Synthesis and anticancer evaluation of new derivatives of 3-phenyl-1,5-dimethyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4] oxadiazine

Article abstract of DOI:10.3184/030823410X520778

The synthesis of new derivatives of 3-phenyl-1,5-dimethyl-1H-[1,2,4] triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazines 5a-e and 7a-e is described through heterocyclisation of hydrazino derivative (3) with aromatic aldehydes or carbon disulfide and alky

Full text of DOI:10.3184/030823410X520778

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 403
JULY, 403–406
Synthesis and anticancer evaluation of new derivatives of 3-phenyl-1,5-
dimethyl-1H-[1,2,4]triazolo[4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazine
Mehdi Bakavolia*, Mohammad Rahimizadeha, Ali Shiria, Marzieh Akbarzadeha, Seyed-Hadi
Mousavib, Hoda Atapour-Mashhadc and Zahra Tayarani-Najaranb
aDepartment of Chemistry, School of Sciences, Ferdowsi University of Mashhad, 91775-1436 Mashhad, Iran
bDepartment of Pharmacology and Pharmacological Research Centre of Medicinal Plants, School of Medicine, Mashhad University of
Medical Sciences, Mashhad, Iran
cDepartment of Chemistry, Payam Noor University, Mashhad, Iran
Thesynthesisofnewderivativesof3-phenyl-1,5-dimethyl-1H-[1,2,4]triazolo[4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazines
5a–e and 7a–e is described through heterocyclisation of hydrazino derivative (3) with aromatic aldehydes or carbon
disulfide and alkyl halides. [(1,5-Dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)
sulfanyl]methyl cyanide was singled out to be tested on different cancer cell lines including HeLa, MCF-7, and HepG2.
Malignant cells were cultured in DMEM medium and incubated with different concentrations of the titled compounds.
Cell viability was quantified by MTT assay.
Keywords: triazolopyrimidooxadiazine, heterocyclisation, anti-cancer, HeLa, MCF-7, HepG2
the chorine atom with hydrazine and gave quantitatively the
hydrazino derivative (3) which was utilised as the precursor for
the synthesis of new tricyclic compounds 5a–e and 7a–e. Thus,
heating under stirring of the compound (3) with various aro-
matic aldehydes in the presence of a few drops of acetic acid in
ethanol resulted in the formation of corresponding hydrazones
4a–e. The latter compounds were cyclised by refluxing in
nitrobenzene as solvent and oxidatizing agent to obtain the
new derivatives of tricyclic compounds 5a–e. The structure
elucidation of these compounds was achieved by their physi-
cal, chemical and spectral data. For example, the IR spectrum
of compound (4d) showed the presence of the characteristic
Over the past decade, fused pyrimidines and heterocyclic
annulated pyrimidines have been the centre of attention due
to their applications as anticancer,1 antiviral,2 antitumor,3
and anti-inflammatory agents.4 Moreover, triazoles and espe-
cially fused triazoles are an important class of heterocyclic
compounds with antifungal,5 bactericidal,5,6 anxiolytic,7,8 anti-
convulsant,9 herbicidal10 or antidepressant11 activities. It
therefore seemed promising to synthesise fused triazolopy-
rimidooxadiazine derivatives as potential pharmacologically
active compounds.
Many methods for the synthesis of 1,2,4-triazoles have
been reported which include utilising toxic reagents such as
phosphorus oxychloride,12 lead tetraacetate13 or bromine.14
Other oxidative reagents like chloramines T,15 iodobenzene
diacetate,16,17 iron(III) chloride18 and CuCl219 as well as elec-
trochemical methods20 have been used to synthesise these
heterocyclic compounds. The synthesis of various triazoles
derivatives was also accomplished by conversion of imino-
phosphoranes into triazolopyrimidines through the initial
aza-Wittig reaction between the iminophosphoranes and the
isocyanate giving a carbodimide as intermediate which easily
undergoes ring closure.21 Various substituted hydrazonoyl
chlorides on heating under reflux in the presence of Et3N for a
long time22 or the treatment of 2-thioxo-1,3,6-trihydropyrimi-
dine-5-carboxylate with the appropriate hydrazonoyl halides
in boiling CHCl323 afforded the corresponding 1,2,4-triazoles.
