiv of K2CO3 as a base, and DMF as a solvent (170 ꢀC,
3 h) was essential to get good yields (46e87%) of benzo[b][1,8]

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
2311
aliphatic and aromatic amines heated with or without Pd(PPh3)4 in
the presence of K2CO3 in DMF produced pyrido[2,3-b]quinoxalin-
4(1H)-ones 6aen (Scheme 2, Table 2). As illustrated in Table 2, alky-
nones 5aec readily reacted with various amines to give the corre-
spondingproductsinmoderatetohighyields. Whilearomaticamines
requiredthe employmentofaPdcatalyst(MethodsBeD), reactionsof
aliphatic amines proceeded smoothly under catalyst free conditions
(Method A). When Pd(PPh3)4 was used as catalyst and combined
with rac-2,20-bis(diphenylphosphino)-1,10-binaphthyl (rac-BINAP) or
2-dicyclohexylphosphino-20-(N,N-dimethylamino)biphenyl (Dave-
Phos), the yields were improved slightly (compounds 6c,g,h). The
nature of the acetylene moiety has little effect on the yield of these
reactions.
O
O
N
N
N
SOCl2
OH
Cl
Fig. 3. Molecular structure of compound 6i.
Cl
N
Cl
4
4(1H)-one derivatives on the basis of readily available hetaryl
alkynones. This palladium-catalyzed methodology is a valuable
addition to heteroannulated pyridine synthesis and represents
a general route to various nitrogen-containing heterocycles, which
constitute an important structural subunit of a variety of bi-
ologically active compounds.
PdCl2(PPh3)2
R'
THF
O
O
N
N
R-NH2
Pd(PPh3)4
DMF
R'
N
N
R
R'
N
Cl
4. Experimental
4.1. General
6a-n
5a-c
Scheme 2. Synthesis of pyrido[2,3-b]quinoxalin-4(1H)-ones 6aen.
NMR spectra were recorded on a Brucker AV 300 instruments. IR
spectra were recorded on a Perkin Elmer FT IR 1600 spectrometer
(ATR). Mass spectra were obtained on a Hewlett-Packard HPGC/MS
5890/5972 instrument (EI, 70 eV) by GC inlet or on an MX-1321
instrument (EI, 70 eV) by direct inlet. Column chromatography
was performed on silica gel (63e200 mesh, Merck) and silica gel
Merck 60F254 plates were used for TLC. All solvents were purified
and dried by standard methods.
Table 2
1,2-Disubstituted pyrido[2,3-b]quinoxalin-4(1H)-ones 6aen
6
R0
R
Yield (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cyclohexyl
n-Heptyl
HOCH2CH2
Bn
Phenethyl
2-MeOephenethyl
Ph
3,4,5-(MeO)3C6H2
Cyclohexyl
n-Heptyl
91,a 90,b 90c
99,a 90,b 87d
41,a 53,b 71c
70a
77,a 84b
69,a 73b
26,b 83,c 80d
64,b 80c
79a
4.2. General procedures for the synthesis of 2-phenylbenzo[b]
[1,8]naphthyridin-4(1H)-ones (3aeu)
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
Octyl
Octyl
Octyl
83,a 82b
84,a 82b
69,a 61b
67,a 70b
58,a 74b
Phenethyl
Cyclohexyl
Phenethyl
3,4,5-(MeO)3C6H2
4.2.1. Method A (for 3ael). A mixture of 2 (0.6 mmol), amine
(0.7 mmol), K2CO3 (1.2 mmol), and Pd(PPh3)4 (0.05 mmol) was
heated in 10 ml DMF for 3 h at 170 ꢀC. The residue was purified by
column chromatography on silica gel to afford the product.
a
Method A: 2 equiv K2CO3, DMF, 160 ꢀC.
b
c
Method B: 2 equiv K2CO3, Pd(PPh3)4 (5 mol %), DMF, 110 ꢀC.
Method C: 2 equiv K2CO3, Pd(PPh3)4 (5 mol %), rac-BINAP (5 mol %), DMF, 110 ꢀC.
Method D: 2 equiv K2CO3, Pd(PPh3)4 (5 mol %), DavePhos (7 mol %), DMF, 110 ꢀC.
4.2.2. Method B (for 3meu). A mixture of 2 (0.6 mmol), amine
(0.7 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) was heated at 90 ꢀC for 6 h. The residue was purified
by column chromatography on silica gel to afford the product.
d
These results clearly show that the present approach could be
applicable to various types of hetaryl ynones, providing a simple
and efficient route to the synthesis of a wide range of the fused
naphthyridine and quinoxaline derivatives, which are of interest as
biologically active compounds. The structures of all the compounds
were deduced from their spectral studies (IR, 1H, 13C NMR, and MS);
most of the mass spectra displayed molecular ion peaks at the
appropriate m/z values. In addition, the structure of 6i was con-
firmed by X-ray single crystal analysis (Fig. 3).11
4.3. General procedures for the synthesis of pyrido[2,3-b]
quinoxalin-4(1H)-ones (6aen)
4.3.1. Method A. Alkylamine (2.0 equiv), K2CO3 (2.0 equiv), and
1.0 equiv of the corresponding 1-(2-chloropyridin-3-yl)prop-2-yn-
1-one 5 are heated at 160 ꢀC in dry DMF under argon atmosphere in
a pressure tube. After 16 h, the solvent was removed in vacuo and
the crude product was purified by column chromatography (eluent:
n-heptane/ethylacetate).
3. Conclusion
In conclusion, we have developed an efficient synthesis of benzo
4.3.2. Method B. Alkylamine (2.0 equiv), K2CO3 (2.0 equiv),
[b][1,8]naphthyridin-4(1H)-one
and
pyrido[2,3-b]quinoxalin-
Pd(PPh3)4 (5 mol %), and 1.0 equiv of the corresponding 1-(2-

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V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
chloropyridin-3-yl)prop-2-yn-1-one 5 are heated at 110 ꢀC in dry
DMF under argon atmosphere in a pressure tube. After approxi-
mately 16 h (controlled by TLC) the solvent was removed in vacuo
and the crude product was purified by column chromatography
(eluent: n-heptaneeethylacetate).
70 eV): m/z (%)¼354 (Mþ, 6), 273 (23), 272 (100), 244 (31); HRMS
(ESI-TOF): calcd for C24H23N2O [MþH]þ 355.18049, found
355.18054. Anal. Calcd for C24H22N2O (354.444): C, 81.33; H, 6.26;
N, 7.90. Found: C, 80.98; H, 6.46; N, 7.75.
5.4. 1-Benzyl-2-phenylbenzo[b][1,8]naphthyridin-4(1H)-one
4.3.3. Method C. This method is similar to Method A, only the
ligand rac-BINAP (5 mol %) was loaded.
(3b)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), benzylamine (75 mg, 0.7 mmol), po-
tassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and
DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3b was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (180 mg, 85%), mp 238 ꢀC. 1H NMR (CDCl3, 300 MHz):
4.3.4. Method D. This method is similar to Method A, only the
ligand DavePhos (7 mol %) was loaded.
5. Analytical data
5.1. 1-(2-Chloroquinolin-3-yl)-3-phenylprop-2-yn-1-ol (1)
d
¼5.71 (s, 2H), 6.21 (s, 1H), 6.78e6.81 (m, 2H), 7.06e7.08 (m, 3H),
7.18e7.22 (m, 2H), 7.28e7.49 (m, 4H), 7.69e7.74 (m, 1H), 7.91 (d, 1H,
3J¼8.1 Hz), 7.98 (d, 1H, 3J¼8.1 Hz), 9.26 (s, 1H); 13C NMR (75 MHz,
Starting with 2-chloroquinoline-3-carbaldehyde (400 mg,
2.1 mmol), phenylacetylene (257 mg, 2.52 mmol), and n-BuLi
(1.016 ml, 2.52 mmol), 1 was isolated after column chromatography
(silica gel, n-heptane/EtOAc¼5:1) as a white solid (600 mg, 98%),
CDCl3):
d¼49.4, 111.6, 120.6, 125.5, 125.7, 126.7, 127.1, 128.2, 128.3,
128.4, 128.5, 129.3, 129.6, 132.2, 135.6, 137.7, 137.9, 149.1, 149.6,
157.4, 178.8; IR (ATR, cmꢁ1):
n¼3048 (w), 1616 (s), 1552 (m), 1494
mp 194e196 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼5.95 (d, 1H,
(w), 1328 (m), 1184 (w), 1145 (m), 1072 (w), 1023 (m), 928 (w), 831
(s), 790 (m), 755 (s), 609 (m); GCeMS (EI, 70 eV): m/z (%)¼362 (Mþ,
63), 271 (100); HRMS (ESI-TOF): calcd for C25H18N2O [MþH]þ
363.42322; found 363.42323. Anal. Calcd for C25H18N2O
(362.42322): C, 82.85; H, 5.01; N, 7.73. Found: C, 82.98; H, 5.21; N,
7.86.
3J¼5.6 Hz), 6.72 (d, 1H, 3J¼5.6 Hz), 7.43 (m, 5H), 7.69 (m, 1H), 7.90
(m, 1H), 8.10 (d, 1H, 3J¼7.4 Hz), 8.20 (d, 1H, 3J¼6.9 Hz), 8.75 (s, 1H);
13C NMR (75 MHz, DMSO-d6):
d
¼60.3, 84.6, 89.2, 121.8, 127.0, 127.5,
127.9, 128.3, 128.7, 128.8, 130.1, 130.9, 131.4, 133.5, 135.9, 136.5,
146.4, 148.3; IR (ATR, cmꢁ1):
n
¼3233 (w), 3065 (w), 2228 (w), 1591
(w), 1489 (m), 1329 (m), 1165 (w), 1068 (m), 929 (m), 857 (w), 779
(m), 747 (s); GCeMS (EI, 70 eV): m/z (%)¼293 (Mþ), 258 (100), 228
(24), 101 (10); HRMS (ESI-TOF): calcd for C18H12NClO [MþH]þ
294.06802, found 294.06773. Anal. Calcd for C18H12ClNO (293.747):
C, 73.60; H, 4.12; N, 4.77. Found: C, 73.63; H, 4.15; N, 4.77.
