Efficient synthesis of novel thieno[3,2-b]-, [2,3-c]- and [3,2-c]pyridones by Sonogashira coupling of bromothiophenes with terminal alkynes and subsequent intramolecular C-N bond-forming reaction

Article abstract of DOI:10.1016/j.tet.2013.02.069

The coupling of bromothiophenes with terminal alkynes using triethylamine or diisopropyl amine under Sonogashira conditions (PdCl₂(PPh ₃)₂, CuI) followed by subsequent addition of amines or ammonium to the intermediate thienyl acetylenes represents a novel access to a wide range of thieno[3,2-b]-, [2,3-c]-, and [3,2-c]pyridones under basic conditions and in excellent yields.

Full text of DOI:10.1016/j.tet.2013.02.069

Tetrahedron 69 (2013) 3167e3181
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of novel thieno[3,2-b]-, [2,3-c]- and [3,2-c]
pyridones by Sonogashira coupling of bromothiophenes with
terminal alkynes and subsequent intramolecular CeN bond-forming
reaction
,
b
,
a
,
,c
Viktor O. Iaroshenko a , Sajid Ali c, Tariq Mahmood Babar a
,
*
Muhammad S.A. Abbasi a, Vyacheslav Ya Sosnovskikh d, Alexander Villinger a,
Andrey Tolmachev e, Peter Langer a
,
f
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, Quaid-i-Azam University, Islamabad 45320, Pakistan
d Department of Chemistry, Ural Federal University, 51 Lenina Ave., 620083 Ekaterinburg, Russia
e Enamine Ltd., Alexandra Matrosova Str. 23, Kyiv 01103, Ukraine
f
€
€
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:
The coupling of bromothiophenes with terminal alkynes using triethylamine or diisopropyl amine under
Sonogashira conditions (PdCl2(PPh3)2, CuI) followed by subsequent addition of amines or ammonium to
the intermediate thienyl acetylenes represents a novel access to a wide range of thieno[3,2-b]-, [2,3-c]-,
and [3,2-c]pyridones under basic conditions and in excellent yields.
Received 9 December 2012
Received in revised form 15 February 2013
Accepted 20 February 2013
Available online 26 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Sonogashira coupling
Bromothiophenes
Terminal alkynes
Thienyl acetylenes
Thieno[3,2-b]-, [2,3-c]-, and [3,2-c]
pyridones
1. Introduction
Functionalized quinolines are very attractive targets for com-
binatorial library synthesis due to their wide range of valuable bi-
ological activities.1 Many natural and synthetic quinolines have
occupied an important place in drug research. At the same time,
a very special position among all drugs containing a quinoline core
is occupied by the fluoroquinolones. The latter constitute a major
class of antibacterial chemotherapeutic agents, which have a broad
spectrum against Gram positive and Gram negative bacteria.2 The
five representatives depicted in Fig. 1 belong to the 200 top-selling
drugs. Examples include norfloxacin Ia3 and ciprofloxacin Ib,4
which were the first two quinolones marketed for human use.
O
O
O
N
O
F
F
OH
OH
OH
N
N
R
N
HN
N
O
Me
Me
Ia: Norfloxacin (R = Et);
Ib: Ciprofloxacin (R = cyclopropyl)
II: Levofloxacin
O
O
O
O
F
F
F
OH
H
N
N
N
N
N
H
OMe
H
H2N
NH
H
* Corresponding author. Tel.: þ49 381 498 6427; fax: þ49 381 498 6412; e-mail
addresses: viktor.iaroshenko@uni-rostock.de, iva108@googlemail.com (V.O.
Iaroshenko).
III: Moxifloxacin
IV: Trovafloxacin
F
Fig. 1. Some marketing drugs containing quinolone framework.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.069

3168
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
Since 1986, more than twenty fluoroquinolones have been ap-
proved and most of them remain on the market.2b The biological
importance of quinolones has led to a considerable amount of
synthetic work in the field of this heterocyclic system5 (Fig. 1).
Continuing our research on the efficient synthesis of drug-like
heteroannulated pyridines,6 of the six theoretically possible par-
ent thienopyridine compounds, we sought to prepare thieno[3,2-
b]-, [2,3-c]-, and [3,2-c]pyridines with the concept of replacing the
benzene ring of the quinoline nucleus by thiophene, a known
bioisostere in other fields of medicinal chemistry (Fig. 2). Earlier,
synthesis of several 4-oxothieno[2,3-b]pyridine-5-carboxylic acids
V, potential bioisosteres of quinolone antibacterials that exhibited
good level of activity against Gram negative and Gram positive
bacterial strains, has been reported.7 Compounds VI have the
ability to penetrate cells and selectively inhibit the surface ex-
pression of the cell adhesion molecules ICAM-1 and E-selectin in
human endothelial cells,8 while the 7-oxothieno[3,2-b]pyridine-6-
carboxamides VII, a new class of non-nucleoside antivirals, possess
remarkable potency versus a broad spectrum of herpesvirus DNA
polymerases and excellent selectivity compared to human DNA
polymerases9 (Fig. 2).
envisaged that 1-(3-bromothiophen-2-yl)-3-arylprop-2-yn-1-ones
1 are suitable substrates for the synthesis of thieno[3,2-b]pyridin-
7-one derivatives 3. The requisite starting material, 3-
bromothiophene-2-carbonyl chloride, was prepared by the deam-
inative bromination of commercially available methyl 3-
aminothiophene-2-carboxylate with tert-butyl nitrite and CuBr2
in acetonitrile,13 followed by alkaline hydrolysis and subsequent
treatment with thionyl chloride according to the described pro-
cedures (see the Experimental part). The preparation of ynones 1
was carried out by Sonogashira cross-coupling reaction14 of 3-
bromothiophene-2-carbonyl chloride with terminal aryl acety-
lenes using PdCl2(PPh3)2 and CuI in the presence of triethylamine in
THF to give ketones 1aed in high yields (70e77%). Then we ex-
amined the reactions of these ketones with a range of commercially
available aromatic and aliphatic amines. After the optimization of
the reaction conditions with regard to the type of catalyst and
solvent, we have found that the use of Pd2(dba)3 (5 mol %), BINAP
(10 mol %), 1.4 equiv of Cs2CO3 as a base, and toluene as a solvent
(110 ꢀC, 10e12 h, argon) was essential to get excellent yields
(70e92%) of 4,5-disubstituted thieno[3,2-b]pyridones 3aez. This is
a palladium-catalyzed tandem reaction consisting of a sequential
double CeN bond formation to give thieno[3,2-b]pyridones 3 from
thienyl acetylenic ketones 1 and primary amines via intermediates
2, from which compound 2h was isolated in 66% yield when the
reaction was run for the short time (5 h) (Scheme 1).
N
N
N
S
S
S
thieno[3,2-b]pyridine thieno[3,2-c]pyridine thieno[2,3-c]pyridine
Me
Br
NH2
O
CO2H
S
X
OMe
Cl
S
S
S
S
N
R
O
O
R
N
S
SOCl
X = OMe, OH
V
VI
Br
Br
Me
N
Ar
Ar
Cl
R2N
Cl
H
i
S
N
S
O
1a-d
O
VII
O
O
ii
RNH
R
Fig. 2. Thieno[3,2-b]-, [3,2-c]-, and [2,3-c]pyridines and some bioactive
representatives.
R
N
NH
Ar
Ar
S
S
Given the broad utility of thienopyridines in medicinal chem-
istry, we were interested in developing novel approaches, com-
mencing with bromothiophenes-based substrates, which would
allow access to these interesting heterocyclic compounds. There are
several different synthetic procedures leading to thienopyridines,10
some of them use 2- and 3-aminothiophenes salts as key in-
termediates in the reactions with 1,3-dicarbonyls and ethoxy-
methylene derivatives of various active methylene compounds
(GouldeJacobs reaction).10gem Though some of the known methods
of preparation of thienopyridines seem to be satisfactory, new
routes starting from different materials are desirable for efficient
structure modifications of these molecules. In this paper we detail
the successful realization of our goal with an efficient synthesis of
diverse thieno[3,2-b]-, [2,3-c]-, and [3,2-c]pyridones by the cou-
pling of bromothiophenes with terminal alkynes under Sonoga-
shira conditions followed by subsequent [5þ1]-cyclization of the
intermediate thienyl acetylenes with a set of aromatic and aliphatic
amines or ammonium.
O
2h
O
3a-z
Scheme 1. Reagents and conditions: i, PdCl2(PPh3)2, CuI, Et3N, THF, Ar, rt, 2 h; ii,
Cs2CO3, Pd2(dba)3, BINAP, Ar, toluene, 110 ꢀC, 10e12 h.
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 ketones 1aed, providing a variety of thieno
[3,2-b]pyridones 3 with high purity after column chromatography.
It can be observed that the process tolerates both electron-donating
(alkyl, alkoxy, diethylamino) and electron-withdrawing (halogeno,
nitro) substituents on the aromatic amines. The structures of all
products 3 were characterized by IR, 1H, 13C NMR spectral data as
well as HRMS analysis. Finally the structures of the representatives
3a and 3m were corroborated by X-ray single crystal analysis (Figs.
3 and 4).
Next, we have obtained a series of thieno[2,3-c]pyridones 6 by
Sonogashira coupling of methyl 3-bromothiophene-2-carboxylate
with various terminal aryl and alkyl alkynes followed by a base-
mediated intramolecular CeN bond-forming reaction (Scheme 2).
It was found that treatment of methyl 3-bromothiophene-2-
carboxylate with the corresponding alkyne in a pressure tube un-
der argon at 70 ꢀC in the presence of PdCl2(PPh3)2 (5 mol %) and CuI
(3 mol %) in diisopropyl amine resulted in the formation of thienyl
2. Results and discussion
Based on the retrosynthetic analysis and on previous experience
of Iaroshenko’s group related to the development of new coupling
reactions of alkynyl thiophenes11 and alkynyl pyridines,12 we

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3169
Table 1
Yields of compounds 1e3
R
Br
1e3
Ar
R
Yield (%)
R
OMe
OMe
1a
1b
1c
1d
2h
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
Ph
4-MeC6H4
4-n-PrC6H4
4-MeOC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
d
77
73
75
70
66
78
80
82
78
82
70
80
80
83
81
78
86
90
92
91
90
89
82
85
78
83
81
85
80
79
82
i
S
S
d
O
O
4a-j
d
d
NH3
4-Et2NC6H4
Ph
R
R
4-MeC6H4
4-EtC6H4
4-MeOC6H4
4-EtOC6H4
2,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2
4-Et2NC6H4
4-FC6H4
3-CF3C6H4
3-BrC6H4
4-NO2C6H4
4-MeC6H4CH2
3-MeOC6H4CH2
PhCH2CH2
c-C6H11
n-C7H15
4-MeOC6H4
4-FC6H4
4-ClC6H4
Ph
3-FC6H4
3,5-Cl2C6H3
4-MeC6H4
4-EtC6H4
4-ClC6H4
ii
NH2
NH
S
S
O
5a-j
O
6a-j
Scheme 2. Reagents and conditions: i, PdCl2(PPh3)2, CuI, diisopropyl amine (DIPA), Ar,
70 ꢀC, 2 h; ii, MeONa, MeOH, reflux, 3e4 h.
Ph
Ph
Ph
Ph
Ph
Ph
3m
3n
3o
3p
3q
3r
Table 2
Yields of compounds 4e6
4e6
R
Yield (%)
4
5
6
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-n-PrC6H4
4-n-PrC6H4
4-n-PrC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
a
b
c
d
e
f
g
h
i
Ph
72
69
68
73
70
70
75
50
51
55
86
88
85
90
84
81
80
86
80
81
75
77
77
72
70
76
75
75
73
70
3s
3t
4-MeC6H4
2-MeC6H4
4-n-PrC6H4
4-t-BuC6H4
4-MeOC6H4
4-FC6H4
n-Pr
3u
3v
3w
3x
3y
3z
n-Bu
n-Am
j
thiophenes has been well documented,15 compounds 4 are hitherto
unreported. Reaction of alkynes 4aej with aqueous ammonia at
heating for 10e12 h in a pressure tube produced amides 5aej in
80e90% yields. These compounds were reacted with MeONa in
methanol at reflux to form thieno[2,3-c]pyridones 6aej in 70e77%
yields by intramolecular cyclization reaction (Table 2). The struc-
tures of compounds 5c and 6d were confirmed by X-ray single
crystal analysis (Figs. 5 and 6).
Fig. 3. Molecular structure of compound 3a.
Fig. 5. Molecular structure of compound 5c.
Fig. 4. Molecular structure of compound 3m.
alkynes 4aej in good to high yields (50e75%). In most cases, the
reaction was complete after 2 h and the products were purified by
silica gel column chromatography. As can be seen from Table 2, this
coupling reaction has virtually no limitations as regards the nature
of the terminus of the alkynyl moiety. Although the chemistry of
Fig. 6. Molecular structure of compound 6d.

3170
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
2-Bromo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile,
the starting material for the synthesis of thieno[3,2-c]pyridones 9,
was obtained by the deaminative bromination of commercially
publication no. 924461e924464 and can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK;
fax: þ44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk, or via
www.ccdc.cam.ac.uk/data_request/cif.
available
2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carbonitrile, following the recently described method,13 in 74%
yield. The requisite thieno[3,2-c]pyridones 9aee can be easily
prepared by the palladium/copper-catalyzed Sonogashira coupling
of the corresponding aryl alkynes with 2-bromo-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carbonitrile, followed by hydroly-
sis of the cyano group of the resultant alkynes 7aeg under the
action of TFAeH2SO4 system to amides 8aeg and their intra-
molecular cyclization with MeONa. The introduction of sub-
stituents on the aryl group has little effect on the yields of these
reactions (Scheme 3, Table 3).
5. Experimental
5.1. General
The dry solvents were purchased directly from Acros Organics as
AcroSeal bottles. Other solvents were purified by distillation. All
reactions were carried out under an inert atmosphere. 1H and 13C
NMR spectroscopy: Bruker AV 300 and Bruker AV 400 spectrome-
ters. References: 0.00 ppm for TMS, 7.26 ppm for CDCl3 (1H NMR)
and 0.00 ppm for TMS, 77.00 ppm for CDCl3 (
13C NMR). The DEPT
method was used for determining the presence of primary, sec-
ondary, tertiary, and quaternary carbon atoms. The 1H NMR spectra
were measured with standard number of scans; 13C NMR spectra
were measured with standard number of scans or when necessary,
with 4000 scans. In case of unclear assignment all possible hy-
drogen and carbon atoms were stated. 19F NMR spectra were
recorded on a Bruker AV 300 (282 MHz) spectrometer. The spectra
were measured with standard number of scans. Mass spectrometry
(MS): Finnigan MAT 95 XP (electron ionization EI, 70 eV). High-
resolution MS (HRMS): Finnigan MAT 95 XP. Only the measure-
ments with an average deviation from the theoretical mass of
ꢁ2 mDa were accounted as correct. Infrared spectroscopy (IR):
Nicolet 550 FT-IR spectrometer with ATR sampling technique for
solids as well as liquids. Signal characterization: w¼weak,
m¼medium, s¼strong. X-ray crystallography: STOE imaging plate
CN
CN
Ar
Br
Ar
i
S
S
7a-g
ii
O
O
NH2
NH
Ar
Ar
iii
S
8a-g
S
9a-e
Scheme 3. Reagents and conditions: i, PdCl2(PPh3)2, CuI, diisopropyl amine (DIPA), Ar,
70 ꢀC, 2 h; ii, TFAeH2SO4, 75 ꢀC, 5 h; iii, MeONa, MeOH, reflux, 3e4 h.
Table 3
diffraction systems with monochromatic Mo-Ka radiation. Ele-
Yields of compounds 7e9
mental analysis (EA): Leco 932 C, H, N, S. UV/vis spectroscopy:
Lambda 2 (PerkineElmer). Melting point determination (mp):
Micro-Hot-Stage Galen TM III Cambridge Instruments. The melting
points are not corrected. Thin layer chromatography (TLC): Merck
Silica 60 F254 aluminum-backed plates from MachereyeNagel. De-
tection with UV light at 254 nm and afterward development with
vanillinesulfuric acid solution (6 g vanillin, 2.5 ml concentrated
H2SO4, 250 ml EtOH). Column chromatography: separation on
Fluka silica gel 60 (0.063e0.200 mm, 70e320 mesh). Eluents were
distilled before use. 3-Bromothiophene-2-carbonyl chloride was
prepared according to the methods reported in the Ref. 16.
7e9
Ar
Yield (%)
7
8
9
a
b
c
d
e
f
Ph
77
77
73
73
75
78
75
75
77
79
74
77
79
72
78
77
80
79
73
d
4-MeC6H4
4-n-PrC6H4
4-t-BuC6H4
4-MeOC6H4
2-MeC6H4
4-FC6H4
g
d
These results clearly show that the present reactions could be
applicable to various types of thienyl alkynes, providing a simple and
efficient route to the synthesis of a wide range of the thienopyridine
derivatives, which are of interest as biologically active compounds.
The structures of all the compounds were deduced from their spec-
tral studies (IR, 1H,13C NMR, and MS); the most of them mass spectra
displayed molecular ion peaks at the appropriate m/z values.
5.1.1. General procedure for the synthesis of 1-(3-bromothiophen-2-
yl)-3-arylprop-2-yn-1-ones (1). A mixture of 3-bromothiophene-
2-carbonyl chloride (0.225 g, 1.0 mmol), PdCl2(PPh3)2 (2 mol %), and
Et3N (1.0 mmol) was stirred in anhydrous THF for 10 min under
argon at room temperature. CuI (4 mol %) was added and the re-
action mixture was stirred for another 10 min before aryl acetylene
(1.0 mmol) was added. After 2 h at room temperature the reaction
mixture was diluted with EtOAc and washed with 0.1 N HCl
(2ꢂ10 ml) and saturated NH4Cl solution (10 ml). The organic phase
was separated, dried (Na2SO4), filtered, and concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography.
3. Conclusion
In conclusion, we have developed an efficient synthesis libraries
of thieno[3,2-b]-, [2,3-c]-, and [3,2-c]pyridine scaffolds on the basis
of thienyl acetylenes, which were prepared by Sonogashira cross-
coupling reaction. This methodology is a valuable addition to
fused pyridine synthesis and represent a novel and general route to
various thienopyridones, which constitute an important structural
subunit of a variety of biologically active compounds.
5.1.2. General procedure for the synthesis of thieno[3,2-b]pyridones
(3). To the ynone 1 (0.5 mmol), Cs2CO3 (0.7 mmol), Pd2(dba)3
(5 mol %), and BINAP (10 mol %) under argon was added toluene
(10 ml) followed by arylamine/alkylamine (0.6 mmol), and the re-
action was stirred at 110 ꢀC for 10e12 h. After cooling to room
temperature, the reaction mixture was preabsorbed onto silica gel
and purified by column chromatography.
4. Crystallographic data
Crystallographic data (excluding structure factors) for the
structure 3a, 3m, 5c, 6d, reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
5.1.3. General procedure for the synthesis of esters (4). A mixture of
methyl 3-bromothiophene-2-carboxylate (0.221 g, 1.0 mmol), aryl/

