One-pot synthesis of N-(imidazo[1,2-a]pyridin-3-yl)-substituted sulfonamides using catalytic zinc chloride

Article abstract of DOI:10.1002/ejoc.201301612

A one-pot two-step synthesis of N-(imidazo[1,2-a]pyridin-3-yl)sulfonamides from easily available arylglyoxal hydrates, 2-aminopyridines, and sulfonamides has been developed. The procedure, using zinc chloride as catalyst, is simple and inexpensive. The desired products were obtained in moderate to good yields under the optimized reaction conditions. Copyright

Full text of DOI:10.1002/ejoc.201301612

FULL PAPER
DOI: 10.1002/ejoc.201301612
One-Pot Synthesis of N-(Imidazo[1,2-a]pyridin-3-yl)-Substituted Sulfonamides
Using Catalytic Zinc Chloride
Chuanming Yu,*[a] Xu Chen,[a] Ran Wu,[a] Guanghui Yang,[a] Jiaoyong Shi,[a] and
Lingling Pan[a]
Keywords: Synthetic methods / Zinc / Nitrogen heterocycles / Sulfonamides
A one-pot two-step synthesis of N-(imidazo[1,2-a]pyridin-3-
yl)sulfonamides from easily available arylglyoxal hydrates, 2-
aminopyridines, and sulfonamides has been developed. The
procedure, using zinc chloride as catalyst, is simple and inex-
pensive. The desired products were obtained in moderate to
good yields under the optimized reaction conditions.
Introduction
The imidazopyridine nucleus, especially the imidazo[1,2-
a]pyridine structure, is found in many pharmaceutical com-
pounds.[1] These show a number of important properties,
such as antifungal,[2] anti-inflammatory,[1c] antitumor,[3]
antiviral,[4] antibacterial,[5] antiprotozoal,[6] antipyretic,[7]
anti-HIV,[8] and antiapoptotic activities.[9] In addition, im-
idazo[1,2-a]pyridine is a substructure of several commer-
cially available drugs, such as Alpidem[10] and Sarpidem
(anxiolytic agents),[11] Olprinone (to treat acute heart fail-
ure),[12] and Zolimidine (used for the treatment of peptic
ulcers).[13] Due to these important uses, imidazo[1,2-a]pyr-
idines have received tremendous attention from synthetic
organic and medicinal chemists. Numerous synthetic meth-
ods have been developed for the synthesis of imidazo[1,2-a]-
pyridine derivatives, such as the condensation of 2-amino-
pyridine with α-halocarbonyl compounds,[14] three-compo-
nent reactions of 2-aminopyridines, aldehydes, and iso-
nitriles[15] or imidazoline-2,4,5-trione[16] or alkynes,[17]
metal-catalyzed C–H activation,[18] Morita–Baylis–Hillman
(MBH) reaction,[19] tetrabutylammonium iodide (TBAI)-
catalyzed oxidative coupling,[20] and a recently reported
iodine-promoted one-pot reaction.[21] Although much pro-
gress has been made in this field, further development of
diverse methods for the construction of various imid-
azo[1,2-a]pyridines is still highly desirable.
Scheme 1. Retrosynthesis of N-(imidazo[1,2-a]pyridin-3-yl)sulfon-
amides.
Scheme 2. Acid-catalyzed tandem N-Boc imine generation/Man-
nich-type reaction.
als.[22] Thus, it is necessary to find an easier and more eco-
nomical method to synthesize this target molecule. As
shown in Scheme 1, N-(imidazo[1,2-a]pyridin-3-yl)sulfon-
amide 5a can be synthesized from the reaction of 2-amino-
pyridine (4a), a nucleophilic reagent bearing two nucleo-
philic sites, and α-keto imine 6, a bielectrophilic reagent.
According to the literature, N-Boc-(tert-butoxycarbonyl)-
imines can be generated in situ from N-Boc-substituted am-
inals, and they can then undergo nucleophilic addition to
form nitrogen-containing compounds (Scheme 2).[23] In-
spired by this work, we planned to use N-tosyl aminal 3a
as a precursor to obtain α-keto imine 6. Compound 3a
could be prepared from phenylglyoxal (1a), a versatile
building block, containing both aldehyde and ketone func-
Recently, the first synthesis of N-(imidazo[1,2-a]pyridin-
3-yl)sulfonamides was reported. For this synthesis, N-(2,2-
dichloro-2-phenylethylidene)arenesulfonamides, which are
not easily accessible reagents, were used as starting materi-
[a] Key Laboratory for Green Pharmaceutical Technologies and
Related Equipment of Ministry of Education, College of
Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou 310014, P. R. China
E-mail: ycm@zjut.edu.cn
http://www.zjut.edu.cn/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301612.
Eur. J. Org. Chem. 2014, 2037–2043
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Yu, X. Chen, R. Wu, G. Yang, J. Shi, L. Pan
FULL PAPER
tional groups, that has been widely used in the synthesis of Table 1. Optimization of reaction conditions.[a]
a broad range of biologically active N-heterocyclic com-
pounds.[24]
In this paper, we report an efficient and simple method
to synthesize N-(imidazo[1,2-a]pyridin-3-yl)sulfonamides in
a one-pot two-step process starting from readily available
arylglyoxal hydrates, 2-aminopyridines, and sulfonamides.
Results and Discussion
According to the literature for the preparation of N,NЈ-
(2-oxo-2-phenylethane-1,1-diyl)dibenzamide,[25]
N-tosyl-
substituted aminal 3a can be easily obtained by the reaction
of phenylglyoxal hydrate (1a) and 4-methylbenzenesulfon-
amide (2a) in toluene at 110 °C for 5 h in almost quantita-
tive yield. However, the purification of 3a proved to be very
tricky, due to the instability of the intermediate N-tosyl-
aminal, which would partly revert to starting material when
the solvent was evaporated. Therefore, a one-pot strategy
that would avoid the isolation of compound 3a was consid-
ered. Once the first step was complete, 2-aminopyridine (4a)
was added to the reaction mixture, which was then stirred
for a further 2 h at 90 °C, and imidazo[1,2-a]pyridine 5a
was obtained in 30% yield (Table 1, entry 1). Considering
the poor solubility of 3a and 5a in the refluxing toluene, a
polar solvent (CH3CN) was added in the second step, and
the yield of 5a increased to 43% (Table 1, entry 2).
