Iodine mediated oxidative cross coupling of 2-aminopyridine and aromatic terminal alkyne: A practical route to imidazo[1,2-: A] pyridine derivatives

Article abstract of DOI:10.1039/c9ob00812h

A novel, transition-metal free route leading to imidazo[1,2-a]pyridine derivatives via iodine mediated oxidative coupling between 2-aminopyridine and aromatic terminal alkyne has been demonstrated. This newly developed method discloses an operationally simple way for the construction of imidazoheterocycles. Commercially available antiulcer drug zolimidine may readily be synthesized employing this method.

Full text of DOI:10.1039/c9ob00812h

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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DOI: 10.1039/C9OB00812H
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Iodine mediated oxidative cross coupling of 2‐aminopyridine and
aromatic terminal alkyne: A practical route to imidazo[1,2‐
a]pyridine derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Surya Kanta Samanta and Mrinal K. Bera*
DOI: 10.1039/x0xx00000x
Dedicated to Professor Hans‐Ulrich Reißig on the occasion of his 70th birthday
A novel, transition‐metal free route leading to imidazo[1,2‐a]pyridine derivatives via iodine
mediated oxidative coupling between 2‐aminopyridine and aromatic terminal alkyne has been
demonstrated. This newly developed method discloses the operationally simple way for the
construction of imidazoheterocycles. Commercially available antiulcer drug zolimidine may readily
be synthesized employing this method.
1
1
Introduction: Molecular iodine mediated organic with a wide ranging biological activities, such as antiviral ,
1
12
13
14
transformations are receiving considerable attention in the antiprotozoal ,
antiharpes ,
antiapoptotic ,
anti‐
1
5
recent years as it is commercially cheap and readily inflammatory and fungicidal to name a few. Due to their
available. Molecular iodine is non‐toxic in nature and wide ranging biological activities of imidazo[1,2‐a]pyridine
environmentally compatible too. Moreover, iodine mediated containing natural products, imidazo[1,2‐a]pyridine is
reactions are operationally simple and iodine can be regarded as an appealing target to synthetic organic
removed from the reaction mixture more convincingly. The chemists. As a result, many elegant synthetic routes leading
mild Lewis acidity of iodine makes it more useful in synthetic towards imidazo[1,2‐a]pyridine scaffold have been
1
6
organic chemistry to carry out various organic reactions developed
and
many commercial drugs featuring
using molecular iodine from catalytic to stoichiometric imidazo[1,2‐a]pyridine backbone have been marketed. The
amount. Various important heterocyclic compounds common drugs decorated with imidazo[1,2‐a]pyridine
2
3
4
5
6
18a‐b
18c
including furan , thiophene , pyrrole, pyridine , indole , scaffold are alpidem
and zolpidem (for the treatment
7
8
19a
19b
pyrazine and quinoxaline , thiazole have been synthesized of anxiety and insomnia), necopidem
and saripidem
employing molecular iodine as an effective reagent. Apart (sedative and anxiolytic drug), optically active GSK812397
2
0a
from this, a number of other synthetically important, (anti HIV drug)
and zolimidine (treatment of peptic
molecular iodine mediated reactions9 have also been ulcer) to name a few.
reported recently.
20b
On the other hand, imidazoheterocycles10 are an important
class of structural unit frequently encountered in various
naturally occurring substances and biologically significant
compounds. In particular, imidazo[1,2‐ a]pyridine structural
motif is most commonly found in many natural products
Department of Chemistry
Indian Institute of Engineering Science and Technology (IIEST), Shibpur
PO‐ Botanic Garden, Howrah‐ 711 103 (WB), India
Phone: 91 9932152526; Fax: 91 33 26682916; e‐mail:
mrinalkbera26@gmail.com
Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Figure 1: Structure of some biologically active imidazo [1,2‐
a]pyridine
†
Electronic Supplementary Information (ESI) available: [details of any In recent past, many effective and elegant metal‐catalysed
supplementary information available should be included here]. See
synthetic routes have been developed for the synthesis of
DOI: 10.1039/x0xx00000x
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DOI: 10.1039/C9OB00812H
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imidazo[1,2‐a]pyridine derivatives16 starting from alkyne and repeated with decreasing amount of iodine (60 mol%) but
‐aminopyridine. But metal catalysts are costly and with same equivalence of 2‐aminopyridine, desired
environmentally hazardous to some extent. Therefore, imidazopyridine derivative 3a was detected with 20%
2
2
‐8
metal‐free synthesis of various heterocyclic compounds
isolated yield and major product was 4a with 62% isolated
including imidazo[1,2‐a]pyridine17 emerges as an important yield (Table 1, entry 3).
research area. we have developed a metal‐free procedure to
synthesize imidazo[1,2‐a]pyridine derivatives via iodine Table 1. Screnning of Optimal condition [a]
mediated oxidative cross coupling of 2‐aminopyridine and
aromatic terminal alkyne (Scheme 1). The successful
implementation of this proposed reaction protocol may lead
to construction of large number of imidazopyridine
derivatives which may be useful for many other purposes.
