Copper-Catalyzed Oxidative Cyclization of 2-Amino-azaarenes with Lignin Models: Synthesis of 3-Phenoxy Imidazo Heterocycles

Article abstract of DOI:10.1021/acs.joc.7b00480

A catalytic oxidative cyclization of 2-aminopyridines or 2-aminobenzothiazole with 2-phenoxyacetophenones (a kind of lignin platform compound) was developed, efficiently providing valuable 3-phenoxy imidazo[1,2-a]pyridines or 3-phenoxy benzo[d]imidazo[2,1-b]thiazoles. The reaction was realized under oxygen by simply using inexpensive CuI as the catalyst.

Full text of DOI:10.1021/acs.joc.7b00480

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Article
Copper-catalyzed oxidative cyclization of 2-amino-azaarenes
with lignin models: synthesis of 3-phenoxy imidazo heterocycles
Jian Zhang, Xiunan Lu, Tingyan Li, Shanlu Wang, and Guofu Zhong
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 21 Apr 2017
Downloaded from http://pubs.acs.org on April 21, 2017
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Copper-catalyzed oxidative cyclization of 2-amino-azaarenes
with lignin models: synthesis of 3-phenoxy imidazo
heterocycles
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Jian Zhang,* Xiunan Lu, Tingyan Li, Shanlu Wang and Guofu Zhong*
College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou
3
10036, China.
Eꢀmail: zhangjian@hznu.edu.cn ; zgf@hznu.edu.cn
S
NH2
S
N
NH2
R1
O
N
N
N
4
N
1
R1
Ar1
O
Ar1
Ar2
N
Ar1
[
Cu]/O2
[Cu]/O2
O
O
2
Ar2
Ar2
- H O
- H O
3
5
2
lignin model
2
benzo[d]imidazo
2,1-b]thiazole
imidazo[1,2-a]pyridine
[
1. oxidative C-H/N-H cross-coupling/cyclization
2
3
4
5
6
. efficient approach to 3-oxo substituted imidazo heterocycles
. O2 as oxidant
. H O as the sole byproduct
2
. inexpensive copper as the catalyst
. lignin model as reagent
Abstract: A catalytic oxidative cyclization of 2ꢀaminopyridines or 2ꢀaminobenzothiazole with
ꢀphenoxyacetophenones (a kind of lignin platform compounds) was developed, efficiently
2
providing valuable 3ꢀphenoxy imidazo[1,2ꢀa]pyridines or 3ꢀphenoxy benzo[d]imidazo[2,1ꢀ
b]thiazoles. The reaction was realized under oxygen by simply using inexpensive CuI as the
catalyst.
Introduction
Lignin, a wide occurring aromatic biopolymer responsible for the strength and shape of
1
plants, constitutes 30% of nonꢀfossil organic carbon. The primary structure of lignin is
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composed of a diversely linked network of electronꢀrich phenylpropanols. Due to world’s
depleting petroleum reserves and lignin’s abundance in nature, intense efforts have been made to
2
,3
controlled conversion of lignin into wellꢀdefined aromatic chemicals.
2ꢀPhenoxyacetoꢀ
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phenones is a kind of lignin platform molecules, which have been widely used as model
3
compounds to produce various aromatics. However, transformation of lignin into valuable
nitrogenꢀcontaining chemicals is still very limited owing to the lack of efficient conversion
methods for ligninꢀderived chemicals.
Imidazo[1,2ꢀa]pyridines have drawn the attention of chemists in recent years due to their
4
immense applications in different fields. In particular, imidazo[1,2ꢀa]pyridines scaffold is one of
the most privileged nitrogen containing heterocycles in drug design, widely used at the core of
5
aꢀf
many pharmaceutical drugs. As a consequence, a large number of synthetic methodologies
have been developed, and there are mainly two routes to construct imidazo[1,2ꢀa]pyridines. One
6
is cyclization by oxidative amination or cascade reactions. The other approach is transitionꢀ
metalꢀcatalyzed functionalization of imidazo[1,2ꢀa]pyridines via direct crossꢀcoupling reactions,
such as alkenylation, ethoxycarbonyl difluoromethylation, trifluoroꢀmethylation, thiocyanation,
7
sulfenylation, nitrosylation and selenylation (Scheme 1, eq. 1). For instance, Cao’s group
developed a copperꢀcatalyzed selective crossꢀcoupling for the synthesis of Cꢀ3 carbonyl
7
g
imidazo[1,2ꢀa]pyridine derivatives.
These methodologies afforded the Cꢀ3 position
functionalized imidazopyridines due to its nucleophilicity. The pharmacological activities of
6
,7
these heterocycles are dependent on the nature of the substituent on the imidazo ring. Among
them, structures related to imidazo[1,2ꢀa]pyridinꢀ3ꢀol with 2ꢀaryl substituents are biologically
8,9
active with both antifungal and anthelmintic activity. Unfortunately, very limited procedures
9
have been developed to make such compounds with special properties. Actually, there is still no
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catalytic, efficient and green method for synthesis of Cꢀ3 oxo substituted imidazo[1,2ꢀ
a]pyridines (Scheme 1, eq. 2 and eq. 3).
Benzo[d]imidazo[2,1ꢀb]thiazole represents another important fused bicyclic sulfur and nitrogenꢀ
1
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containing heterocycles, which have been reported to be associated with promising biological
5gꢀk
activities such as antitumor agents, antimicrobial agents and kinase inhibitors.
However, only
1
0
a few methods have been developed for the synthesis of these fused heterocycles. In particular,
no efficient method has been developed for the synthesis of Cꢀ3 oxo substituted
1
1
benzo[d]imidazo[2,1ꢀb]thiazole derivatives (Scheme 1, eq. 2 and eq. 3).
Scheme 1. Synthesis of C-3 functionalized imidazo heterocycles.