We briefly investigated the effects of various parameters
in the second step in order to optimize the reaction condi-
tions (Table 1). First, various catalysts were tested in the
reaction (Table 1, entries 3–7). To our delight, when ZnCl2
was used in the reaction in toluene/CH3CN at 81 °C, com-
pound 5a was obtained in 60% yield (Table 1, entry 7).
Next, different solvents, including dioxane, DMF, THF,
MeOH, and EtOH, were tested. EtOH gave the best result,
Entry
Catalyst
Solvent
T [°C]
Yield [%][b]
1
2
3
4
5
6
7
8
–
–
toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
toluene
THF
90
81
81
81
81
81
81
85
78
85
64
85
81
77
77
77
65
55
77
77
77
77
30
43
56
55
20
BF3·Et2O
AlCl3
CuCl
pTsOH·H2O
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
48
60[c]
46
9
55
59
64
36
56
70
10
11
12
13
14
15
16
17
18
19
20
21
22
DMF
MeOH
dioxane
iPrOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
77[d]
76[e]
64[e]
60[e]
51[e,f]
81[e, g]
82[e,h]
81[e,i]
EtOH
EtOH
[a] Unless otherwise noted, reaction conditions were phenylglyoxal
hydrate 1a (1.0 mmol, 1.0 equiv.), 4-methylsulfonamide 2a
(2.4 mmol, 2.4 equiv.), 2-aminopyridine 4a (1.2 mmol, 1.2 equiv.),
and 5a was formed in 70% yield (Table 1, entry 14). When toluene (10 mL), solvent (10 mL), catalyst (0.20 equiv.). [b] Isolated
yield of 5a based on 1a. [c] Other Lewis acids, such as CuCl2·H2O,
the ratio of 1a/2a/4a was changed to 1:2.4:1.5, the yield of
5a increased to 76% (Table 1, entry 16). The yield decreased
when the temperature was changed to 65 or 55 °C (Table 1,
I2, LiClO4·3H2O, Cu(OAc)2·H2O, Ni(OTf)3, and FeCl3, were also
tested, but the results were less satisfactory. [d] Molar ratio 1a/2a/
4a = 1:2.4:2.0. [e] Molar ratio 1a/2a/4a = 1:2.4:1.5. [f] Volume ratio
entries 17–18). Interestingly, the yield of 5a reached 81%
when the volume ratio of toluene/EtOH was adjusted to 2:3
(Table 1, entry 20). The same result was achieved with only
0.1 equiv. of the catalyst. Therefore, the optimized condi-
tions were identified (Table 1, entry 22).
toluene/EtOH = 2:1. [g] Volume ratio toluene/EtOH = 2:3. [h] Vol-
ume ratio toluene/EtOH = 1:2. [i] Volume ratio toluene/EtOH =
2:3, ZnCl2 (0.1 equiv.).
glyoxal hydrates 2-furanglyoxal hydrate and 2-thiophenegly-
Having optimized the reaction conditions, we further ex- oxal hydrate performed smoothly to give the corresponding
amined the scope and limitations of this transformation. As products (i.e., 5k and 5l) in 75 and 73% yields. Interestingly,
summarized in Table 2, various arylglyoxal hydrates were methylglyoxal also gave the desired product (i.e., 5m), albeit
found to participate in this reaction, and the electronic na- in a low yield of 28%.
ture of arylglyoxal hydrates had little influence on the effi-
Next, a few substituted sulfonamides were investigated in
ciency of the reaction. Arylglyoxal hydrates bearing elec- the reaction (Table 3). Generally, electron-rich aryl sulfon-
tron-withdrawing (leading to 5e–5i) as well as electron-do- amides showed better reactivity and gave higher yields than
nating groups (leading to 5b–5d) gave the corresponding electron-deficient ones (compare the results for 5n–5q). To
imidazo[1,2-a]pyridines in moderate to excellent yields (60– our surprise, the alkyl sulfonamides such as methanesulfon-
89%). A variety of functional groups, such as F (5i), Cl (5f amide and cyclopropanesulfonamide also participated in
and 5h), Br (5g), and OH (5j), were unaffected under the this reaction to give the corresponding products (i.e., 5r and
reaction conditions, and the desired products were obtained 5s) in 31 and 39% yields. Next, we investigated the scope
in 68–79% yields. Much to our satisfaction, the heteroaryl of substituted aminopyridines (Table 3). Aminopyridines
2038
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Eur. J. Org. Chem. 2014, 2037–2043

One-Pot Synthesis of N-(Imidazo[1,2-a]pyridin-3-yl)sulfonamides
Table 2. Substrate scope of arylglyoxal hydrates.[a]
of the desired products were isolated. The structure of
target compound 5c was further confirmed by X-ray crys-
tallographic analysis (Figure 1).
Entry R1
t [h][b]
Product
Yield [%][c]
1
2
3
4
5
6
7
8
Ph
5
5
6
10
3
5
5
5
5
7
5a
5b
5c
5d
5e
5f
81
70
89
64
60
77
79
76
76
68
75
73
28
4-Me-C6H4
4-MeO-C6H4
3-MeO-C6H4
4-NO2–C6H4
4-Cl-C6H4
4-Br-C6H4
3-Cl-C6H4
4-F-C6H4
4-OH-C6H4
2-furanyl
2-thienyl
5g
5h
5i
9
10
11
12
13[d]
5j
Figure 1. X-ray crystal structure of compound 5c.
6
6
10
5k
5l
Me
5m
A plausible mechanism for this reaction is outlined in
Scheme 3. The first step involves the ZnCl2-catalyzed re-
versible elimination of TsNH2 from N-tosyl-substituted
aminal 3a to produce imine 6,[23] which reacts with ethanol
to form adduct 7.[26] Then the amino group of 4a attacks
the ketone group of 7 to obtain intermediate 8. This is fol-
lowed by an intramolecular nucleophilic substitution reac-
tion to generate intermediate 9. Finally, intermediate 9 loses
a proton to give product 5a (Scheme 3).
