Facile and efficient synthesis of a new class of indole-substituted pyridine derivatives via one-pot multicomponent reactions

Article abstract of DOI:10.1055/s-0029-1216873

A new series of indole-containing pyridine derivatives, 4-aryl-6-(1H-indol-3-yl)-2,2￠-bipyridine-5-carbonitriles, were synthesized via one-pot multicomponent reactions of 3-(cyanoacetyl) indoles, aldehydes, heterocyclic ketones, and ammonium acetate. Part

Full text of DOI:10.1055/s-0029-1216873

PAPER
2697
Facile and Efficient Synthesis of a New Class of Indole-Substituted Pyridine
Derivatives via One-Pot Multicomponent Reactions
I
ndole-Substituted
a
Pyridine
D
i
erivatives Zhao, Xiao-Ping Xu, Song-Lei Zhu, Da-Qing Shi, Yong Zhang, Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science,
Soochow University, Suzhou 215123, P. R. of China
Fax +86(512)65880307; E-mail: chemjsj@suda.edu.cn
Received 18 March 2009; revised 23 April 2009
H2N
N
Abstract: A new series of indole-containing pyridine derivatives,
H
N
R3
4-aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbonitriles, were syn-
N
R1
R1
N
thesized via one-pot multicomponent reactions of 3-(cyano-
acetyl)indoles, aldehydes, heterocyclic ketones, and ammonium
acetate. Particularly valuable features of this method include high
yields of products, broad substrate scope, and straightforward pro-
cedures.
R2
R3
X
N
N
H
R2
O
R4
Key words: pyridine derivatives, indole, one-pot synthesis, multi-
component reactions, heterocycles
aplysinopsins
NH
meridianins A–E
N
HN
Pyridine derivatives have long been the focus of consider-
able attention for their abundant existence in numerous
nature products as well as their extensive applications in
biological, pharmic, and supramolecular science.1–3 In
particular, bipyridines, along with higher oligopyridines,
have attracted widespread attention as key building blocks
in the formation of discrete metallosupramolecular spe-
cies having well-defined geometries and stoichiometries
because of their p-stacking ability, directional hydrogen
bonding, and excellent coordination properties to various
of transition metals.4 Moreover, bipyridines and related
complexes have also found numerous applications in
asymmetric catalysis,5 photoinduced electron transfer,6
artificial photosynthesis,7 and polymer and dendrimer sci-
ence.8 With all these fascinating potential applications,
much research has been devoted to the development of di-
rected synthetic routes to suitable bipyridine units, as well
as effective functionalization strategies.9
N
H
R
R
nortopsentins A–C
Figure 1 Some typical indole-substituted heterocycles
number of efforts have been devoted to the synthesis of in-
dole-containing bipyridine complexes in order to design
suitable labels or probes for indole-binding proteins, such
as serum albumins and tryptophanase. Whereas the indole
moiety serves as the biological recognition unit for these
proteins, the polypyridine units coordinating with a lumi-
nescent transition metal play a role as the environment-
sensitive emitter, which assist in the detection, monitor-
ing, and isolation of these important biomolecules.13
Base on the remarkable range of applications of bipy-
ridines and indole derivatives, we became interested in in-
troducing an indole unit into the bipyridine skeleton.
However, many existing methods for the synthesis of sub-
stituted bipyridines have drawbacks, such as restriction of
the functionalization positions in the well-known
Kröhnke procedure,14 the increasing isomeric mixture
when using Raney nickel catalysts in the Rode proce-
dure,15 and the creation of organophosphorus16 or organo-
sulfur compounds17 in other synthetic strategies. Even
modern synthetic routes such as the Suzuki18 or Negishi
Indole fragments are featured in a wide variety of pharma-
cologically and biologically active compounds,10 the flu-
orescent amino acid tryptophan, the plant growth
regulator indole-3-acetic acid, the neurotransmitter sero-
tonin, and a variety of marine alkaloids containing indole
units, such as the meridianins A–E, are all of crucial im-
portance in plant, animal, and human physiology
(Figure 1).11 Thus, synthetic methods and the structure
decoration of indole derivatives have received increased
attention in recent years.12
Drawn by the extraordinary capacity of bipyridines to cross-coupling19 suffered from narrow scope of sub-
chelated transition metals and the brilliant physiological strates, harsh reaction conditions, generality, and opera-
and biological activities of indole derivatives, a great tional complexity due to the occurrence of several side
reactions. Additionally, to the best of our knowledge,
there have been few reports on the synthesis of bipyridine
SYNTHESIS 2009, No. 16, pp 2697–2708
Advanced online publication: 26.06.2009
DOI: 10.1055/s-0029-1216873; Art ID: F05909SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9
derivatives incorporated indole moieties. Therefore, in-
spired by our previous work, the synthesis of a series of
bisindoles derivatives containing 3,5-dicyanopyridine

2698
K. Zhao et al.
PAPER
O
Ar
N
CN
+
O
CN
NH4OAc
ArCHO
+
Δ
N
N
H
N
NH
Scheme 1
units,20 we devised a simple, efficient, and straightforward acetylpyridine (3), and ammonium acetate (Table 1) was
protocol for the synthesis of a new series of indole-substi- chosen as the model reaction to optimize the reaction con-
tuted bipyridines via a one-pot, multicomponent reaction ditions.
between an aldehyde, 3-(cyanoacetyl)indole, 2-acetylpy-
ridine, and ammonium acetate (Scheme 1).
Firstly, the synthesis of 4a was carried out in different sol-
vents, such as anhydrous ethanol, methanol, acetic acid,
The starting material 3-(cyanoacetyl)indoles 1 were pre- acetonitrile, N,N-dimethylformamide, glycol, and butan-
viously prepared by Kreher and Wagner21 and recently by 1-ol, to investigate their effects on the synthetic proce-
Bergman22 via a new facile approach starting from indoles dure. The results are shown in Table 1 (entries 1–6), from
and cyanoacetic acid (Scheme 2).
which we can see that the best yield was obtained when
butan-1-ol was used as the solvent.
O
The temperature screening was also carried out for the
range 80–110 °C in butan-1-ol (Table 1, entries 7–10), el-
evation of the temperature had some positive effects and
improved the yield of the target product; 100 °C was the
most appropriate temperature that gave acceptable results.
CN
cyanoacetic acid, Ac2O
60–70 °C, 5 min
R
R
N
N
H
H
1
Under these optimal conditions (n-BuOH, 100 °C), a se-
ries of 4-aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbo-
nitriles 4 were synthesized (Table 2).
Scheme 2
In our initial studies, the one-pot reaction of 4-chloro-
During the experiments, the desired products 4a–w were
benzaldehyde (2a), 3-(cyanoacetyl)-1H-indole (1a), 2-
isolated in moderate to good yields, however, monitoring
Table 1 Solvent and Temperature Optimization for the Synthesis of 4a
Cl
O
Cl
CN
+
O
NH4OAc
CN
+
Δ
N
N
H
N
CHO
N
NH
1a
2a
3
4a
Entry
Solvent
MeOH
EtOH
Temp (°C)
Time (h)
Yielda (%)
1
2
80
80
80
80
80
80
80
90
100
110
10
8
43
58
52
60
50
35
68
70
78
71
3
MeCN
glycol
10
9
4
5
DMF
8
6
AcOH
n-BuOH
n-BuOH
n-BuOH
n-BuOH
12
9
7
8
8
9
8
10
8
a Isolated yields.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

PAPER
Indole-Substituted Pyridine Derivatives
2699
Table 2 Synthesis of 4-Aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbonitriles 4
Ar
Ar
O
CN
R1
CN
CN
R1
O
R1
method A or B
N
ArCHO
+
+
+
N
H
N
N
N
N
R2
N
N
R2
R2
1
2
3
4
5
Entry
Product
Ar
R1
R2
Method Aa
Yieldb (%)
Method Ba
Yieldb (%)
Mp (°C)
Time (h)
Time (h)
1
2
4a
4b
4c
4d
4e
4f
4-ClC6H4
4-BrC6H4
4-O2NC6H4
3-O2NC6H4
2,4-Cl2C6H3
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
78
8
95
90
93
91
88
87
81
87
88
79
89
82
80
86
90
88
85
83
89
93
90
80
92
5
5
4
4
6
5
7
8
6
9
6
8
9
8
8
7
8
9
4
5
5
5
6
>300
72
9
>300
3
80
6
>300
4
82
6
272–273
275–277
294–296
288–290
266–268
271–273
283–285
258–260
275–277
253–255
258–259
270-271
262–264
>300
5
73
10
9
6
66
7
4g
4h
4i
4-MeC6H4
4-MeOC6H4
2-MeC6H4
2-MeOC6H4
62
11
11
10
12
10
10
12
13
10
11
3
8
58
9
60
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
55
4k
4l
3,4-OCH2OC6H3
2-thienyl
3-thienyl
2-furyl
1-naphthyl
2-naphthyl
2-ClC6H4
2-BrC6H4
Ph
65
60
4m
4n
4o
4p
4q
4r
4s
60
58
70
76
75c (5a)
80c (5b)
65
3
>300
5-Me
6-Me
7-Me
H
H
7
256–258
>300
4t
Ph
H
66
7
4u
4v
4w
Ph
H
63
8
298–299
243–244
>300
Ph
Me
H
58
9
Ph
5-Br
70
8
a Method A: NH4OAc (3 equiv), n-BuOH, 100 °C; Method B: 1. NH4OAc (3 equiv), n-BuOH, 100 °C, 2. DDQ (50 mol%).
b Isolated yields.
c The non-aromatized 4-aryl-6-(1H-indol-3-yl)-1,4-dihydro-2,2¢-bipyridine-5-carbonitriles 5a,b were isolated.
the synthetic procedure by thin layer chromatography compounds 4 as well as a decrease of the reaction time
showed that the desired aromatized products 4 were ob- (Table 2, Method B).
tained together with non-aromatized products (Table 2,
To examine the efficiency and the applicability of this
Method A). In order to further improve the yield of the fi-
new multi-component reaction, different aldehydes and
nal products, a powerful oxidant 2,3-dichloro-5,6-dicy-
indoles were tested. As shown in Table 2, this protocol
ano-1,4-benzoquinone (DDQ) was added in order to
was readily available to aromatic aldehydes bearing either
promote aromatization. To our great delight, the use of
electron-withdrawing functional groups, such as nitro and
DDQ led to an obvious increase in the yields of the target
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

