One-pot synthesis of 2,3-diarylthieno[2,3-b]-, -[2,3-c]- or-[3,2-c]pyridines from the respective aryl(chloropyridinyl)methanones

Article abstract of DOI:10.3987/COM-13-12745

The title three types of 2,3-diarylthienopyridines can be conveniently prepared from the respective aryl(chloropyridinyl)methanones in one-pot. The starting ketones react with sodium sulfide nonahydrate to generate aryl[(sodiosulfanyl)pyridinyl]methanones

Full text of DOI:10.3987/COM-13-12745

HETEROCYCLES, Vol. 87, No. 8, 2013
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HETEROCYCLES, Vol. 87, No. 8, 2013, pp. 1741 - 1748. © 2013ꢀꢀThe Japan Institute of Heterocyclic Chemistry
Received, 15th May, 2013, Accepted, 12th June, 2013, Published online, 19th June, 2013
DOI: 10.3987/COM-13-12745
ONE-POT SYNTHESIS OF 2,3-DIARYLTHIENO[2,3-b]-, -[2,3-c]- OR
-[3,2-c]PYRIDINES FROM THE RESPECTIVE
ARYL(CHLOROPYRIDINYL)METHANONES
Kazuhiro Kobayashi,* Taira Ohmichi, Wataru Miyatani, Kazuhiro
Nakagawa, and Shohei Yuba
Division of Applied Chemistry, Department of Chemistry and Biotechnology,
Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan; E-mail: kkoba@chem.tottori-u.ac.jp
Abstract – The title three types of 2,3-diarylthienopyridines can be conveniently
prepared from the respective aryl(chloropyridinyl)methanones in one-pot. The
starting ketones react with sodium sulfide nonahydrate to generate
aryl[(sodiosulfanyl)pyridinyl]methanones, which are treated successively with
4-(BrCH2)C6H4EWGs and sodium hydride to give rise to the desired products in
generally good yields.
Since thienopyridine derivatives have received much attention because of their significant biological
utilities,1 a number of efficient approaches for their construction have been developed.2,3 We previously
developed a facile one-pot route to 2,3-disubstitued thieno[2,3-b]-, -[2,3-c]- or -[3,2-c]pyridines through
the reaction of aryl(2-, 3-, or 4-halopyridin-3-, 4-, or 3-yl)methanones, respectively, with sodium sulfide
nonahydrate, followed by successive treatment of the resulting corresponding pyridinethiolates with
BrCH2EWGs (EWG = CN, CO2t-Bu, and Bz) and sodium hydride.3a As an extension of this work, we
hoped to develop a route to 2,3-diarylthieno[2,3-b]-, -[2,3-c]- or -[3,2-c]pyridines, since there are, as far
as we are aware, no general methods for their preparation, though some biological active derivatives have
been synthesized.4 We have now describes the results of our investigation, which provide a facile one-pot
route to these 2,3-diarylthienopyridines (5), (7), or (9) from the respective aryl(chloropyridinyl)-
methanones (1), (6), or (8) and 4-(BrCH2)C6H4EWGs (3) (EWG = CN, NO2, CO2t-Bu, and Bz).
(2-Chloropyridin-3-yl)phenylmethanone (1a), prepared by lithiation of commercially available
2-chloropyridne followed by treatment of the resulting 2-chloro-3-lithiopyridine with
N,N-dimethylbenzamide as described previously,3b was initially chosen as the substrate for the present

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one-pot synthesis. As illustrated in Scheme 1, treatment of 1a with sodium sulfide nonahydrate in DMF at
70 ˚C generated phenyl[2-(sodiosulfanyl)pyridin-3-yl]methanone (2a; Ar = Ph), which was allowed to
react with 4-(BrCH2)C6H4EWGs (3) to afford substitution intermediates (4). Cyclization of these
intermediates with an equivalent of sodium hydride proceeded cleanly and smoothly in general to give,
after aqueous workup and the subsequent purification by column chromatography on silica gel, the
corresponding 2,3-diarylthieno[2,3-b]pyridines (5a-d) in yields listed in Table 1, Entries 1–4. The yields
were relatively good in general, while that of the product using 1-bromomethyl-4-nitrobenzene was rather
lower than those of the others (Entry 2); the reaction gave a rather complicated mixture of products. It
should be noted that the sequence using 2-(bromomethyl)benzonitrile resulted in the formation of an
intractable mixture of products. This may be ascribed to the steric crowdedness between 2- and 3-aryl
groups of the expected product. The other three 2,3-diarylthieno[2,3-b]pyridines (5e-g) were similarly
obtained from aryl(2-chloropyridin-3-yl)methanones (1b) and (1c) (Entries 5-7).