[a] Molar ratio 1/2a/4a = 1:2.4:1.5. [b] Reaction time for the first
step. [c] Isolated yield based on 1. [d] The second step required 8 h.
bearing methyl substituents at the 3- and 5-positions af-
forded the products (i.e., 5t and 5u) in 79 and 70% yields,
respectively. When 2-amino-6-methylpyridine was subjected
to the reaction conditions, only a trace amount of product
was detected, which may be due to the steric hindrance on
the pyridine ring. 2-Aminopyridines bearing halogen sub-
stituents on the aromatic ring, such as chloro (leading to
5v) or bromo (leading to 5w) groups, were tolerated, which
provides the possibility for further functionalization
through cross-coupling reactions. Furthermore, other 2-
amino heterocycles, such as 2-aminopyrimidine and 2-
aminothiozole, were also investigated. Unfortunately, none
Table 3. Substrate scope of aminopyridines and sulfonamides.[a]
Scheme 3. Plausible reaction mechanism.
Entry R2
R3
t [h][b]
Product Yield [%][c]
Conclusions
1
2
3
4
Ph
H
H
H
H
H
H
3-Me
5-Me
5-Cl
5-Br
5
3
10
10
12
12
5
5
5
5
5n
5o
5p
5q
5r
80
90
75
71
31
39
79
70
57
68
4-MeO-C6H4
4-Cl-C6H4
4-NO2–C6H4
Me
Cyclopropyl
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
In conclusion, we have developed a zinc(II)-catalyzed
one-pot method for the preparation of imidazo[1,2-a]pyr-
idine derivatives bearing pharmacophoric sulfonylamino
groups. Various functional groups are tolerated in this reac-
tion system, and the products are formed in moderate to
good yields. In this procedure, the starting materials are
easily available, and the catalyst is nonhazardous and inex-
pensive. Further investigations into the scope of this reac-
tion and its applications to the construction of biologically
and medicinally active molecules are in progress.
5[d]
6[d]
7
5s
5t
8
5u
5v
5w
9[d]
10
[a] Molar ratio 1a/2/4 = 1:2.4:1.5. [b] Reaction time for the first
step. [c] Isolated yield based on 1a. [d] Reaction time for the second
step was 8 h.
Eur. J. Org. Chem. 2014, 2037–2043
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Yu, X. Chen, R. Wu, G. Yang, J. Shi, L. Pan
FULL PAPER
6.99 (d, J = 8.0 Hz, 2 H, Ar), 6.88 (t, J = 6.8 Hz, 1 H, 6-H), 6.63
(d, J = 8.8 Hz, 2 H, Ar), 3.72 (s, 3 H, OCH3), 2.21 (s, 3 H, CH3)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 158.4, 143.0, 142.0,
139.7, 136.9, 129.1, 127.9, 126.3, 125.5, 125.0, 123.4, 116.4, 113.0,
112.4, 112.0, 55.0, 20.9 ppm. MS (ESI): m/z = 393.9 [M + H]+.
HRMS (ESI): calcd. for C21H20N3O3S [M + H]+ 394.1220; found
394.1219.
Experimental Section
General Information: All reagents were obtained from commercial
suppliers, and were used without further purification unless other-
wise indicated. TLC analysis was carried out using precoated glass
plates. Silica gel for column chromatography was purchased from
Qingdao Haiyang Chemical Co., Ltd. IR spectra were recorded
with a Thermo Nicolet AVATAR 370 spectrophotometer in KBr.
Melting points were determined using a Büchi B-540 capillary
N-[2-(3-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenz-
enesulfonamide (5d): White solid (251 mg, 64 %), m.p. 188.5–
1
melting-point apparatus. H and 13C NMR spectra were recorded
190.5 °C. IR (KBr): ν = 3426 (NH), 3274 (NH), 3041, 2968, 2839,
˜
with a Varian instrument at 400 and 100 MHz, respectively, and
tetramethylsilane was used as internal standard. Mass spectra were
measured with a Thermo Finnigan LCQ-Advantage instrument.
High-resolution mass spectra (HRMS) were measured with a
Bruker micrOTOF-Q II instrument using the ESI technique. Sin-
gle-crystal diffraction data for compound 5c were collected with an
Xcalibur Eos Gemini-ultra diffractometer.
1633 (C=N), 1602, 1500, 1425, 1382, 1349 (SO2), 1252, 1232, 1162
(SO2), 1090, 1037 cm–1 1H NMR (400 MHz, [D6]DMSO): δ =
.
10.53 (s, 1 H, NH), 8.17 (d, J = 6.8 Hz, 1 H, 5-H), 7.55 (dt, J =
8.8, 1.2 Hz, 1 H, 8-H), 7.34–7.28 (m, 3 H, 7-H, Ar), 7.21–7.18 (m,
1 H, Ar), 7.15–7.14 (m, 1 H, Ar), 7.04 (t, J = 8.0 Hz, 1 H, Ar),
7.00 (d, J = 7.6 Hz, 2 H, Ar), 6.95 (td, J = 6.8, 1.2 Hz, 1 H, 6-H),
6.73 (ddd, J = 8.0, 2.4, 0.8 Hz, 1 H, Ar), 3.71 (s, 3 H, OCH3), 2.22
(s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 158.4,
142.8, 141.9, 139.5, 136.5, 133.7, 129.0, 128.4, 126.1, 125.5, 123.4,
119.2, 116.5, 113.1, 112.9, 112.0, 54.8, 20.8 ppm. MS (ESI): m/z =
394.0 [M + H]+. HRMS (ESI): calcd. for C21H20N3O3S [M + H]+
394.1220; found 394.1223.
