A new method for the synthesis of [1,2,4]triazolo[1,5-a]-pyridine derivatives

Article abstract of DOI:10.3987/COM-13-12670

[1,2,4]Triazolo[1,5-a]pyridine derivatives were conveniently synthesized by tandem reaction under mild conditions. The reaction mechanism was also proposed.

Full text of DOI:10.3987/COM-13-12670

HETEROCYCLES, Vol. 87, No. 4, 2013, pp. -. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 19th January, 2013, Accepted, 5th February , 2013, Published online, 22nd February, 2013
DOI: 10.3987/COM-13-12670
A NEW METHOD FOR THE SYNTHESIS OF [1,2,4]TRIAZOLO[1,5-a]-
PYRIDINE DERIVATIVES
Wei-Ming Zhao,a Yan-Qing Ge,b* Wei-Ren Xu,c Gui-Long Zhao,c Jiong Jia,a
and Jian-Wu Wanga*
aSchool of Chemistry and Chemical Engineering, Shandong University, Jinan,
Shandong 250100, P. R. China. E-mail: jwwang@sdu.edu.cn
bSchool of Chemical Engineering, Taishan Medical University, Taian, Shandong
271016, P. R. China. E-mail: yqge@yahoo.cn
cTianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin
Institute of Pharmaceutical Research, Tianjin 300193, P. R. China
Abstract – [1,2,4]Triazolo[1,5-a]pyridine derivatives were conveniently
synthesized by tandem reaction under mild conditions. The reaction mechanism
was also proposed.
The [1,2,4]triazolo[1,5-a]pyridine derivatives are a kind of important heterocyclic compounds which
exhibit antifungal, anticancer and anti-inflammatory activity.1-3 Despite possessing outstanding biological
activities, only a few [1,2,4]triazolo[1,5-a]pyridines are known. Some commonly used synthetic methods
are the annulation of 1,2,4-triazole ring starting with amino substituted pyridines by a multistep
procedure.4 Previously, imidazo[1,5-a]pyridines, pyrazolo[1,5-a]pyridines, imidazo[1,2-a]pyridines and
indolizines had been synthesized by a novel tandem reaction in our group.5-8 Herein we are interested to
extend the reaction to synthesize the [1,2,4]triazolo[1,5-a]pyridine heterocycles.
1,2,4-triazoles 1a-f were prepared according to a literature method (Scheme 1)9 only that we used
different reactant. The expected [1,2,4]triazolo[1,5-a]pyridine 3a-l were obtained by the reactions of
1,2,4-triazoles 1a-f and α,β-unsaturated esters 2a-b in the presence of K2CO3 in dry DMF at room
temperature for 6-10 h. The experimental results are collected in Table 1. As observed in Table 1, a
variety of substituted 5-benzoyl-1,2,4-triazoles 1 afforded good yields of these products including a
variety of electron-donating and electron-withdrawing substituents.

R1
R2
O
R2
R3
N
N
N
CO2Et
+
R1
N
NH
CO2Et
N
Br
R3
3a-j
2a-b
1a-f
Scheme 1
Figure 1. Crystal structure of 3k
Table 1. Synthesis of [1,2,4]triazolo[1,5-a]pyridine derivatives
Entry
R1
R2
R3
Intermediate
Product Isolated
Yield(%）
75
1
H
H
H
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
3a
3b
3c
3d
3e
3f
2
H
H
H
H
H
H
H
H
F
Me
H
71
72
69
75
70
68
65
72
68
70
67
3
Me
Me
MeO
MeO
F
4
Me
H
5
6
Me
H
7
3g
3h
3i
8
F
Me
H
9
H
10
11
12
H
F
Me
H
3j
Cl
Cl
Cl
3k
3l
Cl
Me
1f

The structures of products 3 were characterized by spectroscopic methods (1H and 13C NMR, IR, and MS).
The structure of 3k was further confirmed by X-ray crystallographic analysis as shown in Figure 1.
In consideration of the result, we proposed the reaction mechanism as follows: Firstly, there would be an
intermolecular SN2 reaction between 1 and α,β-unsaturated esters 2, through which intermediate 3 was
formed. Afterwards, in the presence of K2CO3, intermediate 4 was deprotonated to form a γ-carbanion of
the ester. In order to be more stable, it would transform to α-carbanion of the ester 5. Then by
intramolecular nucleophilic addition, the α-carbanion reacted with the aldehyde group to obtain
intermediate 6. Afterwards our target product would be gained from 6 by eliminating water. The entire
process is shown in Scheme 2.
B:
R3
O
R3
O
H
H
R3
O
O
B:
N
OEt
OEt
N
O
N
OEt
N
+
N
N
O
N
R2
Br
N
N
R2
1
R2
2
R1
4
5
R1
R1
R3
R3
O
O
+ H+
N
N
N
H2O
N
N
OEt
R2
OEt
OH
N
R2
R1
R1
3
6
Scheme 2
In summary, we described a novel tandem reaction to synthesize [1,2,4]triazolo[1,5-a]pyridine derivatives
under mild conditions in good yields. The reaction mechanism was also proposed. The compounds are
particularly interesting molecules due to their biological activity, which will be presented in due course.
EXPERIMENTAL
All reagents and solvents were purchased from Sinopharm Chemical Reagent Co. Ltd and used without
further purification unless otherwise noted. Starting materials were prepared according to literatures.9
1
Thin-layer chromatography (TLC) was conducted on silica gel 60 F254 plates (Merck KGaA). H NMR
spectra were recorded on a Bruker Avance 300 (300 MHz) spectrometer, using CDCl3 or DMSO-d6 as
solvents and tetramethylsilane (TMS) as an internal standard. Melting points were determined on an

XD-4 digital micro-melting point apparatus and are uncorrected. IR spectra were recorded with an IR
spectrophotometer Avtar 370 FT-IR (Termo Nicolet). MS spectra were recorded on a Trace DSQ mass
spectrometer. Elemental analyses were performed on a Vario EL III (Elementar Analysensysteme GmbH)
spectroanalyzer.
General procedure for the synthesis and analytical data of 1a-1f
To a 250 mL three-necked, round-bottomed flask, 3.45 g (0.05 mol)1,2,4-triazole and triethylamine (7
mL) were dissolved in pyridine (30 mL) at 0 °C under nitrogen. Then benzoyl chloride (0.1 mol) was
added dropwise to the flask. The mixture was stirred for 6 h at rt. After that, sodium hydroxide (0.15 mol)
dissolved in 20 mL water was added in the mixture, refluxing for 1.5 h. Then this system was cooled to
room temperature and added in water (150 mL), adjusted PH value to 5-6 by using diluted hydrochloric
acid. It would precipitate solid compounds. After that, it was filtered and washed with water and ice-cold
EtOAc. The crude intermediates were depurated by column chromatography.
Phenyl(1H-1,2,4-triazol-5-yl)methanone (1a)10
1H NMR (300 MHz, CDCl3): δ 14.83 (s, 1H), 8.83 (s, 1H), 7.57-7.84 (m, 5H). ESI-MS m/z Calcd: 173.1.
Found: 174.1 [M++1].
p-Tolyl(1H-1,2,4-triazol-5-yl)methanone (1b)
1H NMR (300 MHz, CDCl3): δ 14.82 (s, 1H), 8.81 (s, 1H), 7.82-7.85 (m, 2H), 7.29-7.32 (m, 2H), 2.37 (s,
3H). ESI-MS m/z Calcd: 187.1. Found: 188.1 [M++1]. Anal. Calcd for C10H9N3O: C, 64.16; H, 4.85; N,
22.45. Found: C, 64.22; H, 4.91; N, 22.49.
(4-Methoxyphenyl)(1H-1,2,4-triazol-5-yl)methanone (1c)10
1H NMR (300 MHz, CDCl3): δ 14.80 (s, 1H), 8.80 (s, 1H), 7.87-7.92 (m, 2H), 7.00-7.03 (m, 2H), 3.82 (s,
H). ESI-MS m/z Calcd: 203.1. Found: 204.1 [M++1].
(4-Fluorophenyl)(1H-1,2,4-triazol-5-yl)methanone (1d)
1H NMR (300 MHz, CDCl3): δ 14.93 (s, 1H), 8.71 (s, 1H), 8.39-8.43 (m, 2H), 7.38-7.45 (m, 2H).
ESI-MS m/z Calcd: 191.1. Found: 192.1 [M++1]. Anal. Calcd for C9H6FN3O: C, 56.55; H, 3.16; N, 21.98.
Found: C, 56.59; H, 3.20; N, 21.98.
(2-Fluorophenyl)(1H-1,2,4-triazol-5-yl)methanone (1e)
1H NMR (300 MHz, CDCl3): δ 14.86 (s, 1H), 8.74 (s, 1H), 7.70-7.81 (m, 1H), 7.67-7.69 (m, 1H),
7.33-7.39 (m, 2H). ESI-MS m/z Calcd: 191.1. Found: 192.1 [M++1]. Anal. Calcd for C9H6FN3O: C, 56.55;
H, 3.16; N, 21.98. Found: C, 56.57; H, 3.22; N, 22.04.
(2,4-Dichlorophenyl)(1H-1,2,4-triazol-5-yl)methanone (1f) 10
1H NMR (300 MHz, CDCl3): δ 14.89 (s, 1H), 8.76 (s, 1H), 7.78-7.79 (m, 1H), 7.69-7.71 (m, 1H),
7.57-7.60 (m, 1H). ESI-MS m/z Calcd: 241.0. Found: 242.0 [M++1].
General procedure for the synthesis and analytical data of 3a-3l

