Use of ligand-free iron/copper cocatalyst for nitrogen and sulfur cross-coupling reaction with 6-iodoimidazo[1,2- a ]pyridine

Article abstract of DOI:10.1055/s-0034-1380383

A ligand-free cooperative bimetallic iron/copper catalysis system was found to introduce various azoles and thiols onto 6-iodoimidazo[1,2-a] pyridine. After optimization, the inexpensive, nontoxic, air-stable, and commercially available CuO and FeCl₂

Full text of DOI:10.1055/s-0034-1380383

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, A–K
paper
A
Z. Tber et al.
Paper
Synthesis
Use of Ligand-Free Iron/Copper Cocatalyst for Nitrogen and Sulfur
Cross-Coupling Reaction with 6-Iodoimidazo[1,2-a]pyridine
Zahira Tbera,b
RS
N
36–94% yield
14 examples
Marie-Aude Hiebela
Mohamed Akssirab
Gérald Guillaumeta
Sabine Berteina-Raboin*a
Ph
FeCl2•4H2O
RSH
or
N
N
I
CuO
N
Ph
+
ligand-free
N
HetArN
HetArNH
N
41–70% yield
7 examples
Ph
a Institut de Chimie Organique et Analytique (ICOA), Université
d’Orléans UMR-CNRS 7311, BP 6759, rue de Chartres, 45067
Orléans cedex 2, France
b Laboratoire de Chimie Physique et Chimie Bioorganique URAC
22, Université Hassan II-Mohammedia-Casablanca, FST, BP
146, 28800 Mohammedia, Morocco
sabine.berteina-raboin@univ-orleans.fr
Received: 11.12.2014
Accepted after revision: 18.02.2015
Published online: 21.04.2015
NEt2
NMe2
O
O
DOI: 10.1055/s-0034-1380383; Art ID: ss-2014-z0746-op
Cl
N
N
Cl
Abstract A ligand-free cooperative bimetallic iron/copper catalysis
system was found to introduce various azoles and thiols onto 6-iodoim-
idazo[1,2-a] pyridine. After optimization, the inexpensive, nontoxic, air-
stable, and commercially available CuO and FeCl2·4H2O enabled a regio-
selective N- and S-arylation of common nitrogen heterocycles and of a
broad range of mercaptans including aliphatic, aromatic, and heterocy-
clic thiols.
N
N
zolpidem
alpidem
O
CN
N
O
Me
Key words iron, copper, bimetallic catalysis, imidazo[1,2-a]pyridine,
N and S cross-coupling
Cl
HN
N
N
N
Cl
N
saridipem
olprinone
Imidazo[1,2-a]pyridines demonstrate a high pharma-
ceutical and biological potential.1 Several synthetic drugs
exhibiting an imidazo[1,2-a]pyridine motif have already
been commercialized, such as the sedative zolpidem, the
anxiolytic alpidem or saridipem, or the heart failure drug
olprinone (Figure 1).
The synthesis and functionalization of these drugs has
received considerable attention.2 Lately, the possible use of
a low-cost and environmentally sound catalytic system was
made possible by the significant breakthrough reported in-
dependently by Buchwald3 and Taillefer4 groups in copper-
catalyzed cross coupling of N–H heterocycles by using che-
lating agents. Since then several copper catalyst systems
were reported recently to introduce various azoles, amides,
and thiophenols at the 5 and 6 positions of the imidazo[1,2-
a]pyridine.5 However, these modified Ullmann and Gold-
berg coupling reactions still often required the addition of
an external ligand to promote the reaction6 even though ex-
amples of efficient systems in ligand-free conditions are
known.6e Because of its potential low cost and its high ter-
Figure 1 Commercialized drugs with an imidazo[1,2-a]pyridine motif
restrial abundance, interest in iron catalysts has been re-
newed. Kochi et al. were the first to use an iron catalyst in a
cross-coupling reaction;7 it is now being gradually reintro-
duced as copper cocatalyst without ligands or other addi-
tives for arylation, alkylnylation, C–H functionalization, and
conjugate addition reactions.8 Moreover, Taillefer et al. re-
ported the first example of iron/copper co-catalyzed C-, O-,
or N-arylation.4d To the best of our knowledge, no proce-
dure has been reported using a combination of iron salts
with copper as a catalytic system for cross-coupling reac-
tions on imidazo[1,2-a]pyridines. Based on our interest in
developing environmentally sound methods9 and our back-
ground in the synthesis and functionalization of imid-
azo[1,2-a]pyridines,10 we therefore disclose herein a li-
gand-free iron/copper cocatalyst to perform N and S cross-
coupling reactions. In view of our diversity-targeting pur-
pose, we focused on introducing miscellaneous challenging
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

B
Z. Tber et al.
Paper
Synthesis
azoles, and aliphatic, aromatic, and heterocyclic thiols since
it would give an access to numerous biologically active ap-
pealing compounds.
ture of products, a significant improvement was obtained
with the FeCl2·4H2O/CuO system, where 3a was isolated in
61% yield along with 21% of dehalogenated product 2 easily
removed by column chromatography (entry 3). Copper fer-
rite induced interesting results, but the formation of 3a
came along with a small amount of 3b, which is significant-
ly tough to remove (entry 4). Therefore, because of the diffi-
culty of isolating the desired product, this experimental
condition was disfavored. Other copper sources with differ-
ent oxidation states (0, I) were then used but without im-
provement (entries 5 and 6). The combination of FeCl2·4H2O
and CuO gave the best results. The crucial presence of iron
was underlined as CuO alone was not able to efficiently
promote the reaction (entry 8). Even if brominated prod-
ucts undergo reduction slower, brominated imidazo[1,2-
a]pyridines induced no yield improvement even after a lon-
ger reaction time (entry 10). The reduction of the reactivity
was underlined in the case of 6-chloroimidazo[1,2-a]pyri-
First, the conditions described by Taillefer et al.4c at
90 °C were attempted at a higher temperature on our sub-
strate (Table 1, entry 1), but a mixture of 2-phenyl-6-(1H-
pyrazol-1-yl)imidazo[1,2-a]pyridine (3a), 2-phenyl-5-(1H-
pyrazol-1-yl)imidazo[1,2-a]pyridine (3b), and a dehaloge-
nated product 2 was obtained.