General Procedure (5a as an Example): A mixture of phenylglyoxal
hydrate (1a; 152 mg, 1 mmol), TsNH2 (2a; 410 mg, 2.4 mmol), and
anhydrous toluene (10 mL) was heated at reflux. After the reactant
had disappeared (3–5 h, monitored by TLC), 2-aminopyridine (4a;
141 mg, 1.5 mmol), ZnCl2 (14 mg, 10 mol-%), and ethanol (15 mL)
were added, and the resulting mixture was heated at reflux for 2 h.
After that, the solvent was removed under reduced pressure, and
CH2Cl2 (80 mL) was added to the residue. The mixture was washed
with water (2ϫ 30 mL), then the organic phase was dried with
Na2SO4, and the solvents were evaporated in vacuo. The residue
was purified by column chromatography on silica gel (petroleum
ether/CH2Cl2/EtOAc, 2:1:1) to give compound 5a (294 mg, 81%).
4-Methyl-N-[2-(4-nitrophenyl)imidazo[1,2-a]pyridin-3-yl]benzene-
sulfonamide (5e): Pale yellow solid (245 mg, 60 %), m.p. 226.6–
229.0 °C. IR (KBr): ν = 3431 (NH), 2998, 2814, 2742, 1635 (C=N),
˜
1602, 1520 (NO2), 1445, 1346 (NO2), 1245, 1206, 1161 (SO2),
1092 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.76 (s, 1 H,
NH), 8.29 (d, J = 6.8 Hz, 1 H, 5-H), 7.96 (d, J = 8.8 Hz, 2 H, Ar),
7.81 (d, J = 8.8 Hz, 2 H, Ar), 7.61 (d, J = 9.2 Hz, 1 H, 8-H), 7.40–
7.36 (m, 1 H, 7-H), 7.29 (d, J = 8.0 Hz, 2 H, Ar), 7.03 (t, J =
6.8 Hz, 1 H, 6-H), 6.99 (d, J = 8.0 Hz, 2 H, Ar), 2.11 (s, 3 H, CH3)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 145.6, 143.1, 142.4,
138.9, 137.1, 136.3, 129.0, 127.2, 126.2, 123.7, 122.5, 116.7, 114.8,
112.6, 20.4 ppm. MS (ESI): m/z = 409.0 [M + H]+. HRMS (ESI):
calcd. for C20H17N4O4S [M + H]+ 409.0965; found 409.0955.
4-Methyl-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfonamide
(5a): White solid (294 mg, 81%), m.p. 211.4–213.3 °C. IR (KBr): ν
˜
= 3440 (NH), 3051, 3029, 2976, 2795, 2725, 1634 (C=N), 1597,
1501, 1446, 1427, 1334 (SO2), 1238, 1204, 1164 (SO2), 1092 cm–1.
1H NMR (400 MHz, [D6]DMSO): δ = 10.52 (s, 1 H, NH), 8.16 (d,
J = 6.8 Hz, 1 H, 5-H), 7.60 (d, J = 7.2 Hz, 2 H, Ar), 7.55 (d, J =
8.8 Hz, 1 H, 8-H), 7.36–7.28 (m, 3 H, 7-H, Ar), 7.19–7.08 (m, 3 H,
Ar), 7.01 (d, J = 8.0 Hz, 2 H, Ar), 6.95 (t, J = 6.8 Hz, 1 H, 6-H),
2.21 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
143.0, 142.0, 139.6, 136.5, 132.3, 129.0, 127.4, 126.8, 126.6, 126.2,
125.6, 123.4, 116.5, 113.1, 112.0, 20.8 ppm. MS (ESI): m/z = 364.0
[M + H]+. HRMS (ESI): calcd. for C20H18N3O2S [M + H]+
364.1114; found 364.1097.
N-[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenzene-
sulfonamide (5f): White solid (306 mg, 77%), m.p. 226.9–227.4 °C.
IR (KBr): ν = 3443 (NH), 2986, 2813, 2737, 1635 (C=N), 1599,
˜
1503, 1489, 1447, 1404, 1353, 1338 (SO2), 1244, 1205, 1162 (SO2),
1
1093, 1015 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 10.50 (s, 1
H, NH), 8.18 (d, J = 6.8 Hz, 1 H, 5-H), 7.5–7.48 (m, 3 H, 8-H,
Ar), 7.32–7.23 (m, 3 H, 7-H, Ar), 7.14–7.08 (m, 2 H, Ar), 6.97 (d,
J = 8.0 Hz, 2 H, Ar), 6.94 (td, J = 6.8, 0.8 Hz, 1 H, 6-H), 2.23 (s,
3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 143.4,
142.3, 138.5, 136.5, 131.9, 131.3, 129.1, 128.3, 127.6, 126.4, 126.1,
123.7, 116.7, 113.4, 112.5, 21.0 ppm. MS (ESI): m/z = 397.9 [M +
H]+. HRMS (ESI): calcd. for C20H17ClN3O2S [M + H]+ 398.0725;
found 398.0722.
4-Methyl-N-(2-p-tolylimidazo[1,2-a]pyridin-3-yl)benzenesulfonamide
(5b): White solid (263 mg, 70%), m.p. 225.6–226.7 °C. IR (KBr): ν
˜
= 3446 (NH), 3027, 2920, 2807, 2732, 1635 (C=N), 1597, 1509,
1498, 1449, 1352, 1328 (SO2), 1243, 1203, 1161 (SO2), 1091,
1020 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.48 (s, 1 H,
NH), 8.15 (d, J = 6.8 Hz, 1 H, 5-H), 7.53 (d, J = 8.8 Hz, 1 H, 8-
H), 7.48 (d, J = 8.0 Hz, 2 H, Ar), 7.32–7.28 (m, 3 H, Ar, 7-H), 7.02
(d, J = 8.8 Hz, 2 H, Ar), 6.95–6.92 (m, 3 H, Ar, 6-H), 2.27 (s, 3 H,
CH3), 2.23 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO):
δ = 143.1, 142.1, 139.8, 136.8, 136.4, 129.6, 129.1, 128.1, 126.6,
126.3, 125.6, 123.5, 116.5, 112.8, 112.1, 20.9, 20.8 ppm. MS (ESI):
m/z = 378.0 [M + H]+. HRMS (ESI): calcd. for C21H20N3O2S [M
+ H]+ 378.1271; found 378.1243.
