Multicomponent facile synthesis of highly substituted [1,2,4]triazolo[1,5-a] pyrimidines

Article abstract of DOI:10.3184/174751916X14664307728623

A simple and convenient method for one-pot synthesis of a series of potentially biologically active [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives has been developed in solvent-free conditions using maltose as a commercially available, cheap a

Full text of DOI:10.3184/174751916X14664307728623

458 RESEARCH PAPER
VOL. 40 AUGUST, 458–460
JOURNAL OF CHEMICAL RESEARCH 2016
Multicomponent facile synthesis of highly substituted [1,2,4]triazolo[1,5-a]
pyrimidines
Belgheis Adroma, Nourallah Hazeria*, Mojtaba Lashkarib and Malek Taher Maghsoodloua
aDepartment of Chemistry, Faculty of Science, University of Sistan and Baluchestan, PO Box 98135-674 Zahedan, Iran
bFaculty of Science, Velayat University, Iranshahr, Iran
A simple and convenient method for one-pot synthesis of a series of potentially biologically active [1,2,4]triazolo[1,5-a]pyrimidine-6-
carboxamide derivatives has been developed in solvent-free conditions using maltose as a commercially available, cheap and eco-friendly
catalyst. The salient features of the present protocol are mild reaction conditions, good to excellent yields, high atom economy, benign
environmental conditions, easy isolation of products without column chromatography and clean reaction profiles.
Keywords: [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide, multicomponent reaction, maltose, solvent-free conditions
Multicomponent reactions (MCRs) have proven to be useful in
organic chemistry, medicinal chemistry and other industries.1–4
Such protocols can be used for drug design and diversity-
oriented synthesis of heterocycles because of their simplicity,
efficiency and high selectivity.5 This environmentally
friendly process can avoid a waste of time as well as energy
consumption, and often permits a reduction in the number of
steps. MCRs under solvent-free conditions have attracted much
interest from chemists, particularly from the viewpoint of green
chemistry. The possibility of performing MCR reactions under
solvent-free conditions with a catalyst could enhance their
efficiency from an economic as well as an ecological point
of view.6–10 Fused triazole and pyrimidine ring systems have
been studied for several years because of their medicinal and
agricultural significance.11–13 Among their important effects,
triazolopyrimidine derivatives are used as blood pressure
regulators,14 antibacterial agents,15 selective serotonin 5-HT6
receptor antagonists16 and cardiovascular vasodilators.17 In
addition, several triazolopyrimidine-2-sulfonamide derivatives
with herbicidal activity, such as florasulam, flumetsulam and
metosulam, are produced commercially.18 Some important
structures containing fused triazole and pyrimidine scaffolds
have biological activities, such as anti-appetite, anticonvulsant
and anticancer activities.19–21
The use of organic catalysts has received considerable
attention in organic synthesis owing to their important
advantages, such as the possibility of performing reactions
with acid-sensitive substrates, milder reaction conditions and
selectivity.22–24 Maltose has received considerable attention
in organic synthesis owing to its advantages, such as low
cost and ease of handling and isolation. Encouraged by the
remarkable results obtained from the above conditions, and also
in continuation of our ongoing green chemistry programme
that utilises homogeneous systems25–27 in various organic
transformations, we report a simple, mild and convenient
procedure for effecting the one-pot, three-component reaction
of aryl aldehydes, acetoacetanilide and 3-amino-1,2,4-
triazole for preparation of [1,2,4]triazolo[1,5-a]pyrimidine-
6-carboxamide derivatives using maltose as a homogeneous
catalyst under solvent-free conditions (Scheme 1).