The formation of 5-substituted derivatives had already
been observed by Gueiffier et al.5b and seemed to be fa-
vored by the absence of copper. In our case, the use of an
iron catalyst appeared to emphasize this effect since 3b was
obtained in a better yield with FeCl2·4H2O compared with
cesium carbonate alone (Table 1, entries 7 and 9, 58% and
45%, respectively). In order to increase the formation of our
desired product 3a, a survey of the iron/copper catalytic
system was undertaken. While FeCl3/CuO also gave a mix-
Table 1 Optimization of the Iron/Copper Catalytic System for the N-Arylation of Pyrazole with 6-Iodoimidazo[1,2-a]pyridine
N
N
I
N
N
[Fe]/[Cu] (cat.)
N
N
N
N
Ph
+
Ph
HN
Ph
Cs2CO3 (2 equiv)
135 °C, 48 h
N
N
N
2 equiv
1
3a
3b
N
Ph
N
2
Entry
[Fe] cat. (0.3 equiv)
[Cu] cat. (0.1 equiv)
Solvent
Yield (%)a of 2/3a/3b
1
2
Fe(acac)3
FeCl3
CuO
CuO
CuO
DMF
30:20:30
40:20:35
21:61:0
2:60:16b
18:45:25
20:45:30
24:10:58
16:27:26
2:0:45b
DMF
3
FeCl2·4H2O
CuFe2O4 (0.1 equiv)
FeCl2·4H2O
FeCl2·4H2O
FeCl2·4H2O
–
DMF
4
DMF
5
CuI
Cu
DMF
6
DMF
7
–
DMF
8
CuO
–
DMF
9
–
DMF
10
11
12
13
14
FeCl2·4H2O
FeCl2·4H2O
FeCl2·4H2O
FeCl2·4H2O
FeCl2·4H2O
CuO
CuO
CuO
CuO
CuO
DMF
28:40:10b,c
20:0:0b
H2O–MeCN
toluene
i-PrOH
DMF
0:0:0b,d
0:0:0b,e
18:55:0f
a Isolated yields.
b After 86 h.
c 6-Bromoimidazo[1,2-a]pyridine was used instead of the 6-iodo substrate.
d Degradation.
e Starting material recovered.
f Reaction temperature at 90 °C, isolated yield after 72 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

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Z. Tber et al.
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Synthesis
dine, which gave no cross-coupling adduct. Different sol-
vents and temperature were then examined, without in-
ducing any progress. It was found that the optimal coupling
conditions were FeCl2·4H2O (30 mol%), CuO (10 mol%),
Cs2CO3 (2 equiv) with pyrazole (2 equiv) in DMF for 48
hours at 135 °C (entry 3).
In an endeavor to expand the scope of the methodology,
the reactivity of various azoles was examined (Table 2).
We were pleased to observe that the imidazo[1,2-a]pyr-
idines substituted at 6 position 3a–9a were obtained in
moderate to good yields as the major product. However, for
indole and imidazole, a small amount of product substitut-
ed at C5 was isolated (Table 2, entries 5 and 6). Arylation
with indazole proceeded exclusively at N-1, meaning that
the possible previous equilibrium between the copper N-1
and N-2 indazole did not occur.3b It was found that the less
acidic pyrrole NH was successfully introduced with a longer
reaction time without changing the base (entry 4). Then,
the challenging 7-azaindole as well as 1,2,4-triazole gave
regioselectively the expected products 5a and 9a in 45 and
58% yield, respectively. Furthermore, except in the case of
pyrazole, 2-phenylimidazo[1,2-a]pyridine 2 was not ob-
served or only in trace amounts.
Table 2 N-Arylation of 6-Iodoimidazo[1,2-a]pyridine with Various Nitrogen-Containing Heterocycles
FeCl2•4H2O (30 mol%)
NHetAr
N
I
HetArN
CuO (10 mol%)
N
N
+
HetArNH
(2 equiv)
Ph
Ph
+
Ph
Cs2CO3 (2 equiv)
DMF
N
N
N
1
3a–9a
3b–9b
135 °C, 48 h
Entry
1
HetArNH
Product aa
Product ba
N
N
N
NH
–
–
–
–
Ph
N
N
3a, 61%
N
N
N
N
2
Ph
Ph
N
H
N
N
4a, 41%
H
N
N
N
N
3
N
5a, 45%
N
4b
N
NH
Ph
N
6a, 70%
H
N
N
N
N
5
Ph
N
N
Ph
7a, 68%
N
7b, 20%
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Table 2 (continued)
Entry
HetArNH
Product aa
Product ba
N
N
N
N
N
N
6
NH
Ph
N
N
Ph
N
8a, 50%
N
8b, 20%
N
N
N
NH
N
7
–
Ph
N
N
9a, 58%
a Isolated yields.
b Yield after 72 h of reaction.
In order to demonstrate the generality of our method,
extension to the C–S coupling reaction was next examined
with the same catalytic system. Thiols tend to deactivate
metal-based catalysts by a strong coordination and they can
also easily form disulfide moieties.11 In our case, in the
presence of 4-methoxybenzenethiol, 10 was obtained in
75% yield. The combined effect of iron and copper catalyst
was next investigated (Table 3).
Each catalyst alone gave mainly the dehalogenated
product 2; furthermore only traces of the expected product
were obtained with cesium carbonate in the absence of any
catalyst, indicating an efficient cooperative bimetallic catal-
ysis with iron and copper. Next, these conditions were em-
ployed in a wide range of substrates including aromatic, ali-
phatic, and heterocyclic thiols on 6-iodoimidazo[1,2-a]pyr-
idine (Table 4).
tron-withdrawing and -donating groups gave the expected
product with excellent yield. Then, alkyl thiols, which are
known to be more difficult to react than thiols at sp2-car-
bon centers, gave the expected product in moderate to good
yields.12 Cyclic, linear, and branched-chain aliphatic satu-
rated mercaptans were well tolerated. Unlike phenyl
groups, benzylic substituents exhibited a different reactivi-
ty toward the presence of electron-donating and -with-
drawing groups on the aromatic ring products 14 and 15,
respectively. With 4-fluorobenzenethiol, a longer reaction
time was required to obtain completion of the reaction, and
along with 15, the by-product 2 was also isolated in 20%
yield, demonstrating the difficulty of the arylation. Aliphat-
ic thiols, such as the challenging cyclopentyl, and tert-
butylmercaptans reacted with 6-iodoimidazo[1,2-a]pyri-
dine to give 19 and 20 in 69 and 36% yield, respectively.
