A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b][1,3,4] thiadiazol derivatives

Article abstract of DOI:10.1080/17415993.2012.734306

A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H) -one derivatives (7a-7h) have been synthesized from 2-amino-4,5,6,7- tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence. The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in the presence of phosphorus oxychloride afforded the series of title compounds (7a-7h). The structures of all newly synthesized compounds were established on the basis of their IR, ¹H-NMR, ¹³C-NMR and liquid chromatography mass spectrometry spectral data.

Full text of DOI:10.1080/17415993.2012.734306

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A facile synthesis of some novel fused
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol
derivatives
Kerru Nagaraju a , Yalagala Kotaiah a , Chinnam Sampath a
Nallapaneni Harikrishna a & Chunduri Venkata Rao a
,
a Department of Chemistry, Sri Venkateswara University, Tirupati,
517 502, Andhra Pradesh, India
Published online: 27 Nov 2012.
To cite this article: Kerru Nagaraju , Yalagala Kotaiah , Chinnam Sampath , Nallapaneni Harikrishna
& Chunduri Venkata Rao (2013): A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b]
[1,3,4]thiadiazol derivatives, Journal of Sulfur Chemistry, 34:3, 264-275
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Journal of Sulfur Chemistry, 2013
Vol. 34, No. 3, 264–275, http://dx.doi.org/10.1080/17415993.2012.734306
A facile synthesis of some novel fused
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol derivatives
Kerru Nagaraju, Yalagala Kotaiah, Chinnam Sampath, Nallapaneni Harikrishna and
Chunduri Venkata Rao*
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
(Received 19 July 2012; final version received 23 September 2012)
A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives (7a–7h) have been synthesized from
2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence.
The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in the pres-
ence of phosphorus oxychloride afforded the series of title compounds (7a–7h). The structures of all
newly synthesized compounds were established on the basis of their IR, 1H-NMR, 13C-NMR and liquid
chromatography mass spectrometry spectral data.
HN NH2
O
R
O
N
N
O
N
N
S
N
N
N
S
N
S
Keywords: thieno[2,3-d]pyrimidin-4-one; oxopyrimidine; 1,2,4-triazole; 1,3,4-thiadiazole; cycliza-
tion reaction
1. Introduction
A wide variety of heterocyclic benzothiophene systems and their substituted derivatives have been
extensively used for the synthesis of a very large number of biologically important molecules
over many years. It is evident from the literature that certain thienopyrimidine derivatives have
been found to exhibit varied biological activities such as antioxidant, antitumor (1), inhibitors of
VEGFR-2 kinase (2), cytotoxicity (3), and antimicrobial activity (4, 5). Manhas et al. (6) have syn-
thesized various substituted thienopyrimidine derivatives and evaluated their anti-inflammatory
activity (6). Several thienopyrimidiones were also synthesized and evaluated for their use for
selective 5-HT1A receptor ligands (7), anti-hypertensive agents (8), potent gonadotropin-releasing
hormone receptor antagonists (9), and for their fungicidal activities (10). In addition, a large
*Corresponding author. Email: cvrsvu@gmail.com
© 2013 Taylor & Francis