Table 1. Preparation of 2,3-Diarylthienopyridines (5), (7), and (9)
Entry
1
1, 6, 8
EWG
CN
5, 7, 9
5a
5b
5c
5d
5e
Yield/%a
77
47
1a (Ar = Ph)
2
3
4
1a
1a
1a
NO2
CO2t-Bu
Bz
69
78
79
46
70
67
65
86
60
82
87
79
5
6
7
8
1b (Ar = p-Tol)
1b
1c (Ar = 4-MeOC6H4)
6
6
8a (Ar = Ph)
8a
8a
CN
NO2
CN
CN
Bz
CN
NO2
Bz
CN
CN
5f
5g
7a
7b
9a
9b
9c
9d
9e
9f
9
10
11
12
13
14
15
8b (Ar = 3-ClC6H4)
8c (Ar = 4-MeOC6H4)
8c
Bz
76
a Yields of isolated products.

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We then tried to prepare 2,3-diarylthieno[2,3-c]pyridines (7) from (3-chloropyridin-4-
yl)phenylmethanone (6). Scheme 2 shows that the reaction of 6 with sodium sulfide nonahydrate required
slightly higher reaction temperature than that of 1, and the resulting sodium thiolate intermediate was
similarly treated with 4-(BrCH2)C6H4EWGs (3) (EWG = CN and Bz) and then sodium hydride as
described for the preparation of 5 to provide the corresponding required products (7a) and (7b) in
somewhat lower yields than those of 5 as can be seen from Table 1, Entries 8 and 9.
The preparation of 2,3-diarylthieno[3,2-c]pyridines (9) from aryl(4-chloropyridin-3-yl)methanone (8) was
also similarly conducted as shown in Scheme 3. Compounds (8) reacted with sodium sulfide nonahydrate
most cleanly at the lowest temperature of the sequences for the preparation of the three types of
2,3-diarylthienopyridines to generate the corresponding sodium thiolate intermediates, of which treatment
with 4-(BrCH2)C6H4EWGs (3) (EWG = CN, NO2, and Bz) and then sodium hydride afforded the desired
products (9) in good yields in general (Table 1, Entries 10–15), though the product (9b) using
1-bromomethyl-4-nitrobenzene was also only moderate-to-fair (Entry 11).
In the present work, we have developed a versatile method that allows access to three types of
2,3-diarylthienopyridines. The operational simplicity, together with readily availability of the starting
materials, makes the present procedure attractive.
EXPERIMENTAL
All melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are
1
uncorrected. IR spectra were recorded with a Perkin–Elmer Spectrum65 FTIR spectrophotometer. H
NMR spectra were recorded in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR
13
spectrometer operating at 500 MHz or a JEOL LA400FT NMR spectrometer operating at 400 MHz. C
NMR spectra were recorded in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR

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spectrometer operating at 125 MHz or a JEOL LA400FT NMR spectrometer operating at 100 MHz.
High-resolution MS spectra (DART, positive) were measured by a Thermo Scientific Exactive
spectrometer. TLC was carried out on Merck Kieselgel 60 PF254. Column chromatography was performed
using WAKO GEL C-200E. All of the organic solvents used in this study were dried over appropriate
drying agents and distilled prior to use.