As part of our ongoing studies dealing with the synthesis
of various derivatives of fused pyrimidines24–26 and oxadia-
zines,27,28 we describe here the synthesis of new derivatives of
[1,2,4]triazolo[4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazine
5a–e and 7a–e and the outcome of our preliminary evaluations
of their anti-proliferative activity.
1
absorption N–H stretching band around 3320 cm–1. The H
NMR spectrum of compound (4d) also showed a singlet D2O
exchangeable peak at δ 7.98 ppm for N–H proton while the IR
1
and H NMR spectra of compound (5d) revealed the absence
of NH moiety and also showed a molecular ion peak at m/z
390 (M+) and 392 (M+ + 2) in the mass spectrum confirming
the desired structure. (Scheme 1)
On the other hand, heating the hydrazino substituted com-
pound (3) with CS2 in dry pyridine gave the title compound (6)
which was converted to its alkyl derivatives on treatment with
alkyl halides in a mixture of boiling DMF and CH3CN (1:5).
(Scheme 1) The spectral data of compounds 7(a–e) together
with their microanalytical data are in accord with the assigned
structures. For instance, the IR spectrum of compound (6) dis-
played an absorption band at 1365 cm–1 due to C=S group
1
which was disappeared after alkylation. Also, the H NMR
spectrum of product (7d) showed a singlet at 4.48 ppm for the
methylene protons, two singlets at 2.52 and 3.45 ppm corre-
sponding to the two methyl groups and two multiplets around
7.34–7.78 ppm due to the phenyl groups of the product. The
mass spectrum of (7d) showed a molecular ion peak at m/z 402
(M+) corresponding to the molecular formula C21H18N6OS.
Results and discussion
Chemistry
Pharmacological activities
5-Bromo-2-chloro-6-methyl-4-(1-methylhydrazino)pyrimidine
(1) was prepared from the reaction of 5-bromo-2,4-dichloro-
6-methyl pyrimidine with methyl hydrazine according to our
previous published method.29 Treatment of compound (1) with
benzoyl chloride in the presence of K2CO3 in boiling dry
CH3CN afforded 7-chloro-1,5-dimethyl-3-phenyl-1H-pyrim-
ido[4,5-e][1,3,4]oxadiazine (2).27 Subsequent reaction of this
compound with hydrazine hydrate led to the replacement of
Human breast cancer (MCF-7) and human hepatocellular car-
cinoma (HepG2) were obtained from Pasteur Institute (Tehran,
Iran) and maintained at 37°C in a humidified atmosphere
(90%) containing 5% CO2. Cell lines were cultured in Roswell
Park Memorial Institute medium (RPMI) with 5% (v/v) Fetal
Calf Serum (FCS), 100 units/mL penicillin, and 100 µM strep-
tomycin. Cells were seeded overnight, and then incubated with
various concentrations of different compounds for 24 h. For
MTT assay, cells were seeded at 5,000 cell/well onto 96-well
culture plates. For each concentration and time course study,
* Correspondent: E-mail: mbakavoli@yahoo.com

404 JOURNAL OF CHEMICAL RESEARCH 2010
Scheme 1
there was a control sample which remained untreated and
received the equal volume of medium. The cell viability was
determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl tetrazolium (MTT) assay.30,31 Briefly, cells were
seeded (5,000 cell/well) onto flat-bottomed 96-well culture
plates and allowed to grow 24 h followed by treatment with
a typical heterocyclic derivative (7e). After removing the
medium, cells were labeled with MTT solution (5 mg/mL in
PBS) for 4 h and resulting formazan was dissolved in DMSO
(100 µL). The absorption was measured at 570 nm (620 nm as
a reference) in an ELISA reader.
cell line (Hep G2). At first, malignant cells were incubated
with various concentrations of (7e) (50–500 µM). The result
showed compound (7e) decreased cell viability of cells as a
concentration-dependent manner. The IC50 values against
MCF-7 after 24 h and against HepG2 after 48 h were
determined 439.6 and 280.5 µM, respectively (Figs 1 and 2).