Results and discussion
Initially, a mixture containing 3-amino-1,2,4-triazole 1 (1.0 mmol),
benzaldehyde 2 (1.0 mmol) and acetoacetanilide 3 (1.0 mmol)
was reacted in the absence of any catalyst (Table 1, entry 1)
and solvent at 80 °C, but the reaction did not occur. When the
reaction was conducted in the presence of a catalytic amount of
maltose, a satisfactory result was obtained. Use of 25 mol% of
maltose (Table 1, entry 3) was found to be sufficient for obtaining
optimum yields of the desired [1,2,4]triazolo[1,5-a]pyrimidine-6-
carboxamide. Further decrease or increase in the amount of catalyst
did not improve the yield of the product. To identify the optimal
temperature for this reaction in solvent-free conditions, the reaction
was repeated at room temperature (25 °C), 60, 80 and 100 °C for
2 h. As indicated in Table 1, the reaction did not occur at room
temperature; however, the yield at 80 °C was 95% after 20 min.
To explore the scope of this reaction, various aldehydes 2 were
employed under the optimised reaction conditions. Various aryl
aldehydes with different donor and acceptor substituents produced
the corresponding products cleanly, as shown in Table 2, and no
undesirable side reactions were observed. Higher yields and short
reaction times were noticed with electron-deficient aldehydes.
All the new compounds were characterised from their elemental
analysis and IR, 1H NMR and 13C NMR spectra, and the structure
of the products was confirmed by comparison with the literature13.
1
For example, the H NMR spectrum of 4a exhibited a singlet for
the methyl group (δ = 2.19) and a singlet at δ = 3.67 for the methoxy
group. One singlet at 6.55 ppm was attributed to a methine group
(CHN). Ten aromatic hydrogens gave rise to characteristic signals in
the aromatic region of the spectrum. The spectrum also displayed a
Ar
O
O
O
O
Maltose (25 mol%)
solvent free, 80 °C
HN N
Ph
N
N
N
N
H
Ph
+
+
N
Ar
H
NH2
N
H
N
H
3
2
1
4
Scheme 1 Maltose-catalysed synthesis of [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives.
* Correspondent. E-mail: nhazeri@chem.usb.ac.ir; n_hazeri@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2016 459
Table 1 Optimisation of the catalyst for the synthesis of [1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamidesa
Table 2 Synthesis of [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide
derivatives
Entry Catalyst
Mol%
-
Temperature/°C Time/min Yield/%b
Entry Ar
Time/min Yield/%a Product M.p. (lit. m.p.)/°C
1
2
3
4
5
6
7
Maltose
Maltose
Maltose
Maltose
Maltose
Maltose
Maltose
80
80
80
80
25 (r.t.)
60
120
25
20
18
120
40
–
1
2
3
4
5
6
7
8
9
10
3-OMe–C6H4
20
18
22
18
14
25
22
20
16
25
92
94
91
94
95
91
92
94
95
90
4a
4b
4c
4d
4e
4f
4g
4h
4i
244 (246)
246 (248)
252 (254)
245 (247)
277 (279)
251 (253)
241 (243)
226 (228)
238 (240)
258 (260)
20
25
30
25
25
25
84
95
87
–
2,4-Cl2C6H3
2-Cl–C6H4
4-OMe–C6H4
4-F–C6H4
Ph
2-Br–C6H4
2-OMe–C6H4
4-Br–C6H4
4-NO2–C6H4
45
100
18
89
aReaction conditions: 3-amino-1,2,4-triazole, acetoacetanilide and benzaldehyde in the
presence of catalyst.
bIsolated yield.
4j
aIsolated yield.
Maltose
Maltose
H
H
O
Ar
O
O
O
O
O
O
O
Ph
N
HN
N
Ph
N
N
H
N
Ph
+
+
N
H
H
N
Ar
N
N
H
H
H
Ar
NH2
4
1
2
3
X
Scheme 2 Suggested mechanism for the synthesis of [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives.
(NH); 1H NMR (300 MHz, DMSO-d6): δ 2.19 (s, 3H, CH3), 3.67 (s, 3H,
OCH3), 6.53 (s, 1H, Hbenzylic), 6.74 (d, 1H, J = 2.1 Hz, Haromatic), 6.78 (d, 1H,
J = 7.8 Hz, Haromatic), 6.84 (dd, 1H, J = 7.8 Hz, J = 2.4 Hz, Haromatic), 7.02
(t, 1H, J = 7.5 Hz, Haromatic), 7.53 (d, 1H, J = 8.4 Hz, Haromatic), 7.74 (d, 1H,
J = 8.6 Hz, Haromatic), 7.28 (d, 1H, J = 8.1 Hz, Haromatic), 7.53 (d, 1H, J = 0.9 Hz,
broad singlet (δ = 9.78) attributed to the NHCO group, and a singlet
1
at 10.26 ppm was recorded for the NH group. The H-decoupled
13C NMR spectrum of 4a showed 20 distinct carbon signals in
agreement with the expected product.