5.5. 1-(4-Methoxybenzyl)-2-phenylbenzo[b][1,8]naphthyr-
idin-4(1H)-one (3c)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), p-methoxybenzylamine (96 mg,
0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4
(5 mol %), and DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3c was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼3:1) as a yellow solid (146 mg, 64%), mp 174e176 ꢀC. 1H
5.2. 1-(2-Chloroquinolin-3-yl)-3-phenylprop-2-yn-1-one (2)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
ol
1 (400 mg, 1.36 mmol) and activated MnO2 (299 mg,
3.44 mmol), 2 was isolated after column chromatography (silica gel,
n-heptane/EtOAc¼9:1) as a yellow solid (362 mg, 91%), mp
NMR (300 MHz, CDCl3):
d
¼3.64 (s, 3H), 5.65 (s, 2H), 6.59 (d, 2H,
3J¼9.7 Hz), 6.74 (d, 2H, 3J¼9.6 Hz), 7.21 (m, 3H), 7.41 (m, 4H), 7.73
101e103 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d
¼7.60 (m, 3H), 7.82 (m,
(m, 1H), 7.96 (dd, 2H, 3J¼9.7 Hz, 4J¼3.1 Hz), 9.25 (s, 1H); 13C NMR
3H), 8.03 (m, 2H), 8.36 (d, 1H, 3J¼8.1 Hz), 9.30 (s, 1H); 13C NMR
(75 MHz, CDCl3):
d
¼48.8, 55.2, 111.7, 113.6, 120.7, 125.5, 125.7, 128.2,
(75 MHz, DMSO-d6):
d
¼87.5, 94.2, 118.7, 125.8, 127.7, 128.3, 129.0,
128.3, 128.4, 128.5, 129.3, 129.5, 129.9, 132.2, 135.7, 137.5, 137.6,
129.1,129.2,129.8, 131.8,133.2,133.3, 133.8,144.1, 145.6, 147.7,174.6;
149.6, 157.4, 158.7, 178.8; IR (ATR, cmꢁ1):
n
¼2958 (w), 1580 (s), 1511
IR (ATR, cmꢁ1):
n¼3062 (w), 2194 (m), 1630 (s), 1557 (m), 1485 (m),
(m), 1478 (s), 1282 (m), 1245 (s), 1145 (m), 845 (m), 828 (s), 787 (m),
568 (m); GCeMS (EI, 70 eV): m/z (%)¼391 (Mþ, 63), 263 (95), 228
(32), 129 (100), 101 (22), 75 (27); HRMS (ESI-TOF): calcd for
C26H21N2O2 [MþH]þ 393.15975, found 393.16055. Anal. Calcd for
C26H20N2O2 (392.449): C, 79.57; H, 5.14; N, 7.14. Found: C, 79.69; H,
5.26; N, 7.04.
1392 (w), 1319 (m), 1212 (w), 1096 (s), 1000 (w), 978 (m), 805 (w),
775 (m), 749 (s), 597 (m); GCeMS (EI, 70 eV): m/z (%)¼291 (Mþ, 63),
263 (95), 228 (32), 129 (100), 101 (22), 75 (27); HRMS (ESI-TOF):
calcd for C18H11ClNO [MþH]þ 292.05237, found 292.05241. Anal.
Calcd for C18H10ClNO (291.731): C, 74.11; H, 3.46; N, 4.80. Found: C,
73.98; H, 3.56; N, 4.77.
5.6. 1-Phenethyl-2-phenylbenzo[b][1,8]naphthyridin-4(1H)-
5.3. 1-Cyclohexyl-2-phenylbenzo[b][1,8]naphthyridin-4(1H)-
one (3d)
one (3a)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), cyclohexylamine (70 mg, 0.7 mmol),
potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and
DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3a was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (150 mg, 72%), mp 280e282 ꢀC. 1H NMR (300 MHz,
one 2 (170 mg, 0.58 mmol), 2-phenylethanamine (85 mg,
0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4
(5 mol %), and DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3d was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼3:1) as a yellow solid (97 mg, 46%), mp 232 ꢀC. 1H NMR
(300 MHz, CDCl3):
d
¼2.81 (t, 2H, 3J¼8.1 Hz), 4.42 (t, 2H, 3J¼8.1 Hz),
CDCl3):
d
¼0.91e1.70 (m, 8H), 3.15 (m, 2H), 4.00 (m, 1H), 6.08 (s, 1H),
6.01 (s, 1H), 6.71 (d, 2H, 3J¼6.7 Hz), 6.98e7.04 (m, 3H), 7.09e7.12
(m, 2H), 7.28e7.39 (m, 4H), 7.63e7.68 (m, 1H), 7.90 (d, 2H, 3J¼9.3,
7.39 (m, 6H), 7.71 (m,1H), 7.94 (dd, 2H, 3J¼8.3 Hz, 4J¼1.5 Hz), 9.19 (s,
1H); 13C NMR (75 MHz, CDCl3):
d
¼25.3, 26.5, 26.6, 30.5, 63.8, 111.4,
8.1 Hz), 9.13 (s, 1H); 13C NMR (75 MHz, CDCl3):
d¼35.4, 48.4, 110.9,
121.5, 125.1, 125.6, 127.4, 127.5, 128.1, 128.8, 129.2, 129.4, 131.9, 137.1,
125.5, 125.8, 126.6, 128.1, 128.1, 128.3, 128.3, 128.6, 128.6, 128.7,
128.7, 128.8, 129.4, 129.6, 132.4, 135.6, 137.7, 138.2, 148.2, 148.5,
137.2, 148.3, 150.1, 158.3, 178.6; IR (ATR, cmꢁ1):
n
¼3046 (w), 2940
(m), 1616 (m), 1578 (s), 1420 (m), 1164 (w), 1116 (m), 1041 (m), 893
149.1, 149.3, 177.4; IR (ATR, cmꢁ1):
n
¼3044 (w), 1582 (s), 1552 (m),
(w), 976 (m), 844 (s), 796 (m), 758 (s), 617 (m), 537 (m); GCeMS (EI,
1514 (w), 1477 (s), 1445 (m), 1329 (m), 1146 (m), 976 (m), 829 (s),

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
2313
573 (s); GCeMS (EI, 70 eV): m/z (%)¼377 (17), 376 (Mþ, 56), 375
5.10. 1-(3-Morpholinopropyl)-2-phenylbenzo[b][1,8]naph-
thyridin-4(1H)-one (3h)
(100), 180 (28), 105 (28); HRMS (ESI-TOF): calcd for C26H21N2O
[MþH]þ 377.16484, found 377.16543. Anal. Calcd for C26H20N2O
(376.450): C, 82.95; H, 5.35; N, 7.44. Found: C, 82.73; H, 5.26; N,
7.40.
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one (170 mg, 0.58 mmol), 3-(4-morpholino)propylamine
2
(101 mg, 0.7 mmol), potassium carbonate (162 mg, 1.17 mmol),
Pd(PPh3)4 (5 mol %), and DMF (10 ml) were reflux at 170 ꢀC for 3 h,
3h was isolated after column chromatography (silica gel, n-hep-
tane/EtOAc¼2:1) as a solid (200 mg, 87%), mp 188e189 ꢀC. 1H NMR
5.7. 1-Heptyl-2-phenylbenzo[b][1,8]naphthyridin-4(1H)-one
(3e)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), n-heptylamine (81 mg, 0.7 mmol),
potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and
DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3e was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (140 mg, 65%), mp 315 ꢀC. 1H NMR (300 MHz, CDCl3):
(CDCl3, 300 MHz):
d¼1.76 (m, 2H), 2.17 (m, 6H), 3.49 (t, 4H,
3J¼10.2 Hz), 4.43 (dd, 2H, 3J¼8.1 Hz, 4J¼2.7 Hz), 6.11 (s, 1H), 7.43 (m,
6H), 7.74 (m, 1H), 7.94 (dd, 2H, 3J¼12.5 Hz, 4J¼3.2 Hz), 9.22 (s, 1H);
13C NMR (75 MHz, CDCl3):
d
¼25.8, 45.1, 53.4, 53.4, 55.9, 66.8, 66.9,
111.2, 120.9, 125.4, 125.6, 128.1, 128.2, 128.2, 128.7, 128.7, 129.4,
129.5, 132.2, 135.8, 137.6, 149.1, 149.3, 157.0, 178.6; IR (ATR, cmꢁ1):
d
¼0.76 (t, 3H, 3J¼7.5 Hz), 1.13 (m, 8H), 1.62 (t, 2H, 3J¼7.5 Hz), 4.34 (t,
n
¼2914 (w), 2814 (w), 1633 (s), 1551 (m), 1474 (m), 1353 (w), 1264
2H, 3J¼8.1 Hz), 6.14 (s, 1H), 7.44 (m, 6H), 7.75 (m, 1H), 7.98 (d, 2H,
(m), 1114 (s), 1036 (m), 995 (w), 937 (m), 835 (s); GCeMS (EI,
70 eV): m/z (%)¼398 (Mþ, 73), 313 (20), 299 (23), 285 (100), 273
(66), 244 (13), 128 (18), 100 (26); HRMS (ESI-TOF): calcd for
C25H26N3O2 [MþH]þ 400.20195, found 400.20292. Anal. Calcd for
C25H25N3O2 (399.195): C, 75.16; H, 6.31; N,10.52. Found: C, 74.98; H,
6.56; N, 10.54.
3J¼8.5 Hz), 9.24 (s, 1H); 13C NMR (CDCl3, 75 MHz):
¼14.1, 22.5,
d
26.5, 28.5, 28.9, 31.3, 46.7, 111.0, 120.7, 125.3, 125.5, 127.8, 128.1,
128.1,128.5, 128.6, 129.2, 129.4, 132.0,135.9, 137.3,148.9,149.1, 157.1,
178.5; IR (ATR, cmꢁ1):
n
¼3048 (w), 2918 (m), 1632 (s), 1411 (m),
1332 (m), 1126 (w), 1074 (w), 976 (m), 774 (m), 753 (s), 719 (m), 611
(m); GCeMS (EI, 70 eV): m/z (%)¼370 (Mþ, 27), 313 (12), 285 (40),
272 (100), 244 (25), 128 (11); HRMS (ESI-TOF): calcd for C25H27N2O
[MþH]þ 371.21179, found 371.21180. Anal. Calcd for C25H26N2O
(370.487): C, 81.05; H, 7.07; N, 7.56. Found: C, 80.98; H, 7.08, N, 7.49.
5.11. 1-(2-Hydroxyethyl)-2-phenylbenzo[b][1,8]naphthyridin-
4(1H)-one (3i)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), ethanolamine (32 mg, 0.7 mmol), po-
tassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and
DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3i was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (150 mg, 72%), mp 204 ꢀC. 1H NMR (CDCl3, 300 MHz):
5.8. 1-Cyclopropyl-2-phenylbenzo[b][1,8]naphthyridin-4-
(1H)-one (3f)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), cyclopropylamine (40 mg, 0.7 mmol),
potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and
DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3f was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (61 mg, 57%), mp 193 ꢀC. 1H NMR (250 MHz, CDCl3):
d
¼4.01 (dd, 2H, 3J¼9.3 Hz, 4J¼3.1 Hz), 4.50 (dd, 2H, 3J¼8.4 Hz,
4J¼2.9 Hz), 4.86 (t, 1H, 3J¼12.1 Hz), 6.18 (s, 1H), 7.50 (m, 6H), 7.82
(m, 1H), 7.92 (d, 1H, 3J¼7.8 Hz), 8.03 (d, 1H, 3J¼7.9 Hz), 9.10 (s, 1H);
13C NMR (CDCl3, 75 MHz):
d¼50.5, 62.5, 111.6, 120.7, 125.4, 125.9,
d
¼0.94 (m, 2H), 1.46 (m, 2H), 3.45 (m, 1H), 6.24 (s, 1H), 7.50 (m, 6H),
127.5, 128.5, 128.8, 129.3, 129.7, 132.7, 135.8, 138.1, 148.5, 150.2,
7.78 (m, 1H), 7.99 (d, 1H, 3J¼9.7 Hz), 8.10 (d, 1H, 3J¼9.7 Hz), 9.20 (s,
157.8, 178.4; IR (ATR, cmꢁ1):
n
¼3206 (w), 1614 (s), 1480 (s), 1338
1H); 13C NMR (CDCl3, 75 MHz):
d¼12.7, 32.2, 111.6, 120.8, 125.4,
(m), 1293 (m), 1176 (w), 1156 (m), 1066 (m), 959 (w), 825 (s), 612
(m), 559 (m); GCeMS (EI, 70 eV): m/z (%)¼316 (Mþ, 12), 297 (19),
285 (67), 284 (16), 273 (20), 272 (100), 255 (11), 128 (22); HRMS
(ESI-TOF): calcd for C20H17N2O2 [MþH]þ 317.12845, found
317.12854. Anal. Calcd for C20H16N2O2 (316.353): C, 75.93; H, 5.10;
N, 8.86. Found: C, 75.90; H, 5.08; N, 8.86.