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3171
alkyl acetylene (1.1 equiv), PdCl2(PPh3)2 (5 mol %), CuI (3 mol %),
and diisopropyl amine (DIPA) (5 ml) were added to a pressure tube
under argon and then heated for 2 h at 70 ꢀC. After cooling, water
and ethyl acetate were added and the phases were separated. The
aqueous phase was then extracted with ethyl acetate (3ꢂ10 ml).
The combined organic layers were dried (Na2SO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
(ESI): calcd for C13H779BrOS 289.93955, found 289.94027 and calcd
for C13H781BrOS 291.93750, found 291.93839; IR (ATR, cmꢃ1):
n
¼3389 (w), 3099 (w), 2959 (w), 2794 (w), 2437 (w), 2350 (w),
2269 (w), 2192 (s), 1985 (w), 1887 (w), 1803 (w), 1651 (w), 1631 (w),
1584 (s), 1557 (w), 1531 (w), 1486 (s), 1440 (m), 1397 (s), 1347 (w),
1328 (w), 1304 (s), 1198 (s), 1095 (w), 1067 (w), 1027 (w), 966 (w),
962 (s), 918 (w), 902 (w), 877 (s).
6.2. 1-(3-Bromothiophen-2-yl)-3-p-tolylprop-2-yn-1-one (1b)
Yellow solid, yield 73%, mp 71e73 ꢀC. 1H NMR (300 MHz, CDCl3):
5.1.4. General procedure for the synthesis of 3-(aryl/alkylethynyl)
thiophene-2-carboxamides (5). An ethanol solution (10 ml) of the
corresponding compound 4 (0.1 g) was saturated with aqueous
ammonia and heated for 10e12 h in a pressure tube at 70 ꢀC. After
completion of the reaction, solvent was removed under reduced
pressure and the residue was purified with silica gel column
chromatography.
d
¼2.34 (s, 3H, Me), 7.09 (d, J¼5.2 Hz, 1H), 7.15 (d, J¼8.0 Hz, 2H), 7.53
(d, J¼5.2 Hz, 1H), 7.51 (d, J¼8.0 Hz, 2H); GCeMS (EI, 70 eV): m/z
(%)¼306 (Mþ, 81Br, 77), 304 (Mþ, 79Br, 75), 278 (100), 197 (11), 153
(19), 143 (49), 115 (8), 98 (4), 89 (8), 82 (6); HRMS (ESI): calcd for
C14H979BrOS 303.95520, found 303.95576 and calcd for
C14H981BrOS 305.95315, found 305.95370; IR (ATR, cmꢃ1):
n
¼3209
5.1.5. General procedure for the synthesis of thienopyridones (6). To
the methanol solution of the corresponding amide 5 (0.1 g), was
added NaOMe (0.15 g) and was refluxed for 3e4 h. After completion
of the reaction, methanol was removed under reduced pressure
and the residue was diluted with water. The precipitate so formed
was filtered, dried, and recrystallized from MeOH.
(w), 3105 (w), 3027 (w), 2911 (w), 2859 (w), 2291 (w), 2188 (s),
1903 (w), 1664 (w), 1619 (s), 1602 (m), 1505 (m), 1486 (s), 1454 (w),
1445 (w), 1393 (s), 1351 (s), 1304 (w), 1278 (m), 1238 (w), 1188 (m),
1174 (m), 1148 (m), 1116 (w), 1085 (w), 1010 (s), 962 (w), 945 (w),
900 (w), 879 (s), 851 (w), 809 (s).
6.3. 1-(3-Bromothiophen-2-yl)-3-(4-propylphenyl)prop-2-yn-
1-one (1c)
5.1.6. General procedure for the synthesis of methyl 3-(aryl/alkyle-
thynyl)thiophene-2-carboxylates (4) and 2-(arylethynyl)-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carbonitriles (7). A mixture of
methyl 3-bromothiophene-2-carboxylate or 2-bromo-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carbonitrile (1.0 mmol), aryl/alkyl
acetylene (1.1 equiv), PdCl2(PPh3)2 (5 mol %), CuI (3 mol %), and
diisopropyl amine (DIPA) (5 ml) were added to a pressure tube
under argon and then heated for 2 h at 70 ꢀC. After cooling, water
and ethyl acetate were added and the phases were separated. The
aqueous phase was then extracted with ethyl acetate (3ꢂ10 ml).
The combined organic layers were dried (Na2SO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
Yellow oil, yield 75%. 1H NMR (300 MHz, CDCl3):
d
¼0.86 (t,
J¼7.4 Hz, 3H, Me), 1.57 (sext, J¼7.3 Hz, 2H, CH2), 2.55 (t, J¼7.9 Hz,
2H, CH2), 7.08 (d, J¼5.2 Hz, 1H), 7.14 (d, J¼8.3 Hz, 2H), 7.52 (d,
J¼5.2 Hz, 1H), 7.53 (d, J¼8.3 Hz, 2H); 13C NMR (62.9 MHz, CDCl3):
d
¼13.7, 24.1, 38.1, 87.2, 94.8, 116.1, 117.0, 128.9, 133.1, 133.4, 133.9,
138.0, 146.5, 168.2; GCeMS (EI, 70 eV): m/z (%)¼334 (Mþ, 81Br, 57),
332 (Mþ, 79Br, 57), 306 (27), 277 (100), 195 (18), 171 (16), 152 (14),
142 (13), 114 (12); HRMS (ESI): calcd for C16H1379BrOS 331.98650,
found 331.98693 and calcd for C16H1381BrOS 333.98445, found
333.98496; IR (ATR, cmꢃ1):
n
¼3370 (w), 3103 (w), 3083 (w), 2956
(m), 2927 (m), 2868 (m), 2547 (w), 2431 (w), 2273 (w), 2189 (s),
1913 (w), 1625 (m), 1592 (s), 1488 (s), 1463 (w), 1397 (s), 1352 (m),
1302 (m), 1277 (m), 1188 (m), 1174 (s), 1148 (m), 1114 (w), 1085 (w),
1009 (m), 967 (m), 903 (w), 879 (s).
5.1.7. General procedure for the synthesis of 2-(arylethynyl)-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxamides (8). A solution of the
corresponding nitrile 7 (0.15 g) in 7.0 ml of TFAeH2SO4 (4:1, v/v)
mixture was heated at reflux (75 ꢀC). The progress of the reaction
was monitored by TLC analysis. After completion of the reaction
(5 h), the reaction mixture was poured into ice-cold water. The
product thus precipitated out was filtered, washed with water, and
dried.
6.4. 1-(3-Bromothiophen-2-yl)-3-(4-methoxyphenyl)prop-2-
yn-1-one (1d)
Yellow solid, yield 70%, mp 98e100 ꢀC. 1H NMR (250 MHz,
CDCl3):
d
¼3.78 (s, 3H, MeO), 6.86 (d, J¼8.9 Hz, 2H), 7.07 (d, J¼5.2 Hz,
1H), 7.52 (d, J¼5.2 Hz, 1H), 7.57 (d, J¼8.9 Hz, 2H); 13C NMR
5.1.8. General procedure for the synthesis of 5-aryl/alkylthieno[2,3-c]
pyridin-7(6H)-ones (6) and 3-aryl-6,7,8,9-tetrahydro[1]benzothieno
[3,2-c]pyridin-1(2H)-ones (9). To the methanol solution of the cor-
responding amide 5 or 8 (0.1 g), was added NaOMe (0.15 g) and was
refluxed for 3e4 h. After completion of the reaction, methanol was
removed under reduced pressure and the residue was diluted with
water. The precipitate so formed was filtered, dried, and recrys-
tallized from MeOH.
(62.9 MHz, CDCl3):
d¼55.4, 87.4, 95.4, 111.7, 114.4, 115.9, 132.7, 133.2,
133.4, 133.8,161.9, 165.1; GCeMS (EI, 70 eV): m/z (%)¼322 (Mþ, 81Br,
100), 320 (Mþ, 79Br, 99), 294 (58), 277 (68), 251 (16), 169 (21), 159
(62), 144 (15), 131 (4), 116 (15); HRMS (ESI): calcd for C14H979BrOS
319.95011, found 319.95012 and calcd for C14H981BrOS 321.94807,
found 321.94828; IR (ATR, cmꢃ1):
n
¼3099 (w), 2955 (w), 2841 (w),
2587 (w), 2516 (w), 2188 (s), 1893 (w), 1769 (w), 1715 (w), 1668 (m),
1624 (m), 1596 (m), 1567 (w), 1504 (s), 1445 (w), 1423 (m), 1402 (s),
1349 (m), 1305 (w), 1253 (s), 1186 (w), 1168 (m), 1106 (w), 1083 (w),
1020 (m), 957 (w), 913 (w), 880 (s).
6. Analytical data
6.1. 1-(3-Bromothiophen-2-yl)-3-phenylprop-2-yn-1-one (1a)
Yellow solid, yield 77%, mp 81e83 ꢀC. 1H NMR (300 MHz, CDCl3):
6.5. 1-(3-(4-(Diethylamino)phenylamino)thiophen-2-yl)-3-
phenylprop-2-yn-1-one (2h)
d
¼7.09 (d, J¼5.2 Hz, 1H), 7.31e7.42 (m, 3H), 7.54 (d, J¼5.2 Hz, 1H),
Yellow solid, yield 66%, mp 124e126 ꢀC. 1H NMR (300 MHz,
7.59e7.63 (m, 2H); 13C NMR (62.9 MHz, CDCl3):
d
¼87.3, 94.0, 116.4,
CDCl3):
d
¼1.07 (t, J¼7.1 Hz, 6H, 2Me), 3.25 (q, J¼7.1 Hz, 4H, 2CH2),
119.9, 128.7, 131.0, 133.0, 133.6, 134.0, 137.9, 168.2; GCeMS (EI,
70 eV): m/z (%)¼292 (Mþ, 81Br, 54), 290 (Mþ, 79Br, 52), 264 (100),
183 (3), 139 (52), 129 (64), 101 (9), 91 (7), 82 (7), 75 (17); HRMS
6.57 (d, J¼8.9 Hz, 2H), 6.76 (d, J¼5.5 Hz, 1H), 7.00 (d, J¼8.9 Hz, 2H),
7.26e7.35 (m, 4H), 7.54e7.57 (m, 2H), 9.75 (s, 1H, NH); 13C NMR
(62.9 MHz, CDCl3):
d
¼12.5, 44.5, 87.6, 90.7, 112.4, 115.0, 117.6, 120.7,

3172
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
124.4, 128.5, 128.6, 130.1, 132.7, 136.2, 145.6, 155.0, 168.8; GCeMS
(EI, 70 eV): m/z (%)¼374 (Mþ, 83), 359 (100), 329 (13), 302 (17), 272
(4), 226 (3), 180 (3), 137 (4); HRMS (ESI): calcd for C23H22N2OS
C
21H17NOS (MþH) 332.11030, found 332.11020; IR (ATR, cmꢃ1):
n
¼3116 (w), 3052 (w), 2919 (w), 1597 (s), 1480 (m), 1435 (w), 1385
(w), 1312 (w), 1274 (w), 1112 (m), 1010 (m), 1046 (m), 834 (m), 700
(s).
374.14474, found 374.14445; IR (ATR, cmꢃ1):
n
¼3276 (w), 3078 (w),
2968 (m), 2927 (w), 2868 (w), 2198 (s), 1611 (m), 1566 (s), 1517 (s),
1488 (m), 1443 (w), 1381 (s), 1264 (s), 1235 (w), 1196 (m), 1154 (m),
1094 (w), 1076 (w), 1025 (w), 1011 (w), 979 (m), 919 (w), 852 (w),
802 (w), 761 (m).
6.10. 4-(4-Methoxyphenyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3d)
Yellow solid, yield 78%, mp 210e212 ꢀC. 1H NMR (300 MHz,
6.6. 1-(3-Bromothiophen-2-yl)-3-(3,5-
dimethylphenylamino)-3-phenylprop-2-en-1-one (2h)
CDCl3):
d
¼3.70 (s, 3H, MeO), 6.34 (s, 1H), 6.53 (d, J¼5.5 Hz, 1H), 6.75
(d, J¼9.0 Hz, 2H), 7.00 (d, J¼9.0 Hz, 2H), 7.07e7.20 (m, 5H), 7.46 (d,
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼55.4, 113.4, 114.5,
d
Yellow oil, yield 65%, 1H NMR (250 MHz, CDCl3):
d¼2.02 (s, 6H,
119.0, 128.0, 128.5, 128.7, 129.4, 129.6, 131.3, 132.8, 134.8, 147.0,
152.0, 159.4, 173.8; GCeMS (EI, 70 eV): m/z (%)¼333 (Mþ, 100), 305
(14), 290 (10), 260 (4), 216 (6), 188 (9), 160 (8), 134 (4), 116 (3), 102
(5); HRMS (ESI): calcd for C20H15NO2S (MþH) 334.08963, found
2Me), 6.26 (s, 1H), 6.29e6.31 (m, 2H), 6.53e6.55 (m, 1H), 6.96 (d,
J¼5.2 Hz, 1H), 7.21e7.34 (m, 6H), 12.58 (s, 1H, NH); 13C NMR
(62.9 MHz, CDCl3):
d
¼21.1, 98.0, 110.3, 121.0, 126.1, 128.3, 128.4,
129.3, 129.8, 133.0, 135.6, 138.3, 138.8, 140.6, 162.1, 180.8; GCeMS
(EI, 70 eV): m/z (%)¼413 (Mþ, 81Br, 15), 411 (Mþ, 79Br, 15), 396 (16),
332 (35), 250 (10), 222 (100), 207 (25), 189 (13), 103 (5), 77 (11);
HRMS (ESI): calcd for C21H1879BrNOS (MþH) 412.03652, found
412.03621 and calcd for C21H1881BrNOS (MþH) 414.03462, found
334.09029; IR (ATR, cmꢃ1):
n
¼3100 (w), 3047 (w), 3011 (w), 2962
(w), 2836 (w), 1599 (s), 1577 (m), 1505 (s), 1478 (s), 1381 (m), 1317
(w), 1297 (m), 1240 (s), 1176 (m), 1104 (m), 1075 (w), 1067 (w), 1046
(m), 1022 (m), 1011 (m), 973 (w), 946 (w), 919 (m), 881 (w), 833 (s),
754 (s).
414.03422; IR (ATR, cmꢃ1):
n
¼3101 (w), 3087 (w), 2915 (w), 1602
(w), 1581 (m), 1538 (s), 1513 (w), 1481 (m), 1443 (w), 1408 (s), 1347
(w), 1308 (s), 1278 (w), 1254 (m), 1205 (m), 1170 (m), 1113 (w), 1085
(w), 1024 (w), 996 (m), 948 (w), 897 (w), 870 (m), 852 (s).
6.11. 4-(4-Ethoxyphenyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3e)
Yellow solid, yield 82%, mp 182e184 ꢀC. 1H NMR (300 MHz,
6.7. 4,5-Diphenylthieno[3,2-b]pyridin-7(4H)-one (3a)
CDCl3):
d
¼1.31 (t, J¼7.0 Hz, 3H, Me), 3.91 (q, J¼7.0 Hz, 2H, CH2O),
6.36 (s, 1H), 6.54 (d, J¼5.5 Hz, 1H), 6.73 (d, J¼8.9 Hz, 2H), 7.0 (d,
Yellow solid, yield 78%, mp 233e235 ꢀC. 1H NMR (300 MHz,
J¼9.0 Hz, 2H), 7.07e7.16 (m, 5H), 7.46 (d, J¼5.5 Hz, 1H); 13C NMR
CDCl3):
d
¼6.35 (s, 1H), 6.52 (d, J¼5.5 Hz, 1H), 7.06e7.14 (m, 7H),
(62.9 MHz, CDCl3):
d
¼13.6, 62.7, 112.3, 113.9, 118.0, 127.0, 127.4,
7.20e7.30 (m, 3H), 7.46 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
127.6, 128.3, 128.5, 130.3, 131.6, 133.7, 146.0, 151.0, 157.9, 172.8;
GCeMS (EI, 70 eV): m/z (%)¼347 (Mþ, 100), 319 (12), 318 (10), 216
(10), 188 (6); HRMS (ESI): calcd for C21H17NO2S (MþH) 348.10528,
CDCl3):
d
¼113.4, 118.9, 128.0, 128.3, 128.6, 128.7, 129.0, 129.4, 129.5,
131.4, 134.6, 140.1, 146.5, 151.7, 173.8; GCeMS (EI, 70 eV): m/z (%)¼
303 (Mþ, 100), 275 (43), 241 (4), 171 (16), 136 (3), 121 (6), 102 (4), 77
(8); HRMS (ESI): calcd for C19H13NOS (MþH) 304.07906, found
found 348.10526; IR (ATR, cmꢃ1):
n
¼3099 (w), 3052 (w), 2973 (w),
2928 (w), 1606 (m),1588 (m),1509 (m), 1474 (s),1442 (w),1379 (m),
1234 (m), 1177 (w), 1105 (w), 1046 (m), 842 (m), 756 (s), 703 (s).
304.07893; IR (ATR, cmꢃ1):
n
¼3108 (w), 3039 (w), 2917 (w), 2850
(w), 1609 (m), 1591 (s), 1574 (m), 1513 (w), 1480 (s), 1451 (m), 1442
(m), 1423 (w), 1384 (m), 1312 (m), 1276 (m), 1249 (m), 1185 (m),
1158 (m), 1113 (m), 1099 (m), 1067 (m), 1049 (m), 1026 (m), 998 (w),
978 (w), 930 (m), 876 (w), 853 (w), 829 (m), 754 (s).
6.12. 4-(2,4-Dimethoxyphenyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3f)
Yellow gel, yield 70%. 1H NMR (300 MHz, CDCl3):
d¼2.75 (s, 3H,
6.8. 5-Phenyl-4-p-tolylthieno[3,2-b]pyridin-7(4H)-one (3b)
Yellow solid, yield 80%, mp 203e205 ꢀC. 1H NMR (300 MHz,
MeO), 3.59 (s, 3H, MeO), 6.35 (d, J¼2.6 Hz, 1H), 6.39 (dd, J¼8.4,
2.6 Hz,1H), 6.40 (s, 1H), 6.53 (d, J¼5.5 Hz, 1H), 7.02 (d, J¼8.6 Hz, 1H),
7.16e7.22 (m, 5H), 7.50 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
CDCl3):
d
¼2.23 (s, 3H, Me), 6.35 (s, 1H), 6.52 (d, J¼5.5 Hz, 1H), 6.95
CDCl3):
d
¼55.4, 55.5, 99.2, 104.6, 113.0, 118.9, 121.9, 127.7, 128.3,
(d, J¼8.4 Hz, 2H), 7.04 (d, J¼8.1 Hz, 2H), 7.07e7.15 (m, 5H), 7.44 (d,
128.7, 130.1, 131.2, 134.9, 147.1, 152.9, 155.5, 161.3, 171.0, 174.1;
GCeMS (EI, 70 eV): m/z (%)¼363 (Mþ, 100), 335 (8), 320 (4), 304 (3),
289 (3), 276 (4), 260 (5), 218 (3), 175 (4), 130 (5); HRMS (ESI): calcd
for C21H17NO3S (MþH) 364.10019, found 364.10074; IR (ATR, cmꢃ1):
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼21.1, 113.4, 119.0,
d
128.0,128.2,128.5,128.7,129.3,130.1,131.3,134.7,137.5,139.0,146.7,
151.8, 173.8; GCeMS (EI, 70 eV): m/z (%)¼317 (Mþ, 100), 289 (33),
273 (6), 214 (5), 186 (7), 171 (12), 137 (4), 102 (5); HRMS (ESI): calcd
for C20H15NOS (MþH) 318.09471, found 318.09493; IR (ATR, cmꢃ1):
n
¼3057 (w), 3004 (w), 2935 (w), 2837 (w), 1732 (w), 1587 (s), 1507
(s), 1476 (s), 1438 (m), 1420 (m), 1384 (m), 1324 (w), 1304 (m), 1280
(m), 1244 (m), 1207 (s), 1159 (m), 1136 (w), 1110 (m), 1067 (w), 1048
(s), 1023 (s), 923 (m), 907 (m), 835 (s).
n
¼3107 (w), 3051 (w), 2918 (w), 2859 (w), 1607 (m), 1599 (s), 1512
(m), 1480 (s), 1441 (m), 1425 (w), 1384 (m), 1313 (m), 1276 (m), 1250
(w), 1185 (w), 1154 (w), 1112 (m), 1100 (m), 1046 (m), 999 (w), 976
(w), 928 (m), 914 (w), 879 (w), 827 (s), 755 (s).
6.13. 5-Phenyl-4-(3,4,5-trimethoxyphenyl)thieno[3,2-b]pyr-
idin-7(4H)-one (3g)
6.9. 4-(4-Ethylphenyl)-5-phenylthieno[3,2-b]pyridin-7(4H)-
one (3c)
Yellow solid, yield 80%, mp 231e232 ꢀC. 1H NMR (300 MHz,
CDCl3):
2H), 6.70 (d, J¼5.5 Hz, 1H), 7.13e7.20 (m, 5H), 7.51 (d, J¼5.5 Hz, 1H);
13C NMR (62.9 MHz, CDCl3):
d
¼3.61 (s, 6H, 2MeO), 3.78 (s, 3H, MeO), 6.34 (s, 1H), 6.36 (s,
Yellow solid, yield 82%, mp 204e206 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.13 (t, J¼7.6 Hz, 3H, Me), 2.56 (q, J¼7.6 Hz, 2H, CH2), 6.50
d¼56.4, 61.0, 106.3, 113.3, 119.0, 128.0,
(s, 1H), 6.57 (d, J¼5.5 Hz, 1H), 6.99 (d, J¼8.4 Hz, 2H), 7.07e7.16 (m,
128.5, 128.9, 129.0, 131.5, 134.8, 135.4, 138.3, 146.4, 151.7, 153.4,
173.6; GCeMS (EI, 70 eV): m/z (%)¼393 (Mþ, 100), 378 (37), 205
(10), 276 (6); HRMS (ESI): calcd for C22H19NO4S (MþH) 394.11070,
7H), 7.51 (d, J¼5.5 Hz,1H); 13C NMR (62.9 MHz, CDCl3):
¼15.1, 28.3,
d
113.2, 119.0, 128.0, 128.2, 128.7, 128.8, 129.4, 129.8, 131.7, 134.6,
137.6, 145.4, 146.9, 152.1, 173.5; GCeMS (EI, 70 eV): m/z (%)¼331
(Mþ, 100), 303 (21), 288 (8), 274 (6); HRMS (ESI): calcd for
found 394.11110; IR (ATR, cmꢃ1):
2928 (w), 2840 (w), 1598 (s), 1578 (s), 1501 (m), 1468 (s), 1442 (w),
n
¼3116 (w), 3058 (w), 2969 (w),

