A Convenient One-pot Synthesis of N-Fused 1,2,4-Triazoles via Oxidative Cyclization Using Trichloroisocyanuric Acid

Article abstract of DOI:10.1002/jhet.3451

A facile one-pot synthesis of N-fused 1,2,4-triazoles from heterocyclic hydrazines and aldehydes is reported. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products mostly in high yields and in relatively short time. The mild nature of the synthesis and short reaction time are notable advantages of the developed protocol. This protocol is effective toward various substrates having different functionalities.

Full text of DOI:10.1002/jhet.3451

Month 2019 A Convenient One-pot Synthesis of N-Fused 1,2,4-Triazoles via Oxidative
Cyclization Using Trichloroisocyanuric Acid
a
b
a
Ashish Bhatt, *
Rajesh K. Singh, and Ravi Kant
a
Department of Chemistry, Mewar university, Chittorgarh, Rajasthan 312901, India
Department of Pharmacy, Mewar university, Chittorgarh, Rajasthan 312901, India
b
*
E-mail: itsbhatt2007@yahoo.co.in
Received August 5, 2018
DOI 10.1002/jhet.3451
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
A facile one-pot synthesis of N-fused 1,2,4-triazoles from heterocyclic hydrazines and aldehydes is re-
ported. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products
mostly in high yields and in relatively short time. The mild nature of the synthesis and short reaction time
are notable advantages of the developed protocol. This protocol is effective toward various substrates having
different functionalities.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
some of these protocols suffer from the limitations of
harsh conditions, tedious synthetic procedures, time
taking reactions, and unsatisfactory yields. Hence, the
development of milder and more general procedures to
access N-fused 1,2,4-triazoles with high yields in short
reaction time remains desirable.
Fused aromatic heterocycles are among the most
important compound classes in drug discovery and also
play a pivotal role in living organisms [1,2]. In particular,
such scaffolds can be found as building blocks for DNA
(
guanine and adenine) and also in many approved drugs,
The described oxidative cyclization has previously been
reported for the preparation of triazoloquinoxalines [22–28].
Other methods reported in the literature for the cyclization
of the triazole ring usually require a combination of
N-bromosuccinimide and base [29], refluxing orthoesters
[30,31], acids [31,32], desulfurization of thiosemicarbazides
[33], or cyclization of hydrazides in polyphosphoric acid
[31]. A couple of examples of oxidative cyclizations using
chloramine-T have previously been reported [34].
Trichloroisocyanuric acid (TCCA) is a versatile reagent
and is becoming increasingly popular because of its
commercial availability at low cost and lesser
corrosiveness. Our continued interest in the development
of useful synthetic methodologies prompted us to explore
the feasibility of TCCA for the one-pot synthesis of
N-fused 1,2,4-triazoles with high yields. However, it has
not been investigated as a catalyst in the synthesis of
1,2,4-triazoles until now.
including sildenafil, zolpidem, and trazodone, and in
medicinal chemistry studies [3–6] (i.e., tyrosine kinase
c-Src inhibitors [7,8] or P38α inhibitors [8]) (Fig. 1).
1
,2,4-Triazoles have elicited considerable interest among
medicinal chemists because they are considered to be
privileged structural constituents of many pharmaceutical
agents and natural products [9,10]. In particular,
compounds containing N-fused 1,2,4-triazoles, such as
triazolopyridine and triazolopyrazine substructures,
exhibit a wide spectrum of biological activity including
antifungal [11], antimicrobial [12], antiviral [13], anti-
inflammatory [14], antiasthmatic [15], antiproliferative
[16], and hypotonic [17]. In addition, they have often been
used as bioisosteres of esters and amides and as
dipeptidomimetics in a number of pharmacologically
important molecules [18]. On the other hand, they also
play important roles as ligands in organometallic
compounds, as precursors for N-heterocyclic carbenes, as
ionic liquids and as corrosion inhibitors [19].
Due to their importance, many efficient methods have been
developed to access N-fused 1,2,4-triazoles [20]. Among
them, coupling of carboxylic acids or their derivatives with
amidrazones, followed by cyclodehydration is the most
common explored strategy (Scheme 1) [21]. However,
RESULT AND DISCUSSION
Our preliminary investigation began with the reaction of
2-hydrazinopyridine (1a) and benzaldehyde (2a) in the
presence of TCCA (0.3 eq.) in methanol at ambient
©
2019 Wiley Periodicals, Inc.

A. Bhatt, R. K. Singh, and R. Kant
Vol 000
Figure 1. Representative bioactive molecules comprising fused heterocycles related to 1,2,4-triazoles
also increased the product yield from 80% to 95%
Table 1, entry 8). Further increasing the quantity of
TCCA (from 1 to 2 eq.) led to a decrease in the yield to
1% (Table 1, entry 9). Therefore, we decided to perform
Scheme 1. General synthesis of N-fused 1,2,4-triazoles.
(
8
the subsequent reactions of the heterocyclic hydrazines
with different aldehydes in the presence of TCCA (1 eq.)
in ethanol at ambient temperature. The progress of the
reactions was monitored by thin-layer chromatography
(TLC) analysis using EtOAc/hexane as the eluent.
temperature. We were delighted to observe the formation
of the desired product (3a), albeit in a low yield of 71%
(Table 1, entry 1). Next, we optimized the reaction
conditions in order to increase the yield. Thus, different
solvents were screened, and the results are summarized in
Table 1. It was found that ethanol was the most superior
solvent in terms of the reaction time and yield of the
product (Table 1, entry 2). Once we had established a
suitable solvent for the synthesis of N-fused 1,2,4-
triazoles, we then focused on the quantity of TCCA. An
increase in the amount of TCCA (from 0.3 to 1 eq) not
only decreased the reaction time from 1 h to 10 min but
With optimized conditions in hand, the scope of the
reaction was investigated and the results are summarized in
Table 2. As expected, all of the aldehydes employed gave
the corresponding N-fused 1,2,4-triazoles in good to
excellent yields. Benzaldehydes with electron-donating
groups such as o-tolualdehyde (2b) and p-anisaldehyde
(2f) gave the desired products in very good yields
(Table 2, entries 2 and 6). An aromatic aldehyde
with an electronwithdrawing group, 3-trifluoromethyl
Table 1
Optimization of the reaction conditions.
Entry
Solvent
TCCA (eq.)
Time
Yield (%)
1
2
3
4
5
7
8
9
MeOH
EtOH
MeCN
Toluene
AcOH
EtOH
0.3
0.3
0.3
0.3
0.3
0.5
1
1 h
45 min.
1.5 h
1.5 h
1 h
30 min.
10 min.
5 min.
71
80
50
60
65
90
95
81
EtOH
EtOH
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
One-pot Synthesis of N-fused 1,2,4-Triazoles
Table 2
Synthesis of various [1,2,4]triazolo[4,3-a]pyridines, [1,2,4]triazolo[4,3-a]pyrazines, and [1,2,4]triazolo[4,3-a]pyrimidines.
Entry
1
Het/Ar
Product
Time (min)
10
Yield (%)
95
Ph 2a
3a
2
3
2-MeC
6
H
4
2b
2c
10
15
98
85
3b
3 6 4
3-CF C H
3c
4
5
6
7
4-ClC
6
H
4
2d
2e
15
15
10
10
90
91
98
90
3
d
6 4
4-BrC H
3
e
6 4
4-OMeC H 2f
3
f
6 4
4-OHC H 2g
3
g
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Bhatt, R. K. Singh, and R. Kant
Vol 000
Table 2
(
Continued)
Entry
8
Het/Ar
4-CNC
Product
Time (min)
10
Yield (%)
6
H
4
2h
85
3
h
9
4-Me thiazolyl 2i
15
80
3i
1
0
1
2-furyl 2j
15
20
88
82
3j
1
3-indolyl 2k
3k
12
13
14
Ph 2a
Ph 2a
Ph 2a
10
10
10
92
90
86
3
l
3m
3n
benzaldehyde (2c), 4-chlorobenzaldehyde (2d), and 4-
bromobenzaldehyde (2e) gave the corresponding triazole
in 85% (3c), 90% (3d), and 91% (3e) yield, respectively
(Table 2, entries 3, 4, and 5). The heteroaryl aldehyde, 5-
formyl thiazole (2i), 2-formylfuran (2j), and 3-formyl
indole (2k) reacted smoothly, affording the corresponding
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
One-pot Synthesis of N-fused 1,2,4-Triazoles
desired products (3i), (3j), and (3k) in good yield (Table 2,
entries 9, 10, and 11). Pyrazine, pyridazine, and pyrimidine
have also been successfully cyclized with aldehydes
affording the corresponding valuable cyclized products
3-Phenyl-[1,2,4]triazolo[4,3-a]pyridine (3a).