Conclusion
We have described the synthesis of new 3-phenyl-1H-[1,2,4]
triazolo[4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazines 5a–e and
7a–e through heterocyclisation of hydrazino derivative (3)
with aromatic aldehydes and also CS2 and alkylhalides, res-
pectively. Moreover, we have found that these heterocyclic
compounds containing the triazolopyrimidooxadiazine moiety
can be considered as a novel class of antiproliferative agents
In this study, we attempted to show the possible cytotoxic
effects of triazolopyrimidooxadiazine moiety like compound
(7e) on different malignant cancer cell lines including human
breast cancer cell line (MCF-7) and hepatocellular carcinoma

JOURNAL OF CHEMICAL RESEARCH 2010 405
MHz) spectra were recorded on a Bruker AC 100 spectrometer.
Chemical shifts are reported in ppm downfield from TMS as internal
standard; coupling constants J are given in Hertz. The mass spectra
were scanned on a Varian Mat CH-7 at 70 eV. Elemental analysis
was performed on a Thermo Finnigan Flash EA microanalyzer. 3-
(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT), were
purchased from Sigma. RPMI and FCS were purchased from Gibco.
1,5-Dimethyl-7-hydrazino-3-phenyl-1H-pyrimido[4,5-e][1,3,4]
oxadiazine (3): To a solution of 7-chloro-1,5-dimethyl-3-phenyl-1H-
pyrimido[4,5-e][1,3,4]oxadiazine (2)27 (3.7 mmol, 1.1 g) in ethanol
(20 mL), hydrazine hydrate (2 mL) was added and the solution was
refluxed for 5 h. The resulting precipitate was filtered off and recryst-
allised from ethanol. Yield = 77%, m.p. = 200–201 °C, 1H NMR
(DMSO-d6, ppm) δ 2.21 (s, 3H, CH3), 3.22 (s, 3H, CH3–N), 3.95 (br s,
2H, NH2, D2O exchangeable), 5.93 (br s, 1H, NH, D2O exchangeable),
7.31–7.50 (m, 3H, Ph), 7.74–7.89 (m, 2H, Ph); IR (KBr disc) ν 3300,
3295, 1110 cm–1; m/z 270 (M+); Anal. Calcd for C13H14N6O: C, 57.77;
H, 5.22; N, 31.09. Found: C, 57.73; H, 5.05; N, 30.89%.
Synthesis of hydrazones 4a–e; general procedure
To a solution of 3-phenyl-1,5-dimethyl-7-hydrazino-1H-pyrimido[4,
5-e][1,3,4]oxadiazine (3) (0.37 mmol, 0.1 g) and an appropriate aro-
matic aldehydes (0.4 mmol) in ethanol (10 mL), a few drops of glacial
acetic acid was added and the reaction mixture was heated under
reflux condition for 2 h. The resulting solid was consecutively filtered
off, washed with water and recrystallised from ethanol.
Benzaldehyde-1-(1,5-dimethyl-3-phenyl-1H-pyrimido[4,5-e]
[1,3,4]oxadiazin-7-yl) hydrazone (4a): Yield = 85%, m.p. = 210–
213 °C, 1H NMR (CDCl3, ppm) δ 2.18 (s, 3H, CH3–pyrimidine), 3.29
(s, 3H, CH3–N), 7.08–7.92 (m, 11H, Ar and CH=N–), 8.13 (br s, 1H,
NH, D2O exchangable); IR (KBr disc) ν 3200, 1590, 1040 cm–1. m/z
358 (M+); Anal. Calcd for C20H18N6O:C, 67.02; H, 5.06; N, 23.45.
Found: C, 66.89; H, 5.05; N, 23.37%.
Fig. 1 Dose-dependent growth inhibition of MCF-7 cells by
compound (7e) (50–500 µM) after 24 h. Viability was quantified
by MTT assay. The dose inducing 50% cell growth inhibition
(IC50) against MCF-7 was calculated 439.6. Results are Mean
SEM (n = 3). *P < 0.05, **P < 0.01 and ***P < 0.001 compared to
control (C).