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3173
1417 (s), 1385 (w), 1237 (s), 1178 (w), 1123 (s), 1107 (w), 1010 (m),
842 (m), 773 (m), 756 (s), 702 (s), 695 (s).
(12), 102 (9), 76 (8); HRMS (ESI): calcd for C19H1279BrNOS (MþH)
381.98957, found 381.98951 and calcd for C19H1281BrNOS (MþH)
383.98763, found 383.98752; IR (ATR, cmꢃ1):
n
¼3107 (w), 3050
6.14. 4-(4-(Diethylamino)phenyl)-5-phenylthieno[3,2-b]pyr-
idin-7(4H)-one (3h)
(w), 2917 (w), 2858 (w), 1732 (w), 1609 (m), 1599 (m), 1572 (s), 1515
(w), 1474 (s), 1443 (w), 1418 (w), 1380 (m), 1312 (m), 1277 (w), 1249
(w), 1185 (w), 1138 (w), 1101 (m), 1065 (m), 1048 (m), 1029 (w), 997
(w), 980 (w), 928 (w), 877 (w), 858 (w), 834 (m), 776 (m).
Yellow solid, yield 80%, mp 194e196 ꢀC. 1H NMR (250 MHz,
CDCl3):
d
¼1.06 (t, J¼7.2 Hz, 6H, 2Me), 3.24 (q, J¼7.0 Hz, 4H, 2CH2),
6.38 (s, 1H), 6.43 (d, J¼9.1 Hz, 2H), 6.63 (d, J¼5.5 Hz, 1H), 6.84 (d,
6.18. 4-(4-Nitrophenyl)-5-phenylthieno[3,2-b]pyridin-7(4H)-
one (3l)
J¼9.1 Hz, 2H), 7.11e7.19 (m, 5H, Ph), 7.46 (d, J¼5.5 Hz, 1H); 13C NMR
(62.9 MHz, CDCl3):
d
¼11.3, 43.3, 110.3, 112.2, 118.4, 126.8, 126.9,
127.4, 127.7, 128.0, 128.4, 130.0, 134.1, 146.5, 146.6, 151.4, 172.8;
GCeMS (EI, 70 eV): m/z (%)¼374 (Mþ, 67), 359 (100), 330 (9), 302
(8), 273 (3), 228 (3), 171 (6), 136 (4); HRMS (ESI): calcd for
Yellow solid, yield 86%, mp 210e212 ꢀC. 1H NMR (300 MHz,
CDCl3):
7.36 (d, J¼9.0 Hz, 2H), 7.55 (d, J¼5.5 Hz, 1H), 8.15 (d, J¼9.0 Hz, 2H);
13C NMR (62.9 MHz, CDCl3):
d¼6.41 (s, 1H), 6.54 (d, J¼5.5 Hz, 1H), 7.08e7.22 (m, 5H),
C23H22N2OS 374.14474, found 374.14439; IR (ATR, cmꢃ1):
n
¼3541
d
¼114.0, 118.0, 124.8, 128.5, 128.7,
(w), 3389 (w), 3050 (m), 2963 (m), 2925 (w), 1609 (s), 1591 (s), 1517
(s), 1475 (s), 1444 (w), 1422 (w), 1405 (w), 1377 (m), 1355 (m), 1317
(m), 1264 (s), 1197 (m), 1156 (m), 1108 (m), 1073 (m), 1048 (s), 1016
(w), 915 (w), 817 (m), 771 (s).
128.9, 129.3, 129.4, 129.9, 132.4, 133.9, 145.4, 147.3, 151.0, 173.6;
GCeMS (EI, 70 eV): m/z (%)¼348 (Mþ, 100), 320 (24), 274 (18), 273
(10), 172 (7); HRMS (ESI): calcd for C19H12N2O3S (MþH) 349.06414,
found 349.06436; IR (ATR, cmꢃ1):
n
¼3088 (w), 3054 (w), 1587 (s),
1574 (s), 1509 (m), 1486 (s), 1474 (s), 1443 (w), 1307 (m), 1103 (w),
1088 (m), 1041 (w), 827 (m), 730 (m), 697 (s).
6.15. 4-(4-Fluorophenyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3i)
6.19. 4-(4-Methylbenzyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3m)
Yellow solid, yield 83%, mp 183e185 ꢀC. 1H NMR (250 MHz,
CDCl3):
d
¼6.33 (s, 1H), 6.51 (d, J¼5.5 Hz, 1H), 6.93e6.98 (m, 2H),
7.06e7.20 (m, 7H), 7.48 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
Yellow solid, yield 90%, mp 237e239 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼113.5, 116.5 (d, J¼23.0 Hz), 128.1, 128.6, 128.9, 129.4,
CDCl3):
d
¼2.23 (s, 3H, Me), 5.11 (s, 2H, CH2), 6.26 (s, 1H), 6.74 (d,
129.6, 130.4 (d, J¼8.8 Hz), 131.6, 134.4, 136.1 (d, J¼3.4 Hz), 146.5,
J¼8.0 Hz, 2H), 6.87 (d, J¼5.5 Hz, 1H), 7.01 (d, J¼7.9 Hz, 2H),
151.7, 162.1 (d, J¼250.6 Hz), 173.8; 19F NMR (282.4 MHz, CDCl3):
7.22e7.36 (m, 5H), 7.51 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
d
¼ꢃ110.7 (s, CF); GCeMS (EI, 70 eV): m/z (%)¼321 (Mþ, 100), 293
CDCl3):
d
¼21.0, 53.5, 113.7, 118.0, 125.4, 128.5, 128.6, 129.6, 129.7,
(40), 259 (3), 219 (4), 189 (10), 171 (8), 139 (4), 121 (4), 102 (4), 95
129.9, 132.0, 132.9, 134.4, 137.6, 145.5, 152.6, 173.6; GCeMS (EI,
70 eV): m/z (%)¼331 (Mþ, 44), 198 (6), 171 (3), 105 (100), 77 (13);
HRMS (ESI): calcd for C21H17NOS (MþH) 332.11036, found
(5); HRMS (ESI): calcd for C19H12FNOS (MþH) 322.06964, found
322.06965; IR (ATR, cmꢃ1):
n
¼3099 (w), 3061 (w), 2921 (w), 2851
(w), 1595 (s), 1574 (m), 1538 (w), 1504 (s), 1477 (s), 1441 (m), 1410
(w), 1380 (m), 1310 (m), 1295 (w), 1274 (w), 1234 (w), 1211 (s), 1151
(m), 1113 (m), 1099 (m), 1066 (m), 1041 (m), 996 (w), 958 (w), 929
(w), 912 (w), 881 (w), 844 (s), 832 (s).
332.11069; IR (ATR, cmꢃ1):
n
¼3107 (w), 3052 (w), 3020 (w), 2920
(w), 2852 (w), 1597 (s), 1567 (m), 1537 (w), 1515 (w), 1498 (s), 1442
(m), 1427 (w), 1416 (w), 1389 (m), 1347 (m), 1311 (m), 1297 (m),
1244 (m), 1224 (w),1208 (m), 1123 (w), 1099 (s),1068 (m), 1034 (w),
998 (w), 969 (m), 920 (m), 858 (w), 831 (s).
6.16. 5-Phenyl-4-(3-trifluoromethylphenyl)thieno[3,2-b]pyr-
idin-7(4H)-one (3j)
6.20. 4-(3-Methoxybenzyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3n)
Yellow solid, yield 81%, mp 250e252 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼6.36 (s, 1H), 6.51 (d, J¼5.5 Hz, 1H), 7.04e7.17 (m, 5H),
Yellow solid, yield 92%, mp 122e124 ꢀC. 1H NMR (300 MHz,
7.35e7.47 (m, 4H), 7.51 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
CDCl3):
d
¼3.63 (s, 3H, MeO), 5.11 (s, 2H, CH2), 6.26 (s, 1H),
CDCl3):
d
¼113.7, 118.3, 123.0 (q, J¼272.8 Hz), 125.8 (m, 2C), 128.2,
6.39e6.34 (m, 1H), 6.42e6.45 (m, 1H), 6.69e6.72 (m, 1H), 6.88 (d,
J¼5.5 Hz, 1H), 7.10e7.15 (m, 1H), 7.23e7.36 (m, 5H), 7.51 (d,
128.8, 129.0, 129.3, 132.0 (q, J¼33.4 Hz), 132.1, 132.2, 132.3, 134.1,
140.6, 145.9, 151.4, 173.8; 19F NMR (282.4 MHz, CDCl3):
d
¼ꢃ62.9 (s,
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼53.6, 55.1, 111.6, 112.8,
d
CF3); GCeMS (EI, 70 eV): m/z (%)¼371 (Mþ, 100), 343 (45), 273 (4),
241 (3), 171 (13), 145 (7), 121 (3); HRMS (ESI): calcd for
C20H12F3NOS (MþH) 372.06645, found 372.06613; IR (ATR, cmꢃ1):
113.7, 117.7, 117.9, 128.5, 128.7, 129.6, 129.8, 130.1, 132.0, 134.3, 137.6,
145.5, 152.5, 160.0, 173.5; GCeMS (EI, 70 eV): m/z (%)¼347 (Mþ, 71),
198 (3), 171 (2), 121 (100), 91 (19), 78 (10), 65 (5); HRMS (ESI): calcd
for C21H17NO2S (MþH) 348.10528, found 348.10534; IR (ATR,
n
¼3107 (w), 3047 (w), 2922 (w), 1606 (s), 1578 (m), 1537 (w), 1516
(w), 1480 (m), 1444 (m), 1379 (m), 1330 (s), 1264 (w), 1250 (w),
1234 (w), 1191 (m), 1169 (m), 1156 (w), 1115 (s), 1095 (s), 1075 (m),
1051 (m), 1001 (w), 980 (w), 938 (w), 920 (m), 878 (w), 859 (w),
837 (m), 811 (m), 779 (s).
cmꢃ1):
n
¼3108 (w), 3057 (w), 2956 (w), 2831 (w), 1738 (w), 1604
(m), 1589 (s), 1516 (w), 1492 (s), 1457 (w), 1434 (m), 1386 (m), 1354
(w),1314 (w),1289 (m),1255 (m),1202 (m),1182 (w),1158 (m),1105
(s),1078 (w),1069 (w),1035 (m), 993 (w), 960 (m), 949 (w), 916 (w),
876 (w), 845 (s).
6.17. 4-(3-Bromophenyl)-5-phenylthieno[3,2-b]pyridin-
7(4H)-one (3k)
6.21. 4-Phenethyl-5-phenylthieno[3,2-b]pyridin-7(4H)-one
(3o)
Yellow solid, yield 78%, mp 206e208 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼6.33 (s, 1H), 6.53 (d, J¼5.5 Hz, 1H), 7.04e7.18 (m, 7H),
Yellow solid, yield 91%, mp 70e72 ꢀC. 1H NMR (300 MHz, CDCl3):
7.28e7.30 (m, 1H), 7.36e7.40 (m, 1H), 7.49 (d, J¼5.5 Hz, 1H); 13C
d
¼2.81 (t, J¼7.5 Hz, 2H, CH2), 4.13 (t, J¼7.5 Hz, 2H, CH2), 6.24 (s, 1H),
NMR (62.9 MHz, CDCl3):
d¼113.6, 118.6, 122.7, 127.4, 128.2, 128.6,
6.64e6.67 (m, 2H), 7.07e7.11 (m, 5H), 7.17 (d, J¼5.5 Hz, 1H),
129.0, 129.3, 130.7, 131.7, 131.8, 132.2, 134.2, 141.1, 146.0, 151.4, 173.7;
GCeMS (EI, 70 eV): m/z (%)¼383 (Mþ, 81Br, 100), 381 (Mþ, 79Br, 97),
355 (37), 300 (6), 273 (13), 241 (4), 200 (6), 171 (20), 137 (11), 120
7.31e7.41 (m, 3H), 7.68 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
CDCl3):
d
¼35.6, 51.5, 113.6, 117.0, 127.0, 128.5, 128.6, 128.7, 128.8,
129.4, 130.0, 132.3, 134.5, 136.5, 144.8, 152.1, 173.3; GCeMS (EI,

3174
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
70 eV): m/z (%)¼240 (Mþ, 100), 331 (44), 138 (18), 241 (17); HRMS
(ESI): calcd for C21H17NOS (MþH) 332.11030, found 332.11020; IR
1158 (m), 1101 (m), 1066 (m), 1041 (m), 1017 (m), 971 (w), 950 (w),
914 (w), 887 (w), 835 (m), 818 (s).
(ATR, cmꢃ1):
n
¼3492 (w), 3053 (w), 1581 (s), 1533 (m), 1493 (m),
1441 (w), 1359 (w), 1304 (w), 1193 (m), 1105 (m), 846 (w), 750 (s),
698 (s).
6.26. 4-(4-Chlorophenyl)-5-p-tolylthieno[3,2-b]pyridin-
7(4H)-one (3t)
Yellow solid, yield 78%, mp 104e106 ꢀC. 1H NMR (300 MHz,
6.22. 4-Cyclohexyl-5-phenylthieno[3,2-b]pyridin-7(4H)-one
(3p)
CDCl3):
d
¼2.19 (s, 3H, Me), 6.30 (s, 1H), 6.50 (d, J¼5.5 Hz, 1H), 6.91
(d, J¼9.1 Hz, 2H), 6.97 (d, J¼9.1 Hz, 2H), 7.04 (d, J¼8.7 Hz, 2H), 7.24
(d, J¼8.7 Hz, 2H), 7.46 (d, J¼5.5 Hz,1H); 13C NMR (62.9 MHz, CDCl3):
Yellow solid, yield 90%, mp 231e233 ꢀC. 1H NMR (300 MHz,
d
¼20.2, 112.5, 115.4, 117.6, 119.1, 127.7, 127.9, 128.2, 128.7, 128.9,
CDCl3):
d
¼0.89e2.24 (m, 10H), 6.13 (s, 1H), 7.25e7.28 (m, 2H),
7.38e7.43 (m, 4H), 7.45 (d, J¼5.6 Hz, 1H), 7.62 (d, J¼5.6 Hz, 1H); 13C
130.7, 133.9, 138.1, 145.2, 150.7, 172.8; GCeMS (EI, 70 eV): m/z (%)¼
353 (Mþ, 37Cl, 36), 351 (Mþ, 35Cl,100), 323 (38), 286 (3), 273 (5), 235
(3), 200 (8), 172 (12), 137 (12), 115 (7); HRMS (ESI): calcd for
C20H14ClNOS (MþH) 353.04846, found 353.04852; IR (ATR, cmꢃ1):
NMR (62.9 MHz, CDCl3):
d¼24.9, 25.9, 30.5, 62.4, 113.4, 119.3, 127.9,
128.8, 129.3, 130.8, 132.3, 136.0, 143.22, 152.8, 173.0; GCeMS (EI,
70 eV): m/z (%)¼309 (Mþ, 48), 227 (100), 199 (14), 171 (4), 154 (3),
96 (3); HRMS (ESI): calcd for C19H19NOS (MþH) 310.12602, found
n
¼3270 (w), 3188 (w), 3033 (w), 2917 (w), 2860 (w), 1731 (w), 1587
310.12561; IR (ATR, cmꢃ1):
n
¼3080 (w), 2932 (w), 2856 (w), 1737
(s), 1506 (m), 1475 (s), 1424 (w), 1404 (w), 1377 (m), 1332 (w), 1307
(m), 1271 (w), 1251 (w), 1242 (w), 1184 (w), 1171 (w), 1089 (m), 1067
(w), 1041 (m), 1014 (m), 947 (w), 914 (w), 818 (s).
(w), 1604 (m), 1592 (s), 1538 (w), 1511 (w), 1481 (s), 1447 (m), 1425
(w), 1389 (m), 1347 (w), 1336 (m), 1308 (m), 1253 (m), 1194 (w),
1175 (m), 1149 (w), 1101 (s), 1067 (m), 1019 (w), 997 (m), 934 (w),
897 (w), 872 (w), 845 (s).
6.27. 4-Phenyl-5-(4-propylphenyl)thieno[3,2-b]pyridin-
7(4H)-one (3u)
6.23. 4-Heptyl-5-phenylthieno[3,2-b]pyridin-7(4H)-one (3q)
Yellow solid, yield 83%, mp 141e143 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼0.75 (t, J¼7.4 Hz, 3H, Me), 1.46 (sext, J¼7.4 Hz, 2H, CH2),
Yellow gel, yield 89%. 1H NMR (300 MHz, CDCl3):
d
¼0.75 (t,
2.39 (t, J¼7.9 Hz, 2H, CH2), 6.35 (s, 1H), 6.51 (d, J¼5.5 Hz, 1H), 6.89
(d, J¼8.3 Hz, 2H), 6.96 (d, J¼8.3 Hz, 2H), 7.05e7.08 (m, 2H),
7.21e7.29 (m, 3H), 7.43 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz,
J¼7.1 Hz, 3H, Me),1.02e1.59 (m, 9H), 3.89 (t, J¼8.0 Hz, 2H, CH2), 6.19
(s, 1H), 7.11 (d, J¼5.5 Hz, 1H), 7.28e7.32 (m, 2H), 7.41e7.43 (m, 3H),
7.67 (d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼12.9, 21.3,
d
CDCl3):
d
¼13.5, 24.0, 37.4, 113.3, 118.9, 128.0, 128.5, 128.6, 128.8,
25.2, 27.4, 28.4, 30.3, 49.3, 112.5, 116.1, 127.6, 127.7, 128.4, 128.8,
129.2, 129.4, 131.2,131.9,140.2,143.4,146.4, 151.8, 173.8; GCeMS (EI,
70 eV): m/z (%)¼345 (Mþ, 100), 317 (12), 288 (49), 272 (3), 254 (2),
201 (3), 172 (4), 136 (3), 115 (3); HRMS (ESI): calcd for C22H19NOS
131.1, 133.7, 144.0, 151.0, 172.2; IR (ATR, cmꢃ1):
(m), 2856 (w), 1737 (w), 1581 (s), 1535 (s), 1493 (m), 1466 (w), 1370
(w), 1299 (w), 1193 (m), 1099 (s), 1019 (w), 845 (m), 768 (s), 703 (s).
n
¼3057 (w), 2921
(MþH) 346.12602, found 346.12579; IR (ATR, cmꢃ1):
¼3120 (w),
n
3050 (w), 2954 (w), 2928 (w), 2856 (w), 1601 (m), 1587 (s), 1520
(w), 1478 (s), 1453 (m), 1410 (m), 1382 (m), 1338 (w), 1312 (m), 1270
(m),1206 (w),1184 (w),1164 (w),1107 (m),1044 (m),1019 (w),1000
(w), 961 (w), 916 (w), 871 (w), 829 (s), 759 (s).
6.24. 4-(4-Methoxyphenyl)-5-p-tolylthieno[3,2-b]pyridin-
7(4H)-one (3r)
Yellow solid, yield 82%, mp 175e177 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼2.20 (s, 3H, Me), 3.73 (s, 3H, MeO), 6.36 (s, 1H), 6.53 (d,
6.28. 4-(3-Fluorophenyl)-5-(4-propylphenyl)thieno[3,2-b]pyr-
idin-7(4H)-one (3v)
J¼5.5 Hz, 1H), 6.76 (d, J¼9.0 Hz, 2H), 6.92e7.02 (m, 6H), 7.46 (d,
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼21.1, 55.4, 113.4, 114.5,
d
Yellow solid, yield 81%, mp 138e140 ꢀC. 1H NMR (300 MHz,
118.9, 128.5, 128.7, 129.2, 129.5, 131.2, 131.9, 133.0, 138.6, 147.0, 152.1,
159.4, 173.9; GCeMS (EI, 70 eV): m/z (%)¼347 (Mþ, 100), 319 (17),
304 (8), 276 (3), 260 (3), 216 (7), 188 (10), 160 (8), 134 (4), 115 (7);
HRMS (ESI): calcd for C21H17NO2S (MþH) 348.10528, found
CDCl3):
d
¼0.75 (t, J¼7.4 Hz, 3H, Me), 1.46 (sext, J¼7.3 Hz, 2H, CH2),
2.40 (t, J¼7.9 Hz, 2H, CH2), 6.31 (s, 1H), 6.53 (d, J¼5.5 Hz, 1H),
6.81e6.85 (m, 1H), 6.90e6.99 (m, 6H), 7.21e7.29 (m, 1H), 7.45 (d,
348.10517; IR (ATR, cmꢃ1):
n
¼3086 (w), 3044 (w), 3005 (w), 2963
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼12.6, 23.0, 36.5, 112.4,
d
(w), 2916 (w), 2838 (w), 1737 (w), 1599 (s), 1585 (m), 1537 (w), 1506
(s), 1478 (m), 1380 (m), 1313 (w), 1297 (m), 1274 (w), 1244 (s), 1176
(m), 1147 (w), 1105 (m), 1068 (w), 1046 (m), 973 (w), 915 (w), 878
(w), 837 (m), 825 (s).
115.8 (d, J¼20.8 Hz), 115.30 (d, J¼23.1 Hz), 117.6, 123.7 (d, J¼3.3 Hz),
127.2, 127.5, 128.1, 129.7 (d, J¼9.0 Hz),130.6 (2C), 140.4 (d, J¼9.6 Hz),
142.7, 145.0, 150.6, 161.5 (d, J¼250.2 Hz), 172.7; 19F NMR
(282.4 MHz, CDCl3):
d¼ꢃ110.0 (s, CF); GCeMS (EI, 70 eV): m/z (%)¼
363 (Mþ, 100), 335 (12), 306 (48), 272 (2), 219 (3), 191 (3), 139 (3),
6.25. 4-(4-Fluorophenyl)-5-p-tolylthieno[3,2-b]pyridin-
7(4H)-one (3s)
115 (5); HRMS (ESI): calcd for C22H18FNOS (MþH) 364.11659, found
364.11671; IR (ATR, cmꢃ1):
n
¼3114 (w), 3033 (w), 2958 (w), 2926
(w), 2869 (w), 1615 (m), 1593 (s), 1524 (w), 1480 (s), 1412 (w), 1377
(m), 1340 (w), 1317 (m), 1285 (w), 1269 (w), 1256 (w), 1242 (w),
1186 (s), 1155 (w), 1100 (m), 1077 (m), 1046 (m), 1005 (w), 975 (w),
910 (w), 876 (m), 835 (s).
Yellow solid, yield 85%, mp 215e217 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼2.15 (s, 3H, Me), 6.28 (s, 1H), 6.48 (d, J¼5.5 Hz, 1H),
6.90e6.98 (m, 6H), 7.08e7.13 (m, 2H), 7.44 (d, J¼5.5 Hz, 1H); 13C
NMR (62.9 MHz, CDCl3):
d
¼21.1, 113.4, 116.5 (d, J¼23.0 Hz), 118.7,
128.4, 128.8, 129.2, 130.4 (d, J¼8.8 Hz), 131.5, 131.6, 136.5 (d,
6.29. 4-(3,5-Dichlorophenyl)-5-(4-propylphenyl)thieno[3,2-b]
pyridin-7(4H)-one (3w)
J¼3.3 Hz), 138.9, 146.4, 151.8, 162.9 (d, J¼250.3 Hz), 173.7; 19F NMR
(282.4 MHz, CDCl3):
d¼ꢃ110.9 (s, CF); GCeMS (EI, 70 eV): m/z (%)¼
335 (Mþ, 100), 307 (41), 291 (5), 219 (6), 190 (6), 171 (4), 146 (5), 115
Yellow solid, yield 85%, mp 80e82 ꢀC. 1H NMR (300 MHz,
(5), 95 (4); HRMS (ESI): calcd for C20H14FNOS (MþH) 336.08529,
CDCl3):
d
¼0.02 (t, J¼7.3 Hz, 3H, Me), 0.74 (sext, J¼7.6 Hz, 2H, CH2),
found 336.08595; IR (ATR, cmꢃ1):
n
¼3116 (w), 3040 (w), 2919 (w),
1.69 (t, J¼7.9 Hz, 2H, CH2), 5.57 (s, 1H), 5.80 (d, J¼5.5 Hz, 1H),
2872 (w), 1603 (m), 1595 (s), 1524 (w), 1495 (m), 1479 (s), 1424 (w),
1415 (w),1384 (m),1315 (m),1276 (w),1254 (w),1214 (m),1184 (m),
6.21e6.23 (m, 4H), 6.26 (d, J¼1.8 Hz, 2H), 7.48 (t, J¼1.8 Hz, 1H), 6.76
(d, J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼13.5, 24.0, 37.5,
d

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3175
113.7, 118.2, 127.4, 128.5, 128.8, 129.1, 129.3, 131.1, 132.0, 135.7, 141.8,
144.1, 145.6, 151.4, 173.8; GCeMS (EI, 70 eV): m/z (%)¼417 (Mþ, 37Cl,
37Cl, 14), 415 (Mþ, 37Cl, 35Cl, 74), 413 (Mþ, 35Cl, 35Cl, 100), 385 (10),
356 (44), 320 (4), 284 (3), 234 (5), 206 (10), 171 (3), 136 (3), 115 (6);
HRMS (ESI): calcd for C22H17Cl2NOS (MþH) 414.04807, found
d
¼51.1, 82.9, 94.2, 121.8, 126.3, 127.3, 127.7, 129.4, 130.8, 131.0, 132.3,
160.8; GCeMS (EI, 70 eV): m/z (%)¼242 (Mþ, 100), 227 (72), 211
(40), 199 (23), 184 (7), 171 (13), 139 (52), 113 (8), 105 (7), 91 (6);
HRMS (ESI): calcd for C14H10O2S 242.03960, found 242.03984; IR
(ATR, cmꢃ1):
n
¼3100 (m), 2951 (w), 1702 (s), 1596 (w), 1571 (w),
414.04721; IR (ATR, cmꢃ1):
n
¼3050 (w), 2958 (w), 2927 (w), 2867
1521 (m), 1505 (w), 1485 (w), 1432 (m), 1408 (m), 1373 (m), 1353
(w), 1288 (m), 1236 (s), 1187 (w), 1097 (m), 1072 (s), 1026 (m), 1003
(w), 994 (m), 934 (m), 878 (m), 845 (m), 784 (s), 755 (s).
(w), 1605 (m), 1568 (s), 1522 (w), 1496 (w), 1475 (m), 1422 (m), 1374
(m), 1338 (w), 1309 (m), 1257 (m), 1202 (w), 1185 (w), 1103 (m),
1061 (s), 1020 (w), 996 (w), 929 (w), 907 (w), 831 (m), 800 (s).
6.34. Methyl 3-(p-tolylethynyl)thiophene-2-carboxylate (4b)
6.30. 5-(4-Methoxyphenyl)-4-p-tolylthieno[3,2-b]pyridin-
7(4H)-one (3x)
Yellow oil, yield 0.177 g, 69%. 1H NMR (300 MHz, CDCl3):
d
¼2.29
(s, 3H, Me), 3.85 (s, 3H, MeO), 7.09 (d, J¼7.9 Hz, 2H), 7.12 (d,
Yellow solid, yield 80%, mp 172e174 ꢀC. 1H NMR (300 MHz,
J¼5.1 Hz, 1H), 7.38 (d, J¼5.2 Hz, 1H), 7.40 (d, J¼8.7 Hz, 2H); 13C NMR
CDCl3):
d
¼2.26 (s, 3H, Me), 3.66 (s, 3H, MeO), 6.33 (s, 1H), 6.52 (d,
(75.4 MHz, CDCl3):
d
¼20.5, 51.1, 82.3, 94.6, 118.8, 126.6, 128.1, 129.3,
J¼5.5 Hz, 1H), 6.63 (d, J¼8.8 Hz, 2H), 6.95 (d, J¼8.3 Hz, 2H), 7.00 (d,
130.7, 131.0, 132.0, 137.9, 160.8; GCeMS (EI, 70 eV): m/z (%)¼256
(Mþ, 100), 241 (79), 225 (27), 213 (28), 197 (6), 185 (9), 169 (5), 139
(5), 112 (9), 98 (6); HRMS (ESI): calcd for C15H12O2S 256.05525,
J¼8.9 Hz, 2H), 7.06 (d, J¼8.0 Hz, 2H), 7.43 (d, J¼5.5 Hz, 1H); 13C NMR
(62.9 MHz, CDCl3):
d
¼21.1, 55.1, 113.3, 113.4, 119.0, 127.0, 128.2,
128.4, 130.1, 130.7, 131.1, 137.7, 138.9, 146.7, 151.7, 159.6, 173.8;
GCeMS (EI, 70 eV): m/z (%)¼347 (Mþ, 100), 332 (3), 319 (18), 304
(13), 260 (5), 214 (7), 186 (8), 152 (3), 130 (4); HRMS (ESI): calcd for
C21H17NO2S (MþH) 348.10528, found 348.10458; IR (ATR, cmꢃ1):
found 256.05572; IR (ATR, cmꢃ1):
n¼3108 (w), 2949 (w), 2206 (w),
1708 (s), 1604 (w),1525 (m),1502 (m), 1429 (m), 1407 (m),1376 (m),
1284 (m), 1231 (s), 1182 (w), 1118 (w), 1094 (m), 1072 (s), 1021 (w),
999 (w), 936 (m), 893 (w), 878 (w), 814 (s), 772 (s).
n
¼3087 (w), 3063 (w), 2932 (w), 2838 (w), 1737 (w), 1590 (s), 1574
(m), 1510 (m), 1473 (m), 1414 (w), 1376 (m), 1312 (m), 1292 (m),
1269 (w), 1248 (s), 1237 (s), 1175 (m), 1151 (w), 1109 (m), 1070 (w),
1042 (m), 1024 (m), 961 (w), 940 (w), 915 (w), 870 (w), 825 (s).
6.35. Methyl 3-(o-tolylethynyl)thiophene-2-carboxylate (4c)
Yellow oil, yield 0.175 g, 68%. 1H NMR (250 MHz, CDCl3):
d
¼2.48
(s, 3H, Me), 3.83 (s, 3H, MeO), 7.08e7.17 (m, 4H), 7.36 (d, J¼5.1 Hz,
6.31. 4-(4-Ethylphenyl)-5-(4-methoxyphenyl)thieno[3,2-b]
pyridin-7(4H)-one (3y)
1H), 7.46 (d, J¼7.6 Hz,1H); 13C NMR (62.9 MHz, CDCl3):
¼20.6, 52.1,
d
87.6, 94.3, 122.6, 125.5, 127.4, 128.8, 129.5, 130.4, 131.3, 132.3, 132.9,
140.6, 161.8; GCeMS (EI, 70 eV): m/z (%)¼256 (Mþ, 43), 241 (43),
224 (56), 213 (100), 195 (46), 184 (19), 165 (8), 152 (44), 139 (8), 127
(8), 112 (14), 98 (8); HRMS (ESI): calcd for C15H12O2S 256.05525,
Yellow gel, yield 79%. 1H NMR (300 MHz, CDCl3):
d
¼1.13 (t,
J¼7.6 Hz, 3H, Me), 2.55 (q, J¼7.6 Hz, 2H, CH2), 3.65 (s, 3H, MeO), 6.33
(s, 1H), 6.53 (d, J¼5.5 Hz, 1H), 6.62 (d, J¼8.9 Hz, 2H), 6.97 (d,
J¼8.4 Hz, 2H), 6.99 (d, J¼8.8 Hz, 2H), 7.08 (d, J¼8.5 Hz, 2H), 7.43 (d,
found 256.05563; IR (ATR, cmꢃ1):
n
¼2948 (w), 2205 (w), 1716 (m),
1694 (s), 1598 (w),1568 (w),1525 (m), 1483 (m),1454 (w),1434 (m),
1409 (m),1376 (m),1298 (m), 1283 (m), 1232 (s),1200 (w),1188 (w),
1158 (w), 1096 (m), 1074 (s), 1001 (m), 938 (m), 878 (w), 848 (m),
819 (w), 754 (s).
J¼5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼15.1, 28.3, 55.1, 113.3,
d
113.4, 119.1, 127.0, 128.3, 128.4, 128.8, 130.7, 131.1, 137.8, 145.1, 146.7,
151.7, 159.6, 173.8; GCeMS (EI, 70 eV): m/z (%)¼361 (Mþ, 100), 333
(16), 318 (15), 289 (3), 273 (2), 260 (6), 214 (11),185 (2); HRMS (ESI):
calcd for C22H19NO2S (MþH) 362.12093, found 362.12142; IR (ATR,
6.36. Methyl 3-((4-propylphenyl)ethynyl)thiophene-2-
carboxylate (4d)
cmꢃ1):
n
¼3041 (w), 2963 (w), 2930 (w), 2836 (w), 1592 (s), 1496
(m), 1473 (s), 1416 (w), 1377 (m), 1311 (w), 1291 (m), 1272 (w), 1246
(s), 1175 (m), 1105 (m), 1066 (w), 1043 (m), 1027 (m), 968 (w), 915
(w), 829 (s).
Yellow oil, yield 0.207 g, 73%. 1H NMR (300 MHz, CDCl3):
d¼0.86
(t, J¼7.4 Hz, 3H, Me), 1.57 (sext, J¼7.6 Hz, 2H, CH2), 2.52 (t, J¼7.8 Hz,
2H, CH2), 3.85 (s, 3H, MeO), 7.09 (d, J¼8.4 Hz, 2H), 7.11 (d, J¼5.2 Hz,
1H), 7.37 (d, J¼5.1 Hz, 1H), 7.42 (d, J¼8.3 Hz, 2H); 13C NMR
6.32. 4-(4-Chlorophenyl)-5-(4-methoxyphenyl)thieno[3,2-b]
pyridin-7(4H)-one (3z)
(75.4 MHz, CDCl3):
d
¼12.7, 23.2, 36.9, 51.1, 82.3, 94.6, 119.0, 127.5,
129.3, 130.2, 130.7, 131.0, 131.9, 142.7, 160.8; GCeMS (EI, 70 eV): m/z
(%)¼284 (Mþ, 83), 269 (11), 255 (100), 240 (33), 184 (9), 170 (8), 152
(10), 139 (8); HRMS (ESI): calcd for C17H16O2S 284.00866, found
Yellow solid, yield 82%, mp 84e86 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼3.68 (s, 3H, MeO), 6.31 (s, 1H), 6.51 (d, J¼5.5 Hz, 1H), 6.66
(d, J¼8.8 Hz, 2H), 6.99 (d, J¼8.8 Hz, 2H), 7.06 (d, J¼8.7 Hz, 2H), 7.26
284.00868; IR (ATR, cmꢃ1):
n
¼2953 (m), 2208 (m), 1697 (s), 1605
(d, J¼8.7 Hz, 2H), 7.47 (d, J¼5.5 Hz,1H); 13C NMR (62.9 MHz, CDCl3):
(w), 1530 (m), 1503 (m), 1434 (s), 1410 (m), 1379 (m), 1353 (w), 1297
(m), 1232 (s), 1188 (w), 1095 (m), 1074 (s), 1019 (w), 1001 (w), 968
(w), 939 (m), 878 (m), 839 (m), 813 (w), 790 (w), 770 (s).
d
¼55.2, 113.5, 113.6, 118.6, 126.6, 128.6, 129.8, 129.9, 130.7, 131.5,
134.8, 138.8, 146.2, 151.4, 159.8, 173.8; GCeMS (EI, 70 eV): m/z (%)¼
369 (Mþ, 37Cl, 39), 367 (Mþ, 35Cl, 100), 339 (20), 324 (18), 289 (2),
260 (10), 235 (7), 200 (11), 172 (12), 152 (4), 130 (4); HRMS (ESI):
calcd for C20H14ClNO2S (MþH) 368.05065, found 368.05043; IR
6.37. Methyl 3-((4-tert-butylphenyl)ethynyl)thiophene-2-
carboxylate (4e)
(ATR, cmꢃ1):
n
¼3087 (w), 3050 (w), 2930 (w), 2836 (w), 1731 (w),
1598 (s), 1587 (m), 1574 (m), 1520 (m), 1474 (s), 1403 (w), 1376 (m),
1312 (m), 1292 (m), 1246 (s), 1175 (m), 1103 (m), 1088 (m), 1067 (w),
1026 (m), 914 (w), 828 (s).
Yellow oil, yield 0.210 g, 70%. 1H NMR (300 MHz, CDCl3):
d
¼1.25
(s, 9H, 3Me), 3.86 (s, 3H, MeO), 7.12 (d, J¼5.1 Hz, 1H), 7.30 (d,
J¼8.6 Hz, 2H), 7.38 (d, J¼5.1 Hz, 1H), 7.44 (d, J¼8.6 Hz, 2H); 13C NMR
(62.9 MHz, CDCl3):
d
¼31.1, 34.8, 83.3, 95.5, 117.1, 119.8, 125.3, 127.2,
6.33. Methyl 3-(phenylethynyl)thiophene-2-carboxylate (4a)
131.5, 132.1, 133.1, 133.5, 152.0, 161.9; GCeMS (EI, 70 eV): m/z (%)¼
298 (Mþ, 45), 283 (100), 251 (16), 240 (6), 179 (7), 139 (6), 112 (12);
HRMS (ESI): calcd for C18H18O2S 298.10220, found 298.10236; IR
Yellow oil, yield 0.175 g, 72%. 1H NMR (300 MHz, CDCl3):
d¼3.85
(s, 3H, MeO), 7.12 (d, J¼5.1 Hz, 1H), 7.26e7.28 (m, 3H), 7.38 (d,
(ATR, cmꢃ1):
n
¼3106 (w), 2954 (m), 2210 (w), 1922 (w), 1805 (w),
J¼5.1 Hz, 1H), 7.49e7.52 (m, 2H); 13C NMR (62.9 MHz, CDCl3):
1702 (s), 1650 (w), 1573 (w), 1528 (m), 1503 (m), 1463 (w), 1434 (s),

3176
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
1409 (m), 1374 (m), 1365 (m), 1354 (w), 1288 (m), 1241 (s), 1188 (w),
1157 (w), 1117 (w), 1099 (m), 1073 (m), 1024 (w), 1015 (w), 970 (w),
905 (w), 879 (m), 846 (w), 830 (m), 784 (s).
6.42. Methyl 3-(hept-1-ynyl)thiophene-2-carboxylate (4j)
Yellow oil, yield 0.131 g, 55%. 1H NMR (300 MHz, CDCl3):
d¼0.85
(t, J¼7.2 Hz, 3H, Me), 1.26e1.41 (m, 4H, 2CH2), 1.58 (quint, J¼7.6 Hz,
2H, CH2), 2.40 (t, J¼7.1 Hz, 2H, CH2), 3.83 (s, MeO), 7.02 (d, J¼5.2 Hz,
6.38. Methyl 3-((4-methoxyphenyl)ethynyl)thiophene-2-
carboxylate (4f)
1H), 7.39 (d, J¼5.2 Hz,1H); 13C NMR (75.4 MHz, CDCl3):
¼13.9,19.7,
d
22.2, 28.2, 29.6, 31.1, 52.2, 117.1, 130.1, 131.2, 132.5, 132.9, 161.2;
GCeMS (EI, 70 eV): m/z (%)¼236 (Mþ, 20), 204 (13), 193 (14), 189
(14), 180 (100), 175 (21), 165 (28), 149 (16), 137 (21), 121 (12), 108
(11), 93 (7); HRMS (ESI): calcd for C13H16O2S 236.08655, found
Yellow oil, yield 0.192 g, 70%. 1H NMR (250 MHz, CDCl3):
d¼3.72
(s, 3H, MeO), 3.83 (s, 3H, MeO), 6.78 (d, J¼8.9 Hz, 2H), 7.08 (d,
J¼5.1 Hz, 1H), 7.35 (d, J¼5.1 Hz, 1H), 7.43 (d, J¼8.9 Hz, 2H); 13C NMR
236.08722; IR (ATR, cmꢃ1):
(w), 1505 (m), 1434 (s), 1411 (s), 1377 (m), 1352 (m), 1269 (m), 1241
(s), 1189 (w), 1158 (w), 1072 (s), 967 (w), 930 (w), 877 (s), 818 (w),
765 (s).
n
¼2929 (m), 2228 (w), 1720 (s), 1525
(62.9 MHz, CDCl3):
d
¼52.1, 55.2, 82.9, 95.6, 114.0, 114.9, 127.8, 130.4,
131.9, 132.6, 133.3, 160.0, 161.9; GCeMS (EI, 70 eV): m/z (%)¼272
(Mþ, 100), 257 (68), 241 (14), 229 (12), 214 (9), 201 (8), 186 (7), 169
(20), 158 (6), 144 (5), 126 (7); HRMS (ESI): calcd for C15H12O3S
272.05012, found 272.05037; IR (ATR, cmꢃ1):
n
¼3112 (w), 2953 (w),
6.43. 3-(Phenylethynyl)thiophene-2-carboxamide (5a)
2204 (w), 1702 (s), 1650 (w), 1601 (m),1566 (w), 1526 (m), 1503 (m),
1466 (w), 1452 (w), 1434 (s), 1410 (m), 1373 (m), 1292 (m), 1240 (s),
1179 (m), 1170 (m), 1100 (m), 1073 (m), 1023 (m), 935 (w), 905 (w),
931 (s), 783 (s).
White solid, yield 0.080 g, 86%, mp 145e147 ꢀC. 1H NMR
(300 MHz, CDCl3):
d
¼6.46 (s, 2H, NH2), 7.13 (d, J¼5.1 Hz, 1H),
7.29e7.35 (m, 3H), 7.41 (d, J¼5.1 Hz, 1H), 7.44e7.47 (m, 2H); 13C
NMR (62.9 MHz, CDCl3):
d¼83.2, 96.3, 121.3, 121.5, 128.6, 129.4,
6.39. Methyl 3-((4-fluorophenyl)ethynyl)thiophene-2-
carboxylate (4g)
129.9, 131.6, 131.7, 140.4, 163.1; GCeMS (EI, 70 eV): m/z (%)¼227
(Mþ, 100), 211 (19), 198 (14), 171 (18), 139 (37), 113 (8); HRMS (ESI):
calcd for C13H9NOS 227.03994, found 227.03968; IR (ATR, cmꢃ1):
Yellow oil, yield 0.195 g, 75%. 1H NMR (300 MHz, CDCl3):
d
¼3.82
n
¼3428 (m), 3131 (m), 2957 (w), 2208 (w), 1950 (w), 1656 (s), 1599
(s, 3H, MeO), 6.92e6.98 (m, 2H), 7.09 (d, J¼5.1 Hz, 1H), 7.36 (d,
(s), 1518 (w), 1503 (w), 1485 (m), 1469 (w), 1417 (s), 1397 (m), 1350
(m), 1279 (w), 1238 (w), 1170 (m), 1158 (w), 1127 (m), 1103 (w), 1070
(m), 1048 (w), 1029 (m), 1010 (w), 978 (m), 915 (m), 880 (m), 847
(m), 780 (m), 750 (s), 686 (s).
J¼5.2 Hz, 1H), 7.44e7.49 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
d
¼52.1, 83.7, 94.2, 115.7 (d, J¼22.1 Hz), 119.0 (d, J¼3.5 Hz), 127.3,
130.5, 131.9, 133.3, 133.7 (d, J¼8.5 Hz), 161.7, 162.8 (d, J¼250.2 Hz);
19F NMR (282.4 MHz, CDCl3):
d
¼ꢃ110.0 (s, CF); GCeMS (EI, 70 eV):
m/z (%)¼260 (Mþ, 100), 245 (74), 229 (38), 217 (31), 202 (6), 189
6.44. 3-(p-Tolylethynyl)thiophene-2-carboxamide (5b)
(14), 157 (56), 131 (9), 114 (6), 100 (5); HRMS (ESI): calcd for
C14H9FO2S 260.03018, found 260.03069; IR (ATR, cmꢃ1):
n
¼3081
White solid, yield 0.085 g, 88%, mp 143e144 ꢀC. 1H NMR
(m), 2949 (w), 2214 (w), 1711 (s), 1673 (w), 1644 (w), 1633 (w), 1599
(m), 1524 (m), 1501 (s), 1469 (w), 1454 (w), 1433 (s), 1409 (m), 1383
(m), 1303 (s), 1219 (s), 1189 (w), 1156 (m), 1102 (m), 1092 (w), 1080
(s), 1015 (w), 1005 (w), 939 (m), 848 (w), 831 (s), 770 (s).
(300 MHz, CDCl3):
d
¼2.31 (s, 3H, Me), 6.51 (s, 2H, NH2), 6.98 (d,
J¼5.3 Hz, 1H), 7.12 (d, J¼7.8 Hz, 2H), 7.35 (d, J¼8.1 Hz, 2H), 7.41 (d,
J¼5.3 Hz, 1H); 13C NMR (75.4 MHz, CDCl3):
¼21.6, 82.7, 96.7, 110.0,
d
118.4, 121.6, 129.4, 129.9, 131.5, 131.7, 139.9, 163.3; GCeMS (EI,
70 eV): m/z (%)¼241 (Mþ, 100), 226 (17), 212 (21), 198 (5), 185 (5),
171 (8), 112 (5); HRMS (ESI): calcd for C14H11NOS 241.05559, found
6.40. Methyl 3-(pent-1-ynyl)thiophene-2-carboxylate (4h)
241.05621; IR (ATR, cmꢃ1):
n
¼3439 (m), 3143 (m), 2201 (w), 1651
(s), 1594 (s), 1524 (w), 1501 (m), 1462 (w), 1425 (s), 1372 (m), 1349
(m), 1309 (w), 1275 (w), 1240 (w), 1211 (w), 1185 (m), 1160 (w), 1106
(m), 1089 (w), 1044 (w), 975 (m), 877 (m), 817 (s), 774 (s), 709 (s).
Yellow oil, yield 0.104 g, 50%. 1H NMR (300 MHz, CDCl3):
d
¼1.00
(t, J¼7.4 Hz, 3H, Me), 1.59 (sext, J¼7.4 Hz, 2H, CH2), 2.39 (t, J¼7.0 Hz,
2H, CH2), 3.81 (s, 3H, MeO), 7.00 (d, J¼5.1 Hz, 1H), 7.32 (d, J¼5.1 Hz,
1H); 13C NMR (75.4 MHz, CDCl3):
d
¼13.5, 21.7, 22.0, 52.0, 75.3, 97.1,
6.45. 3-(o-Tolylethynyl)thiophene-2-carboxamide (5c)
117.1, 128.4, 130.1, 132.5, 161.9; GCeMS (EI, 70 eV): m/z (%)¼208
(Mþ, 6), 193 (14), 180 (100), 165 (18), 161 (9), 149 (18), 137 (11), 120
(8), 108 (8), 93 (7); HRMS (ESI): calcd for C11H12O2S 208.05525,
White solid, yield 0.080 g, 85%, mp 136e137 ꢀC. 1H NMR
(300 MHz, CDCl3):
d
¼2.43 (s, 3H, Me), 6.24 (s, 2H, NH2), 7.11e7.26
found 208.05515; IR (ATR, cmꢃ1):
n
¼2955 (m), 2229 (w), 1717 (s),
(m, 4H), 7.41e7.43 (m, 2H); 13C NMR (62.9 MHz, CDCl3):
d
¼20.8,
1697 (s), 1524 (m), 1505 (m), 1434 (s), 1410 (s), 1377 (m), 1352 (w),
1337 (w), 1268 (m), 1242 (m), 1221 (s), 1188 (w), 1158 (w), 1072 (s),
1022 (w), 998 (w), 962 (w), 933 (w), 877 (m), 847 (w), 766 (s).
86.9, 95.4, 121.3, 121.6, 125.9, 129.5, 129.8, 130.0, 131.8, 132.1, 140.0,
140.2, 163.0; GCeMS (EI, 70 eV): m/z (%)¼241 (Mþ, 12), 224 (100),
212 (33), 195 (28), 184 (5), 171 (6), 152 (26), 136 (12), 112 (7), 98 (6);
HRMS (ESI): calcd for C14H11NOS (MþH) 242.00634, found
6.41. Methyl 3-(hex-1-ynyl)thiophene-2-carboxylate (4i)
242.06315; IR (ATR, cmꢃ1):
n
¼3423 (s), 3132 (m), 2202 (w), 1657 (s),
1600 (s), 1557 (w), 1538 (w), 1516 (w), 1483 (m), 1450 (m), 1416 (s),
1394 (m),1349 (m),1292 (w),1271 (w),1174 (w),1162 (w),1129 (m),
1100 (m), 1073 (w), 1045 (w), 981 (m), 943 (m), 891 (w), 867 (w),
851 (m), 775 (s), 748 (s), 714 (s).
Yellow oil, yield 0.115 g, 51%. 1H NMR (300 MHz, CDCl3):
d¼0.82
(t, J¼7.2 Hz, 3H, Me), 1.29e1.45 (m, 4H, 2CH2), 2.17 (t, J¼7.1 Hz, 2H,
CH2), 3.82 (s, 3H, MeO), 7.01 (d, J¼5.1 Hz, 1H), 7.39 (d, J¼5.1 Hz, 1H);
13C NMR (75.4 MHz, CDCl3):
d
¼13.4, 18.8, 21.8, 30.3, 52.1, 97.2, 117.1,
130.1, 131.2, 132.4, 132.9, 161.1; GCeMS (EI, 70 eV): m/z (%)¼222
(Mþ, 9), 207 (4), 193 (11), 180 (100), 165 (24), 161 (18), 149 (12), 137
(17), 121 (10), 108 (8), 93 (5); HRMS (ESI): calcd for C12H14O2S
6.46. 3-((4-Propylphenyl)ethynyl)thiophene-2-carboxamide
(5d)
222.07090, found 222.07135; IR (ATR, cmꢃ1):
n
¼2955 (m), 2231
White solid, yield 0.085 g, 90%, mp 158e159 ꢀC. 1H NMR
(w), 1723 (s), 1525 (w), 1506 (m), 1456 (w), 1435 (s), 1411 (s), 1378
(m), 1353 (m), 1317 (w), 1284 (w), 1243 (s), 1189 (w), 1158 (w), 1077
(s), 968 (w), 932 (w), 878 (m), 851 (w), 819 (w), 767 (s).
(300 MHz, CDCl3):
2H, CH2), 2.55 (t, J¼7.9 Hz, 2H, CH2), 5.95 (s, 2H, NH2), 7.12 (d,
J¼5.2 Hz, 1H), 7.13 (d, J¼8.1 Hz, 2H), 7.37 (d, J¼8.2 Hz, 2H), 7.41 (d,
d
¼0.87 (t, J¼7.4 Hz, 3H, Me), 1.58 (sext, J¼7.5 Hz,

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3177
J¼5.1 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
d
¼13.7, 24.2, 37.9, 82.7,
1159 (w), 1131 (w), 1112 (m), 1089 (m), 1060 (w), 1014 (w), 908 (w),
875 (w), 823 (w), 767 (s), 708 (s).
96.6, 118.6, 121.6, 128.8, 129.9, 131.5, 131.6, 140.1, 144.6, 162.9;
GCeMS (EI, 70 eV): m/z (%)¼269 (Mþ, 60), 240 (100), 212 (10), 196
(5), 184 (5), 170 (5), 152 (8), 139 (5); HRMS (ESI): calcd for
6.51. 3-(Hex-1-ynyl)thiophene-2-carboxamide (5i)
C16H15NOS 269.08689, found 269.08756; IR (ATR, cmꢃ1):
n
¼3385
(m), 3154 (m), 2926 (m), 2209 (w), 1632 (s), 1608 (s), 1526 (m), 1497
(m), 1436 (s), 1398 (m), 1353 (m), 1278 (w), 1205 (w), 1186 (w), 1167
(w), 1124 (m), 1087 (m), 1072 (w), 1018 (m), 978 (s), 949 (w), 886
(w), 843 (m), 790 (s), 725 (s).
Colorless oil, yield 0.075 g, 80%. 1H NMR (300 MHz, CDCl3):
d
¼0.88 (t, J¼7.2 Hz, 3H, Me), 1.35 (m, 2H, CH2), 1.65 (quint, J¼7.8 Hz,
2H, CH2), 2.41 (t, J¼7.1 Hz, 2H, CH2), 6.66 (s, 2H, NH2), 7.00 (d,
J¼5.1 Hz, 1H), 7.34 (d, J¼5.1 Hz, 1H); 13C NMR (75.4 MHz, CDCl3):
d
¼13.5, 19.2, 22.0, 30.4, 98.5, 122.3, 129.6, 131.9, 139.6, 163.5;
6.47. 3-((4-tert-Butylphenyl)ethynyl)thiophene-2-
carboxamide (5e)
GCeMS (EI, 70 eV): m/z (%)¼207 (Mþ, 17), 192 (5), 178 (24), 165
(100), 147 (6), 136 (22), 121 (7), 109 (7), 93 (6); HRMS (ESI): calcd for
C11H13NOS 207.07124, found 207.07147; IR (ATR, cmꢃ1):
n
¼3430
White solid, yield 0.079 g, 84%, mp 179e181 ꢀC. 1H NMR
(m), 3159 (m), 2929 (m), 2223 (m), 1652 (s), 1596 (s), 1519 (w), 1455
(w), 1419 (s), 1393 (m), 1348 (m), 1323 (w), 1298 (w), 1239 (w), 1209
(w), 1186 (w), 1132 (w), 1105 (w), 1071 (w), 1050 (w), 1035 (w), 992
(w), 978 (w), 959 (w), 928 (w), 898 (m), 770 (s), 711 (s).
(300 MHz, CDCl3):
d
¼1.25 (s, 9H, 3Me), 6.41 (s, 2H, NH2), 7.12 (d,
J¼5.1 Hz, 1H), 7.33 (d, J¼8.7 Hz, 2H), 7.39 (d, J¼5.1 Hz, 1H), 7.39 (d,
J¼8.6 Hz, 2H); 13C NMR (75.4 MHz, CDCl3):
¼30.0, 33.9, 81.7, 95.6,
d
117.4, 120.5, 124.6, 128.8, 130.3, 130.6, 139.2, 152.0, 162.1; GCeMS
(EI, 70 eV): m/z (%)¼283 (Mþ, 52), 268 (100), 251 (9), 240 (5), 179
(6), 112 (11); HRMS (ESI): calcd for C17H17NOS 283.10254, found
6.52. 3-(Hept-1-ynyl)thiophene-2-carboxamide (5j)
283.10272; IR (ATR, cmꢃ1):
n
¼3443 (m), 3115 (m), 2954 (m), 1658
Colorless oil, yield 0.076 g, 81%. 1H NMR (300 MHz, CDCl3):
(s), 1601 (s), 1552 (w), 1524 (w), 1497 (w), 1462 (w), 1426 (m), 1397
(m),1362 (m),1349 (m),1265 (m),1197 (w),1170 (w),1108 (m),1072
(w), 1016 (m), 981 (m), 946 (w), 850 (w), 834 (s), 777 (s).
d
¼0.83 (t, J¼7.2 Hz, 3H, Me), 1.24e1.37 (m, 4H, 2CH2), 1.54 (quint,
J¼7.6 Hz, 2H, CH2), 2.40 (t, J¼7.2 Hz, 2H, CH2), 6.67 (s, 2H, NH2), 7.00
(d, J¼5.1 Hz, 1H), 7.34 (d, J¼5.1 Hz, 1H); 13C NMR (75.4 MHz, CDCl3):
d
¼12.9,18.5, 21.1, 27.0, 28.6, 30.1, 74.3, 97.5,121.2,128.6,130.9,138.6,
6.48. 3-((4-Methoxyphenyl)ethynyl)thiophene-2-
carboxamide (5f)
162.5; GCeMS (EI, 70 eV): m/z (%)¼221 (Mþ, 28), 206 (5), 192 (10),
178 (39), 165 (100), 152 (7), 141 (8), 136 (25), 120 (9), 109 (9), 93 (6);
HRMS (ESI): calcd for C12H15NOS (MþH) 222.09471, found
White solid, yield 0.077 g, 81%, mp 188e189 ꢀC. 1H NMR
222.09427; IR (ATR, cmꢃ1):
n
¼3431 (m), 3153 (m), 2926 (s), 2223
(300 MHz, CDCl3):
d
¼3.77 (s, 3H, MeO), 6.21 (s, 2H, NH2), 6.84 (d,
(w), 1657 (s), 1597 (s), 1538 (w), 1519 (w), 1455 (w), 1421 (s), 1394
(m), 1347 (m), 1325 (w), 1241 (w), 1110 (w), 1071 (w), 1052 (w), 1022
(w), 975 (w), 889 (w), 862 (w), 770 (s), 707 (s).
J¼8.7 Hz, 2H), 7.11 (d, J¼5.1 Hz, 1H), 7.39 (d, J¼8.8 Hz, 2H), 7.40 (d,
J¼5.1 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
¼55.3, 82.2, 96.6, 113.5,
d
114.3, 121.7, 129.9, 131.6, 133.1, 134.5, 160.5, 163.0; GCeMS (EI,
70 eV): m/z (%)¼257 (Mþ, 100), 242 (82), 214 (15), 186 (10), 169 (12),
154 (5), 144 (5), 136 (5), 126 (5), 115 (6); HRMS (ESI): calcd for
C14H11NO2S (MþH) 258.05833, found 258.05846; IR (ATR, cmꢃ1):
6.53. 5-Phenylthieno[2,3-c]pyridin-7(6H)-one (6a)
White solid, yield 0.075 g, 75%, mp 169e170 ꢀC. 1H NMR
n
¼3425 (m), 3130 (m), 2201 (m), 1657 (s), 1600 (s), 1567 (w), 1558
(300 MHz, CDCl3):
(m, 3H), 7.64e7.67 (m, 2H), 7.67 (d, J¼5.2 Hz, 1H), 10.53 (s, 1H, NH);
13C NMR (75.4 MHz, CDCl3):
d¼6.88 (s, 1H), 7.21 (d, J¼5.2 Hz, 1H), 7.39e7.47
(w),1521 (m),1500 (m),1453 (w),1417 (m),1397 (m),1348 (m),1306
(w), 1293 (m), 1254 (m), 1180 (m), 1149 (w), 1126 (w), 1110 (m), 1070
(w), 1029 (m), 976 (m), 955 (w), 939 (w), 895 (w), 831 (s), 771 (s).
d
¼100.6, 123.6, 125.3, 127.3, 128.2,
128.5, 132.9, 133.1, 140.6, 146.0, 159.0; GCeMS (EI, 70 eV): m/z (%)¼
227 (Mþ, 100), 198 (4), 171 (12), 149 (6), 121 (3), 95 (5); HRMS (ESI):
calcd for C13H9NOS 227.03994, found 227.04038; IR (ATR, cmꢃ1):
6.49. 3-((4-Fluorophenyl)ethynyl)thiophene-2-carboxamide
(5g)
n
¼3143 (w), 2917 (w), 1650 (s), 1613 (w), 1600 (w), 1576 (w), 1558
(w), 1538 (w), 1525 (w), 1498 (s), 1448 (w), 1425 (w), 1355 (w), 1307
(w),1259 (m), 1207 (w), 1185 (m), 1157 (w), 1131 (m), 1095 (w), 1078
(w), 1053 (m), 1029 (w), 967 (w), 920 (w), 905 (w), 879 (m), 832
(m), 810 (s), 759 (s).
White solid, yield 0.076 g, 80%, mp 161e162 ꢀC.1H NMR (300 MHz,
CDCl3):
d
¼6.40 (s, 2H, NH2), 6.99e7.05 (m, 2H), 7.12 (d, J¼5.1 Hz, 1H),
7.42 (d, J¼5.2 Hz,1H), 7.44e7.47 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
d
¼83.0, 95.2,116.0 (d, J¼22.2Hz),117.6(d, J¼3.6 Hz),121.1,130.0,131.7,
133.6 (d, J¼8.6 Hz), 140.4, 163.0, 163.1 (d, J¼251.8 Hz); 19F NMR
6.54. 5-p-Tolylthieno[2,3-c]pyridin-7(6H)-one (6b)
(282.4 MHz, CDCl3):
d
¼ꢃ108.6 (s, CF); IR (ATR, cmꢃ1):
¼3429 (m),
n
3130 (m), 2210 (w), 1893 (w), 1657 (s), 1597 (s), 1556 (w), 1519 (m),
1499 (m), 1469 (w), 1424 (s), 1398 (m), 1349 (m), 1296 (w), 1276 (w),
1220 (m), 1172 (w), 1154 (m), 1127 (w), 1091 (m), 1072 (w), 1014 (m),
979 (m), 957 (w), 943 (w), 880 (w), 849 (m), 932 (s).
White solid, yield 0.077 g, 77%, mp 254e255 ꢀC. 1H NMR
(300 MHz, CDCl3):
3H), 7.49 (d, J¼8.1 Hz, 2H), 7.68 (d, J¼5.1 Hz, 1H), 9.72 (s, 1H, NH);
13C NMR (75.4 MHz, CDCl3):
d¼2.35 (s, 3H, Me), 6.85 (s, 1H), 7.18e7.25 (m,
d
¼21.2, 101.2, 124.7, 126.0, 130.1, 131.2,
134.1, 135.3, 137.1, 139.9, 141.4, 147.2; GCeMS (EI, 70 eV): m/z (%)¼
241 (Mþ, 100), 226 (3), 212 (3), 197 (2), 184 (3), 171 (4), 149 (4), 121
(3), 95 (4); HRMS (ESI): calcd for C14H11NOS (MþH) 242.06341,
6.50. 3-(Pent-1-ynyl)thiophene-2-carboxamide (5h)
Colorless oil, yield 0.080 g, 86%. 1H NMR (300 MHz, CDCl3):
found 242.06378; IR (ATR, cmꢃ1):
n
¼3135 (w), 2914 (w), 1625 (s),
d
¼0.98 (t, J¼7.4 Hz, 3H, Me), 1.59 (sext, J¼7.2 Hz, 2H, CH2), 2.40 (t,
1613 (m), 1568 (w), 1511 (m), 1471 (m), 1453 (w), 1303 (w), 1280
(w), 1185 (m), 1153 (w), 1131 (m), 1109 (w), 1057 (w), 1043 (m), 1020
(w), 935 (w), 892 (m), 852 (m), 830 (m), 805 (s).
J¼7.1 Hz, 2H, CH2), 6.33 (s, 2H, NH2), 7.01 (d, J¼5.1 Hz, 1H), 7.35 (d,
J¼5.1 Hz, 1H); 13C NMR (75.4 MHz, CDCl3):
¼13.6, 21.5, 21.9, 75.5,
d
98.4, 122.3, 129.4, 131.9, 139.6, 163.6; GCeMS (EI, 70 eV): m/z (%)¼
193 (Mþ, 3), 178 (15), 165 (100), 147 (4), 136 (14), 120 (6), 109 (6), 93
(5); HRMS (ESI): calcd for C10H11NOS (MþH) 194.06341, found
6.55. 5-o-Tolylthieno[2,3-c]pyridin-7(6H)-one (6c)
194.06375; IR (ATR, cmꢃ1):
n
¼3456 (s), 3136 (s), 1656 (s), 1597 (s),
White solid, yield 0.077 g, 77%, mp 160e161 ꢀC. 1H NMR
1501 (m), 1462 (w), 1423 (s), 1371 (m), 1350 (m), 1275 (w), 1239 (w),
(250 MHz, CDCl3):
d¼2.31 (s, 3H, Me), 6.59 (s, 1H), 7.21e7.31 (m,