Starting Materials. Butyllithium was supplied by Asia Lithium Corporation. All other chemicals used in
this study were commercially available.
Aryl(chloropyridinyl)methanones (1), (6), and (8). These compounds were prepared by treating the
respective chlorolithiopyridines5 with N,N-dimethylbenzamides under the conditions reported previously.3
Physical, spectral, and analytical data for new compounds follow.
(2-Chloropyridin-3-yl)(4-methylphenyl)methanone (1b): yield: 56%; a pale-yellow oil; Rf 0.33
(AcOEt–hexane 1:4); IR (neat) 1670, 1604 cm–1; 1H NMR (400 MHz) ! 2.44 (s, 3H), 7.29 (d, J = 7.8 Hz,
2H), 7.38 (dd, J = 7.8, 4.9 Hz, 1H), 7.70 (d, J = 7.8 Hz, 2H), 7.73 (dd, J = 4.9, 2.0 Hz, 1H), 8.54 (dd, J =
4.9, 2.0 Hz, 1H). Anal. Calcd for C13H10ClNO: C, 67.39; H, 4.35; N, 6.05. Found: C, 67.37; H, 4.42; N,
6.08.
(3-Chlorolphenyl)(4-chloropyridin-3-yl)methanone (8b): yield: 58%; a pale-yellow oil; Rf 0.39
(AcOEt–hexane 1:3); IR (neat) 1678 cm–1; 1H NMR (400 MHz) ! 7.39–7.45 (m, 2H), 7.60 (d, J = 9.2 Hz,
1H), 7.64 (d, J = 7.4 Hz, 1H), 7.79 (br s, 1H), 8.60 (s, 1H), 8.65 (d, J = 5.2 Hz, 1H). Anal. Calcd for
C12H7Cl2NO: C, 57.17; H, 2.80; N, 5.56. Found: C, 57.03; H, 2.93; N, 5.54.
General Procedure for the Preparation of 2,3-Diarylthienopyridines (5), (7), and (9). A mixture of 1,
6, or 8 (1.0 mmol) in DMF (6 mL) containing Na2S·9H2O (0.26 g, 1.1 mmol) was heated at 70 ˚C for 1,
80 ˚C for 6, or 60 ˚C for 8 under stirring until consumption of the starting material had been confirmed by
TLC analyses (silica gel; AcOEt–hexane 1:2; ca. 3 h). To the cooled (rt) mixture was added a solution of
4-(BrCH2)C6H4EWG (0.90 mmol) in DMF (2 mL) and the mixture was stirred for 10 min. Then, the
mixture was cooled to 0 ˚C and NaH (60 % in mineral oil; 40 mg, 1.0 mmol) was added in portions. After
5 min, saturated aqueous NH4Cl (15 mL) was added and the mixture was extracted with AcOEt (3 " 10
mL). The combined extracts were washed with brine (2 " 10 mL) and brine (10 mL), dried (Na2SO4), and
concentrated by evaporation. The residue was purified column chromatography on silica gel
(THF–hexane 3:10) to give the desired products.
4-(3-Phenylthieno[2,3-b]pyridin-2-yl)benzonitrile (5a):
a
white solid; mp 176–178 ˚C
1
(hexane–CH2Cl2); IR (KBr) 2226, 1600 cm–1; H NMR (500 MHz) ! 7.27–7.33 (m, 3H), 7.42–7.45 (m,
5H), 7.55 (d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.0 Hz, 1H), 8.61 (d, J = 2.9 Hz, 1H); 13C NMR (125 MHz) !
111.52, 118.45, 120.09, 128.28, 129.14, 129.98, 130.14, 131.19, 132.17, 132.89, 133.71, 134.15, 136.89,
138.40, 147.48, 160.86. HR-MS. Calcd for C20H13N2S (M+H): 313.0799. Found: m/z 313.0781. Anal.