125.6,128.2,128.4,128.5,129.3,129.4,132.1,136.8,137.1,148.9,151.7,
158.2, 179.3; IR (KBr, cmꢁ1):
n
¼3060 (w), 1633 (s), 1616 (m), 1350
(w), 1263 (m), 1143 (w),1031 (m), 931 (w), 885 (w), 791 (m), 773 (s),
744 (s), 605 (m); GCeMS (EI, 70 eV): m/z (%)¼312 (Mþ, 25), 311
(100), 283 (21); HRMS (ESI-TOF): calcd for C21H17N2O [MþH]þ
313.13354, found 313.13355. Anal. Calcd for C21H16N2O (312.126): C,
80.75; H, 5.16; N, 8.97. Found: C, 80.98; H, 5.06; N, 8.97.
5.12. 1-(3-Methoxybenzyl)-2-phenylbenzo[b][1,8]naphthyr-
idin-4(1H)-one (3j)
5.9. 2-Phenylbenzo[b][1,8]naphthyridin-4(1H)-one (3g)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), 3-methoxybenzylamine (96 mg,
0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4
(5 mol %), and DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3j was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼2:1) as a solid (120 mg, 52%), mp 114e116 ꢀC. 1H NMR
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), allylamine (40 mg, 0.7 mmol), potas-
sium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4 (5 mol %), and DMF
(10 ml) were refluxed at 170 ꢀC for 3 h, 3g was isolated after column
chromatography (silica gel, n-heptane/EtOAc¼2:1) as a yellow solid
(141 mg, 90%), mp 286e288 ꢀC. 1H NMR (250 MHz, CDCl3):
d¼6.37
(300 MHz, CDCl3):
d
¼3.67 (s, 3H), 6.29 (s, 1H), 6.48e6.51 (m, 2H),
(s,1H), 7.58 (m, 5H), 7.90 (m, 3H), 7.99 (d,1H, 3J¼8.0 Hz), 8.23 (d,1H,
6.72 (d, 1H, 3J¼5.3 Hz), 7.07 (t, 1H, 3J¼8.1 Hz), 7.28e7.59 (m, 7H),
3J¼8.6 Hz), 9.20 (s, 1H), 12.33 (s, 1H, NH); 13C NMR (CDCl3, 75 MHz):
7.79e7.85 (m, 1H), 8.02 (d, 1H, 3J¼8.1 Hz), 8.09 (d, 1H, 3J¼8.1 Hz),
d
¼106.2, 119.3, 125.2, 126.7, 127.7, 127.7, 128.7, 128.8, 129.8, 130.8,
9.36 (s, 1H); 13C NMR (CDCl3, 75 MHz):
112.7, 119.1, 120.6, 125.5, 125.7, 128.2, 128.3, 128.5, 129.3, 129.3,
129.6, 132.3, 135.7, 137.7, 139.6, 149.2, 149.6, 157.5, 159.6, 178.9; IR
d
¼49.3, 55.1, 111.7, 112.3,
132.5, 133.6, 136.6, 148.7, 149.0, 150.2, 153.1, 178.2; IR (ATR, cmꢁ1):
n
¼1650 (w), 1540 (m), 1454 (m), 1227 (w), 1266 (m), 1154 (w), 958
(w), 855 (m), 791 (m), 740 (s), 690 (s), 613 (m), 547 (s); GCeMS (EI,
70 eV): m/z (%)¼273 (18), 272 (Mþ, 100), 271 (13), 245 (18), 244
(78), 243 (14), 242 (11), 122 (11); HRMS (ESI-TOF): calcd for
C18H13N2O [MþH]þ 273.10224, found 273.10223. Anal. Salcd for
C18H12N2O (272.095): C, 79.39; H, 4.44; N, 10.29. Found: C, 79.19; H,
4.46; N, 10.26.
(ATR, cmꢁ1):
n
¼2921 (w), 1660 (m), 1631 (m), 1582 (s), 1486 (w),
1349 (m), 1274 (m), 1158 (m), 1092 (m), 976 (m), 847 (m), 698 (s);
GCeMS (EI, 70 eV): m/z (%)¼393 (11), 392 (Mþ, 54), 391 (100), 283
(10), 121 (17); HRMS (EI): calcd for C26H19N2O2 [M]þ 391.14410,
found 391.14442. Anal. Calcd for C20H19N2O2 (392.449): C, 74.11; H,
3.46; N, 4.8. Found: C, 73.98; H, 3.56; N, 4.77.

2314
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
5.13. 1-(2-Chlorobenzyl)-2-phenylbenzo[b][1,8]naphthyridin-
4(1H)-one (3k)
5.16. 1-(3,4-Dimethoxyphenyl)-2-phenylbenzo[b][1,8]naph-
thyridin-4(1H)-one (3n)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one
2
(170 mg, 0.58 mmol), 2-chlorobenzylamine (99 mg,
one 2 (170 mg, 0.58 mmol), 3,4-dimethoxyaniline (95 mg,
0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4
(5 mol %), and DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3k was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼2:1) as a yellow solid (200 mg, 86%), mp 238 ꢀC. 1H NMR
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3n was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼1:1) as
a yellow solid (150 mg, 76%), mp 235 ꢀC. 1H NMR (CDCl3, 300 MHz):
(CDCl3, 300 MHz):
d
¼5.81 (s, 2H), 6.33 (s, 1H), 6.76 (d, 1H,
d
¼3.66 (s, 3H), 3.81 (s, 3H), 6.35 (s,1H), 6.66 (s,1H), 6.71 (s, 2H), 7.19
3J¼8.6 Hz), 7.17 (m, 1H), 7.21 (m, 3H), 7.47 (m, 4H), 7.79 (m, 1H), 7.95
(m, 5H), 7.43 (t, 1H, 3J¼7.5 Hz), 7.65 (t, 1H, 3J¼8.3 Hz), 7.75 (d, 1H,
(d, 1H, 3J¼8.7 Hz), 8.07 (d, 1H, 3J¼8.7 Hz), 9.38 (s, 1H); 13C NMR
3J¼9.0 Hz), 7.95 (d, 1H, 3J¼8.8 Hz), 9.25 (s, 1H); 13C NMR (CDCl3,
(CDCl3, 75 MHz):
d
¼47.6, 111.7, 120.5, 125.6, 125.8, 126.8, 127.2,
75 MHz):
d
¼55.9, 56.1, 110.3, 111.4, 114.0, 120.2, 122.9, 125.6, 125.7,
127.8, 127.9, 128.1, 128.4, 128.5, 128.6, 129.2, 129.3, 129.7, 132.1,
128.0, 128.2, 128.2, 128.6, 128.7, 128.8, 129.0, 129.1, 131.9, 136.2,
132.3, 135.2, 135.6, 137.6, 149.1, 149.5, 157.4, 178.7; IR (ATR, cmꢁ1):
137.3, 148.4, 148.4, 148.7, 149.1, 150.8, 157.1, 179.1; IR (ATR, cmꢁ1):
n
¼2964 (w), 1616 (s), 1552 (m), 1499 (w), 1410 (m), 1328 (m), 1200
n
¼2833 (w), 1633 (m), 1509 (m), 1471 (m), 1398 (s), 1255 (s), 1208
(w), 1147 (m), 1088 (w), 850 (w), 832 (s), 611 (m); GCeMS (EI,
70 eV): m/z (%)¼397 (43), 396 (Mþ, 51), 395 (100), 361 (19), 283
(15), 125 (18); HRMS (ESI-TOF): calcd for C25H17ClN2O [MþH]þ
397.11022, found 397.11104. Anal. Calcd for C25H16ClN2O (396.868):
C, 75.66; H, 4.32; N, 7.06. Found: C, 75.98, H, 4.46; N, 7.06.
(m), 1132 (m), 1026 (s), 841 (m), 759 (s), 705 (s); GCeMS (EI, 70 eV):
m/z (%)¼409 (19), 408 (Mþ, 78), 407 (100), 391 (12), 321 (14); HRMS
(ESI-TOF): calcd for C26H21N2O3 [MþH]þ 409.15467, found
409.15504. Anal. Calcd for C26H20N2O3 (408.449): C, 76.45; H, 4.94;
N, 6.86. Found: C, 75.97; H, 4.91; N, 6.84.
5.14. 1-(3-(1H-Imidazol-1-yl)propyl)-2-phenylbenzo[b][1,8]
naphthyridin-4-(1H)-one (3l)
5.17. 1-(3,5-Dimethoxyphenyl)-2-phenylbenzo[b][1,8]naph-
thyridin-4(1H)-one (3o)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), N-(3-aminopropyl)imidazole (88 mg,
0.7 mmol), potassium carbonate (162 mg, 1.17 mmol), Pd(PPh3)4
(5 mol %), and DMF (10 ml) were refluxed at 170 ꢀC for 3 h, 3l was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼2:1) as a yellow solid (135 mg, 70%), mp 229 ꢀC. 1H NMR
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one
2 (170 mg, 0.58 mmol), 3,5-dimethoxyaniline (95 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3o was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼1:1) as
a yellow solid (135 mg, 64%), mp 239 ꢀC. 1H NMR (CDCl3, 300 MHz):
(CDCl3, 250 MHz):
d
¼2.19 (m, 2H), 3.90 (dd, 2H, 3J¼6.3 Hz,
4J¼2.4 Hz), 4.41 (dd, 2H, 3J¼7.5 Hz, 4J¼3.1 Hz), 6.18 (s, 1H), 6.76 (s,
1H), 7.02 (s, 1H), 7.41 (m, 3H), 7.54 (m, 4H), 7.84 (m, 1H), 8.01 (dd,
2H, 3J¼7.3 Hz, 4J¼3.2 Hz), 9.28 (s, 1H); 13C NMR (CDCl3, 75 MHz):
d
¼3.58 (s, 6H), 6.30 (m, 4H), 7.19 (m, 5H), 7.41 (t, 1H, 3J¼7.6 Hz), 7.63
(t, 1H, 3J¼7.8 Hz), 7.76 (d, 1H, 3J¼8.7 Hz), 7.93 (d, 1H, 3J¼7.3 Hz), 9.22
(s, 1H); 13C NMR (CDCl3, 75 MHz):
111.4, 120.0, 120.2, 125.6, 125.7, 127.9, 128.0, 128.7, 128.9, 128.9,
129.1, 131.9, 136.1, 137.3, 140.5, 149.0, 149.1, 150.4, 156.6, 160.4, 179.1;
d
¼55.5, 55.6, 100.4, 109.3, 109.4,
d
¼30.2, 43.8, 44.5, 111.4, 120.6, 125.4, 125.8, 127.9, 127.9, 128.0,
129.0, 129.1, 129.3, 129.9, 132.5, 135.4, 137.7, 137.8, 137.9, 149.0, 149.1,
156.5, 156.5, 178.5; IR (KBr, cmꢁ1):
n
¼2921 (w), 1660 (m), 1631 (m),
IR (ATR, cmꢁ1):
n
¼3053 (w), 1637 (m), 1582 (s), 1403 (m), 1316 (m),
1582 (s), 1486 (w), 1349 (m), 1274 (m), 1158 (m), 1092 (m), 976 (m),
847 (m), 698 (s); GCeMS (EI, 70 eV): m/z (%)¼380 (Mþ, 28), 299
(13), 285 (100), 273 (18), 272 (17), 207 (25); HRMS (ESI-TOF): calcd
for C24H21N4O [MþH]þ 381.17099, found 381.17188. Anal. Calcd for
C24H20N4O (380.442): C, 75.77; H, 5.30; N,14.73. Found: C, 75.98; H,
5.46; N, 14.66.