3178
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
5H), 7.70 (d, J¼5.2 Hz, 1H), 9.49 (s, 1H, NH); 13C NMR (62.9 MHz,
146.3, 158.9, 162.6 (d, J¼246.8 Hz); 19F NMR (282.4 MHz, CDCl3):
CDCl3):
d
¼20.0, 29.6, 104.0, 124.5, 126.2, 129.3, 129.6, 130.9, 134.1,
d
¼ꢃ112.3 (s, CF); GCeMS (EI, 70 eV): m/z (%)¼245 (Mþ, 100), 218
134.3, 136.0, 141.4, 146.8, 159.2; GCeMS (EI, 70 eV): m/z (%)¼241
(Mþ, 100), 222 (16), 212 (4), 195 (3), 184 (4), 152 (4), 95 (5); HRMS
(ESI): calcd for C14H11NOS (MþH) 242.06341, found 242.06299; IR
(6), 189 (14), 172 (2), 149 (6), 122 (4), 95 (10); HRMS (ESI): calcd for
C13H8FOS 245.03051, found 245.03040; IR (ATR, cmꢃ1):
n
¼3271 (w),
3146 (w), 3043 (w), 1650 (s), 1615 (m), 1557 (w), 1526 (w), 1506 (s),
1455 (w), 1434 (w), 1424 (w), 1394 (w), 1372 (w), 1360 (w), 1307
(w), 1276 (m), 1221 (s), 1160 (s), 1133 (m), 1107 (m), 1048 (s), 1014
(w), 937 (w), 911 (m), 888 (m), 833 (s).
(ATR, cmꢃ1):
n
¼3451 (w), 3255 (w), 3126 (w), 3017 (w), 2920 (w),
2851 (w), 1608 (s), 1557 (m), 1524 (w), 1487 (w), 1454 (w), 1403
(w), 1370 (w), 1307 (w), 1292 (w), 1276 (w), 1261 (w), 1159 (w),
1131 (m), 1106 (m), 1039 (m), 939 (w), 880 (m), 859 (w), 830 (m),
756 (s), 715 (s).
6.60. 5-Propylthieno[2,3-c]pyridin-7(6H)-one (6h)
6.56. 5-(4-Propylphenyl)thieno[2,3-c]pyridin-7(6H)-one (6d)
White solid, yield 0.072 g, 72%, mp 198e199 ꢀC. 1H NMR
White solid, yield 0.075 g, 75%, mp 95e96 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼0.93 (t, J¼7.4 Hz, 3H, Me), 1.70 (sext, J¼7.3 Hz, 2H, CH2),
2.60 (t, J¼7.7 Hz, 2H, CH2), 6.42 (s,1H), 7.09 (d, J¼5.2 Hz,1H), 7.60 (d,
(250 MHz, CDCl3):
d
¼0.90 (t, J¼7.4 Hz, 3H, Me), 1.61 (sext, J¼7.3 Hz,
J¼5.2 Hz, 1H), 11.99 (s, 1H, NH); 13C NMR (75.4 MHz, CDCl3):
¼13.5,
d
2H, CH2), 2.58 (t, J¼7.9 Hz, 2H, CH2), 6.86 (s, 1H), 7.19 (d, J¼5.2 Hz,
22.0, 35.0, 101.5, 124.1, 126.8, 133.3, 144.2, 147.4, 161.1; GCeMS (EI,
70 eV): m/z (%)¼193 (Mþ, 66), 178 (22), 165 (100), 151 (4), 137 (46),
122 (7), 109 (14), 95 (12), 69 (8); HRMS (ESI): calcd for C10H11NOS
1H), 7.24 (d, J¼8.3 Hz, 2H), 7.58 (d, J¼8.3 Hz, 2H), 7.66 (d, J¼5.2 Hz,
1H), 10.74 (s, 1H, NH); 13C NMR (62.9 MHz, CDCl3):
d
¼13.8, 24.3,
37.7, 101.2, 124.6, 126.2, 127.9, 129.3, 131.4, 133.9, 141.8, 144.5, 147.2,
160.1; GCeMS (EI, 70 eV): m/z (%)¼269 (Mþ, 71), 240 (100), 225 (2),
210 (3), 184 (4), 152 (2); HRMS (ESI): calcd for C16H15NOS
193.05559, found 193.05534; IR (ATR, cmꢃ1):
n¼3130 (w), 3059 (w),
2957 (w), 2866 (w), 2800 (w), 1632 (s), 1557 (w), 1524 (m), 1471
(m),1453 (m),1427 (w),1377 (m),1313 (w),1228 (w),1165 (m),1129
(m), 1077 (m), 1048 (s), 995 (w), 911 (m), 858 (w), 830 (m), 807 (m),
784 (m).
269.08689, found 269.08749; IR (ATR, cmꢃ1):
n
¼3260 (w), 2951
(w), 2866 (w), 1622 (s), 1601 (m), 1564 (w), 1539 (w), 1514 (m), 1464
(w), 1455 (w), 1433 (w), 1423 (w), 1395 (w), 1349 (w), 1306 (w),
1294 (w), 1273 (w), 1187 (m), 1131 (m), 1107 (w), 964 (w), 949 (w),
884 (m), 834 (w), 796 (s).
6.61. 5-Butylthieno[2,3-c]pyridin-7(6H)-one (6i)
White solid, yield 0.073 g, 73%, mp 114e115 ꢀC. 1H NMR
6.57. 5-(4-tert-Butylphenyl)thieno[2,3-c]pyridin-7(6H)-one
(6e)
(300 MHz, CDCl3):
d
¼0.83 (t, J¼7.3 Hz, 3H, Me), 1.35 (m, 2H, CH2),
1.65 (quint, J¼7.8 Hz, 2H, CH2), 2.61 (t, J¼7.8 Hz, 2H, CH2), 6.46 (s,
1H), 7.11 (d, J¼5.1 Hz, 1H), 7.64 (d, J¼5.1 Hz, 1H), 11.32 (s, 1H, NH);
White solid, yield 0.070 g, 70%, mp 246e247 ꢀC. 1H NMR
13C NMR (75.4 MHz, CDCl3):
d
¼13.7, 22.1, 30.8, 30.9, 32.9, 101.9,
(300 MHz, CDCl3):
d
¼1.25 (s, 9H, 3Me), 6.87 (s, 1H), 7.21 (d,
124.1, 133.8, 144.0, 147.6, 160.5; GCeMS (EI, 70 eV): m/z (%)¼207
(Mþ, 47), 192 (4), 178 (11), 165 (100), 137 (24), 122 (8), 109 (7), 95
(8); HRMS (ESI): calcd for C11H13NOS 207.07124, found 207.07176;
J¼5.2 Hz, 1H), 7.45 (d, J¼8.6 Hz, 2H), 7.58 (d, J¼8.6 Hz, 2H), 7.67 (d,
J¼5.1 Hz, 1H), 10.26 (s, 1H, NH); 13C NMR (75.4 MHz, CDCl3):
¼31.2,
d
34.8, 101.3, 124.7, 125.9, 126.3, 131.1, 131.3, 134.0, 141.5, 147.2, 153.0,
159.9; GCeMS (EI, 70 eV): m/z (%)¼283 (Mþ, 65), 268 (100), 252 (4),
240 (12), 210 (3), 120 (11); HRMS (ESI): calcd for C17H17NOS (MþH)
IR (ATR, cmꢃ1):
n
¼3454 (w), 3267 (w), 2957 (m), 2930 (m), 2860
(m), 1615 (s), 1552 (w), 1528 (m), 1463 (m), 1427 (m), 1372 (m), 1326
(w), 1302 (w), 1281 (w), 1259 (w), 1227 (w), 1211 (w), 1167 (m), 1124
(w), 1101 (w), 1087 (m), 1047 (m), 1016 (w), 981 (w), 894 (m), 848
(m), 835 (m), 773 (s), 722 (s).
284.11036, found 284.10983; IR (ATR, cmꢃ1):
n
¼3261 (w), 3139 (w),
3040 (w), 2958 (m), 2865 (w), 1626 (s), 1605 (m), 1562 (w), 1537
(w), 1517 (m), 1461 (m), 1423 (w), 1392 (w), 1361 (m), 1305 (w),
1266 (m), 1201 (w), 1126 (m), 1058 (w), 1042 (m), 1016 (w), 950 (w),
906 (m), 887 (m), 839 (m), 817 (s).
6.62. 5-Pentylthieno[2,3-c]pyridin-7(6H)-one (6j)
White solid, yield 0.070 g, 70%, mp 142e143 ꢀC. 1H NMR
6.58. 5-(4-Methoxyphenyl)thieno[2,3-c]pyridin-7(6H)-one
(6f)
(300 MHz, CDCl3):
d
¼0.83 (t, J¼7.1 Hz, 3H, Me), 1.28e1.33 (m, 4H,
2CH2), 1.67 (quint, J¼7.6 Hz, 2H, CH2), 2.60 (t, J¼7.8 Hz, 2H, CH2),
6.42 (s, 1H), 7.09 (d, J¼5.2 Hz, 1H), 7.60 (d, J¼5.1 Hz, 1H), 11.62 (s, 1H,
White solid, yield 0.076 g, 76%, mp 141e142 ꢀC. 1H NMR
NH); 13C NMR (75.4 MHz, CDCl3):
d¼13.9, 22.3, 28.4, 31.1, 33.2,
(250 MHz, CDCl3):
d
¼3.81 (s, 3H, MeO), 6.87 (s, 1H), 6.96 (d,
101.4, 124.1, 133.4, 133.7, 144.3, 147.4, 160.9; GCeMS (EI, 70 eV): m/z
(%)¼221 (Mþ, 45), 192 (6), 178 (21), 165 (100), 137 (23), 122 (6), 109
(6), 95 (5); HRMS (ESI): calcd for C12H15NOS (MþH) 222.09471,
J¼8.9 Hz, 2H), 7.22 (d, J¼5.2 Hz, 1H), 7.58 (d, J¼6.8 Hz, 2H), 7.71 (d,
J¼5.2 Hz,1H),10.31 (s,1H, NH); 13C NMR (62.9 MHz, CDCl3):
¼55.4,
d
101.4,114.8,124.6,126.2,127.5,134.5,141.3,141.5,147.6,159.6,160.9;
GCeMS (EI, 70 eV): m/z (%)¼257 (Mþ, 100), 242 (24), 214 (21), 187
(5), 128 (3), 115 (7), 95 (4); HRMS (ESI): calcd for C14H11NO2S
found 222.09495; IR (ATR, cmꢃ1):
n
¼3128 (w), 2951 (m), 2853 (m),
1645 (w), 1621 (s), 1529 (m), 1470 (m), 1435 (m), 1386 (w), 1372 (w),
1340 (w), 1316 (w), 1300 (w), 1267 (w), 1241 (w), 1226 (w), 1200
(w), 1169 (m), 1105 (w), 1091 (m), 1049 (m), 1007 (w), 986 (w), 962
(w), 912 (m), 859 (m), 835 (m), 774 (m), 722 (s).
257.05050, found 257.05104; IR (ATR, cmꢃ1):
n
¼3255 (w), 3129 (w),
3071 (w), 2831 (w), 1620 (m), 1604 (s), 1556 (w), 1530 (w), 1514 (s),
1468 (w),1454 (w),1435 (w),1394 (w) 1360 (w),1313 (w),1287 (m),
1248 (s), 1202 (w), 1179 (m), 1133 (m), 1062 (w), 1044 (m), 937 (w),
921 (w), 882 (m), 856 (m), 812 (s).
6.63. 2-(Phenylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
phene-3-carbonitrile (7a)
6.59. 5-(4-Fluorophenyl)thieno[2,3-c]pyridin-7(6H)-one (6g)
White solid, yield 0.075 g, 75%, mp 279e280 ꢀC. 1H NMR
Yellow solid, yield 77%, mp 79e80 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.75e1.80 (m, 4H, 2CH2), 2.58e2.66 (m, 4H, 2CH2),
7.18e7.29 (m, 3H), 7.46e7.49 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
(300 MHz, CDCl3):
J¼5.1 Hz, 1H), 7.79e7.84 (m, 2H), 8.08 (d, J¼5.1 Hz, 1H), 11.76 (s, 1H,
NH); 13C NMR (75.4 MHz, CDCl3):
¼100.9, 115.6 (d, J¼21.7 Hz),
125.2, 127.8, 129.2 (d, J¼8.6 Hz), 130.4 (d, J¼3.1 Hz), 134.3, 140.9,
d
¼7.03 (s, 1H), 7.32e7.37 (m, 2H), 7.42 (d,
d
¼20.8, 21.8, 23.4, 23.9, 79.0, 98.6, 113.2, 113.4, 120.9, 127.4, 128.2,
128.4, 130.6, 135.3, 137.7; GCeMS (EI, 70 eV): m/z (%)¼263 (Mþ,
d
100), 235 (75), 190 (8), 145 (5); HRMS (ESI): calcd for C17H13NS
(MþH) 264.08410, found 264.08450; IR (ATR, cmꢃ1):
¼2923 (s),
n

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3179
2215 (s), 1939 (w), 1596 (w), 1540 (m), 1494 (w), 1436 (m), 1403
6.68. 2-(o-Tolylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
(m), 1349 (w), 1337 (w), 1298 (m), 1260 (w), 1185 (w), 1144 (w),
1109 (m), 1067 (m), 1026 (m), 951 (w), 916 (m), 880 (m), 942 (w),
745 (s), 682 (s).
phene-3-carbonitrile (7f)
Yellow solid, yield 78%, mp 88e89 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.75e1.81 (m, 4H, 2CH2), 2.45 (s, 3H, Me), 2.59e2.67 (m,
4H, 2CH2), 7.07e7.22 (m, 3H), 7.43 (d, J¼7.5 Hz, 1H); 13C NMR
6.64. 2-(p-Tolylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
phene-3-carbonitrile (7b)
(62.9 MHz, CDCl3):
d¼19.7, 20.8, 21.8, 23.4, 23.9, 82.8, 97.7, 113.2,
113.3, 120.7, 124.6, 128.2, 128.6, 128.7, 130.8, 135.3, 137.5, 139.5;
GCeMS (EI, 70 eV): m/z (%)¼277 (Mþ, 100), 262 (5), 249 (40), 221
(5), 216 (6), 189 (5), 115 (7); HRMS (ESI): calcd for C18H15NS
Yellow solid, yield 77%, mp 110e112 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.74e1.80 (m, 4H, 2CH2), 2.29 (s, 3H, Me), 2.58e2.65 (m,
277.09197, found 277.09155; IR (ATR, cmꢃ1):
n
¼2917 (m), 2216 (s),
4H, 2CH2), 7.09 (d, J¼7.9 Hz, 2H), 7.36 (d, J¼8.1 Hz, 2H); 13C NMR
1549 (m), 1494 (w), 1461 (m), 1434 (m), 1402 (w), 1375 (w), 1347
(w), 1336 (w), 1295 (m), 1198 (w), 1181 (w), 1155 (w), 1138 (w),
1093 (m), 1029 (m), 986 (w), 951 (w), 882 (m), 865 (w), 846 (w),
761 (s).
(62.9 MHz, CDCl3):
d
¼21.6, 21.8, 22.8, 24.4, 24.9, 100.0, 114.1, 114.3,
118.8, 129.2, 129.8, 131.1, 136.2, 138.4, 13.9.5; GCeMS (EI, 70 eV): m/z
(%)¼277 (Mþ, 100), 249 (62), 233 (5), 190 (5); HRMS (ESI): calcd for
C18H15NS 277.09197, found 277.09204; IR (ATR, cmꢃ1):
n
¼2931 (s),
2223 (s), 1547 (m), 1512 (w), 1504 (w), 1445 (m), 1403 (w), 1348 (w),
1294 (m),1259 (w), 1240 (w),1178 (w), 1141 (w),1104 (m), 1077 (w),
1041 (w), 1017 (w), 949 (w), 900 (w), 880 (m), 844 (w), 813 (s).
6.69. 2-((4-Fluorophenyl)ethynyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-3-carbonitrile (7g)
Yellow solid, yield 75%, mp 89e91 ꢀC. 1H NMR (300 MHz, CDCl3):
6.65. 2-((4-Propylphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-3-carbonitrile (7c)
d
¼1.75e1.80 (m, 4H, 2CH2), 2.58e2.66 (m, 4H, 2CH2), 6.95e7.01 (m,
2H), 7.44e7.48 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
d
¼21.8, 22.8,
Yellow solid, yield 73%, mp 58e59 ꢀC. 1H NMR (300 MHz, CDCl3):
24.4, 24.9, 79.7, 98.5, 114.2, 114.4, 115.8 (d, J¼22.3 Hz), 118.0 (d,
J¼3.6 Hz), 129.2, 133.7 (d, J¼8.5 Hz), 136.3, 138.8, 163.0 (d,
d
¼0.85 (t, J¼7.4 Hz, 2H, CH2), 1.56 (sext, J¼7.3 Hz, 2H, CH2),
J¼251.4 Hz); 19F NMR (282.4 MHz, CDCl3):
d
¼ꢃ109.0 (s, CF);
1.75e1.79 (m, 4H, 2CH2), 2.53 (t, J¼7.3 Hz, 3H, Me), 2.57e2.64 (m,
4H, 2CH2), 7.08 (d, J¼8.2 Hz, 2H), 7.38 (d, J¼8.2 Hz, 2H); 13C NMR
GCeMS (EI, 70 eV): m/z (%)¼281 (Mþ, 100), 253 (83), 240 (5), 208
(62.9 MHz, CDCl3):
d¼13.7, 21.8, 22.8, 24.2, 24.4, 24.9, 38.0, 79.5,
(8), 163 (7); HRMS (ESI): calcd for C17H12FNS 281.06690, found
281.06701; IR (ATR, cmꢃ1):
1546 (m),1509 (s),1456 (m), 1433 (m), 1348 (w),1335 (w), 1294 (w),
1259 (w), 1233 (s), 1153 (s), 1093 (m), 1025 (w), 985 (w), 950 (w),
879 (m), 833 (s).
n
¼2908 (m), 2221 (s), 1899 (w), 1598 (s),
100.1, 114.1, 114.3, 119.0, 128.6, 129.8, 131.6, 136.2, 138.4, 144.3;
GCeMS (EI, 70 eV): m/z (%)¼305 (Mþ, 94), 276 (100), 260 (5), 248
(23); HRMS (ESI): calcd for C20H19NS 305.12327, found 305.12307;
IR (ATR, cmꢃ1):
n
¼2930 (s), 2221 (s), 1604 (w), 1546 (m), 1513 (w),
1459 (m), 1434 (m), 1401 (w), 1348 (w), 1338 (w), 1293 (m), 1258
(w), 1240 (w), 1188 (w), 1178 (w), 1136 (w), 1104 (m), 1053 (w), 1030
(w), 985 (w), 950 (w), 903 (w), 880 (m), 809 (s).
6.70. 2-(Phenylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
phene-3-carboxamide (8a)
6.66. 2-((4-tert-Butylphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo
[b]thiophene-3-carbonitrile (7d)
White solid, yield 75%, mp 178e179 ꢀC. 1H NMR (300 MHz,
CDCl3):
2.79e2.83 (m, 2H, CH2), 5.75 (s, NH2), 7.28e7.32 (m, 3H),
7.40e7.44 (m, 2H); 13C NMR (75.4 MHz, CDCl3):
d
¼1.69e1.78 (m, 4H, 2CH2), 2.64e2.69 (m, 2H, CH2),
Yellow solid, yield 73%, mp 132e134 ꢀC. 1H NMR (300 MHz,
d
¼22.3, 22.8, 25.3,
CDCl3):
d
¼1.25 (s, 9H, 3Me), 1.75e1.80 (m, 4H, 2CH2), 2.58e2.66 (m,
26.2, 82.0, 98.8, 120.2, 122.0, 128.5, 129.1, 131.3, 136.5, 137.0, 138.8,
165.8; GCeMS (EI, 70 eV): m/z (%)¼281 (Mþ, 100), 266 (20), 253
(11), 234 (5), 225 (6), 202 (6), 176 (6), 105 (6); HRMS (ESI): calcd
for C17H15NOS 281.08689, found 281.08649; IR (ATR, cmꢃ1):
4H, 2CH2), 7.30 (d, J¼8.6 Hz, 2H), 7.41 (d, J¼8.6 Hz, 2H); 13C NMR
(62.9 MHz, CDCl3):
d¼21.8, 22.8, 24.4, 24.9, 31.1, 34.9, 79.5, 100.0,
114.1, 114.3, 118.8, 125.4, 129.8, 131.4, 136.2, 138.3, 152.6; GCeMS (EI,
70 eV): m/z (%)¼319 (Mþ, 57), 304 (100), 276 (14), 261 (5), 235 (5),
138 (5), 124 (10); HRMS (ESI): calcd for C21H21NS 319.13892, found
n
¼3373 (m), 3173 (m), 2932 (m), 1639 (s), 1613 (m), 1573 (w),
1546 (w), 1494 (w), 1470 (m), 1433 (m), 1368 (m), 1331 (w), 1294
(m), 1254 (w), 1180 (w), 1165 (w), 1124 (w), 1097 (w), 1070 (w),
1025 (w), 997 (w), 987 (w), 953 (w), 914 (m), 883 (m), 839 (m),
751 (s).
319.13931; IR (ATR, cmꢃ1):
n
¼2944 (s), 2218 (s), 1909 (w), 1790 (w),
1660 (w), 1603 (w), 1545 (m), 1505 (w), 1456 (m), 1435 (m), 1403
(m), 1361 (m), 1346 (w), 1334 (w), 1294 (m), 1264 (m), 1200 (w),
1135 (w), 1115 (m), 1095 (m), 1013 (m), 950 (m), 899 (w), 878 (m),
831 (s).
6.71. 2-(p-Tolylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
6.67. 2-((4-Methoxyphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo
phene-3-carboxamide (8b)
[b]thiophene-3-carbonitrile (7e)
White solid, yield 77%, mp 209e210 ꢀC. 1H NMR (300 MHz,
Yellow solid, yield 75%, mp 88e90 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.68e1.78 (m, 4H, 2CH2), 2.30 (s, 3H, Me), 2.64e2.68 (m,
CDCl3):
d
¼1.75e1.78 (m, 4H, 2CH2), 2.58e2.65 (m, 4H, 2CH2), 3.75
2H, CH2), 2.79e2.83 (m, 2H, CH2), 5.78 (s, 2H, NH2), 7.10 (d, J¼7.9 Hz,
(s, 3H, MeO), 6.80 (d, J¼8.9 Hz, 2H), 7.41 (d, J¼8.9 Hz, 2H); 13C NMR
2H), 7.31 (d, J¼8.1 Hz, 2H); 13C NMR (62.9 MHz, CDCl3):
¼21.5,
d
(62.9 MHz, CDCl3):
d¼21.8, 22.8, 24.4, 24.9, 55.3, 79.0, 100.0, 113.8,
22.4, 22.8, 25.3, 26.2, 81.4, 99.2, 118.9, 120.6, 129.3, 131.2, 136.1,
137.0, 138.5, 139.4, 165.1; GCeMS (EI, 70 eV): m/z (%)¼295 (Mþ,
100), 280 (18), 267 (8), 252 (5), 239 (6), 203 (7), 176 (5), 139 (5), 119
(9); HRMS (ESI): calcd for C18H17NOS 295.10254, found 295.10273;
113.9, 114.1, 114.4, 133.3, 134.0, 136.1, 138.1, 160.3; GCeMS (EI,
70 eV): m/z (%)¼293 (Mþ, 100), 278 (12), 265 (37), 250 (9), 222 (7);
HRMS (ESI): calcd for C18H15NOS 293.08689, found 293.08751; IR
(ATR, cmꢃ1):
n
¼2950 (m), 2839 (m), 2217 (s), 1600 (s), 1563 (w),
IR (ATR, cmꢃ1):
n
¼3374 (m), 3198 (m), 2921 (m), 1635 (s), 1614 (m),
1547 (m), 1504 (m), 1454 (m), 1439 (m), 1416 (w), 1347 (w), 1334
(w), 1317 (w), 1287 (m), 1249 (s), 1182 (w), 1167 (m), 1103 (m), 1076
(w), 1025 (s), 962 (w), 951 (w), 941 (w), 829 (s).
1546 (w), 1512 (w), 1469 (m), 1431 (m), 1366 (m), 1333 (w), 1294
(w), 1251 (w), 1179 (w), 1162 (w), 1106 (m), 1068 (w), 1021 (w), 952
(w), 941 (w), 878 (w), 833 (w), 812 (s).