N-[2-(4-Bromophenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenzene-
sulfonamide (5g): White solid (348 mg, 79%), m.p. 231.5–233.5 °C.
IR (KBr): ν = 3440 (NH), 2982, 2812, 2734, 1635 (C=N), 1599,
˜
1503, 1488, 1445, 1401, 1381, 1337 (SO2), 1243, 1204, 1162 (SO2),
1
1093, 1010 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 10.57 (s, 1
H, NH), 8.24 (d, J = 6.8 Hz, 1 H, 5-H), 7.56 (d, J = 9.2 Hz, 1 H,
8-H), 7.52–7.47 (m, 2 H, Ar), 7.37–7.32 (m, 1 H, 7-H), 7.29 (d, J
= 8.4 Hz, 4 H, Ar), 7.02 (d, J = 8.4 Hz, 2 H, Ar), 6.98 (d, J =
N-[2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenz-
enesulfonamide (5c): White solid (349 mg, 89 %), m.p. 209.6–
211.2 °C. IR (KBr): ν = 3428 (NH), 2978, 2840, 2809, 2728, 1633, 6.8 Hz, 1 H, 6-H), 2.27 (s, 3 H, CH3) ppm. 13C NMR (100 MHz,
˜
1613 (C=N), 1508, 1454, 1397, 1334 (SO2), 1300, 1249, 1160 (SO2),
[D6]DMSO): δ = 143.2, 142.2, 138.5, 136.5, 131.6, 130.4, 128.96,
128.4, 126.2, 125.8, 123.5, 120.4, 116.6, 113.3, 112.2, 20.9 ppm. MS
1
1090, 1028 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 10.41 (s, 1
H, NH), 8.09 (d, J = 6.8 Hz, 1 H, 5-H), 7.51–7.45 (m, 3 H, Ar, 8- (ESI): m/z = 441.9 [M + H]+ . HRMS (ESI): calcd. for
H), 7.28 (d, J = 8.0 Hz, 2 H, Ar), 7.23 (t, J = 7.6 Hz, 1 H, 7-H),
C20H17BrN3O2S [M + H]+ 442.0219; found 442.0213.
2040
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 2037–2043

One-Pot Synthesis of N-(Imidazo[1,2-a]pyridin-3-yl)sulfonamides
N-[2-(3-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenzene-
sulfonamide (5h): White solid (302 mg, 76%), m.p. 198.4–199.4 °C.
= 3.6 Hz, 1 H, Thienyl), 6.90 (t, J = 6.8 Hz, 1 H, 6-H), 6.80 (dd, J
= 4.8, 3.6 Hz, 1 H, Thienyl), 2.29 (s, 3 H, CH3) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 147.2, 143.1, 142.4, 142.3, 136.9,
IR (KBr): ν = 3437 (NH), 2977, 2800, 2728, 1634 (C=N), 1597,
˜
1573, 1501, 1473, 1428, 1367, 1335 (SO2), 1237, 1203, 1164 (SO2), 132.0, 129.1 126.5, 126.0, 123.6, 116.5, 112.6, 112.3, 110.7, 107.9,
1093 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.61 (s, 1 H,
NH), 8.26 (d, J = 6.8 Hz, 1 H, 5-H), 7.60–7.53 (m, 3 H, 8-H, Ar),
7.38–7.32 (m, 1 H, 7-H), 7.30 (d, J = 8.4 Hz, 2 H, Ar), 7.20 (dt, J
= 8.0, 1.6 Hz, 1 H, Ar), 7.19–7.14 (m, 1 H, Ar), 7.02–6.98 (m, 3
H, 6-H, Ar), 2.21 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 143.0, 142.2, 138.0, 136.1, 134.4, 132.5, 129.2, 129.0,
126.7, 126.1, 125.9, 125.1, 123.6, 116.6, 113.5, 112.3, 20.8 ppm. MS
(ESI): m/z = 398.0 [M + H]+ . HRMS (ESI): calcd. for
C20H17ClN3O2S [M + H]+ 398.0725; found 398.0705.
21.0 ppm. MS (ESI): m/z = 370.0 [M + H]+. HRMS (ESI): calcd.
for C18H16N3O2S2 [M + H]+ 370.0678; found 370.0680.
4-Methyl-N-(2-methylimidazo[1,2-a]pyridin-3-yl)benzenesulfon-
amide (5m): White solid (84 mg, 28%), m.p.217.6–220.1 °C. IR
(KBr): ν = 3434 (NH), 3026, 2964, 2809, 2707, 1637 (C=N), 1597,
˜
1581, 1497, 1444, 1440, 1334 (SO2), 1284, 1255, 1165 (SO2),
1090 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.18 (s, 1 H,
NH), 8.09 (dt, J = 6.8, 1.2 Hz, 1 H, 5-H), 7.58–7.48 (m, 2 H, Ar),
7.40–7.36 (m, 3 H, 8-H, Ar), 7.22 (ddd, J = 9.2, 6.8, 1.2 Hz, 1 H,
7-H), 6.87 (td, J = 6.8, 1.2 Hz, 1 H, 6-H), 2.39 (s, 3 H, CH3), 1.59
(s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 143.5,
141.6, 138.3, 136.5, 129.6, 126.7, 124.7, 123.1, 115.9, 114.0, 111.6,
21.1, 11.92 ppm. MS (ESI): m/z = 301.9 [M + H]+. HRMS (ESI):
calcd. for C15H16N3O2S [M + H]+ 302.0958; found 302.0962.
N-[2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenzene-
sulfonamide (5i): White solid (289 mg, 76%), m.p. 225.8–227.9 °C.