4-Methylbenzaldehyde-1-(1,5-dimethyl-3-phenyl-1H-pyrimido
[4,5-e] [1,3,4]oxadiazin-7-yl) hydrazone (4b): Yield = 82%, m.p. =
220–224 °C, 1H NMR (CDCl3, ppm) δ 2.29 (s, 3H, CH3–pyrimidine),
2.37 (s, 3H, CH3-phenyl), 3.29 (s, 3H, CH3–N), 7.07–7.91 (m, 10H, Ar
and CH=N–), 8.10 (br s, 1H, NH, D2O exchangable); IR (KBr disc)
ν 3279, 1588, 1025 cm–1. m/z 372 (M+); Anal. Calcd for C21H20N6O:
C, 67.73; H, 5.41; N, 22.57. Found: C, 67.70; H, 5.46; N, 22.53%.
4-Methoxybenzaldehyde-1-(1,5-dimethyl-3-phenyl-1H-pyrimido
[4,5-e][1,3,4] oxadiazin-7-yl) hydrazone (4c): Yield = 76%, m.p. =
208–210 °C, 1H NMR (CDCl3, ppm) δ 2.37 (s, 3H, CH3–pyrimidine),
3.37 (s, 3H, CH3-N), 3.79 (s, 3H, OCH3), 6.88–7.93 (m, 10H, Ar and
CH=N–), 8.03 (br s, 1H, NH, D2O exchangable); IR (KBr disc)
ν 3100, 1620, 1045 cm–1. m/z 388 (M+); Anal. Calcd for C21H20N6O2:
C, 64.94; H, 5.19; N, 21.64. Found: C, 64.89; H, 5.15; N, 21.61%.
4-Chlorobenzaldehyde-1-(1,5-dimethyl-3-phenyl-1H-pyrimido
[4,5-e] [1,3,4]oxadiazin-7-yl) hydrazone (4d): Yield = 80%, m.p. =
249–251 °C, 1H NMR (CDCl3, ppm) δ 2.32 (s, 3H, CH3–pyrimidine),
3.31 (s, 3H, CH3-N), 7.25–7.91 (m, 10H, Ar and CH=N–), 7.98 (br s,
1H, NH, D2O exchangable); IR (KBr disc) ν 3320, 1610, 1030 cm–1;
m/z 392 (M+), 394 (M+ + 2); Anal. Calcd for C20H17ClN6O: C, 61.15;
H, 4.36; N, 21.39; Found: C, 61.11; H, 4.32; N, 21.20%.
4-Nitrobenzaldehyde-1-(1,5-dimethyl-3-phenyl-1H-pyrimido[4,
5-e][1,3,4]oxadiazin-7-yl) hydrazone (4e): Yield = 75%, m.p. = 281–
283 °C, 1H NMR (CDCl3, ppm) δ 2.28 (s, 3H, CH3–pyrimidine), 3.28
(s, 3H, CH3-N), 7.32–8.33 (m, 10H, Ar and CH=N–), 8.42 (br s, 1H,
NH, D2O exchangable); IR (KBr disc) ν 3100, 1590, 1025 cm–1. m/z
403 (M+); Anal. Calcd for C20H17N7O3: C, 59.55; H, 4.25; N, 24.31.
Found: C, 59.46; H, 4.20; N, 24.25%.
Fig. 2 Dose-dependent growth inhibition of malignant cell
lines by compounds (7e) (50 to 500 µM) after 48 h. Viability was
quantified by MTT assay. The dose inducing 50% cell growth
inhibition (IC50) against HepG2 was calculated 280.5. Results
are Mean SEM (n = 3). *P < 0.05, **P < 0.01 and ***P < 0.001
compared to control (C).
Synthesis of 7-aryl-1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,3’:1,2]
pyrimido[4,5-e][1,3,4]oxadiazines 5a–e; general procedure
A mixture of appropriate hydrazone 4a–e (2 mmol) in nitrobenzene
(2 mL) was heated under reflux for 6 h. After the completion of the
reaction which was monitored by TLC using CHCl3: MeOH (9:1), the
solvent was removed under reduced pressure and the resulting solid
was recrystallised from benzene.
on the basis of a cell-based screening method. Further work is
in progress in our laboratory to explain the mechanism of the
cell death in cancer cell lines.
1,5-Dimethyl-3,7-diphenyl-1H-[1,2,4]triazolo[4’,3’:1,2]pyrimido
1
[4,5-e][1,3,4] oxadiazine (5a): Yield = 52%, m.p. = 219–221 °C, H
NMR (CDCl3, ppm) δ 2.03 (s, 3H, CH3–pyrimidine), 3.49 (s, 3H,
CH3–N), 7.32–7.92 (m, 10H, Ar); IR (KBr disc) ν 1675, 1042 cm–1.
m/z 356 (M+); Anal. Calcd for C20H16N6O: C, 67.40; H, 4.53; N, 23.58.
Found: C, 67.36; H, 4.48; N, 23.52%.
Experimental
Melting points were recorded on an Electrothermal type 9100
melting point apparatus and are not corrected. The H NMR (100
1

406 JOURNAL OF CHEMICAL RESEARCH 2010
1,5-Dimethyl-7-(4-methylphenyl)-3-phenyl-1H-[1,2,4]triazolo
[4’,3’:1,2] pyrimido[4,5-e][1,3,4]oxadiazine (5b): Yield = 45%, m.p.
7-(Benzylsulfanyl)-1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,3’:
1,2]pyrimido[4,5-e][1,3,4]oxadiazine (7d): Yield = 79%, m.p. = 210
–211 °C, 1H NMR (CDCl3, ppm) δ 2.52 (s, 3H, CH3–pyrimidine), 3.45
(s, 3H, CH3-N), 4.48 (s, 2H, CH2), 7.34–7.53 (m, 3H, ph), 7.71–7.78
(m, 2H, ph), IR: ν 3030, 2990, 1590 cm–1, m/z 402 (M+), Anal. Calcd
for C21H18N6OS: C, 62.67; H, 4.51; N, 20.88; S, 7.97. Found: C, 62.57;
H, 4.49; N, 20.84; S, 7.91%.
1
= 217–221 °C, H NMR (CDCl3, ppm) δ 2.05 (s, 3H, CH3–pyrimi-
dine), 3.50 (s, 3H, CH3-phenyl), 3.88 (s, 3H, CH3-N), 7.18–7.84 (m,
9H, Ar); IR (KBr disc) ν 1664, 1019 cm–1. m/z 370 (M+); Anal. Calcd
for C21H18N6O:C, 68.09; H, 4.90; N, 22.69. Found: C, 67.95; H, 4.84;
N, 22.59%.
7-(4-Methoxyphenyl)-1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo
[4’,3’:1,2] pyrimido[4, 5-e][1,3,4]oxadiazine (5c): Yield = 40%,
m.p. = 180–183 °C, 1H NMR (CDCl3, ppm) δ 2.04 (s, 3H, CH3–pyri-
midine), 3.48 (s, 3H, CH3-N), 3.88 (s, 3H, OCH3), 6.89–7.89 (m, 9H,
Ar); IR (KBr disc) ν 1667, 1035 cm–1. m/z 386 (M+); Anal. Calcd for
C21H18N6O2 (%): C, 65.27; H, 4.70; N, 21.75. Found: C, 65.17; H,
4.68; N, 21.67%.
[(1,5-Dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,3’:1,2]pyrimido[4,5-
e][1,3,4]oxadiazin-7-yl)sulfanyl]methyl cyanide (7e): Yield = 63%,
m.p. = 238–240 °C, 1H NMR (CDCl3, ppm) δ 2.77 (s, 3H, CH3–pyri-
midine), 3.47 (s, 3H, CH3-N), 4.03 (s, 2H, CH2CN), 7.40–7.85 (m,
5H, ph), IR: ν 3020, 2980, 2220, 1570 cm–1, m/z 351 (M+), Anal. Calcd
for C16H13N7OS: C, 54.69; H, 3.73; N, 27.90; S, 9.13. Found: C, 54.60;
H, 3.70; N, 27.87; S, 9.02%.
7-(4-Chlorophenyl)-1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,
3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazine (5d): Yield = 55%, m.p. =
266–267 °C, 1H NMR (CDCl3, ppm) δ 2.05 (s, 3H, CH3–pyrimidine),
3.48 (s, 3H, CH3–N), 7.38–7.89 (m, 9H, Ar); IR (KBr disc) ν 1667,
1017 cm–1. m/z 390 (M+), 392 (M+ + 2); Anal. Calcd for C20H15ClN6O:
C, 61.46; H, 3.87; N, 21.50. Found: C, 61.39; H, 3.86; N, 21.49%.
1,5-Dimethyl-7-(4-nitrophenyl)-3-phenyl-1H-[1,2,4]triazolo[4’,3’:
1,2]pyrimido[4,5-e][1,3,4]oxadiazine (5e): Yield = 61%, m.p. = 280–
282 °C, 1H NMR (CDCl3, ppm) δ 2.09 (s, 3H, CH3–pyrimidine), 3.47
(s, 3H, CH3–N), 7.31–8.50 (m, 9H, Ar); IR (KBr disc) ν 1664, 1019
cm–1. m/z 401 (M+); Anal. Calcd for C20H15N7O3: C, 59.85; H, 3.77;
N, 24.43. Found: C, 59.79; H, 3.73; N, 24.40%.
Received 11 May 2010; accepted 15 June 2010
Paper 1000118 doi: 10.3184/030823410X520778
Published online: 28 July 2010
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Preparation of 7-alkylsulfinyl-1,5-dimethyl-3-phenyl-1H-[1,2,4]
triazolo [4’,3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazines 7a–e; general
procedure
To a solution of compound (6) (0.3 mmol, 0.7 g) and an appropriate
alkyl halide (0.9 mmol) in a mixture of DMF:MeCN (1:5) (12 mL) as
solvent, Et3N (0.9 mmol) was added and the solution was refluxed for
4 h. After the completion of the reaction which was monitored by TLC
using chloroform: methanol (9:1), the solvent was removed under
reduced pressure. The crude solid was recrystallised from ethanol.
1,5-Dimethyl-7-(methylsulfanyl)-3-phenyl-1H-[1,2,4]triazolo[4’,
3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazine (7a): Yield = 75%, m.p. =
238–240 °C, 1H NMR (CDCl3, ppm) δ 2.70 (s, 3H, CH3–pyrimidine),
2.77 (s, 3H, CH3–S), 3.45 (s, 3H, CH3–N), 7.35–7.56 (m, 3H, ph),
7.70–7.89 (m, 2H, ph), IR: ν 3020, 2990, 1592 cm–1, m/z 326 (M+),
Anal. Calcd for C15H14N6OS: C, 55.20; H, 4.32; N, 25.75; S, 9.82.
Found: C, 55.17; H, 4.22; N, 25.66; S, 9.79%.
7-(Ethylsulfanyl)-1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4’,3’:
1,2]pyrimido[4,5-e][1,3,4]oxadiazine (7b): Yield = 67%, m.p. = 221
1
–223 °C, H NMR (CDCl3, ppm) δ 1.43 (t, 3H, CH3), 2.73 (s, 3H,
CH3–pyrimidine), 3.28 (q, 2H, CH2), 3.45 (s, 3H, CH3-N), 7.36–7.53
(m, 3H, ph), 7.74–7.88 (m, 2H, ph), IR: ν 3010, 2980, 1590 cm–1, m/z
340 (M+), Anal. Calcd for C16H16N6OS: C, 56.45; H, 4.74; N, 24.69;
S, 9.42. Found: C, 56.40; H, 4.62; N, 24.51; S, 9.33%.
1,5-Dimethyl-3-phenyl-7-(n-propylsulfanyl)-1H-[1,2,4]triazolo[4’,
3’:1,2]pyrimido[4,5-e][1,3,4]oxadiazine (7c): Yield = 70%, m.p. =
201–202 °C, 1H NMR (CDCl3, ppm) δ 1.05 (t, 3H, CH3), 1.85 (sextet,
2H, CH2), 2.74 (s, 3H, CH3–pyrimidine), 3.31 (t, 2H, CH2), 3.46
(s, 3H, CH3–N), 7.40–7.61 (m, 3H, ph), 7.75–7.89 (m, 2H, ph), IR:
ν 3015, 2985, 1580 cm–1, m/z 354 (M+), Anal. Calcd for C17H18N6OS:
C, 57.61; H, 5.12; N, 23.71; S, 9.05. Found: C, 57.56; H, 5.01;
N, 23.66; S, 8.90%.

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