2700
K. Zhao et al.
PAPER
halo substituents (Table 2, entries 1–5), or electron-donat- were sufficiently stable to be isolated from the reaction
ing ones, such as alkyl and alkoxy (Table 2, entries 7–11), system in good yields, which indicated that substitution at
as well as heterocyclic aldehydes, such as thiophene-2- the 2-position of the aldehydes might have some subtle ef-
carbaldehyde, thiophene-3-carbaldehyde, and furan-2- fects, which would prevent the further aromatization ob-
carbaldehyde (Table 2, entries 12–14). In addition, steri- served in other cases in Table 2. However, 5a and 5b were
cally bulky 1- and 2-naphthaldehyde (Table 2, entries 15 transformed into the aromatized products 4q and 4r with
and 16) gave the target compounds 4o,p in high yields. the addition of a stoichiometric amount of DDQ. To our
During the experiments, subtle electronic effects were ob- disappointment, aliphatic aldehydes did not take part in
served in the substituents, for example, arylaldehydes related reactions effectively.
with electron-withdrawing groups reacted rapidly and
gave better yields of final products, while the electron-
rich groups might decrease the reactivities of the sub-
strates, so that they required longer reaction times and the
yields were a little lower. Moreover, reactions of substi-
tuted 3-(cyanoacetyl)indoles 1 were smooth and gave the
In order to further expand the scope of application of this
protocol, 2-acetylpyridine (3) was replaced by 3-acetylpy-
ridine (6) (Table 3) and 2-acetylthiophene (8) (Table 4)
and these reacted smoothly to give the corresponding in-
dole-containing pyridine derivatives 7 and 9, respectively.
Aliphatic ketones were also tested, however, no target
anticipated products in excellent yields. Interestingly,
compounds were obtained because of their deficient reac-
when the aldehydes bearing a halide substituent at the 2-
tivities.
position (Table 2, entries 17 and 18) were applied, the
non-aromatized 1,4-dihydropyridine derivatives 5a,b
Table 3 Synthesis of 4-Aryl-6-(1H-indol-3-yl)-2,3¢-bipyridine-5-carbonitriles 7
O
Ar
O
CN
CN
1. NH4OAc, n-BuOH, 100 °C
2. DDQ
ArCHO
+
+
N
N
H
N
NH
N
1a
2
6
7
Entry
Product
7a
Ar
4-ClC6H4
Time (h)
12
Yielda (%)
Mp (°C)
278–280
>300
1
2
3
4
5
72
75
70
70
68
7b
4-O2NC6H4
Ph
10
14
16
12
7c
282–284
233–235
293–294
7d
4-MeOC6H4
2-furyl
7e
a Isolated yields.
Table 4 Synthesis of 4-Aryl-2-(1H-indol-3-yl)-6-(2-thienyl)nicotinonitriles 9
Ar
O
CN
O
CN
1. NH4OAc, n-BuOH, 100 °C
2. DDQ
ArCHO
+
+
N
S
N
H
S
NH
1a
2
9
8
Entry
Product
9a
Ar
4-ClC6H4
Time (h)
13
Yielda (%)
Mp (°C)
>300
1
2
3
4
5
68
70
73
69
65
9b
4-BrC6H4
4-O2NC6H4
3-O2NC6H4
Ph
12
10
10
16
>300
9c
>300
9d
285–286
283–285
9e
a Isolated yields.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

PAPER
Indole-Substituted Pyridine Derivatives
2701
O
O
CN
Ar
+
ArCHO
CN
N
N
H
H
2
11
1a
H
NH
O
NH
NH3
N
N
N
3
10
12
Ar
Ar
CN
CN
NH HO
NH2
O
N
N
N
H
N
H
14
13
Ar
Ar
N
CN
CN
aromatization
– H2O
N
H
N
N
N
H
N
H
5
4
Scheme 3
Although the detailed mechanism of the above reaction
remains to be fully clarified, formation of the final prod-
ucts, 4-aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carboni-
triles 4 for instance, might undergo a sequential procedure
containing a typical Knoevenagel condensation following
by a Hantzsch condensation (Scheme 3).
Firstly, condensation between 3-(cyanoacetyl)indole 1a
and aldehyde 2 gave intermediate 11 and 2-acetylpyridine
(3) and ammonium acetate gave intermediate 12. Then, 11
was attacked by 12 via a Michael addition to give 13,
which could isomerize to intermediate 14. Intramolecular
cyclization of 14 gave the dihydro intermediate 5, which
could further undergo dehydrogenation to afford the fully
aromatized products 4 (Scheme 3). This type of dehydro-
genation is well precedented.23
In this study, all the products were characterized by melt-
ing point, IR, NMR, and HRMS data. Furthermore, the
structures of 4f24 and 5b25 were confirmed by X-ray crys-
tallographic analysis (Figures 2 and 3).
Figure 2 Crystal structure of 4f
In conclusion, we have demonstrated a simple and effi-
cient approach to the synthesis of a series of indole-substi-
tuted pyridine derivatives via multicomponent reactions
of aldehydes, 3-(cyanoacetyl)indoles, heterocyclic ke-
tones, and ammonium acetate in butan-1-ol at 100 °C,
which incorporates an indole, a pyridine, and another
(het)arene into a single molecule in just one-step. The
most fascinating characteristics of this procedure are the
excellent yields of the target compounds, the broad scope
of the substrates, the short reaction time, and the conve-
nient and straightforward synthetic routes.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