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The main goal of our research is the design and synthesis of valuable chemicals from easily
1
2
available starting materials. Thus, the immense applications of imidazo[1,2ꢀa]pyridines and
benzo[d]imidazo[2,1ꢀb]thiazoles together with the widely occurring ligninꢀderived compounds,
such as 2ꢀphenoxy acetophenone derivatives, prompted us to explore novel and green
methodologies for the synthesis of special and valuable 3ꢀO substituted imidazo heterocycles.
Molecular oxygen is considered as an ideal oxidant in view of green and sustainable chemistry
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due to its abundant, natural and environmental friendly properties. Herein, we disclosed an
efficient aerobic oxidative annulation between 2ꢀaminoꢀazaarenes and lignin models, delivering
valuable 3ꢀO imidazo[1,2ꢀa]pyridine and benzo[d]imidazo [2,1ꢀb]thiazole derivatives (Scheme 1,
eq. 4).
Results and Discussion
Our tactics for oxidative conversion of the lignin models would commence with imine
formation from ketone and amine by water elimination, and the enamine formed from imine
6
,14
might undergo following intramolecular cyclization by CꢀN bond formation, providing the Cꢀ
Oꢀsubstituted imidazo heterocycles. 2ꢀPhenoxyacetoꢀphenone (2a) as a lignin model substrate
3
was examined to react with 2ꢀaminopyridine (1a) under copperꢀcatalyzed conditions. To our
delight, the reaction provided desired imidazo[1,2ꢀa]pyridine product 3a in 59% using toluene as
1
5
the solvent (Table 1, entry 1). Next, a series of representative solvents were examined (Table 1,
entries 2ꢀ5). High polar aprotic solvents such as DMF led to only 25% yield (Table 1, entry 2).
Meanwhile, the reaction proceeded much better in 1,4ꢀdioxane, with 71% yield obtained (Table 1,
entry 3). Interestingly, protic solvent such as ethanol also led to moderate yield (Table 1, entry 4).
It is worthy to note that the desired imidazo[1,2ꢀa]pyridine (3a) was obtained in 77% yield using
6
,14ꢀ15
DCE as the solvent, and no amide was detected (Table 1, entry 5).
The structure of a newly
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a
Table 1. Optimization of reaction conditions
entry
catalyst
CuI
ligand
solvent
toluene
DMF
yield (%)
59
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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0
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0
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-
CuI
ꢀ
25
CuI
ꢀ
dioxane
EtOH
71
CuI
ꢀ
42
CuI
CuI
ꢀ
DCE
77
ꢀ
H
O
45
2
b
7
CuI
ꢀ
ꢀ
53
8
9
CuI
1,10ꢀPhen
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
42
CuI
pyridine
21
10
CuBr2
CuBr2
CuI
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
70
c
1
1
81
d
12
65
e
f
13
CuI
60
14
ꢀ
< 5
11
15
FeCl3
16
RuCl3
24
a
Unless otherwise described, the reaction conditions were as follows: 2ꢀamino pyridine (1a, 0.6 mmol), 2ꢀ
o
phenoxyacetophenone (2a, 0.2 mmol), catalyst (5 mol%), ligand (10 mol%), solvent (0.8 mL), 100 C, 16 h,
b
under oxygen (1 atm). The isolated yield was obtained by silica gel column chromatography. Without solvent
c
d
e
f
2
.2 equiv. CuBr was used under N . 20 mol% CuI was used. Microwave irradiation. Without copper salt.
2 2
synthesized compound 3a was unambiguously confirmed by single crystal Xꢀray diffraction
studies (see the ESI for details). Notably, the reaction can be performed in water or even without
any solvent, producing the desired heterocycles in 45% and 53% yields respectively (entries 6
and 7). Addition of Nꢀcontaining ligands was not effective, even leading to lower yields (Table 1,
entries 8 and 9). Employment of other copper salt such as CuBr could not further improve the
2
yield (Table 1, entry 10). Interestingly, if 2.2 equivalent amount of CuBr was used, the reaction
2
also provided 3a in 81% yield under inert atmosphere, indicating that reꢀoxidation of the reduced
6
,14
copper by molecular oxygen completes the catalytic cycle (Table 1, entry 11).
The reaction
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can not been further improved by using 20 mol% CuI (Table 1, entry 12). Also, microwave
irradiation failed to promote the reaction more efficiently (Table 1, entry 13). Moreover, the
reaction remained sluggish in the absence of copper salt (Table 1, entry 14). Other transitionꢀ
metal salts, such as FeCl and RuCl , only showed very limited catalytic activity (Table 1, entries
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5 and 16).
a
Table 2. Synthesis of imidazo[1,2ꢀa]pyridines
a
Unless otherwise described, the reaction conditions were as follows: 2ꢀamino pyridine (1, 0.6 mmol), 2ꢀ
o
phenoxyacetophenone (2, 0.2 mmol), CuI (5 mol%), DCE (0.8 mL), 100 C, 14ꢀ16 h, under oxygen (1 atm).
b
The yields indicated are isolated yields were obtained by silica gel column chromatography. Gram scale (2a,
c
d
1
.02 g, 4.8 mmol, 1.0 equiv.). 2ꢀMethoxyꢀacetophenone was used. 1ꢀ(4ꢀMethoxyphenꢀ oxy)ꢀ5ꢀmethylꢀhexanꢀ
ꢀone was used.