IR (KBr): ν = 3446 (NH), 2977, 2799, 2730, 1635 (C=N), 1604,
˜
1597, 1559, 1505, 1505, 1429, 1335 (SO2), 1225, 1165 (SO2), 1093,
1014 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.53 (s, 1 H,
NH), 8.19 (d, J = 6.8 Hz, 1 H, 5-H), 7.64–7.57 (m, 2 H, Ar), 7.54
(d, J = 8.8 Hz, 1 H, 8-H), 7.35–7.28 (m, 3 H, 7-H, Ar), 7.03 (d, J
= 8.0 Hz, 2 H, Ar), 6.99–6.91 (m, 3 H, 6-H, Ar), 2.23 (s, 3 H, CH3)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 162.46, 160.03, 143.0,
142.0, 138.7, 136.6, 129.0, 128.6, 126.2, 125.6, 123.5, 116.5, 114.4,
114.2, 112.9, 112.1, 20.7 ppm. MS (ESI): m/z = 382.0 [M + H]+.
HRMS (ESI): calcd. for C20H17FN3O2S [M + H]+ 382.1020; found
382.1018.
N-(2-Phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfonamide (5n):
White solid (279 mg, 80%), m.p. 222.7–223.6 °C. IR (KBr): ν =
˜
3428 (NH), 3054, 2966, 2792, 2720, 1635 (C=N), 1558, 1506, 1447,
1333 (SO2), 1168 (SO2), 1093, 1027 cm–1 1H NMR (400 MHz,
.
[D6]DMSO): δ = 10.68 (s, 1 H, NH), 8.12 (d, J = 6.8 Hz, 1 H, 5-
H), 7.71–7.65 (m, 2 H, Ar), 7.56 (dt, J = 9.2, 0.8 Hz, 1 H, 8-H),
7.51 (dd, J = 8.4, 1.2 Hz, 2 H, Ar), 7.4–7.39 (m, 1 H, 7-H), 7.35–
7.25 (m, 3 H, Ar), 7.17–7.12 (m, 3 H, Ar), 6.94 (td, J = 6.8, 0.8 Hz,
1 H, 6-H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 142.0,
139.8, 139.4, 132.5, 132.3, 128.6, 127.5, 127.1, 126.5, 126.1, 125.5,
123.3, 116.5, 113.0, 112.0 ppm. MS (ESI): m/z = 350 [M + H]+.
HRMS (ESI): calcd. for C19H16N3O2S [M + H]+ 350.0958; found
350.0960.
N-[2-(4-Hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenz-
enesulfonamide (5j): White solid (258 mg, 68 %), m.p. 242.8–
243.6 °C. IR (KBr): ν = 3441 (NH), 3342 (OH), 3111, 1634 (C=N),
˜
1615, 1596, 1515, 1447, 1370, 1356 (SO2), 1274, 1235, 1165 (SO2),
1091 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.39 (s, 1 H,
NH), 9.41 (s, 1 H, OH), 8.09 (d, J = 6.8 Hz, 1 H, 5-H), 7.49 (d, J
= 8.8 Hz, 1 H, 8-H), 7.41 (d, J = 8.8 Hz, 2 H, Ar), 7.35 (d, J =
8.4 Hz, 2 H, Ar), 7.30–7.24 (m, 1 H, 7-H), 7.07 (d, J = 8.0 Hz, 2
H, Ar), 6.90 (t, J = 6.8 Hz, 1 H, 6-H), 6.50 (d, J = 8.8 Hz, 2 H,
Ar), 2.27 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ
= 156.8, 143.2, 141.9, 140.0, 137.0, 129.1, 128.0, 126.3, 125.3, 123.3,
116.3, 114.4, 112.0, 111.8, 21.0 ppm. MS (ESI): m/z = 380.0 [M +
H]+. HRMS (ESI): calcd. for C20H18 N3O3S [M + H]+ 380.1063;
found 380.1044.
4-Methoxy-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfon-
amide (5o): White solid (341 mg, 90%), m.p. 209.6–211.2 °C. IR
(KBr): ν = 3436 (NH), 2966, 2941, 2840, 1635 (C=N), 1596, 1579,
˜
1496, 1322 (SO2), 1262, 1245, 1156 (SO2), 1093, 1028 cm–1 1H
.
NMR (400 MHz, [D6]DMSO): δ = 10.45 (s, 1 H, NH), 8.18 (d, J
= 6.8 Hz, 1 H, 5-H), 7.65–7.62 (m, 2 H, Ar), 7.55 (d, J = 9.2 Hz,
1 H, 8-H), 7.37–7.30 (m, 3 H, 7-H, Ar), 7.19–7.10 (m, 3 H, Ar),
6.96 (t, J = 6.8 Hz, 1 H, 6-H), 6.72 (d, J = 8.8 Hz, 2 H, Ar), 3.71
(s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 162.3,
142.1, 139.6, 132.4, 130.9, 128.5, 127.6, 127.1, 126.7, 125.7, 123.6,
116.6, 113.9, 113.2, 112.2, 55.4 ppm. MS (ESI): m/z = 380.0 [M +
H]+. HRMS (ESI): calcd. for C20H18 N3O3S [M + H]+ 380.1063;
found 380.1075.
N-[2-(Furan-2-yl)imidazo[1,2-a]pyridin-3-yl]-4-methylbenzenesulfon-
amide (5k): White solid (265 mg, 75%), m.p. 208.0–208.9 °C. IR
(KBr): ν = 3446 (NH), 3025, 2808, 2744, 1635 (C=N), 1558, 1540,
˜
1506, 1353, 1336 (SO2), 1255, 1204, 1163 (SO2), 1093, 1067,
1013 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.47 (s, 1 H,
NH), 8.17 (d, J = 6.8 Hz, 1 H, 5-H), 7.51 (d, J = 9.2 Hz, 1 H, 8-
H), 7.45 (d, J = 8.4 Hz, 2 H, Ar), 7.35–7.28 (m, 2 H, 7-H, Furyl),
7.20 (d, J = 8.0 Hz, 2 H, Ar), 6.96 (t, J = 6.8 Hz, 1 H, 6-H), 6.51
(d, J = 2.8 Hz, 1 H, Furyl), 6.31 (dd, J = 3.2, 2.0 Hz, 1 H, Furyl),
2.30 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
147.2, 143.1, 142.4, 142.3, 136.9, 132.0, 129.1 126.5, 126.0, 123.6,
116.5, 112.6, 112.3, 110.7, 107.9, 21.0 ppm. MS (ESI): m/z = 354.0
[M + H]+. HRMS (ESI): calcd. for C18H16 N3O3S [M + H]+
354.0907; found 354.0912.