Intermediate 1 (6 mmol), α,β-unsaturated esters (12 mmol), potassium carbonate (1.8 g, 13.2 mmol) and
DMF (30 mL) were added to a 100 mL round-bottomed flask. The reaction system was stirred for 6-10 h.
Then the mixture was poured into water (200 mL) and extracted with CH2Cl2 (3 x 50 mL). Organic layers
were combined and dried over anhydrous Na2SO4, then filtered. By rotary evaporation, the mixture was
concentrated. After that, these crude products were depurated by using column chromatography.
Ethyl 8-phenyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3a)
1
Yellow solid: mp 77-79 °C. H NMR (300 MHz, CDCl3): δ 8.64 (d, 1H, J = 6.9 Hz), 8.41 (s, 1H),
13
7.48-7.50 (m, 6H), 4.10-4.17 (q, 2H, J = 7.2 Hz), 0.98-1.02 (t, 3H, J = 7.2 Hz). C NMR (75.4 MHz,
CDCl3): δ 166.9, 155.6, 150.9, 134.6, 131.4, 129.7, 129.4, 128.8, 127.6, 114.8, 77.9, 77.5, 77.1, 62.3, 14.0.
IR (KBr) ν = 3112, 3068, 2925, 1712, 1536, 1486, 1366, 1324, 1257, 1183, 1124, 767, 657 cm-1. ESI-MS
m/z Calcd: 267.1. Found: 268.1 [M++1]. Anal. Calcd for C15H13N3O2: C, 67.40; H, 4.90; N, 15.72. Found:
C, 67.38; H, 4.94; N, 15.74.
Ethyl 6-methyl-8-phenyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3b)
1
Yellow oil. H NMR (300 MHz, CDCl3): δ 8.45 (s, 1H), 8.33 (s, 1H), 7.55-7.59 (m, 2H), 7.44-7.51 (m,
13
3H), 4.10-4.17 (q, 2H, J = 7.2 Hz), 2.44 (s, 3H), 0.97-1.02 (t, 3H, J = 7.2 Hz). C NMR (75.4 MHz,
CDCl3): δ 167.0, 154.4, 148.8, 135.1, 133.3, 129.1, 128.5, 128.3, 126.1, 121.4, 77.4, 77.0, 76.6, 61.8, 16.7,
13.6. IR (KBr) ν = 3101, 3061, 2981, 2928, 1229, 1498, 1323, 1241, 1185, 1141, 788, 699 cm-1. ESI-MS
m/z Calcd: 281.1. Found: 282.1 [M++1]. Anal. Calcd for C16H15N3O2: C, 68.31; H, 5.37; N, 14.94. Found:
C, 68.34; H, 5.35; N, 14.99.
Ethyl 8-p-tolyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3c)
Yellow oil. 1H NMR (300MHz, CDCl3): δ 8.61 (d, 1H, J = 7.2 Hz), 8.39 (s, H), 7.46 (d, 1H, J = 7.2 Hz),
7.39-7.41 (m, 2H), 7.27-7.31 (m, 2H), 4.13-4.20 (q, 2H, J = 7.2 Hz), 2.43 (s, 3H), 1.03-1.08 (t, 3H, J =
13
7.2 Hz). C NMR (75.4 MHz, CDCl3): δ 166.5, 155.0, 150.5, 138.8, 131.9, 131.1, 130.6, 129.1, 126.9,
114.3, 77.4, 77.0, 76.6, 61.8, 21.4, 13.6. IR (KBr) ν = 3110, 2981, 2922, 1718, 1492, 1324, 1258, 1180,
1134, 820, 758 cm-1. ESI-MS m/z Calcd: 281.1. Found: 282.1 [M++1]. Anal. Calcd for C16H15N3O2: C,
68.31; H, 5.37; N, 14.94. Found: C, 68.30; H, 5.35; N, 14.98.
Ethyl 6-methyl-8-p-tolyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3d)
1
Yellow solid: mp 115-117 °C. H NMR (300 MHz, CDCl3): δ 8.42 (s, 1H), 8.31 (s, 1H), 7.46-7.49 (m,
2H), 7.27-7.30 (m, 2H), 4.13-4.20 (q, 2H, J = 7.2 Hz), 2.41-2.43 (m, 6H), 1.03-1.08 (t, 3H, J = 7.2 Hz).
13C NMR (75.4 MHz, CDCl3): δ 167.1, 154.4, 149.0, 139.0, 134.8, 130.6, 129.1, 128.3, 125.9, 121.4, 77.5,
77.0, 76.6, 61.8, 21.4, 16.7, 13.7. IR (KBr) ν = 3103, 2963, 2926, 1727, 1609, 1500, 1434, 1322, 1250,
1181, 1140, 831, 665 cm-1. ESI-MS m/z Calcd: 295.1. Found: 296.1 [M++1]. Anal. Calcd for C17H17N3O2:
C, 69.14; H, 5.80; N, 14.23. Found: C, 69.20; H, 5.85; N, 14.29.
Ethyl 8-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3e)