1150 (s), 1060 (m), 950 (w), 826 (m), 773 (m), 705 (m), 613 (w);
GCeMS (EI, 70 eV): m/z (%)¼409 (15), 408 (Mþ, 66), 407 (100), 153
(10); HRMS (ESI-TOF): calcd for C26H21N2O3 [MþH]þ 409.15467,
found 409.15580. Anal. Calcd for C26H20N2O3 (408.449): C, 76.45; H,
4.94; N, 6.86. Found: C, 76.37; H, 4.89; N, 6.85.
5.15. 1-(4-Methoxyphenyl)-2-phenylbenzo[b][1,8]naphthyr-
idin-4(1H)-one (3m)
5.18. 2-Phenyl-1-(3,4,5-trimethoxyphenyl)benzo[b][1,8]naph-
thyridin-4(1H)-one (3p)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), 3,4,5-trimethoxyaniline (113 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3p was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼1:1) as
a yellow solid (173 mg, 77%), mp 253 ꢀC. 1H NMR (CDCl3, 300 MHz):
one
2 (170 mg, 0.58 mmol), p-methoxyaniline (76 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3m was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼1:1) as
a yellow solid (142 mg, 73%), mp 290 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼3.81 (s, 3H), 6.43 (s, 1H), 6.84 (d, 2H, 3J¼9.0 Hz), 7.12 (d, 2H,
d
¼3.62 (s, 6H), 3.78 (s, 3H), 6.35 (s, 1H), 6.39 (s, 2H), 7.22 (m, 5H),
3J¼9.0 Hz), 7.26 (m, 5H), 7.51 (t, 1H, 3J¼8.9 Hz), 7.72 (t, 1H,
7.44 (t, 1H, 3J¼7.6 Hz), 7.67 (t, 1H, 3J¼7.6 Hz), 7.80 (d, 1H, 3J¼9.1 Hz),
3J¼8.9 Hz), 7.82 (d, 1H, 3J¼6.2 Hz), 8.04 (d, 1H, 3J¼9.0 Hz), 9.38 (s,
7.96 (d, 1H, 3J¼9.1 Hz), 9.26 (s, 1H); 13C NMR (CDCl3, 75 MHz):
1H); 13C NMR (CDCl3, 75 MHz):
d
¼55.4, 111.3, 113.6, 113.7, 120.2,
d
¼56.3, 61.1, 108.6, 111.4, 120.1, 125.6, 125.7, 125.8, 128.3, 128.5,
125.6,125.7,128.0,128.6,128.7,129.0,129.0,129.1,131.3,131.3,131.9,
128.6,128.9,129.0,129.2,129.4,132.1,134.4,136.2,137.4,137.7,149.1,
131.9, 136.1, 137.3, 149.1, 150.9, 157.1, 158.8, 179.2; IR (ATR, cmꢁ1):
150.5, 152.9, 156.8, 179.1; IR (ATR, cmꢁ1):
n
¼2964 (w), 1637 (m),
n
¼2921 (w), 1660 (m), 1631 (m), 1582 (s), 1486 (w), 1349 (m), 1274
1556 (w), 1495 (m), 1404 (m), 1227 (s), 949 (w), 854 (w), 825 (m),
712 (m), 643 (m); GCeMS (EI, 70 eV): m/z (%)¼439 (28), 438 (Mþ,
100), 437 (63), 423 (21), 392 (13), 391 (20); HRMS (ESI-TOF): calcd
for C27H23N2O4 [MþH]þ 439.16523, found 439.16492. Anal. Calcd
for C27H22N2O4 (438.475): C, 73.96; H, 5.06; N, 6.39. Found: C,
73.37; H, 4.99; N, 6.35.
(m), 1158 (m), 1092 (m), 976 (m), 847 (m), 698 (s); GCeMS (EI,
70 eV): m/z (%)¼379 (14), 378 (Mþ, 65), 377 (100); HRMS (ESI-TOF):
calcd for C25H19N2O2 [MþH]þ 379.14410, found 379.14384. Anal.
Calcd for C25H18N2O2 (378.423): C, 79.35; H, 4.79; N, 7.40. Found: C,
78.98; H, 4.69; N, 7.40.

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
2315
5.19. 2-Phenyl-1-(3,5-dimethylphenyl)benzo[b][1,8]naphthyr-
idin-4(1H)-one (3q)
5.22. 1-(4-Ethylphenyl)-2-phenylbenzo[b][1,8]naphthyridin-
4(1H)-one (3t)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), p-ethylaniline (75 mg, 0.62 mmol),
Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and toluene
(10 ml) were refluxed at 90 ꢀC for 6 h, 3t was isolated after column
chromatography (silica gel, n-heptane/EtOAc¼3:1) as a yellow solid
one
2 (170 mg, 0.58 mmol), 3,5-dimethylaniline (75 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3q was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (128 mg, 58%), mp 255 ꢀC. 1H NMR (CDCl3,
(96 mg, 50%), mp 229 ꢀC. 1H NMR (CDCl3, 300 MHz):
d¼1.31 (t, 3H,
300 MHz):
d
¼2.27 (s, 6H), 6.45 (s, 1H), 6.85 (s, 2H), 6.91 (s, 1H), 7.27
3J¼7.8 Hz), 2.55 (m, 2H), 6.34 (s, 1H), 7.02 (q, 4H, 3J¼9.5 Hz), 7.14 (s,
5H), 7.4 (t, 1H, 3J¼7.5 Hz), 7.61 (t, 1H, 3J¼6.8 Hz), 7.72 (d, 1H,
3J¼8.5 Hz), 7.94 (d, 1H, 3J¼8.3 Hz), 9.24 (s, 1H); 13C NMR (CDCl3,
(s, 5H), 7.53 (t, 1H, 3J¼6.7 Hz), 7.74 (t, 1H, 3J¼6.8 Hz), 7.85 (d, 1H,
3J¼9.3 Hz), 8.10 (d, 1H, 3J¼9.3 Hz), 9.37 (s, 1H); 13C NMR (CDCl3,
75 MHz):
d
¼21.1, 111.2, 120.1, 125.5, 125.6, 127.8, 128.0, 128.1, 128.6,
75 MHz):
d
¼15.2, 28.4, 111.3, 120.1, 125.6, 125.7, 127.7, 127.8, 128.6,
128.7, 128.7, 128.8, 128.9, 129.1, 129.5, 131.9, 136.1, 137.3, 138.0,
128.7, 128.8, 129.0, 129.1, 129.2, 130.2, 130.3, 131.9, 131.9, 136.1, 136.7,
138.1, 138.8, 149.1, 150.7, 157.0, 179.9; IR (ATR, cmꢁ1):
n
¼3057 (w),
137.3, 143.9, 149.1, 150.8, 157.0, 179.3; IR (ATR, cmꢁ1):
n¼3029 (w),
1628 (m), 1550 (m), 1403 (s), 1335 (m), 138 (s), 1438 (m), 1148 (m),
971 (m), 840 (m), 756 (s), 588 (m); GCeMS (EI, 70 eV): m/z (%)¼
377 (17), 376 (Mþ, 73), 375 (100), 347 (10); HRMS (ESI-TOF): calcd
for C26H21N2O [MþH]þ 377.16484, found 377.16412. Anal. Calcd for
C26H20N2O (376.450): C, 82.95; H, 5.35; N, 7.44. Found: C, 82.87; H,
5.29; N, 7.44.
3004 (w), 1637 (m), 1473 (m), 1184 (w), 1062 (w), 828 (s), 778 (m),
739 (m), 560 (m), 545 (w); GCeMS (EI, 70 eV): m/z (%)¼377 (12),
376 (Mþ, 54), 375 (100); HRMS (ESI-TOF): calcd for C26H21N2O
[MþH]þ 377.16484, found 377.16561. Anal. Calcd for C26H20N2O
(376.450): C, 82.95; H, 5.35; N, 7.44. Found: C, 82.92; H, 5.26; N,
7.43.
5.20. 2-Phenyl-1-(2,4-dimethoxyphenyl)benzo[b][1,8]naph-
thyridin-4(1H)-one (3r)
5.23. 1-(2-Fluorophenyl)-2-phenylbenzo[b][1,8]naphthyridin-
4(1H)-one (3u)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), 3,5-dimethoxyaniline (126 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3r was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼2:1) as
a yellow solid (126 mg, 53%), mp 275 ꢀC. 1H NMR (CDCl3, 300 MHz):
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one
2 (170 mg, 0.58 mmol), p-methoxyaniline (76 mg,
0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and
toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3u was isolated after
column chromatography (silica gel, n-heptane/EtOAc¼1:1) as
a yellow solid (62 mg, 29%), mp 243 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼3.52 (s, 3H), 3.75 (s, 3H), 6.35 (m, 3H), 7.03 (d,1H, 3J¼7.3 Hz), 7.20
d
¼6.36 (s, 1H), 7.04 (m, 3H), 7.18 (m, 7H), 7.45 (m, 1H), 7.68 (m, 2H),
(m, 5H), 7.64 (t, 1H, 3J¼7.3 Hz), 7.43 (t, 1H, 3J¼6.4 Hz), 7.74 (d, 1H,
7.97 (d, 1H, 3J¼8.4 Hz), 9.26 (s, 1H); 19F NMR (CDCl3, 282 MHz):
3J¼8.3 Hz), 7.97 (d, 1H, 3J¼8.3 Hz), 9.27 (s, 1H); 13C NMR (CDCl3,
d
¼ꢁ118.4; 13C NMR (75 MHz, CDCl3):
¼111.3, 115.7, 116.1, 120.0,
d
75 MHz):
d
¼55.4, 55.5, 99.0, 104.1, 110.8, 120.3, 121.6, 125.4, 125.6,
124.1, 124.2, 126.1 (d, J¼16 Hz), 126.3 (d, J¼230 Hz), 128.1, 128.4,
128.5, 129.1, 129.2, 129.3, 129.4, 130.2, 131.7, 131.8, 133.5 (d,
J¼10 Hz), 135.1 (d, J¼10 Hz), 136.3 (d, J¼40 Hz), 137.4, 137.5, 149.2,
127.6, 127.7, 128.4, 128.5, 128.6, 128.8, 129.1, 131.7, 131.8, 136.1, 137.1,
149.3, 150.6, 156.2, 157.8, 160.7, 179.5; IR (ATR, cmꢁ1):
n
¼2921 (w),
1660 (m), 1631 (m), 1582 (s), 1486 (w), 1349 (m), 1274 (m), 1158 (m),
1092 (m), 976 (m), 847 (m), 698 (s); GCeMS (EI, 70 eV): m/z (%)¼
408 (Mþ, 3), 378 (28), 377 (100); HRMS (ESI-TOF): calcd for
C26H21N2O3 [MþH]þ 409.15467, found 409.15496. Anal. Calcd for
C26H20N2O3 (408.449): C, 76.45; H, 4.94; N, 6.86. Found: C, 76.63; H,
5.05; N, 6.98.