4-Chloro-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfon-
amide (5p): White solid (287 mg, 75%), m.p. 224.2–225.0 °C. IR
(KBr): ν = 3445 (NH), 2983, 2808, 2736, 1634 (C=N), 1585, 1503,
˜
1476, 1447, 1434, 1343 (SO2), 1236, 1204, 1166 (SO2), 1093 cm–1.
1H NMR (400 MHz, [D6]DMSO): δ = 10.80 (s, 1 H, NH), 8.29 (d,
J = 6.8 Hz, 1 H, 5-H), 7.62–7.52 (m, 3 H, 8-H, Ar), 7.42–7.38 (m,
2 H, Ar), 7.38–7.32 (m, 1 H, 7-H), 7.26–7.10 (m, 5 H, Ar), 7.01 (t,
J = 6.8 Hz, 1 H, 6-H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ
= 1421, 139.4, 138.1, 137.7, 132.1, 128.6, 128.0, 127.5, 127.0, 126.6,
125.8, 123.5, 116.5, 113.0, 112.3 ppm. MS (ESI): m/z = 384.0 [M
+ H]+. HRMS (ESI): calcd. for C19H15ClN3O2S [M + H]+
384.0568; found 384.0580.
4-Methyl-N-[2-(thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl]benzene-
sulfonamide (5l): White solid (269 mg, 73%), m.p. 226.7–228.6 °C.
IR (KBr): ν = 3446 (NH), 3025, 2808, 2744, 1635 (C=N), 1558,
4-Nitro-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfonamide
˜
1540, 1506, 1353, 1336 (SO2), 1255, 1204, 1163 (SO2), 1093, 1067, (5q): Yellow solid (279 mg, 71%), m.p. 237.5–238.4 °C. IR (KBr):
1013 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.55 (s, 1 H,
NH), 7.99 (d, J = 6.8 Hz, 1 H, 5-H), 7.52 (d, J = 8.8 Hz, 1 H, 8-
H), 7.45 (d, J = 8.0 Hz, 2 H, Ar), 7.39 (d, J = 5.2 Hz, 1 H, Thienyl),
7.33–7.26 (m, 1 H, 7-H), 7.17 (d, J = 8.4 Hz, 2 H, Ar), 7.09 (d, J
ν = 3439 (NH), 3205, 3109, 3065, 1648 (C=N), 1605, 1591, 1520,
˜
1499, 1443, 1347 (SO2), 1267, 1234, 1142 (SO2), 1091 cm–1 1H
.
NMR (400 MHz, [D6]DMSO): δ = 11.40 (s, 1 H, NH), 8.39 (d, J
= 6.0 Hz, 1 H, 5-H), 7.93 (d, J = 8.4 Hz, 2 H, Ar), 7.71–7.56 (m,
Eur. J. Org. Chem. 2014, 2037–2043
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2041

C. Yu, X. Chen, R. Wu, G. Yang, J. Shi, L. Pan
FULL PAPER
3 H, 8-H, Ar), 7.51 (d, J = 5.6 Hz, 2 H, Ar), 7.46–7.36 (m, 1 H, 7- 1 H, NH), 7.99–7.89 (m, 1 H, 5-H), 7.73–7.66 (m, 2 H, Ar), 7.61
H), 7.13–6.99 (m, 4 H, 6-H, Ar) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 149.0, 145.5, 141.5, 137.5, 131.7, 127.7, 127.5,
126.8, 126.5, 123.8, 123.7, 115.9, 114.23, 112.7 ppm. MS (ESI): m/z
(d, J = 9.6 Hz, 1 H, 8-H), 7.36–7.33 (m, 3 H, 7-H, Ar), 7.23–7.15
(m, 3 H, Ar), 7.07 (d, J = 8.0 Hz, 2 H, Ar), 2.24 (s, 3 H, CH3)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 143.5, 140.8, 140.5,
= 395.0 [M + H]+. HRMS (ESI): calcd. for C19H15N4O4S 136.4, 132.0, 129.4, 127.7, 127.4, 126.7, 126.5, 126.3, 121.2, 119.3,
[M + H]+ 395.0809; found 395.0808.
117.7, 113.9, 21.0 ppm. MS (ESI): m/z = 398.0 [M + H]+. HRMS
(ESI): calcd. for C20H17Cl N3O2S [M + H]+ 398.0725; found
398.0728.
N-(2-Phenylimidazo[1,2-a]pyridin-3-yl)methanesulfonamide (5r):
White solid (89 mg, 31%), m.p. 206.4–208.1 °C. IR (KBr): ν = 3428
˜
(NH), 3080, 2973, 2689, 1633 (C=N), 1568, 1498, 1445, 1411, 1398,
N-(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)-4-methylbenzene-
sulfonamide (5w): Pale yellow solid (300 mg, 68 %), m.p. 220.6–
1329 (SO2), 1244, 1206, 1157 (SO2) cm–1 1H NMR (400 MHz,
.
[D6]DMSO): δ = 10.20 (s, 1 H, NH), 8.34 (dd, J = 6.8, 1.2 Hz, 1
H, 5-H), 8.12–8.05 (m, 2 H, Ar), 7.60 (dd, J = 8.8, 1.0 Hz, 1 H, 8-
H), 7.50–7.44 (m, 2 H, Ar), 7.41–7.31 (m, 2 H, 7-H, Ar), 7.02 (t, J
= 6.8 Hz, 1 H, 6-H), 2.79 (s, 3 H, CH3) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 142.2, 139.4, 132.7, 128.2, 127.8, 127.0, 125.7,
123.6, 116.7, 113.2, 112.3, 41.2 ppm. MS (ESI): m/z = 287.9 [M +
H]+. HRMS (ESI): calcd. for C14H14N3O2S [M + H]+ 288.0801;
found 288.0805.