solid; yield: 84.9 mg (95%); m.p. 171–173°C; H-NMR
Off-white
1
(500 MHz, CDCl ): δ 8.30 (dt, J = 7.0, 1.2 Hz, 1H),
3
7.88–7.82 (m, 3H), 7.63–7.55 (m, 3H), 7.31 (ddd,
(
3l), (3m), and (3n) in good yields.
J = 9.3, 6.5, 1.1 Hz, 1H), 6.89 (td, J = 6.8, 1.1 Hz, 1H);
13
C-NMR (126 MHz, CDCl ): δ 150.3, 146.8, 130.3,
3
1
29.4, 128.3, 127.5, 126.5, 122.7, 116.6, 114.5; LCMS:
+
CONCLUSION
m/z = 196 [M + H] ; calcd for C H N : C, 73.83; H,
12 9 3
4
.65; N, 21.52. Found: C, 73.80; H, 4.61; N, 21.48.
In conclusion, we have developed a short and efficient
3-(o-Tolyl)-[1,2,4]triazolo[4,3-a]pyridine (3b).
solid; yield: 93.9 mg (98%); m.p. 148–150°C; H-NMR
Off-white
1
synthesis of N-fused 1,2,4-triazoles using a mild and
straightforward one-pot oxidative cyclization method
using TCCA which is a low cost commercially available
reagent. A variety of substituents are tolerated allowing
the synthesis of diverse products in good to excellent
yields. The main advantage of this procedure is to access
N-fused 1,2,4-triazoles with high yields and short reaction
time. The newly developed synthetic route is believed to
be valuable for the construction of building blocks and
also for medicinal chemistry studies comprising N-fused
(500 MHz, CDCl ): δ 7.84 (d, J = 9.3 Hz, 1H), 7.80 (d,
3
J = 7.0 Hz, 1H), 7.51–7.45 (m, 2H), 7.45–7.40 (m, 1H),
7.37 (td, J = 7.3, 1.4 Hz, 1H), 7.30 (ddd, J = 9.3, 6.5,
1.2 Hz, 1H), 6.84 (td, J = 6.7, 1.1 Hz, 1H), 2.27 (s, 3H);
13
C-NMR (126 MHz, CDCl ): δ 149.8, 146.3, 138.6,
3
131.1, 130.5, 130.3, 127.1, 126.3, 125.6, 122.7, 116.6,
113.9, 19.8; LCMS: m/z = 210 [M + H] ; calcd for
+
C H N : C, 74.62; H, 5.30; N, 20.08. Found: C, 74.59;
13 11 3
H, 5.28; N, 20.05.
1,2,4-triazole moiety.
3-(3-(Trifluoromethyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine
(
1
3c). Light yellow solid; yield: 102.5 mg (85%); m.p.
1
54–156°C; H-NMR (500 MHz, CDCl ): δ 8.28 (d,
3
EXPERIMENTAL
All solvents and reagents were purchased
J = 7.0 Hz, 1H), 8.14 (d, J = 1.7 Hz, 1H), 8.11–8.05 (m,
H), 7.89 (d, J = 9.3 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H),
7.76 (t, J = 7.8 Hz, 1H), 7.36 (ddd, J = 9.3, 6.5, 1.1 Hz,
1
General.