2
With this optimized catalytic conditions in hand, we turned to examine the scope of the
differently substituted ketones (Table 2). It was observed that installing electronꢀdonating
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functional group such as methoxyl group to Cꢀterminus phenyl ring resulted in corresponding
product in higher yield, while installing electronꢀdeficient functional group gave opposite result
(Table 2, 3b and 3c). Electron effects on Oꢀterminus phenyl ring gave the same results (Table 2,
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d-3f). Ketones 2 with alkyl groups were also examined. To our delight, both of 2ꢀ
methoxyacetophenone and 1ꢀ(4ꢀmethoxyphenoxy)ꢀ5ꢀmethylꢀhexanꢀ2ꢀone reacted smoothly and
provided corresponding heterocyclic products in good yields (Table 2, 3g and 3h). Differently
functionalized 2ꢀaminopyridines were also tested to react with ketones 2. A series of functional
1
groups R on pyridyl ring of 1, such as CN, COOMe, Br, F and Cl, could be well tolerated in the
catalytic conditions, regardless of electronꢀdonating or electronꢀwithdrawing properties (Table 2,
3i-3o). Furthermore, 2ꢀaminoisoquinoline also reacted well, affording fused imidazo isoquinoline
3
p in 49% yield. However, 2ꢀaminoꢀ6ꢀmethylpyridine was totally inactive due to its steric
hinderance even at elevated temperatures. This oxidative cyclization also proceeded well on
gram scale, and the product 3a was obtained in 71% yield, showing the robustness of this method.
a
Table 3. Synthesis of fused benzoimidazothiazole derivatives from 2ꢀaminobenzothiazole
a
Unless otherwise described, the reaction conditions were as follows: 2ꢀaminobenzothiazole (4, 0.6 mmol), 2ꢀ
o
phenoxyacetophenone (2, 0.2 mmol), CuI (5 mol%), DCE (0.8 mL), 100 C, 16 h, under oxygen (1 atm). The
isolated yields were obtained by silica gel column chromatography.
Considering the wide utilizations of benzo[d]imidazo [2,1ꢀb]thiazoles, we turned to examine
the reaction of 2ꢀaminoꢀbenzothiazole (4) with ketones 2, employing the same oxidative catalytic
conditions (Table 3). Satisfactorily, ketones (2) bearing electronꢀdonating as well as electronꢀ
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withdrawing substituents reacted well and afforded the corresponding benzo[d]ꢀimidazo[2,1ꢀ
b]thiazoles with excellent yields (Table 3, 5a-5e).
6,14ꢀ15
On the basis of the results obtained above and previous reports,
a plausible mechanism is
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illustrated in Scheme 2. The first step involves a coupling of the substrates 1 or 4 and 2 to
produce imine I with the elimination of water. The imine I is then equilibrates to enamine II. A
oneꢀelectron oxidation of intermediate II by copper catalyst leads to nitrenium ion IV by hydride
abstraction. Finally, intermediate IV undergoes intraꢀmolecular nucleophilic cyclization to give
intermediate V, and the subsequent proton elimination occurs to afford product 3 or 5.
Scheme 2. Proposed mechanism
In conclusion, we have developed a simple and efficient catalytic oxidative annulation method
for the cyclization of lignin model 2ꢀphenoxyacetophenones with 2ꢀaminopyridines or 2ꢀ
aminobenzothiazole. With the assistance of catalytic amount of copper salt, this aerobic protocol
provides an efficient, greener and straightforward methodology for the preparation of
biologically valuable imidazo[1,2ꢀa]pyridines and benzo[d]imidazo[2,1ꢀb]thiazꢀoles, producing
water as the sole byꢀproduct. These novel and special Cꢀ3 oxoꢀsubstituted imidazo heterocycles
could have important impact on drug discovery.
■
Experimental Section
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General considerations
All commercially available reagents for the catalytic reactions were used as received: AR
grade 1, 2ꢀdichloroethane, 2ꢀamino pyridines and CuI were obtained from TCI. The starting
3
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materials of lignin model were prepared according to the reported method. H NMR spectra
were performed on a Bruker 500 MHz spectrometer and are reported in ppm downfield from
SiMe (δ = 0.0) and relative to the signal of chloroformꢀd (δ = 7.27 ppm, singlet). Protonꢀ
4
1
3
decoupled CNMR spectra were recorded on a 500 (125 MHz) or ECAꢀ400 (100 MHz)
spectrometer and are reported in ppm using solvent as an internal standard (CDCl at 77.23
3
ppm). IR spectra were recorded as thin films on KBr plates on a BioꢀRad FTS 165 FTIR
ꢀ1
spectrometer and are reported in frequency of absorption (cm ). High resolution mass spectral
analysis (HRMS) was performed on Waters QꢀTof Permies Mass Spectrometer. Note: the
obtained imidazo[1,2ꢀa]pyridines and benzo[d]imidazo[2,1ꢀb]thiazoles are generally instable,
suffering from slow and gradual degradation under air, and they should been kept under an inert
atmosphere.
General Procedure for the Synthesis of imidazo[1,2-a]pyridines and benzo[d]imidazo[2,1-
b]thiazoles
An oven dried vial was charged with CuI (1.9 mg, 0.010 mmol, 5 mol%), 2ꢀaminopyridine 1
(
0.6 mmol) or 2ꢀaminobenzothiazole 4 (0.6 mmol), ketone 2 (0.2 mmol) and dry 1,2ꢀ
dichloroethane (0.8 mL). The vial was then sealed under an oxygen atmosphere, and the reaction
was heated to 100 °C with stirring for 14ꢀ16 h. After cooling down, the mixture was diluted with
ethyl acetate, filtered and washed with water and brine. The organic layer was dried over
anhydrous Na SO , filtered and concentrated to give the crude product, which was purified
2
4
through a flash column chromatography (ethyl acetate in hexane solution) to afford 3 or 5 as
product.
Characterization data for the imidazo[1,2-a]pyridines and benzo[d]imidazo[2,1-b]thiazoles
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ꢀPhenoxyꢀ2ꢀphenyl imidazo[1,2ꢀa]pyridine (3a):
This compound was prepared by the General Procedure described above and was obtained as a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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9
0
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6
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8
9
0
1
white solid (44 mg, yield = 77%), m.p.: 145ꢀ146 °C. H NMR (500 MHz, CDCl ): δ = 8.05 (d, J
3
=
7.6 Hz, 2H), 7.73 (d, J = 6.8 Hz, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.39 (t, J = 7.2 Hz, 2H), 7.25ꢀ
7
.31 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 7.10 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.74 (t, J
1
3
= 6.8 Hz, 1H). C NMR (125 MHz, CDCl ): δ = 156.1, 139.9, 132.5, 131.1, 130.2, 128.7, 127.8,
3
ꢀ1
1
1
26.5, 124.4, 123.7, 121.6, 117.9, 115.0, 112.3. FTIR (NaCl, cm ): 3053.3, 2985.8, 1647.2,
495.6, 1421.5, 1390.1, 1362.2, 1265.3, 1201.7, 895.0, 738.7, 706.0. HRMS (ESIꢀTOF) m/z:
+
[M+H] Calculated for C H N O 287.1184; Found 287.1184.
1
9
14
2
3ꢀPhenoxyꢀ2ꢀ(4ꢀmethoxyphenyl) imidazo[1,2ꢀa]pyridine (3b)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (54 mg, yield = 86%), m.p.: 145ꢀ147 °C. H NMR (400 MHz, CDCl ): δ = 7.99ꢀ8.01
3
(
m, 2H), 7.71ꢀ7.74 (dt, J = 1.2 Hz, J = 6.8 Hz, 1H), 7.61ꢀ7.64 (dt, J = 1.2 Hz, J = 9.2 Hz, 1H),
7
1
1
.28ꢀ7.33 (m, 2H), 7.09ꢀ7.19 (m, 2H), 6.93ꢀ6.97 (m, 4H), 6.72ꢀ6.75 (td, J = 6.8 Hz, J = 0.8 Hz,
13
H), 3.82 (s, 3H). C NMR (100 MHz, CDCl ): δ = 159.3, 156.2, 139.8, 131.2, 130.2, 129.3,
3
ꢀ1
27.8, 125.2, 124.1, 123.6, 121.5, 117.6, 115.0, 114.1, 112.1, 55.2. FTIR (NaCl, cm ): 3053.3,
2985.8, 1707.0, 1568.1, 1506.4, 1421.5, 1359.8, 1265.3, 1201.7, 1032.0, 895.0, 837.1, 738.7,
+
7
06.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 317.1285; Found 317.1282.
2
0
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3ꢀPhenoxyꢀ2ꢀ(4ꢀfluorophenyl) imidazo[1,2ꢀa]pyridine (3c)
1
1
1
1
1
1
1
1
1
1
2
2
2
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2
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2
2
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5
6
7
8
9
0
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (33 mg, yield = 55%), m.p.: 114ꢀ115 °C. H NMR (400 MHz, CDCl ): δ = 8.02ꢀ
3
8.05 (m, 2H), 7.74ꢀ7.76 (dt, J = 6.8 Hz, J = 1.2 Hz, 1H), 7.62ꢀ7.64 (dt, J = 9.2 Hz, J = 1.2 Hz,
1
H), 7.28ꢀ7.35 (m, 2H), 7.18ꢀ7.22 (qd, J = 6.8 Hz, J = 1.2 Hz, 1H), 7.07ꢀ7.15 (m, 3H), 6.95ꢀ6.97
13
(
m, 2H), 6.75ꢀ6.79 (td, J = 6.8 Hz, J = 0.8 Hz, 1H). C NMR (100 MHz, CDCl ): δ = 162.4 (J =
3
2
46 Hz), 156.0, 139.9, 130.3 (J = 16 Hz), 128.8, 128.7, 128.2 (J = 8 Hz), 124.4, 123.8, 121.6,
ꢀ1
117.8, 115.6 (J = 21 Hz), 115.0, 112.4. FTIR (NaCl, cm ): 3053.3, 2985.8, 1574.2, 1504.5,
1
489.1, 1421.5, 1392.6, 1359.8, 1265.3, 1201.7, 1159.2, 895.0, 842.5, 738.7, 704.5. HRMS
+
(
ESIꢀTOF) m/z: [M+H] Calculated for C H FN O 305.1090; Found 305.1088.
1
9
13
2
3
ꢀ(4ꢀbromophenoxy)ꢀ2ꢀphenyl imidazo[1,2ꢀa]pyridine (3d)
This compound was prepared by the General Procedure described above and was obtained as a
1
pink oil (49 mg, yield = 67%). H NMR (500 MHz, CDCl3): δ = 7.92ꢀ7.94 (m, 2H), 7.64 (d, J =
7
.0 Hz, 1H), 7.56 (d, J = 9.5 Hz, 1H), 7.29ꢀ7.34 (m, 4H), 7.18ꢀ7.22 (m, 1H), 7.09ꢀ7.13 (m, 1H),
1
3
6
.75ꢀ6.78 (m, 2H), 6.67ꢀ6.70 (td, J = 1.0 Hz, J = 7.0 Hz, 1H). C NMR (125 MHz, CDCl ): δ =
3
155.3, 140.0, 133.1, 132.3, 131.3, 129.7, 128.7，127.9, 126.5, 124.5, 121.4, 118.0, 116.8, 116.2,
ꢀ
1
1
12.5. FTIR (NaCl, cm ): 3053.3, 2985.8, 1481.3, 1421.5, 1362.6, 1265.3, 1201.7, 1159.2, 895.0,
1
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4
4
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5
5
5
5
5
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6
+
7
38.7, 706.2. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H BrN O 365.0290, 367.0271;
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9
13
2
Found 365.0288, 368.0302.
0
1
2
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0
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ꢀ(4ꢀIodophenoxy)ꢀ2ꢀphenyl imidazo[1,2ꢀa]pyridine (3e)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (47 mg, yield = 57%), m.p.: 138ꢀ140 °C. H NMR (500 MHz, CDCl ): δ = 7.91ꢀ7.93
3
(
m, 2H), 7.62 (d, J = 7.0 Hz, 1H), 7.55 (d, J = 9.5 Hz, 1H), 7.51(d, J = 9.0 Hz, , 2H), 7.32 (t, J =
13
7
.5 Hz, 2H), 7.18ꢀ7.22 (m, 1H), 7.09ꢀ7.12 (m, 1H), 6.63ꢀ6.69 (m, 3H). C NMR (125 MHz,
CDCl ): δ = 156.1,140.0,139.1,132.3,131.3,129.5,127.2, 126.5, 124.5, 121.4, 118.0, 117.3, 112.5,
3
ꢀ1
8
6.5. FTIR (NaCl, cm ): 3942.5, 3689.8, 3053.3, 2985.8, 2684.9, 1684.2, 1645.2, 1577.8, 1562.3,
1
506.4, 1479.4, 1433.1, 1421.5, 1390.7, 1363.7, 1265.3, 1203.6, 1161.2, 1149.6, 1004.9, 895.0,
+
8
23.6, 752.2, 727.2, 706.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H IN O 413.0151;
19 13
2
Found 413.0153.
3
ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀimidazo[1,2ꢀa]pyridine (3f)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (66 mg, yield = 95%), m.p.: 121ꢀ122 °C. H NMR (400 MHz, CDCl ): δ = 8.02ꢀ8.04
3
(dd, J = 2.0 Hz, J = 6.8 Hz, 2H), 7.79 (d, J = 6.8 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.14ꢀ7.18 (m,
1
H), 7.05ꢀ7.07 (m, 2H), 6.93ꢀ6.95 (dd, J = 2.0 Hz, J = 6.8 Hz, 2H), 6.70ꢀ6.76 (m, 2H), 6.55 (d, J
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=
7.6 Hz, 1H). C NMR (100 MHz, CDCl ): δ = 159.3, 149.0, 145.1, 139.7, 131.3, 129.7, 127.8,
3
ꢀ
1
25.3, 124.2, 124.1, 121.5, 121.1, 117.5, 114.7, 114.1, 112.8, 112.1, 56.2, 55.2. FTIR (NaCl, cm
1
): 3053.3, 2986.8, 1701.2, 1614.4, 1568.1, 1498.7, 1456.3, 1421.5, 1394.5, 1361.7, 1265.3,
1
1
1
1
1
1
1
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8
9
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6
7
8
9
0
1
251.8, 1199.7, 1174.7, 1114.9, 1030.0, 895.0, 837.2, 738.7, 704.0. HRMS (ESIꢀTOF) m/z:
+
[
M+H] Calculated for C H N O 347.1396; Found 347.1393.
2
1
18
2
3
3
ꢀMethoxyꢀ2ꢀphenyl imidazo[1,2ꢀa]pyridine (3g)
This compound was prepared by the General Procedure described above and was obtained as a
1
colorless oil (32 mg, yield = 71%). H NMR (400 MHz, CDCl ): δ = 8.12 (d, J = 8.0 Hz, 2H),
3
7
.98 (d, J = 6.8 Hz, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz,
1
3
1H), 7.12ꢀ7.16 (m, 1H), 6.83 (t, J = 6.8 Hz, 1H). C NMR (100 MHz, CDCl ): δ = 139.0, 133.4,
3
ꢀ1
1
13.5, 128.7, 127.4, 126.4, 123.7, 121.3, 117.9, 113.2, 112.0, 61.1. FTIR (NaCl, cm ): 2985.8,
1
707.0, 1587.4, 1568.1, 1501.2, 1421.6, 1386.8, 1359.8, 1265.3, 1207.8, 968.3, 896.0, 748.4,
+
706.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 225.1028; Found 225.1029.
1
4
12
2
3
ꢀ(4ꢀMethoxyphenoxy)ꢀ2ꢀisopentyl imidazo[1,2ꢀa]pyridine (3h)
This compound was prepared by the General Procedure described above and was obtained as a
1
colourless oil (38 mg, yield = 61%). H NMR (400 MHz, CDCl ): δ = 7.69 (d, J = 6.8 Hz, 1H),
3
7
.50 (d, J = 9.2 Hz, 1H), 7.06ꢀ7.10 (m, 1H), 6.80 (s, 4H), 6.67ꢀ6.71 (m, 1H), 3.75 (s, 3H), 2.66 (t,
13
J = 8.0 Hz, 2H), 1.53ꢀ1.63 (m, 3H), 0.86 (d, J = 6.4 Hz, 6H). C NMR (100 MHz, CDCl ): δ
3
=155.6, 151.1, 139.4, 133.6, 131.7, 123.2, 121.3, 117.4, 115.7, 114.9, 111.7, 55.7, 37.9, 27.9,
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5
5
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5
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5
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6
ꢀ1
2
4.6, 22.4. FTIR (NaCl, cm ): 3053.3, 2985.8, 1562.2, 1502.6, 1421.5, 1265.3, 1198.05, 1031.9,
+
8
95.0, 831.2, 738.7, 706.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 311.1760;
1
9
22
2
2
Found 311.1756.
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2
3
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6
7
8
9
0
1
2
3
4
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6
7
8
9
0
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6
7
8
9
0
3
ꢀPhenoxyꢀ2ꢀphenylꢀ7ꢀcyano imidazo[1,2ꢀa]pyridine (3i)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (42 mg, yield = 67%), m.p.: 204ꢀ206 °C. H NMR (400 MHz, CDCl ): δ = 7.98ꢀ8.03
3
(m, 3H), 7.78ꢀ7.80 (dd, J = 1.2 Hz, J = 7.2 Hz, 1H), 7.29ꢀ7.41 (m, 5H), 7.12 (t, J = 7.2 Hz, 1H),
13
6
1
.90ꢀ6.92 (m, 2H), 6.86ꢀ6.88 (dd, J = 1.6 Hz, J = 6.8 Hz, 1H). C NMR (100 MHz, CDCl ): δ =
3
55.5, 137.4, 135.0, 131.7, 131.4, 130.4, 128.9, 128.7, 126.8, 124.3, 124.0, 122.2, 117.7, 115.0,
ꢀ1
112.6, 106.7. FTIR (NaCl, cm ): 3053.3, 3009.1, 2304.9, 2227.8, 1556.6, 1485.2, 1421.5, 1361.7,
+
1
265.3, 1203.6, 1159.2, 895.0, 746.5, 704.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for
C H N O 312.1137; Found 312.1138.