Journal of Sulfur Chemistry 265
number of tetrahydrobenzothienopyrimidinone derivatives were reported for their analgesic, anti-
inflammatory, antimicrobial, and anticonvulsant activities (11–13). In the past few years, the
synthesis of 1,2,4-triazole and 1,3,4-thiadiazole derivatives have received considerable attention
as a result of their biological importance and their important roles in organic and medicinal chem-
istry. They show a wide range of therapeutic activities, such as antioxidant (14), antimicrobial
(15–17), antiviral (18), anti-inflammatory (19–22), in vitro anti-HIV, antitumor (23), and antibac-
terial (24, 25) activities. Moreover, much interest has also been focused on their antihypertensive
(26), antituberculosis (27), antidepressant, anxiolytic (28), analgesic (29, 30), and in vitro cyto-
toxicity (31) activities. The search for versatile and widely applicable methods for the synthesis
of new heterocyclic compounds and novel molecules is a major topic in contemporary organic
synthesis. Thus, the aim of the present work is the synthesis of thienopyrimidine derivatives
containing the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol moiety.
2. Results and discussion
In the present investigation, we have synthesized novel fused pentacyclic [1,2,4]triazolo[3,4-
b][1,3,4]thiadiazolo thienopyrimidines from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carbonitrile (1) using the reaction sequences shown in Schemes 1 and 2. The starting material
1 was prepared via a multicomponent condensation between elemental sulfur, cyclohex-
anone, and activated melanonitrile in diethyl amine using the Gewald reaction conditions
reported in the literature (32). One of the convenient synthetic methods to construct the oxo-
pyrimidine ring system employs treatment of amino and cyano functionality, with formic
acid at refluxing temperature. Compound 1 upon refluxing with formic acid and concentrated
sulfuric acid at 110◦C (5) resulted in the formation of 5,6,7,8-tetrahydro[1]benzothieno[2,3-
d]pyrimidin-4(3H)-one (2). Compound 2 on treatment with ethyl bromoacetate and potassium
O
O
O
CN
H2SO4/
HCOOH
Reflux
N
BrCH2COOEt
K2CO3/Acetone
NH
O
NH2
S
1
N
N
S
S
3
2
NH2NH2.H2O
EtOH
Reflux
O
S
H
N
SK+
H
N
O
N
NH2
H
CS2/KOH
EtOH
N
N
O
O
N
5
N
S
S
4
Water,
Reflux
H2N
NH2NH2.H2O
H2N
O
O
N
N
SH
S
N
N
N
N
NH
N
N
N
S
S
6
Scheme 1. Synthetic pathways to 3-(4-amino-5-mercapto-4H-[1,2,4]triazol-3-ylmethyl)-5,6,7,
8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one.

266 K. Nagaraju et al.
R
N
H2N
N
O
S
N
O
SH
POCl3,
RCOOH
N
N
N
N
N
N
N
Reflux
S
N
S
(7a–7h)
6
Scheme 2. Synthetic pathway to [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives. (a) R =
C6H5; (b) R = 4-C6H4Cl; (c) R = 4-C7H7OCH3; (d) R = 4-C6H4NO2; (e) R = 4-C6H4OH; (f)
R = 4-C6H4CH3; (g) R = 4-C6H4Br; (h) R = 4-C6H4NH2.
carbonate in acetone gave (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)-acetic
acid methyl ester (3). Compound 3 on treatment with hydrazine hydrate in absolute
ethanol (33) furnished (4-oxo-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-3-yl)-acetic
acid hydrazide (4).
The key intermediate 4 was treated with carbon disulfide in the presence of potas-
sium hydroxide in ethanol to afford the corresponding intermediated potassium dithio-
carbazinate salt 5, which underwent ring closure with an excess of 80% hydrazine
hydrate upon reflux to give 3-(4-amino-5-mercapto-4H-[1,2,4]triazol-3-ylmethyl)-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d] pyrimidin-4(3H)-one (6). The IR spectra of 6 showed charac-
teristic absorption bands at 3456, 2896, 1658 and 1573 cm−1 for the NH2, CH, C O and C N
stretching vibrations, respectively, and its H-NMR showed a broad one proton singlet for the
=
=
1
SH group at δ = 12.74 and the -NH2 group as a two proton singlet at δ = 5.70. Furthermore,