1
Yellow solid: mp 99-101 °C. H NMR (300 MHz, CDCl3): δ 8.60 (d, H, J = 6.9 Hz), 8.41 (s, 1H),
7.44-7.49 (m, 3H), 7.02-7.05 (m, 2H), 4.15-4.22 (q, 2H, J = 7.2 Hz), 3.87 (s, 3H), 1.06-1.11 (t, 3H, J =
13
7.2 Hz). C NMR (75.4 MHz, CDCl3): δ 167.2, 160.7, 155.4, 151.0, 131.8, 131.2, 131.1, 127.2, 126.6,
114.6, 77.9, 77.5, 77.1, 62.3, 55.9, 14.2. IR (KBr) ν = 3747, 3674, 2922, 2850, 1716, 1650, 1558, 1509,
1458, 1385, 1325, 1116, 839, 760 cm-1. ESI-MS m/z Calcd: 297.1. Found: 298.1 [M++1]. Anal. Calcd for
C16H15N3O3: C, 64.64; H, 5.09; N, 14.13. Found: C, 64.67; H, 5.12; N, 14.19.
Ethyl 8-(4-methoxyphenyl)-6-methyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3f)
1
Yellow oil. H NMR (300 MHz, CDCl3): δ 8.41 (s, 1H), 8.32 (s, 1H), 7.52-7.57 (m, 2H), 6.99-7.04 (m,
13
2H), 4.16-4.22 (q, 2H, J = 7.2 Hz), 3.86 (s, 3H), 2.42 (s, 3H), 1.06-1.11 (t, 3H, J = 7.2 Hz). C NMR
(75.4 MHz, CDCl3): δ 167.2, 160.2, 154.3, 149.0, 134.7, 130.6, 127.9, 125.8, 121.4, 114.1, 77.4, 77.0,
76.6, 61.8, 55.4, 16.7, 13.8. IR (KBr) ν = 3748, 3673, 2824, 2854, 1717, 1650, 1558, 1506, 1459, 1385,
1324, 1117, 720 cm-1. ESI-MS m/z Calcd: 311.1. Found: 312.1 [M++1]. Anal. Calcd for C17H17N3O3: C,
65.58; H, 5.50; N, 13.50. Found: C, 65.54; H, 5.52; N, 13.56.
Ethyl 8-(4-fluorophenyl)[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3g)
1
Yellow oil. H NMR (300 MHz, CDCl3): δ 8.64 (d, 1H, J = 7.2 Hz), 8.40 (s, 1H), 7.47-7.52 (m, 3H),
13
7.17-7.23 (m, 3H), 4.14-4.21 (q, 2H, J = 7.2 Hz), 1.05-1.10 (t, 3H, J = 7.2 Hz). C NMR (75.4 MHz,
CDCl3): δ 167.8, 161.5, 155.1, 150.5, 131.5, 131.1, 130.7, 130.4, 127.3, 114.3, 77.4, 77.0, 76.6, 61.9, 13.8.
IR (KBr) ν = 3112, 2925, 2853, 1719, 1603, 1493, 1368, 1326, 1233, 1180, 839, 760 cm-1. ESI-MS m/z
Calcd: 285.1. Found: 286.1 [M++1]. Anal. Calcd for C15H12FN3O2: C, 63.15; H, 4.24; N, 14.73. Found: C,
63.14; H, 4.30; N, 14.79.
Ethyl 8-(4-fluorophenyl)-6-methyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3h)
1
Yellow oil. H NMR (300 MHz, CDCl3): δ 8.41 (s, 1H), 8.32 (s, 1H), 7.52-7.57 (m, 2H), 6.99-7.04 (m,
13
2H), 4.15-4.22 (q, 2H, J = 7.2 Hz), 3.86 (s, 3H), 1.06-1.11 (t, 3H, J = 7.2 Hz). C NMR (75.4 MHz,
CDCl3): δ 167.2, 160.2, 154.3, 149.0, 134.7, 130.6, 127.9, 125.8, 121.4, 114.1, 77.4, 77.0, 76.6, 61.8, 16.7,
12.9. IR (KBr) ν = 2924, 2854, 1721, 1602, 1495, 1458, 1321, 1246, 1142, 841 cm-1. ESI-MS m/z Calcd:
299.1. Found: 300.1 [M++1]. Anal. Calcd for C16H14FN3O2: C, 64.21; H, 4.71; N, 14.04. Found: C, 64.24;
H, 4.70; N, 14.09.
Ethyl 8-(2-fluorophenyl)[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3i)
Yellow solid: mp 120-122 °C. 1H NMR (300 MHz, CDCl3): δ 8.68 (d, 1H, J = 7.2 Hz), 8.43 (s, 1H), 7.40
(d, 1H, J = 7.2 Hz), 7.45-7.54 (m, 2H), 7.17-7.34 (m, 2H), 4.17-4.24 (q, 2H, J = 7.2 Hz), 1.05-1.10 (t, 3H,
J = 7.2 Hz). 13C NMR (75.4 MHz, CDCl3): δ 165.7, 161.8, 158.5, 155.7, 150.8, 131.4, 126.5, 124.5, 122.6,
115.8, 77.9, 77.5, 77.1, 62.4, 14.0. IR (KBr) ν = 3446, 2925, 2853, 1702, 1651, 1540, 1457, 1324, 1254,
757 cm-1. ESI-MS m/z Calcd: 285.1. Found: 286.1 [M++1]. Anal. Calcd for C15H12FN3O2: C, 63.15; H,
4.24; N, 14.73. Found: C, 63.17; H, 4.20; N, 14.79.