2702
K. Zhao et al.
PAPER
were then filtered off and then washed with cool anhyd EtOH
(2 × 0.5 mL) to give the pure products.
4-(4-Chlorophenyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbo-
nitrile (4a)
Yellow solid; mp >300 °C.
IR (KBr): 3351, 3057, 2221, 1575, 1538, 1492, 1368, 1213, 1016,
797, 744 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.85 (br s, 1 H, NH), 8.79 (d,
J = 4.4 Hz, 1 H, ArH), 8.58 (d, J = 8.0 Hz, 1 H, ArH), 8.42–8.39 (m,
2 H, ArH), 8.30 (s, 1 H, ArH), 8.11 (dt, J = 7.6, 1.6 Hz, 1 H, ArH),
7.83 (d, J = 8.4 Hz, 2 H, ArH), 7.69 (d, J = 8.4 Hz, 2 H, ArH), 7.60–
7.56 (m, 2 H, ArH), 7.29–7.24 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.29, 157.14, 153.79,
149.57, 137.69, 136.33, 135.56, 134.73, 130.50, 129.33, 128.80,
128.50, 125.93, 125.25, 122.37, 121.52, 121.15, 120.84, 118.48,
116.11, 112.68, 112.08, 102.70.
HRMS: m/z [M]+ calcd for C25H1535ClN4: 406.0985; found:
406.0991.
Figure 3 Crystal structure of 5b
4-(4-Bromophenyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbo-
nitrile (4b)
Yellow solid; mp >300 °C.
Melting points were recorded on an Electrothermal digital melting
point apparatus and are uncorrected. IR spectra were recorded on a
Varian FT-1000 spectrophotometer using KBr optics. H NMR
IR (KBr): 3333, 3057, 2222, 1573, 1538, 1489, 1440, 1369, 1213,
1013, 744 cm–1.
1
(400 MHz) and 13C NMR (75 MHz) spectra were recorded on a
Varian Mercury MHz spectrometer using DMSO-d6 (solvent) and
TMS (internal standard). HRMS were obtained using a Microma
GCT-TOF instrument. X-ray diffraction data were recorded on a
Rigaku Mercury CCD area detector with graphite monochromated
Mo-Ka radiation.
1H NMR (400 MHz, DMSO-d6): d = 11.88 (br s, 1 H, NH), 8.74 (d,
J = 4.0 Hz, 1 H, ArH), 8.53 (d, J = 8.0 Hz, 1 H, ArH), 8.41–8.37 (m,
2 H, ArH), 8.22 (s, 1 H, ArH), 8.04 (t, J = 7.6 Hz, 1 H, ArH), 7.76
(d, J = 8.4 Hz, 2 H, ArH), 7.67 (d, J = 8.0 Hz, 2 H, ArH), 7.57 (d,
J = 7.2 Hz, 1 H, ArH), 7.54–7.51 (m, 1 H, ArH), 7.29–7.23 (m, 2 H,
ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.23, 157.07, 153.71,
153.61, 149.41, 137.42, 136.36, 135.81, 131.59, 130.55, 128.71,
126.00, 125.05, 124.40, 122.35, 121.45, 121.28, 120.82, 118.48,
115.94, 112.73, 112.06, 102.31.
HRMS: m/z [M]+ calcd for C25H1579BrN4: 450.0480; found:
450.0467.
4-Aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbonitriles 4,
4-Aryl-6-(1H-indol-3-yl)-2,3¢-bipyridine-5-carbonitriles 7, and
4-Aryl-2-(1H-indol-3-yl)-6-(2-thienyl)nicotinonitriles 9;
General Procedure
A mixture of 3-(cyanoacetyl)indole 1 (1 mmol), aldehyde 2 (1
mmol), heterocyclic ketone 3, 6, or 8 (1 mmol), and NH4OAc (3
mmol) in n-BuOH (3 mL) was stirred at 100 °C for several hours
(see Tables 2– 4). When the starting materials had been consumed,
a mixture of the non-aromatized 1,4-dihydropyridine derivative and
the aromatized target product was obtained (TLC monitoring). The
former was aromatized by the addition of DDQ (50 mol%) and the
mixture was allowed to cool to r.t. The solid was filtered off and
washed with cool anhyd EtOH (2 × 0.5 mL) to give 4, 7, and 9 as
yellow powders (TLC pure) without further purification. Com-
pounds for crystallographic analysis were recrystallized (anhyd
EtOH and DMF).
6-(1H-Indol-3-yl)-4-(4-nitrophenyl)-2,2¢-bipyridine-5-carboni-
trile (4c)
Yellow solid; mp >300 °C.
IR (KBr): 3401, 3059, 2217, 1565, 1539, 1431, 1347, 1237, 793,
753 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.93 (br s, 1 H, NH), 8.79 (d,
J = 4.8 Hz, 1 H, ArH), 8.59 (d, J = 8.0 Hz, 1 H, ArH), 8.46–8.41 (m,
4 H, ArH), 8.33 (s, 1 H, ArH), 8.13 (dt, J = 8.0, 1.6 Hz, 1 H, ArH),
8.08 (d, J = 8.8 Hz, 2 H, ArH), 7.61–7.56 (m, 2 H, ArH), 7.30–7.25
(m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.37, 157.30, 153.68,
153.02, 149.67, 148.17, 143.06, 137.81, 136.35, 130.29, 128.92,
125.88, 125.42, 123.80, 122.44, 121.60, 121.11, 120.93, 118.21,
116.12, 112.59, 112.13, 102.65.
4-Aryl-6-(1H-indol-3-yl)-1,4-dihydro-2,2¢-bipyridine-5-carbo-
nitriles 5a, 5b and 4-Aryl-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-
carbonitriles 4q, 4r; General Procedure
A mixture of 3-(cyanoacetyl)indole 1 (1 mmol), 2-chloro- or 2-bro-
mobenzaldehyde (1 mmol), 2-acetylpyridine (3, 1 mmol), and
NH4OAc (3 mmol) in n-BuOH (3 mL) was stirred at 100 °C for 3 h.
When the starting materials had been consumed, the non-aroma-
tized 1,4-dihydropyridine derivatives 5a or 5b deposited from the
reaction system without the appearance of the aromatized products.
The solid was filtered off and washed with cool anhyd EtOH
(2 × 0.5 mL) to give 5a,b as shiny yellow powders (TLC pure) with-
out further purification. Compounds for crystallographic analysis
were recrystallized (anhyd EtOH). The aromatized products 4q and
4r could be synthesized from 5a and 5b, respectively, by the addi-
tion of a stoichiometric amount of DDQ. The aromatized products
HRMS: m/z [M]+ calcd for C25H15N5O2: 417.1226; found:
417.1233.
6-(1H-Indol-3-yl)-4-(3-nitrophenyl)-2,2¢-bipyridine-5-carboni-
trile (4d)
Yellow solid; mp 272–273 °C.
IR (KBr): 3366, 3073, 2214, 1564, 1540, 1526, 1436, 1351, 741,
692 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.90 (br s, 1 H, NH), 8.79 (d,
J = 4.0 Hz, 1 H, ArH), 8.64 (s, 1 H, ArH), 8.59 (d, J = 8.0 Hz, 1 H,
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

PAPER
Indole-Substituted Pyridine Derivatives
2703
ArH), 8.45–8.43 (m, 3 H, ArH), 8.36 (s, 1 H, ArH), 8.26 (d, J = 7.6
Hz, 1 H, ArH), 8.12 (t, J = 7.6 Hz, 1 H, ArH), 7.91 (t, J = 8.0 Hz, 1
H, ArH), 7.60–7.56 (m, 2 H, ArH), 7.28–7.26 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.34, 157.31, 153.70,
152.65, 149.66, 147.82, 138.13, 137.78, 136.37, 135.32, 130.44,
128.98, 125.92, 125.40, 124.43, 123.56, 122.47, 121.60, 121.18,
120.97, 118.43, 116.28, 112.64, 112.17, 102.80.
IR (KBr): 3373, 3058, 2213, 1609, 1577, 1529, 1513, 1427, 1254,
781, 765 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.86 (br s, 1 H, NH), 8.77 (d,
J = 4.4 Hz, 1 H, ArH), 8.57 (d, J = 8.0 Hz, 1 H, ArH), 8.40–8.38 (m,
2 H, ArH), 8.29 (s, 1 H, ArH), 8.10 (dt, J = 8.0, 1.6 Hz, 1 H, ArH),
7.77 (d, J = 8.8 Hz, 2 H, ArH), 7.59–7.55 (m, 2 H, ArH), 7.29–7.23
(m, 2 H, ArH), 7.17 (d, J = 8.8 Hz, 2 H, ArH), 3.87 (s, 3 H, CH3).
HRMS: m/z [M]+ calcd for C25H15N5O2: 417.1226; found:
417.1224.
13C NMR (75 MHz, DMSO-d6): d = 160.58, 157.48, 156.97,
154.71, 154.03, 149.67, 137.73, 136.39, 130.29, 128.90, 128.83,
126.08, 125.25, 122.42, 121.54, 121.26, 120.89, 119.08, 116.10,
114.30, 112.85, 112.16, 102.64, 55.38.
4-(2,4-Dichlorophenyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-car-
bonitrile (4e)
Yellow solid; mp 275–277 °C.
HRMS: m/z [M]+ calcd for C26H18N4O: 402.1481; found: 402.1463.
IR (KBr): 3343, 3055, 2221, 1589, 1535, 1476, 1439, 1214, 820,
741 cm–1.
6-(1H-Indol-3-yl)-4-(2-tolyl)-2,2¢-bipyridine-5-carbonitrile (4i)
Yellow solid; mp 271–273 °C.
1H NMR (400 MHz, DMSO-d6): d = 11.94 (br s, 1 H, NH), 8.77 (d,
J = 4.8 Hz, 1 H, ArH), 8.60 (d, J = 7.6 Hz, 1 H, ArH), 8.47–8.44 (m,
1 H, ArH), 8.39 (d, J = 3.2 Hz, 1 H, ArH), 8.23 (s, 1 H, ArH), 8.13
(dt, J = 7.6, 1.2 Hz, 1 H, ArH), 7.94 (d, J = 2.0 Hz, 1 H, ArH), 7.74–
7.67 (m, 2 H, ArH), 7.61–7.56 (m, 2 H, ArH), 7.30–7.27 (m, 2 H,
ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.41, 156.73, 153.67,
152.03, 149.68, 137.80, 136.41, 135.09, 134.67, 132.48, 132.13,
129.29, 128.70, 127.87, 125.79, 125.41, 122.51, 121.60, 121.19,
120.99, 117.58, 116.70, 112.47, 112.18, 103.90.
IR (KBr): 3331, 3057, 2219, 1581, 1535, 1438, 1366, 1147, 785,
743 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.91 (br s, 1 H, NH), 8.77 (d,
J = 4.0 Hz, 1 H, ArH), 8.62 (d, J = 8.0 Hz, 1 H, ArH), 8.50–8.47 (m,
1 H, ArH), 8.42 (d, J = 2.8 Hz, 1 H, ArH), 8.18 (s, 1 H, ArH), 8.13
(t, J = 7.6 Hz, 1 H, ArH), 7.60–7.57 (m, 2 H, ArH), 7.47–7.38 (m, 4
H, ArH), 7.30–7.28 (m, 2 H, ArH), 2.27 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 157.12, 156.85, 155.81,
153.97, 149.75, 137.88, 136.93, 136.44, 134.87, 130.46, 129.35,
128.81, 126.15, 126.96, 125.40, 122.52, 121.63, 121.33, 121.00,
118.14, 116.74, 112.66, 112.22, 104.12, 19.45.
HRMS: m/z [M]+ calcd for C25H1437Cl2N4: 444.0537; found:
444.0532.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1531.
6-(1H-Indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carbonitrile (4f)
Yellow solid; mp 294–296 °C.
6-(1H-Indol-3-yl)-4-(2-methoxyphenyl)-2,2¢-bipyridine-5-car-
bonitrile (4j)
IR (KBr): 3337, 3050, 2218, 1573, 1535, 1438, 1214, 1145, 850,
745, 703 cm–1.
Yellow solid; mp 283–285 °C.
IR (KBr): 3353, 3057, 2218, 1583, 1535, 1495, 1249, 1142, 756,
747 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.89 (br s, 1 H, NH), 8.78 (d,
J = 4.4 Hz, 1 H, ArH), 8.58 (d, J = 8.0 Hz, 1 H, ArH), 8.41 (d,
J = 5.2 Hz, 2 H, ArH), 8.31 (s, 1 H, ArH), 8.11 (dt, J = 8.0, 1.6 Hz,
1 H, ArH), 7.81–7.79 (m, 2 H, ArH), 7.66–7.56 (m, 5 H, ArH),
7.29–7.24 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.36, 157.09, 155.05,
153.91, 149.62, 137.68, 136.83, 136.39, 129.77, 128.82, 128.65,
126.04, 125.26, 122.42, 121.53, 121.25, 120.89, 118.74, 116.29,
112.78, 112.15, 102.78.
1H NMR (400 MHz, DMSO-d6): d = 11.88 (br s, 1 H, NH), 8.75 (d,
J = 4.8 Hz, 1 H, ArH), 8.58 (d, J = 8.0 Hz, 1 H, ArH), 8.43–8.41 (m,
1 H, ArH), 8.35 (d, J = 2.8 Hz, 1 H, ArH), 8.22 (s, 1 H, ArH), 8.10
(dt, J = 7.6, 1.6 Hz, 1 H, ArH), 7.58–7.53 (m, 3 H, ArH), 7.48 (dd,
J = 7.6, 1.6 Hz, 1 H, ArH), 7.29–7.23 (m, 3 H, ArH), 7.15 (t, J = 7.6
Hz, 1 H, ArH), 3.84 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 157.08, 156.55, 156.04,
154.04, 153.04, 149.71, 137.82, 136.42, 131.39, 130.23, 128.52,
125.99, 125.73, 125.30, 122.47, 121.53, 121.21, 120.93, 120.84,
118.40, 117.36, 112.72, 112.20, 111.89, 104.88, 55.64.
HRMS: m/z [M]+ calcd for C25H16N4: 372.1375; found: 372.1371.
6-(1H-Indol-3-yl)-4-(4-tolyl)-2,2¢-bipyridine-5-carbonitrile (4g)
Yellow solid; mp 288–290 °C.
HRMS: m/z [M]+ calcd for C26H18N4O: 402.1481; found: 402.1481.
IR (KBr): 3331, 3057, 2222, 1578, 1540, 1439, 1370, 1216, 1142,
743 cm–1.
4-(1,3-Benzodioxol-5-yl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-
carbonitrile (4k)
Brown solid; mp 258–260 °C.
1H NMR (400 MHz, DMSO-d6): d = 11.89 (br s, 1 H, NH), 8.79 (d,
J = 4.4 Hz, 1 H, ArH), 8.58 (d, J = 8.0 Hz, 1 H, ArH), 8.40–8.39 (m,
2 H, ArH), 8.30 (s, 1 H, ArH), 8.13 (dt, J = 8.0, 1.6 Hz, 1 H, ArH),
8.08 (d, J = 8.8 Hz, 2 H, ArH), 7.61–7.56 (m, 2 H, ArH), 7.43 (d,
J = 8.0 Hz, 2 H, ArH), 7.27–7.25 (m, 2 H, ArH), 2.43 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 157.36, 156.99, 155.02,
153.93, 149.54, 139.51, 137.67, 136.32, 133.89, 129.33, 128.71,
128.50, 125.98, 125.17, 122.31, 121.49, 121.15, 120.77, 118.73,
116.13, 112.76, 112.04, 102.72, 20.82.
IR (KBr): 3372, 3055, 2213, 1580, 1564, 1533, 1500, 1449, 1224,
1038, 766 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.86 (br s, 1 H, NH), 8.78 (d,
J = 4.0 Hz, 1 H, ArH), 8.57 (d, J = 8.0 Hz, 1 H, ArH), 8.39 (d,
J = 2.4 Hz, 2 H, ArH), 8.27 (s, 1 H, ArH), 8.10 (t, J = 7.6 Hz, 1 H,
ArH), 7.59–7.56 (m, 2 H, ArH), 7.42 (s, 1 H, ArH), 7.30–7.25 (m,
3 H, ArH), 7.15 (d, J = 8.0 Hz, 1 H, ArH), 6.17 (s, 2 H, CH2).
13C NMR (75 MHz, DMSO-d6): d = 157.38, 156.96, 154.65,
153.97, 149.62, 148.66, 147.63, 137.70, 136.35, 130.53, 128.83,
126.02, 125.22, 123.13, 122.37, 122.51, 121.20, 120.84, 118.89,
116.22, 112.80, 112.11, 109.00, 108.65, 102.83, 101.72.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1541.
6-(1H-Indol-3-yl)-4-(4-methoxyphenyl)-2,2¢-bipyridine-5-car-
bonitrile (4h)
Light yellow solid; mp 266–268 °C.
HRMS: m/z [M]+ calcd for C26H16N4O2: 416.1273; found:
416.1256.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

2704
K. Zhao et al.
PAPER
6-(1H-Indol-3-yl)-4-(2-thienyl)-2,2¢-bipyridine-5-carbonitrile
(4l)
124.72, 122.52, 121.67, 121.38, 121.00, 118.16, 117.63, 112.71,
112.21, 104.76.
Yellow solid; mp 275–277 °C.
HRMS: m/z [M]+ calcd for C29H18N4: 422.1531; found: 422.1535.
IR (KBr): 3397, 3073, 2218, 1563, 1537, 1436, 1422, 1449, 1247,
1137, 1011, 796, 781, 749 cm–1.
6-(1H-Indol-3-yl)-4-(2-naphthyl)-2,2¢-bipyridine-5-carboni-
trile (4p)
Yellow solid; mp 262–264 °C.
1H NMR (400 MHz, DMSO-d6): d = 11.91 (br s, 1 H, NH), 8.81 (d,
J = 4.4 Hz, 1 H, ArH), 8.55 (d, J = 8.0 Hz, 1 H, ArH), 8.41–8.40 (d,
J = 4.0 Hz, 2 H, ArH), 8.39–8.36 (m, 1 H, ArH), 8.09 (dt, J = 7.6,
2.0 Hz, 1 H, ArH), 7.99–7.97 (m, 2 H, ArH), 7.60–7.57 (m, 2 H,
ArH), 7.38–7.35 (m, 1 H, ArH), 7.31–7.24 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 158.07, 157.18, 153.64,
149.62, 146.59, 137.67, 137.54, 136.35, 130.39, 129.86, 129.03,
128.75, 126.07, 125.35, 122.42, 121.50, 121.23, 120.90, 119.19,
115.03, 112.66, 112.15, 100.63.
IR (KBr): 3409, 3053, 2220, 1668, 1574, 1541, 1436, 784, 743
cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.91 (br s, 1 H, NH), 8.78 (d,
J = 4.0 Hz, 1 H, ArH), 8.59 (d, J = 8.0 Hz, 1 H, ArH), 8.44–8.40 (m,
3 H, ArH), 8.35 (s, 1 H, ArH), 8.14–8.03 (m, 4 H, ArH), 7.88 (d,
J = 8.4 Hz, 1 H, ArH), 7.65–7.63 (m, 2 H, ArH), 7.58–7.55 (m, 2 H,
ArH), 7.28–7.27 (m, 2 H, ArH).
HRMS: m/z [M]+ calcd for C23H14N4S: 378.0939; found: 378.0940.
13C NMR (75 MHz, DMSO-d6): d = 162.50, 157.47, 157.22,
155.10, 154.05, 149.66, 137.69, 136.50, 134.53, 134.32, 133.18,
132.65, 128.87, 128.54, 127.73, 127.44, 126.92, 126.15, 125.96,
125.30, 122.55, 121.67, 121.39, 121.01, 118.87, 116.59, 112.94,
112.22, 102.98.
6-(1H-Indol-3-yl)-4-(3-thienyl)-2,2¢-bipyridine-5-carbonitrile
(4m)
Red solid; mp 253–255 °C.
IR (KBr): 3377, 3093, 2213, 1581, 1566, 1532, 1456, 1431, 1236,
1135, 772 cm–1.
HRMS: m/z [M]+ calcd for C29H18N4: 422.1531; found: 422.1517.
4-(2-Chlorophenyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbo-
nitrile (4q)
Yellow solid; mp >300 °C.
1H NMR (400 MHz, DMSO-d6): d = 11.87 (br s, 1 H, NH), 8.77 (d,
J = 4.0 Hz, 1 H, ArH), 8.55 (d, J = 8.0 Hz, 1 H, ArH), 8.39 (d,
J = 2.8 Hz, 2 H, ArH), 8.36 (s, 1 H, ArH), 8.25 (s, 1 H, ArH), 8.08
(t, J = 7.6 Hz, 1 H, ArH), 7.83–7.81 (m, 1 H, ArH), 7.67 (d, J = 4.8
Hz, 1 H, ArH), 7.58–7.55 (m, 2 H, ArH), 7.29–7.23 (m, 2 H, ArH).
IR (KBr): 3326, 3060, 2223, 1573, 1535, 1472, 1440, 1367, 1214,
1148, 742 cm–1.
13C NMR (75 MHz, DMSO-d6): d = 157.50, 157.14, 153.92,
149.48, 149.13, 137.51, 137.00, 136.32, 128.68, 127.57, 127.46,
127.43, 126.02, 125.09, 122.31, 121.44, 121.21, 120.76, 118.97,
115.66, 112.76, 112.03, 101.81.
1H NMR (400 MHz, DMSO-d6): d = 11.91 (br s, 1 H, NH), 8.78 (d,
J = 4.0 Hz, 1 H, ArH), 8.60 (d, J = 8.0 Hz, 1 H, ArH), 8.47–8.46 (m,
1 H, ArH), 8.39 (s, 1 H, ArH), 8.22 (s, 1 H, ArH), 8.13 (t, J = 7.6
Hz, 1 H, ArH), 7.73 (d, J = 7.2 Hz, 1 H, ArH), 7.67 (d, J = 7.2 Hz,
1 H, ArH), 7.61–7.57 (m, 4 H, ArH), 7.29–7.27 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.35, 156.78, 153.75,
153.16, 149.79, 137.94, 136.46, 135.76, 131.36, 131.29, 130.90,
129.81, 128.78, 127.74, 125.88, 125.52, 122.60, 121.67, 121.27,
121.09, 117.80, 116.83, 112.54, 112.27, 104.11.
HRMS: m/z [M]+ calcd for C23H14N4S: 378.0939; found: 378.0928.
4-(2-Furyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbonitrile
(4n)
Yellow solid; mp 258–259 °C.
IR (KBr): 3402, 3310, 3118, 2219, 1589, 1550, 1485, 1432, 1247,
1029, 756 cm–1.
HRMS: m/z [M]+ calcd for C25H1535ClN4: 406.0985; found:
406.0974.
1H NMR (400 MHz, DMSO-d6): d = 11.88 (br s, 1 H, NH), 8.81 (d,
J = 4.4 Hz, 1 H, ArH), 8.66 (s, 1 H, ArH), 8.53 (d, J = 8.0 Hz, 1 H,
ArH), 8.37 (d, J = 2.8 Hz, 1 H, ArH), 8.33 (d, J = 7.6 Hz, 1 H, ArH),
8.11–8.06 (m, 2 H, ArH), 7.67 (d, J = 3.6 Hz, 1 H, ArH), 7.60–7.55
(m, 2 H, ArH), 7.28–7.21 (m, 2 H, ArH), 6.86–6.85 (m, 1 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.92, 157.27, 153.79,
149.61, 148.00, 146.08, 141.46, 137.65, 136.33, 128.85, 126.07,
125.30, 122.40, 121.39, 121.23, 120.85, 119.19, 114.07, 113.05,
112.66, 112.11, 111.22, 97.20.
4-(2-Bromophenyl)-6-(1H-indol-3-yl)-2,2¢-bipyridine-5-carbo-
nitrile (4r)
Yellow solid; mp >300 °C.
IR (KBr): 3322, 3056, 2222, 1593, 1571, 1532, 1472, 1439, 774,
743 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.92 (br s, 1 H, NH), 8.76 (d,
J = 4.0 Hz, 1 H, ArH), 8.60 (d, J = 8.0 Hz, 1 H, ArH), 8.49–8.47 (m,
1 H, ArH), 8.40 (d, J = 2.4 Hz, 1 H, ArH), 8.19 (s, 1 H, ArH), 8.11
(t, J = 7.6 Hz, 1 H, ArH), 7.88 (d, J = 8.0 Hz, 1 H, ArH), 7.64–7.56
(m, 4 H, ArH), 7.51 (t, J = 7.6 Hz, 1 H, ArH), 7.29–7.27 (m, 2 H,
ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.33, 156.76, 154.80,
153.77, 149.79, 137.93, 137.86, 136.49, 132.92, 131.41, 130.71,
128.77, 128.20, 125.91, 125.51, 122.62, 121.67, 121.34, 121.11,
117.79, 116.76, 112.60, 112.30, 104.04.
HRMS: m/z [M]+ calcd for C23H14N4O: 362.1168; found: 362.1168.
6-(1H-Indol-3-yl)-4-(1-naphthyl)-2,2¢-bipyridine-5-carboni-
trile (4o)
Yellow solid; mp 270–271 °C.
IR (KBr): 3415, 3057, 2218, 1534, 1457, 1431, 1238, 805, 779, 747
cm–1.
HRMS: m/z [M]+ calcd for C25H1579BrN4: 450.0495; found:
450.0480.
1H NMR (400 MHz, DMSO-d6): d = 11.88 (br s, 1 H, NH), 8.73 (d,
J = 4.0 Hz, 1 H, ArH), 8.65 (d, J = 8.0 Hz, 1 H, ArH), 8.53–8.51 (m,
1 H, ArH), 8.40 (d, J = 2.4 Hz, 1 H, ArH), 8.30 (s, 1 H, ArH), 8.16–
8.10 (m, 3 H, ArH), 7.73–7.55 (m, 7 H, ArH), 7.30–7.28 (m, 2 H,
ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.08, 156.98, 154.46,
153.96, 149.70, 137.85, 136.44, 134.60, 133.17, 130.16, 129.66,
128.80, 129.58, 127.26, 127.18, 126.49, 126.02, 125.43, 125.36,
6-(5-Methyl-1H-indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carbo-
nitrile (4s)
Yellow solid; mp 256–258 °C.
IR (KBr): 3319, 3055, 2915, 2223, 1573, 1527, 1370, 1217, 784,
762, 698 cm–1.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

PAPER
Indole-Substituted Pyridine Derivatives
2705
1H NMR (400 MHz, DMSO-d6): d = 11.77 (br s, 1 H, NH), 8.80 (d,
J = 4.0 Hz, 1 H, ArH), 8.60 (d, J = 8.0 Hz, 1 H, ArH), 8.36 (d,
J = 2.8 Hz, 1 H, ArH), 8.30 (s, 1 H, ArH), 8.24 (s, 1 H, ArH), 8.13
(dt, J = 7.6, 1.6 Hz, 1 H, ArH), 7.81–7.79 (m, 2 H, ArH), 7.66–7.58
(m, 4 H, ArH), 7.45 (d, J = 8.0 Hz, 1 H, ArH), 7.11 (d, J = 8.4 Hz,
1 H, ArH), 2.49 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 157.55, 157.15, 155.21,
154.06, 149.81, 137.85, 136.92, 134.76, 129.90, 129.52, 128.94,
128.75, 126.32, 125.44, 124.05, 121.58, 121.04, 118.83, 116.21,
112.36, 111.87, 102.74, 21.68.
6-(5-Bromo-1H-indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carboni-
trile (4w)
Yellow solid; mp >300 °C.
IR (KBr): 3343, 3059, 2218, 1577, 1547, 1531, 1447, 1369, 889,
760, 697 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 12.03 (br s, 1 H, NH), 8.80 (d,
J = 4.0 Hz, 1 H, ArH), 8.61 (s, 1 H, ArH), 8.51 (d, J = 7.6 Hz, 1 H,
ArH), 8.46 (s, 1 H, ArH), 8.31 (s, 1 H, ArH), 8.13–8.09 (m, 1 H,
ArH), 7.79–7.78 (m, 2 H, ArH), 7.63–7.54 (m, 5 H, ArH), 7.41–7.39
(m, 1 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.08, 156.63, 155.09,
153.85, 149.73, 137.57, 136.66, 135.04, 130.01, 129.79, 128.80,
128.60, 127.73, 125.33, 124.89, 123.70, 121.24, 118.46, 116.59,
114.13, 113.48, 112.31, 102.84.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1532.
6–(6-Methyl-1H-indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carbo-
nitrile (4t)
Yellow solid; mp >300 °C.
HRMS: m/z [M]+ calcd for C25H1579BrN4: 450.0480; found:
450.0482.
IR (KBr): 3333, 3055, 2915, 2219, 1579, 1535, 1508, 1445, 1370,
1218, 1165, 811, 701 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.73 (br s, 1 H, NH), 8.77 (d,
J = 4.8 Hz, 1 H, ArH), 8.56 (d, J = 8.0 Hz, 1 H, ArH), 8.32 (d,
J = 2.8 Hz, 1 H, ArH), 8.29 (d, J = 8.0 Hz, 1 H, ArH), 8.27 (s, 1 H,
ArH), 8.08 (t, J = 7.6 Hz, 1 H, ArH), 7.78–7.76 (m, 2 H, ArH),
7.61–7.55 (m, 4 H, ArH), 7.35 (s, 1 H, ArH), 7.08 (d, J = 8.0 Hz, 1
H, ArH), 2.46 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 157.41, 157.09, 155.10,
153.96, 149.67, 137.75, 136.88, 136.81, 131.64, 129.81, 128.86,
128.69, 128.25, 125.31, 123.96, 122.72, 121.56, 121.05, 118.80,
116.16, 112.73, 111.86, 102.57, 21.35.
4-(2-Chlorophenyl)-6-(1H-indol-3-yl)-1,4-dihydro-2,2¢-bipyri-
dine-5-carbonitrile (5a)
Colorless solid; mp 246–248 °C.
IR (KBr): 3382, 3294, 3060, 2189, 1671, 1599, 1567, 1474, 1435,
765, 744 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.84 (br s, 1 H, NH), 8.66 (br
s, 1 H, NH), 8.59 (d, J = 4.4 Hz, 1 H, ArH), 8.00 (d, J = 2.8 Hz, 1
H, ArH), 7.93 (d, J = 8.0 Hz, 1 H, ArH), 7.87–7.83 (m, 1 H, ArH),
7.76 (d, J = 8.0 Hz, 1 H, ArH), 7.61 (dd, J = 8.0, 1.6 Hz, 1 H, ArH),
7.55–7.50 (m, 2 H, ArH), 7.46–7.43 (m, 1 H, ArH), 7.41–7.38 (m,
1 H, ArH), 7.33 (dt, J = 8.0, 1.6 Hz, 1 H, ArH), 7.26–7.22 (m, 1 H,
ArH), 7.20–7.17 (m, 1 H, ArH), 5.91 (dd, J = 5.2, 1.2 Hz, 1 H, CH),
5.11 (d, J = 5.2 Hz, 1 H, CH).
13C NMR (75 MHz, DMSO-d6): d = 149.46, 148.34, 146.10,
142.47, 137.17, 136.16, 133.19, 131.08, 130.61, 129.46, 128.65,
128.09, 127.51, 124.61, 123.56, 122.13, 121.68, 120.34, 119.24,
119.15, 112.41, 107.95, 101.06, 74.90, 38.79.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1533.
6-(7-Methyl-1H-indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carbo-
nitrile (4u)
Yellow solid; mp 298–299 °C.
IR (KBr): 3334, 3053, 2220, 1566, 1533, 1449, 1372, 1219, 1174,
745, 702 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.84 (br s, 1 H, NH), 8.79 (d,
J = 4.0 Hz, 1 H, ArH), 8.58 (d, J = 8.0 Hz, 1 H, ArH), 8.38 (d,
J = 2.4 Hz, 1 H, ArH), 8.31 (s, 1 H, ArH), 8.24 (d, J = 8.0 Hz, 1 H,
ArH), 8.11 (t, J = 7.6 Hz, 1 H, ArH), 7.81–7.79 (m, 2 H, ArH),
7.63–7.57 (m, 4 H, ArH), 7.17 (t, J = 7.6 Hz, 1 H, ArH), 7.07 (d,
J = 7.2 Hz, 1 H, ArH), 2.56 (s, 3 H, CH3).
HRMS: m/z [M]+ calcd for C25H1735ClN4: 408.1142; found:
408.1138.
4-(2-Bromophenyl)-6-(1H-indol-3-yl)-1,4-dihydro-2,2¢-bipyri-
dine-5-carbonitrile (5b)
Colorless solid; mp 262–264 °C.
13C NMR (75 MHz, DMSO-d6): d = 157.51, 157.12, 155.11,
153.95, 149.72, 137.83, 136.88, 135.87, 129.86, 128.89, 128.73,
128.59, 125.78, 125.37, 122.93, 121.57, 121.31, 121.14, 118.84,
118.78, 116.30, 113.17, 103.02, 16.82.
IR (KBr): 3382, 3308, 3130, 2185, 1599, 1566, 1543, 1465, 1435,
764, 743 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.80 (br s, 1 H, NH), 8.62 (br
s, 1 H, NH), 8.58 (d, J = 4.8 Hz, 1 H, ArH), 7.99 (d, J = 2.8 Hz, 1
H, ArH), 7.90 (d, J = 8.0 Hz, 1 H, ArH), 7.84 (dt, J = 7.6, 1.6 Hz, 1
H, ArH), 7.77 (d, J = 8.0 Hz, 1 H, ArH), 7.67 (d, J = 8.0, 1.6 Hz, 1
H, ArH), 7.62 (dd, J = 7.6, 1.6 Hz, 1 H, ArH), 7.55 (d, J = 8.0, 1.6
Hz, 1 H, ArH), 7.48 (t, J = 7.6 Hz, 1 H, ArH), 7.40–7.37 (m, 1 H,
ArH), 7.26–7.17 (m, 3 H, ArH), 5.90 (dd, J = 4.8, 1.2 Hz, 1 H, CH),
5.10 (d, J = 5.2 Hz, 1 H, CH).
13C NMR (75 MHz, DMSO-d6): d = 149.46, 148.37, 146.10,
144.23, 137.18, 136.18, 133.08, 132.72, 130.90, 129.03, 128.75,
127.58, 124.64, 123.59, 122.16, 121.71, 121.56, 120.37, 119.26,
119.21, 112.44, 107.94, 101.15, 75.15, 41.38.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1531.
6-(1-Methyl-1H-indol-3-yl)-4-phenyl-2,2¢-bipyridine-5-carbo-
nitrile (4v)
Yellow solid; mp 243–244 °C.
IR (KBr): 3053, 3008, 2934, 2216, 1575, 1564, 1539, 1471, 1363,
1242, 752 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 8.79 (d, J = 4.8 Hz, 1 H, ArH),
8.57 (d, J = 8.0 Hz, 1 H, ArH), 8.41 (d, J = 7.2 Hz, 1 H, ArH), 8.38
(s, 1 H, ArH), 8.31 (s, 1 H, ArH), 8.11 (dt, J = 7.6, 1.6 Hz, 1 H,
ArH), 7.80–7.78 (m, 2 H, ArH), 7.63–7.57 (m, 5 H, ArH), 7.37–7.29
(m, 2 H, ArH), 3.96 (s, 3 H, CH3).
HRMS: m/z [M]+ calcd for C25H1779BrN4: 452.0637; found:
452.0625.
13C NMR (75 MHz, DMSO-d6): d = 157.19, 156.99, 155.20,
153.90, 149.74, 137.86, 136.94, 136.83, 132.54, 129.88, 128.91,
128.70, 126.37, 125.41, 122.53, 121.60, 121.39, 121.20, 118.58,
116.39, 111.87, 110.56, 102.84, 33.20.
4-(4-Chlorophenyl)-6-(1H-indol-3-yl)-2,3¢-bipyridine-5-carbo-
nitrile (7a)
Yellow solid; mp 278–280 °C.
IR (KBr): 3369, 2217, 1594, 1575, 1533, 1493, 1447, 1360, 1089,
1015, 739 cm–1.
HRMS: m/z [M]+ calcd for C26H18N4: 386.1531; found: 386.1532.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

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K. Zhao et al.
PAPER
4-(2-Furyl)-6-(1H-indol-3-yl)-2,3¢-bipyridine-5-carbonitrile
(7e)
1H NMR (400 MHz, DMSO-d6): d = 11.85 (br s, 1 H, NH), 9.50 (s,
1 H, ArH), 8.74 (d, J = 4.8 Hz, 1 H, ArH), 8.66 (dd, J = 8.0, 1.6 Hz,
1 H, ArH), 8.40–8.37 (m, 2 H, ArH), 8.05 (s, 1 H, ArH), 7.86 (d,
J = 8.4 Hz, 2 H, ArH), 7.68 (d, J = 8.4 Hz, 2 H, ArH), 7.63–7.60 (m,
1 H, ArH), 7.56 (d, J = 8.0 Hz, 1 H, ArH), 7.30–7.22 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.53, 156.25, 154.03,
151.05, 148.65, 136.40, 135.44, 134.90, 133.05, 130.98, 129.01,
128.80, 125.97, 124.03, 122.50, 121.27, 120.93, 118.66, 116.75,
112.77, 112.21, 104.31, 101.98.
Brown solid; mp 293–294 °C.
IR (KBr): 3137, 3102, 3045, 2214, 1591, 1534, 1487, 1446, 1233,
1031, 752, 740 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.84 (br s, 1 H, NH), 9.48 (s,
1 H, ArH), 8.74 (d, J = 4.4 Hz, 1 H, ArH), 8.64 (d, J = 7.6 Hz, 1 H,
ArH), 8.39 (d, J = 2.4 Hz, 1 H, ArH), 8.31 (d, J = 7.2 Hz, 1 H, ArH),
8.25 (s, 1 H, ArH), 8.11 (s, 1 H, ArH), 7.72 (d, J = 3.6 Hz, 1 H,
ArH), 7.64–7.61 (m, 1 H, ArH), 7.55 (d, J = 7.6 Hz, 1 H, ArH),
7.27–7.20 (m, 2 H, ArH), 6.86 (s, 1 H, ArH).
HRMS: m/z [M]+ calcd for C25H1535ClN4: 406.0985; found:
406.0986.
13C NMR (75 MHz, DMSO-d6): d = 158.19, 156.21, 150.93,
148.38, 148.13, 146.12, 141.72, 136.28, 134.65, 132.96, 128.94,
126.00, 123.90, 122.35, 121.21, 120.76, 118.92, 114.35, 112.98,
112.62, 112.05, 111.80, 96.60.
6-(1H-Indol-3-yl)-4-(4-nitrophenyl)-2,3¢-bipyridine-5-carboni-
trile (7b)
Yellow solid; mp >300 °C.
IR (KBr): 3358, 2216, 1569, 1535, 1349, 853, 742, 700 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.93 (br s, 1 H, NH), 9.53 (d,
J = 1.6 Hz, 1 H, ArH), 8.76–8.75 (m, 1 H, ArH), 8.70–8.68 (m, 1 H,
ArH), 8.46 (d, J = 8.8 Hz, 2 H, ArH), 8.42–8.38 (m, 2 H, ArH), 8.16
(s, 1 H, ArH), 8.12 (d, J = 8.8 Hz, 2 H, ArH), 7.66–7.63 (m, 1 H,
ArH), 7.58–7.56 (m, 1 H, ArH), 7.29–7.23 (m, 2 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.51, 156.43, 153.20,
151.21, 148.68, 148.24, 142.90, 136.44, 134.95, 132.92, 130.70,
129.12, 125.95, 124.10, 123.76, 122.61, 121.28, 121.06, 118.40,
116.73, 112.71, 112.27, 101.86.
HRMS: m/z [M]+ calcd for C23H14N4O: 362.1168; found: 362.1169.
4-(4-Chlorophenyl)-2-(1H-indol-3-yl)-6-(2-thienyl)nicotinoni-
trile (9a)
Yellow solid; mp >300 °C.
IR (KBr): 3340, 3052, 2211, 1595, 1580, 1528, 1491, 1434, 1236,
1143, 835, 743 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.84 (br s, 1 H, NH), 8.55–
8.53 (m, 1 H, ArH), 8.42 (d, J = 2.8 Hz, 1 H, ArH), 8.13 (d, J = 3.2
Hz, 1 H, ArH), 7.92 (s, 1 H, ArH), 7.85 (d, J = 4.8 Hz, 1 H, ArH),
7.79 (d, J = 8.4 Hz, 2 H, ArH), 7.67 (d, J = 8.4 Hz, 2 H, ArH), 7.57–
7.54 (m, 1 H, ArH), 7.28–7.24 (m, 3 H, ArH).
HRMS: m/z [M]+ calcd for C25H15N5O2: 417.1226; found:
417.1227.
13C NMR (75 MHz, DMSO-d6): d = 157.20, 153.79, 153.70,
143.59, 136.35, 135.56, 134.73, 131.28, 130.84, 129.04, 128.86,
128.77, 128.53, 126.05, 122.52, 121.78, 120.87, 118.90, 114.40,
112.41, 112.12, 100.17.
HRMS: m/z [M]+ calcd for C24H1435ClN3S: 411.0597; found:
411.0598.
6-(1H-Indol-3-yl)-4-phenyl-2,3¢-bipyridine-5-carbonitrile (7c)
Yellow solid; mp 282–284 °C.
IR (KBr): 3205, 3104, 2223, 1582, 1567, 1533, 1447, 1218, 748,
701 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.90 (br s, 1 H, NH), 9.51 (d,
J = 2.0 Hz, 1 H, ArH), 8.73 (d, J = 4.8 Hz, 1 H, ArH), 8.67 (d,
J = 8.0 Hz, 1 H, ArH), 8.41 (d, J = 2.8 Hz, 1 H, ArH), 8.39–8.37 (m,
1 H, ArH), 8.06 (s, 1 H, ArH), 7.84–7.82 (m, 2 H, ArH), 7.63–7.60
(m, 4 H, ArH), 7.57–7.55 (m, 1 H, ArH), 7.28–7.22 (m, 2 H, ArH).
4-(4-Bromophenyl)-2-(1H-indol-3-yl)-6-(2-thienyl)nicotinoni-
trile (9b)
Yellow solid; mp >300 °C.
13C NMR (75 MHz, DMSO-d6): d = 157.49, 156.11, 155.24,
150.91, 148.58, 136.60, 136.34, 134.79, 133.06, 129.75, 128.93,
128.84, 128.66, 125.97, 123.89, 122.38, 121.24, 120.80, 118.67,
116.74, 112.78, 112.09, 101.99.
IR (KBr): 3332, 3049, 2213, 1572, 1526, 1433, 1237, 1143, 1010,
830, 742 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.84 (br s, 1 H, NH), 8.56–
8.54 (m, 1 H, ArH), 8.42 (d, J = 2.8 Hz, 1 H, ArH), 8.12 (d, J = 3.2
Hz, 1 H, ArH), 7.91 (s, 1 H, ArH), 7.85 (d, J = 4.8 Hz, 1 H, ArH),
7.80 (d, J = 8.4 Hz, 2 H, ArH), 7.71 (d, J = 8.4 Hz, 2 H, ArH), 7.57–
7.55 (m, 1 H, ArH), 7.28–7.23 (m, 3 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.14, 153.70, 153.64,
143.48, 136.28, 135.83, 131.57, 130.89, 128.85, 128.72, 128.35,
128.30, 125.99, 123.32, 122.39, 121.73, 120.74, 118.72, 114.24,
114.18, 112.38, 111.98, 99.98.
HRMS: m/z [M]+ calcd for C25H16N4: 372.1375; found: 372.1377.
6-(1H-Indol-3-yl)-4-(4-methoxyphenyl)-2,3¢-bipyridine-5-car-
bonitrile (7d)
Yellow solid; mp 233–235 °C.
IR (KBr): 3216, 3163, 2962, 2213, 1607, 1581, 1536, 1514, 1260,
1186, 812, 751 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.83 (br s, 1 H, NH), 8.49 (s,
1 H, ArH), 8.73 (d, J = 4.4 Hz, 1 H, ArH), 8.65 (d, J = 8.0 Hz, 1 H,
ArH), 8.40–8.36 (m, 2 H, ArH), 8.00 (s, 1 H, ArH), 7.80 (d, J = 8.4
Hz, 2 H, ArH), 7.62–7.59 (m, 1 H, ArH), 7.56 (d, J = 8.0 Hz, 1 H,
ArH), 7.28–7.21 (m, 2 H, ArH), 7.16 (d, J = 8.0 Hz, 2 H, ArH), 3.87
(s, 3 H, CH3).
HRMS: m/z [M]+ calcd for C24H1479BrN3S: 455.0092; found:
455.0091.
2-(1H-Indol-3-yl)-4-(4-nitrophenyl)-6-(2-thienyl)nicotinoni-
trile (9c)
Yellow solid; mp >300 °C.
13C NMR (100 MHz, DMSO-d6): d = 160.68, 157.69, 156.02,
154.91, 150.95, 148.64, 136.43, 134.88, 133.23, 130.67, 128.95,
128.74, 126.10, 124.02, 122.49, 121.37, 120.92, 119.17, 116.60,
114.21, 112.93, 112.21, 101.83, 55.45.
IR (KBr): 3400, 2213, 1572, 1526, 1436, 1347, 1237, 854, 740
cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.85 (br s, 1 H, NH), 8.57–
8.54 (m, 1 H, ArH), 8.47–8.43 (m, 3 H, ArH), 8.14 (d, J = 3.2 Hz, 1
H, ArH), 8.05 (d, J = 8.4 Hz, 2 H, ArH), 7.99 (s, 1 H, ArH), 7.87 (d,
J = 4.8 Hz, 1 H, ArH), 7.57–7.55 (m, 1 H, ArH), 7.29–7.25 (m, 3 H,
ArH).
HRMS: m/z [M]+ calcd for C26H18N4O: 402.1482; found: 402.1481.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

PAPER
Indole-Substituted Pyridine Derivatives
2707
13C NMR (75 MHz, DMSO-d6): d = 157.17, 153.93, 152.85,
148.16, 143.46, 143.06, 136.37, 131.53, 130.56, 129.09, 128.96,
128.76, 126.01, 123.75, 122.59, 121.78, 120.95, 118.63, 114.39,
112.33, 112.17, 99.96.
HRMS: m/z [M]+ calcd for C24H14N4O2S: 422.0837; found:
422.0838.
(4) (a) Constable, E. C. Tetrahedron 1992, 48, 10013.
(b) Sauvage, J. P.; Collin, J. P.; Chambron, J. C.; Guillerez,
S.; Coudret, C.; Balzani, V.; Barigelletti, F.; De Cola, L.;
Flamigni, L. Chem. Rev. 1994, 94, 993. (c) Bernhard, S.;
Barron, J. A.; Houston, P. L.; Abruna, H. D.; Ruglovksy, J.
L.; Gao, X.; Malliaras, G. G. J. Am. Chem. Soc. 2002, 124,
13624. (d) Newkome, G. R.; Patri, A. K.; Holder, E.;
Schubert, U. S. Eur. J. Org. Chem. 2004, 235.
2-(1H-Indol-3-yl)-4-(3-nitrophenyl)-6-(2-thienyl)nicotinoni-
trile (9d)
Yellow solid; mp 285–286 °C.
IR (KBr): 3388, 2215, 1573, 1526, 1438, 1349, 1236, 740 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.90 (br s, 1 H, NH), 8.66–
8.65 (m, 1 H, ArH), 8.56–8.54 (m, 1 H, ArH), 8.46–8.44 (m, 2 H,
ArH), 8.26 (d, J = 8.0 Hz, 1 H, ArH), 8.18 (d, J = 4.0 Hz, 1 H, ArH),
8.08 (s, 1 H, ArH), 7.93 (d, J = 8.0 Hz, 1 H, ArH), 7.90–7.88 (m, 1
H, ArH), 7.57–7.55 (m, 1 H, ArH), 7.30–7.25 (m, 3 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.76, 157.22, 156.71,
154.71, 153.72, 150.39, 138.51, 137.08, 132.07, 130.90, 129.19,
126.65, 126.39, 125.99, 123.14, 122.21, 121.87, 121.60, 121.51,
119.06, 118.03, 113.38, 112.86, 112.57, 105.55.
(5) (a) Namba, K.; Cui, S.; Wang, J.; Kishi, Y. Org. Lett. 2005,
7, 5417. (b) Namba, K.; Wang, J.; Cui, S.; Kishi, Y. Org.
Lett. 2005, 7, 5421.
(6) (a) Juris, A.; Balzani, V.; Barigelletti, F.; Campagna, S.;
Belser, A.; von Zelewsky, A. Coord. Chem. Rev. 1988, 84,
85. (b) Balzani, V.; Juris, A.; Venturi, M.; Campagna, S.;
Serroni, S. Chem. Rev. 1996, 96, 759.
(7) Meyer, T. J. Acc. Chem. Res. 1989, 22, 163.
(8) (a) Dupray, L. M.; Devenney, M.; Striplin, D. R.; Meyer, T.
J. J. Am. Chem. Soc. 1997, 119, 10243. (b) Newkome, G.
R.; Patri, A. K.; Godinez, L. A. Chem. Eur. J. 1999, 5, 1445.
(c) Constable, E. C.; Harverson, P.; Oberholzer, M. Chem.
Commun. 1996, 1821.
(9) (a) Schubert, U. S.; Eschbaumer, C.; Heller, M. Org. Lett.
2000, 2, 3373. (b) Tu, S.-J.; Jiang, B.; Yao, C.-S.; Jiang, H.;
Zhang, J.-Y.; Jia, R.-H.; Zhang, Y. Synthesis 2007, 1366.
(c) Tu, S.-J.; Jiang, B.; Zhang, Y.; Zhang, J.-Y.; Jia, R.-H.;
Yao, C.-S. Chem. Lett. 2006, 35, 1338.
HRMS: m/z [M]+ calcd for C24H14N4O2S: 422.0837; found:
422.0852.
2-(1H-Indol-3-yl)-4-phenyl-6-(2-thienyl)nicotinonitrile (9e)
Yellow solid; mp 283–285 °C.
(10) Houlihan, W. J.; Remers, W. A.; Brown, R. K. Indoles: Part
I; Wiley: New York, 1992.
IR (KBr): 3307, 3062, 2220, 1573, 1539, 1526, 1431, 1238, 1140,
760, 695 cm–1.
(11) (a) Creed, D. Photochem. Photobiol. 1984, 39, 537.
(b) Gupta, L.; Talwar, A.; Palne, N. S.; Gupta, S.; Chauhan,
P. M. S. Bioorg. Med. Chem. Lett. 2007, 17, 4075.
(c) Jiang, B.; Xiong, X.; Yang, C. Bioorg. Med. Chem. Lett.
2001, 11, 475. (d) Sakemi, S.; Sun, H. H. J. Org. Chem.
1991, 56, 4304.
(12) (a) Yan, C.-G.; Wang, Q.-F.; Song, X.-K.; Sun, J. J. Org.
Chem. 2009, 74, 710. (b) Wang, S.-Y.; Ji, S.-J. Synlett 2007,
2222. (c) Zhu, S.-L.; Ji, S.-J.; Zhang, Y. Tetrahedron 2007,
63, 9365. (d) Wang, S.-Y.; Ji, S.-J. Tetrahedron 2006, 62,
1527.
1H NMR (400 MHz, DMSO-d6): d = 11.88 (br s, 1 H, NH), 8.56–
8.54 (m, 1 H, ArH), 8.43 (d, J = 2.8 Hz, 1 H, ArH), 8.16 (d, J = 3.6
Hz, 1 H, ArH), 7.95 (s, 1 H, ArH), 7.85 (d, J = 4.8 Hz, 1 H, ArH),
7.78–7.76 (m, 2 H, ArH), 7.61–7.55 (m, 4 H, ArH), 7.28–7.23 (m,
3 H, ArH).
13C NMR (75 MHz, DMSO-d6): d = 157.27, 154.99, 153.74,
143.70, 136.79, 136.39, 131.16, 129.74, 129.03, 128.90, 128.85,
128.75, 128.42, 126.13, 122.54, 121.86, 120.88, 119.06, 114.49,
112.50, 112.13, 100.30.
(13) (a) Lo, K. K.-W.; Tsang, K. H.-K.; Hui, W.-K.; Zhu, N.
Chem. Commun. 2003, 44, 2704. (b) Lo, K. K.-W.; Tsang,
K. H.-K.; Hui, W.-K.; Zhu, N. Inorg. Chem. 2005, 44, 6100.
(c) Bowyer, P. K.; Black, D. St. C.; Craig, D. C.; Rae, A. D.;
Willis, A. C. J. Chem. Soc., Dalton Trans. 2001, 1948.
(14) (a) Kröehnke, F. Angew. Chem., Int. Ed. Engl. 1963, 2, 380;
Angew. Chem. 1963, 75, 317. (b) Kröehnke, F. Synthesis
1976, 1.
HRMS: m/z [M]+ calcd for C24H15N3S: 377.0987; found: 377.0985.
Acknowledgment
The work was partially supported by the National Natural Science
Foundation of China (No. 20672079), Natural Science Foundation
of Jiangsu Province (No. BK2006048), Nature Science of Jiangsu
Province for Higher Education (No. 05KJB150116), Nature Sci-
ence Key Basic Research of Jiangsu Province for Higher Education
(No. 06KJA15007), the Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20060285001), and Key Labo-
ratory of Organic Synthesis of Jiangsu Province (No. JSK008).
(15) (a) Rode, T.; Breitmaier, E. Synthesis 1987, 574.
(b) Baxter, P. N. W.; Connor, J. A. J. Organomet. Chem.
1988, 355, 193. (c) Vögtle, F.; Hochberg, R.;
Kochendoerfer, F.; Windscheif, P. M.; Volkmann, M.;
Jansen, M. Chem. Ber. 1990, 123, 2181. (d) Percec, V.;
Barboiu, B.; Kim, H.-J. J. Am. Chem. Soc. 1998, 120, 305.
(16) (a) Uchida, Y.; Kajita, R.; Kawasaki, Y.; Oae, S.
Tetrahedron Lett. 1995, 36, 4077. (b) Uchida, Y.; Kozawa,
H. Tetrahedron Lett. 1989, 30, 6365. (c) Uchida, Y.;
Onoue, K.; Tada, N.; Nagao, F. Tetrahedron Lett. 1989, 30,
567. (d) Newkome, G. R.; Hager, D. C. J. Am. Chem. Soc.
1978, 100, 5567.
(17) (a) Furukawa, N.; Shibutani, T.; Fujihara, H. Tetrahedron
Lett. 1989, 30, 7091. (b) Oae, S.; Takeda, T.; Wakabayashi,
S. Tetrahedron Lett. 1988, 29, 4445. (c) Kawai, T.;
Furukawa, N. Tetrahedron Lett. 1984, 25, 2549.
(18) (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis
1984, 936. (b) Lehmann, U.; Henze, O.; Schlüter, D. Chem.
Eur. J. 1999, 5, 854.
References
(1) Yates, F.; Courts, R. T.; Casy, A. F. Pyridine and Its
Derivatives: Supplement IV; Abramovitch, R. A., Ed.;
Wiley: New York, 1975, 445.
(2) Yates, F. S. Comprehensive Heterocyclic Chemistry, Vol. 2;
Katritzky, A. R.; Rees, C. W., Eds.; Pergamon: Oxford,
1984, 511.
(3) (a) Dowell, R. I.; Hales, N. J.; Tucker, H. Eur. J. Med. Chem.
1993, 28, 513. (b) Zhou, X.-W.; Zhuang, Z.-L.; Chen, Q.-X.
J. Protein Chem. 1999, 18, 735. (c) Zhang, B.; Breslow, R.
J. Am. Chem. Soc. 1998, 120, 5854.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York

2708
K. Zhao et al.
PAPER
l (Mo-Ka) = 0.71070 Å, m = 0.082 mm–1, F(000) = 388,
3.10° < q < 25.34°, RI>2s(I) = 0.0544, wRI>2s(I) = 0.1159,
largest diff. peak and hole: 0.158 and –0.205 e Å–3. CCDC
reference number 684602.
(19) Savage, S. A.; Smith, A. P.; Fraser, C. L. J. Org. Chem.
1998, 63, 10048.
(20) Zhu, S.-L.; Ji, S.-J.; Su, X.-M.; Sun, C.; Liu, Y. Tetrahedron
Lett. 2008, 49, 1777.
(21) Kreher, R.; Wagner, P. H. Chem. Ber. 1980, 113, 3675.
(22) Slatt, J.; Romero, I.; Bergman, J. Synthesis 2004, 2760.
(23) (a) Devi, I.; Kumarb, B. S. D.; Bhuyan, P. J. Tetrahedron
Lett. 2003, 44, 8307. (b) Evdokimov, N. M.; Magedov, I.
V.; Kireev, A. S.; Kornienko, A. Org. Lett. 2006, 8, 899.
(24) Structural parameters for 4f: data collection: Rigaku
Mercury CCD area detector; C25H16N4, yellow solid, crystal
dimension 0.55 × 0.35 × 0.30 mm, triclinic, space group P1,
a = 9.7744 (16) Å, b = 9.7927 (11) Å, c = 11.233 (2) Å,
a = 73.121 (13)°, b = 86.008 (16)°, g = 63.853 (10)°,
V = 921.5 (2) Å3, Mr = 372.42, Z = 2, Dc = 1.171 Mg/m3,
(25) Structural parameters for 5b: data collection: Rigaku
Mercury CCD area detector; C25H17BrN4, colorless solid,
crystal dimension 0.27 × 0.20 × 0.16 mm, triclinic, space
group P1, a = 11.286 (2) Å, b = 13.516 (2) Å, c = 14.423 (3)
Å, a = 90.685 (2)°, b = 108.077 (3)°, g = 102.674 (3)°,
V = 2032.9 (6) Å3, Mr = 452.33, Z = 4, Dc = 1.478 Mg/m3,
l (Mo-Ka) = 0.71075 Å, m = 2.042 mm–1, F(000) = 916,
3.10° < q < 25.50°, RI>2s(I) = 0.0586, wRI>2s(I) = 0.1540,
largest diff. peak and hole: 2.424 and –0.662 e Å–3. CCDC
reference number 713488.
Synthesis 2009, No. 16, 2697–2708 © Thieme Stuttgart · New York