Journal of Sulfur Chemistry 267

268 K. Nagaraju et al.

Journal of Sulfur Chemistry 269

270 K. Nagaraju et al.
the formation of 6 was also supported by its mass spectrum which exhibited a molecular ion
(M+) peak at m/z = 334 with 100% relative abundance corresponding to the molecular formula
C13H14N6OS2.
Interestingly, the resultant triazole 6 was further converted into [1,2,4]-trizolo-[3,4-b][1,3,4]-
thiadiazoles (7a–7h) in a one-pot reaction by condensation with various substituted aromatic acids
in the presence of phosphorus oxychloride followed by an intramolecular ring closure to form the
five-membered ring in very good yield (Scheme 2). The structures of the synthesized compounds
7a–7h were assigned on the basis of spectral studies. The physical data, IR, 1H-NMR, 13C-NMR,
elemental analysis, and mass spectral data for all the synthesized compounds are reported in the
experimental section. The IR spectra of the title compounds 7a–7h showed absorption bands at
2943–2857, 1696–1651, and 1593–1473 cm−1for the CH, C O, and C N stretching vibrations,
respectively. The absence of the –NH2 and –SH proton signals in the H-NMR spectrum of
=
=
1
7a–7h is indicative of the conversion of 6 to [1,2,4]-triazolo-[3,4-b]-[1,3,4]-thiadiazoles (7a–7h)
on treatment with RCOOH in POCl3.
3. Conclusions
In summary, we have developed a synthesis of novel substituted phenyl [1,2,4]-triazolo[3,4-
b][1,3,4]thiadiazole derivatives. The structures of the synthesized compounds were conformed
with their spectral data. In the present investigation, thin layer chromatography (TLC) monitoring
reveals that a mixture of products is not formed.
4. Experimental
Melting points were determined in open capillaries on a Mel-Temp apparatus and are uncorrected.
All the reactions were monitored by TLC on precoated silica gel 60 F254 (mesh); spots were

Journal of Sulfur Chemistry 271
visualized with UV light. Merck silica gel (60–120 mesh) was used for column chromatography.
The IR spectra were recorded on a Perkin-Elmer BX1 FTIR Spectrophotometer as KBr pellets and
the wave numbers weregiven in cm−1. 1H NMR (400 MHz)and 13CNMR(100 MHz)spectrawere
recordedonaBrukerAMX400 MHzNMRspectrometerinCDCl3/DMSO-d6 solutionusingTMS
as an internal standard. The mass spectra were recorded on an Agilent 1100 LC/MSD instrument
with the methodAPI-ES at 70 eV.All chemical shifts are reported in δ (ppm) usingTMS as an inter-
nal standard. Elemental analyses were recorded on a Thermo Finnigan Flash EA 1112 analyzer.
4.1. Procedure for the preparation of 5,6,7,8-tetrahydro[1]benzothieno[2,3-d]
pyrimidin-4(3H)-one (2)
Concentrated sulfuric acid (4 ml) at 0–5◦C was added to a mixture of 2-amino-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carbonitrile (1) (1 g, 5.6 mmol) in formic acid (10 ml). The
mixture was refluxed for 2 h and allowed to cool to room temperature (rt). The mixture was
poured into ice cold water. The solid separated was filtered and purified by recrystallization with
ethanol.
Yield: 91% (brown color solid); mp 188–200◦C; IR (KBr) (νmax cm−1): 2836 (CH), 1651
1
=
=
(C O), 1581 (C N); H NMR (400 MHz; DMSO-d6): δH 1.78–1.85 (m, 4H, CH2), 2.77 (t,
JHH = 5.2 Hz, 2H, CH2), 2.91 (t, JHH = 5.6 Hz, 2H, CH2), 8.02 (s, 1H, CH-pyrimidine), 12.32
(br s, 1H, NH); 13C NMR (100 MHz; DMSO-d6): δC 21.73, 22.43, 24.40, 25.29, 122.68, 130.79,
132.09, 144.75, 157.62, 162.38; liquid chromatography mass spectrometry (LCMS) (70 eV):
m/z = 205 (M–H)−. Anal. Calcd for C10H10N2OS: C, 58.23; H, 4.89; N, 13.58; O, 7.76; S,
15.55; found: C, 58.12; H, 4.76; N, 13.45; O, 7.71; S, 15.97%.
4.2. Procedure for the preparation of (4-oxo-5,6,7,8-tetrahydro[1]benzothieno
[2,3-d]pyrimidin-3-yl)-acetic acid methyl ester (3)
Asolutionofcompound 2(2.06 g, 10 mmol), ethylbromoacetate(1.3 ml, 12 mmol), andpotassium
carbonate (3.45 g, 25 mmol) in 20 ml acetone was stirred for 2 h. The precipitated solid obtained
after the evaporation of acetone was washed with cold water and recrystallized from ethanol.
Yield: 80% (yellow color solid); mp 189–191◦C; IR (KBr) (νmax cm−1): 2945 (CH), 1736
1
=
=
(COOEt), 1674 (C O), 1558 (C N) ; H NMR (400 MHz; DMSO-d6): δH 1.28 (t, JHH
=
8.0 Hz, 3H, CH2 CH3) 1.81–1.87 (m, 4H, CH2), 2.82 (t, JHH = 5.6 Hz, 2H, CH2), 2.93 (t,
JHH = 6.0 Hz, 2H, CH2), 4.24 (q, JHH = 8.0 Hz, 2H, CH2CH3), 4.84 (s, 2H, CH2CO), 8.36 (s, 1H,
CH-pyrimidine); 13C NMR (100 MHz; DMSO-d6): δC 13.97, 21.69, 22.34, 24.50, 25.22, 46.78,
61.22, 121.57, 130.78, 133.36, 147.49, 156.71, 161.66, 167.82; LCMS (70 eV): m/z = 293
(M+H)+. Anal. Calcd for C14H16N2O3S: C, 57.52; H, 5.52; N, 9.58; O, 16.42; S, 10.97; found:
C, 57.45; H, 5.58; N, 9.57; O, 16.46; S, 10.95%.
4.3. Procedure for the synthesis of (4-oxo-5,6,7,8-tetrahydro[1]benzothieno
[2,3-d]pyrimidin-3-yl)-acetic acid hydrazide (4)
A mixture of 3 (2.92 g, 10 mmol) and hydrazine hydrate (1.4 ml, 30 mmol) in ethanol (30 ml) was
refluxed for 3 h. The reaction mixture was concentrated, cooled, and poured into ice cold water.
The separated solid was filtered, dried, and recrystallized from ethanol.
Yield: 88% (pale yellow color solid); mp 243–245◦C; IR (KBr) (νmax cm−1): 3278 (NH2),
1
=
=
2916 (CH), 1658 (CONH), 1620 (C O), 1558 (C N) ; H NMR (400 MHz; DMSO-d6): δH
1.79–1.85 (m, 4H, CH2), 2.79 (t, JHH = 8.0 Hz, 2H, CH2), 2.89 (t, JHH = 8.0 Hz, 2H, CH2), 4.35
(s, 2H, CH2CO), 4.61 (s, 2H, NH2), 8.28 (s, 1H, CH-pyrimidine), 9.45 (s, 1H, CONH); 13C NMR

272 K. Nagaraju et al.
(100 MHz; DMSO-d6): δC 21.73, 22.38, 24.50, 25.27, 46.36, 121.62, 130.76, 132.76, 148.08,
156.81, 161.63, 166.06; LCMS (70 eV): m/z = 277 (M–H)−. Anal. Calcd for C12H14N4O2S: C,
51.78; H, 5.07; N, 20.13; O, 11.50; S, 11.52; found: C, 51.65; H, 5.12; N, 20.07; O, 11.57; S,
11.59%.
4.4. Procedure for the synthesis of potassium dithiocarbazinate (5)
To a solution of 4 (5.56 g, 20 mmol) and potassium hydroxide (1.68 g, 30 mmol) in 20 ml of cool
ethanol was added (1.5 ml, 25 mmol) carbon disulfide and the mixture was stirred for 12 h. The
obtained solid was filtered, washed with anhydrous ether (50 ml), and dried in vacuum.
4.5. Procedure for the preparation of 3-(4-amino-5-mercapto-4H-[1,2,4]triazol-3-ylmethyl)-
5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (6)
Hydrazine hydrate (1.9 ml, 40 mmol) was added to a suspension of potassium compound (7.84 g,
20 mmol) in water (25 ml). The suspension was refluxed for 18 h until a green color was obtained.
Then, the reaction mixture was cooled, diluted, and acidified with acetic acid. The precipitated
solid was filtered off, washed, and recrystallized from ethanol.
Yield: 63% (pale brown color solid); mp 254–256◦C; IR (KBr) (νmax cm−1): 3456 (NH2), 2896
1
=
=
(CH), 2736 (SH), 1658 (C O), 1573 (C N); H NMR (400 MHz; DMSO-d6): δH 1.78–1.82
(m, 4H, CH2), 2.80 (t, JHH = 8.0 Hz, 2H, CH2), 2.90 (t, JHH = 8.0 Hz, 2H, CH2), 5.29 (s, 2H,
CH2), 5.70 (s, 2H, NH2), 8.45 (s, 1H, CH-pyrimidine), 12.74 (br s, 1H, SH); 13C NMR (100 MHz;
DMSO-d6): δC 21.69, 22.34, 24.51, 25.25, 40.20, 121.67, 130.85, 133.30, 147.65, 148.11, 156.53,
161.56, 166.82; LCMS (70 eV): m/z = 333 (M–H)−. Anal. Calcd for C13H14N6OS2: C, 46.69;
H, 4.22; N, 25.13; O, 4.78; S, 19.18; Found: C, 49.56; H, 4.32; N, 25.07; O, 3.04; S, 18.01%.
4.6. General procedure for the synthesis of 3-[6-(4-subtituted phenyl)-[1,2,4]triazolo[3,4-b]
[1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-
one (7a–7h)
An equimolar mixture of compound 6 (3.34 g, 10 mmol) and aromatic acids (10 mmol) in phos-
phorus oxychloride (10 ml) was refluxed for 5–8 h. The reaction mixture was cooled to rt and then
gradually poured onto crushed ice with stirring. The mixture was allowed to stand overnight and
the separated solid was filtered, treated with dilute sodium hydroxide solution, washed thoroughly
with cold water, dried, and recrystallized from ethanol.
4.6.1. 3-(6-Phenyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl)-5,6,7,8-tetrahydro[1]
benzothieno[2,3-d]pyrimidin-4(3H)-one (7a)
Yield: 84% (brown color solid); mp 266–268◦C; IR (KBr) (νmax cm−1): 2857 (CH), 1683 (C O),
=
1
=
−
1481 (C N), 763 (C S); H NMR (400 MHz; DMSO-d6): δH 1.65–1.86 (m, 4H, 2CH2), 2.67 (t,
JHH = 8.0 Hz, 2H, CH2), 2.94 (t, JHH = 8.0 Hz, 2H, CH2), 5.60 (s, 2H, CH2), 7.58–7.65 (m, 5H,
Ar–H), 8.51 (s, 1H, CH-pyrimidine); 13C NMR (100 MHz; DMSO-d6): δC 21.68, 21.91, 22.34,
22.72, 24.51, 119.57, 121.36, 127.03, 128.50, 129.67, 130.91, 133.00, 147.68, 148.72, 157.09,
160.86, 162.39, 187.16; LCMS (70 eV): m/z = 421 (M+H)+. Anal. Calcd for C20H16N6OS2: C,
57.12; H, 3.84; N, 19.99; found: C, 57.22; H, 3.76; N, 19.85%.

Journal of Sulfur Chemistry 273
4.6.2. 3-[6-(4-Chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7b)
Yield: 78% (brown color solid); mp 210–212◦C; IR (KBr) (νmax cm−1): 2879 (CH), 1696 (C O),
=
1
=
−
1473 (C N), 833 (C S); H NMR (400 MHz; DMSO-d6): δH 1.65–1.70 (m, 4H, 2CH2), 2.59
(t, JHH = 8.0 Hz, 2H, CH2), 2.95 (t, JHH = 8.0 Hz, 2H, CH2), 5.59 (s, 2H, CH2), 7.49 (d, JHH
=
8.0 Hz, 2H, Ar–H), 7.62 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.50 (s, 1H, CH-pyrimidine); 13C NMR
(100 MHz; DMSO-d6): δC 21.81, 22.64, 22.96, 24.08, 38.16, 119.03, 121.83, 126.68, 129.50,
130.73, 132.01, 136.19, 147.42, 149.95, 157.38, 161.43, 164.82, 173.59; LCMS (70 eV): m/z =
455 (M+H)+. Anal. Calcd for C20H15ClN6OS2: C, 52.80; H, 3.32; N, 18.47; found: C, 52.68; H,
3.28; N, 18.31%.
4.6.3. 3-[6-(4-Methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7c)
Yield: 73% (brown color solid); mp 218–220°C; IR (KBr) (νmax cm−1): 2894 (CH), 1688 (C O),
=
1
=
−
1573 (C N), 802 (C S); H NMR (400 MHz; DMSO-d6): δH 1.71–1.79 (m, 4H, 2CH2), 2.75 (t,
JHH = 8.0 Hz, 2H, CH2), 2.82 (t, JHH = 8.0 Hz, 2H, CH2), 3.69 (s, 3H, OCH3), 5.66 (s, 2H,
CH2), 7.83 (d, JHH = 8.0 Hz, 2H, Ar–H), 7.96 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.57 (s, 1H,
CH-pyrimidine); 13C NMR (100 MHz; DMSO-d6): δC 20.00, 20.63, 22.80, 24.23, 38.49, 54.06,
113.47, 122.06, 127.12, 128.28, 130.65, 133.86, 138.07, 148.44, 149.29, 156.81, 163.11, 167.09,
178.23; LCMS (70 eV): m/z = 451 (M+H)+. Anal. Calcd for C21H18N6O2S2: C, 55.98; H,
4.03; N, 18.65; found: C, 55.86; H, 4.12; N, 18.46%.
4.6.4. 3-[6-(4-Nitrophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7d)
Yield: 81% (orange color solid); mp 280–282◦C; IR (KBr) (νmax cm−1): 2943 (CH), 1682 (C O),
=
1
=
−
1527 (C N), 856 (C S); H NMR (400 MHz; DMSO-d6): δH 1.65–1.70 (m, 4H, 2CH2), 2.59
(t, JHH = 8.0 Hz, 2H, CH2), 2.74 (t, JHH = 8.0 Hz, 2H, CH2), 5.62 (s, 2H, CH2), 8.17 (d, JHH
=
8.0 Hz, 2H, Ar–H), 8.35 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.52 (s, 1H, CH-pyrimidine); 13C NMR
(100 MHz; DMSO-d6): δC 21.59, 21.74, 22.23, 25.68, 37.11, 116.36, 121.72, 125.53, 127.94,
130.52, 132.38, 137.61, 148.25, 149.05, 158.93, 160.28, 164.64, 171.49; LCMS (70 eV): m/z =
466 (M+H)+. Anal. Calcd for C20H15N7O3S2: C, 51.60; H, 3.25; N, 21.06; found: C, 51.76; H,
3.21; N, 21.15%.
4.6.5. 3-[6-(4-Hydroxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one (7e)
Yield: 79% (brown color solid); mp 246–248◦C; IR (KBr) (νmax cm−1): 3417 (OH), 2943 (CH),
1
=
=
−
1682 (C O), 1527 (C N), 856 (C S); H NMR (400 MHz; DMSO-d6): δH 1.68–1.73 (m, 4H,
2CH2), 2.46 (t, JHH = 8.0 Hz, 2H, CH2), 2.69 (t, JHH = 8.0 Hz, 2H, CH2), 5.48 (s, 2H, CH2), 7.68
(d, JHH = 8.0 Hz, 2H, Ar–H), 7.84 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.05 (s, 1H, CH-pyrimidine),
10.36 (s, 1H, Ar–OH); 13C NMR (100 MHz; DMSO-d6): δC 21.16, 22.69, 23.85, 24.43, 38.60,
117.74, 119.82, 126.95, 128.48, 131.04, 133.53, 138.24, 149.37, 151.99, 159.31, 161.93, 162.26,
169.18; LCMS (70 eV): m/z = 437 (M+H)+. Anal. Calcd for C20H16N6O2S2: C, 55.03; H, 3.69;
N, 19.25; found: C, 55.21; H, 3.61; N, 19.12%.