Ethyl 8-(2-fluorophenyl)-6-methyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3j)
1
Yellow solid: mp 135-137 °C. H NMR (300 MHz, CDCl3): δ 8.50 (s, 1H), 8.33 (s, 1H), 7.39-7.50 (m,
13
2H), 7.18-7.28 (m, 2H), 4.10-4.17 (q, 2H, J = 7.2 Hz), 2.47 (s, 3H), 0.97-1.02 (t, 3H, J = 7.2 Hz). C
NMR (75.4 MHz, CDCl3): δ 166.2, 161.6, 158.3, 154.6, 148.6, 131.1, 127.0, 124.2, 121.6, 115.9, 77.4,
77.0, 76.6, 61.8, 16.9, 13.6. IR (KBr) ν = 3443, 2924, 2854, 1718, 1651, 1540, 1500, 1457, 1328, 1260,
758 cm-1. ESI-MS m/z Calcd: 299.1. Found: 300.1 [M++1]. Anal. Calcd for C16H14FN3O2: C, 64.21; H,
4.71; N, 14.04. Found: C, 64.23; H, 4.74; N, 14.05.
Ethyl 8-(2,4-dichlorophenyl)[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3k)
1
Yellow solid: mp 96-98 °C. H NMR (300 MHz, CDCl3): δ 8.70 (d, 1H, J = 7.2 Hz), 8.40 (s, 1H),
7.68-7.71 (d, 1H, J = 7.2 Hz), 7.55-7.60 (m, 1H), 7.39-7.42 (m, 1H), 7.26-7.32 (m, 1H), 4.26-4.33 (q, 2H,
13
J = 7.2 Hz), 1.08-1.13 (t, 3H, J = 7.2 Hz). C NMR (75.4 MHz, CDCl3): δ 164.5, 155.3, 150.1, 135.4,
134.0, 132.3, 131.3, 129.5, 127.2, 114.3, 77.4, 77.0, 76.6, 62.1, 13.6. IR (KBr) ν = 3119, 2982, 1724,
1588, 1467, 1322, 1240, 1120, 863, 751 cm-1. ESI-MS m/z Calcd: 335.0. Found: 336.0 [M++1]. Anal.
Calcd for C15H11Cl2N3O2: C, 53.59; H, 3.30; N, 12.50. Found: C, 53.64; H, 3.33; N, 12.54.
Ethyl 8-(2,4-dichlorophenyl)-6-methyl[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (3l)
1
Yellow oil. H NMR (300 MHz, CDCl3): δ 8.52 (s, 1H), 8.32 (s, 1H), 7.56-7.57 (m, 1H), 7.34-7.38 (m,
13
1H), 7.27-7.30 (m,1H), 4.11-4.18 ( q, 2H, J = 7.2 Hz), 2.48 (s, 3H), 1.01-1.06 (t, 3H, J = 7.2 Hz). C
NMR (75.4 MHz, CDCl3): δ 165.8, 154.7, 148.2, 135.8, 134.8, 131.8, 131.4, 129.7, 127.2, 121.5, 77.5,
77.1, 76.7, 61.9, 17.0, 13.7. IR (KBr) ν = 3093, 2918, 1729, 1589, 1501, 1322, 1241, 1142, 863, 781 cm-1.
ESI-MS m/z Calcd: 349.0. Found: 350.0 [M++1]. Anal. Calcd for C16H13Cl2N3O2: C, 54.87; H, 3.74; N,
12.00. Found: C, 54.84; H, 3.76; N, 12.05.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the Science and Technology Special Major Project for Significant
New Drugs Formulation (2011ZX09401-009), the Natural Science Foundation of Shandong Province (No.
ZR2012BL04) for financial support of this work.
REFERENCES (AND NOTES)
1. Y. Luo and Y. Hu, Arch. Pharm. Chem. Life Sci., 2006, 339, 262.
2. T. Liu and Y. Hu, Bioorg. Med. Chem. Lett., 2002, 12, 2411.
3. S. P. East, C. B. White, O. Barker, S. Barker, J. Bennett, D. Brown, E. A. Boyd, C. Brennan, C.
Chowdhury, I. Collins, E. Convers-Reignier, B. W. Dymock, R.Fletcher, D. J. Haydon, M. Gardiner,
S. Hatcher, P. Ingram, P. Lancett, P. Mortenson, K. Papadopoulos, C. Smee, H. B.
Thomaides-Brears, H. Tye, J. Workman, and L. G. Czaplewski, Bioorg. Med. Chem. Lett., 2009, 19,

894.
4. G. Jones and D. R. Sliskovic, Adv. Heterocycl. Chem., 1983, 34, 86.
5. J. W. Wang, J. Jia, D. J. Hou, H. M. Li, and J. Yin, Chin. J. Org. Chem., 2003, 23, 173.
6. Y. Q. Ge, J. Jia, Y. Li, L. Yin and J. W. Wang, Heterocycles, 2009, 78, 197.
7. Y. Q. Ge, J. Jia, H. Yang, G. L. Zhao, F. X. Zhan, and J. W. Wang, Heterocycles, 2009, 78, 725.
8. J. Jia, Y. Q. Ge, X. T. Tao, and J. W. Wang, Heterocycles, 2010, 81, 185.
9. L. A. M. Bastiaansen and E. F. Godefroi, Synthesis, 1978, 675.
10. S. Ohta, I. Kawasaki, A. Fukuno, M. Yamashita, T. Tada, and T. Kawabata, Chem. Pharm. Bull.,
1993, 41, 1226.