3180
V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
6.72. 2-((4-Propylphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo[b]
6.76. 2-((4-Fluorophenyl)ethynyl)-4,5,6,7-tetrahydrobenzo[b]
thiophene-3-carboxamide (8c)
thiophene-3-carboxamide (8g)
White solid, yield 79%, mp 175e177 ꢀC. 1H NMR (300 MHz,
White solid, yield 72%, mp 170e172 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼0.86 (t, J¼7.4 Hz, 3H, Me), 1.57 (sext, J¼7.4 Hz, 2H, CH2),
CDCl3):
2.78e2.82 (m, 2H, CH2), 5.86 (s, 2H, NH2), 6.96e7.02 (m, 2H),
7.38e7.43 (m, 2H); 13C NMR (62.9 MHz, CDCl3):
d
¼1.69e1.78 (m, 4H, 2CH2), 2.64e2.68 (m, 2H, CH2),
1.68e1.78 (m, 4H, 2CH2), 2.53 (q, J¼7.3 Hz, 2H, CH2), 2.64e2.68 (m,
2H, CH2), 2.80e2.84 (m, 2H, CH2), 7.10 (d, J¼8.3 Hz, 2H), 7.33 (d,
d
¼22.3, 22.8, 25.3,
J¼8.3 Hz, 2H); 13C NMR (62.9 MHz, CDCl3):
d¼13.6, 22.4, 22.8, 24.2,
26.1, 81.7, 97.6, 115.9 (d, J¼22.3 Hz), 118.2 (d, J¼3.6 Hz), 119.9, 133.3
25.3, 26.2, 37.9, 81.4, 99.3, 119.1, 120.6, 128.7, 131.2, 136.1, 137.0,
138.5, 144.2, 165.1; GCeMS (EI, 70 eV): m/z (%)¼323 (Mþ, 100), 308
(15), 294 (20), 266 (7), 203 (8), 175 (5), 147 (7); HRMS (ESI): calcd
for C20H21NOS 323.13384, found 323.13322; IR (ATR, cmꢃ1):
(d, J¼8.6 Hz), 136.6, 136.9, 138.9, 163.0 (d, J¼250.9 Hz), 165.1; 19F
NMR (282.4 MHz, CDCl3):
d
¼ꢃ109.2 (s, CF); GCeMS (EI, 70 eV): m/z
(%)¼299 (Mþ, 100), 284 (21), 271 (11), 243 (7), 220 (6), 183 (5), 176
(6), 163 (5), 123 (9); HRMS (ESI): calcd for C17H14FNOS 299.07746,
n
¼3367 (m), 3176 (m), 2926 (m), 1637 (s), 1613 (s), 1546 (w), 1513
found 299.07765; IR (ATR, cmꢃ1):
n
¼3362 (m), 3174 (m), 2932 (m),
(w), 1463 (m), 1433 (m), 1368 (m), 1334 (w), 1295 (m), 1251 (w),
1242 (w), 1178 (w), 1164 (w), 1095 (m), 1017 (w), 950 (w), 878 (w),
837 (m), 809 (m).
1638 (s), 1615 (m), 1598 (m), 1546 (w), 1510 (m), 1468 (m), 1434 (m),
1368 (w), 1334 (w), 1294 (w), 1226 (s), 1180 (w), 1153 (m), 1093 (m),
1012 (w), 951 (w), 879 (w), 830 (s).
6.77. 3-Phenyl-6,7,8,9-tetrahydro[1]benzothieno[3,2-c]pyr-
idin-1(2H)-one (9a)
6.73. 2-((4-tert-Butylphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo
[b]thiophene-3-carboxamide (8d)
White solid, yield 78%, mp 238e240 ꢀC. 1H NMR (300 MHz,
White solid, yield 74%, mp 149e150 ꢀC. 1H NMR (300 MHz,
CDCl3):
3.07e3.08 (m, 2H, CH2), 6.86 (s, 1H), 7.32e7.43 (m, 3H), 7.67e7.71
(m, 2H), 10.97 (s, 1H, NH); 13C NMR (75.4 MHz, CDCl3):
d
¼1.75e1.84 (m, 4H, 2CH2), 2.72e2.75 (m, 2H, CH2),
CDCl3):
d
¼1.25 (s, 9H, 3Me), 1.72e1.75 (m, 4H, 2CH2), 2.60e2.66 (m,
2H, CH2), 2.80e2.82 (m, 2H, CH2), 5.74 (s, 2H, NH2), 7.31 (d,
J¼8.7 Hz, 2H), 7.36 (d, J¼8.7 Hz, 2H); 13C NMR (75.4 MHz, CDCl3):
d¼22.3, 23.0,
25.4, 26.0, 100.5, 126.2, 128.4, 129.1, 129.3, 133.8, 134.0, 135.1, 139.5,
148.4, 160.9; GCeMS (EI, 70 eV): m/z (%)¼281 (Mþ, 100), 266 (5),
253 (29), 225 (9), 210 (3), 190 (4), 165 (3), 152 (2), 140 (3), 117 (2), 90
(4); HRMS (ESI): calcd for C17H15NOS 281.08689, found 281.08734;
d
¼22.4, 22.8, 25.4, 26.3, 31.1, 34.9, 81.4, 99.2, 118.9, 120.6, 125.5,
131.1, 136.2, 137.0, 138.5, 152.6, 165.2; GCeMS (EI, 70 eV): m/z (%)¼
337 (Mþ, 100), 322 (30), 304 (11), 294 (5), 280 (5), 203 (6), 147 (6);
HRMS (ESI): calcd for C21H23NOS (MþH) 338.15731, found
IR (ATR, cmꢃ1):
n
¼3137 (w), 3074 (w), 3022 (w), 2928 (m), 2847
338.15713; IR (ATR, cmꢃ1):
n
¼3452 (m), 3154 (m), 2925 (m), 1665
(w),1688 (m),1633 (s), 1594 (m),1551 (m),1504 (m), 1443 (m),1403
(w), 1361 (w), 1334 (w), 1286 (m), 1230 (m), 1178 (w), 1159 (w), 1147
(w), 1137 (w), 1066 (w), 1035 (w), 994 (m), 966 (w), 948 (w), 912
(m), 829 (m), 756 (s).
(s), 1596 (m), 1537 (w), 1504 (w), 1454 (m), 1415 (m), 1360 (m), 1291
(m),1265 (w), 1250 (m), 1193 (w), 1163 (w),1112 (m),1087 (w), 1025
(w), 1015 (w), 956 (w), 878 (w), 830 (s).
6.74. 2-((4-Methoxyphenyl)ethynyl)-4,5,6,7-tetrahydrobenzo
[b]thiophene-3-carboxamide (8e)
6.78. 3-p-Tolyl-6,7,8,9-tetrahydro[1]benzothieno[3,2-c]pyr-
idin-1(2H)-one (9b)
White solid, yield 77%, mp 212e214 ꢀC. 1H NMR (300 MHz,
White solid, yield 77%, mp 254e256 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.72e1.77 (m, 4H, 2CH2), 2.64e2.67 (m, 2H, CH2),
CDCl3):
d
¼1.80e1.82 (m, 4H, 2CH2), 2.34 (s, 3H, Me), 2.72e2.74 (m,
2.80e2.83 (m, 2H, CH2), 3.76 (s, 3H, MeO), 5.67 (s, 2H, NH2), 6.81 (d,
2H, CH2), 3.06e3.08 (m, 2H, CH2), 6.86 (s, 1H), 7.21 (d, J¼8.2 Hz, 2H),
J¼8.9 Hz, 2H), 7.36 (d, J¼8.9 Hz, 2H); 13C NMR (75.4 MHz, CDCl3):
7.54 (d, J¼8.2 Hz, 2H),10.51 (s, 1H, NH); 13C NMR (75.4 MHz, CDCl3):
d
¼22.4, 22.8, 25.3, 26.3, 55.3, 80.8, 99.2, 114.0, 114.2, 120.8, 132.9,
d
¼24.8, 26.1, 26.8, 29.2, 29.7, 104.7, 129.9, 130.7, 133.7, 134.7, 137.4,
135.9, 137.0, 138.2, 160.3, 165.2; GCeMS (EI, 70 eV): m/z (%)¼311
(Mþ, 100), 296 (18), 283 (11), 268 (11), 156 (4), 121 (4); HRMS (ESI):
calcd for C18H17NO2S (MþH) 312.10528, found 312.10501; IR (ATR,
139.2, 143.6, 143.7, 153.0, 164.9; GCeMS (EI, 70 eV): m/z (%)¼295
(Mþ,100), 280 (6), 267 (21), 252 (6), 239 (6),190 (4),148 (3),133 (2);
HRMS (ESI): calcd for C18H17NOS (MþH) 296.11036, found
cmꢃ1):
n
¼3387 (m), 3177 (m), 2932 (m), 2540 (w), 2203 (w), 1617
296.11088; IR (ATR, cmꢃ1):
n
¼3364 (w), 3138 (w), 3077 (w), 3011
(m), 1601 (s), 1558 (w), 1543 (w), 1512 (m), 1462 (m), 1431 (m), 1369
(w), 1331 (w), 1291 (m), 1249 (s), 1172 (m), 1161 (m), 1098 (m), 1022
(m), 952 (w), 877 (w), 827 (s).
(w), 2915 (m), 2837 (w), 2728 (w), 1687 (m), 1635 (s), 1599 (m),
1564 (w), 1552 (w), 1519 (m), 1445 (w), 1424 (w), 1399 (w), 1360
(w), 1335 (w), 1321 (w), 1286 (m), 1247 (m), 1196 (w), 1171 (w), 1128
(m), 1068 (w), 1038 (w), 993 (m), 965 (w), 937 (w), 881 (m), 837
(w), 817 (m), 786 (s).
6.75. 2-(o-Tolylethynyl)-4,5,6,7-tetrahydrobenzo[b]thio-
phene-3-carboxamide (8f)
6.79. 3-(4-Propylphenyl)-6,7,8,9-tetrahydro[1]benzothieno
[3,2-c]pyridin-1(2H)-one (9c)
White solid, yield 79%, mp 169e170 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.68e1.80 (m, 4H, 2CH2), 2.39 (s, 3H, Me), 2.65e2.69 (m,
2H, CH2), 2.79e2.83 (m, 2H, CH2), 5.83 (s, 2H, NH2), 7.08e7.23 (m,
White solid, yield 80%, mp 228e230 ꢀC. 1H NMR (300 MHz,
3H), 7.38 (d, J¼7.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3):
d¼20.7,
CDCl3):
d
¼0.89 (t, J¼7.4 Hz, 3H, Me), 1.60 (sext, J¼7.4 Hz, 2H, CH2),
22.3, 22.8, 25.3, 26.2, 85.5, 98.1, 120.6, 121.8, 125.7, 128.4, 129.1,
129.7, 131.7, 135.9, 137.0, 138.7, 140.0; GCeMS (EI, 70 eV): m/z (%)¼
295 (Mþ, 100), 278 (48), 267 (10), 250 (16), 234 (12), 221 (10), 202
(10),178 (8),165 (8),139 (10), 119 (10),115 (9); HRMS (ESI): calcd for
1.79e1.81 (m, 4H, 2CH2), 2.57 (t, J¼7.7 Hz, 2H, CH2), 2.73 (m, 2H,
CH2), 3.07 (m, 2H, CH2), 6.82 (s, 1H), 7.20 (d, J¼8.3 Hz, 2H), 7.60 (d,
J¼8.3 Hz, 2H), 11.07 (s, 1H, NH); 13C NMR (75.4 MHz, CDCl3):
¼13.7,
d
22.4, 23.1, 24.3, 25.4, 26.0, 37.7, 100.0, 126.2, 127.1, 129.1, 131.3, 134.0,
134.6, 139.9, 144.1, 148.5, 161.1; GCeMS (EI, 70 eV): m/z (%)¼323
(Mþ, 100), 308 (11), 294 (22), 281 (11), 265 (12), 249 (7), 233 (6),
207 (17), 186 (5), 148 (11); HRMS (ESI): calcd for C20H21NOS
C18H17NOS 295.10254, found 295.10150; IR (ATR, cmꢃ1):
n
¼3363
(m), 3173 (m), 2930 (m), 1635 (s),1614 (m),1547 (w), 1494 (w),1468
(m), 1434 (m), 1368 (m), 1333 (w), 1294 (m), 1272 (w), 1252 (w),
1180 (w), 1166 (w), 1120 (m), 1040 (m), 951 (w), 939 (w), 879 (w),
817 (w), 803 (w), 749 (s).
323.13384, found 323.13353; IR (ATR, cmꢃ1):
n
¼3359 (w), 3255 (w),
3138 (w), 3077 (w), 3013 (w), 2925 (m), 2852 (w), 1683 (w), 1632

V.O. Iaroshenko et al. / Tetrahedron 69 (2013) 3167e3181
3181
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Tolmachev, A. O. Synthesis 2009, 1865e1875; (d) Iaroshenko, V. O.; Wang, Y.;
Zhang, B.; Volochnyuk, D.; Sosnovskikh, V. Y. Synthesis 2009, 2393e2402; (e)
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P. J. Org. Chem. 2011, 2899e2903; (h) Iaroshenko, V. O.; Bunescu, A.;
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P. Eur. J. Med. Chem. 1998, 33, 33e42; (e) Bompart, J.; Giral, L.; Malicorne, G.;
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(s), 1595 (m), 1557 (m), 1517 (m), 1462 (w), 1454 (w), 1434 (m), 1417
(w),1402 (m),1376 (w),1333 (m),1287 (m),1247 (m),1195 (w),1170
(w), 1125 (m), 1093 (w), 1035 (w), 991 (m), 952 (w), 885 (m), 829
(m), 787 (s).
6.80. 3-(4-tert-Butylphenyl)-6,7,8,9-tetrahydro[1]benzo-
thieno[3,2-c]pyridin-1(2H)-one (9d)
White solid, yield 79%, mp 283e285 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.28 (s, 9H, 3Me), 1.75e1.83 (m, 4H, 2CH2), 2.71e2.77 (m,
2H, CH2), 3.06e3.09 (m, 2H, CH2), 6.81 (s,1H), 7.43 (d, J¼8.7 Hz, 2H),
7.55 (d, J¼8.7 Hz, 2H),10.20 (s,1H, NH); 13C NMR (75.4 MHz, CDCl3):
d
¼22.3, 23.0, 25.4, 26.0, 31.2, 34.7, 100.3, 125.7, 126.2, 130.8, 134.0,
134.3, 135.0, 139.4, 148.6, 152.8, 160.9; IR (ATR, cmꢃ1):
n
¼3075 (w),
2931 (m), 2826 (w), 2778 (w), 2715 (w), 2682 (w), 1682 (w), 1622
(s), 1600 (s), 1516 (m), 1462 (w), 1454 (w), 1442 (w), 1427 (w), 1384
(w), 1361 (s), 1268 (m), 1202 (w), 1170 (w), 1134 (w), 1111 (w), 1066
(w), 1018 (w), 993 (m), 967 (m), 902 (m), 824 (w), 838 (s), 801 (s),
773 (s).
6.81. 3-(4-Methoxyphenyl)-6,7,8,9-tetrahydro[1]benzothieno
[3,2-c]pyridin-1(2H)-one (9e)
White solid, yield 73%, mp 265e268 ꢀC. 1H NMR (300 MHz,
CDCl3):
d
¼1.80e1.84 (m, 4H, 2CH2), 2.72e2.76 (m, 2H, CH2),
3.04e3.08 (m, 2H, CH2), 3.8 (s, 3H, CH3), 6.82 (s, 1H), 6.92 (d,
J¼8.6 Hz, 2H), 7.60 (d, J¼8.6 Hz, 2H), 10.67 (s, 1H, NH); GCeMS (EI,
70 eV): m/z (%)¼311 (Mþ, 100), 296 (17), 283 (28), 268 (3), 231 (3),
181 (6), 169 (5), 131 (8), 119 (8); HRMS (ESI): calcd for C18H17NO2S
311.09745, found 311.09732; IR (ATR, cmꢃ1):
n
¼3271 (w), 3134 (w),
3077 (w), 2928 (m), 2832 (w), 1633 (s), 1606 (m), 1567 (m), 1515 (s),
1470 (w), 1451 (m), 1423 (w),1398 (w),1361 (w),1339 (w), 1317 (w),
1285 (m), 1243 (s), 1178 (m), 1138 (m), 1118 (m), 1064 (w), 1028 (m),
993 (m), 938 (w), 879 (m), 851 (w), 806 (s).
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€
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