13
from commercial sources and used without further
purification. Melting points were determined on a Stuart
SMP3 melting point apparatus without corrections.
1H), 6.97 (td, J = 6.8, 1.1 Hz, 1H); C-NMR (126 MHz,
CDCl ): δ 150.7, 145.4, 131.9 (q, J (C, F) = 33.1 Hz),
3
131.3, 130.0, 127.6, 127.5, 126.9 (q, J (C, F) = 3.9 Hz),
1
13
H-NMR and
C-NMR spectra were recorded on
125.1 (q, J (C, F) = 3.9 Hz), 122.3, 117.0, 114.9; LCMS:
+
AV-500 Bruker using the solvents indicated with 500
and 126 MHz, respectively. Elemental analyses
were performed with a VarioEL analyzer. Liquid
chromatography mass spectra were obtained on a Waters
ACQUITY LCMS/Xevo G2QTof instrument. TLC was
performed on silica gel 60 F254 (Merck) TLC plates
using hexane/EtOAc (3:2 v/v) as the mobile phase.
Column chromatography was carried out using Merck
silica gel (200–300 mesh) and hexane/EtOAc (3:2 v/v) as
the eluent.
m/z = 264 [M + H] ; calcd for C13
H
8
F
3
N
: C, 59.32; H,
3
3.06; N, 15.96. Found: C, 59.30; H, 3.01; N, 15.93.
3-(4-Chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridine (3d).
Off-white solid; yield: 94.5 mg (90%); m.p. 198–200°C;
1
H-NMR (500 MHz, CDCl ): δ 8.25 (dt, J = 7.0, 1.2 Hz,
3
1H), 7.84 (dt, J = 9.3, 1.2 Hz, 1H), 7.81–7.76 (m, 2H),
7.60–7.53 (m, 2H), 7.31 (ddd, J = 9.3, 6.5, 1.1 Hz, 1H),
1
3
6.91 (ddd, J = 7.5, 6.6, 1.1 Hz, 1H);
(126 MHz, CDCl ): δ 150.6, 145.8, 136.4, 129.7, 129.5,
127.3, 125.1, 122.4, 116.9, 114.6; LCMS: m/z = 230
C-NMR
3
+
[
M + H] ; calcd for C H ClN : C, 62.76; H, 3.51; N,
General procedure for the one-pot synthesis of N-fused
,2,4-triazole 3a–n. To a stirred solution of heterocyclic
12 8 3
1
18.30. Found: C, 62.73; H, 3.47; N, 18.26.
hydrazine 1 (1 mmol) and aldehyde 2 (1.2 mmol) in
3-(4-Bromophenyl)-[1,2,4]triazolo[4,3-a]pyridine (3e).
Ethanol (10 mL) were added TCCA (232.41 mg,
White solid; yield: 113.9 mg (91%); m.p. 200–202°C;
1
1
mmol). The mixture was stirred at ambient temperature
until the starting material was completely consumed
monitored by TLC, 10 min.). The reaction mixture was
H-NMR (500 MHz, CDCl ): δ 8.26 (d, J = 7.1 Hz, 1H),
3
7.86 (d, J = 9.3 Hz, 1H), 7.74 (s, 4H), 7.32 (ddd, J = 9.3,
6.5, 1.1 Hz, 1H), 6.92 (ddd, J = 7.4, 6.6, 1.1 Hz, 1H);
(
13
quenched with sat. NaHCO3 solution (20 mL) and
extracted with ethyl acetate (50 mL). The organic layer
was washed with water (40 mL), dried over Na SO ,
C-NMR (126 MHz, CDCl
): δ 150.7, 145.8, 132.6,
3
129.6, 127.2, 125.6, 124.7, 122.4, 117.0, 114.6; LCMS:
+
m/z = 274 [M + H] ; calcd for C12H BrN : C, 52.58; H,
8 3
2
4
and evaporated. The resulting crude compound was
purified by silica gel column chromatography (EtOAc/
hexane, 4:6 v/v), affording the pure N-fused 1,2,4-
triazole 3.
2.94; N, 15.33. Found: C, 52.55; H, 2.91; N, 15.29.
3-(4-Methoxyphenyl)[1,2,4]triazolo[4,3-a]pyridine (3f).
Off-white solid; yield: 101.1 mg (98%); m.p. 122–124°C.
1
H-NMR (500 MHz, CDCl ): δ 8.23 (dt, J = 7.0, 1.2 Hz,
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Bhatt, R. K. Singh, and R. Kant
Vol 000
13
1H), 7.80 (d, J = 9.3 Hz, 1H), 7.77–7.73 (m, 2H), 7.26
1.1 Hz, 1H); C-NMR (126 MHz, DMSO- d ): δ 148.8,
6
(
6
ddd, J = 9.3, 6.5, 1.1 Hz, 1H), 7.09 (d, J = 8.7 Hz, 2H),
.84 (td, J = 6.8, 1.0 Hz, 1H), 3.89 (s, 3H); C-NMR
142.8, 136.1, 127.1, 125.6, 125.0, 124.3, 122.5, 120.8,
1
3
120.3, 115.6, 113.8, 111.9, 101.3; LCMS: m/z = 235
+
(126 MHz, CDCl ): δ 161.1, 150.4, 146.7, 129.8, 126.9,
[M + H] ; calcd for C H N : C, 71.78; H, 4.30; N,
3
14 10 4
1
22.6, 118.9, 116.8, 114.8, 114.0, 55.5; LCMS: m/
23.92. Found: C, 71.75; H, 4.28; N, 23.89.
+
3
-phenyl-[1,2,4]triazolo[4,3-a]pyrazine (3 l).
Off-white
z = 226 [M + H] ; calcd for C H N O: C, 69.32; H,
4
1
3 11 3
1
.92; N, 18.66. Found: C, 69.29; H, 4.89; N, 18.62.
solid; yield: 81.9 mg (92%); m.p. 161–163°C; H-NMR
4
-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)phenol (3g).
White
solid; yield: 87.1 mg (90%); m.p. 248–250°C. H-NMR
500 MHz, DMSO-d ): δ 10.03 (s, 1H), 8.48 (dd, J = 7.1,
(500 MHz, CDCl ): δ 9.43 (d, J = 1.6 Hz, 1H), 8.23 (dd,
3
1
J = 4.9, 1.7 Hz, 1H), 7.95 (d, J = 4.8 Hz, 1H), 7.90–7.86
13
(
(m, 2H), 7.66–7.61 (m, 3H); C-NMR (126 MHz,
6
1.2 Hz, 1H), 7.81 (dd, J = 9.3, 1.2 Hz, 1H), 7.76–7.64
CDCl ): δ 147.2, 146.0, 145.1, 130.9, 130.4, 129.6,
3
(
(
m, 3H), 7.39 (ddd, J = 9.2, 6.5, 1.1 Hz, 1H), 7.03–6.95
128.1, 125.6, 115.2; LCMS: m/z = 197 [M + H]+; calcd
13
m, 3H); C-NMR (126 MHz, DMSO-d ): δ 159.0,
for C H N : C, 67.34; H, 4.11; N, 28.55. Found: C,
6
11 8 4
1
49.6, 146.2, 129.7, 127.5, 123.8, 117.1, 116.0, 115.6,
67.31; H, 4.09; N, 28.51.
6-Chloro-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine (3m).
+
114.1; LCMS: m/z = 212 [M + H] ; calcd for C H N O:
1
2 9 3
C, 68.24; H, 4.29; N, 19.89. Found: C, 68.21; H, 4.25;
White solid; yield: 71.8 mg (90%); m.p. 197–199°C;
1
N, 19.87.
H-NMR (500 MHz, CDCl ): δ 8.49–8.45 (m, 2H), 8.17
3
3
-(4-Cyanophenyl)-[1,2,4]triazolo[4,3-a]pyridine (3h).
(d, J = 9.6 Hz, 1H), 7.61–7.54 (m, 3H), 7.17 (d,
1
13
White solid; yield: 85.7 mg (85%); m.p. 261–263°C; H-
J = 9.6 Hz, 1H); C-NMR (126 MHz, CDCl ): δ 149.4,
3
NMR (500 MHz, CDCl ): δ 8.35–8.31 (m, 1H), 8.06–
148.1, 143.6, 130.7, 128.8, 127.7, 126.6, 125.5, 121.8;
3
+
8.01 (m, 2H), 7.90 (dd, J = 8.8, 1.8 Hz, 3H), 7.38 (ddd,
LCMS: m/z = 231 [M + H] ; calcd for C H ClN : C,
11
7
4
J = 9.3, 6.6, 1.1 Hz, 1H), 6.99 (td, J = 6.8, 1.1 Hz, 1H);
57.28; H, 3.06; N, 24.29. Found: C, 57.25; H, 3.02; N,
24.26.
1
3
C-NMR (126 MHz, CDCl ): δ 151.0, 145.0, 133.1,
3
1
31.1, 128.5, 127.7, 122.3, 118.0, 117.2, 115.1, 113.8;
3-Phenyl-[1,2,4]triazolo[4,3-a]pyrimidine (3n).
White
solid; yield: 76.6 mg (86%); m.p. 174–176°C; H-NMR
(500 MHz, CDCl ): δ 8.70 (dd, J = 3.8, 1.9 Hz, 1H),
8.64 (dd, J = 7.0, 1.9 Hz, 1H), 7.87–7.81 (m, 2H), 7.64–
+
1
LCMS: m/z = 221 [M + H] ; calcd for C H N : C,
1
3 8 4
70.90; H, 3.66; N, 25.44. Found: C, 70.88; H, 3.62; N,
3
2
5.41.
13
5
-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-4-methylthiazole
7
.55 (m, 3H), 6.98 (dd, J = 7.0, 3.8 Hz, 1H); C-NMR
(
1
3i).
Brown solid; yield: 79.2 mg (80%); m.p. 127–
(
1
126 MHz, CDCl ): δ 154.1, 153.9, 145.7, 130.8, 130.7,
29.5, 128.0, 125.9, 110.2; LCMS: m/z = 197 [M + H] ;
3
1
29°C; H-NMR (500 MHz, CDCl ): δ 9.00 (s, 1H), 8.01
+
3
(dt, J = 6.9, 1.1 Hz, 1H), 7.89 (dt, J = 9.3, 1.2 Hz, 1H),
calcd for C H N : C, 67.34; H, 4.11; N, 28.55. Found:
11 8 4
7
1
.38 (ddd, J = 9.3, 6.5, 1.1 Hz, 1H), 6.97 (td, J = 6.7,
.0 Hz, 1H), 2.58 (s, 3H); C-NMR (126 MHz, CDCl3):
C, 67.31; Hs, 4.09; N, 28.52.
1
3
δ 155.7, 154.1, 150.5, 139.2, 127.7, 122.6, 116.9, 115.0,
+
1
14.8, 16.6; LCMS: m/z = 217 [M + H] ; calcd for
Acknowledgment. The authors are thankful to Department of
Chemistry, Mewar University, Chittorgarh, Rajasthan, for
experimental and spectroscopic analysis of synthesized
compounds.
C H N S: C, 55.54; H, 3.73; N, 25.91. Found: C, 55.51;
1
0 8 4
H, 3.71; N, 25.88.
3
-(Furan-2-yl)-[1,2,4]triazolo[4,3-a]pyridine (3j).
brown solid; yield: 74.6 mg (88%); m.p. 92–94°C; H-
Light
1
NMR (500 MHz, CDCl ): δ 8.75 (d, J = 7.1 Hz, 1H),
3
7.83 (d, J = 9.3 Hz, 1H), 7.70–7.67 (m, 1H), 7.34–7.26
REFERENCES AND NOTES
(
m, 2H), 6.94 (td, J = 6.8, 1.1 Hz, 1H), 6.66 (dd, J = 3.5,
[
[
1] Bhatt, A.; Singh, R. K.; Kant, R. Chem Biol Lett 2016, 3, 38.
2] Bhatt, A.; Singh, R. K.; Kant, R. Chem Biol Lett 2017, 4, 73.
13
1
1
1
.8 Hz, 1H); C-NMR (126 MHz, CDCl ): δ 149.9,
3
43.6, 143.0, 139.6, 127.5, 124.3, 116.6, 114.6, 112.1,
[3] Endo, K.; Deguchi, K.; Matsunaga, H.; Tomaya, K.; Yamada,
K. Bioorg Med Chem 2014, 22, 3072.
+
11.2; LCMS: m/z = 186 [M + H] ; calcd for C H N O:
1
0 7 3
[
4] Nagamatsu, T.; Fujita, T.; Endo, K. J Chem Soc, Perkin Trans
2000 33.
5] Nagamatsu, T.; Yamasaki, H.; Fujita, T.; Endo, K.; Machida,
C, 64.86; H, 3.81; N, 22.69. Found: C, 64.82; H, 3.79;
N, 22.65.
1
[
3
-(1H-Indol-3-yl)-[1,2,4]triazolo[4,3-a]pyridine (3k).
H. J Chem Soc, Perkin Trans 1 1999 3117.
Pinkish-white solid; Yield: 88.01 mg (82%); m.p. 244–
[6] Kobe, B.; Kobe, J.; Smee, D. F.; Jerman-Blazic-Dzonova, B.;
Solmajer, T. Eur J Med Chem 1992, 27, 259.
1
2
8
8
1
6
7
46°C; H-NMR (500 MHz, DMSO-d ): δ 11.89 (s, 1H),
6
[7] Mukaiyama, H.; Nishimura, T.; Kobayashi, S.; Ozawa, T.;
.65 (dt, J = 7.1, 1.1 Hz, 1H), 8.26 (d, J = 2.8 Hz, 1H),
.16 (dd, J = 7.8, 1.0 Hz, 1H), 7.84 (dt, J = 9.3, 1.2 Hz,
H), 7.55 (dt, J = 8.0, 0.9 Hz, 1H), 7.40 (ddd, J = 9.3,
.5, 1.1 Hz, 1H), 7.26 (ddd, J = 8.1, 7.0, 1.3 Hz, 1H),
.19 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H), 7.03 (td, J = 6.7,
Kamada, N.; Komatsu, Y.; Kikuchi, S.; Oonota, H.; Kusama, H. Bioorg
Med Chem 2007, 15, 868.
[
8] Ozawa, T.; Tsuji, E.; Ozawa, M.; Handa, C.; Mukaiyama, H.;
Nishimura, T.; Kobayashi, S.; Okazaki, K. Bioorg Med Chem 2008, 16, 10311.
9] Wencheng, X.; Linna, Z.; Yanzhen, Y.; Dezhi, Y.; Guisen, Z.
Chem Biol Lett 2014, 1, 44.
[
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
One-pot Synthesis of N-fused 1,2,4-Triazoles
[10] Kumar, P.; Achieng, A. O.; Rajendran, V.; Ghosh, P. C.;
[25] Jørgensen, M.; Bruun, A. T.; Rasmussen, L. K.; Larsen, M.
Singh, B. K.; et al. Sci Rep 2017, 7, 6724.
WO2013034755A1, 2013.
[
11] Collin, X.; Sauleau, A.; Coulon, J. Bioorg Med Chem Lett
003, 13, 2601.
12] Papakonstantinou-Garoufalias, S.; Pouli, N.; Marakos, P.;
Chytyroglou-Ladas, A. Farmacoterapia 2002, 57, 973.
[26] Kumar, D.; Chandra, S. K.; Dhillon, H.; Rao, V. S.; Varma, R.