222.4 °C. IR (KBr): ν = 3435 (NH), 3090, 2991, 2923, 2801, 2734,
˜
1733, 1625, 1597, 1552, 1498, 1431, 1409, 1381, 1338 (SO2), 1327,
1227, 1195, 1163 (SO2), 1092, 1071, 1050 cm–1 1H NMR
.
(400 MHz, [D6]DMSO): δ = 10.56 (s, 1 H, NH), 7.94 (d, J = 1.2 Hz,
1 H, 5-H), 7.78–7.71 (m, 2 H, Ar), 7.54 (dd, J = 9.2, 0.8 Hz, 1 H,
8-H), 7.40 (dd, J = 9.2, 2.0 Hz, 1 H, 7-H), 7.37 (d, J = 8.4 Hz, 2
H, Ar), 7.22–7.20 (m, 3 H, Ar), 7.09 (d, J = 8.0 Hz, 2 H, Ar), 2.26
(s, 3 H, CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 143.6,
140.5, 136.5, 131.9, 129.4, 128.5, 127.7, 127.4, 126.7, 126.3, 123.2,
117.9, 113.6, 106.2, 21.0 ppm. MS (ESI): m/z = 442.0 [M + H]+.
HRMS (ESI): calcd. for C20H17BrN3 O2S [M + H]+ 442.0219;
found 442.0209.
N-(2-Phenylimidazo[1,2-a]pyridin-3-yl)cyclopropanesulfonamide
(5s): White solid (122 mg, 39%), m.p. 205.0–206.2 °C. IR (KBr): ν
˜
= 3437 (NH), 3054, 3012, 2789, 2732, 1631 (C=N), 1497, 1446,
1326 (SO2), 1237, 1142 (SO2), 1069, 1042 cm–1 1H NMR
.
(400 MHz, [D6]DMSO): δ = 10.19 (s, 1 H, NH), 8.34 (dt, J = 6.8,
1.0 Hz, 1 H, 5-H), 8.16–8.08 (m, 2 H, Ar), 7.59 (dt, J = 9.2, 1.0 Hz,
1 H, 8-H), 7.49–7.40 (m, 2 H, Ar), 7.39–7.30 (m, 2 H, 7-H, Ar),
7.01 (td, J = 6.8, 1.2 Hz, 1 H, 6-H), 2.45–2.38 (m, 1 H, CH), 0.74
(d, J = 3.6 Hz, 2 H, CH2), 0.66 (d, J = 7.2 Hz, 2 H, CH2) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 142.0, 139.6, 132.9, 128.0,
127.7, 127.1, 125.6, 123.6, 116.6, 113.4, 112.2, 31.1, 5.7 ppm. MS
(ESI): m/z = 314.0 [M + H]+ . HRMS (ESI): calcd. for
C16H16N3O2S [M + H]+ 314.0958; found 314.0952.
CCDC-957561 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of all compounds, crystal data and
details of X-ray experiments for compounds 5c.
Acknowledgments
4-Methyl-N-(8-methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)benzene-
sulfonamide (5t): White solid (298 mg, 79%), m.p.173.1–174.6 °C.
The authors gratefully acknowledge financial support from the
National Natural Science Foundation of China (NSFC) (grant
numbers 21006097, 21276237, 21176222).
IR (KBr): ν = 3436 (NH), 3034, 2972, 2925, 2727, 1631 (C=N),
˜
1598, 1563, 1495, 1446, 1390, 1356 (SO2), 1332, 1260, 1205, 1157
(SO2), 1092 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.11 (d, J =
6.8 Hz, 1 H, 5-H), 7.31–7.20 (m, 4 H, 7-H, Ar), 7.04–7.01 (m, 2 H,
Ar), 6.97 (t, J = 7.3 Hz, 2 H, Ar), 6.79 (d, J = 8.2 Hz, 2 H, Ar),
6.72 (t, J = 6.8 Hz, 1 H, 6-H), 2.61 (s, 3 H, CH3), 2.19 (s, 3 H,
CH3) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 142.9, 142.3,
139.1, 136.6, 132.5, 129.0, 127.4, 126.7, 126.6, 126.2, 126.0, 124.0,
121.2, 113.4, 112.0, 20.8, 16.0 ppm. MS (ESI): m/z = 378.0 [M +
H]+. HRMS (ESI): calcd. for C21H20N3O2S [M + H]+ 378.1271;
found 378.1275.
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4-Methyl-N-(6-methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)benzene-
sulfonamide (5u): White solid (264 mg, 70%), m.p. 230.4–231.8 °C.
IR (KBr): ν = 3436 (NH), 2975, 2923, 2800, 2734, 1597, 1511,
˜
1490, 1433 (SO2), 1412, 1381, 1337, 1214, 1164 (SO2), 1094 cm–1.
1H NMR (400 MHz, [D6]DMSO): δ = 10.45 (s, 1 H, NH), 7.72 (s,
1 H, 5-H), 7.70–7.63 (m, 2 H, Ar), 7.45 (d, J = 9.2 Hz, 1 H, 8-H),
7.35 (d, J = 8.0 Hz, 2 H, Ar), 7.18–7.11 (m, 4 H, 7-H, Ar), 7.05 (d,
J = 8.0 Hz, 2 H, Ar), 2.24 (s, 3 H, CH3), 2.23 (s, 3 H, CH3) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 143.0, 141.0, 139.5, 136.9,
132.5, 129.1, 128.3, 127.4, 126.8, 126.5, 126.2, 121.1, 120.7, 115.9,
112.8, 20.8, 17.5 ppm. MS (ESI): m/z = 378.0 [M + H]+. HRMS
(ESI): calcd. for C21H20 N3O2S [M + H]+ 378.1271; found
378.1270.
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˜
1556, 1500, 1446, 1416, 1382, 1338 (SO2), 1328, 1229, 1199, 1163
1
(SO2), 1094 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 10.61 (s,
2042
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Eur. J. Org. Chem. 2014, 2037–2043

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Received: October 28, 2013
Published Online: January 27, 2014
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2043