274 K. Nagaraju et al.
4.6.6. 3-[6-(4-Methylphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7f)
Yield: 66% (brown color solid); mp 212–214◦C; IR (KBr) (νmax cm−1): 2892 (CH), 1664 (C O),
=
1
=
−
1536 (C N), 796 (C S); H NMR (400 MHz; DMSO-d6): δH 1.71–1.76 (m, 4H, 2CH2), 2.38
(t, JHH = 8.0 Hz, 2H, CH2), 2.52 (t, JHH = 8.0 Hz, 2H, CH2), 3.04 (s, 3H, Ar–CH3), 5.51 (s,
2H, CH2), 7.28 (d, JHH = 8.0 Hz, 2H, Ar–H), 7.61 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.37 (s, 1H,
CH-pyrimidine); 13C NMR (100 MHz; DMSO-d6): δC 20.37, 21.88, 23.16, 24.92, 26.08, 37.53,
115.26, 120.18, 124.11, 129.63, 129.98, 132.49, 139.28, 147.72, 153.57, 159.26, 162.01, 165.35,
171.48; LCMS (70 eV): m/z = 433 (M–H)−. Anal. Calcd for C21H18N6OS2: C, 58.04; H, 4.18;
N, 19.34; found: C, 58.12; H, 4.23; N, 19.27%.
4.6.7. 3-[6-(4-Bromophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7g)
Yield: 73% (yellow color solid); mp 264–266◦C; IR (KBr) (νmax cm−1): 2941 (CH), 1672 (C O),
=
1
=
−
1593 (C N), 764 (C S); H NMR (400 MHz; DMSO-d6): δH 1.68–1.74 (m, 4H, 2CH2), 2.42
(t, JHH = 8.0 Hz, 2H, CH2), 2.68 (t, JHH = 8.0 Hz, 2H, CH2), 5.04 (s, 2H, CH2), 7.31 (d, JHH
=
8.0 Hz, 2H, Ar–H), 7.73 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.68 (s, 1H, CH-pyrimidine); 13C NMR
(100 MHz; DMSO-d6): δC 20.92, 21.48, 22.10, 24.28, 38.44, 118.76, 121.59, 125.06, 130.23,
132.47, 133.61, 138.80, 146.39, 149.33, 154.53, 159.78, 162.95, 168.89; LCMS (70 eV): m/z =
467 (M+H)+. Anal. Calcd for C20H15BrN6OS2: C, 51.40; H, 3.24; N, 17.98; found: C, 51.32; H,
3.14; N, 17.72%.
4.6.8. 3-[6-(4-Amino-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-
tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (7h)
Yield: 81% (brown color solid); mp 283–285◦C; IR (KBr) (νmax cm−1): 3428 (NH2), 2859 (CH),
1
=
=
−
1651 (C O), 1527 (C N), 829 (C S); H NMR (400 MHz; DMSO-d6): δH 1.71–1.75 (m, 4H,
CH2), 2.52 (t, JHH = 8.0 Hz, 2H, CH2), 2.74 (t, JHH = 8.0 Hz, 2H, CH2), 5.04 (s, 2H, NH2),
5.51 (s, 2H, CH2), 7.42 (d, JHH = 8.0 Hz, 2H, Ar–H), 7.96 (d, JHH = 8.0 Hz, 2H, Ar–H), 8.26
(s, 1H, CH-pyrimidine); 13C NMR (100 MHz; DMSO-d6): δC 21.04, 21.42, 23.91, 25.18, 38.73,
118.38, 120.69, 124.28, 127.51, 130.17, 137.36, 139.52, 147.01, 149.99, 157.38, 160.64, 162.75,
172.93; LCMS (70 eV): m/z = 436 (M+H)+. Anal. Calcd for C20H16N6O2S2: C, 55.03; H, 3.69;
N, 19.25; found: C, 55.12; H, 3.61; N, 19.36%.
Acknowledgements
One of the authors (KN) is gratefully acknowledge the CSIR New Delhi for the financial assistance.
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