S. Green Chem 2004, 6, 156.
[27] Dubey, P. K.; Naidu, A.; Kumar, K. S. Org Chem: Indian J
2008, 4, 475.
2
[
[
[
13] De Clercq, E. J Clin Virol 2004, 30, 115.
14] Navidpour, L.; Shadnia, H.; Shafaroodi, H.; Amini, M.;
[28] Aggarwal, R.; Sumran, G. Synth Commun 2006, 36, 1873.
[29] Nitlikar, L. H.; Darandale, S. N.; Shinde, D. B. Lett Org Chem
2013, 10, 348.
[30] Graceffa, R.; Kaller, M.; La, D.; Lopez, P.; Patel, V. F.; Zhong,
W. US20100120774A1, 2010.
[31] Kim, D.; Wang, L.; Beconi, M.; Eiermann, G. J.; Fisher, M.
H.; He, H.; Hickey, G. J.; Kowalchick, J. E.; Leiting, B.; Lyons, K.;
Marsilio, F.; McCann, M. E.; Patel, R. A.; Petrov, A.; Scapin, G.; Patel,
S. B.; Roy, R. S.; Wu, J. K.; Wyvratt, M. J.; Zhang, B. B.; Zhu, L.;
Thornberry, N. A.; Weber, A. E. J Med Chem 2005, 48, 141.
[32] Guan, L. P.; Zhang, R. P.; Chang, Y.; Gan, X. X. Asian J
Chem 2013, 25, 3660.
Dehpour, A. R.; Shafiee, A. Bioorg Med Chem 2007, 15, 1976.
15] Naito, Y.; Akahoshi, F.; Takeda, S.; Okada, T.; Kajii, M.;
Nishimura, H.; Sugiura, M.; Fukaya, C.; Kagitani, Y. J Med Chem
996, 39, 3019.
16] Saha, A. K.; Liu, L.; Simoneaux, R.; Decorte, B.; Meyer, C.;
Skrzat, S.; Breslin, H. J.; Kukla, M. J.; End, D. W. Bioorg Med Chem Lett
[
1
[
2
005, 15, 5407.
[
971, 14, 1078.
[
17] Hester, J. B. Jr.; Rudzik, A. D.; Kamdar, B. V. J Med Chem
1
18] Hitotsuyanagi, Y.; Motegi, S.; Fukaya, H.; Takeya, K. J Org
Chem 2002, 67, 3266.
[33] Comas, H.; Bernardinelli, G.; Swinnen, D. J Org Chem 2009,
74, 5553.
[34] Bourgeois, P.; Cantegril, R.; Chêne, A.; Gelin, J.; Mortier, J.;
Moyroud, J. Synth Comm 1993, 23, 3195.
[
[
[
19] Dash, C.; Shaikh, M. M.; Ghosh, P. J Chem Sci 2011, 123, 97.
20] Holm, S. C.; Straub, B. F. Org Prep Proced Int 2011, 43, 319.
21] Meanwell, N. A.; Romine, J. L.; Rosenfeld, M. J.; Martin, S.
W.; Trehan, A. K.; Wright, J. J. K.; Malley, M. F.; Gougoutas, J. Z.;
Brassard, C. L.; Buchanan, J. O.; Federic, M. E.; Fleming, J. S.;
Gamberdella, M.; Hartl, K. S.; Zavoico, G. B.; Seiler, S. M. J Med Chem
1
993, 36, 3884.
22] Aggarwal, R.; Sumran, G.; Kumar, R.; Aggarwal, A.; Parkash,
V. Indian J Heterocycl Chem 2006, 16, 1.
23] utchinson, J. H.; Seiders, T. J.; Stearns, B. A.; Wang, B.; Scott,
J.M.; Truong, Y. P. H US 20070173508A1, 2007.
24] Jørgensen, M.; Bruun, A. T.; Rasmussen, L. K. WO
013034758A1, 2013.
SUPPORTING INFORMATION
[
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
[
[
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet