Synthesis of some new pyridones, fused pyrimidines, and fused 1,2,4-triazines

Article abstract of DOI:10.1002/jhet.351

(Chemical Equation Presented) Cyclocondensation of hydrazides, 3-aminopyrazoles, 3-amino-1,2,4-triazole, 2-aminobenzoimidazole, pyrazole-3-diazonium salts, 1,2,4-triazol-3-diazonium salt, or benzoimidazole-2-diazonium salt with sodium salt of 3-hydroxy-1-(2-naphthyl) prop-2-en-1-one gave 2-pyridones, pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidine, benzo[4,5]imidazo[1,2-a]pyrimidine, (pyrazolo[5,1-c][1,2,4]triazin-3-yl)-methanone, [1,2,4]triazolo[5,1-c][1,2,4] triazin-3-yl-methanone, or benzo[4,5]imidazo[2,1-c] [1,2,4]triazin-3-yl- methanone derivatives, respectively, which will be tested for anti-tumor and anti-cancer activates.

Full text of DOI:10.1002/jhet.351

May 2010
Synthesis of Some New Pyridones, Fused Pyrimidines,
and Fused 1,2,4-Triazines
517
Mahmoud A. Mohamed*
Textile Department, Faculty of Industrial Education, Beni-Suef University, Beni-Suef, Egypt
*E-mail: mahmoud71_2000@yahoo.com
Received September 3, 2009
DOI 10.1002/jhet.351
Published online 2 April 2010 in Wiley InterScience (www.interscience.wiley.com).
Cyclocondensation of hydrazides, 3-aminopyrazoles, 3-amino-1,2,4-triazole, 2-aminobenzoimidazole,
pyrazole-3-diazonium salts, 1,2,4-triazol-3-diazonium salt, or benzoimidazole-2-diazonium salt with
sodium salt of 3-hydroxy-1-(2-naphthyl)prop-2-en-1-one gave 2-pyridones, pyrazolo[1,5-a]pyrimidines,
triazolo[1,5-a]pyrimidine, benzo[4,5]imidazo[1,2-a]pyrimidine, (pyrazolo[5,1-c][1,2,4]triazin-3-yl)-meth-
anone, [1,2,4]triazolo[5,1-c][1,2,4]triazin-3-yl-methanone, or benzo[4,5]imidazo[2,1-c] [1,2,4]triazin-3-yl-
methanone derivatives, respectively, which will be tested for anti-tumor and anti-cancer activates.
J. Heterocyclic Chem., 47, 517 (2010).
INTRODUCTION
[2,1-c]triazine derivatives which will be tested for anti-
tumor and anti-cancer activates are reported.
Chemotherapeutic anticancer agents continue to be an
active area of research at many companies and research
centers [1–3]. So that, pyridine, pyrazolopyrimidine, and
trazine derivatives have received considerable attention
due to their wide range of applications in chemotherapy,
such as anti-inflammatory, anti-tumor, anti-mycobacte-
rial, anti-fungal, and anti-viral activities [4–6]. Recently,
it has been reported that many pyridine and pyrazolopyri-
midine derivatives showed strong cytotoxicity against
several human cancer cell lines [6–9]. Pyrazolo[4,3-d]py-
rimidine and pyrazolo[1,5-a]pyrimidine derivatives were
reported to be inhibitors of tyrosine kinase and cyclin-de-
pendent kinases (CDK) which are involved in mediating
the transmission of mitogenic signals and numerous other
cellular events [3,10–15], including cell proliferation,
migration, differentiation, metabolism, and immune
response. It was also found that many of these derivatives
may block proliferation of various cancer cell lines [16].
In view of these reports and in continuation with the pre-
vious work, here a successful trial for synthesizing new
derivatives of pyridones, pyrazolo[1,5-a]pyrimidines, tri-
azolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyra-
zolo[5,1-c]triazine, triazolo[5,1-c]triazine, and imidazo
RESULTS AND DISCUSSION
As a part of our program directed for the development
of efficient and simple procedures for the synthesis of
antimetabolites [17–19], we have recently reported dif-
ferent and successful approaches for the synthesis of 2-
pyridones [17,19]. The synthesized compounds act as
intermediates for synthesis of deazafolic acid ring sys-
tem and deazapyrimidine nucleosides, which reported to
be significantly active, both in vitro and in vivo [20,21].
They also act as inhibitor of dihydrofolate reductase
[22], cytotoxicity against various experimental tumors as
potential as methotrexate [23,24], and one of the most
effective antimetabolites currently used in treatment of
various solid tumors [25,26]. This prompted our interest
to the synthesis and study of the chemistry of this class
of compounds [17,18]. Although N-amino-2-pyridones
have proved to be useful synthetic intermediates, there
are few procedures for their preparation and they are
usually obtained in low yield by the reaction of hydra-
zine with 2-pyridones [27,28]. I have reported in this
part, one step synthesis of 2-pyridones from the reaction
C
V
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M. A. Mohamed
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Scheme 1
of 3-hydroxy-1-(2-naphthyl)prop-2-en-1-one 1 with dif-
ferent hydrazides. Thus, it has been found that salt 1
reacted with cyanoacetic acidhydrazide 2 to give a tri-
substituted 2-pyridone. Two modes of cyclization are
feasible, giving a 1,2,3,6- or 1,2,3,4-tetrasubstituted
products, as outlined in Scheme 1. First, initial attack by
a methylene carbanion takes place at the formyl group
of the salt 1 and subsequent Michael cyclization fol-
lowed by elimination of two moles of water to give the
1,2,3,6-trisubstituted product 4. Second, initial nucleo-
philic attack by the methylene carbon takes place at the
ketonic group, followed by cyclization and elimination
of water giving 1,2,3,4-trisubstituted isomer 6. In fact,
only one isomer was obtained, which was suggested to be
4 due to the fact that initial attack of the active methylene
carbon at the unhindered formyl group leading to 4 being
much more probable than attack at the hindered and elec-
tronically disfavored ketonic group [29]. Spectral studies
did not allow us to distinguish between structures 4 and
zide 7 and arylsulfonylcyanoacetohydrazide 10 deriva-
tives represents a novel, one step, synthesis of N-aryli-
deneamino- and N-arylsulphonylamino-2-pyridones,
respectively. Thus, it has been found that, salt 1 reacted
with arylidenecyanoacetohydrazide 7 to give N-arylide-
neamino-2-pyridones 9, whereas 1 reacted with arylsufo-
nylcyanoacetohydrazide 10 to give N-arylsulfonylamino-
2-pyridones 12. The structure of compound 12b was
established on the basis of its elemental analysis and
spectral data (IR, 1H-NMR, and MS). Thus, the mass
spectra of 12b was compatible with the molecular for-
1
mula C23H17N3O3S (Mþ 415) and the H-NMR showed
a signal at d ¼ 2.35 ppm assigned for methyl group.
Moreover, both 7 and 12 can be obtained from the reac-
tion of 4 with aldehydes or arylsufonylchlorides, respec-
tively, as shown in Scheme 2.
Analogously, treatment of sodium 3-hydroxy-1-(2-
naphthyl)prop-2-en-1-one 1 with appropriate amounts of
3-aminopyrazoles 13 [31], in the presence of piperidine
acetate afforded pyrazolo[1,5-a]pyrimidines 15. Struc-
ture of the product 15b was confirmed by elemental
1
6. H-NMR for the product revealed the absence of CH2
and the presence of 2-naphthyl protons from d ¼ 7.54–
8.66 ppm whereas the amino group has two protons at d
¼ 2.70 ppm in solution. No significant amounts of the
alternative regioisomers could be detected. To establish
structure of the product, the crystal structure of a similar
previous work has been reported [19,29,30]. The X-ray
analysis of this work confirms the exclusive presence of
the regioisomer 4 [29].
1
analysis and spectral data (IR, H–NMR, and MS). The
mass spectra of 15b was compatible with the molecular
1
formula C23H17N3 (Mþ 335) and H NMR for the prod-
uct revealed the presence of a CH3 protons at d ¼ 2.41
ppm and methine H of pyrazole at d ¼ 6.22 ppm and
methine 2H of pyrimidine at d ¼ 8.52 and 8.78 ppm in
solutions as shown in Figure 1.
The reaction of sodium salts of 3-hydroxy-1-(2-naph-
thyl)prop-2-en-1-one 1 with arylidenecyanoacetohydra-
The reaction seemed to proceed via initial nucleo-
philic attack by the exocyclic amino group of
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Synthesis of Some New Pyridones, Fused Pyrimidines, and Fused 1,2,4-Triazines
519
Scheme 2
aminopyrazoles 13 at the ketonic group, which formed
in situ from salt 1 with water, followed by cyclization
and elimination of two moles of water to give the prod-
ucts 15 Scheme 3. It has been suggested that the forma-
tion of the alternative isomeric products 17 is based on
the initial attack of endocyclic amino group at the
ketonic group. The latter suggestion is excluded due to
the higher nucleophilicity of the exocyclic primary
amino group than the endocyclic amino group which
previously reported [17,29,30].
[1,2,4]triazolo[5,1-c][1,2,4]triazin-3-yl-methanone 27, or
benzo[4,5] imidazo[2,1-c][1,2,4]triazin-3-yl-naphthalen-
2-yl-methanone 30, respectively, Scheme 5. The struc-
ture of 24 was confirmed by elemental analysis and
1
spectral data (IR, H-NMR, and MS). The mass spectra
of 24a was compatible with the molecular formula
C22H14N4O (Mþ 350) and IR for the product revealed
the presence carbonyl group at 1,665 cmꢀ1
.
EXPERIMENTAL
Similarly, treatment of sodium 3-hydroxy-1-(2-naph-
thyl)prop-2-en-1-one 1 with 3-amino-1,2,4-triazole or 2-
aminobenzoimidazole in the presence of piperidine ace-
tate afforded 5-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]py-
rimidine 19 or 2-(naphthalen-2-yl)benzo[4,5]imidazo[1,2-
a]pyrimidine 21, respectively, Scheme 4. The structure of
19 was confirmed by elemental analysis and spectral data
(IR, 1H–NMR, and MS). The mass spectra of 19 was com-
patible with the molecular formula C15H10N4 (Mþ 246)
and 1H NMR for the product revealed the presence
methine H of triazole at d ¼ 8.27 ppm and methine 2H of
pyrimidine at d ¼ 7.54 and 8.52 ppm.
All melting points are uncorrected IR spectra were
obtained (KBr disk) on a Perkin Elmer 11650 FT-IR
instrument. The 1H-NMR spectra were measured on a
Varian 400 MHz spectrometer for solutions in (CD3)2
SO using Si(CH3)4 as an internal standard. Mass spectra
were recorded on a Varian MAT 112 spectrometer. Ana-
lytical data were obtained from the Microanalytical Data
Center at Cairo University.
Finally, the reaction of sodium 3-hydroxy-1-(2-naph-
thyl)prop-2-en-1-one 1 with pyrazole-3-diazonium salts
22, 1,2,4-triazol-3-diazonium salt 25, or benzoimida-
zole-2-diazonium salt 28 in the presence of piperidine
acetate afforded naphthalen-2-yl-(pyrazolo[5,1-c][1,2,4]
triazin-3-yl)-methanone derivatives 24, naphthalene-2-yl-
Figure 1. 1H NMR d values for 15b.
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M. A. Mohamed
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Scheme 3
Scheme 4
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Synthesis of Some New Pyridones, Fused Pyrimidines, and Fused 1,2,4-Triazines
521
Scheme 5
solution and the performed solid product was filtered off
and recrystallized from ethanol.
Method (B) for preparation of 2-pyridones (9a–d) or
(12a,b). An equimolar amount of aldehydes or arylsulfo-
2-Pyridones (4), (9a–d), (12a,b), Pyrazolo[1,5-
a]pyrimidines (15a–f), Triazolo[1,5-a]pyrimidine (19),
Benzo[4,5]imidazo[1,2-a]pyrimidine (21), (pyra-
zolo [5,1-c][1,2,4] triazin-3-yl)-methanones (24a–f),
[1,2,4] Triazolo[5,1-c] [1,2,4]triazin-3-yl-methanone
(27), or Benzo[4,5] imidazo [2,1-c][1,2,4]triazin-3-yl-
methanone (30). General method (A). A mixture of 3-
hydroxy-1-(2-naphthyl)prop-2-en-1-one 1 (0.01 mole),
cyanoacitic acidhydrazide 2, arylidenecyanoacetohydra-
zides 7, arylsulfonylcyanoacetohydrazides 10, 3-amino-
pyrazoles 13, 3-amino-1,2,4-triazole, 2-aminobenzoimi-
dazole, pyrazole-3-diazonium salts 19, 1,2,4-triazol-3-di-
azonium salts 22, or benzoimidazole-2-diazonium salts
25 (0.01 mole) in piperidine acetate (1 mL), {pipridine
þ acetic acid þ H2O}, and H2O (3 mL) was refluxed
for 5 min. Acetic acid (1.5 mL) was added to the hot
nylchlorides was added to a cold solution of compounds 4
in pyridine. The mixture was stirred for 12h and then
poured over ice-water mixture and neutralized with dil.
HCl. The formed solid product was filtered off to produce
2-pyridones 9 or 12, respectively.
2-Pyridone (4). Yellow crystals from EtOH, (yield
72%), m.p. 278–280oC, mmax/cmꢀ1 (KBr) 3388 and
3168 (NH2), 3043 (CH, aromatic), 2210.9 (CN), 1643
(CO); 1H-NMR (300 MHz, DMSO-d6): d ¼ 2.49 (s,
2H, NH2), 7.54–8.73 (m, 9H, aromatic); m/z 261 (Calcd
for C16H11N3O (261.29):C, 73.55; H, 4.24; N, 16.08%.
Found: C, 73.37; H, 4.36; N, 15.92%).
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2-Pyridones (9a–d).
9a. Pale yellow crystals from
1H), 7.01–8.05 (m, 11H, aromatic), 8.52 (d, 1H), 8.78
(d, 1H); m/z 335 (Calcd for C23H17N3 (335.41): C,
82.36; H, 5.11; N, 12.53%. Found: C, 82.27; H, 5.04;
N, 12.56%).
EtOH, (yield 74%), m.p. 235oC, mmax/cmꢀ1 (KBr) 3048
(CH, aromatic), 2206.3 (CN), 1662 (CO); H-NMR (300
1
MHz, DMSO-d6): d ¼ 6.13–7.71 (m, 14H, aromatic),
8.10 (s, 1H, ¼¼CH); m/z 349 (Calcd for C23H15N3O
(349.40): C, 79.07; H, 4.33; N, 12.03%. Found: C,
79.16; H, 4.14; N, 12.12%).
15c. Colorless crystals from EtOH, (yield 71%), m.p.
1
225oC, mmax/cmꢀ1 (KBr) 3051 (CH, aromatic); H-NMR
(300 MHz, CDCl3): d ¼ 6.23 (s, 1H), 7.02–8.02 (m,
11H, aromatic), 8.57 (d, 1H), 8.75 (d, 1H); m/z 355
(Calcd for C22H14ClN3 (355.83): C, 74.26; H, 3.97; Cl,
9.96; N, 11.81%. Found: C, 74.15; H, 4.05; Cl, 9.87; N,
11.90%).
9b. Pale yellow crystals from EtOH, (yield 79%), m.p.
230oC, mmax/cmꢀ1 (KBr) 3033 (CH, aromatic), 2198.3
1
(CN), 1675 (CO); H-NMR (300 MHz, DMSO-d6): d ¼
2.35 (s, 3H, CH3), 6.27–7.70 (m, 13H, aromatic), 8.07
(s, 1H, ¼¼CH); m/z 363 (Calcd for C24H17N3O (363.42):
C, 79.32; H, 4.72; N, 11.56%. Found: C, 79.38; H, 4.64;
N, 11.62%).
15d. Colorless crystals from EtOH, (yield 82%), m.p.
1
220oC, mmax/cmꢀ1 (KBr) 3062 (CH, aromatic); H NMR
(300 MHz, CDCl3): d ¼ 6.53 (s, 1H), 7.22–7.89 (m,
14H, aromatic), 8.51 (d, 1H), 8.78 (d, 1H); m/z 371
(Calcd for C26H17N3 (371.45): C, 84.07; H, 4.61; N,
11.31%. Found: C, 84.16; H, 4.52; N, 11.36%).
9c. Pale yellow crystals from EtOH, (yield 77%), m.p.
220oC, mmax/cmꢀ1 (KBr) 3064 (CH, aromatic), 2208.3
1
(CN), 1671 (CO); H-NMR (300 MHz, DMSO-d6): d ¼
15e. Colorless crystals from EtOH, (yield 73%), m.p.
1
3.76 (s, 3H, CH3), 6.29–7.73 (m, 13H, aromatic), 8.09
(s, 1H, ¼¼CH); m/z 379 (Calcd for C24H17N3O2
(379.42): C, 75.98; H; 4.52; N, 11.07%. Found: C,
75.92; H; 4.61; N, 11.12%).
190oC, mmax/cmꢀ1 (KBr) 3073 (CH, aromatic); H NMR
(300 MHz, CDCl3): d ¼ 7.22–7.89 (m, 12H, aromatic),
8.12 (d, 1H), 8.51 (s, 1H), 8.62 (d, 1H); m/z 321 (Calcd
for C22H15N3 (321.38): C, 82.22; H, 4.70; N, 13.07%.
Found: C, 82.26; H, 4.65; N, 13.02%).
9d. Pale yellow crystals from EtOH, (yield 71%),
m.p. 200oC, mmax/cmꢀ1 (KBr) 3051 (CH, aromatic),
2199.1 (CN), 1661 (CO); 1H-NMR (300 MHz,
DMSO-d6): d ¼ 6.31-7.72 (m, 13H, aromatic), 8.12
(s, 1H, ¼¼CH); m/z 383 (Calcd for C23H14ClN3O
(383.84): C, 71.97; H, 3.68; Cl, 9.24; N, 10.95%.
Found: C, 72.03; H, 3.64; Cl, 9.31; N, 11.02%).
15f. Colorless crystals from EtOH, (yield 75%), m.p.
225oC, mmax/cmꢀ1 (KBr) 3053(CH, aromatic), 1223
1
(CN); H NMR (300 MHz, CDCl3): d ¼ 7.22–7.89 (m,
7H, aromatic), 7.60 (d, 1H), 8.15 (s, 1H), 8.51 (d, 1H);
m/z 270 (Calcd for C17H10N4 (270.30): C, 75.54; H,
3.73; N, 20.73%. Found: C, 75.51; H, 3.82; N, 20.80%).
Triazolo[1,5-a]pyrimidine (19). Colorless crystals from
EtOH, (yield 72%), m.p. 210oC, mmax/cmꢀ1 (KBr)
2-Pyridones (12a,b).
12a. Pale yellow crystals from
EtOH, (yield 73%), m.p. 220oC, mmax/cmꢀ1 (KBr) 3350
(NH), 3061 (CH, aromatic), 2208.1 (CN), 1666 (CO);
1H-NMR (300 MHz, DMSO-d6): d ¼ 2.0 (s, 1H, NH),
6.13–7.93 (m, 14H, aromatic); m/z 401 (Calcd for
C22H15N3O3S (401.45): C, 65.82; H, 3.77; N, 10.47; S,
7.99%. Found: C, 65.93; H, 3.65; N, 10.54; S, 8.05%).
12b. Pale yellow crystals from EtOH, (yield 75%), m.p.
290oC, mmax/cmꢀ1 (KBr) 3361 (NH), 3064 (CH, aromatic),
1
3053(CH, aromatic); H NMR (300 MHz, CDCl3): d ¼
7.32–7.89 (m, 7H, aromatic), 7.52 (d, 1H), 8.27 (s, 1H),
8.50 (d, 1H); m/z ¼ 246 (Calcd for C15H10N4 (246.27):
C, 73.16; H, 4.09; N, 22.75%. Found: C, 73.19; H, 4.13;
N, 22.64%).
Benzo[4,5]imidazo[1,2-a]pyrimidine (21). Colorless crys-
tals from EtOH, (yield 78%), m.p. 230oC, mmax/cmꢀ1
(KBr) 3053(CH, aromatic); 1H NMR (300 MHz,
CDCl3): d ¼ 7.31–7.89 (m, 11H, aromatic), 7.52 (d,
1H), 8.50 (d, 1H); m/z 295 (Calcd for C20H13N3
(295.35): C, 81.34; H, 4.44; N, 14.23%. Found: C,
1
2210.1 (CN), 1664 (CO); H NMR (300 MHz, DMSO-
d6): d ¼ 2.1 (s, 1H, NH), 2.35 (s, 3H, CH3), 6.15–7.94 (m,
13H, aromatic); MS: m/z ¼ 415 (2.56, M), 345 (36.34%),
280 (53.54%), 238 (85.33%), 234 (39.34%), 121
(80.65%), 92 (90.54%), 69 (100%); (Calcd for
C23H17N3O3S (415.47): C, 66.49; H, 4.12; N, 10.11; S,
7.72%. Found: C, 66.52; H, 4.07; N, 10.21; S, 7.80%).
81.39; H, 4.38; N, 14.27%).
(Pyrazolo[5,1-c][1,2,4]triazin-3-yl)-methanones (24a–f).
24a. Colorless crystals from AcOH, (yield 75%), m.p.
210oC, mmax/cmꢀ1 (KBr) 3073 (CH, aromatic), 1665
(CO); 1H NMR (300 MHz, DMSO-d6): d ¼ 6.53 (s,
1H), 7.22–8.22 (m, 12H, aromatic), 9.56 (s, 1H); m/z
350 (Calcd for C22H14N4O (350.38): C, 75.42; H, 4.03;
N, 15.99%. Found: C, 75.45; H, 4.12; N, 16.04%).
24b. Colorless crystals from AcOH, (yield 73%), m.p.
194oC, mmax/cmꢀ1 (KBr) 3082 (CH, aromatic), 1665
(CO); 1H NMR (300 MHz, DMSO-d6): d ¼ 2.35 (s,
3H, CH3), 6.21 (s, 1H), 7.12–8.22 (m, 11H, aromatic),
Pyrazolo[1,5-a]pyrimidines
(15a–f).
15a. Colorless
crystals from EtOH, (yield 78%), m.p. 210oC, mmax
/
cmꢀ1 (KBr) 3073 (CH, aromatic); H NMR (300 MHz,
CDCl3): d ¼ 6.53 (s, 1H), 7.22–7.89 (m, 13H, aro-
matic), 8.50 (d, 1H); m/z 321 (Calcd for C22H15N3
(321.38): C, 82.22; H, 4.70; N, 13.07%. Found: C,
82.20; H, 4.77; N, 13.13%).
1
15b. Colorless crystals from EtOH, (yield 75%), m.p.
1
194oC, mmax/cmꢀ1 (KBr) 3082 (CH, aromatic); H NMR
(300 MHz, CDCl3): d ¼ 2.41 (s, 3H, CH3), 6.21 (s,
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9.46 (s, 1H); m/z 364 (Calcd for C23H16N4O (364.41):
C, 75.81; H, 4.43; N, 15.37%. Found: C, 75.87; H, 4.52;
N, 15.41%).
24c. Colorless crystals from AcOH, (yield 71%), m.p.
225oC, mmax/cmꢀ1 (KBr) 3051 (CH, aromatic), 1663
(CO); 1H NMR (300 MHz, DMSO-d6): d ¼ 6.53 (s,
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384 (Calcd for C22H13ClN4O (384.83): C, 68.67; H,
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24d. Colorless crystals from AcOH, (yield 79%), m.p.
max/cmꢀ1 (KBr) 3062 (CH, aromatic),
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[13] Angelucci, A.; Schenone, S.; Gravina, G. L.; Muzi, P.; Festuccia,
C.; Vicentini, C.; Botta, M.; Bologna, M. Eur. J. Cancer 2006, 42, 2838.
[14] Farley, M. E.; Hoffman, W. F.; Rubino, R. S.; Hungate, R.
W.; Tebben, A. J.; Rutledge, R. Z. R. Z.; McFall, R. C.; Huckle, W.
R.; Kendall, R. L.; Coll, K. E.; Thomas, K. A. Bioorg Med Chem Lett
2002, 12, 2767.
220oC,
m
1
1654(CO); H NMR (300 MHz, DMSO-d6): d ¼ 6.53
(s, 1H), 7.32–8.22 (m, 14H, aromatic), 9.46 (s, 1H); m/z
400 (Calcd for C26H16N4O (400.44): C, 77.99; H, 4.03;
N, 13.99%. Found: C, 78.05; H, 4.11; N, 14.04%).
24e. Colorless crystals from AcOH, (yield 77%), m.p.
226–230oC, mmax/cmꢀ1 (KBr) 3073 (CH, aromatic), 1646
(CO); 1H NMR (300 MHz, DMSO-d6): d ¼ 7.22–7.89 (m,
12H, aromatic), 8.40 (s, 1H), 9.46 (s, 1H); MS: m/z ¼ 350
(34.57%, Mþ 1), 350 (100%, M), 321 (9.27%), 154
(85.33%), 126 (58.26%), 100 (3.93%), 69 (4.95%), 55
(8.15%) (Calcd for C22H14N4O (350.38): C, 75.42; H, 4.03;
N, 15.99%. Found: C, 75.37; H, 4.06; N, 15.92%).
[15] Farley, M. E.; Rubino, R. S.; Hoffman, W. F.; Hambaugh,
S. R.; Arrington, K. L.; Hungate, R. W.; Bilodeau, M. T.; Tebben, A.
J.; Rutledge, R. Z.; Kendall, R. L.; McFall, R. C.; Huckle, W. R.;
Coll, K. E.; Thomas, K. A. Bioorg Med Chem Lett 2002, 12, 3537.
[16] Krystof, V.; Moravcova, D.; Paprskarova, M.; Barbier, P.;
Peyrot, V.; Hlobikova, A.; Havlicek, L.; Stramd, M. Eur J Med Chem
2006, 41, 1405.
24f. Colorless crystals from AcOH, (yield 77%), m.p.
225oC, mmax/cmꢀ1 (KBr) 3064(CH, aromatic), 1653
1
(CO), 1221 (CN); H NMR (300 MHz, DMSO-d6): d ¼
7.32–8.22 (m, 7H, aromatic), 7.63 (s, 1H), 9.36 (s, 1H);
m/z 299 (Calcd for C17H9N5O (299.29): C, 68.22; H,
[17] Ahmed, O. M.; Mohamed, M. A.; Ahmed R. R.; Ahmed, S.
A. Eur J Med Chem 2009, 44, 3519.
3.03; N, 23.40%. Found: C, 68.15; H, 3.23; N, 23.64%).
[1,2,4]Triazolo[5,1-c][1,2,4]triazin-3-yl-methanone
[18] Ahmed, S. A.; El-Ghandour, A. H. H.; Abdelhamid, A. O.;
Mohamed, M. A.; Mohamed, B. M. J Chem Res 2008, 1, 26.
[19] Elgemeie, G. H.; Elghandour, A. H.; Elzanate A. M.;
Mohamed, M. A. Mansora Sci Bull 2004, 31.
(27) Color-less crystals from AcOH, (yield 74%), m.p.
260oC, mmax/cmꢀ1 (KBr) 3053(CH, aromatic), 1665
1
[20] Temple, C.; Elliot, R. D.; Montgomery, J. A. J Org Chem
1982, 47, 761.
(CO); H NMR (300 MHz, DMSO-d6): d ¼ 7.32–8.21
(m, 7H, aromatic), 8.27 (s, 1H), 9.46 (s, 1H); m/z ¼
[21] Taylor, E. C.; Palmer, D. C.; George, T. J.; Fletcher, S. R.;
Tseng, C. P.; Horrion, P. J.; Beardsley G. P. J Org Chem 1983, 48, 4852.
[22] Stone, S. R.; Montgomery, J. A.; Morrision, J. F. Biochem
Pharmcol 1974, 33, 175.
275 (Calcd for C15H9N5O (275.27): C, 65.45; H, 3.30;
N, 25.44%. Found: C, 65.36; H, 3.22; N, 25.51%).
Benzo[4,5] imidazo[2,1-c][1,2,4]triazin-3-yl-methanone
(30) Colorless crystals from AcOH, (yield 76%), m.p.
[23] Grivsky, E. M.; Lee, S.; Sigel, S. W.; Durch, D. S.; Nichol,
C. A. J Med Chem 1980, 23, 327.
230oC, mmax/cmꢀ1 (KBr) 3053(CH, aromatic), 1665
1
[24] Ensminger, W. D.; Grindey, G. B.; Hoglind, J. A. In
Advances in Cancer Chemotherapy; Rosowsky, A., Ed.; Marcel Dek-
ker: New York, 1976; 1, p 61.
(CO); H NMR (300 MHz, CDCl3): d ¼ 7.32–8.22 (m,
11H, aromatic), 9.45 (s, 1H); m/z 324 (Calcd for
C20H12N4O (324.34): C, 74.06; H, 3.73; N, 17.27%.
Found: C, 74.13; H, 3.67; N, 17.32%).
[25] DeGraw, J. I.; Christine, P. H.; Kisliuk, R. L.; Gaumont,
Y.; Sirotnak, F. M. J Med Chem 1990, 33, 673.
[26] Taylor, E. C.; Harrington, P. J.; Fletcher, S. R.; Beardsley,
G. P.; Moran, R. G. J Med Chem 1985, 28, 914.
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Pergmon Press: Elmsford, NY, 1985.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet