The efficient synthesis of 3-[6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole

Article abstract of DOI:10.1002/jhet.3866

This study presents an efficient synthesis of 3-[6-(substituted-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-yl]-1H-indazole via dehydrative condensation with cyclization of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol and fluorinated or nonfluorinated carboxylic acids in presence of phosphorous oxychloride. The multistep reaction pathway proceeds through different compounds. Present synthesis has the advantages of easily accessible starting materials, convenient synthesis, simple reaction condition, wider substrate scope, and higher yield (75% to 90% isolated).

Full text of DOI:10.1002/jhet.3866

Received: 13 October 2019
DOI: 10.1002/jhet.3866
Revised: 6 December 2019
Accepted: 7 December 2019
A R T I C L E
The efficient synthesis of 3-[6-(substituted)-[1,2,4]triazolo
3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole
[
Santosh Raut | Abdul Hadi | Mohd Arif Pathan
Chemistry Department, Maulana Azad
Abstract
College of Arts, Science and Commerce,
Aurangabad, Maharashtra, India
This study presents an efficient synthesis of 3-[6-(substituted-phenyl)-[1,2,4]triazolo
3,4-b][1,3,4] thiadiazol-3-yl]-1H-indazole via dehydrative condensation with cycli-
[
Correspondence
zation of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol and fluorinated or
nonfluorinated carboxylic acids in presence of phosphorous oxychloride. The multi-
step reaction pathway proceeds through different compounds. Present synthesis has
the advantages of easily accessible starting materials, convenient synthesis, simple
reaction condition, wider substrate scope, and higher yield (75% to 90% isolated).
Mohd Arif Pathan, Chemistry
Department, Maulana Azad College of
Arts, Science and Commerce,
Aurangabad, Maharashtra, India.
Email: arif7172@rediffmail.com
[14,15]
1
| INTRODUCTION
like analgesic, anti-inflammatory, ulcerogenic,
antibacterial.
and
[16]
A large number of fluorinated and nonfluorinated hetero-
cyclic compounds show various pharmacological activi-
ties. Because of this, organic chemists work day and
night to synthesize more active pharmacophores. A liter-
ature survey revealed that indazole derivatives are the
least studied among all the heterocycles studied for their
medicinal activities, although natural products con-
taining indazole moieties are rare.
The literature survey shows that synthetic indazole
derivatives give biological activities like anti-inflamma-
The precedent literature shows that various catalyses
and methods have been reported by different researchers
for the synthesis of indazoles and its derivatives. The fre-
quently used procedures involve chromium tricarbonyl
[17]
[18]
complex,
3-carboxyindazole,
polyphosphoric acid–catalyzed cyclization of
trimethylsilylindazole/
[19]
CSF,
2,6-dihydroxyacetophenone hydrazones, using NaHSO3/
[20]
[1]
[21]
DMF,
palladium-catalyzed intramolecular amination
[22]
reaction of N-tosyl hydrazones trimethylsilylindazole as
[23]
well as aryl halides,
catalyzed synthesis of indazole.
fluorobenzaldehydes and their oximes with hydrazine yield
and copper metal complex–
[
2]
[3]
[4]
[5]
[24]
tory,
contraceptive properties,
estrogen receptor, inhibition of protein kinase, and
antimicrobial,
anti-HIV,
antitumor,
and
Condensation of o-
[6]
high binding affinity for
[
7]
[25]
indazoles,
while 3-substituted indazole and ben-
[8]
5
-HT-2 and HT-3 receptor antagonism ; selective
zoisoxazoles synthesis via palladium catalyzed cyclization
[26]
compound 3-aminoindazole is a nonsteroidal anti-
reactions indazole N-oxide through 1,7-electrocyclization
[
9]
[27]
inflammatory candidate with analgesic properties. It
is also reported as a dopamine receptor antagonist
of azomethine ylides
cyclization of o-substituted aryl
[28]
hydrazones with halogens, nitro and methoxy
group as
[10]
used for antipsychotic treatment.
Fluorinated
substituent are already reported in the literature. A similar
3
-aminoindazoles have been used in psychiatric disorders
type of simple derivatives is also synthesized by various
[11]
[29–31]
such attention deficit disorder.
Not only indazole
researchers
using POCl3.
derivatives are biologically active; a combination of
triazolo with thiadiazoles is also a potent active antimi-
crobial agent.
The compounds having 1,2,4-triazolo[3,4-b]-1,3,4-thia-
diazole nucleus also exhibit various biological activities
Keeping the importance of indazole and combination
of triazolo with thiadiazoles derivatives, the research
group decided to synthesize 3-[6-(substituted-phenyl)-
[1,2,4]triazo-lo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole
using simple, efficient, and convenient method.
[12,13]
J Heterocycl Chem. 2020;1–15.
wileyonlinelibrary.com/journal/jhet
© 2020 John Wiley & Sons, Ltd.
1

2
RAUT ET AL.
2
| RESULTS AND DISCUSSION
3-carboxylic acid hydrazide dithiocarbamate is neutral-
ized with 50% hydrochloric acid, it gives 5-(1H-indazol-
[
32,33]
The method used for the multistep synthesis of fluori-
nated and nonfluorinated 3-[6-(substituted-phenyl)-
3-yl)-[1,3,4]oxadiazole-2-thiol 6
with strong smell of
H S gas; then, the obtained product was refluxed in
2
[
8
1,2,4]triazolo[3,4-b][1, 3, 4] thiadiazol-3-yl]-1H-indazole
(a-v) was based on the commercial availability of raw
excess of hydrazine hydrate to form 4-amino-5-(1H-
indazol-3-yl)-4H-[1,2,4]triazole-3-thiol 5 (Scheme 3). But
in the present work, 1 Eq potassium salt of 1H-indazole-
3-carboxylic acid hydrazide dithiocarbamate 4 is directly
reacted with 2 Eq of hydrazine hydrate in water as sol-
material, conventionality, and handling simplicity, thus
for the synthesis of the aimed products, condensation
and cyclization reaction appeared to be the best and most
precise in presence of phosphorous oxychloride. The
well-known and simple esterification reaction was per-
formed for the synthesis of 1H-indazole-3-carboxylic acid
ethyl ester 2. 1H-indazole-3-carboxylic acid ethyl ester
then reacted with excess amount of hydrazine hydrate
under reflux in ethanol solvent to selectively afford 1H-
indazole-3-carboxylic acid hydrazide 3 (Scheme 1). The
ꢀ
ꢀ
vent at 90 C to 95 C to form 5 with 92% of isolated yield
(Scheme 2).
Spectroscopic
methods
like
infrared
1
(IR) spectroscopy, mass spectroscopy, and H NMR con-
firmed the formation of intermediate 6 from neutraliza-
tion of 4 with 50% hydrochloric acid. IR spectroscopic
−
1
values were at 660 to 782 cm for aromatic protons ArH,
1248 cm− for cyclic C─N bond vibrations, 1615 cm for
1
−1
1
H-indazole-3-carboxylic acid hydrazide obtained in the
−
1
second step were reacted with carbon disulfide and potas-
sium hydroxide in presence of absolute alcohol, and the
reaction mass was stirred for 12 hours to obtain potas-
sium salt of 1H-indazole-3-carboxylic acid hydrazide
dithiocarbamate 4. If the potassium salt of 1H-indazole-
the C N vibrations, 1360 cm for cyclic ether (C─O),
and 3066 cm− for cyclic amines (N─H). Mass spectra at
218.81 also support the intermediate 6 formation. For the
1
1
H NMR study, δ 7.25-8.53 multiplates for aromatic pro-
tons were present on indazole-fused benzene ring, singlet
NH2
O
O
COOH
N
O
NH
.
C H OH
NH NH H O
2 2 2
2
5
N
N
N
N
H SO , Reflux.
N
C H OH, Reflux.
88.63%
H
2
4
2
5
H
H
3
1
2
CS , KOH,
2
7
3.68%
C H OH, rt.
2
5
SK
S
SH
N
HN
NH
N
O
N
NH2
.
NH NH H O,
2
2
2
N
N
N
O
N
H O, 90-95 C.
2
H
H
SCHEME 1 Synthesis of 4-
Amino-5-(1H-indazol-3-yl)-4H-
5
4
90%
82%
[1,2,4] triazole-3-thiol 5 from 4
SK
S
SH
SH
N
N
N
HN
NH
N
O
O
N
NH2
.
NH NH H O,
5
0% HCl,
2
2
2
N
N
N
H O, 90-95 OC.
N
2
N
H
N
Neutralized,
H S.
SCHEME 2 Synthesis of 4-Amino-5-
(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-
thiol 5 from 5-(1H-Indazol-3-yl)-[1,3,4]
oxadiazole-2-thiol 6
H
H
-
2
5
4
6
8
4%
8
8.24%

RAUT ET AL.
3
SH
NH
substituted cinnamic acid 7i and 7u and 4-amino-5-(1H-
N
N
S
N
1
N
N
R1
indazol-3-yl)-4H-[1,2,4]tria-zole-3-thiol 5. From the
H
N
N
2
O
NMR spectroscopic data, J = 16.0 to 16.8 values of two
protons on the double bond in both compounds 8i and
8u respectively have trans (E) geometry as given in
(Scheme 1).
Similarly, 3-[6-(2-trifluoromethyl-pyridin-3-yl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole 8t is
successively synthesized from 2-trifluoromethyl-nicotinic
acid 7t. Under the standard reaction condition, the con-
densation of 5 and 7t gives 8t with 86% of yield in 4 hours
POCl3,
0-95 OC.
N
+
R
1
OH
N
N
9
N
H
H
7
(a and m)
a = R = C H
6 5
5
8
(a and m)
8a = R = C H
6 5
7
1
1
7m = R = 4-FC H
8m = R = 4-FC H
1
6 4
1 6 4
SCHEME 3 Cyclization of 5 and 7(a-v) to form 8(a-v)
(
Scheme 5). A similar type of molecules possesses pyri-
was at δ 3.36 for S─H proton, and highly deshielded pro-
ton from indazole N─H gives singlet chemical shift at
δ 13.48.
Finally, the intermolecular condensation or cycliza-
tion of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-
dine ring without trifluoromethyl group, and the indazole
[
14,15]
part shows various biological activities.
In the pre-
sent study, the compound bearing the trifluoromethyl
group and indazole nucleus was synthesized, which may
have enhance the biological activity of compound 8t.
When aliphatic carboxylic acid ie. trifluoro acetic acid
is reacted with 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]tri-
azole-3-thiol 5 under standard reaction condition to
3
-thiol 5 with substituted-carboxylic acid 7(a-v) gives
desired products 3-[6-(substituted-phenyl)-[1,2,4]triazolo
3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole 8(a-v) in 75% to
0% yield shown in Table 1 (Scheme 4). In the present
[
9
afford
3-(6-trifluoromethyl-[1,2,4]triazolo[3,4-b][1,3,4]
synthesis, we used 0.01 mol of 5 and 0.02 mol of 7(a-v) to
shift the equilibrium fast towards product formation;
excess amounts of substituted-carboxylic acid 7(a-v)
were easily separated from the reaction mass by
simple neutralization using saturated solution of sodium
bicarbonate.
We optimize the standard reaction condition for the
synthesis of the final product, ie, substituted-carboxylic
acid 7(a-v) (0.02 mol) and 4-amino-5-(1H-indazol-3-yl)-
thiadiazol-3-yl)-1H-indazole 8v with 80% yield within
5 hours of reaction time.
If the reverse synthesis is carried out by the prepara-
tion of 4-amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole-
3-thiol 9 from 4-methoxy-benzoic acid, then 1H-indazole-
3-carboxylic acid 1 is reacted with 4-methoxy-benzoic acid
9 to afford 3-[3-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-b]
[1,3,4] thiadiazol-6-yl]-1H-indazole 10 (Scheme 7) instead
[
1,3,4]
of 3-[6-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-b]
diazol-3-yl]-1H-indazole 8k.
thia-
4
H-[1,2,4]triazole-3-thiol 5 (0.01 mol) in POCl (15 mL)
3
ꢀ
ꢀ
was heated at 90 C to 95 C for a time as mentioned in
Table 1. The excess of carboxylic acid shift equilibrium
fast towards the product formation, and after completion
of the reaction, the excess amount of carboxylic acid is
neutralized with aqueous concentrated sodium bicarbon-
ate solution to afford a pure product. We also studied the
The spectroscopic data of all synthesized compounds
show the formation of particular products, ie, compound
−1
8a has IR band at 747 to 846 cm for indazole ring C─H
−1
vibrations, 1248 cm for cyclic C─N bond vibrations,
1549 cm− for the C N vibrations, 1694 cm for aro-
1
−1
matic protons ArH, and cyclic amines (N─H) at
−1
effect of combined solvents like ethanol and POCl with
2913 cm . Mass spectra at 319 also confirm the product
3
1
different proportions as reported in Table 2 for com-
formation. For the H NMR study, δ 7.45 to 7.76 is for aro-
pounds 8a and 8 m. We observed that 5 mL of POCl and
matic protons present on phenyl ring (m, 5H, ArH), for δ
8.29 to 8.73, these chemical shift values for aromatic pro-
tons present on indazole fused benzene ring, and highly
deshielded proton from indazole N─H gives singlet at
14.26. Fourteen different carbons associated with 8a also
give 14 C NMR signals, and these confirm the product.
The indazoles shows various biological activities, and
their combination with two fused five-member heterocy-
clic rings containing nitrogen and sulfur atoms enhances
the biological activities. Similarly synthesized compounds
having fluorine atoms may also show good biological
activities to the nonfluorinated compounds. Recently,
3
1
0 mL of ethanol give good results, but changing the pro-
portion of POCl and ethanol or vise versa gives unac-
3
ceptable results with more fluctuation on both products.
We also found that an amount of POCl in excess of or
3
13
less than 10 mL adversely affects the percent yield as well
as the time required for completion. So, finally, we
decided to synthesize the aimed products using 10 mL of
ꢀ
ꢀ
POCl at 90 C to 95 C and make it a standard procedure
3
for further synthesis of other derivatives.
Secondly, we are reporting the synthesis of products
containing C C (from cinnamic group) bond by using

4
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5

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8
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9
researchers are focus on the synthesis of fluorinated com-
pounds; fluorine gives a hydrophilic and lipophilic
nature to compound, and because of these properties, its
compounds are more biologically active. Hence, here,
we are reporting the synthesis of heterocyclic com-
pounds having indazole bearing fused five-member het-
erocyclic rings with fluorinated and nonfluorinated
phenyl groups.
3 | CONCLUSION
In summary, we disclosed a series of efficient synthesis of
3-[6-(substituted-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadi
azol-3-yl]-1H-indazole via dehydrative condensation with
cyclization of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]tri-
azole-3-thiol and fluorinated or nonfluorinated carboxylic
acids in presence of phosphorous oxychloride. The multi-
step reaction pathway proceeds through a number of
different compounds. The advantages of the present syn-
thesis were convenient synthesis, simple reaction condi-
tion, easily accessible starting materials, 75% to 90% of
isolated yield, and wider substrate scope.
N
S
N
N
N
Z
COOH POCl ,
3
+
5
N
4 | EXPERIMENTAL SECTION
4.1 | General
Z
0-95 OC.
9
N
H
Z = H = 7i
Z = H = 8i 78%
Z = CF = 7u
3
Z = CF = 8u 85%
3
All condensation/cyclization reactions were performed in
electric oven–dried glassware under atmospheric pressure.
All the starting chemical material, reagents, and solvents
SCHEME 4 Cyclization of 7i or 7u with 5 to form 8i or 8u
TABLE 2 Optimization of reaction
condition at different concentrations of
solvent
a
Entry
POCl
3
in mL
Ethanol in mL
Time, h
7
Compound, % Yield
8a (65)
1
2
3
4
5
6
7
8
9
15
5
--
--
10
8a (62)
10
5
--
4.5
9
8a (86)
10
15
15
--
8a (21)
10
5
13.5
16
8a (35)
8a (18)
15
5
8.5
9
8m (68)
8m (52)
8m (90)
8m (24)
8m (32)
8m (18)
--
10
5
--
5.5
8
1
1
1
0
1
2
10
15
15
10
5
11.5
18.5
Bold values represents optimum condition at which maximum yield is achieved.
a
Isolated yields of product.
N
S
N
N
S
N
N
N
CF3
N
N
N
COOH
POCl3,
O
POCl3,
0-95 OC.
F C
3
+
5
N
+
OH
5
N
90-95 OC.
F
C
3
N
CF3
N
9
N
H
8
t 86%
7v
H
8
v 80%
7t
SCHEME 6 Cyclization of 7v and 5 to form 8v
SCHEME 5 Cyclization of 5 and 7t to form 8t

10
RAUT ET AL.
N
SCHEME 7 Cyclization of 1 and 9 to
form 10
N
N
N
SH
POCl3,
S
N
N
+
1
NH2
N
O
H CO
90-95 C.
3
H CO
3
N
N
9
H
10
82%
used were of analytical grade (AR) and used without further
purification. Melting point of all the synthesized compounds
was taken on a precision melting point apparatus (DBK
instrument), and all are uncorrected. IR spectra of the com-
pounds are obtained in potassium bromide (KBr) disks on a
4.3 | Synthesis of 1H-indazole-
3-carboxylic acid hydrazide (3)
In a clean and dry 250 mL RBF charged 9.5 g (0.05 mol)
of 1H-indazole-3-carboxylic acid ethyl ester (2) and
95 mL (10vol.) of ethyl alcohol, stirred the reaction mass
well. Dropwise addition of 5 g (0.1 mol) of Hydrazine
hydrate was completed in 10 minutes at rt. The reaction
1
13
Bruker IR spectrometer, and H NMR and C spectra were
recorded in CDCl or DMSO solvent on a Bruker Avance-II
3
400 MHz spectrometer. A mass spectrum was recorded on a
ꢀ
Waters ZQ-4000 spectrometer. The yield of the synthesized
compounds mentioned is for isolated product.
mixture is heated to reflux temperature (78 C) for 3 hours.
Progress of reaction was monitored on TLC plate. After
completion of reaction concentrate the reaction mass to
obtain a solid, cooled and filtered out. The products are
recrystallized in methanol as solvent.
4
3
.2 | Synthesis of 1H-indazole-
-carboxylic acid ethyl ester (2)
ꢀ
ꢀ
Weight of dry product 7.8 g, mp 200 C to 202 C, Yield
8.63%.
IR (cm ): 1525-1600 (C C), 1339 (─CH ), 1674
8
−
1
The lotwise addition of 1H-indazole-3-carboxylic acid (1)
6.2 g (0.1 mol) in the previously taken mixture of etha-
nol 162 mL (10vol.) and catalytic amount of sulfuric acid
g (0.051 mol) were completed in 20 minutes at the
3
+
1
(C N), 1596 (amide) 3181 (N─H). Mass (m/z) ES :
1
Expected 177.07, observed 177.00. H NMR (CDCl ) δ
3
5
(ppm): 4.49 (s, 2H, ─NH ), 9.56 (s, 1H, ─NH), 7.23 (d,
2
ꢀ
ꢀ
room temperature (25 C to 28 C) in 500 mL RBF. The
suspension was stirred to form a clear solution. Then, the
reaction mixture was heated to reflux (78 C) for 3 to
J = 8.2 Hz, 1H), 7.41 (dd, J = 8.2, 8.5 Hz, 1H), 7.68 (dd,
J = 8.5, 8.1 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 13.47 (s, 1H,
ꢀ
13
─NH). C NMR (CDCl ) δ (ppm): 111.0, 121.8, 122.0,
3
4
hours. Progress of reaction was checked by using TLC
122.3, 126.9, 138.1, 141.3, and 162.4.
plate in the mobile phase N-hexane: ethyl acetate (8:2).
After completion of reaction, reaction mass was cooled to
rt and poured in 200 mL of water and 100 mL of ethyl
acetate and neutralized with saturated solution of sodium
bicarbonate, and the organic layer was separated. The
aqueous layer was extracted with (50 mL × 2) ethyl ace-
tate. All organic layer was collected and washed with
4.4 | General procedure for the synthesis
of potassium-1H-indazole-3-carboxylic acid
hydrazide dithiocarbamate 4
A mixture of substituted carboxylic acid hydrazide
3 (0.01 mol), KOH (0.84 g, 0.015 mol), and 2 mL CS in
2
1
00 mL water, dried over anhydrous sodium sulfate, and
absolute alcohol 30 mL was stirred for 14 hours at room
temperature (24 C to 30 C), and the product was isolated
by simple evaporation of solvent on Petri dish.
ꢀ
ꢀ
filtered and concentrated on Rota-vapor, and the solid
obtained was filtered, washed with chilled ethyl acetate
(
10 mL), and recrystallized using ethanol.
ꢀ
Weight of dry product 14 g, mp 137 C, Yield 73.68%.
4.5 | General procedure for the synthesis
of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]
triazole-3-thiol 5
−
1
IR (cm ): 1525-1600 (C C), 1670 (C N), 1710 (ester)
+
3
1
3
281 (N─H). Mass (m/z) ES : Expected 191.08, observed
1
91.10. H NMR (CDCl ) δ (ppm): 1.48 (t, J = 14.4 Hz,
3
H), 4.57 (q, J = 14 Hz, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.44
Potassium salt (0.01 mol) 4 was taken in excess of hydra-
ꢀ
(
8
dd, J = 8.0, 7.8 Hz, 1H), 7.65 (dd, J = 7.8, 8.2 Hz, 1H),
.21 (d, J = 8.2 Hz, 1H), 12.46 (s, 1H, NH). C NMR
zine hydrate and 25 mL of water then heated (90 C to
13
ꢀ
95 C) up to the evolution of H S gas completed nearly
2
(
1
CDCl ) δ (ppm): 14.20, 61.16, 111.6, 121.4, 121.6, 123.1,
26.5, 139.7, 141.3, and 163.3.
3 to 5 hours in oil bath. After completion reaction moni-
tored by TLC, mixture was cooled and poured into
3

RAUT ET AL.
11
crushed ice and neutralized with glacial acetic acid. The
white precipitate obtained was filtered and purified by
crystallization from 50% ethanol.
108.00, 110.19, 112.89, 116.61, 118.09, 121.94, 122.49,
128.27, 131.94, 136.94, 138.59, 142.81, 148.73, 152.36.
+
1
Mass (m/z) ES : Expected 233.06, observed 233.20. H
NMR (CDCl ) δ (ppm): 3.02 (s, 1H, S─H), 4.29 (s, 2H,
4.6.3 | 3-[3-(1H-Indazol-3-yl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-6-yl]-
phenol (8c)
3
NH ), 7.33 (d, J = 8.0 Hz, 1H), 7.41 (dd, J = 8.0, 8.3 Hz,
2
1
1
H), 7.66 (dd, J = 8.3, 8.2 Hz, 1H), 8.46 (d, J = 8.2 Hz,
H), 13.48 (s, 1H, ─NH).
ꢀ
ꢀ
+
mp 132 C to 134 C, Mass (m/z) ES : Expected 335.06,
1
observed 335.07. H NMR: δ 3.35 (s, 1H, OH), 7.43 (s, 1H,
4
.6 | General procedure for the synthesis
ArH), 7.63 (d, J = 7.8 Hz, 1H, ArH), 7.79 (dd, J = 7.8,
8.0 Hz, 1H, ArH), 8.07 (d, J = 8.0 Hz, 1H, ArH), 8.50 (d,
J = 7.9 Hz, 1H, ArH), 7.28 (dd, J = 7.9, 8.3 Hz, 1H, ArH),
7.60 (dd, J = 8.3, 8.2 Hz, 1H, ArH), 7.65 (d, J = 8.2 Hz,
of 3-[6-(substituted-phenyl)-[1,2,4]triazolo
[
(
3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole 8
a-v)
1H, ArH), 13.02 (s, 1H, NH).
A mixture of substituted carboxylic acid (0.02 mol) 7(a-v)
and 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol
ꢀ
ꢀ
5
(0.01 mol) in POCl (10 mL) was heated at 90 C to 95 C
4.6.4 | 2-[3-(1H-Indazol-3-yl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-6-yl]-
phenol (8d)
3
for 4 to 6 hours. After completion of reaction observed by
TLC, the reaction mixture was cooled to room temperature
and poured into crushed ice, neutralized with concentrated
sodium bicarbonate solution, and the precipitate that sepa-
rates out was filtered, washed with chilled water, and crys-
tallized from 1:1 solution of ethanol and ethyl acetate.