179.4; IR (ATR, cmꢁ1):
n
¼2919 (w), 1581 (s), 1554 (m), 1209 (m),
1156 (w), 1031 (m), 950 (m), 851 (w), 774 (s), 562 (m); GCeMS (EI,
70 eV): m/z (%)¼367 (13), 366 (Mþ, 52), 365 (16), 348 (26), 347
(100), 346 (7); HRMS (ESI-TOF): calcd for C24H16FN2O [MþH]þ
367.12412, found 367.12471. Anal. Calcd for C24H15FN2O (366.387):
C, 78.68; H, 4.13; N, 7.65. Found: C, 78.38; H, 4.10; N, 7.62.
5.21. 1-(4-(Diethylamino)phenyl)-2-phenylbenzo[b][1,8]
naphthyridin-4(1H)-one (3s)
5.24. 1-(3-Chloroquinoxalin-2-yl)-3-phenylprop-2-yn-1-one
(5a)
Starting with 1-(2-chloroquinolin-3-yl)-3-phenylprop-2-yn-1-
one 2 (170 mg, 0.58 mmol), N,N-dimethylbenzene-1,4-diamine
(112 mg, 0.62 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4
(5 mol %), and toluene (10 ml) were refluxed at 90 ꢀC for 6 h, 3s was
isolated after column chromatography (silica gel, n-heptane/
EtOAc¼3:1) as a yellow solid (167 mg, 77%), mp 320 ꢀC. 1H NMR
Yield 3.10 g (53%), pale green crystals, mp 81e83 ꢀC. 1H NMR
(CDCl3, 300 MHz):
7.79e7.90 (m, 2H), 8.03e8.06 (m, 1H), 8.19e8.23 (m, 1H); 13C NMR
(CDCl3, 63 MHz):
¼88.3, 97.0, 119.7, 128.3, 128.7, 130.1, 131.1, 131.3,
133.4, 133.5, 139.8, 142.5, 144.0, 146.4, 175.3; IR (ATR, cmꢁ1):
d
¼7.34e7.48 (m, 3H), 7.63e7.66 (m, 2H),
d
(CDCl3, 300 MHz):
d
¼1.31 (t, 6H, 3J¼7.6 Hz), 2.49 (q, 4H, 3J¼7.6 Hz),
n
¼3290 (w), 3105 (w), 3068 (w), 3045 (w), 2992 (w), 2956 (w),
5.59 (s, 1H), 5.71 (d, 2H, 3J¼8.0 Hz), 6.14 (d, 2H, 3J¼8.7 Hz), 6.42 (s,
5H), 6.66 (t, 1H, 3J¼7.7 Hz), 6.87 (t, 1H, 3J¼7.7 Hz), 7.04 (d, 1H,
3J¼8.0 Hz), 7.19 (d, 1H, 3J¼7.2 Hz), 8.5 (s, 1H); 13C NMR (CDCl3,
2926 (w), 2872 (w), 2855 (w), 2191 (s), 1725 (w), 1652 (s), 1592
(m), 1572 (w), 1557 (m), 1536 (m), 1505 (w), 1485 (m), 1461 (m),
1441 (m), 1418 (w), 1382 (w), 1347 (m), 1321 (m), 1305 (m), 1286
(m), 1260 (m), 1228 (w), 1212 (w), 1178 (w), 1147 (m), 1132 (m),
75 MHz):
d
¼12.4, 44.4, 111.1, 111.2, 120.3, 125.5, 127.1, 127.8, 127.9,
128.5,128.7,129.0,129.1,129.2,130.7,130.8,131.7,136.5,136.6,137.2,
1080 (s), 1025 (m), 1002 (w); UV (CH2Cl2, nm): lmax (log
3
)¼235
147.1, 149.2, 151.2, 157.7, 179.2; IR (ATR, cmꢁ1):
n
¼2968 (w), 1634
(5.44), 248 (5.40), 309 (5.09); MS (EI, 70 eV): m/z (%)¼294 (Mþ,
(m), 1515 (s), 1473 (m), 1262 (m), 1195 (m), 1009 (w), 827 (m), 741
(s), 701 (m), 605 (m); GCeMS (EI, 70 eV): m/z (%)¼420 (22), 419
(Mþ, 72), 418 (18), 405 (30), 404 (100), 374 (24), 159 (10); HRMS
(ESI-TOF): calcd for C28H26N3O [MþH]þ 420.20704, found
420.20700. Anal. Calcd for C28H25N3O (419.518): C, 80.16; H, 6.01; N,
10.02. Found: C, 80.21; H, 6.06; N, 10.02.
37Cl, 10), 292 (Mþ, 35Cl, 29), 264 (22), 229 (31), 129 (100), 102 (14),
35
75 (21), 51 (8); HRMS (ESI): calcd for C17
H
ClN2O [MþH]þ
10
37
293.04762, found 293.04727; calcd for C17
H
ClN2O [MþH]þ
10
295.04519, found 295.04518. Anal. Calcd for C17H9ClN2O
(292.719): C, 69.75; H, 3.10; N, 9.57. Found: C, 69.62; H, 3.09; N,
9.56.

2316
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
5.25. 3-(4-tert-Butylphenyl)-1-(3-chloroquinoxalin-2-yl)
prop-2-yn-1-one (5b)
(m, 2H), 6.39 (s, 1H), 7.40e7.49 (m, 5H), 7.71e7.86 (m, 2H),
8.00e8.03 (m, 1H), 8.39e8.43 (m, 1H); 13C NMR (CDCl3, 63 MHz):
d
¼14.0, 22.4, 26.4, 28.4, 28.8, 31.4, 46.8, 113.8, 128.0, 128.1, 128.8,
129.4, 129.8, 130.9, 132.7, 135.2, 137.2, 140.9, 142.7, 145.5, 156.8,
177.8; IR (ATR, cmꢁ1):
Yield 0.32 g (58%), yellow solid, mp 110e112 ꢀC. 1H NMR (CDCl3,
300 MHz):
7.79e7.88 (m, 2H), 7.99e8.03 (m, 1H), 8.16e8.19 (m, 1H); 13C NMR
(CDCl3, 63 MHz):
¼31.0, 35.2, 88.3, 97.9, 116.6, 125.8, 128.3, 130.1,
131.0, 133.2, 133.5, 139.8, 142.4, 143.9, 146.7, 155.3, 175.4; IR (ATR,
cmꢁ1):
d
¼1.26 (s, 9H), 7.36e7.39 (m, 2H), 7.55e7.58 (m, 2H),
n¼3055 (w), 2999 (w), 2951 (m), 2923 (m),
2852 (m), 1637 (s), 1633 (s), 1570 (m), 1544 (s), 1489 (m), 1475 (s),
1455 (m), 1443 (s), 1427 (m), 1403 (m), 1380 (w), 1353 (s), 1300 (m),
1286 (m), 1273 (m), 1260 (m), 1236 (m), 1223 (m), 1181 (w), 1164
(m), 1132 (m), 1085 (w), 1074 (w), 1037 (w), 1003 (w); UV (CH2Cl2,
d
n
¼3282 (w), 3068 (w), 2960 (m), 2902 (w), 2864 (w), 2181
(s), 1939 (w), 1646 (s), 1598 (m), 1558 (m), 1539 (w), 1504 (m), 1481
(w), 1460 (m), 1402 (w), 1386 (w), 1361 (m), 1347 (w), 1328 (m),
1299 (w), 1282 (w), 1266 (m), 1210 (w), 1202 (w), 1188 (w), 1144
(m), 1129 (m), 1121 (w), 1108 (w), 1073 (s), 1022 (w), 1013 (m); UV
nm): lmax (log
3 )¼228 (5.71), 250 (5.55), 295 (5.35), 432 (4.04); MS
(EI, 70 eV): m/z (%)¼371 (Mþ, 52), 342 (10), 314 (13), 286 (51), 273
(100), 245 (42), 129 (25), 102 (15), 41 (8); HRMS (ESI): calcd for
C24H26N3O [MþH]þ 372.20704, found 372.20713. Anal. Calcd for
C24H25N3O (371.475): C, 77.60; H, 6.78; N, 11.31. Found: C, 77.73; H,
6.79; N, 11.42.
(CH2Cl2, nm): lmax (log
3
)¼228 (5.78), 254 (5.58), 297 (5.40); MS
(EI): m/z (%)¼350 (Mþ, 37Cl, 10), 348 (Mþ, 35Cl, 30), 333 (19), 305
(21), 277 (6), 185 (100), 170 (22), 155 (27), 115 (8), 102 (19), 51 (3);
HRMS (ESI): calcd for C21H18ClN2O ([MþH]þ, 35Cl) 349.11022, found
349.11068; calcd for C21H18ClN2O ([MþH]þ, 37Cl) 351.10803, found
351.10852.