Lastly, we also extended the scope of thiol substrates to thi-
ols bearing benzo[d]thiazole. Our iron/copper system was
able to efficiently promote the coupling reaction, allowing
access to interesting heterocyclic sulfide derivatives.13 Be-
In general, the reactions were very clean and the ex-
pected products were synthesized in moderate to excellent
yields. First, different aromatic thiols were introduced
(products 10–13). It was found that substrates with elec-
Table 3 Extension to C–S Coupling reactions
SH
I
S
catalyst
N
N
+
Ph
Ph
Cs2CO3 (2 equiv)
DMF
135 °C, 24 h
N
N
MeO
MeO
(2 equiv)
1
10
Entry
[Fe] cat. (0.3 equiv)
[Cu] cat. (0.1 equiv)
Yield (%)a of 10/2
1
2
3
4
FeCl2·4H2O
CuO
–
75:0
FeCl2·4H2O
25:50
35:46
8:20b
–
–
CuO
–
a Isolated yields.
b Recovered 6-iodoimidazo[1,2-a]pyridine: 60%.
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Z. Tber et al.
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Synthesis
sides, it is worth noting that except in the case of 4-fluoro-
benzenethiol, neither dehalogenated product 2 nor diaryl
disulfides were formed during the reaction.
In summary, we have developed an efficient cooperative
bimetallic iron/copper catalyst system to introduce various
azoles and thiols on 6-iodoimidazo[1,2-a]pyridine. Af-
ter optimization, it was found that CuO (10 mol%) and
FeCl2·4H2O (30 mol%) in the presence of Cs2CO3 (2 equiv)
promoted a regioselective N-arylation of common nitrogen
heterocycles in moderate to good yields. Next, the scope of
the reaction was widened to a broad range of mercaptans
including aliphatic, aromatic, and heterocyclic thiols, with-
out changing the experimental conditions. It is the first
general method, which is able to successfully introduce this
wide variety of substituents. The salient features of our
method are the use of the inexpensive, nontoxic, air-stable,
and commercially available iron and copper salts. The coop-
erative effect of Cu and Fe was demonstrated and avoided
the additional use of ligands.
Table 4 S-Arylation and S-Alkylation of 6-Iodoimidazo[1,2-a]pyridine with Various Mercaptans
FeCl2·4H2O (30 mol%)
RS
I
CuO 10 mol%
N
N
Ph
RSH
+
Ph
Cs2CO3 (2 equiv)
135 °C, 48 h
DMF
N
N
(2 equiv)
1
10–23
R = hetaryl,
aryl, alkyl
Entry
1
Product
Entry
Product
75%
S
N
10
Ph
N
MeO
S
N
Ph
2
11
80%
N
F3C
S
S
N
N
N
Ph
3
4
12
13
74%
70%
N
N
OMe
Ph
S
N
N
N
Ph
Ph
Ph
5
14
70%
OMe
S
N
N
6
7
15
16
45%a
F
S
60%
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Table 4 (continued)
Entry
Product
Entry
Product
73%
EtS
N
8
9
17
18
19
20
Ph
N
i-PrS
N
51%
69%
36%
Ph
N
S
N
10
11
Ph
N
t-BuS
N
Ph
N
N
S
N
Ph
12
13
21
22
94%
S
N
N
N
S
Ph
Ph
60%b
S
N
O2N
EtO
S
N
N
S
14
23
92%
N
a Yield after 72 h of reaction, 20% of 2.
b Yield after 28 h of reaction.
All reactions were run under an inert atmosphere (argon) with oven-
dried (120 °C) glassware using standard techniques for manipulating
air-sensitive compounds. The reactions were monitored by TLC anal-
ysis using silica gel (60 F254) plates. Compounds were visualized by
UV irradiation. Flash column chromatography was performed on sili-
ca gel 60 (230–400 mesh, 0.040 0.063 mm). Petroleum ether (PE) re-
fers to a hydrocarbon mixture with a boiling range of 40–60 °C. Melt-
ing points were taken on samples in open capillary tubes and are un-
corrected. The IR spectra of compounds were recorded on a Thermo
Scientific Nicolet iS10 (ATR, neat). 1H and 13C NMR spectra were re-
corded on a spectrometer at 250.13 MHz (13C, 62.9 MHz) or 400.13
MHz (13C, 100.62 MHz). Chemical shifts are given in parts per million
from TMS as internal standard. Standard abbreviations are used to de-
note the proton spectra multiplicities. Coupling constants (J) are re-
ported in Hertz (Hz). High-resolution mass spectra (HRMS) were per-
formed on a Maxis Bruker 4G by the ‘Federation de Recherche’
ICOA/CBM (FR2708) platform.
luted with CH2Cl2 (20 mL), the CH2Cl2 layer was washed with H2O (2 ×
10 mL), and dried (MgSO4). After filtration and concentration under
reduced pressure, the crude product was purified by flash chromatog-
raphy on silica gel (EtOAc–PE, 1:2) to afford 1 as a white solid; yield:
2.037 g (70%); mp 196–197 °C.
IR (neat): 695, 768, 1516, 2995 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 7.33 (t, J = 7.4 Hz, 1 H), 7.41–
7.46 (m, 4 H), 7,95 (d, J = 7.6 Hz, 2 H), 8.31 (s, 1 H), 8.90 (s, 1 H).
13C NMR (100.62 MHz DMSO-d6): δ = 76.0, 108.9, 117.9, 125.6 (2 ×
CH), 127.9, 128.7 (2 × CH), 131.4, 132.4, 133.4, 143.4, 144.6.
MS (IS): m/z = 321 [M + 1].
N-Arylation Reaction; General Procedure
Under an argon atmosphere, Cs2CO3 (203 mg, 0.624 mmol), CuO (2
mg, 0.031 mmol) and FeCl2·4H2O (19 mg, 0.093 mmol) were placed as
a suspension in DMF (3 mL) in a sealed tube. After stirring for 5 min
under argon, 1 (100 mg, 0.312 mmol) and the respective azole (0.624
mmol) were added to the mixture and then heated to 135 °C. After 48
h at this temperature, the mixture was cooled to r.t. and diluted with
CH2Cl2 (10 mL). Next, the mixture was filtered on Celite. The resulting
filtrate was washed with H2O (3 × 5 mL) and dried (MgSO4). After fil-
tration and concentration under reduced pressure, the crude product
was purified by flash chromatography on silica gel.
6-Iodo-2-phenylimidazo[1,2-a]pyridine (1)14
Under an argon atmosphere, 2-amino-5-iodopyridine (2 g, 9.09
mmol) and NaHCO3 (916 mg, 10.90 mmol) were added to a solution
of 2-bromoacetophenone (1.99 g, 9.99 mmol) in EtOH (20 mL). The
resulting solution was heated to reflux for 12 h and then cooled down
to r.t. After concentration under reduced pressure, the residue was di-
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2-Phenylimidazo[1,2-a]pyridine (2)14
HRMS (ESI): m/z [M + H]+ calcd for C20H15N4: 311.1291; found:
311.1293.
Obtained as a by-product in the reactions of 1 with pyrazole (Table 2,
entry 1) and 1 with 4-fluorobenzyl mercaptan (Table 4, entry 6); yel-
low solid; mp 132–133 °C.
2-Phenyl-6-(1H-pyrrolo[2,3-b]pyridin-1-yl)imidazo[1,2-a]pyri-
dine (5a)
IR (neat): 916, 1080, 1142, 1243, 1369, 1474, 3035 cm–1
.
Prepared from 7-azaindazole (73 mg, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (3:7); yield: 43 mg
(45%); brown solid; mp 138–141 °C.
1H NMR (250.13 MHz, CDCl3): δ = 6.73 (t, J = 6.7 Hz, 1 H), 7.14 (dd, J =
6.9, 8.9 Hz, 1 H), 7.32 (ddd, J = 7.3, 3.7, 1.2 Hz, 1 H), 7.38–7.47 (m, 2 H),
7.62 (d, J = 9.1 Hz, 1 H), 7.82 (s, 1 H), 7.95 (d, J = 7.3 Hz, 2 H), 8.07 (d,
J = 6.8 Hz, 1 H).
IR (neat): 692, 722, 777, 894, 1221, 1275, 1426, 1514, 1592 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 6.68 (d, J = 3.5 Hz, 1 H), 7.18 (dd, J =
7.8, 4.7 Hz, 1 H), 7.34 (t, J = 7.3 Hz, 1 H), 7.42–7.44 (t, J = 7.6 Hz, 2 H),
7.50 (d, J = 3.6 Hz, 2 H), 7.75 (d, J = 9.5 Hz, 1 H), 8.00 (m, 4 H), 8.39 (d,
J = 4.0 Hz, 1 H), 8.84 (s, 1 H).
13C NMR (62.9 MHz, DMSO-d6): δ = 108.2, 112.5, 117.6, 124.7, 125.7,
126.1 (2 × CH), 128.0, 128.8 (2 × CH), 133.8, 145.9, 145.7.
MS (IS): m/z = 195 [M + H].
13C NMR (100.62 MHz, CDCl3): δ = 102.6, 109.4, 117.3, 117.8, 121.2,
121.7, 122.7, 126.2, 126.2 (2 × CH), 127.5, 128.3, 128.9 (2 × CH), 129.6,
133.7, 143.9, 144.2, 147.0, 147.8.
HRMS (ESI): m/z [M + H]+ calcd for C20H15N4: 311.1291; found:
311.1293.
2-Phenyl-6-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridine (3a) and
2-Phenyl-5-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridine (3b)
Prepared from pyrazole (42 mg, 0.624 mmol) and separated by col-
umn chromatography using EtOAc–PE (2:8) as eluent.
3a
2-Phenyl-6-(1H-pyrrol-1-yl)imidazo[1,2-a]pyridine (6a)
Yield: 50 mg (61%); rusty red solid; mp 179–180 °C.
Prepared from pyrrole (86 mL, 0.624 mmol) and purified by column
chromatography eluting with EtOAc–PE (5:95); yield: 56 mg (70%);
brown solid; mp 146–148 °C.
IR (neat): 702, 801, 920, 1051, 1229, 1394, 1543 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 6.51 (t, J = 2.1 Hz, 1 H), 7.34 (t, J =
7.4 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.48 (dd, J = 9.7, 2.0 Hz, 1 H), 7.69
(d, J = 9.6 Hz, 1 H), 7.75 (d, J = 1.6 Hz, 1 H), 7.87 (d, J = 2.4 Hz, 1 H), 7.90
(s, 1 H), 7.96 (d, J = 7.4 Hz, 2 H), 8.61 (d, J = 1.5 Hz, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 108.3, 109.5, 117.2, 118.0, 118.8,
126.3 (2 × CH), 127.5, 128.5, 129.0 (2 × CH), 129.1, 133.6, 141.7, 144.4,
147.3.
IR (neat): 613, 802, 1122, 1299, 1482, 1648 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 6.28 (s, 2 H), 6.88 (s, 2 H), 7.15 (d, J =
9.3 Hz, 1 H), 7.34 (t, J = 7.4 Hz, 1 H), 7.32 (t, J = 7.4 Hz, 2 H), 7.53 (d, J =
9.5 Hz, 1 H), 7.70 (s, 1 H), 7.83 (d, J = 7.5 Hz, 2 H), 7.99 (s, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 109.2, 111.1 (2 × CH), 117.7, 118.0,
120.1 (2 × CH), 121.3, 126.2 (2 × CH), 128.3, 128.9 (2 × CH), 129.4,
133.6, 144.2, 147.0;
HRMS (ESI): m/z [M + H]+ calcd for C16H13N4: 261.1135; found:
261.1137.
HRMS (ESI): m/z [M + H]+ calcd for C17H14N3: 260.1182; found:
260.1186.
3b
Brown solid; mp 165–166 °C.
IR (neat): 724, 775, 1083, 1390, 1525, 1526, 1643 cm–1
6-(1H-Indol-1-yl)-2-phenylimidazo[1,2-a]pyridine (7a) and 5-(1H-
Indol-1-yl)-2-phenylimidazo[1,2-a]pyridine (7b)
.
1H NMR (400.13 MHz, CDCl3): δ = 6.59 (t, J = 2.2 Hz, 1 H), 6.81 (d, J =
7.1 Hz, 1 H), 7.22–7.29 (t, J = 7.1 Hz, 1 H), 7.32 (t, J = 7.4 Hz, 1 H), 7.42
(t, J = 7.6 Hz, 2 H), 7.70 (d, J = 9.0 Hz, 1 H), 7.88 (d, J = 2.5 Hz, 1 H),
7.93–8.00 (m, 3 H), 8.21 (s, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 106.8, 107.1, 108.2, 117.1, 124.3,
126.5 (2 × CH), 128.4, 128.9 (2 × CH), 131.3, 133.3, 133.7, 142.9, 146.5,
147.0.
Prepared from indole (73 mg, 0.624 mmol) and separated by column
chromatography eluting with EtOAc–PE (1:9).
7a
Yield: 66 mg (68%); red ochre solid; mp 203–204 °C.
IR (neat): 695, 715, 737, 761, 775, 809, 1218, 1537 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 6.74 (d, J = 3.3 Hz, 1 H), 7.16 (t,
J = 7.4 Hz, 1 H), 7.23 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.47 (t,
J = 7.6 Hz, 2 H), 7.51 (dd, J = 9.5, 2.1 Hz, 1 H), 7.57 (d, J = 8.2 Hz, 1 H),
7.64–7.71 (m, 2 H), 7.77 (d, J = 9.5 Hz, 1 H), 8.01 (d, J = 7.5 Hz, 2 H),
8.47 (s, 1 H), 8.92 (d, J = 2.3 Hz, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C16H13N4: 261.1135; found:
261.1137.
1-(2-Phenylimidazo[1,2-a]pyridin-6-yl)-1H-indazole (4a)
Prepared from indazole (73 mg, 0.624 mmol) and purified by column
chromatography eluting with EtOAc–PE (2:8) as eluent; yield: 80 mg
(41%); beige solid; mp 199–200 °C.
13C NMR (100.62 MHz, DMSO-d6): δ = 103.6, 110.2, 110.3, 117.1,
120.4, 120.9, 122.4, 122.6, 123.6, 125.6 (2 × CH), 126.3, 127.9, 128.8 (2
× CH), 128.8, 129.0, 133.7, 135.8, 143.5, 145.5.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3: 310.1339; found:
310.1342.
IR (neat): 624, 737, 815, 1201, 1336, 1466, 1539 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 7.26 (t, J = 7.4 Hz, 1 H), 7.33 (t, J =
7.2 Hz, 1 H), 7.39–7.51 (m, 3 H), 7.58 (d, J = 9.3 Hz, 1 H), 7.66 (d, J = 8.4
Hz, 1 H), 7.77 (d, J = 9.1 Hz, 1 H), 7.82 (d, J = 8.1 Hz, 1 H), 7.91 (s, 1 H),
7.96 (d, J = 7.5 Hz, 2 H), 8.22 (s, 1 H), 8.48 (s, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 109.3, 109.9, 117.9, 120.3, 121.7,
122.0, 122.0, 125.4, 126.2 (2 × CH), 127.8, 128.4 (2 × CH), 128.4, 128.9,
133.4, 136.1, 139.3, 144.4, 147.2.
7b
Yield: 19 mg (20%); yellow solid; mp 139–140 °C.
IR (neat): 691, 716, 734, 762, 1455, 1519 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

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Z. Tber et al.
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Synthesis
1H NMR (400.13 MHz, CDCl3): δ = 6.85 (d, J = 3.3 Hz, 1 H), 6.91 (d, J =
7.1 Hz, 1 H), 7.10 (d, J = 7.7 Hz, 1 H), 7.23–7.28 (m, 2 H), 7.29–7.34 (m,
2 H), 7.35–7.41 (m, 3 H), 7.49 (s, 1 H), 7.73–7.79 (m, 2 H), 7.87 (d, J =
7.6 Hz, 2 H).
13C NMR (100.62 MHz, CDCl3): δ = 106.0, 106.1, 110.2, 110.9, 117.0,
121.7 (2 × CH), 123.6, 124.7, 126.3 (2 × CH), 127.4, 128.4, 128.8 (2 ×
CH), 129.1, 132.4, 133.5, 136.2, 146.4, 147.0.
S-Arylation/Alkylation Reaction General Procedure
Under an argon atmosphere, Cs2CO3 (203 mg, 0.624 mmol), CuO
(2mg, 0.031mmol), and FeCl2·4H2O (19 mg, 0.093 mmol) were placed
as a suspension in DMF (3 mL) in a sealed tube. After stirring for 5 min
under argon, 1 (100 mg, 0.312 mmol) and the respective thiol (0.624
mmol) were added to the mixture and then heated to 135 °C. After 24
h at this temperature, the mixture was cooled to r.t. and diluted with
EtOAc (10 mL) and filtered on Celite. The filtrate was washed with aq
5 N NaOH (2 × 5 mL) and H2O (2 × 5 mL) and dried (MgSO4). After fil-
tration and concentration under reduced pressure, the crude product
was purified by flash chromatography on silica gel.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3: 310.1339; found:
310.1342.
6-(1H-Imidazol-1-yl)-2-phenylimidazo[1,2-a]pyridine (8a) and
5-(1H-Imidazol-1-yl)-2-phenylimidazo[1,2-a]pyridine (8b)
6-(4-Methoxyphenylsulfanyl)-2-phenylimidazo[1,2-a]pyridine
(10)
Prepared from imidazole (42 mg, 0.624 mmol) and separated by col-
umn chromatography eluting with EtOAc–PE (2:8).
Prepared from 4-methoxythiophenol (76 mL, 0.624 mmol) and puri-
fied by column chromatography eluting with EtOAc–PE (2:8); yield:
77 mg (75%); beige solid; mp 135–136 °C.
8a
Yield: 40 mg (50%); brown solid; mp 154–156 °C.
IR (neat): 719, 814, 1025, 1338, 1492, 1589 cm–1
.
IR (neat): 653, 692, 779, 804, 1050, 1226 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 3.81 (s, 3 H), 6.89 (d, J = 8.6 Hz, 2 H),
7.10 (dd, J = 9.6, 1.8 Hz, 1 H), 7.32 (t, J = 7.7 Hz, 1 H), 7.37 (dd, J = 8.4,
6.6 Hz, 2 H), 7.43 (t, J = 7.6 Hz, 2 H), 7.55 (d, J = 9.4 Hz, 1 H), 7.79 (s, 1
H), 7.92 (d, J = 7.6 Hz, 2 H), 8.10 (s, 1 H).
1H NMR (400.13 MHz, CDCl3): δ = 7.21–7.30 (m, 3 H), 7.38 (t, J = 7.4
Hz, 1 H), 7.45 (t, J = 7.4 Hz, 2 H), 7.72 (d, J = 9.5 Hz, 1 H), 7.82 (s, 1 H),
7.93 (s, 1 H), 7.96 (d, J = 7.8 Hz, 2 H), 8.26 (d, J = 2.4 Hz, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 109.3, 118.5, 119.2, 119.3, 121.2,
125.8, 126.2 (2 × CH), 128.6, 129.0 (2 × CH), 131.0, 133.2, 136.4, 144.4,
147.7.
HRMS (ESI): m/z [M + H]+ calcd for C16H13N4: 261.1135; found:
261.1137.
13C NMR (100.62 MHz, CDCl3): δ = 55.5, 108.4, 115.2 (2 × CH), 117.6,
122.2, 125.0, 126.1 (2 × CH), 126.2, 128.2, 128.5, 128.9 (2 × CH), 133.5,
133.7 (2 × CH), 144.6, 146.4, 159.8.
HRMS (ESI): m/z [M + H]+ calcd for C20H17N2OS: 333.1056; found:
333.1059.
8b
2-Phenyl-6-{[4-(trifluoromethyl)phenyl]thio}imidazo[1,2-a]pyri-
Yield: 16 mg (20%); orange solid; mp 162–163 °C.
dine (11)
IR (neat): 656, 717, 1243, 1478, 1518, 1642, 3109 cm–1
.
Prepared from 4-(trifluoromethyl)thiophenol (85 μL, 0.624 mmol)
and purified by column chromatography eluting with EtOAc–PE (3:7);
yield: 92 mg (80%); beige solid; mp 150–151 °C.
1H NMR (250.13 MHz, CDCl3): δ = 6.84 (dd, J = 7.1, 1.0 Hz, 1 H), 7.28–
7.48 (m, 6 H), 7.62 (s, 1 H), 7.75 (d, J = 9.1 Hz, 1 H), 7.91 (dd, J = 8.6, 1.7
Hz, 3 H).
IR (neat): 726, 1063, 1165, 1240, 1420, 1604, 3008 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 7.19 (dd, J = 9.3, 1.6 Hz, 1 H), 7.27
(d, J = 9.0 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 2 H), 7.51
(d, J = 8.3 Hz, 2 H), 7.66 (d, J = 9.3 Hz, 1 H), 7.88 (s, 1 H), 7.96 (d, J = 7.3
Hz, 2 H), 8.40 (s, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 108.6, 116.60, 118.5, 124.0 [q,
J(CF3) = 272 Hz], 126.1 [q, J(CF3) = 4 Hz, 2 × CH], 126.3 (2 × CH), 127.5
(2 × CH), 128.5 [q, J(CF3) = 33 Hz], 128.6, 129.0 (2 × CH), 130.25,
130.45, 133.3, 142.2, 144.9, 147.2.
13C NMR (62.9 MHz, DMSO-d6): δ = 105.0, 109.3, 118.0, 119.4, 124.5,
126.3 (2 × CH), 128.7, 128.9 (2 × CH), 130.0, 131.3, 133.0, 137.4, 146.8,
147.1.
HRMS (ESI): m/z [M + H]+ calcd for C16H13N4: 261.1135; found:
261.1134.
2-Phenyl-6-(1H-1,2,4-triazol-1-yl)imidazo[1,2-a]pyridine (9a)
Prepared from 1,2,4-triazole (43 mg, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (9:1); yield: 94 mg
(58%); beige solid; mp 223–225 °C.
19F NMR (376 MHz, CDCl3): δ = –62.53 (s).
HRMS (ESI): m/z [M + H]+ calcd for C20H13F3N2S: 371.0824; found:
IR (neat): 778, 814, 993, 1042, 1273, 1344, 1500 cm–1
.
3710829.
1H NMR (400.13 MHz, DMSO-d6): δ = 7.34 (t, J = 7.4 Hz, 1 H), 7.45 (t,
J = 7.6 Hz, 2 H), 7.78 (s, 2 H), 7.99 (d, J = 7.5 Hz, 2 H), 8.31 (s, 1 H), 8.51
(s, 1 H), 9.15 (s, 1 H), 9.28 (s, 1 H).
13C NMR (100.62 MHz, DMSO-d6): δ = 110.6, 117.3, 118.8, 118.9,
125.1 (2 × CH), 125.7, 128.0, 128.8 (2 × CH), 133.4, 143.0, 143.7, 145.8,
152.6.
6-[(3-Methoxyphenyl)thio]-2-phenylimidazo[1,2-a]pyridine (12)
Prepared from 3-methoxythiophenol (77 μL, 0.624 mmol) and puri-
fied by column chromatography eluting with EtOAc–PE (3:7); yield:
74 mg (72%); beige solid; mp 139–140 °C.
IR (neat): 679, 719, 764, 857, 1035, 1243, 1480, 1576, 1588 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 3.72 (s, 3 H), 6.83 (d, J = 6.8 Hz, 3
H), 7.21–7.29 (m, 2 H), 7.35 (t, J = 7.0 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 2 H),
7.64 (d, J = 9.3 Hz, 1 H), 7.98 (d, J = 7.4 Hz, 2 H), 8.42 (s, 1 H), 8.85 (s, 1
H).
HRMS (ESI): m/z [M + H]+ calcd for C15H12N5: 262.1087; found:
262.1090.
13C NMR (100.62 MHz, DMSO-d6): δ = 55.2, 109.7, 112.3, 113.6, 116.5,
117.3, 120.3, 125.6 (2 × CH), 127.9, 128.8 (2 × CH), 129.8, 130.4, 130.8,
133.4, 137.4, 143.9, 145.1, 159.8.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

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Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C20H17N2OS: 333.1056; found:
333.1059.
1H NMR (400.13 MHz, CDCl3): δ = 3.99 (s, 2 H), 7.14 (t, J = 7.7 Hz, 3 H),
7.25 (d, J = 7.0 Hz, 3 H), 7.32 (t, J = 7.4 Hz, 1 H), 7.42 (t, J = 7.6 Hz, 2 H),
7.54 (d, J = 9.3 Hz, 1 H), 7.69 (s, 1 H), 7.91 (d, J = 8.2 Hz, 3 H).
2-Phenyl-6-(phenylthio)imidazo[1,2-a]pyridine (13)15
13C NMR (100.62 MHz, CDCl3): δ = 41.0, 108.3, 117.3, 119.4, 126.2 (2 ×
CH), 127.5, 128.3, 128.7 (2 × CH), 128.9 (2 × CH), 128.9, 129.0 (2 × CH),
130.3, 133.4, 137.4, 144.7, 146.2.
HRMS (ESI): m/z [M + H]+ calcd for C20H17N2S: 317.1107; found:
317.1110.
Prepared from thiophenol (63 μL, 0.624 mmol) and purified by col-
umn chromatography eluting with EtOAc–PE (3:7); yield: 66 mg
(70%); creamy white solid; mp 163–164 °C.
IR (neat): 683, 721, 735, 813, 1024, 1245, 1476, 1581 cm–1
.
1H NMR (400.13 MHz, CDCl3): δ = 7.15 (dd, J = 9.6, 1.8 Hz, 1 H), 7.18 –
7.32 (m, 5 H), 7.33 (t, J = 7.7 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 2 H), 7.57 (d,
J = 9.4 Hz, 1 H), 7.80 (s, 1 H), 7.93 (d, J = 7.5 Hz, 2 H), 8.25 (s, 1 H).
13C NMR (100.62 MHz, CDCl3): δ = 108.6, 118.0, 119.2, 126.3 (2 × CH),
127.0, 128.4, 128.9, 129.0 (2 × CH), 129.4 (2 × CH), 129.5 (2 × CH),
130.0, 133.6, 136.3, 144.93, 146.8.
6-(Ethylthio)-2-phenylimidazo[1,2-a]pyridine (17)16
Prepared from ethanethiol (46 μL, 0.624 mmol) and purified by col-
umn chromatography eluting with EtOAc–PE (1:9); yield: 58 mg
(73%); beige solid; mp 134–135 °C.
IR (neat): 688, 762, 772, 816, 1073, 1243, 1418, 1619 cm–1
.
HRMS (ESI): m/z [M + H]+ calcd for C19H15N2S: 303.0950; found:
303.0952.
1H NMR (400.13 MHz, acetone-d6): δ = 1.27 (t, J = 7.3 Hz, 3 H), 2.94 (q,
J = 7.3 Hz, 2 H), 7.21–7.40 (m, 2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.53 (d, J =
9.4 Hz, 1 H), 8.04 (d, J = 7.6 Hz, 2 H), 8.24 (s, 1 H), 8.54 (s, 1 H).
13C NMR (100.62 MHz, acetone-d6): δ = 14.0, 28.9, 108.8, 116.9, 119.6,
6-[(4-Methoxybenzyl)thio]-2-phenylimidazo[1,2-a]pyridine (14)
125.8 (2 × CH), 127.7, 127.9, 128.5 (2 × CH), 128.8, 134.3, 144.4, 145.8.
HRMS (ESI): m/z [M + H]+ calcd for C15H15N2S: 255.0950; found:
255.0953.
Prepared from 4-methoxy-α-toluenethiol (86 μL, 0.624 mmol) and
purified by column chromatography eluting with EtOAc–PE (2:8);
yield: 76 mg (70%); beige solid; mp 124–126 °C.
IR (neat): 722, 801, 1029, 1244, 1508, 1607 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 3.70 (s, 3 H), 4.14 (s, 2 H), 6.84
(d, J = 8.1 Hz, 2 H), 7.19 (d, J = 8.2 Hz, 2 H), 7.26 (dd, J = 9.5, 1.8 Hz, 1
H), 7.33 (t, J = 7.3 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.54 (d, J = 9.3 Hz, 1
H), 7.94 (d, J = 7.6 Hz, 2 H), 8.49 (s, 1 H), 8.31 (s, 1 H).
6-(Isopropylthio)-2-phenylimidazo[1,2-a]pyridine (18)
Prepared from 2-propanethiol (57 μL, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (3:7); yield: 43 mg
(51%); beige solid; mp 136–137 °C.
13C NMR (100.62 MHz, DMSO-d6): δ = 38.2, 55.0, 109.2, 113.8 (2 ×
CH), 116.5, 119.0, 125.6 (2 × CH), 127.9, 128.0, 128.8 (2 × CH), 128.9,
129.2, 130.0 (2 × CH), 133.6, 143.7, 144.7, 158.3.
IR (neat): 687, 817, 1027, 1208, 1237, 1418, 1619 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 1.24 (s, 3 H), 1.26 (s, 3 H), 3.37–
3.45 (m, 1 H), 7.27–7.37 (m, 2 H), 7.46 (t, J = 7.6 Hz, 2 H), 7.58 (d, J =
9.3 Hz, 1 H), 7.96 (d, J = 7.5 Hz, 2 H), 8.37 (s, 1 H), 8.68 (s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C21H19N2OS: 347.1213; found:
347.1215.
13C NMR (100.62 MHz, DMSO-d6): δ = 22.8 (2 × CH3), 38.5, 109.2,
116.5, 117.9, 125.6 (2 × CH), 127.9, 128.7 (2 × CH), 129.8, 130.2, 133.6,
143.9, 144.9.
6-[(4-Fluorobenzyl)thio]-2-phenylimidazo[1,2-a]pyridine (15)
HRMS (ESI): m/z [M + H]+ calcd for C16H17N2S: 269.1107; found:
269.1110.
Prepared from 4-fluorobenzyl mercaptan (73 μL, 0.624 mmol) and
separated from the by-product 2 (20%) by column chromatography
eluting with EtOAc–PE (2:8); yield: 47 mg (45%); beige solid; mp 113–
114 °C.
6-(Cyclopentylthio)-2-phenylimidazo[1,2-a]pyridine (19)
IR (neat): 777, 1015, 1156, 1200, 1330, 1414, 1598, 2920 cm–1
.
Prepared from cyclopentanethiol (67 μL, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (2:8); yield: 63 mg
(69%); beige solid; mp 103–105 °C.
1H NMR (400.13 MHz, CDCl3): δ = 3.99 (s, 2 H), 6.94 (t, J = 8.5 Hz, 2 H),
7.11 (t, J = 7.2 Hz, 3 H), 7.34 (t, J = 7.3 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 2 H),
7.54 (d, J = 9.3 Hz, 1 H), 7.74 (s, 1 H), 7.93 (d, J = 7.6 Hz, 2 H), 7.97 (s, 1
H).
13C NMR (100.62 MHz, CDCl3): δ = 40.4, 108.2, 115.5 [d, J(CF3) = 21.5
Hz, 2 × CH)], 117.5, 118.8, 126.20 (2 × CH), 128.4, 128.9 (2 × CH),
129.2, 130.1, 130.64 [d, J(CF3) = 8.1 Hz, 2 × CH], 133.3 [d, J(CF3) = 3.2
Hz], 133.5, 144.9, 146.7, 162.19 [d, J(CF3) = 246.3 Hz].
IR (neat): 689, 725, 798, 1070, 1414, 1519, 2937 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 1.48–1.60 (m, 4 H), 1.69–1.74
(m, 2 H), 1.93–2.00 (m, 2 H), 3.56–3.65 (m, 1 H), 7.25–7.36 (m, 2 H),
7.44 (t, J = 7.6 Hz, 2 H), 7.55 (d, J = 9.4 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 2 H),
8.34 (s, 1 H), 8.64 (d, J = 1.8 Hz, 1 H).
13C NMR (100.62 MHz, DMSO-d6): δ = 24.2 (2 × CH2), 32.8 (2 × CH2),
46.7, 109.2, 116.5, 119.5, 125.6 (2 × CH), 127.9, 128.4, 128.8 (2 × CH),
129.4, 133.5, 143.7, 144.7.
19F NMR (376 MHz, CDCl3): δ = –114.67 (s).
HRMS (ESI): m/z [M + H]+ calcd for C20H16FN2S: 335.1013; found:
335.1015.
HRMS (ESI): m/z [M + H]+ calcd for C18H19N2S: 295.1263; found:
295.1264.
6-(Benzylthio)-2-phenylimidazo[1,2-a]pyridine (16)
6-(tert-Butylthio)-2-phenylimidazo[1,2-a]pyridine (20)15
Prepared from benzyl mercaptan (73 μL, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (1:1); yield: 58 mg
(60%); brown solid; mp 149–150 °C.
Prepared from tert-butylthiol (70 μL, 0.624 mmol) and purified by
column chromatography eluting with EtOAc–PE (2:8); yield: 32 mg
(36%); beige solid; mp 148–149 °C.
IR (neat): 688, 699, 719, 770, 813, 1083, 1338, 1419, 1674 cm–1
.
IR (neat): 672, 726, 807, 1163, 1320, 1367, 1412, 1471, 1623 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

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Z. Tber et al.
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Synthesis
1H NMR (400.13 MHz, CDCl3): δ = 1.33 (s, 9 H), 7.28 (d, J = 10.6 Hz, 1
H), 7.35 (t, J = 7.3 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.59 (d, J = 9.3 Hz, 1
H), 7.86 (s, 1 H), 7.95 (d, J = 7.4 Hz, 2 H), 8.30 (s, 1H).
13C NMR (100.62 MHz, CDCl3): δ = 30.8 (3 × CH3), 46.3, 108.2, 116.6,
117.7, 126.3 (2 × CH), 128.3, 128.9 (2 × CH), 132.2, 133.47, 133.6,
145.1, 146.5.
Acknowledgment
We acknowledge the OMJ (Office Mediterranéen de la Jeunesse) for
financial support to Zahira Tber.
Supporting Information
HRMS (ESI): m/z [M + H]+ calcd for C17H19N2S: 283.1263; found:
Supporting information for this article is available online at
283.1267.
http://dx.doi.org/10.1055/s-0034-1380383.
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2-[(2-Phenylimidazo[1,2-a]pyridin-6-yl)thio]benzo[d]thiazole
(21)
References
Prepared from 2-mercaptobenzothiazole (104 mg, 0.624 mmol) and
purified by column chromatography eluting with EtOAc–PE (1.9);
yield: 105 mg (94%); beige solid; mp 181–182 °C.
(1) For latest articles, see: (a) Miller, J. F.; Chong, P. K.; Shotwell, J.
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IR (neat): 750, 720, 814, 1020, 1422, 1459, 1617 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 7.32–7.35 (m, 2 H), 7.42–7.46
(m, 4 H), 7.77 (d, J = 9.4 Hz, 1 H), 7.85 (d, J = 8.1 Hz, 1 H), 7.94 (d, J = 7.9
Hz, 1 H), 8.00 (d, J = 7.6 Hz, 2 H), 8.50 (s, 1 H), 9.21 (s, 1 H).
13C NMR (62.9 MHz DMSO-d6): δ = 110.2, 169.0, 153.5, 145.8, 144.3,
135.0, 133.7, 113.3, 117.7, 121.6, 121.9, 124.7, 125.9 (2 × CH), 126.7,
128.4 (2 × CH), 129.0, 130.7, 133.1.
HRMS (ESI): m/z [M + H]+ calcd for C20H14N3S2: 360.0624; found:
360.0627.
6-Nitro-2-[(2-phenylimidazo[1,2-a]pyridin-6-yl)thio]benzo[d]thi-
azole (22)
Prepared from 6-nitro-2-mercaptanbenzothiazole (132 mg, 0.624
mmol) and purified by column chromatography eluting with EtOAc–
PE (1:9); yield: 75 mg (60%); yellow solid; mp 239–240 °C.
IR (neat): 683, 722, 813, 883, 1022, 1275, 1510 cm–1
.
1H NMR (400.13 MHz, DMSO-d6): δ = 7.38 (t, J = 7.3 Hz, 1 H), 7.48 (t,
J = 7.6 Hz, 2 H), 7.57 (dd, J = 9.1, 1.9 Hz, 1 H), 7.82 (d, J = 9.3 Hz, 1 H),
7.97–8.07 (m, 3 H), 8.30 (dd, J = 9.1, 2.5 Hz, 1 H), 8.53 (s, 1 H), 8.98 (d,
J = 2.4 Hz, 1 H), 9.27 (s, 1 H).
13C NMR (100.62 MHz, DMSO-d6): δ = 110.1, 112.3, 118.0, 118.8,
121.7, 122.1, 125.9 (2 × CH), 128.3, 128.9 (2 × CH), 130.2, 133.1, 134.2,
135.4, 143.7, 144.3, 146.1, 157.4, 177.4.
HRMS (ESI): m/z [M + H]+ calcd for C20H13N4O2S2: 405.0474; found:
405.0474.
6-Ethoxy-2-[(2-phenylimidazo[1,2-a]pyridin-6-yl)thio]ben-
zo[d]thiazole (23)
Prepared from 6-ethoxy-2-mercaptanbenzothiazole (132 mg, 0.624
mmol) and purified by column chromatography eluting with EtOAc–
PE (1:9); yield: 115 mg (92%); beige solid; mp 164–165 °C.
IR (neat): 724, 818, 936, 1218, 1256, 1446, 1599 cm–1
.
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1H NMR (400.13 MHz, DMSO-d6): δ = 1.31 (t, J = 7.0 Hz, 3 H), 4.01 (q,
J = 6.9 Hz, 2 H), 7.04 (dd, J = 9.0, 2.6 Hz, 1 H), 7.37 (t, J = 7.3 Hz, 1 H),
7.42–7.57 (m, 4 H), 7.75 (dd, J = 9.2, 3.3 Hz, 2 H), 8.00 (d, J = 7.6 Hz, 2
H), 8.49 (s, 1 H), 9.17 (s, 1 H).
13C NMR (100.62 MHz DMSO-d6): δ = 14.5, 63.7, 105.5, 110.0, 113.5,
115.6, 117.6, 122.1, 125.8 (2 × CH), 128.2, 128.8 (2 × CH), 130.4, 133.2,
133.3, 136.5, 144.2, 145.7, 147.7, 156.0, 164.8.
HRMS (ESI): m/z [M + H]+ calcd for C22H18N3OS2: 404.0886; found:
404.0883.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K

K
Z. Tber et al.
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–K