A plausible mechanism for the formation of products 4a is shown
in Scheme 2. Initially, the intermediate X is formed in situ from the
reaction of acetoacetanilide with an aldehyde. Then, nucleophilic
attack of 3-amino-1,2,4-triazole in the presence of the catalyst upon
cyclisation afforded the desired product 4a.28–30
Haromatic), 7.56 (d, 1H, J = 1.8 Hz, Haromatic), 7.68 (s, 1H, Haromatic), 9.78 (s, 1H,
NH), 10.26 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6): δ 17.8 (CH3),
55.4 (OCH3), 60.5 (Cbenzylic), 103.9, 113.3, 113.5, 119.6, 119.9, 120.0, 123.7,
129.0, 130.1, 137.0, 139.3, 142.7, 148.2, 150.4, 159.6, 165.2 (C=O). Anal.
calcd for C20H19N5O2: C, 66.47; H, 5.30; N, 19.38; found: C, 66.95; H, 5.51;
N, 19.66.
Conclusion
In conclusion, we have developed an efficient method for the
synthesis of N,7-diaryl-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-
a]-pyrimidine-6-carboxamides via a one-pot, three-component
reaction under solvent-free conditions. The environmentally benign
and inexpensive catalyst maltose was used as a catalyst in the
reaction process.
7-(2,4-Dichlorophenyl)-4,7-dihydro-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4b): Brown solid; yield 94%;
m.p. 246–248 °C; IR (KBr, cm−1): 1600 (C=C), 1670 (CON), 3304 (NH);
1H NMR (300 MHz, DMSO-d6): δ 2.17 (s, 3H, CH3), 6.92 (s, 1H, Hbenzylic),
7.03 (t, 1H, J = 7.5 Hz, Haromatic), 7.27 (t, 2H, J = 7.8 Hz, Haromatic), 7.35 (d,
1H, J = 8.4 Hz, Haromatic), 7.42 (dd, 1H, J = 8.4 Hz, J = 1.8 Hz, Haromatic),
7.50 (d, 2H, J = 8.1 Hz, Haromatic), 7.56 (d, 1H, J = 1.8 Hz, Haromatic), 7.66 (s,
1H, Haromatic), 9.88 (s, 1H, NH), 10.39 (s, 1H, NH); 13C NMR (300 MHz,
DMSO-d6): δ 17.6 (CH3), 57.8 (Cbenzylic), 102.7, 119.8, 119.9, 123.8, 128.3,
129.1, 129.5, 131.9, 133.6, 134.0, 137.2, 137.4, 139.2, 139.3, 148.2, 150.6,
164.8 (C=O). Anal. calcd for C19H15Cl2N5O: C, 57.01; H, 3.78; N, 17.50;
found: C, 57.39; H, 4.02; N, 17.81.
Experimental
Melting points and IR spectra of all compounds were measured on an
Electrothermal 9100 apparatus and a JASCO FTIR 460 Plus spectrometer,
respectively. The 1H NMR and 13C NMR spectra were recorded on Bruker
DRX-300 Avance instrument with DMSO as a solvent. All reagents
and solvents obtained from Fluka and Merck were used without further
purification.