Previous work
,
Product[b]
RX
R1
entry Iodine source Solvent Temprature
0
o
(equiv)
( C)
110
110
110
100
100
80
ratio(3a/4a)
Trace (3a)
0/88
AcOH, 80 C
N
R1
CHO
EWG
X
R2
R2
16a
CH3CN or ROH
X=O,S,NH
N
N
N
N
NH2
NH2
1c
2d
3
I
I
I
(0.8)
(0.8)
(0.6)
( 0.4)
(0.2)
(0.2)
(0.3)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Ar
2
2
2
Cu(OAc)2
N
Ar
R
R
R
EWG 16b
DMF/DMSO
N
o
1
30 C
Cu(OTf) 2 (20 mol%)
MeCN, O2
N
Ar
R
X
16c
16d
N
20/62
52/28
64/0
NH2
6
00C 12h
X = Cl, Br, I
Ar
Ar
N
4
I
2
Ag salt
R
R
Ar
Dioxane, N2
0
N
N
NH2
110 C
5
I
2
This work
6
I
2
2
67/0
I2 (30 mol%)
N
R2
R2
o
DMSO,90 C
N
R1
R1
R1
10-12h
R2
21 examples
7
I
RT
ND
N
NH2
I2 (30 mol%)
N
N
o
8
I2 (0.3)
DMSO
DMSO
DMSO
90
90
90
74/0
58/0
42/0
DMSO,125 C
16-18h
SMe
*
*
*
Metal free approach
Broad substrates scope
Mild condition
9
examples
9e
I
I
I
(0.3)
2
2
2
1
0f
(0.3)
(0.3)
NIS
Scheme 1. Coupling of 2‐amino pyridine and aromatic
terminal alkyne for synthesis of Imidazo[1,2‐a]pyridine
derivatives
1
1g
DMSO
DMSO
DMSO
DMSO
EtOH
90
90
90
90
90
90
Trace (3a)
36/0
ND
Result and discussion: We initiated our synthetic study by
choosing phenylacetylene(1a) and 2‐aminopyridine (2a) as
our model compounds. At first reaction of 1a (1.0 equiv) and
12
1
1
3
4
KI
0
2
a (1.0 equiv) at 110 C product 3a has been produced in
trace amount (entry 1).When compound 1a (1.0 equiv) and
TBAI
ND
2
a (2.0 equiv) were allowed to react with molecular iodine
0
(
1.0 equiv) in DMSO at 110 C, any desired imidazopyridine
product 3a was not found (entry 2). Rather, compound 4a
being isolated and detected as one with one extra 2‐
aminopyridine unit had been incorporated in the initially
formed imidazopyridine moiety. Being encouraged by the
initial result we kept on decreasing molecular iodine, as
product 3a is our desired product. When the reaction was
15
I
2
( 0.3)
( 0.3)
35/0
28/0
1
6
I
2
DMF
2
| J. Name., 2012, 00, 1‐3
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1
1
7
8
I
2
(0.3)
‐
CH
3
CN
90
90
ND
ND
Table 2. Generation of imidazo (1,2‐a)pyridine derivative
using substituted 2‐amino pyridine and terminal alkyne
[
a,b]
DMSO
[
a] Reaction condition: 1a (1.0 equiv), 2a (1.2 equiv), I
2
(30
0
mol%), DMSO (2.0 ml), reflux at 90 C (10‐12 hr)
[
[
[
[
[
[
b] Isolated yield based on 2a , ND = Not detected
c] 1 equiv of 2a was used
d] 2 equiv of 2a was used
e] 2.5 TBHP was used
N
N
N
N
N
N
3
a, 74%
3b, 70%
3c, 45%
N
N
N
N
N
N
nBu
Cl
Et
F
f] 2.5 H
2
O
2
was used
g] 2 equiv IBX was used
3
d, 58%
3e, 67%
3f, 75%
NO2
Cl
N
N
N
N
N
N
Cl
Further lowering of iodine to 40 mol% improves the yield of
3
3
i, 71%
a to 52% but 4a was still forming to a considerable amount
3g, 70%
3h, 77%
OH
2
8%, Table 1, entry 4). Again lowering of iodine to 20 mol%
N
N
N
N
N
Br
OMe
N
and 2a to 1.0 equivalent, 3a was detected exclusively with
yeild 64% (Table 1, entry 5). The best result was obtainted
when the amount of iodine was reduced to 30 mol% and the
2
9
not detected at all. Different additives were also screened to
check whether they have any effect either on yield or on
product ratio. But in presence of oxidizing additives, such as
3
j, 66%
3k, 55%
3l, 60%
N
N
N
O
N
N
N
S
‐aminopyridine was used only 1.0 equivalent at temprature
3
n, 65%
0
3m, 53%
3o, 57%
0 C (Table 1, entry 8). At this optimized condition, 4a was
N
N
N
N
N
N
N
3
q, 68%
3
p, 67%
3r, 70%
N
N
N
N
N
N
TBHP and H
2
O the desired product was obtained but with
2
Br
Cl
inferior yields in every case (Table 1, entry 9 and 10). On the
other hand, different iodine sources were also tried to
promote the reaction. While IBX and NIS were found to be
effective to promote the reaction though with lower yield
3
s, 67%
3t, 61%
3u, 64%
N
N
N
N
N
N
N
3
v, 0%
3w, 0%
3x, 0%
(
Table 1, Entry 11‐12), KI and TBAI were found to be
ineffective (Table 1, entry 13‐14). Apart from DMSO,
different solvent system were tested for the reaction. The
reaction in DMF and EtOH (Table 1, entry 15‐16) furnished
desired compounds though in lower yield but reaction
[
a] Reaction condition: 1a (1.0 equiv), 2a (1.2 equiv), I
2
(30
0
mol%), DMSO (2.0 ml), reflux at 90 C (10‐12 hr)
[b] Isolated yield based on 2a
carried out in CH
7).
3
CN proved unsuccessful. (Table 1, entry
1
On the other hand, differently substituted 2‐aminopyridine
After having reached the optimized condition, we directed derivatives were also investigated as substrate under the
out attention to exploring the substrate scope of the standard reaction condition and found to be successful with
reaction. A variety of differently substituted aromatic satisfactory yield (Table 2, entry 3q‐3u). Unfortunately, the
terminal alkynes were subjected to optimized reaction alkyne with aliphatic substituent such as, n‐pentyl and
condition with 2‐aminopyridine 2a. Then they smoothly cyclopentyl were proved to be unreactive with 2‐
furnished corresponding imidazopyridine derivatives (Table aminopyridine 2a under the present reaction condition; and
2
, entry 3b‐3l) with good to excellent yield. It was observed no desired product was detected (Table 2, entry 3w‐3x).
that the aromatic alkynes with electron withdrawing groups Substrate scope was further extended to 2‐aminopyrazine
provides the best yield (Table 2, entry 3f‐3i), whereas the with phenylacetylene under the optimized reaction
alkynes with electron donating substituent (Table 2, Entry condition; but we ended up with a complex reaction profile
3
k‐3l) gives forth slightly lower yield. The reaction was (Table 2, entry 3v).
successful even with polyaromatic alkyne (3m) with Most of the compounds in this series are solid and we focus
moderate yield. Different heterocyclic acetylene such as, (3‐ on having a crystal structure of any of the solid compounds
Thienyl)acetylene,(2‐Furyl)acetylene and(2‐Pyridyl)acetylene for structure confirmation. Compound 3f was crystallised
reacted smoothly with 2‐aminopyridine under the optimized from 30% ethylacetate in n‐hexane to obtain a white crystal
reaction condition to furnish the corresponding suitable for X‐ray analysis (Figure 2).
imidazopyridine derivatives (Table 2, entry 3n‐3p) with
comparable yields.
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a
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&
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o
io
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o
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under standard condition to afford methylthiolated
imidazopyridine derivatives (Table 3, Entry 7a‐7h) with
moderate to good yield. Phenyl acetylene 1a reacts
smoothly with 2‐aminopyridine in DMSO‐d
moderate yield.
6
to afford 7i in
Figure 2: Molecular structure of 3f (ORTEP) with 50% Table 3. One pot synthesis of thiomethyl ether substituted
imidazo [1,2‐a] pyridina[
a,b]
probability
We anticipated that the reaction might also be successful for
bis acetylenic system; and therefore, 1,3‐diethynyl benzene
5
was exposed to 2‐aminopyridine 2a (2 equivalent) and
taking iodine twice the standard reaction condition.
Interestingly it was observed that the reaction proceeded
smoothly to furnish bis‐imidazopyridine compound 6 with
satisfactory yield (Scheme 2).
N
N
N
N
Me
F
nBu
Cl
N
N
SMe
a,71%
SMe
7b, 68%
SMe
7c, 56%
7
N
N
N
N
N
N
N
Et
I2 (60 mol%)
N
SMe
7d, 62%
SMe
7e, 65%
SMe
7f, 63%
o
DMSO, 90 C
N
NH2
2
a
5
6, 63%
N
N
N
N
N
N
N
OMe
CMe3
N
SMe
g, 51%
SMe
7h, 40%
SCD3
7i, 64%
Scheme 2. Scope of the protocol with 1,3 diethenyl
7
benzene
[
a] Reaction condition: 1a (1.0 equiv), 2a (1.2 equiv), I
2
(30
Sulfenyl groups are frequently found in many natural
products and synthetic analogues with important biological
features.21 Therefore, direct sulfenylation has emerged as
one important process in organic chemistry. A variety of
direct sulfenylating reactions on various heterocyclic
compounds have been developed in recent past using
0
mol%), DMSO (2.0 ml), reflux at 125 C (16‐18 hr)
[
b] Isolated yield based on 2a
Commercially successful anti‐ulcer drug zolimidine can
readily be accessible employing our newly developed
method. As demonstrated in scheme 4, 2‐aminopyridine 1a
and 4‐ethynylphenylmethylsulfane 8 were allowed to react
under standard reaction condition to afford cyclized product
imidazopyridine derivative 9 in 67% yield. SMe group
remains intact under I mediated reaction condition. mCPBA
oxidation of SMe group went in a straight forward way to
produce target molecule zolimidine in excellent yield.
2
2
different sulfenylating agent, such as, disulfide, sodium
sulfinate,23 sulfonyl hydrazide, sulfenyl halides, thiols,
24
25
26
N‐thioimide,27 and arenesulfonyl chloride .
28
On the contrary, DMSO is known to decompose at higher
2
temperature in presence of iodine to produce thiomethyl
radical29 which may be useful for methylthiolation reaction.
We anticipated that if the reaction is carried out at higher
temperature, concomitant methylthiolation may take place
to the target compound imidazo[1,2‐a]pyridine derivatives
at C‐3 position. Therefore, 2‐aminopyridine 1a and aromatic
terminal acetylene were allowed to react under optimized
0
reaction condition but at 125 C and methylthiolated
imidazo[1,2‐a]pyridine derivative 7a was isolated with fairly
good yield (Scheme 3).
Scheme 4. Synthesis of Zolimidine employing newly
developed protocol.
Scheme 3. Concomitant thiomethylation to imidazo[1,2‐
a]pyridine derivative at elevated temperature.
In order to investigate the reaction mechanism we have
carried out couple of experiments as shown in Scheme 5.
According to literature precedence,1 we envision that the
d‐e
To explore the substrate scope, a series of terminal aromatic terminal alkyne will be transformed into α‐oxa
acetylenes were subjected to react with 2‐aminopridine aldehyde via α‐iodo aryl ketone intermediate when exposed
4
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to molecular iodine in DMSO under heating condition. To coupling followed by HI liberation to produce desired
check the intermediacy of phenylglyoxal, 2‐amino pyridine compound 3a. Liberated HI is further oxidised by DMSO to
1
a (1.0 eq.) was treated with phenyl glyoxal (1.0 eq.) in regenerate I
2
and complete the catalytic cycle by releasing
o
DMSO at 90 C under iodine free condition and no desired dimethyl sulphide. But at higher iodine concentration 1a gets
product 3a was detected, Scheme 5a. Again increasing the oxidised by DMSO to afford phenyl glyoxal which is readily
1
7d
amount of 2a to 2.0 eq. and keeping other reaction captured by 2a to produce 4a . At relatively higher
0
28
temperature (125 C), in situ generated thiomethyl radical
parameter identical compound 4a was obtained as sole
product, Scheme 5a. These experiments rulled out the
participation of phenylglyoxal as intermediate in case of 3a
whereas 4a might be forming via the intermediacy of 11.
When the reaction between 1a and 2a were carried out
recombines with 3a to afford 7a in moderate yield.
Conclusions
replacing DMSO as solvent with ethanol and DMF with 30 In summary, we have developed a transition metal‐free,
o
mol% of iodine at 90 C, the desired product 3a was isolated environmentally benign molecular iodine mediated coupling
but reaction remained largely incomplete, Scheme 5b. When reaction of 2‐aminopyridine and commercially available
the reaction is carried out in DMSO under N
atmosphere, it aromatic terminal acetylene to afford imidazo[1,2‐a]pyridine
2
provides 3a with usual yield. These experiments prove that derivatives which is commonly available in various natural
DMSO acts as internal oxidant which oxidise iodide to iodine. products and pharmaceutical candidates. On the contrary,
method for imidazopyridine formation with concomitant
a)
methylthiolation is also developed at higher temperature.
Our discovery leads to a short, operationally simple and
straightforward route to imidazo[1,2‐a]pyridine and a large
array of similar compounds may be prepared. High level of
regio and chemoselectivity, broad substrate scope and wide
range of functional group tolerance make this method more
attractive.
N
O
CHO
N
N
2
a (2 eqv.)
2a (1 eqv.)
NH
a, yield 82%
o
DMSO, 90 C
o
N
N
DMSO, 90 C
4
3a, yield 0%
1
1 (1 eqv.)
b)
I2 (30 mol%)
N
N
0oC
9
N
NH2
3
a
1
a
2a
in ethanol , yield 35%
in DMF, yield 28%
Experimental
General methods:
Scheme 5. Control experiment for the oxidative cyclisation
All reactions were performed under an atmosphere of
nitrogen in oven dried flasks. TLC was performed on pre‐
coated silica gel plates. TLC plates were visualized under UV
light at 254 nm and iodine vapour. 1H NMR spectra were
recorded on Bruker 400 MHz, 500 MHz spectrometer and
On reviewing the existing literature29‐30 and control
experiment we propose a possible mechanistic pathway of
the reaction as depicted in Scheme 5. We assume that the
reaction proceeds through iodonium bridge intermediate 12.
The nitrogen lone pair of aromatic ring of 2a attacks 12 from
less hindered side to produce 13 which undergoes direct C‐N
1
1
3C {1H} NMR spectra were recorded on a Bruker 100 MHz,
25 MHz spectrometer using CDCl and DMSO‐d as solvent
3
6
with TMS as the internal standard. The chemical shifts value
at 7.26 and 77.0 ppm are referenced for CDCl solvent . The
3
data of HRMS was carried out on a high‐resolution mass
spectrometer instrument. Melting points were measured
with a LabX India digital melting point apparatus and are
uncorrected. X‐ray structural analysis were conducted
Bruker D8‐Venture X‐ray analysis instrument. All the
commercial reagents were used from different commercial
source without further purification.
N
NH2
I2
2
a
N
NH2
I
N
NH
I
1
3
1
a
I
1
2
N
SMe DMSO
o
N
N
I
N
N
N
I
1
25 C
Ref-29c,d
3a
HI
Typical procedure for synthesis of product 3a:
SMe
H
14
To a 10 ml round bottom flask was charged with Terminal
alkyne 2a (120 mg, 1.1 mmol), iodine (80.7 mg, 0.25 mmol)
and DMSO (2 mL) at room temperature. The mixture was
HI
I
N
N
N
N
SMe
DMSO
7a SMe
0
heated at 90 C for half an hour. After that, 2‐aminopyridine
1
a (188 mg, 2.0 mmol) was added; and the resulting mixture
2
HI
I2
Me2S
H2O
0
was heated to 90 C for 10‐12 h under nitrogrn atmosphere.
After completion of the reaction and addition of water (50
mL), the mixture was extracted with EtOAc (3 × 50 mL). The
combined organic layer was washed with 10% aqueous
Scheme 6. Plausible reaction mechanism for the iodine
mediated coupling
Na
2
S
2
O
3
solution, brine solution and dried over anhydrous
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SO
Journal Name
Na
2
4
and concentrated under reduced pressure. The δ(ppm): 8.12 (d, J= 7 Hz, 1H), 7.90‐7.87 (m, 2H), 7.84 (s, 1H),
residue was purified by column chromatography on silica gel 7.66 (d, J= 9 Hz, 1H), 7.28 (t, J= 4.1 Hz, 2H), 7.19‐7.16 (m,
(
3
eluent: pet ether/EtOAc = 3:1) to yield the desired product 1H), 6.79‐6.77 (m, 1H), 2.74‐2.68(m,2H), 1.29 (t, J= 7.5
1
3
a as a white solid (148.6 mg, 74% yield).
Hz,3H). C NMR(125 MHz, CDCl ) δ(ppm): 145.6, 145.4,
3
Typical procedure for synthesis of procedure 7a:
To a 10 ml round bottom flask was charged with Terminal 15.4. HRMS ESI (m/z): Calculated for C15
145.3, 128.2, 126.2, 125.6, 124.8, 117.2, 112.5, 107.8, 28.6,
+
H
N
14 2
[M + H] :
alkyne 2a (120 mg, 1.0 mmol), iodine (80.7 mg, 0.25 mmol) 223.1235, found: 223.1230.
and DMSO (2.0 mL) at room temperature.The mixture was 2‐(4‐fluorophenyl)imidazo[1,2‐a]pyridine (3f) : White solid
0
0
1
heated at 100 C for half an hour. After that, 2‐aminopyridine (159 mg, 75%), mp 168‐170 C. H NMR (400 MHz, CDCl
3
)
1
a (188 mg, 2.0 mmol) was added and the resulting mixture δ(ppm): 8.05 (d, J=6.8 Hz, 1H), 7.87‐7.84 (m, 2H), 7.75 (s,
0
was heated to 125 C for 16‐18 h under nitrogrn atmosphere. 1H), 7.55 (d, J= 9.2 Hz, 1H), 7.13‐7.04 (m, 3H), 6.72 (t, J= 6.8
After completion of the reaction and addition of water (5.0 Hz, 1H ). C NMR(100 MHz, CDCl ) δ(ppm): 162.6 (d, JC‐F =
1
3
3
mL), the mixture was extracted with EtOAc (3 × 50 mL). The 44.7 Hz), 145.6, 144.8, 129.9, 127.6(d, JC‐F = 25.7 Hz),125.6,
combined organic layer was washed with 10% aqueous 124.8, 115.6(d, JC‐F = 21.2 Hz), 112.5, 107.8. HRMS ESI (m/z):
+
Na
2
S
2
O
3
solution, brine solution and dried over anhydrous Calculated for C13
H
9
FN
2
[M+H] : 213.0828, found: 213.0826 .
Na
2
SO and concentrated under reduced pressure. The 2‐(4‐chlorophenyl)imidazo[1,2‐a]pyridine (3g) : White solid
4
0
1
residue was purified by column chromatography on silica gel (160 mg, 70%), mp 214‐216 C. H NMR (400 MHz, CDCl
3
) δ
(
eluent: pet ether/EtOAc = 3:1) to yield the desired product (ppm): 8.05 (d, J=6.8 Hz, 1H), 7.82 (d, J= 8.4 Hz, 2H), 7.78 (s,
3
2
a as a white solid (148.6 mg, 71%).
1H), 7.56 (d, J= 9.2 Hz, 1H), 7.34 (d, J= 8.8 Hz, 2H), 7.13‐7.09
13
‐phenylimidazo[1,2‐a]pyridine (3a) : White solid (144 mg, (m, 1H), 6.72 (t, J= 6.8 Hz, 1H ). C NMR(125 MHz, CDCl
3
) δ
) δ(ppm): (ppm): 145.7, 144.7, 133.7, 132.3, 128.8, 127.3, 125.6, 124.8,
.0 (d, J=6.8 Hz, 1H), 7.87 (d, J=7.2 Hz, 2H), 7.75 (s, 1H), 7.53 117.5, 112.5, 108.1. HRMS ESI (m/z): Calculated for
0
1
yield 74%), mp 136‐138 C. H NMR (400 MHz,CDCl
8
3
+
(
d, J=8.8 Hz, 1H), 7.35 (t, J=7.6 Hz, 2H), 7.25 (t, J=7.6 Hz, 1H),
C
13
H
9
ClN
2
[M+H] : 229.0533, found: 229.0536 .
1
3
7
.1 (t, J=7.8 Hz, 1H), 6.66 (t, J=8.0 Hz,1H). C NMR(100 2‐(3‐nitrophenyl)imidazo[1,2‐a]pyridine (3h) : White solid
0
1
MHz,CDCl
3
) δ (ppm): 145.8, 145.7, 133.7, 128.7, 128.0, (184 mg, 77%), mp 194‐196 C. H NMR (400 MHz, CDCl ) δ
3
1
26.1, 125.6, 124.7, 117.5, 112..4, 108.1. HRMS ESI (m/z): (ppm): 8.77 (d, J =1.2 Hz, 1H), 8.43 (d, J=6.0 Hz, 1H), 8.20 (t,
+
Calculated for C13
H
10
N
2
[M+ H] : 195.0922, found: 195.0924.
J=6.4 Hz, 2H), 8.03 (s, 1H), 7.76‐ 7.64 (m, 2H), 7.33‐7.29 (m,
1
3
2
‐(p‐tolyl)imidazo[1,2‐a]pyridine (3b) : White solid (145.3 1H ), 6.92 (t, J=5.2 Hz, 1H). C NMR(125 MHz, CDCl
3
) δ
) δ(ppm): (ppm): 148.8, 145.7, 143.2, 135.4, 131.8, 129.7, 125.8, 125.7,
.05 (d, J=6.8 Hz, 1H), 7.84 (d, J=8.0 Hz, 2H), 7.78 (s, 1H), 7.6 122.5, 120.8, 117.7, 113.2, 109.1. HRMS ESI (m/z):
0
1
mg, 70%), mp 146‐148 C. H NMR (400 MHz, CDCl
3
8
+
(
d, J=9.2 Hz, 1H), 7.25 (d, J=5.6 Hz, 2H), 7.13 (t, J= 7.8 Hz, Calculated for
13
C H
9
3
N O
2
[M+H] : 240.0773,
found:
1
3
1
H), 6.72 (t, J=6.6 Hz, 1H), 2.38 (s, 3H). C NMR(100 MHz, 240.0768.
CDCl
3
) δ(ppm): 145.9, 145.6, 130.9, 129.5, 125.9, 125.5, 2‐(2,4‐dichlorophenyl)imidazo[1,2‐a]pyridine (3i) : White
0
1
1
24.5, 117.4, 112.3, 107.8, 21.3. HRMS ESI (m/z): Calculated solid (186 mg,71%), mp 163‐165 C. H NMR (400 MHz,
+
for C14
H
12
N
2
[M + H] : 209.1079, found: 209.1073.
CDCl
3
) δ (ppm): 8.19 (t, J=5.2 Hz, 2H), 8.06 (d, J=6.4 Hz, 1H),
2
‐(4‐(tert‐butyl)phenyl)imidazo[1,2‐a]pyridine (3c) : brown 7.54 (d, J =9.2 Hz, 1H), 7.22 (d, J=2.0 Hz, 1H), 7.29 (t, J=6.4
1
13
oil (113 mg, 45%). H NMR (400 MHz, CDCl
J=6.8 Hz, 1H), 7.82 (d, J=8.4 Hz, 2H), 7.77 (s, 1H), 7.57 (d, NMR(100 MHz, CDCl
J=8.8 Hz, 1H),7.39 (d, J=8.4 Hz, 2H), 7.09 (t, J=8.4 Hz, 1H ), 131.7, 130.9, 130.0, 127.4, 125.8, 125.2, 117.6, 112.6, 112.4.
3
) δ(ppm): 8.04 (d, Hz, 1H), 7.13 (d, J=7.6 Hz, 1H), 6.73 (t, J=6.8 Hz, 1H).
C
3
) δ (ppm): 144.5, 140.8, 133.6, 132.1,
.70 (t, J= 6.8 Hz, 1H), 1.23 (s, 9H). 1 C NMR(100 MHz, CDCl
δ(ppm): 145.7, 145.5, 133.4, 128.8, 126.6, 125.8, 125.7, found: 263.0142.
24.7, 117.4, 112.5, 107.8, 34.6, 31.3, 31.3, 31.2. HRMS ESI 2‐(4‐bromophenyl)imidazo[1,2‐a]pyridine (3j) : White solid
3
)
HRMS ESI (m/z): Calculated for C13
H
Cl
2
N [M+H] : 263.0143,
+
6
3
8
2
1
+
0
1
(
m/z): Calculated for C17
H
N
18 2
[M+H] : 251.1548, found: (180 mg, 66%), mp 220‐222 C. H NMR (400 MHz, CDCl ) δ
3
2
2
51.1556.
(ppm) = 8.09 (d, J= 6.4 Hz, 1H), 7.81 (d, J=8.4Hz, 3H), 7.62‐
‐(4‐butylphenyl)imidazo[1,2‐a]pyridine (3d) : Gummy solid 7.53 (m, 3H), 7.17 (t, J=7.6 Hz, 1H), 6.78 (t, J= 6.8 Hz, 1H ). 13
C
1
(
145 mg, 58%). H NMR (400 MHz, CDCl
3
) δ (ppm): 8.07 (d, J= NMR (100 MHz, CDCl ) δ(ppm) = 145.7, 144.7, 132.8, 131.8,
3
6
.4 Hz, 1H), 7.85 (d, J=8.0 Hz, 2H), 7.78 (s, 1H), 7.62 (d, J=9.2 127.5, 125.6, 124.9, 121.8, 117.6, 112.6, 108.3. HRMS ESI
+
Hz, 1H), 7.24 (d, J=8.0 Hz, 2H), 7.71‐7.18 (m, 1H), 6.73 (t, (m/z): Calculated for C13
H
9
BrN
2
[M+H] : 273.0627, found:
J=6.6 Hz, 1H), 2.64 (t, J=7.8 Hz, 2H), 1.67‐1.59 (m, 2H), 1.40‐ 273.0632.
1
.33 (m, 2H), 0.95‐0.92 (t, J=7.4 Hz, 3H). 1 C NMR (100 MHz,
3
CDCl ) δ (ppm): 145.6, 145.4, 143.0, 130.8, 128.8, 126.0, 2‐(4‐methoxyphenyl)imidazo[1,2‐a]pyridine (3k) : White
3
0
1
1
1
2
2
25.5, 124.7, 121.1, 117.3, 112.5, 107.8, 35.5, 33.5, 22.4, solid (123 mg, 55%), mp 131‐133 C. H NMR (500 MHz,
+
3.9. HRMS ESI (m/z): Calculated for C14
51.1548, found: 251.1552.
H
12
N
2
O [M+H] : CDCl
3
) δ (ppm) = 8.12 (d, J=8.0 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H),
7.79 (s,1H), 7.65 (d, J=7.4 Hz, 1H), 7.18 (t, J=4.8 Hz, 1H), 7.00
‐(4‐ethylphenyl)imidazo[1,2‐a]pyridine (3e) : White solid (d, J= 4.4 Hz, 2H), 6.78 (t, J =7.2 Hz, 1H), 3.87(s,1H). 13
C
0
1
(
149 mg, 67%), mp 142‐144 C. H NMR (500 MHz, CDCl
3
)
NMR(125 MHz, CDCl
3
) δ (ppm): 159.7, 145.4, 127.4, 126.1,
6
| J. Name., 2012, 00, 1‐3
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Or gP al en ai cs e& d Bo i on mo to al edc j uu lsat r mC ha re gmi ni ss try
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DOI: 10.1039/C9OB00812H
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ARTICLE
1
25.5, 124.7, 117.1, 114.2, 112.4, 107.2, 55.3. HRMS ESI 1H), 7.43 (t, J=7.6 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.02 (d,
+
13
(
m/z): Calculated for C14
H
12
N
2
O [M+H] : 225.1028, found: J=9.2 Hz, 1H), 2.32 (s, 3H). C NMR(100 MHz, CDCl
= 146.1, 135.6, 133.9, 128.7, 127.8, 125.9, 124.8, 115.8,
‐(imidazo[1,2‐a]pyridin‐2‐yl)phenol (3l): White solid (126 115.0, 107.5, 21.4. HRMS ESI (m/z): Calculated for C14
3
) δ (ppm)
2
25.1031.
3
H
12 2
N :
0
1
mg, 60%), mp 206‐208 C. H NMR (500 MHz, DMSO‐d
6
) δ 209.1079, found : 209.1077.
(
1
2
ppm): 9.46 (s, 1H), 8.51 (d, J=9.2 Hz, 1H), 7.71 (d, J= 8.4 Hz, 7‐methyl‐2‐(p‐tolyl)imidazo[1,2‐a]pyridine (3s) : White solid
0
1
H), 7.56 (d, J=9.4 Hz, 1H), 7.40‐7.32 (m, 2H), 7.25‐7.21 (m, (148 mg, 67%), mp 140‐142 C. H NMR (500 MHz, CDCl
3
) δ
H), 6.90‐6.87 (m,1H), 6.73‐6.71 (m, 1H). 1 C NMR(125 MHz, (ppm): 7.99 (d, J=6.8 Hz, 1H), 7.85 (d, J=8.10 Hz, 2H), 7.75 (s,
3
DMSO‐d
6
) δ (ppm): 158.1, 145.2, 145.0, 135.7, 130.1, 127.3, 1H), 7.43 (s, 1H), 7.26 (d, J=7.9 Hz, 2H), 6.63 (d, J=6.8 Hz, 1H),
1
3
1
25.2, 117.1, 116.9, 115.2, 112.9, 112.6, 109.5. HRMS ESI 2.41 (d, J=4.1 Hz, 6H). C NMR(125 MHz, CDCl ) δ (ppm):
m/z): Calculated for C13
3
+
(
H
N
10 2
O [M+H] : 211.0871, found: 144.9, 145.5, 137.6, 135.5, 131.0, 129.3, 125.9, 124.7, 115.7,
2
11.0874.
114.9, 107.1, 21.3, 21.2. HRMS ESI (m/z): Calculated for
+
2
‐(naphthalen‐1‐yl)imidazo[1,2‐a]pyridine (3m) : brown oil
C
15
H
14
N
2
[M+H] : 223.1235, found: 223.1240 .
1
(
(
(
130 mg, 53%), H NMR (500 MHz, CDCl
m, 1H), 8.15 (d, J=6.5 Hz, 1H), 7.93‐7.89 (m, 2H), 7.85‐7.83 (166 mg, 61%), mp 203‐205°C. H NMR (400 MHz, CDCl
m, 2H), 7.74‐7.72 (m, 1H), 7.58‐7.52 (m,3H), 7.23‐7.20 (m, (ppm): 8.26 (d, J= 8 Hz, 1H), 7.94 (t, J=7.6 Hz, 2H), 7.54 (s,
3
) δ (ppm): 8.83‐8.61 6‐bromo‐2‐phenylimidazo[1,2‐a]pyridine (3t) : White solid
1
3
) δ
1
1
1
H), 6.83‐6.80 (m, 1H). 13C NMR(125 MHz, CDCl
45.3, 145.1, 128.5, 128.3, 127.7, 126.4, 125.9, 125.8, 125.5, J=7.2 Hz, 1H), 7.24‐7.21 (m, 1H). C NMR(125 MHz, CDCl
25.4, 124.6, 117.6, 112.4, 111.2. HRMS ESI (m/z): (ppm): 146.3, 143.8, 128.8, 128.4, 126.1, 125.6, 117.9, 108.2,
3
) δ (ppm): 1H), 7.53 (d, J=9.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 2H), 7.35 (t,
1
3
3
) δ
+
+
Calculated for C17
H
12
N
2
[M+H] : 245.1079, found: 245.1076.
107.2. HRMS ESI (m/z): calculated for C13
H
9
BrN [M+H] :
2
2
‐(furan‐2‐yl)imidazo[1,2‐a]pyridine (3n) : Yellowish Green 273.0027, found: 273.0030.
1
oil (120 mg, 65%). H NMR (500 MHz, CDCl
d, J=6.5 Hz, 1H), 7.77 (s, 1H), 7.59 (d, J=9.0 Hz, 1H), 7.46 (t, (146 mg, 64%), mp 208‐210 C. H NMR (400 MHz, CDCl
J=1.5 Hz, 1H), 7.16‐7.13 (m, 1H), 6.90 (d, J=3.5 Hz, 1H), 6.77‐ (ppm): 8.17 (s,1H), 7.93 (d, J= 7.6 Hz, 2H), 7.82 (s,1H), 7.61
.74 (m, 1H). 6.50‐6.49 (m, 1H). 13C NMR(125 MHz, CDCl
) δ (d, J= 8.4 Hz, 1H),m7.44 (t, J= 7.2 Hz, 2H), 7.35 (t, J= 6.8 Hz,
ppm): 149.5, 145.6, 142.0, 137.8, 125.6, 125.0, 117.3, 112.6, 1H), 7.16 (d, J = 9.6 Hz, 1H). C NMR(100 MHz, CDCl
3
) δ (ppm): 8.07 6‐chloro‐2‐phenylimidazo[1,2‐a]pyridine (3u) : White solid
0
1
(
3
) δ
6
(
3
13
3
)
1
C
2
12.5, 111.5, 107.8, 106.8. HRMS ESI (m/z): Calculated for δ(ppm): 146.4, 143.8, 132.8, 128.8, 128.5, 126.4, 126.1,
+
11
H
8
N
2
O [M+H] : 185.0715, found: 185.0717.
123.4, 120.9, 117.7, 108.5. HRMS ESI (m/z): Calculated for
+
‐(thiophen‐3‐yl)imidazo[1,2‐a]pyridine (3o) : White solid
C
13
H
9
ClN
2
[M+H] : 229.0533, found: 229.0528
0
1
(
114 mg, 57%), mp 140‐142 C. H NMR (400 MHz, CDCl
ppm): 8.11 (d, J=6.4 Hz, 1H), 8.81 (d, J=2 Hz, 1H), 7.75 (s, (4a) : Light yellow solid (252 mg, 88%), mp 228‐230 C. H
3
) δ 2‐phenyl‐N‐(pyridin‐2‐yl)imidazo[1,2‐a]pyridin‐3‐amine
0
1
(
1
H), 7.62 (d, J=9.2 Hz, 1H), 7.52 (d, J=5.2 Hz, 1H), 7.40‐7.38 NMR (400 MHz, CDCl
3
) δ (ppm): 8.21 (d, J=4.0 Hz, 1H), 8.05
(d, J=7.2 Hz, 2H), 7.89 (J=6.4 Hz, 1H), 7.67 (d, J=9.2 Hz, 1H),
) δ (ppm): 145.3, 141.8, 135.4, 126.1, 7.43‐7.36 (m, 3H), 7.43‐7.24 (m, 2H), 6.83‐6.77 (m, 2H), 6.71
13
(
m, 1H), 7.18 (t, J=7.2 Hz, 1H), 6.78 (t, J=6.8 Hz, 1H).
C
NMR(100 MHz, CDCl
3
1
3
1
25.9, 124.8, 121.5, 117.2, 112.5, 108.0. HRMS ESI (m/z): (s, 1H), 6.13 (d, J=8.0 Hz, 1H). C NMR(100 MHz, CDCl ) δ
3
+
Calculated for C11
H
8
N
2
S[M+H] : 201.0376, found: 201.0481 .
(ppm): 157.0, 148.5, 142.9, 139.5, 138.7, 137.8, 130.3, 129.3,
2
0
+
solid (131 mg, 67%), mp 130‐132 C.
1
H NMR (400 MHz, CDCl ) δ (ppm): 8.63 (d, J=4.4 Hz, 1H), 287.1294.
8
7
6
1
1
.26 (s, 1H), 7.54 (d, J=9.2 Hz, 1H), 8.21‐8.15 (m, 2H), 7.81‐ 3‐(3‐(imidazo[1,2‐a]pyridin‐2‐yl)phenyl)imidazo[1,2‐
.78 (m, 1H), 7.65 (d, J=9.2 Hz, 1H), 7.24‐7.18‐7 (m, 1H), a]pyridine (6) : Following the general procedure B taking
.83‐6.80 (m, 1H). 13C NMR(100 MHz, CDCl
) δ (ppm): 144.5, iodine (0.6 equiv) and 2a (2 equiv) reacted with 1a produced
3
0
1
40.8, 133.6, 132.1, 131.7, 130.9, 130.0, 127.4, 125.8, 125.2, light yellow solid (195 mg, 63%), mp 155‐157 C. H NMR
17.6, 112.6, 112.4. HRMS ESI (m/z): Calculated for C12
H
N
9 3
(500 MHz, CDCl
7.95 (d, J=7.6 Hz, 1H), 7.85 (s, 1H), 7.68 (d, J=9.2 Hz, 2H),
3
) δ (ppm): 8.12 (d, J=6.8 Hz, 2H), 8.05 (s, 2H),
+
[M+H] : 196.0875, found: 196.0869.
7
‐methyl‐2‐phenylimidazo[1,2‐a]pyridine (3q) : White solid 7.46‐7.37 (m, 2H), 7.20 (d, J= 8Hz, 1H), 6.81 (t, J= 6.8Hz, 2H).
0
1
13
(
(
142 mg, 68%), mp 178‐180 C. H NMR (500 MHz, CDCl
ppm): 8.02 (d, J=5.2 Hz, 2H), 7.98‐7.96 (m, 2H), 7.80 (s, 1H), 131.6, 130.5, 128.4, 127.3, 122.8, 115.5, 113.2, 107.5. HRMS
3
) δ
C NMR(125 MHz, CDCl ) δ (ppm): 148.5, 142.1, 138.6,
3
+
7
2
1
2
2
6
.45‐7.44 (m, 2H), 7.35 (t, J= 6 Hz, 1H), 6.67‐6.65 (m, 1H), ESI (m/z): Calculated for C20
H
N
14 4
[M+H] : 311.1297, found:
13
.42 (s, 3H). C NMR(125 MHz, CDCl
3
) δ (ppm): 146.0, 145.4, 311.1313.
35.6, 133.8, 128.6, 127.8, 126.0, 124.8, 115.8, 115.0, 107.5, 3‐(methylthio)‐2‐phenylimidazo[1,2‐a]pyridine (7a) : light
+
0
1
1.3. HRMS ESI (m/z): Calculated for C14
09.1079, found : 209.1082 .
H
12
N
2
[M+H] : yellow solid (170 mg, 71%), mp 70‐72 C. H NMR (400 MHz,
CDCl ) δ (ppm): 8.42 (d, J=6.8 Hz, 1H), 8.22 (t, J=7.6 Hz, 2H),
3
‐methyl‐2‐phenylimidazo[1,2‐a]pyridine (3r) : White solid 7.61 (d, J=8.8 Hz, 1H), 7.42 (t, J=7.6Hz, 2H), 7.33 (d, J=7.2 Hz,
0
1
13
(
146 mg, 70%), mp 174‐176 C. H NMR (400 MHz, CDCl
3
) δ 1H), 7.25‐7.21 (m, 1H), 6.89‐6.86 (m, 1H), 2.20 (s, 3H).
C
(
ppm) = 7.96‐7.91 (m, 3H), 7.79 (s, 1H), 7.54 (d, J=9.2 Hz, NMR(100 MHz, CDCl
3
) δ (ppm): 147.5, 146.3, 132.6, 131.8,
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DOI: 10.1039/C9OB00812H
ARTICLE
Journal Name
1
31.3, 130.0, 128.9, 126.5, 122.7, 117.7, 115.9, 113.1, 18.2. 2‐(4‐(tert‐butyl)phenyl)‐3‐(methylthio)imidazo[1,2‐
[M+H] : 241.0799, a]pyridine (7h) : Gummy solid (118 mg, 40%). 1H NMR (400
+
HRMS ESI (m/z): Calculated for C13
found: 241.0795.
H
8
Cl
2
N
2
MHz, CDCl
7.96‐7.93 (m, 1H), 7.65 (d, J= 12 Hz, 1H), 7.50‐7.45 (m, 3H),
Yellow solid (172 mg, 68%), mp 108‐110 C. H NMR (400 7.29‐7.27 (m, 1H), 6.94‐6.89 (m, 1H), 2.25 (s, 3H), 1.36 (s,
3
) δ (ppm): 8.48‐8.45 (m, 1H), 8.23‐8.20 (m, 1H),
3
‐(methylthio)‐2‐(p‐tolyl)imidazo[1,2‐a]pyridine (7b)
:
0
1
1
3
MHz, CDCl
3
) δ (ppm) 8.46 (d, J=6.8 Hz, 1H), 8.18 (d, J=8 Hz, 9H). C NMR(125 MHz, CDCl
3
) δ (ppm); 151.3, 148.9, 146.3,
1
H), 7.65 (d, J=9.2 Hz, 1H), 7.30‐7.25 (m, 3H), 6.91 (d, J=6.4 130.9, 127.9, 126.7, 125.7, 125.5, 125.3, 124., 117.5, 112.6,
1
3
Hz, 1H), 2.41 (s, 3H), 2.24 (s, 3H). C NMR(100 MHz, CDCl
3
) δ 111.0, 34.6, 31.3, 31.2, 31.1, 18.1.
(
ppm): 148.7, 146.1, 138.2, 130.6, 129.1, 128.2, 126.1, 124.2, HRMS ESI (m/z): Calculated for
C
15
H
14
N
OS [M+H]+:
2
1
17.4, 112.8, 111.2, 21.3, 18.0. HRMS ESI (m/z): Calculated 297.1425, found: 297.1430 .
+
for C13
2
H
8
Cl
2
N
2
[M+H] : 255.0956, found: 255.0958.
3‐(d ‐methylthio)‐2‐phenylimidazo[1,2‐a]pyridine (7i) : light
3
0
1
‐(4‐butylphenyl)‐3‐(methylthio)imidazo[1,2‐a]pyridine (7c) brown solid (156 mg, 64%), mp 68‐70 C. H NMR (400 MHz,
1
:
(
Gummy solid (166 mg, 56%). H NMR (400 MHz, CDCl
ppm) = 8.47 (d, J=6.8 Hz, 1H), 8.20 (d, J=8.0 Hz, 2H), 7.66 (d, 7.71 (d, J=8.8 Hz, 1H), 7.48 (t, J=6.8 Hz, 1H), 7.38 (t, J=7.2 Hz,
J=9.2 Hz, 1H), 7.29 (t, J= 7.6 Hz, 3H), 6.93 (t, J=6.8 Hz, 1H), 2H), 7.31 (t, J=7.6 Hz, 1H), 6.95 (t, J=6.8 Hz, 1H) . 13
3
) δ CDCl ) δ (ppm): 8.47 (d, J=6.8 Hz, 1H), 8.25 (d, J=7.6 Hz, 2H),
3
C
2
1
CDCl
.67 (t, J=7.6 Hz, 2H), 2.62 (s, 3H), 1.67‐1.61 (m, 2H), 1.42‐ NMR(100 MHz, CDCl ) δ (ppm): 148.8, 146.1, 133.3, 128.4,
3
.36 (m, 2H), 0.96‐0.93 (t, J= 7.2 Hz, 3H). 13C NMR(100 MHz, 126.3, 124.3, 117.5, 113.0, 111.6. HRMS ESI (m/z):
+
3
) δ (ppm): 145.9, 143.5, 130.1, 128.6, 128.2, 126.5, Calculated for
C
14
9
H D
3
2
N S
[M+H] : 244.0988, found:
1
25.7,124.2, 117.3, 113.1, 111.3, 35.6, 33.4, 22.5, 18.2, 13.8. 244.0996.
+
HRMS ESI (m/z): Calculated for C13
found: 297.1430.
H
8
Cl
2
N
2
[M+H] : 297.1425, 2‐(4‐(methylthio)phenyl)imidazo[1,2‐a]pyridine (9) : White
0
1
solid (156 mg, 65%), mp 130‐132 C. H NMR (500 MHz,
CDCl ) δ (ppm): 8.12 (d, J=6.5Hz, 1H), 7.90‐7.89 (m, 2H), 7.84
) δ (s, 1H), 7.68 (d, J=9.0 Hz, 1H), 7.34‐7.32 (m, 2H), 7.23‐7.20
2‐(4‐ethylphenyl)‐3‐(methylthio)imidazo[1,2‐a]pyridine
3
1
(
7d) : brown oil (166 mg, 62%). H NMR (400 MHz, CDCl
3
1
3
(
ppm): 8.46 (d, J=7.2 Hz, 1H), 8.19 (d, J=8.0 Hz,2H), 7.68 (d, (m, 1H), 6.83‐6.80 (m, 1H), 2.54 (s, 3H). C NMR(125 MHz,
J=8.8 Hz, 1H), 7.33‐7.26 (m, 3H), 6.92 (d, J=6.8 Hz, 1H), 2.74‐ CDCl
3
) δ (ppm): 145.3, 144.9, 138.6, 130.1, 126.8, 126.5,
2
.68 (m, 2H), 2.25 (s, 3H), 1.29 (t, J=7.6 Hz, 3H). 13C NMR(100 125.6, 125.1, 117.2, 112.7, 107.8, 15.8. HRMS ESI (m/z):
+
MHz, CDCl
3
) δ (ppm): 146.3, 144.6, 131.1, 128.3, 127.8, Calculated for
C
14
H
12
N
2
S [M+H] : 241.0799,
found:
1
25.9, 124.3, 117.7, 112.7, 111.01 28.6, 18.1, 15.5. HRMS ESI 241.0808.
+
(
m/z): Calculated for C16
H
N
16 2
S [M+H] : 269.1112, found: 2‐(4‐(methylsulfonyl)phenyl)imidazo[1,2‐a]pyridine (10) :
2
2
69.1115.
To a 10 ml round bottom flask was added 2‐(4‐
‐(4‐fluorophenyl)‐3‐(methylthio)imidazo[1,2‐a]pyridine
(methylthio)phenyl)imidazo[1,2‐a]pyridine 9, (70 mg, 1.0
0
1
0
(
(
(
(
7e) : White solid (168 mg, 65%), mp 102‐104 C. H NMR equiv) and ethyl acetate (3 ml) at 0 C. After that mCPBA (100
400 MHz, CDCl ) δ (ppm): 8.47 (d, J=6.4 Hz, 1H), 8.30‐8.27 mg) in solution of ethyl acetate was added to the flask and
3
m, 2H), 7.65 (d, J=9.2 Hz, 1H), 7.32‐7.28 (m, 1H), 7.19‐7.14 stirred for 12h under nitrogen atmosphere. After completion
m, 2H), 6.96‐6.93 (m, 1H), 2.25 (s, 3H); 1 C NMR(125 MHz, of the reaction, reaction mixture is diluted with water (5 ml)
3
CDCl
3
) δ (ppm): 162.9(d, JC‐F = 246.5 Hz), 148.0, 146.3, 130.0 and extracted with ethyl acetate (3×25 ml), concentrate the
(
1
d, JC‐F = 7.1 Hz), 126.0, 124.2, 117.6, 115.3(d, JC‐F = 22.4 Hz), organic layer followed column chromatography to afford 10
12.7,111.1, 18.1. HRMS ESI (m/z): Calculated for C14
1
H
11FN
2
S
as a White solid (190 mg, 70%), mp 244‐246 °C; H NMR (400
MHz, CDCl ) δ (ppm): 8.17 (d, J=8.4 Hz, 3H), 8.03‐7.99 (m,
+
[M+H] : 259.0705, found: 259.0712.
3
2
‐(4‐chlorophenyl)‐3‐(methylthio)imidazo[1,2‐a]pyridine
3H), 7.68 (d, J=9.2 Hz, 1 H), 7.24 (d, J=8 Hz, 1 H), 6.85 (d,
1
13
(
7f) : brown gummy solid (172 mg, 63%). H NMR (400 MHz, J=6.8 Hz, 1H), 3.10 (s, 3H). C NMR(125 MHz, CDCl
3
) δ
CDCl
3
) δ (ppm): 8.47 (d, J=6.8 Hz, 1H), 8.20 (d, J=8.4 Hz, 2H), (ppm): 140.5, 140.1, 127.9, 126.8, 126.0, 117.5, 114.7, 113.6,
7
2
1
1
2
2
.66‐7.59 (m, 3H), 7.32‐7.26 (m, 1H), 6.95 (t, J=6.8 Hz, 1H), 112.9, 109.7, 44.58. HRMS ESI (m/z): Calculated for
13
+
.25 (s, 3H). C NMR(100 MHz, CDCl
3
) δ (ppm): 147.5, 146.3,
C
13
H
Cl
8 2
2
N [M+H] : 273.0698, found: 273.0690.
32.7, 131.5, 129.7, 126.2, 124.3, 122.5, 117.6, 112.9, 111.6,
+
8.1. HRMS ESI (m/z): Calculated for C14
H
11ClN
2
S [M+H] :
Conflicts of interest
75.0710, found: 275.0713.
‐(4‐methoxyphenyl)‐3‐(methylthio)imidazo[1,2‐a]pyridine
1
(7g) : brown oil (138 mg, 51%). H NMR (400 MHz, CDCl
3
) δ There are no conflict to declare.
(
ppm): 8.45 (t, J=6.8 Hz, 1H), 8.23 (d, J=8.4 Hz, 2H), 7.67 (d,
J=8.8 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.01 (d, J=8.8 Hz, 2H),
Acknowledgements
1
3
6
.92 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.24 (s, 3H). C NMR(100
MHz, CDCl ) δ (ppm): 159.8, 148.4, 129.6, 126.1, 124.2,
17.2, 113.8, 112.7, 110.6, 55.3, 18.1. HRMS ESI (m/z):
3
Financial support from DST‐SERB New Delhi (Grant No:
SB/S1/OC‐15/2014) and Council of Scientific and Industrial
Research(CSIR) (Grant No: 02(0270)/16/EMR‐II) are most
1
+
Calculated for C15
H
14
N
2
OS [M+H] : 271.0905,
found:
2
71.0907.
8
| J. Name., 2012, 00, 1‐3
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ARTICLE
gratefully acknowledged. One of the authors, SKS gratefully
thanks CSIR New Delhi for financial support in form of CSIR‐
JRF. Both the authors would like to sincerely thank
Sophisticated Analytical Instruments Facility (SAIF), IIEST
Shibpur for single crystal X‐ray analysis.
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