Secondly, similar synthesis was carried out as the
above procedure with changing 10 mL of POCl3 by
ꢀ
ꢀ
1
+
mp 142 C to 144 C, Mass (m/z) ES : Expected 335.06,
observed 335.12. H NMR: δ 7.21 (d, J = 8.1 Hz, 1H,
ArH), 7.42 (dd, J = 8.1, 7.6 Hz, 1H, ArH), 7.52 (dd,
J = 7.6, 7.5 Hz, 1H, ArH), 7.59 (d, J = 7.5 Hz, 1H, ArH),
7.61 (d, J = 8.0 Hz, 1H, ArH), 7.94 (dd, J = 8.0, 8.2 Hz,
1H, ArH), 8.00 (dd, J = 8.2, 8.6 Hz, 1H, ArH), 8.13 (d,
J = 8.6 Hz, 1H, ArH), 14.02 (s, 1H, NH).
1
0 mL of ethanol containing 5 mL of POCl as solvent at
3
ꢀ
ꢀ
reflux temperature (77 C to 79 C).
4
.6.1 | 3-(6-Phenyl-[1,2,4]triazolo[3,4-b]
4.6.5 | 3-[6-(2-Chloro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8e)
[
1,3,4]thiadiazol-3-yl)-1H-indazole (8a)
ꢀ
ꢀ
−1
mp 247 C to 249 C, IR (cm ): 747-846 (indazole C─H),
694 (ArH), 1248 (C─N), 1549 (C N), 2913 (N─H). Mass
ꢀ
ꢀ
+
1
mp 238 C to 240 C, Mass (m/z) ES : Expected 353.03,
+
1
1
(m/z) ES : Expected 319.07, observed 319.00. H NMR: δ
observed 353.03. H NMR: δ 7.52 (d, J = 7.6 Hz, 1H, ArH),
7
.45-7.76 (m, 5H, ArH), 8.73 (d, J = 8.0 Hz, 1H, ArH), 8.29
7.41 (dd, J = 7.6, 7.9 Hz, 1H, ArH), 7.65 (dd, J = 7.9,
8.0 Hz, 1H, ArH), 7.72 (d, J = 8.0 Hz, 1H, ArH), 8.02 (d,
J = 7.9 Hz, 1H, ArH), 7.37 (dd, J = 7.9, 8.1 Hz, 1H, ArH),
7.58 (dd, J = 8.1, 7.6 Hz, 1H, ArH), 7.69 (d, J = 7.6 Hz, 1H,
(dd, J = 8.0, 7.5 Hz 1H, ArH), 8.33 (dd, J = 7.5, 7.9 Hz, 1H,
1
3
ArH), 8.86 (d, J = 7.9 Hz, 1H, ArH), 14.26 (s, 1H, NH).
C
NMR: δ 112.02, 119.99, 120.98, 124.21, 126.14, 126.36,
28.33, 129.78, 130.80, 135.28, 142.12, 146.06, 153.79, 162.20.
13
1
ArH), 14.34 (s, 1H, NH). C NMR: δ 112.59, 116.23,
120.01, 122.89, 122.98, 124.56, 126.06, 126.79, 128.19,
132.02, 134.49, 138.63, 142.47, 144.94, 158.52, 161.71.
4
.6.2 | 4-[3-(1H-Indazol-3-yl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-6-yl]-
phenol (8b)
4.6.6 | 3-[6-(4-Chloro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8f)
ꢀ
ꢀ
1
+
mp 256 C to 258 C, Mass (m/z) ES : Expected 335.06,
observed 335.19. H NMR: δ 3.37 (s, 1H, OH), 7.35 (d,
J = 8.4 Hz, 2H, ArH), 7.70 (d, J = 8.4 Hz, 2H, ArH), 8.30
ꢀ
1
+
mp 170 C, Mass (m/z) ES : Expected 353.03, observed
(d, J = 8.0 Hz, 1H, ArH), 7.32 (dd, J = 8.0, 8.3 Hz, 1H,
353.09. H NMR: δ 6.39 (d, J = 7.8 Hz, 2H, ArH), 7.58 (d,
ArH), 7.46 (dd, J = 8.3, 8.2 Hz, 1H, ArH), 7.55 (d,
J = 8.2 Hz, 1H, ArH), 13.98 (s, 1H, NH). C NMR: δ
J = 7.8 Hz, 2H, ArH), 8.29 (d, J = 8.2 Hz, 1H, ArH), 7.45
(dd, J = 8.2, 8.4 Hz, 1H, ArH), 7.56 (dd, J = 8.2, 7.9 Hz, 1H,
13

12
RAUT ET AL.
13
ArH), 7.61 (d, J = 7.9 Hz, 1H, ArH), 14.24 (s, 1H, NH).
NMR: δ 111.99, 119.95, 121.16, 124.21, 126.33, 127.17,
28.13, 130.69, 131.24, 135.40, 142.09, 145.18, 150.84, 162.43.
C
7.52 (dd, J = 8.3, 8.0 Hz, 1H, ArH), 7.65 (d, J = 8.0 Hz, 1H,
ArH), 14.23 (s, 1H, NH). C NMR: δ 21.55, 112.03, 121.08,
13
1
121.17, 121.67, 123.02, 124.21, 126.31, 126.94, 127.01,
128.36, 130.34, 130.69, 131.25, 150.35.
4
.6.7 | 3-[6-(4-Nitro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8g)
4.6.11 | 3-[6-(4-Methoxy-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8k)
ꢀ
ꢀ
+
mp 180 C to 182 C, Mass (m/z) ES : Expected 364.06,
observed 364.06. H NMR: δ 8.07 (d, J = 8.7 Hz, 2H,
ArH), 7.65 (d, J = 8.7 Hz, 2H, ArH), 8.09 (d, J = 8.0 Hz,
1
ꢀ
ꢀ
+
mp 208 C to 210 C, Mass (m/z) ES : Expected 349.08,
1
observed 349.09. H NMR: δ 3.84 (s, 3H, OCH ), 7.20 (d,
3
1
H, ArH), 7.27 (dd, J = 8.0, 8.2 Hz, 1H, ArH), 7.30 (dd,
J = 8.0 Hz, 2H, ArH), 7.51 (d, J = 8.0 Hz, 2H, ArH), 8.35
(d, J = 8.2 Hz, 1H, ArH), 7.00 (dd, J = 8.2, 8.6 Hz, 1H,
ArH), 7.20 (dd, J = 8.6, 8.0 Hz, 1H, ArH), 7.88 (d,
J = 8.0 Hz, 1H, ArH), 13.99 (s, 1H, NH). C NMR: δ 56.15,
111.25, 114.15, 115.30, 121.23, 122.52, 124.15, 127.50,
J = 8.2, 8.0 Hz, 1H, ArH), 7.65 (d, J = 8.0 Hz, 1H, ArH),
13
14.01 (s, 1H, NH). C NMR: δ 110.00, 112.26, 114.50,
118.71, 121.67, 122.77, 123.02, 126.94, 128.23, 142.94,
144.18, 148.59, 152.10, 159.31.
13
131.75, 141.22, 142.78, 154.19, 162.43, 163.22, 167.70.
4
.6.8 | 3-[6-(3-Nitro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8h)
4.6.12 | 4-[3-(1H-Indazol-3-yl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-6-yl]-
phenylamine (8l)
ꢀ
ꢀ
1
+
mp 210 C to 212 C, Mass (m/z) ES : Expected 364.06,
observed 364.09. H NMR: δ 8.41 (s, 1H, ArH), 8.44 (d,
J = 8.2 Hz, 1H, ArH), 8.22 (dd, J = 8.2, 7.6 Hz, 1H, ArH),
ꢀ
ꢀ
1
+
mp 188 C to 190 C, Mass (m/z) ES : Expected 334.08,
8
.31 (d, J = 7.6 Hz, 1H, ArH), 8.53 (d, J = 8.4 Hz, 1H,
observed 334.08. H NMR: δ 3.42 (s, 2H, NH ), 6.20 (d,
2
ArH), 7.72 (dd, J = 8.4, 8.1 Hz, 1H, ArH), 8.29 (dd,
J = 8.1, 7.6 Hz, 1H, ArH), 8.35 (d, J = 7.6 Hz, 1H, ArH),
J = 8.7 Hz, 2H, ArH), 6.71 (d, J = 8.7 Hz, 2H, ArH), 7.32
(d, J = 8.1 Hz, 1H, ArH), 7.50 (dd, J = 8.1, 8.2 Hz, 1H,
ArH), 7.72 (dd, J = 8.2, 8.0 Hz, 1H, ArH), 8.29 (d,
J = 8.0 Hz, 1H, ArH), 13.75 (s, 1H, NH). C NMR: δ
111.21, 113.03, 114.11, 121.09, 121.77, 122.53, 127.52,
13
14.38 (s, 1H, NH). C NMR: δ 112.92, 117.99, 118.98,
121.01, 124.21, 126.14, 126.30, 128.68, 129.70, 130.80,
135.28, 142.12, 146.06, 153.79, 160.03, 162.20.
13
129.27, 130.07, 131.90, 141.20, 143.28, 148.00, 150.35.
4
.6.9 | 3-(6-Styryl-[1,2,4]triazolo[3,4-b]
[
1,3,4]thiadiazol-3-yl)-1H-indazole (8i)
4.6.13 | 3-[6-(4-Fluoro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8m)
ꢀ
ꢀ
+
mp 142 C to 144 C, ES : Expected 345.09, observed
1
3
45.17. H NMR: δ 2.50 (d, J = 16.2, 1H, CH CH), 3.41 (d,
ꢀ
1
+
J = 16.2, 1H, CH CH), 7.28-7.47 (m, 5H, ArH), 8.09 (d,
J = 8.0 Hz, 1H, ArH), 7.26 (dd, J = 8.0, 8.6 Hz, 1H, ArH),
mp 168 C, Mass (m/z) ES : Expected 337.06, observed
337.23. H NMR: δ 7.42 (d, J = 8.1 Hz, 2H, ArH), 7.58 (d,
7
.50 (dd, J = 8.6, 8.2 Hz, 1H, ArH), 7.60 (d, J = 8.2 Hz, 1H,
J = 8.1 Hz, 2H, ArH), 8.13 (d, J = 7.5 Hz, 1H, ArH), 7.55
13
ArH), 14.36 (s, 1H, NH). C NMR: δ 112.18, 120.13,
1
1
(dd, J = 7.5, 8.0 Hz, 1H, ArH), 7.60 (dd, J = 8.0, 7.8 Hz, 1H,
13
20.98, 123.18, 124.08, 126.23, 126.29, 127.70, 128.49,
30.08, 132.48, 133.52, 134.94, 140.28, 147.00, 148.12.
ArH), 8.07 (d, J = 7.8 Hz, 1H, ArH), 12.16 (s, 1H, NH).
NMR: δ 117.07, 118.09, 121.08, 121.17, 125.06, 127.20,
30.69, 131.25, 146.12, 150.85, 158.01, 164.23, 166.06, 168.14.
C
1
4
.6.10 | 3-(6-p-Tolyl-[1,2,4]triazolo[3,4-b]
[
1,3,4]thiadiazol-3-yl)-1H-indazole (8j)
4.6.14 | 3-[6-(3-Fluoro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8n)
ꢀ
ꢀ
+
mp 287 C to 289 C, Mass (m/z) ES : Expected 333.09,
observed 333.08. H NMR: δ 2.50 (s, 3H, CH ), 7.50 (d,
J = 7.7 Hz, 2H, ArH), 7.58 (d, J = 7.7 Hz, 2H, ArH), 8.01 (d,
J = 8.1 Hz, 1H, ArH), 7.43 (dd, J = 8.1, 8.3 Hz, 1H, ArH),
1
3
ꢀ
ꢀ
1
+
mp 288 C to 290 C, Mass (m/z) ES : Expected 337.06,
observed 337.49. H NMR: δ 7.32 (s, 1H, ArH), 7.47

RAUT ET AL.
13
(d, J = 7.5 Hz, 1H, ArH), 7.49 (dd, J = 7.5, 8.0, 1H,
4.6.18 | 3-[6-(2,3,5,6-Tetrafluoro-phenyl)-
ArH), 7.99 (d, J = 8.0 Hz, 1H, ArH), 8.00 (d,
J = 7.9 Hz, 1H, ArH), 7.50 (dd, J = 7.9, 7.4 Hz, 1H,
ArH), 7.53 (dd, J = 7.9, 7.4 Hz, 1H, ArH), 8.10 (d,
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-
1H-indazole (8r)
13
ꢀ
ꢀ
1
+
J = 7.4 Hz, 1H, ArH), 13.08 (s, 1H, NH). C NMR: δ
mp 118 C to 120 C, Mass (m/z) ES : Expected 391.03,
1
1
1
12.20, 116.18, 117.25, 120.18, 121.80, 122.59, 124.15,
27.79, 129.94, 130.42, 132.61, 163.80, 164.38, 165.89,
66.37, 167.21.
observed 391.00. H NMR: δ 6.31 (s, 1H, ArH), 8.21 (d,
J = 7.7 Hz, 1H, ArH), 7.32 (dd, J = 7.7, 8.0 Hz, 1H, ArH),
7.48 (dd, J = 8.0, 8.2 Hz, 1H), 7.66 (dd, J = 8.2 Hz, 1H,
13
ArH), 13.79 (s, 1H, NH). C NMR: δ 109.41, 110.18,
14.48, 116.18, 118.62, 121.33, 127.51, 131.74, 140.88,
141.23, 144.91, 152.41, 157.77, 160.78.
1
4.6.15 | 3-[6-(2-Fluoro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8o)
4
.6.19 | 3-[6-(3-Chloro-2-fluoro-phenyl)-
ꢀ
ꢀ
1
+
mp 162 C to 164 C, Mass (m/z) ES : Expected 337.06,
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-
1H-indazole (8s)
observed 337.02. H NMR: δ 7.31 (d, J = 7.9 Hz, 1H,
ArH), 7.34 (dd, J = 7.9, 7.5 Hz, 1H, ArH), 7.51 (dd,
J = 7.5, 7.8 Hz, 1H, ArH), 7.53 (d, J = 7.8 Hz, 1H, ArH),
ꢀ
+
mp 172 C, Mass (m/z) ES : Expected 371.02, observed
371.02. H NMR: δ 6.70 (d, J = 7.6 Hz, 1H, ArH), 7.65 (dd,
J = 7.6, 8.0 Hz, 1H, ArH), 8.07 (d, J = 8.0 Hz, 1H, ArH),
8.31 (d, J = 7.6 Hz, 1H, ArH), 6.73 (dd, J = 7.6, 8.1 Hz, 1H,
ArH), 7.67 (dd, J = 8.1, 8.0 Hz, 1H, ArH), 7.83 (d,
1
8
1
.21 (d, J = 8.2 Hz, 1H, ArH), 7.47 (dd, J = 8.2, 7.9 Hz,
H, ArH), 7.99 (dd, J = 7.9, 7.3 Hz, 1H, ArH), 8.01 (d,
13
J = 7.3 Hz, 1H, ArH), 13.98 (s, 1H, NH). C NMR: δ
1
1
1
11.25, 116.01, 117.07, 117.33, 120.45, 121.22, 122.59,
27.55, 129.87, 130.35, 132.53, 132.61, 141.21, 163.66,
64.28, 166.83.
13
J = 8.0 Hz, 1H, ArH), 13.67 (s, 1H, NH). C NMR: δ
111.24, 121.12, 121.90, 122.60, 125.38, 126.90, 127.53, 130.43,
131.70, 132.02, 135.88, 136.08, 139.58, 141.23, 142.63, 166.48.
4
.6.16 | 3-[6-(2,4-Difluoro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8p)
4.6.20 | 3-[6-(2-Trifluoromethyl-pyridin-
3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-
3
-yl]-1H-indazole (8t)
ꢀ
ꢀ
1
+
mp 132 C to 134 C, Mass (m/z) ES : Expected 355.05,
ꢀ
ꢀ
+
observed 355.05. H NMR: δ 7.72 (s, 1H, ArH), 7.34 (d,
J = 7.8 Hz, 1H, ArH), 7.50 (d, J = 7.8 Hz, 1H, ArH), 7.82 (d,
mp 188 C to 190 C, ES : Expected 388.05, observed 388.00.
1
H NMR: δ 7.33 (d, J = 7.7 Hz, 1H, ArH), 7.36 (dd, J = 7.7,
J = 8.1 Hz, 1H, ArH), 7.32 (dd, J = 8.1, 8.3 Hz, 1H, ArH),
8.3 Hz, 1H, ArH)), 7.71 (d, J = 8.3 Hz, 1H, ArH), 8.33 (d,
J = 7.8 Hz, 1H, ArH), 7.31 (dd, J = 7.8, 7.7 Hz, 1H, ArH),
7.36 (dd, J = 7.7, 8.1 Hz, 1H, ArH), 7.81 (d, J = 8.3, 1.9 Hz,
7
.34 (dd, J = 8.3, 8.0 Hz, 1H, ArH), 7.72 (d, J = 8.0 Hz, 1H,
13
ArH), 13.81 (s, 1H, NH). C NMR: δ 107.68, 111.26, 113.35,
13
113.52, 113.55, 121.14, 122.60, 127.56, 131.73, 135.48,
1H, ArH), 12.29 (s, 1H, NH). C NMR: δ 111.27, 121.21,
135.66, 141.22, 142.83, 155.82, 159.10, 161.13.
121.86, 122.63, 125.76, 127.00, 127.58, 128.46, 131.12,
134.49, 135.10, 141.23, 142.81, 155.68, 157.74, 164.64.
4
.6.17 | 3-[6-(2,6-Difluoro-phenyl)-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-
indazole (8q)
4.6.21 | 3-{6-[2-(4-Trifluoromethyl-
phenyl)-vinyl]-[1,2,4]triazolo[3,4-b][1,3,4]
thiadiazol-3-yl}-1H-indazole (8u)
ꢀ
ꢀ
+
mp 158 C to 160 C, Mass (m/z) ES : Expected 355.05,
observed 355.07. H NMR: δ 8.09 (d, J = 8.0 Hz, 2H,
ArH), 7.43 (dd, J = 8.0, 8.0 Hz, 1H, ArH), 7.65 (d,
1
ꢀ
1
+
mp 130 C, Mass (m/z) ES : Expected 413.08, observed
413.06. H NMR: δ 2.50 (d, J = 16.4 Hz, 1H, CH CH), 3.34
J = 8.2 Hz, 1H, ArH), 7.28 (dd, J = 8.2, 8.0 Hz, 1H, ArH),
(d, J = 16.4 Hz, 1H, CH CH), 7.60 (7.47 (d, J = 8.7 Hz, 2H,
ArH), 8.14 (d, J = 8.7 Hz, 2H, ArH), 8.16 (d, J = 8.2 Hz, 1H,
ArH), 7.58 (dd, J = 8.2, 8.0 Hz, 1H, ArH), 7.62 (dd, J = 8.0,
7.6 Hz, 1H, ArH), 8.02 (d, J = 7.6 Hz, 1H, ArH), 12.64 (s,
7
1
1
1
.30 (dd, J = 8.0, 7.8 Hz, 1H, ArH), 7.60 (d, J = 7.8 Hz,
13
H, ArH), 14.02 (s, 1H, NH). C NMR: δ 112.18, 118.05,
21.67, 123.29, 126.95, 127.19, 134.02, 156.12, 158.39,
61.23, 162.79, 164.08, 166.79, 168.00.
13
1H, NH). C NMR: δ 110.89, 114.12, 118.21, 119.30, 120.12,

14
RAUT ET AL.
1
1
20.59, 120.91, 123.46, 123.86, 126.56, 125.51, 133.46,
33.73, 140.84, 144.23, 148.85, 154.00.
REFERENCES AND NOTES
[1] A. Schmidt, A. Beutler, B. Snovydovych, Eur. J. Org. Chem.
008, 2008, 4073.
2
[
[
2] S. Caron, E. Vazquez, Org. Process Res. Dev. 2001, 5, 587.
3] X. Li, S. Chu, V. A. Feher, M. Khalili, Z. Nie, S. Margosiak,
V. Nikulin, J. Levin, K. G. Sprankle, M. E. Tedder,
R. Almassy, K. Appelt, K. M. Yager, J. Med. Chem. 2003,
4
.6.22 | 3-(6-Trifluoromethyl-[1,2,4]
triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-1H-
indazole (8v)
4
6, 5663.
[
4] (a) J. D. Rodgers, B. L. Johnson, H. Wang, R. A. Greenberg,
S. Erickson-Viitanen, R. M. Klabe, B. C. Cordova,
M. M. Rayner, G. N. Lam, C. H. B. Chang, Chem. Lett. 1996, 6,
2919. (b) J. H. Sun, C. A. Teleha, J. S. Yan, J. D. Rodgers,
D. A. Nugiel, J. Org. Chem. 1997, 62, 5627.
ꢀ
1
+
mp 156 C, Mass (m/z) ES : Expected 311.03, observed
3
(
11.03. H NMR: δ 8.30 (d, J = 7.9 Hz, 1H, ArH), 7.18
dd, J = 7.9, 8.2 Hz, 1H, ArH), 7.32 (dd, J = 8.2, 8.0 Hz,
H, ArH), 7.66 (dd, J = 8.2 Hz, 1H, ArH), 13.59 (s, 1H,
NH). C NMR: δ 110.01, 112.94, 118.26, 124.79, 126.91,
32.07, 136.12, 138.00, 152.23, 152.69, 154.49.
1
13
[5] M. A. Jakupec, E. Reisner, A. Eichinger, M. Pongratz,
V. B. Arion, M. Galanski, C. G. Hartinger, B. K. Keppler,
J. Med. Chem. 2005, 48, 2831.
1
[6] G. Corsi, G. Palazzo, C. Germani, P. S. Barcellona,
B. Silvestrini, J. Med. Chem. 1976, 19, 778.
4
.7 | 5-(1H-Indazol-3-yl)-[1,3,4]
[7] Y. L. Artyom, S. K. Anton, Z. V. Alexander, J. Org. Chem.
2005, 70(2), 596. https://doi.org/10.1021/jo048671t.
oxadiazole-2-thiol (6)
[8] Y. K. Bae, C. S. Cho, Appl. Organomet. Chem. 2013, 27(4), 224.
https://doi.org/10.1002/aoc.2956.
ꢀ
−1
mp 159 C, IR (cm ): 660-782 (indazole C─H), 1248
C─N), 1615 (C N), 2729 (S─H), 3066 (N─H). Mass (m/
[9] H. Kawakubo, K. Fukuzaki, T. Sone, Chem. Pharm. Bull. 1987,
(
35, 2292.
+
1
z) ES : Expected 219.03, observed 218.81. H NMR
[
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(CDCl ) δ (ppm): 3.36 (s, 1H, S─H), 7.25 (d, J = 8.2 Hz,
3
1
H), 7.47 (dd, J = 8.2, 8.3 Hz, 1H), 7.54 (dd, J = 8.3,
.0 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 13.48 (s, 1H, ─NH).
C NMR: δ 111.46, 118.13, 120.00, 122.32, 126.23, 132.08,
38.01, 140.12, 143.04.
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ꢀ
ꢀ
1
+
mp 190 C to 192 C, Mass (m/z) ES : Expected 349.08,
2
observed 349.28. H NMR: δ 3.86 (s, 3H, OCH ), 7.24 (d,
J = 8.7 Hz, 2H, ArH), 7.58 (d, J = 8.7 Hz, 2H, ArH), 8.13
d, J = 8.0 Hz, 1H, ArH), 7.10 (dd, J = 8.0, 8.9 Hz, 1H,
ArH), 7.26 (dd, J = 8.9, 8.4 Hz, 1H, ArH), 7.61 (d,
3
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5
1
1
5.88, 115.41, 117.26, 119.46, 121.08, 121.17, 125.06,
30.69, 131.25, 142.32, 144.94, 147.38, 148.09, 149.82,
50.84.
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ACKNOWLEDGMENTS
One of the authors, Raut S.V., is thankful to CSIR for pro-
viding SRF fellowship for this work. The authors are
thankful to Principal, Maulana Azad Collage, Auranga-
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(
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
(
synthesis-of-series-of-indazole-derivative-as-potent-
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How to cite this article: Raut S, Hadi A,
Pathan MA. The efficient synthesis of 3-[6-
2
(
substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-
-yl]-1H-indazole. J Heterocycl Chem. 2020;1–15.
https://doi.org/10.1002/jhet.3866
5
3
30] P. P. Kattimani, R. R. Kamble, A. Dorababu, R. K. Hunnur,
A. A. Kamble, H. C. Devarajegowda, J. Heterocyclic Chem.
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017, 00, 00. https://doi.org/10.1002/jhet.2813.