20
13
3
3
ꢀPhenoxyꢀ2ꢀphenylꢀ7ꢀmethyl imidazo[1,2ꢀa]pyridine (3j)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (39 mg, yield = 65%), m.p.: 158ꢀ160 °C. H NMR (500 MHz, CDCl ): δ = 7.93ꢀ
3
7
2
.95(m, 2H), 7.53 (d, J = 5.0 Hz, 1H), 7.16ꢀ7.30 (m, 6H), 7.02 (t, J = 5.5 Hz, 1H), 6.86ꢀ6. 87 (m,
1
3
H), 6.48ꢀ6.49 (dd, J = 1.5 Hz, J =7.0 Hz, 1H), 2.31 (s, 3H). C NMR (125 MHz, CDCl ): δ =
3
156.3, 140.4, 135.3, 132.7, 130.7, 130.6,130.2, 129.7, 128.6, 127.5, 126.4, 123.6, 120.9, 116.2,
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ꢀ1
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15.0, 114.9, 21.4. FTIR (NaCl, cm ): 3053.3, 2985.8, 2924.1, 1643.4, 1583.6, 1568.1, 1489.1,
1
446.6, 1421.5, 1394.5, 1363.7, 1265.3, 1201.7, 1159.2, 1072.4, 1026.1, 895.0, 731.0, 704.0.
+
HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 301.1341; Found 301.1345.
2
0
16
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
ꢀPhenoxyꢀ2ꢀphenyl imidazo[1,2ꢀa]pyridineꢀ7ꢀcarboxylic acid methyl ester (3k)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (53 mg, yield = 77%), m.p.: 132ꢀ134 °C. H NMR (400 MHz, CDCl ): δ = 8.35ꢀ8.36
3
(
dd, J = 0.8 Hz, J = 1.6 Hz, 1H), 8.03ꢀ8.05 (m, 2H), 7.73ꢀ7.75 (dd, J = 0.8 Hz, J = 7.2 Hz, 1H),
7
.25ꢀ7.40 (m, 6H), 7.08ꢀ7.12 (td, J = 8.0 Hz, J = 0.8 Hz, 1H), 6.90ꢀ6.93 (m, 2H), 3.94 (s, 3H).
1
3
C NMR (100 MHz, CDCl ): δ = 165.7, 155.8, 138.6, 134.2, 132.0, 131.3, 130.3, 128.7, 128.3,
3
ꢀ1
126.7, 125.6, 124.0, 121.1, 120.7, 115.0, 111.7, 52.6. FTIR (NaCl, cm ): 3053.3, 3004.5, 2304.9,
1
718.6, 1556.6, 1487.1, 1404.2, 1367.5, 1334.7, 1265.3, 1232.5, 1203.6, 1159.2, 1091.7, 895.0,
+
7
38.7, 704.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 345.1239; Found
21
16
2
3
345.1238.
N
N
Br
O
3ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ6ꢀbromo imidazo[1,2ꢀa]pyridine (3l)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (41 mg, yield = 57%), m.p.: 159ꢀ161°C. H NMR (400 MHz, CDCl ): δ = 7.99ꢀ8.01
3
(m, 2H), 7.86ꢀ7.87 (dd, J = 0.8 Hz, J = 1.6 Hz, 1H), 7.49ꢀ7.51 (dd, J = 0.8 Hz, J = 9.6 Hz, 1H),
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1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
7
.20ꢀ7.38 (m, 6H), 7.09ꢀ7.13 (m, 1H), 6.92ꢀ6.95 (m, 2H). C NMR (100 MHz, CDCl ): δ =
3
1
55.8, 138.2, 132.2, 132.0, 130.3, 130.1, 128.7, 128.1, 127.9, 126.5, 124.0, 121.6, 118.6, 115.0,
ꢀ1
107.3. FTIR (NaCl, cm ): 3053.3, 3012.2, 1596.3, 1526.3, 1489.1, 1421.5, 1401.3, 1325.1,
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
265.3, 1199.7, 1159.2, 895.0, 798.5, 738.7, 704.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated
for C H BrN O 365.0284; Found 365.0277.
1
9
13
2
3ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ7ꢀmethyl imidazo[1,2ꢀa]pyridine (3m)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (67 mg, yield = 93%), m.p.: 154ꢀ156 °C. H NMR (400 MHz, CDCl ): δ = 7.95ꢀ7.98
3
(
dd, J = 2.0 Hz, J = 6.8 Hz, 2H), 7.63 (d, J = 7.2 Hz, 1H), 7.31 (d, J = 1.2 Hz, 1H), 7.01ꢀ7.05 (m,
2H), 6.87ꢀ6.90 (m, 2H), 6.66ꢀ6.70 (m, 1H), 6.50ꢀ6.54 (m, 2H), 4.03 (s, 3H), 3.78 (s, 3H), 2.36 (s,
13
3
H). C NMR (100 MHz, CDCl ): δ = 159.1, 149.0, 145.3, 140.2, 135.0, 130.7, 129.3, 127.7,
3
ꢀ1
1
25.5, 124.1, 121.1, 120.8, 115.9, 114.7, 114.6, 114.0, 112.7, 56.2, 55.2, 21.4. FTIR (NaCl, cm ):
3053.3, 2983.9, 2839.2, 1695.4, 1643.4, 1614.4, 1570.1, 1498.7, 1456.3, 1440.8, 1421.5, 1392.6,
1
361.7, 1296.2, 1265.3, 1249.9, 1199.7, 1170.8, 1114.9, 1030.0, 895.0, 837.1, 738.7, 704.0.
+
HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 361.1552; Found 361.1553.
22
20
2
3
N
OMe
N
F
O
OMe
3
ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ6ꢀfluoro imidazo[1,2ꢀa]pyridine (3n)
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This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (48 mg, yield = 66%), m.p.: 134ꢀ136 °C. H NMR (400 MHz, CDCl ): δ = 7.96ꢀ7.99
3
(m, 2H), 7.70ꢀ7.72 (m, 1H), 7.51ꢀ7.55 (m, 1H), 7.01ꢀ7.06 (m, 3H), 6.89ꢀ6.93 (m, 2H), 6.69ꢀ6.73
1
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
m, 1H), 6.53 (d, J = 7.6 Hz, 1H). C NMR (100 MHz, CDCl ): δ = 159.4, 155.3 (J = 236 Hz),
3
1
1
1
1
49.1, 144.8, 137.2, 133.0, 131.1, 127.8, 125.0, 124.5, 121.1, 118.1 (J = 9 Hz), 116.0 (J = 26 Hz),
ꢀ1
14.9, 114.1, 112.9, 108.2 (J = 41 Hz), 56.2, 55.2. FTIR (NaCl, cm ): 3053.3, 2839.2, 2304.9,
651.1, 1564.3, 1535.3, 1500.6, 1421.5, 1421.5, 1369.5, 1328.9, 1298.1, 1265.3, 1251.8, 1209.4,
+
180.4, 1116.8, 1208.1, 839.0, 810.1, 746.5, 704.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated
for C H FN O 365.1301; Found 365.1302.
2
1
17
2
3
3
ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ6ꢀchloro imidazo[1,2ꢀa]pyridine (3o)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (53 mg, yield = 70%), m.p.: 130ꢀ132 °C. H NMR (400 MHz, CDCl ): δ = 7.96ꢀ7.98
3
(dd, J = 2.0 Hz, J = 6.8 Hz, 2H), 7.82ꢀ7.83 (dd, J = 0.8 Hz, J = 2.0 Hz, 1H), 7.49ꢀ7.52 (dd, J =
0.8 Hz, J = 9.6 Hz, 1H), 7.05ꢀ7.10 (m, 3H), 6.90ꢀ6.92 (dd, J = 2.0 Hz, J = 6.8 Hz, 2H), 6.69ꢀ6.74
1
3
(
m, 1H), 6.52 (d, J = 8.0 Hz, 1H), 4.04 (s, 3H), 3.80 (s, 3H). C NMR (100 MHz, CDCl ): δ =
3
1
59.5, 149.1, 144.9, 138.0, 132.5, 130.1, 127.9, 125.5, 124.8, 124.5, 121.2, 120.5, 119.4, 117.9,
ꢀ1
114.8, 114.2, 112.9, 56.2, 55.3. FTIR (NaCl, cm ): 3015.6, 2839.2, 1498.7, 1419.6, 1392.6,
1
7
325.1, 1298.1, 1265.3, 1251.8, 1199.7, 1174.7, 1116.7, 1028.1, 895.0, 837.1, 798.5, 738.7,
+
04.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H ClN O 381.1006; Found 381.1003.
2
1
17
2
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2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
ꢀ(2ꢀMethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl) imidazo[2,1ꢀa]isoquinoline (3p)
This compound was prepared by the General Procedure described above and was obtained as a
1
white solid (39 mg, yield = 49%), m.p.: 108ꢀ110 °C. H NMR (400 MHz, CDCl ): δ = 8.72 (d, J
3
=
8.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.61ꢀ7.67 (m, 3H), 7.54 (t, J = 7.2 Hz, 1H), 6.92ꢀ7.07 (m,
1
3
5H), 6.68ꢀ6.72 (m, 1H), 6.58 (d, J = 8.0 Hz, 1H), 4.05 (s, 3H), 3.81 (s, 3H). C NMR (100 MHz,
CDCl ): δ = 159.0, 149.0, 145.7, 129.3, 128.2, 128.1, 127.6, 127.1, 124.1, 122.9, 121.2, 119.1,
3
ꢀ1
1
14.8, 114.1, 112.8, 112.7, 56.3, 55.2. FTIR (NaCl, cm ): 3005.6, 2839.2, 1583.6, 1578.6,
1498.7, 1454.3, 1419.6, 1377.2, 1265.3, 1251.8, 1199.7, 1174.7, 1026.1, 895.0, 792.7, 738.7,
+
7
04.0. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O 397.1552; Found 397.1549.
2
5
20
2
3
3
ꢀphenoxyꢀ2ꢀphenylbenzo[d] imidazo[2,1ꢀb]thiazole (5a)
This compound was prepared by the General Procedure described above and was obtained as a
1
brown solid (58 mg, yield = 85%), m.p.: 173ꢀ174 °C. H NMR (500 MHz, CDCl ): δ = 7.82 (d,
3
J = 8.0 Hz, 2H), 7.51ꢀ7.56 (m, 1H), 7.35ꢀ7.37 (m, 1H), 7.24ꢀ7.27 (m, 4H), 7.12ꢀ7.16 (m, 3H),
13
6
1
2
.99ꢀ7.02 (m, 3H). C NMR (125 MHz, CDCl ): δ = 155.5, 141.2, 132.6, 131.4, 131.1, 130.6,
3
ꢀ
1
29.3, 128.9, 127.6, 126.1, 125.2, 124.5, 123.8, 122.9, 122.8, 114.0, 112.4. FTIR (KCl, cm ):
359.2，1488.0，1372.1，1210.7，1161.3，1022.6，743.6，667.9，499.8. HRMS (ESIꢀTOF)
+
m/z: [M+H] Calculated for C H N OS 343.0900; Found 343.0900.
2
1
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
3ꢀ(1,3ꢀbenzodioxolꢀ5ꢀoyl)ꢀ2ꢀ(4ꢀmethoxyphenyl) benzo[d] imidazo[2,1ꢀb]thiazole (5b)
This compound was prepared by the General Procedure described above and was obtained as a
1
dark red oil (72 mg, yield = 86%). H NMR (500 MHz, CDCl ): δ = 7.83 (d, J = 8.0 Hz, 2H),
3
7
6
.62 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 7.5 Hz, 1H), 7.23ꢀ7.28 (m, 2H), 6.89 (d, J = 8.0 Hz, 2H),
13
.64ꢀ6.68 (m, 2H), 6.48 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H), 5.92 (s, 2H), 3.79 (s, 3H). C NMR
(
125 MHz, CDCl ): δ = 158.8, 151.9, 148.9, 143.8, 142.0, 131.7, 130.5, 129.9, 126.8, 126.3,
3
ꢀ
1
25.3, 124.7, 124.0, 114.1, 114.0, 113.3, 108.5, 106.6, 101.8, 97.8, 55.3. FTIR (KCl, cm
1
):3774.3，3033.3，3896.9，2390.9，2348.9，1658.9，1563.3，1529.9，1402.13，832.2，
+
7
45.3. HRMS (ESIꢀTOF) m/z: [M+Na] Calculated for C H N O SNa 439.0723; Found
2
3
16
2
4
439.0718.
3ꢀ(4ꢀmethoxyphenoxy)ꢀ2ꢀ(4ꢀchlorophenyl)benzo[d] imidazo[2,1ꢀb]thiazole (5c)
This compound was prepared by the General Procedure described above and was obtained as a
1
yellow solid (70 mg, yield = 86%), m.p.: 183ꢀ184 °C. H NMR (500 MHz, CDCl ): δ = 7.75
3
(brs, 2H), 7.52ꢀ7.54 (m, 1H), 7.36ꢀ7.37 (m, 1H), 7.16ꢀ7.21 (m, 4H), 6.88 (d, J = 9.0 Hz, 2H),
1
3
6
1
.74 (d, J = 9.0 Hz, 2H), 3.64 (s, 3H). C NMR (125 MHz, CDCl ): δ = 155.9, 150.3, 132.9,
3
32.7, 131.6, 131.2, 129.9, 129.3, 129.2, 128.8, 126.7, 126.3, 124.9, 124.0, 115.7, 115.3, 113.5,
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
ꢀ1
5
5.7. FTIR (KCl, cm ): 3564.3, 3472.4, 3354.9, 2351.5, 1494.4, 1455.0, 1417.0, 1393.0,
+
1
359.68, 1181.1, 828.8. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H ClN O S
2
2
16
2
2
407.0616; Found 407.0619.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3ꢀ(4ꢀmethoxyphenoxy)ꢀ2ꢀ(4ꢀmethoxyphenyl) benzo[d] imidazo[2,1ꢀb]thiazole (5d)
This compound was prepared by the General Procedure described above and was obtained as a
1
dark red oil (78 mg, yield = 97%). H NMR (500 MHz, CDCl ): δ = 7.75 (d, J = 8.5 Hz, 2H),
3
7.53 (t, J = 4.0 Hz, 1H), 7.37 (t, J = 4.5 Hz, 1H), 7.14ꢀ7.17 (m, 2H), 6.90 (d, J = 9.0 Hz, 2H),
1
3
6
.80 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 9.0 Hz, 2H), 3.70 (s, 3H), 3.64 (s, 3H). C NMR (125
MHz, CDCl ): δ = 157.7, 154.7, 149.5, 130.7, 129.5, 128.8, 125.8, 125.2, 124.3, 123.6, 122.9,
3
ꢀ1
1
14.9, 114.7, 114.2, 113.6, 113.0, 112.3, 54.5, 54.2. FTIR (KCl, cm ): 3564.2, 3444.6, 2969.4,
+
2
350.1, 1704.2, 1682.3, 1567.7, 1245.8, 1173.3, 830.3. HRMS (ESIꢀTOF) m/z: [M+H]
Calculated for C H N O S 403.1111; Found 403.1109.
2
3
18
2
3
3
ꢀ(4ꢀmethoxyphenoxy)ꢀ2ꢀphenyl benzo[d] imidazo[2,1ꢀb]thiazole (5e)
This compound was prepared by the General Procedure described above and was obtained as a
1
yellow oil (71 mg, yield = 95%). H NMR (500 MHz, CDCl ): δ = 7.82 (d, J = 7.5 Hz, 2H),
3
7
.51ꢀ7.53 (m, 1H), 7.36ꢀ7.38 (m, 1H), 7.25 (t, J = 8.0 Hz. 2H), 7.11ꢀ7.16 (m, 3H), 6.90 (d, J =
1
3
9
.0 Hz, 2H), 6.73 (d, J = 9.0 Hz, 2H), 3.63 (s, 3H). C NMR (125 MHz, CDCl ): δ = 154.7,
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49.4, 141.0, 133.1, 131.6, 131.0, 130.6, 128.9, 127.6, 126.0, 125.2, 124.5, 123.7, 122.9, 114.7,
ꢀ1
14.2, 112.4, 54.6. FTIR (KCl, cm ): 3417.9, 3355.2, 2341.0, 1887.5, 1714.9, 1574.2, 1372.2,
+
1208.2, 1022.9, 744.8. HRMS (ESIꢀTOF) m/z: [M+H] Calculated for C H N O S 373.1005;
22
17
2
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Found 373.1009.
■
ASSOCIATED CONTENT
Supporting Information
1
13
H, C NMR spectra
AUTHOR INFORMATION
Corresponding Author
Eꢀmail: zhangjian@hznu.edu.cn; zgf@hznu.edu.cn.
■
*
Notes
The authors declare no competing financial interest.
■ACKNOWLEDGMENTS
We gratefully acknowledge National Natural Science Foundation of China (NSFC) (21502037,
1373073, 21672048), Natural Science Foundation of Zhejiang Province (ZJNSF)
2
(LY15B020008), the PCSIRT (IRT 1231) and Hangzhou Normal University for financial
support. G. Z. acknowledges a Qianjiang Scholar award from Zhejiang Province, China.
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Chem. 2014
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For selected examples of biologically active imidazo[1,2ꢀa]pyridyl derivatives, see: (a)
Harrison, T. S.; Keating, G. M. CNS Drugs 2005 19, 65. (b) Andreani, A.; Granaiola,
M.; Locatelli, A.; Morigi, R. J. Med. Chem 2012 55, 2078. (c) AlꢀTel, T. H.; Alꢀ
2011 46, 1874. and references cited
, 54, 5859.
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Nguyen, J. D.; Matsuura, B. S.; Stephenson, C. R. J. J. Am. Chem. Soc
(a) Rahimi, A.; Ulbrich, A.; Coon, J. J.; Stahl, S. S. Nature 2014
,
.
,
,
0
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9
0
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