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Calcd for C20H12N2S: C, 76.90; H, 3.87; N, 8.97. Found: C, 77.03; H, 4.15; N, 8.71.
2-(4-Nitrophenyl)-3-phenylthieno[2,3-b]pyridine (5b): a yellow solid; mp 178–181 ˚C (hexane–Et2O);
1
IR (KBr) 1518, 1345 cm–1; H NMR (500 MHz) ! 7.29–7.31 (m, 2H), 7.34 (dd, J = 8.0, 4.6 Hz, 1H),
7.44–7.47 (m, 3H), 7.49 (d, J = 8.6 Hz, 2H), 7.90 (dd, J = 8.0, 1.7 Hz, 1H), 8.12 (d, J = 8.6 Hz, 2H), 8.63
(dd, J = 4.6, 1.7 Hz, 1H);13C NMR (125 MHz) ! 120.19, 123.73, 128.41, 129.23, 130.01, 130.34, 131.33,
133.42, 133.70, 134.18, 136.48, 140.41, 147.09, 147.65, 160.98. HR-MS. Calcd for C19H13N2O2S (M+H):
333.0697. Found: m/z 333.0696. Anal. Calcd for C19H12N2O2S: C, 68.66; H, 3.64; N, 8.43. Found: C,
68.61; H, 3.68; N, 8.29.
1,1-Dimethylethyl 4-(3-Phenylthieno[2,3-b]pyridin-2-yl)benzoate (5c): a pale-yellow solid; mp
201–203 ˚C (hexane–CH2Cl2); IR (KBr) 1712, 1605 cm–1; 1H NMR (400 MHz) ! 1.58 (s, 9H), 7.26–7.30
(m, 3H), 7.37–7.42 (m, 4H), 7.86–7.89 (m, 4H), 8.59 (d, J = 4.6 Hz, 1H); 13C NMR (125 MHz) ! 28.12,
81.17, 119.87, 127.93, 128.95, 129.43, 129.50, 130.09, 130.87, 131.36, 131.93, 134.18, 134.30, 137.70,
138.36, 147.02, 160.89, 165.19. HR-MS. Calcd for C24H22NO2S (M+H): 388.1371. Found: m/z 388.1372.
Anal. Calcd for C24H21NO2S: C, 74.39; H, 5.46; N, 3.61. Found: C, 74.30; H, 5.56; N, 3.46.
Phenyl[4-(3-phenylthieno[2,3-b]pyridin-2-yl)phenyl]methanone (5d): a white solid; mp 182–185 ˚C
1
(hexane–CH2Cl2); IR (KBr) 1654 cm–1; H NMR (500 MHz) ! 7.17–7.23 (m, 3H), 7.31–7.40 (m, 7H),
7.49 (t, J = 7.4 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.80 (dd, J = 8.0, 1.1 Hz, 1H),
8.50 (dd, J = 4.6, 1.1 Hz, 1H);13C NMR (125 MHz) ! 119.92, 128.01, 128.26, 128.99, 129.43, 129.89,
130.05, 130.20, 130.95, 132.19, 132.46, 134.07, 134.31, 136.66, 137.29, 137.79, 138.01, 147.12, 160.85,
195.92. HR-MS. Calcd for C26H18NOS (M+H): 392.1109. Found: m/z 392.1092. Anal. Calcd for
C26H17NOS: C, 79.77; H, 4.38; N, 3.58. Found: C, 79.70; H, 4.28; N, 3.38.