5.29. 1-(2-Hydroxyethyl)-2-phenylpyrido[2,3-b]quinoxalin-
4(1H)-one (6c)
Yellow solid, mp 243e245 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼4.04
5.26. 1-(3-Chloroquinoxalin-2-yl)undec-2-yn-1-one (5c)
(t, 3J¼4.9 Hz, 2H), 4.57 (t, 2H, 3J¼4.9 Hz), 6.21 (s, 1H), 7.46e7.72 (m,
7H), 7.86e7.89 (m, 1H), 8.04e8.07 (m, 1H); 13C NMR (CDCl3,
Yield 0.19 g (35%), yellow oil. 1H NMR (CDCl3, 300 MHz):
63 MHz):
d
¼48.3, 58.0, 113.0, 127.7, 128.5, 129.5, 129.6, 130.0, 133.1,
d
¼0.77e0.82 (m, 3H), 1.20e1.24 (m, 8H), 1.37e1.46 (m, 2H),
135.2, 137.2, 139.8, 141.5, 145.7, 157.0, 176.3; IR (ATR, cmꢁ1):
n¼3335
1.56e1.65 (m, 2H), 2.46 (t, 2H, 3J¼7.0 Hz), 7.76e7.87 (m, 2H),
(w), 3050 (w), 2955 (w), 2924 (w), 2877 (w), 2730 (w), 1622 (s),
1615 (s), 1581 (w), 1565 (w), 1546 (m), 1538 (m), 1494 (m), 1474 (s),
1449 (m),1427 (m),1405 (m),1377 (w),1353 (s), 1338 (m),1295 (w),
1282 (m),1262 (m),1230 (m), 1188 (w),1168 (w),1147 (m), 1116 (w),
7.99e8.02 (m,1H), 8.13e8.16 (m,1H); 13C NMR (DMSO-d6, 63 MHz):
d
¼14.0, 19.6, 22.6, 27.5, 28.9, 29.0, 29.1, 31.8, 81.0, 101.6, 128.3, 129.9,
131.0, 133.1, 139.7, 142.4, 143.8, 146.7, 175.5; IR (ATR, cmꢁ1):
n
¼3302
(w), 3066 (w), 2956 (w), 2918 (s), 2852 (m), 2284 (w), 2205 (m),
1661 (s), 1607 (w), 1574 (w), 1553 (w), 1531 (m), 1504 (w), 1479 (w),
1466 (m), 1458 (m), 1427 (w), 1415 (w), 1380 (w), 1349 (m), 1324
(w), 1315 (w), 1290 (m), 1279 (m), 1243 (w), 1230 (w), 1200 (w),
1162 (s), 1129 (m), 1118 (m), 1108 (m), 1062 (w), 1045 (s), 1028 (m);
1071 (m), 1053 (m), 1010 (w); UV (CH2Cl2, nm): lmax (log
3 )¼228
(5.71), 247 (5.55), 295 (5.33), 431 (3.99); MS (EI, 70 eV): m/z (%)¼
317 (Mþ, 22), 298 (11), 286 (74), 273 (100), 257 (13), 245 (33), 207
(14), 129 (32), 102 (17); HRMS (ESI): calcd for C19H16N3O2 [MþH]þ
318.12370, found 318.12453.
UV (CH2Cl2, nm): lmax (log
3
)¼238 (5.27), 248 (5.29), 310 (4.93); MS
(EI, 70 eV): m/z (%)¼328 (Mþ, 85), 243 (71), 191 (44), 163 (100), 129
(14), 102 (19), 65 (9), 41 (8); HRMS (ESI): calcd for C19H22ClN2O
([MþH]þ, 35Cl) 329.14152, found 329.14231, ([MþNa]þ, 37Cl)
353.12115, found 353.12139. Anal. Calcd for C19H21ClN2O (328.84):
C, 69.40; H, 6.44; N, 8.52. Found: C, 69.62; H, 6.71; N, 8.89.
5.30. 1-Benzyl-2-phenylpyrido[2,3-b]quinoxalin-4(1H)-one
(6d)
Pale orange solid, mp 205e208 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼5.65 (s, 2H), 6.44 (s, 1H), 6.79e6.82 (m, 2H), 7.08e7.09 (m, 3H),
7.20e7.41 (m, 5H), 7.68e7.78 (m, 2H), 7.89e7.93 (m, 1H), 8.37e8.41
(m,1H); 13C NMR (CDCl3, 63 MHz):
¼49.6,114.2,126.6,127.4,128.0,
128.3, 128.5, 128.6, 129.6, 129.9, 130.9, 132.9, 134.8, 137.0, 137.0,
141.1,142.7,145.8,157.1,177.9; IR (ATR, cmꢁ1):
3044 (w), 3023 (w), 2999 (w), 2960 (w), 1641 (s), 1622 (m), 1574
(m), 1548 (m), 1495 (w), 1485 (w), 1476 (s), 1453 (m), 1444 (s), 1410
(m), 1401 (m), 1359 (s), 1336 (m), 1330 (m), 1293 (w), 1275 (s), 1253
(m), 1231 (m), 1198 (w), 1188 (w), 1159 (w), 1138 (m), 1103 (w), 1078
5.27. 1-Cyclohexyl-2-phenylpyrido[2,3-b]quinoxalin-4(1H)-
one (6a)
d
n
¼3110 (w), 3058 (w),
Yellow solid, mp 238e240 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.91e1.78 (m, 8H), 2.97e3.11 (m, 2H), 3.99e4.09 (m, 1H), 6.35 (s,
1H), 7.37e7.49 (m, 5H), 7.70e7.85 (m, 2H), 8.00e8.03 (m, 1H),
8.37e8.40 (m, 1H); 13C NMR (CDCl3, 63 MHz):
¼25.3, 26.5, 30.6,
64.3, 114.0, 127.4, 127.8, 128.9, 129.5, 129.8, 130.8, 132.6, 136.3, 137.6,
140.5, 141.8, 146.5, 157.8, 177.8; IR (ATR, cmꢁ1):
d
(w), 1039 (w), 1023 (w); UV (CH2Cl2, nm): lmax (log
3
)¼228 (5.79),
n
¼3057 (w), 3026
254 (5.64), 296 (5.45), 428 (4.20); MS (EI, 70 eV): m/z (%)¼363 (Mþ,
57), 334 (3), 273 (15), 245 (12), 129 (5), 91 (100), 69 (13), 57 (12), 44
(44); HRMS (ESI): calcd for C24H18N3O [MþH]þ 364.14444, found
364.14515. Anal. Calcd for C24H17N3O (363.411): C, 79.32; H, 4.72; N,
11.56. Found: C, 79.34; H, 4.75; N, 11.57.
(w), 2992 (w), 2950 (w), 2928 (w), 2914 (m), 2854 (m), 1631 (s),
1578 (m), 1545 (s), 1538 (m), 1504 (w), 1489 (m), 1476 (s), 1453 (m),
1442 (m), 1427 (s), 1417 (m), 1393 (m), 1352 (s), 1340 (s), 1304 (m),
1268 (s), 1242 (m), 1230 (m), 1192 (w), 1178 (w), 1165 (w), 1154 (w),
1139 (m),1122 (s),1098 (m),1072 (m),1047 (m),1029 (m),1020 (m);
UV (CH2Cl2, nm): lmax (log
3
)¼237 (5.37), 247 (5.38), 311 (5.01), 434
5.31. 1-Phenethyl-2-phenylpyrido[2,3-b]quinoxalin-4(1H)-
one (6e)
(4.09); MS (EI, 70 eV): m/z (%)¼355 (Mþ, 13), 298 (2), 273 (100), 245
(45), 205 (5), 129 (5), 102 (11), 55 (6), 41 (6); HRMS (ESI): calcd for
C23H22N3O [MþH]þ 356.17574, found 356.17642. Anal. Calcd for
C23H21N3O (355.432): C, 77.72; H, 5.96; N, 11.82. Found: C, 77.79; H,
5.92; N, 11.82.
Yellow solid, mp 295e297 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼2.92
(t, 2H, 3J¼7.6 Hz), 4.55 (t, 2H, 3J¼7.6 Hz), 6.36 (s, 1H), 6.79e6.83 (m,
2H), 7.11e7.14 (m, 3H), 7.25e7.29 (m, 2H), 7.45e7.48 (m, 3H),
7.73e7.90 (m, 2H), 8.05e8.09 (m, 1H), 8.41e8.44 (m, 1H); 13C NMR
5.28. 1-Heptyl-2-phenylpyrido[2,3-b]quinoxalin-4(1H)-one
(6b)
(CDCl3, 63 MHz):
128.8, 129.6, 129.9, 131.0, 132.9, 135.0, 137.2, 137.7, 140.9, 142.7,
145.5, 156.8, 177.8; IR (ATR, cmꢁ1):
2953 (w), 1651 (w), 1629 (s), 1579 (m), 1574 (m), 1551 (m), 1545 (m),
1495 (m), 1475 (m), 1448 (m), 1441 (m), 1425 (m), 1407 (m), 1373
d
¼35.2, 48.3, 113.8, 126.7, 128.0, 128.1, 128.6, 128.7,
n
¼3059 (w), 3021 (w), 2992 (w),
Yellow solid, mp 136e138 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.77
(t, 3H, 3J¼6.9 Hz), 1.09e1.18 (m, 8H), 1.56e1.63 (m, 2H), 4.30e4.35

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
2317
(m), 1254 (m), 1333 (m), 1300 (w), 1288 (m), 1269 (m), 1258 (m),
1236 (m),1226 (m),1216 (m), 1176 (w), 1164 (m), 1142 (m),1105 (w),
5.35. 2-(4-tert-Butylphenyl)-1-cyclohexylpyrido[2,3-b]qui-
noxalin-4(1H)-one (6i)
1075 (w), 1039 (w), 1028 (w), 1001 (m); UV (CH2Cl2, nm): lmax
(log
3 )¼228 (5.72), 247 (5.59), 295 (5.39), 428 (4.22); MS (EI, 70 eV):
Yellow solid, mp 254e256 ꢀC. 1H NMR (CDCl3, 300 MHz):
¼0.94e1.03 (m, 2H), 1.18e1.26 (m, 1H), 1.32 (s, 9H), 1.53e1.58 (m,
m/z (%)¼377 (Mþ, 9), 286 (77), 273 (100), 245 (14), 129 (26), 102
(10), 69 (9), 44 (2); HRMS (ESI): calcd for C25H20N3O [MþH]þ
378.16009, found 378.15962.
d
1H), 1.71e1.78 (m, 4H), 2.96e3.10 (m, 2H), 4.03e4.13 (m, 1H), 6.35
(s, 1H), 7.29e7.32 (m, 2H), 7.45e7.48 (m, 2H), 7.68e7.73 (m, 1H),
7.77e7.83 (m, 1H), 7.99e8.02 (m, 1H), 8.35e8.38 (m, 1H); 13C
NMR (CDCl3, 63 MHz):
125.8, 127.3, 127.8, 129.4, 130.8, 132.5, 133.3, 137.6, 140.4, 141.8,
146.5, 153.2, 158.2, 177.8; IR (ATR, cmꢁ1):
2961 (m), 2929 (m), 2850 (m), 1643 (s), 1615 (w), 1577 (m), 1548
(m), 1520 (w), 1505 (m), 1488 (m), 1475 (m), 1454 (m), 1424 (m),
1412 (w), 1397 (m), 1353 (s), 1335 (m), 1301 (m), 1267 (s), 1247
(m), 1232 (m), 1201 (w), 1165 (w), 1154 (w), 1134 (m), 1121 (m),
1094 (m), 1047 (m), 1020 (m), 1003 (w); UV (CH2Cl2, nm): lmax
d
¼25.3, 26.6, 30.6, 31.2, 34.9, 64.2, 114.1,
5.32. 1-(2-Methoxyphenethyl)-2-phenylpyrido[2,3-b]quinox-
alin-4(1H)-one (6f)
n
¼3060 (w), 3045 (w),
Yellow solid, mp 200e202 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼2.90
(t, 2H, 3J¼6.7 Hz), 3.32 (s, 3H), 4.64 (t, 2H, 3J¼6.6 Hz), 6.25 (s, 1H),
6.55e6.58 (m, 1H), 6.66e6.67 (m, 2H), 7.02e7.05 (m, 3H), 7.31e7.41
(m, 3H), 7.72e7.87 (m, 1H), 8.03e8.06 (m, 1H), 8.40e8.43 (m, 2H);
13C NMR (CDCl3, 63 MHz):
126.1, 128.0, 128.1, 128.2, 128.5, 129.4, 129.4, 130.7, 130.9, 132.7,
d
¼29.6, 47.0, 54.7, 110.0, 113.7, 120.5,
(log
3
)¼228 (5.69), 248 (5.57), 291 (5.37), 426 (4.19); MS (EI,
70 eV): m/z (%)¼411 (Mþ, 10), 329 (100), 314 (44), 286 (22), 272
(11), 129 (9), 55 (7), 41 (8); HRMS (ESI): calcd for C27H30N3O
[MþH]þ 412.23834, found 412.23900. Anal. Calcd for C27H29N3O
(411.539): C, 78.80; H, 7.10; N, 10.21. Found: C, 78.39; H, 7.19; N,
10.52.
135.2, 137.4, 140.8, 142.6, 145.8, 157.3, 157.5, 177.8; IR (ATR, cmꢁ1):
n
¼3055 (w), 3019 (w), 2938 (w), 2834 (w), 1627 (s), 1601 (w), 1579
(m), 1545 (m), 1492 (m),1473 (s),1462 (m), 1451 (m),1441 (m), 1423
(m),1399 (m),1370 (w),1353 (s),1334 (m),1290 (m),1268 (m),1244
(s), 1215 (m), 1175 (w), 1160 (m), 1139 (m), 1093 (m), 1074 (w), 1039
(m), 1030 (m), 1001 (m); UV (CH2Cl2, nm): lmax (log
3
)¼228 (5.70),
247 (5.56), 295 (5.36), 432 (4.04); MS (EI, 70 eV): m/z (%)¼407 (Mþ,
44), 286 (52), 273 (100), 245 (21), 129 (32), 91 (15), 77 (6); HRMS
(ESI): calcd for C26H22N3O2 [MþH]þ 408.17065, found 408.17072.
Anal. Calcd for C26H21N3O2 (407.464): C, 76.64; H, 5.19; N, 10.13.
Found: C, 76.77; H, 5.31; N, 10.31.
5.36. 2-(4-tert-Butylphenyl)-1-heptylpyrido[2,3-b]quinox-
alin-4(1H)-one (6j)
Yellow solid, mp 167e169 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.76
(t, 3H, 3J¼6.8 Hz), 1.07e1.12 (m, 8H), 1.33 (s, 9H), 1.58e1.63 (m, 2H),
4.34 (t, 2H, 3J¼7.6 Hz), 6.40 (s, 1H), 7.32e7.49 (m, 4H), 7.71e7.85 (m,
2H), 7.99e8.02 (m, 1H), 8.39e8.42 (m, 1H); 13C NMR (CDCl3,
5.33. 1,2-Diphenylpyrido[2,3-b]quinoxalin-4(1H)-one (6g)
Yellow crystals, mp 305e307 ꢀC. 1H NMR (CDCl3, 300 MHz):
63 MHz):
125.6, 127.8, 127.9, 129.3, 130.9, 132.2, 132.6, 137.2, 140.8, 142.7,
145.5,153.1,157.1,177.7; IR (ATR, cmꢁ1):
(w), 2957 (m), 2923 (m), 2912 (m), 2859 (m), 1637 (s), 1573 (m),
1547 (s), 1510 (m), 1489 (s), 1476 (s), 1465 (s), 1451 (s), 1431 (m),
1404 (m), 1381 (w), 1360 (s), 1352 (s), 1335 (m), 1301 (w), 1285 (m),
1266 (s), 1255 (s), 1230 (m), 1216 (w), 1201 (m), 1161 (m), 1145 (w),
1134 (m), 1125 (m), 1110 (w), 1084 (w), 1028 (w), 1003 (w); UV
d
¼13.9, 22.4, 26.3, 28.3, 28.7, 31.2, 31.4, 34.8, 46.7, 113.8,
n¼3062 (w), 3046 (w), 3011
d
¼6.63 (s, 1H), 7.13e7.18 (m, 6H), 7.27e7.32 (m, 4H), 7.68e7.78 (m,
3H), 8.38e8.41 (m, 1H); 13C NMR (CDCl3, 63 MHz):
¼112.9, 127.1,
127.3, 127.4, 127.8, 128.0, 128.2, 128.6, 129.2, 129.8, 131.7, 134.2,
135.4, 137.3, 140.1, 141.7, 145.9, 155.5, 177.2; IR (ATR, cmꢁ1):
d
n
¼3054
(w), 3043 (w), 1634 (s), 1595 (w), 1572 (w),1550 (m),1540 (m),1496
(m), 1476 (s), 1455 (w), 1443 (w), 1421 (w), 1401 (m), 1358 (m), 1337
(w), 1316 (w), 1299 (w), 1273 (m), 1250 (w), 1231 (w), 1211 (w), 1188
(w), 1164 (w), 1148 (w), 1137 (w), 1112 (w), 1075 (w), 1033 (w), 1003
(CH2Cl2, nm): lmax (log
3
)¼228 (5.72), 247 (5.59), 293 (5.39), 428
(4.19); MS (EI, 70 eV): m/z (%)¼427 (Mþ, 60), 398 (9), 370 (16), 342
(20), 329 (100), 314 (31), 286 (36), 272 (10), 129 (18), 57 (6), 41 (4);
HRMS (ESI): calcd for C28H34N3O [MþH]þ 428.26964, found
428.26997.
(w); UV (CH2Cl2, nm): lmax (log
3
)¼236 (5.37), 248 (5.37), 311
(5.00), 428 (4.08); MS (EI, 70 eV): m/z (%)¼349 (Mþ, 95), 320 (30),
218 (10), 129 (6), 102 (4), 77 (7); HRMS (ESI): calcd for C23H16N3O
[MþH]þ 350.12879, found 350.12812. Anal. Calcd for C23H15N3O
(349.385): C, 79.07; H, 4.33; N, 12.03. Found: C, 79.16; H, 4.41; N,
12.05.
5.37. 2-(4-tert-Butylphenyl)-1-phenethylpyrido[2,3-b]quinox-
alin-4(1H)-one (6k)
5.34. 2-Phenyl-1-(3,4,5-trimethoxyphenyl)pyrido[2,3-b]qui-
noxalin-4(1H)-one (6h)
Yellow solid, mp 281e283 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼1.36
(s, 9H), 2.89 (t, 2H, 3J¼7.7 Hz), 4.57 (t, 2H, 3J¼7.7 Hz), 6.39 (s, 1H),
6.77e6.80 (m, 2H), 7.10e7.12 (m, 3H), 7.23e7.25 (m, 2H), 7.46e7.49
(m, 2H), 7.73e7.89 (m, 2H), 8.05e8.08 (m, 1H), 8.41e8.44 (m, 1H);
Yellow solid, mp 281e283 ꢀC. 1H NMR (CDCl3, 300 MHz):
d¼3.63
(s, 6H), 3.79 (s, 3H), 6.38 (s, 2H), 6.59 (s, 1H), 7.20e7.21 (s, 5H),
13C NMR (CDCl3, 63 MHz):
d
¼31.3, 34.9, 35.2, 48.1, 113.8, 125.7,
126.7, 127.9, 127.9, 128.5, 128.7, 129.5, 130.9, 132.0, 132.8, 137.2,
137.8, 140.8, 142.7, 145.5, 153.2, 156.9, 177.8; IR (ATR, cmꢁ1):
7.69e7.85 (m, 3H), 8.36e8.40 (m, 1H); 13C NMR (CDCl3, 63 MHz):
d
¼56.3, 61.0, 108.2, 113.9, 128.1, 128.3, 128.6, 129.3, 129.7, 130.8,
132.7, 133.5, 135.4, 136.3, 138.0, 141.1, 142.7, 146.8, 153.0, 156.4,
178.2; IR (ATR, cmꢁ1):
n
¼3054
(w), 3021 (w), 2952 (w), 2901 (w), 2867 (w), 1632 (s), 1579 (m),
1546 (m), 1505 (w), 1490 (m), 1475 (m), 1463 (m), 1448 (m), 1424
(m), 1404 (m), 1373 (w), 1354 (m), 1332 (m), 1287 (m), 1267 (m),
1234 (m), 1213 (m), 1201 (w), 1191 (w), 1178 (w), 1160 (m), 1136 (m),
1119 (w), 1101 (w), 1073 (w), 1027 (w), 1015 (w); UV (CH2Cl2, nm):
n
¼3060 (w), 3011 (w), 2985 (w), 2967 (w),
2935 (w), 2841 (w), 2823 (w), 1636 (m), 1598 (m), 1574 (m), 1552
(m), 1538 (w), 1495 (m), 1475 (m), 1464 (m), 1453 (m), 1416 (m),
1398 (m), 1365 (m), 1335 (m), 1308 (m), 1288 (w), 1265 (m), 1232
(s), 1168 (w), 1149 (m), 1108 (s), 1098 (s), 1038 (w), 1030 (w), 1004
lmax (log
3
)¼228 (5.67), 247 (5.53), 293 (5.33), 434 (4.04); MS (EI,
(s); UV (CH2Cl2, nm): lmax (log
3
)¼229 (5.71), 254 (5.57), 295 (5.37),
70 eV): m/z (%)¼433 (Mþ, 10), 329 (100), 314 (17), 286 (87), 272 (6),
129 (28), 102 (8), 57 (22), 41 (5); HRMS (ESI): calcd for C29H28N3O
[MþH]þ 434.22269, found 434.22380. Anal. Calcd for C29H27N3O
(433.544): C, 80.34; H, 6.28; N, 9.69. Found: C, 80.29; H, 6.61; N,
9.63.
431 (4.07); MS (EI, 70 eV): m/z (%)¼439 (Mþ, 100), 424 (30), 392
(10), 251 (7), 141 (5), 102 (5); HRMS (ESI): calcd for C26H22N3O4
[MþH]þ 440.16048, found 440.16076. Anal. Calcd for C26H21N3O4
(439.463): C, 71.06; H, 4.82; N, 9.56. Found: C, 71.11; H, 4.75; N, 9.90.

2318
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 2309e2318
5.38. 1-Cyclohexyl-2-octylpyrido[2,3-b]quinoxalin-4(1H)-one
(6l)
1070 (m), 1024 (w),1005 (m); UV (CH2Cl2, nm):
l
(log
3
)¼227 (5.76),
254 (5.62), 296 (5.43), 428 (4.22); MS (EI): m/z (%)¼475 (Mþ, 60),
460 (8), 390 (48), 377 (100), 362 (19), 334 (10), 181 (8); HRMS (ESI):
calcd for C28H34N3O4 [MþH]þ 476.25438, found 476.25329. Anal.
Calcd for C28H33N3O4 (475.579): C, 70.71; H, 6.99; N, 8.84. Found: C,
70.78; H, 6.93; N, 8.70.