7-(2-Chlorophenyl)-4,7-dihydro-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4c): White solid; yield 91%;
m.p. 252–254 °C; IR (KBr, cm−1): 1595 (C=C), 1671 (CON), 3297 (NH);
1H NMR (300 MHz, DMSO-d6): δ 2.17 (s, 3H, CH3), 6.95 (s, 1H, Hbenzylic),
7.01 (t, 1H, J = 7.5 Hz, Haromatic), 7.22–7.39 (m, 6H, Haromatic), 7.49 (d, 1H,
J = 8.1 Hz, Haromatic), 7.65 (s, 1H, Haromatic), 9.86 (s, 1H, NH), 10.33 (s, 1H,
NH);13C NMR (300 MHz, DMSO-d6): δ 17.5 (CH3), 58.2 (Cbenzylic), 103.1,
119.8, 119.9, 123.7, 128.0, 129.0, 130.1, 130.3, 130.6, 132.6, 137.2, 138.1,
139.2, 139.3, 148.2, 150.4, 164.9 (C=O). Anal. calcd for C19H16ClN5O: C,
62.38; H, 4.41; N, 19.14; found: C, 62.56; H, 4.32; N, 19.25.
Synthesis of N,7-diaryl-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]-
pyrimidine-6-carboxamides (4a–j); general procedure
Maltose (25 mol%, 0.096 g) was added into a mixture of benzaldehyde
(1.0 mmol), 3-amino-1,2,4-triazole (1.0 mmol) and acetoacetanilide
(1.0 mmol), then the reaction mixture was heated to 80 °C and stirred for the
appropriate time (Table 1). After completion of the reaction (monitored by
TLC), the reaction mixture was washed with H2O (3 × 10 mL). The catalyst
is soluble in water and was removed from the reaction mixture. Then, the
residue was recrystallised from EtOH.
4,7-Dihydro-7-(3-methoxyphenyl)-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4a): White solid; yield
92%; m.p. 244–246 °C; IR (KBr, cm−1) 1596 (C=C), 1672 (CON), 3279
4,7-Dihydro-7-(4-methoxyphenyl)-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4d): White solid; yield 94%;
m.p. 245–247 °C; IR (KBr, cm−1): 1596 (C=C), 1672 (CON), 3297 (NH),

460 JOURNAL OF CHEMICAL RESEARCH 2016
1H NMR (300 MHz, DMSO-d6): δ 2.18 (s, 3H, CH3), 3.70 (s, 3H, OCH3),
6.50 (s, 1H, Hbenzylic), 6.86 (d, 2H, J = 8.7 Hz, Haromatic), 7.01 (t, 1H, J = 7.5 Hz,
Haromatic), 7.17 (d, 2H, J = 8.4 Hz, Haromatic), 7.26 (t, 2H, J = 7.5 Hz, Haromatic),
7.53 (d, 2H, J = 7.5 Hz, Haromatic), 7.64 (s, 1H, Haromatic), 9.74 (s, 1H, NH),
10.20 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6): δ 17.7 (CH3), 55.5
(OCH3), 60.1 (Cbenzylic), 104.1, 114.2, 119.8, 119.9, 123.7, 128.8, 129.0, 133.3,
136.8, 139.4, 148.0, 150.2, 159.4, 165.3 (C=O). Anal. calcd for C20H19N5O2:
C, 66.47; H, 5.30; N, 19.38; found: C, 66.69; H, 5.44; N, 19.60.
4,7-Dihydro-5-methyl-7- (4-nitrophenyl) -N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4j): Light brown solid; yield
90%; m.p. 258–260 °C; IR (KBr, cm−1): 1600 (C=C), 1672 (CON), 3260
(NH); 1H NMR (300 MHz, DMSO-d6): δ 2.20 (s, 3H, CH3), 6.70 (s, 1H,
Hbenzylic), 7.02 (t, 1H, J = 7.5 Hz, Haromatic), 7.26 (t, 1H, J = 7.8 Hz, Haromatic),
7.50 (d, 4H, J = 8.7 Hz, Haromatic), 7.71 (s, 1H, Haromatic), 8.20 (d, 2H, J = 8.7 Hz,
Haromatic), 9.83 (s, 1H, NH), 10.44 (s, 1H, NH).Anal. calcd for C19H16N6O3: C,
60.63; H, 4.28; N, 22.33; found: C, 60.99; H, 4.53; N, 22.65.