4-[3-(4-Methylphenyl)thieno[2,3-b]pyridin-2-yl]benzonitrile (5e): a pale-yellow solid; mp 176–178 ˚C
(hexane–AcOEt); IR (KBr) 2226, 1603 cm–1; 1H NMR (400 MHz) ! 2.43 (s, 3H), 7.16 (d, J = 7.8 Hz, 2H),
7.25 (d, J = 7.8 Hz, 2H), 7.31 (dd, J = 8.2, 4.4 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.3 Hz, 2H),
13
7.89 (dd, J = 8.2, 1.5 Hz, 1H), 8.61 (dd, J = 4.4, 1.5 Hz, 1H); C NMR (125 MHz) ! 21.31, 111.46,
118.51, 120.04, 129.84, 129.87, 130.14, 130.70, 131.26, 132.17, 132.99, 134.31, 136.60, 138.18, 138.60,
147.42, 160.91. HR-MS. Calcd for C21H15N2S (M+H): 327.0956. Found: m/z 327.0964. Anal. Calcd for
C21H14N2S: C, 77.27; H, 4.32; N, 8.58. Found: C, 77.03; H, 4.37; N, 8.57.
3-(4-Methylphenyl)-2-(4-nitrophenyl)thieno[2,3-b]pyridine (5f): an orange-yellow solid; mp 199–202
˚C (hexane–AcOEt); IR (KBr) 1513, 1346 cm–1; 1H NMR (400 MHz) ! 2.43 (s, 3H), 7.18 (d, J = 7.8 Hz,
2H), 7.25 (d, J = 7.8 Hz, 2H), 7.32 (dd, J = 7.8, 3.9 Hz, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.90 (dd, J = 7.8,
13
1.9 Hz, 1H), 8.13 (d, J = 8.8 Hz, 2H), 8.62 (dd, J = 3.9, 1.9 Hz, 1H); C NMR (125 MHz) ! 21.32,
120.11, 123.70, 129.84, 129.93, 130.30, 130.63, 131.36, 133.49, 134.28, 136.14, 138.31, 140.58, 147.03,
147.58, 160.99. HR-MS. Calcd for C20H15N2O2S (M+H): 347.0854. Found: m/z 347.0839. Anal. Calcd for

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C20H14N2O2S: C, 69.35; H, 4.07; N, 8.09. Found: C, 69.05; H, 4.29; N, 7.99.
4-[3-(4-Methoxyphenyl)thieno[2,3-b]pyridin-2-yl]benzonitrile (5g): a pale-yellow solid; mp 198–201
˚C (hexane–AcOEt); IR (KBr) 2225, 1604 cm–1; 1H NMR (400 MHz) ! 3.87 (s, 3H), 6.98 (d, J = 8.8 Hz,
2H), 7.20 (d, J = 8.8 Hz, 2H), 7.32 (dd, J = 8.3, 4.4 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 8.3 Hz,
2H), 7.89 (dd, J = 8.3, 1.5 Hz, 1H), 8.60 (dd, J = 4.4, 1.5 Hz, 1H);13C NMR (125 MHz) ! 55.31, 111.44,
114.62, 118.51, 120.04, 125.80, 130.13, 131.16 (2C), 131.22, 132.19, 134.35, 136.44, 138.65, 147.42,
159.54, 160.88. HR-MS. Calcd for C21H15N2OS (M+H): 343.0905. Found: m/z 343.0887. Anal. Calcd for
C21H14N2OS: C, 73.66; H, 4.12; N, 8.18. Found: C, 73.64; H, 4.24; N, 8.18.
4-(3-Phenylthieno[2,3-c]pyridin-2-yl)benzonitrile (7a):
a
yellow solid; mp 155–158 ˚C
1
(hexane–CH2Cl2); IR (KBr) 2227 cm–1; H NMR (500 MHz) ! 7.27–7.30 (m, 2H), 7.44–7.46 (m, 5H),
7.51 (dd, J = 5.7, 1.1 Hz, 1H), 7.57 (d, J = 8.6 Hz, 2H), 8.52 (d, J = 5.7 Hz, 1H), 9.19 (d, J = 1.1 Hz, 1H);
13C NMR (125 MHz) ! 112.09, 117.56, 118.29, 128.40, 129.16, 129.96, 130.20, 132.26, 133.21, 134.40,
135.50, 137.99, 142.25, 143.88, 144.44, 145.66. HR-MS. Calcd for C20H13N2S (M+H): 313.0799. Found:
m/z 313.0784. Anal. Calcd for C20H12N2S: C, 76.90; H, 3.87; N, 8.97. Found: C, 76.84; H, 4.07; N, 8.87.