Yellow solid, mp 115e117 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.69e0.73 (m, 3H), 1.12e1.30 (m, 7H), 1.55e1.67 (m, 5H),
1.83e1.86 (m, 2H), 2.45e2.46 (m, 6H), 2.61e2.66 (m, 2H), 3.07e3.10
(m, 2H), 4.13e4.18 (m, 1H), 6.23 (s, 1H), 7.58e7.63 (m, 1H),
7.68e7.73 (m, 1H), 7.88e7.91 (m, 1H), 8.19e8.22 (m, 1H); 13C NMR
Acknowledgements
(CDCl3, 63 MHz):
31.3, 35.4, 61.4, 112.3, 127.5, 129.1, 130.2, 132.1, 136.8, 139.8, 141.1,
146.0, 158.0, 177.6; IR (ATR, cmꢁ1):
2851 (w), 1639 (s), 1576 (w), 1549 (m), 1543 (m), 1476 (m), 1466 (m),
1423 (w), 1391 (w), 1348 (m), 1321 (w), 1295 (m), 1278 (m), 1230
(m), 1188 (w), 1159 (w), 1139 (w), 1118 (w), 1070 (w), 1053 (w), 1030
(w), 1017 (w), 1002 (w), 893 (w), 870 (w), 833 (s), 775 (s), 765 (s),
724 (m), 685 (w), 677 (w), 661 (w), 610 (w); UV (CH2Cl2, nm): lmax
d
¼13.7, 22.2, 25.1, 26.6, 28.6, 28.7, 28.8, 28.9, 30.2,
Financial support by DAAD (scholarships for S.M. and A.G.) is
gratefully acknowledged.
n¼3058 (w), 3046 (w), 2923 (m),
References and notes
1. Litvinov, V. P. Adv. Heterocycl. Chem. 2006, 91, 189e300.
(log
3
)¼237 (5.37), 248 (5.37), 310 (5.02), 421 (3.98); MS (EI, 70 eV):
2. (a) Matsumoto, J.; Miyamoto, T.; Minamida, A.; Nishimura, Y.; Egawa, H.;
Nishimura, H. J. Med. Chem. 1984, 27, 292e301; (b) Miyamoto, T.; Egawa, H.;
Matsumoto, J. Chem. Pharm. Bull. 1987, 35, 2280e2285.
3. (a) Kaatz, G. W.;Seo, S. M.; Aeschlimann, J. R.; Houlihan, H. H.; Mercier, R.-C.; Rybak,
M. J. Antimicrob. Agents Chemother. 1998, 42, 254e256; (b) Vilsmaier, E.; Goerz, T.
Synthesis1998, 739e744;(c)Garey, K.W.;Amsden, G.W. Pharmacotherapy1999,19,
21e34.
m/z (%)¼391 (Mþ, 66), 310 (23), 281 (29), 224 (52), 211 (100), 183
(22), 129 (4); HRMS (ESI): calcd for C25H34N3O [MþH]þ 392.26964,
found 392.27078.
5.39. 2-Octyl-1-phenethylpyrido[2,3-b]quinoxalin-4(1H)-one
4. (a) Kotljarov, A.; Irgashev, R. A.; Iaroshenko, V. O.; Sevenard, D. V.; Sosnovskikh,
V. Y. Synthesis 2009, 3233e3242; (b) Kotljarov, A.; Iaroshenko, V. O.;
Volochnyuk, D. M.; Irgashev, R. A.; Sosnovskikh, V. Y. Synthesis 2009,
3869e3879; (c) Iaroshenko, V. O.; Mkrtchyan, S.; Ghazaryan, G.; Hakobyan, A.;
Maalik, A.; Supe, L.; Villinger, A.; Tolmachev, A.; Ostrovskyi, D.; Sosnovskikh, V.
Y.; Ghochikyan, T. V.; Langer, P. Synthesis 2011, 469e479; (d) Mkrtchyan, S.;
Iaroshenko, V. O.; Dudkin, S.; Gevorgyan, A.; Vilches-Herrera, M.; Ghazaryan,
G.; Volochnyuk, D.; Ostrovskyi, D.; Ahmed, Z.; Villinger, A.; Sosnovskikh, V. Y.;
Langer, P. Org. Biomol. Chem. 2010, 8, 5280e5284; (e) Iaroshenko, V. O.;
Mkrtchyan, S.; Gevorgyan, A.; Vilches-Herrera, M.; Sevenard, D. V.; Villinger, A.;
Ghochikyan, T. V.; Saghiyan, A.; Sosnovskikh, V. Y.; Langer, P. Tetrahedron 2012,
2532e2543; (f) Iaroshenko, V. O.; Mkrtchyan, S.; Gevorgyan, A.; Miliutina, M.;
Villinger, A.; Volochnyuk, D.; Sosnovskikh, V. Y.; Langer, P. Org. Biomol. Chem.
2012, 10, 890e894; (g) Iaroshenko, V. O.; Wang, Y.; Zhang, B.; Volochnyuk, D.;
Sosnovskikh, V. Ya. Synthesis 2009, 2393e2402; (h) Iaroshenko, V. O.;
Ostrovskyi, D.; Petrosyan, A.; Mkrtchyan, S.; Villinger, A.; Langer, P. Journal of
Organic Chemistry 2011, 2899e2903; (i) Fatunsin, O.; Iaroshenko, V. O.;
Dudkin, S.; Mkrtchyan, S.; Villinger, A.; Langer, P. Tetrahedron Letters 2010, 51,
4693e4695; (j) Iaroshenko, V. O.; Specowius, V.; Vlach, K.; Vilches-Herrera, M.;
Ostrovskyi, D.; Mkrtchyan, S.; Villinger, A.; Langer, P. Tetrahedron 2011, 67,
5663e5677; (k) Iaroshenko, V. O.; Bunescu, A.; Spannenberg, A.; Langer, P.
Chemistry - A European Journal 2011, 17, 7188e7192; (l) Iaroshenko, V. O.;
Mkrtchyan, S.; Villinger, A. Synthesis 2013, 205e218; (m) Iaroshenko, V. O.;
Vilches-Herrera, M.; Gevorgyan, A.; Arakelyan, K.; Ostrovskyi, D.; Abbasi, M. S. A.;
Mkrtchyan, S.; Supe, L.; Hakobyan, A.; Villinger, A.; Volochnyuk, D. M.;
Tolmachev, A. Tetrahedron 2013, 69, 1217e1228; (n) Iaroshenko, V. O.; Ali, I.;
Mkrtchyan, S.; Semeniuchenko, V.; Ostrovskyi, D.; Langer, P. Synlett 2012, 18,
2603e2605.
(6m)
Yellow solid, mp 144e146 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.80e0.84 (m, 3H), 1.22e1.35 (m, 9H), 1.61e1.66 (m, 3H), 2.56 (t,
2H, 3J¼7.7 Hz), 3.08 (t, 2H, 3J¼7.6 Hz), 4.70 (t, 2H, 3J¼7.6 Hz), 6.35 (s,
1H), 7.17e7.27 (m, 5H), 7.72e7.84 (m, 1H), 7.81e7.84 (m, 1H),
8.03e8.06 (m, 1H), 8.37e8.40 (m, 1H); 13C NMR (CDCl3, 63 MHz):
d
¼14.0, 22.6, 28.5, 29.1, 29.2, 29.3, 31.7, 33.7, 35.4, 46.2, 111.7, 127.0,
128.0, 128.8, 128.8, 129.4, 130.9, 132.7, 137.0, 137.9, 140.7, 142.5,
145.4, 157.6, 177.9; IR (ATR, cmꢁ1):
n
¼3048 (w), 3024 (w), 2982 (w),
2948 (w), 2929 (m), 2856 (m), 1634 (s), 1612 (m), 1583 (m), 1548
(m), 1541 (m), 1489 (m), 1475 (m), 1466 (m), 1435 (m), 1418 (m),
1399 (m),1370 (m),1353 (s),1331 (m),1322 (w),1299 (m),1292 (m),
1279 (m), 1271 (m), 1234 (m), 1224 (m), 1208 (w), 1169 (m), 1156
(m), 1134 (m), 1121 (m), 1092 (w), 1074 (w), 1030 (m), 1013 (w); UV
(CH2Cl2, nm): lmax (log
3
)¼228 (5.73), 254 (5.60), 296 (5.40), 428
(4.21); MS (EI, 70 eV): m/z (%)¼413 (Mþ, 45), 322 (100), 238 (16),
224 (30), 211 (73), 183 (14), 129 (13), 105 (9); HRMS (ESI): calcd for
C27H32N3O [MþH]þ 414.25399, found 414.25453. Anal. Calcd for
C27H31N3O (413.555): C, 78.42; H, 7.56; N, 10.16. Found: C, 78.39; H,
7.59; N, 10.22.
5. Iaroshenko, V. O.; Knepper, I.; Zahid, M.; Kuzora, R.; Dudkin, S.; Villinger, A.;
Langer, P. Org. Biomol. Chem. 2012, 10, 2955e2959.
6. Vijavalakshmi, S.; Ragunath, L.; Rajendran, S. P. Heterocycl. Commun. 2001, 7,
177e182.
5.40. 2-Octyl-1-(3,4,5-trimethoxyphenyl)pyrido[2,3-b]qui-
noxalin-4(1H)-one (6n)
7. Salman, G. A.; Hussain, M.; Iaroshenko, V.; Villinger, A.; Langer, P. Adv. Synth.
Catal. 2011, 353, 331e336.
8. (a) Lin, C.-F.; Lu, W.-D.; Wang, I.-W.; Wu, M.-J. Synlett 2003, 2057e2061; (b)
Waldo, J. P.; Larock, R. C. J. Org. Chem. 2007, 72, 9643e9647.
9. Baruah, B.; Bhuyan, P. J. Tetrahedron 2009, 65, 7099e7104.
Yellow solid, mp 189e191 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
¼0.77e0.81 (m, 3H), 1.15e1.20 (m, 10H), 1.52e1.59 (m, 2H), 2.48 (t,
2H, 3J¼7.7 Hz), 3.79 (s, 6H), 3.94 (s, 3H), 6.46 (s, 2H), 6.47 (s, 1H),
7.64e7.79 (m, 3H), 8.32e8.35 (m, 1H); 13C NMR (CDCl3, 63 MHz):
10. (a) Bernini, R.; Cacchi, S.; Fabrizi, G.; Sferrazza, A. Synthesis 2009, 1209e1219;
(b) Zhao, T.; Xu, B. Org. Lett. 2010, 12, 212e215.
d
¼14.0, 22.5, 28.7, 29.0, 29.1, 29.2, 31.7, 34.0, 56.4, 61.1, 106.8, 111.1,
128.3, 129.4, 130.7, 132.4, 133.2, 136.2, 138.6, 140.9, 142.7, 147.2,
153.9, 158.3, 178.2; IR (ATR, cmꢁ1):
11. Crystallographic data (excluding structure factors) for the structures 3f, and 6i,
reported in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication nos. 919223 & 919224 and
can be obtained free of charge on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: þ44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk, or
via www.ccdc.cam.ac.uk/data_request/cif.
n
¼3078 (w), 3061 (w), 2922 (m),
2846 (w), 1640 (s), 1596 (m), 1581 (m), 1545 (m), 1500 (m), 1480
(m), 1467 (m), 1455, (m), 1419 (m), 1400 (m), 1361 (m), 1341 (m),
1313 (m), 1274 (m), 1232 (s), 1206 (m), 1170 (w), 1144 (w), 1117 (s),
12. Mahesh, R.; Perumal, R. V.; Pandi, P. V. Biol. Pharm. Bull. 2004, 27, 1403e1405.