7-(4-Fluorophenyl)-4,7-dihydro-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4e): White solid; yield 95%;
m.p. 277–279 °C; IR (KBr, cm−1): 1596 (C=C), 1664 (CON), 3271 (NH);
1H NMR (300 MHz, DMSO-d6): δ 2.19 (s, 3H, CH3), 6.56 (s, 1H, Hbenzylic),
6.99–7.04 (m, 1H, Haromatic), 7.12–7.18 (m, 2H, Haromatic), 7.23–1.32 (m, 4H,
Haromatic), 7.49–7.52 (m, 2H, Haromatic), 9.78 (s, 1H, NH), 10.29 (s, 1H, NH);
13C NMR (300 MHz, DMSO-d6): δ 17.7 (CH3), 60.0 (Cbenzylic), 103.8, 115.6,
115.9, 119.9, 120.0, 123.8, 129.0, 129.6, 129.7, 137.0, 137.1, 139.2, 139.3,
148.2, 150.4, 160.6, 163.8, 165.3 (C=O). Anal. calcd for C19H16FN5O: C,
65.32; H, 4.62; N, 20.05; found: C, 65.91; H, 4.97; N, 20.34.
4,7-Dihydro-5-methyl-N,7-diphenyl-[1,2,4]triazolo[1,5-a]pyrimidine-
6-carboxamide (4f): White solid; yield 91%; m.p. 252–254 °C; IR (KBr,
cm−1): 1595 (C=C), 1661 (CON), 3295 (NH); 1H NMR (300 MHz,
DMSO-d6): δ 2.19 (s, 3H, CH3), 6.55 (s, 1H, Hbenzylic), 7.02 (t, 1H, J = 7.5 Hz,
Haromatic), 7.21–7.35 (m, 7H, Haromatic), 7.50 (s, 1H, Haromatic), 7.53 (d, 2H,
J = 1.2 Hz, Haromatic), 7.66 (s, 1H, Haromatic), 9.78 (s, 1H, NH), 10.25 (s, 1H,
NH); 13C NMR (300 MHz, DMSO-d6): δ 17.7 (CH3), 60.7 (Cbenzylic), 104.0,
104.0, 119.9, 120.0, 123.7, 127.4, 128.5, 128.9, 129.0, 136.9, 137.0, 139.3,
139.4, 141.2, 148.2, 150.4, 165.2 (C=O). Anal. calcd for C19H17N5O: C,
68.87; H, 5.17; N, 21.13; found: C, 69.04; H, 5.09; N, 21.03.
We gratefully acknowledge financial support from the Research
Council of the University of Sistan and Baluchestan.
Received 15 March 2016; accepted 10 May 2016
Paper 1603985 doi: 10.3184/174751916X14664307728623
Published online: 22 July 2016
References
1
2
3
4
J. Zhu and H. Bienayme, Multicomponent reactions, Wiley-VCH, Weinheim,
2005, p. 169.
R.C. Nuno, M. Francesco, M.S.D.C. Pedro and M.P.G. Pedro, Chem. Rev., 2010,
110, 6169.
S. Jimenez-Alonso, H. Chavez, A. Estevez-Braan, A. Ravelo, G. Feresin and A.
Tapia, Tetrahedron, 2008, 64, 8938.
F. Shirini, S. Akbari-Dadamahaleh, A. Mohammad-Khah and A. Reza
Aliakbar, C. R. Chim., 2013, 16, 207.
5
6
B.A. Amol and Y.T. Jeong, Tetrahedron Lett., 2013, 54, 1302.
X. Li, B. Zhou, J. Zhang, M. She, S. An, H. Ge, C. Li, B. Yin, J. Li and Z. Shi,
Eur. J. Org. Chem., 2012, 8, 1626.
7
8
9
M. Li, B. Zhanga and Y. Gu, Green Chem., 2012, 14, 2421.
M. Veeranarayana Reddy and Y.T. Jeong, Synlett, 2012, 23, 2985.
M. Veeranarayana Reddy, J. Kim and Y.T. Jeong, J. Fluorine Chem., 2012, 135,
155.
7- (2-Bromophenyl)-4,7-dihydro-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4g): White solid; yield 92%;
m.p. 241–243 °C; IR (KBr, cm−1): 1594 (C=C), 1661 (CON), 3312 (NH);
1H NMR (300 MHz, DMSO-d6): δ 2.17 (s, 3H, CH3), 6.93 (s, 1H, Hbenzylic),
7.01 (t, 1H, J = 7.5 Hz, Haromatic), 7.17 (d, 1H, J = 2.7 Hz, Haromatic), 7.19–7.27
(m, 2H, Haromatic), 7.30–7.38 (m, 2H, Haromatic), 7.48 (d, 1H, J = 0.9 Hz,
Haromatic), 7.50 (d, 1H, J = 1.2 Hz, Haromatic), 7.54 (d, 1H, J = 7.5 Hz, Haromatic),
7.64 (s, 1H, Haromatic), 9.87 (s, 1H, NH), 10.33 (s, 1H, NH); 13C NMR (300
MHz, DMSO-d6): δ 17.6 (CH3), 60.4 (Cbenzylic), 103.5, 119.8, 119.9, 122.8,
123.7, 128.6, 129.0, 130.6, 133.3, 136.9, 137.0, 139.2, 139.3, 139.8, 148.2,
150.4, 165.0 (C=O). Anal. calcd for C19H16BrN5O: C, 55.62; H, 3.93; N,
17.07; found: C, 56.11; H, 4.15; N, 17.44.
10 M. Veeranarayana Reddy, G. Chandra Sekhar Reddy and Y.T. Jeong,
Tetrahedron, 2012, 68, 6820.
11 C.B. Vu, P. Shields, B. Peng, G. Kumaravel, X.W. Jin, D. Phadke, J. Wang, T.
Engber, E. Ayyub and R.C. Petter, Bioorg. Med. Chem. Lett., 2004, 14, 4835.
12 R. Jackson, D. Ghosh and G. Paterson, Pest. Manag. Sci., 2000, 56, 1065.
13 V.L. Gein, T.M. Zamaraeva and M.I. Vakhrin, Russ. J. Gen. Chem., 2014, 84,
82.
14 Y. Sato, Y. Shimoji, H. Fujita, H. Nishino, H. Mizuno, S. Kobayashi and S.
Kumakura, J. Med. Chem., 1980, 23, 927.
15 H.M. Abdel-Rahman, N.A. El-Koussi and H.Y. Hassan, Arch. Pharm. Chem.
Life. Sci., 2009, 342, 94.
16 A.V. Ivachtchenko, E.S. Golovina, M.G. Kadieva, A.G. Koryakova, S.M.
Kovalenko, O.D. Mitkin, I.M. Okun, I.M. Ravnyeyko, S.E. Tkachenko and O.V.
Zaremba, Bioorg. Med. Chem., 2010, 18, 5282.
17 T. Novinson, R.H. Springer, D.E. O’Brien, M.B. Scholten, J.P. Miller and R.K.
Robins, J. Med. Chem., 1982, 25, 420.
18 W.A. Kleschick, M.J. Costales, J.E. Dunbar, R.W. Meikle, W.T. Monte, N.R.
Pearson, S.W. Snider and A.P. Vinogradoff, Pest. Manag. Sci., 1990, 29, 341.
19 Q. Chen, X.L. Zhu, L.L. Jiang, Z.M. Liu and G.F. Yang, Eur. J. Med. Chem.,
2008, 43, 595.
4,7-Dihydro-7-(2-methoxyphenyl)-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4h): White solid; yield
94%; m.p. 226–228 °C; IR (KBr, cm−1): 1596 (C=C), 1672 (CON), 3296
1
(NH); H NMR (300 MHz, DMSO-d6): δ = 2.13 (s, 3H, CH3), 3.63 (s,
3H, OCH3), 6.85 (s, 1H, Hbenzylic), 6.87 (d, 1H, J = 7.5 Hz, Haromatic), 6.94 (d,
1H, J = 7.8 Hz, Haromatic), 7.01 (t, 2H, J = 7.2 Hz, Haromatic), 7.18–7.28 (m, 3H,
Haromatic), 7.52–7.55 (m, 2H, Haromatic), 7.60 (s, 1H, Haromatic), 9.77 (s, 1H, NH),
10.12 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6): δ 17.5 (CH3), 55.6
(OCH3), 56.2 (Cbenzylic), 103.9, 112.2, 119.7, 119.8, 120.9, 123.5, 128.6, 129.0,
129.4, 129.8, 136.8, 139.6, 148.9, 150.0, 151.0, 157.0, 165.3 (C=O). Anal.
calcd for C20H19N5O2: C, 66.47; H, 5.30; N, 19.38; found: C, 66.70; H, 5.51;
N, 19.30.
20 S.A. Said, A.E.G. Amr, N.M. Sabry and M.M. Abdalla, Eur. J. Med. Chem.,
2009, 44, 4787.
21 N. Zhang, S. Kaloustian, T. Nguyen, J. Afragola, R. Hernande, J. Lucas, J.
Gibbons and C. Beyer, J. Med. Chem., 2007, 50, 319.
22 S. Chandrasekhar, K. Johny and C.R. Reddy, Tetrahedron Asymmetry, 2009,
20, 1742.
23 A. Khalafi-Nezhad, A. Parhami, A. Zare, A.R. Moosavi-Zare, A. Hasaninejad
and F. Panahi, Synthesis, 2008, 4, 617.
24 M.G. Dekamin, S. Sagheb-Asl and M.R. Naimi-Jamal, Tetrahedron Lett., 2009,
50, 4063.
4,7-Dihydro-7- (4-bromophenyl)-5-methyl-N-phenyl-[1,2,4]
triazolo[1,5-a]pyrimidine-6-carboxamide (4i): White solid; yield
95%; m.p. 238–240 °C; IR (KBr, cm−1): 1594 (C=C), 1661 (CON), 3312
(NH); 1H NMR (300 MHz, DMSO-d6): δ 2.13 (s, 3H, CH3), 3.63 (s, 3H,
OCH3), 6.85 (s, 1H, Hbenzylic), 6.87 (d, 1H, J = 7.5 Hz, Haromatic), 6.94 (d,
1H, J = 7.8 Hz, Haromatic), 7.01 (t, 2H, J = 7.2 Hz, Haromatic), 7.18–7.28 (m,
3H, Haromatic), 7.52–7.55 (m, 2H, Haromatic), 7.60 (s, 1H, Haromatic), 9.77 (s, 1H,
NH), 10.12 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6): δ 17.8 (CH3),
60.1 (Cbenzylic), 103.5, 119.9, 120.0, 121, 8, 123.8, 129.0, 129.7, 131.7, 131.9,
132.8, 137.2, 137.3, 139.2, 140.4, 148.1, 150.5, 165.2 (C=O). Anal. calcd for
C19H16BrN5O: C, 55.62; H, 3.93; N, 17.07; found: C, 55.94; H, 3.99; N, 17.33.
25 B. Adrom, N. Hazeri, M.T. Maghsoodlou and M. Mollamohammadi, Res.
Chem. Intermed., 2015, 41, 4741.
26 M.R. Mousavi, N. Hazeri, M.T. Maghsoodlou, S. Salahi and S.M. Habibi-
Khorassani, Chin. Chem. Lett., 2013, 24, 411.
27 M. Lashkari, M.T. Maghsoodlou, N. Hazeri, S.M. Habibi-Khorassani, S.S.
Sajadikhah and R. Doostmohamadi, Synth. Commun., 2013, 43, 635.
28 H. Wang, M. Lee, Z. Peng, B. Blázquez, E. Lastochkin, M. Kumarasiri, R.
Bouley, M. Chang and S. Mobashery, J. Med. Chem., 2015, 58, 4194.
29 V.V. Tkachenko, E.A. Muravyova, S.M. Desenko, O.V. Shishkin, S.V. Shishkina,
D.O. Sysoiev, T.J.J. Müller and V.A. Chebanov, Beilstein J. Org. Chem., 2014,
10, 3019.
30 K.R. Gopinath, K.J. Rajendraprasad, K.N. Venugopala, M. Krishnappa, Indo.
Am. J. Pharma. Res., 2015, 5, 2786.