Phenyl[4-(3-phenylthieno[2,3-c]pyridin-2-yl)phenyl]methanone (7b): a pale-yellow solid; mp
179–180 ˚C (hexane–CH2Cl2); IR (KBr) 1658 cm–1; 1H NMR (500 MHz) ! 7.32 (dd, J = 8.0, 1.7 Hz, 2H),
7.39–7.52 (m, 8H), 7.59 (t, J = 7.4 Hz, 1H), 7.73 (d, J = 8.6 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 8.51 (d, J =
5.7 Hz, 1H), 9.18 (s, 1H);13C NMR (125 MHz) ! 117.42, 126.28, 128.14, 128.28, 129.01, 129.47, 129.88,
130.02, 130.23, 132.53, 133.58, 133.71, 135.48, 137.15, 137.31, 143.49, 143.69, 144.31, 145.84, 195.81.
HR-MS. Calcd for C26H18NOS (M+H): 392.1109. Found: m/z 392.1093. Anal. Calcd for C26H17NOS: C,
79.77; H, 4.38; N, 3.58. Found: C, 80.00; H, 4.61; N, 3.29.
4-(3-Phenylthieno[3,2-c]pyridin-2-yl)benzonitrile (9a):
a
white solid; mp 180–182 ˚C
(hexane–CH2Cl2); IR (KBr) 2225, 1602 cm–1; 1H NMR (500 MHz) ! 7.33 (d, J = 7.4 Hz, 2H), 7.42 (d, J =
8.0 Hz, 2H), 7.45–7.47 (m, 3H), 7.56 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 5.7 Hz, 1H), 8.53 (d, J = 5.7 Hz,
1H), 8.90 (s, 1H); 13C NMR (125 MHz) ! 111.76, 116.77, 118.38, 128.53, 129.21, 130.05, 130.12, 132.27,
133.16, 134.37, 136.64, 137.61, 138.05, 143.62, 146.35, 145.39. HR-MS. Calcd for C20H13N2S (M+H):
313.0799. Found: m/z 313.0774. Anal. Calcd for C20H12N2S: C, 76.90; H, 3.87; N, 8.97. Found: C, 76.75;
H, 4.01; N, 8.66.
2-(4-Nitrophenyl)-3-phenylthieno[3,2-c]pyridine (9b):
a
yellow solid; mp 162–165 ˚C
(hexane–CH2Cl2); IR (KBr) 1518, 1345 cm–1; 1H NMR (500 MHz) ! 7.35 (d, J = 7.4 Hz, 2H), 7.46–7.48
(m, 5H), 7.84 (dd, J = 5.7, 1.1 Hz, 1H), 8.13 (d, J = 9.2 Hz, 2H), 8.54 (d, J = 5.7 Hz, 1H), 8.91 (s, 1H);
13C NMR (125 MHz) ! 116.78, 123.79, 128.63 (2C), 129.27, 130.05, 130.29, 133.09, 134.84, 136.61,
139.98, 143.71, 146.45, 146.49, 147.18. HR-MS. Calcd for C19H13N2O2S (M+H): 333.0697. Found: m/z
333.0691. Anal. Calcd for C19H12N2O2S: C, 68.66; H, 3.64; N, 8.43. Found: C, 68.55; H, 3.59; N, 8.46.

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Phenyl[4-(3-phenylthieno[3,2-c]pyridin-2-yl)phenyl]methanone (9c): a white solid; mp 105–108 ˚C
1
(hexane–CH2Cl2); IR (KBr) 1657 cm–1; H NMR (400 MHz) ! 7.36–7.50 (m, 9H), 7.59 (d, J = 7.3 Hz,
1H), 7.73 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.83 (d, J = 5.9 Hz, 1H), 8.52 (d, J = 5.9 Hz, 1H),
8.90 (s, 1H); 13C NMR (125 MHz) ! 116.75, 128.27, 128.30, 129.07, 129.42, 129.91, 130.15, 130.29 (2C),
132.52, 133.55, 133.64, 136.86, 137.29, 137.42, 138.78, 143.31, 146.18, 146.33, 195.89. HR-MS. Calcd
for C26H18NOS (M+H): 392.1109. Found: m/z 392.1123. Anal. Calcd for C26H17NOS: C, 79.77; H, 4.38; N,
3.58. Found: C, 79.56; H, 4.70; N, 3.54.
4-[3-(3-Chlorophenyl)thieno[3,2-c]pyridin-2-yl]benzonitrile (9d): a white solid; mp 190–192 ˚C
(hexane–CH2Cl2); IR (KBr) 2232, 1600 cm–1; 1H NMR (500 MHz) ! 7.20 (d, J = 7.4 Hz, 1H), 7.36–7.43
13
(m, 5H), 7.60 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 5.2 Hz, 1H), 8.55 (d, J = 5.2 Hz, 1H), 8.69 (s, 1H); C
NMR (125 MHz) ! 112.13, 116.80, 118.25, 128.33, 128.78, 130.00, 130.12, 130.50, 132.41, 132.62,
134.99, 135.12, 136.28, 137.55, 138.43, 143.80, 146.08, 146.32. HR-MS. Calcd for C20H12ClN2S (M+H):
347.0409. Found: m/z 347.0425. Anal. Calcd for C20H11ClN2S: C, 69.26; H, 3.20; N, 8.08. Found: C,
69.15; H, 3.23; N, 7.87.
4-[3-(4-Methoxyphenyl)thieno[3,2-c]pyridin-2-yl]benzonitrile (9e): a yellow solid; mp 203–206 ˚C
(hexane–CH2Cl2); IR (KBr) 2225, 1605 cm–1; 1H NMR (400 MHz) ! 3.88 (s, 3H), 6.99 (d, J = 8.8 Hz, 2H),
7.25 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 7.8 Hz, 2H), 7.57 (d, J = 7.8 Hz, 2H), 7.82 (d, J = 4.9 Hz, 1H), 8.52
(d, J = 4.9 Hz, 1H), 8.91 (s, 1H); 13C NMR (125 MHz) ! 55.30, 111.60, 113.97, 114.66, 116.84, 118.42,
125.09, 130.07, 131.21, 132.26, 134.08, 136.79, 137.12, 138.22, 143.43, 146.35, 159.67. HR-MS. Calcd
for C21H15N2OS (M+H): 343.0905. Found: m/z 343.0891. Anal. Calcd for C21H14N2OS: C, 73.66; H, 4.12;
N, 8.18. Found: C, 73.50; H, 4.38; N, 8.08.
Phenyl{4-[3-(4-methoxyphenyl)thieno[3,2-c]pyridin-2-yl]}phenyl}methanone (9f): a yellow solid; mp
1
154–158 ˚C (hexane–CH2Cl2); IR (KBr) 1654 cm–1; H NMR (400 MHz) ! 3.87 (s, 3H), 6.98 (d, J = 7.8
Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.49 (t, J = 7.4 Hz, 2H), 7.59 (t, J = 7.4 Hz,
1H), 7.74 (d, J = 7.8 Hz, 2H), 7.79 (d, J = 7.4 Hz, 2H), 7.82 (d, J = 5.9 Hz, 1H), 8.51 (d, J = 5.9 Hz, 1H),
13
8.91 (s, 1H); C NMR (100 MHz) ! 55.27, 114.55, 116.76, 125.58, 128.32, 129.40, 129.93, 130.32,
131.31, 132.52, 133.36, 136.75, 136.98, 137.32, 137.66, 138.24, 143.28, 146.25, 146.31, 159.50, 195.93.
HR-MS. Calcd for C27H20NO2S (M+H): 422.1214. Found: m/z 422.1202. Anal. Calcd for C27H19NO2S: C,
76.93; H, 4.54; N, 3.32. Found: C, 77.10; H, 4.30; N, 2.99.
ACKNOWLEDGEMENTS
Mrs. Miyuki Tanmatsu of our University is thanked for her assistance in recording mass spectra and
performing combustion analyses.

1748
HETEROCYCLES, Vol. 87, No. 8, 2013
REFERENCES
1. (a) M. A. M. Gad-Elkareem, A. M. Abdel-Fattah, and M. A. A. Elneairy, J. Sulfur Chem., 2011, 32,
273; (b) L. Feng, I. Reynisdóttir, and J. Reynisson, Eur. J. Med. Chem., 2012, 54, 463; (c) M.
Aleksic, R. Nhili, L. Uzelac, I. Jarak, S. Depauw, M.-H. David-Cordonnier, M. Kralj, S. Tomic, and
G. Karminski-Zamola, J. Med. Chem., 2012, 55, 5044; (d) J. Tang, K. E. Lackey, and S. H.
Dickerson, Bioorg. Med. Chem. Lett., 2013, 23, 66; (e) W. Fugel, A. E. Oberholzer, B. Gscholoessl,
R. Dzikowski, N. Pressburger, L. Preu, L. H. Pearl, B. M. Ratin, I. Okun, C. Doerig, S. Kruggel, T.
Lemcke, L. Meijer, and C. Kunick, J. Med. Chem., 2013, 56, 264; (f) U. Le, B. J. Melancon, T. M.
Bridge, P. N. Vinson, T. J. Utley, A. Lamsal, A. L. Rodriguez, D. Venable, D. J. Sheffer, C. K. Jones,
A. L. Blobaum, M. R. Wood, J. S. Daniels, P. J. Conn, C. M. Niswender, C. W. Lindsey, and C. R.
Hopkins, Bioorg. Med. Chem. Lett., 2013, 23, 346. See also pertinent references cited in these papers
and ref. 3c.
2. For recent reports: (a) M. A. Mohamed, J. Heterocycl. Chem., 2012, 49, 200; (b) B. Gao, D. Dong, J.
Zhang, C. Ding, C. Dong, Y. Liang, and R. Zhang, Synthesis, 2012, 201; (c) R. O. Steen, L. J.
Nurkkala, and S. J. Simon, J. Heterocycl. Chem., 2012, 49, 1290; (d) R. K. Chinnagolla, S.
Pimparkar, and M. Jeganmohan, Org. Lett., 2012, 14, 3032; (e) L. Zheng, J. Ju, Y. Bin, and R. Hua,
J. Org. Chem., 2012, 77, 5794; (f) D. Peixoto, A. Begouin, and M.-J. R. P. Queiroz, Tetrahedron,
2012, 68, 7082. See also pertinent references cited in these papers and ref. 3c.
3. (a) K. Kobayashi, T. Kozuki, and H. Konishi, Heterocycles, 2009, 78, 2993; (b) K. Kobayashi, T.
Suzuki, M. Horiuchi, Y. Shiroyama, and H. Konishi, Synthesis, 2011, 2897; (c) K. Kobayashi, T.
Suzuki, and Y. Egara, Helv. Chim. Acta, 2013, 96, 69.
4. (a) C. Willemann, R. Grünert, P. J. Bednarski, and R. Troschütz, Bioorg. Med. Chem., 2009, 17,
4406; (b) D. Cravo, F. Lepifre, S. Hallakou-Bozec, and C. Charon, PCT Int. Appl., 2009, WO
2009124636 (Chem. Abstr., 2009, 151, 470176); (c) D. Chen, K. C. Lee, L. R. Terrell, and R.
Lamont, PCT Int. Appl., 2011, WO 2011075559 (Chem. Abstr., 2011, 155, 123374).
5. G. W. Gribble and M. G. Saulnier, Tetrahedron Lett., 1980, 21, 4137.