Synthesis of some new nitrogen bridge-head triazolopyridines, pyridotriazines, and pyridotriazepines incorporating 6-methylchromone moiety

Article abstract of DOI:10.1002/jhet.1608

Some new triazolo[1,5-a]pyridines, pyrido[1,2-b][1,2,4]triazines, and pyrido[1,2-b][1,2,4]triazepines incorporating 6-methylchromone moiety were prepared from the reaction of 1,6-diamino-4-(6-methyl-4-oxo-4H-chromen-3-yl)-2- oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4) with some electrophilic reagents.

Full text of DOI:10.1002/jhet.1608

Month 2013
Synthesis of Some New Nitrogen Bridge-head Triazolopyridines,
Pyridotriazines, and Pyridotriazepines Incorporating 6-Methylchromone
Moiety
*
M. Abdel-megid, M. A. Ibrahim, Y. Gabr, N. M. El-Gohary, and E. A. Mohamed
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711 Cairo, Egypt
*
E-mail: magdy_ahmed1977@yahoo.com
Received August 17, 2011
DOI 10.1002/jhet.1608
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
R`
NC
N
NC
N
N
R`
R
O
O
N
O
O
N
R
H3C
H3C
N
H
NH2
CN
CN
O
O
CH3
NC
N
NC
O
N
O
N
N
N
H3C
H3C
N
H
N
N
CN
CN
O
Some new triazolo[1,5-a]pyridines, pyrido[1,2-b][1,2,4]triazines, and pyrido[1,2-b][1,2,4]triazepines
incorporating 6-methylchromone moiety were prepared from the reaction of 1,6-diamino-4-(6-methyl-
4-oxo-4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4) with some electrophilic reagents.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
new nitrogen bridge-head triazolo[1,5-a] pyridines, pyrido
[1,2-b][1,2,4]triazines, and pyrido[1,2-b][1,2,4]triazepines
linked 6-methyl chromone moiety.
Chromone derivatives exhibited significant biological
activities such as anticancer[1,2], antitumor [3,4], antiviral
[5], antibiotic [6], antimicrobial [7], antifungal [8], antiox-
idant [9,10], plant growth inhibitors [11], and physiologi-
cal activity [12]. Polyfunctional pyridines are highly
reactive intermediates that have been extensively used in
heterocyclic synthesis [13–15]. On the other hand, 1,2,4-
triazoles [16], 1,2,4-triazines [17], and 1,2,4-triazepines
[18] are considered as important nitrogen heterocyclic rings
because of their interesting biological activity. o-Diamines
are very active substrates for building of various heterocyclic
systems [19,20]. In symmetrical diamines, the product will be
the same irrespective of which amine participates first in the
reaction. In the case of unsymmetrical diamines, the electron-
withdrawing/donating nature of substituents influences the
initial participation of a particular amino group in the reaction,
resulting in chemoselective products. On the basis of above
observations and as a part of our aforementioned work
directed for the synthesis of new polynuclear bioactive
heterocyclic systems [21,22], the present work aims to study
the chemical reactivity of 1,6-diamino-4-(6-methyl-4-oxo-
4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarboni-
trile (4) toward various electrophilic reagents to furnish some
RESULTS AND DISCUSSION
The starting compound 1,6-diamino-4-(6-methyl-4-oxo-
4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarbo-
nitrile (4) was prepared by refluxing an alcoholic solution
of [(6-methyl-4-oxo-4H-chromen-3-yl)methylene]malono-
nitrile (2) [23] with cyanoacetohydrazide or N0-[6-methyl-
4-oxo-4H-chromone-3-yl]-2-cyanoacetohydrazone (3) [24]
with malononitrile in the presence of piperidine as a
catalyst (Scheme 1) [25]. The IR spectrum of compound
4 showed characteristic absorption bands at 3418, 3313
(2 NH2), 2262 (2 CꢀN), 1680 (C═Opyridone), and
1
1634 cmꢁ1 (C═Og-pyrone). Also, the H NMR spectrum of
compound 4 revealed three characteristic singlet signals
at 2.26, 8.50, and 9.40 ppm attributed to the CH3, H-5chro-
and H-2chromone, respectively. In addition, the 1H
mone
NMR spectrum showed two exchangeable signals at 4.59
and 10.22 ppm because of the N-NH2 and C-NH2 protons,
respectively; these results confirm the difference in nucleo-
philicity between the two amino groups. Thus, it is
© 2013 HeteroCorporation

M. Abdel-megid, M. A. Ibrahim, Y. Gabr, N. M. El-Gohary, and E. A. Mohamed
Vol 000
Scheme 1. Formation of 1,6-diaminopyridone 4.
O
O
O
H3C
CN
H3C
CHO
CH2(CN)2
H2O
CN
O
1
2
EtOH
NH2NHCOCH2CN
NH2NHCOCH2CN
70%
EtOH/piperidine
O
O
NC
NH2
NH2
H
N
O
O
N
H3C
N
CN
H3C
CH2(CN)2
O
O
EtOH/piperidine
68%
CN
expected that the hydrazide b-nitrogen (N-NH2) is more
nucleophilic and will react more rapidly with the electron
deficient carbon than the second amino group (C-NH2).
Compound 4 was further deduced from its mass spectrum
that showed the molecular ion peak at m/z 333, which
agrees well with the molecular formula C17H11N5O3 and
supports the identity of the structure.
absorption bands at 3396, 3185 (2 NH), 2216 (2CꢀN),
1680 (C═Opyridone), 1630 (C═Og-pyrone) and 1300 cmꢁ1
(C═S). In addition, the H NMR spectrum showed two
exchangeable signals at 7.88 and 8.85ppm because of two
NH protons. The 13C NMR spectrum showed characteristic
signals at 19.8, 187.0, and 192.5 ppm assigned to CH3,
C═S, and C═Og-pyrone, respectively.
1
o-Diamines are ready-made nucleophilic centers for the
synthesis of fused nitrogen heterocyclic rings [19,20]. Thus,
compound 4 is a useful precursor for the synthesis of some
new triazolopyridones by the reaction with some monoelec-
trophilic reagents such as carbon disulfide, acetic anhydride,
and anthranilic acid. Heterocyclization of compound 4 with
CS2 in pyridine under reflux yielded 7-(6-methyl-4-oxo-4H-
chromen-3-yl)-5-oxo-2-thioxo-1H-2,3,4,5-tetrahydro[1,2,4]
triazolo[1,5-a]pyridine-6,8-dicarbonitrile (5) (Scheme 2)
[26]. Formation of compound 5 occurs via a nucleophilic
addition of the amino group (N-NH2) to CS2 followed by
triazole ring-closure through the loss of one molecule of
H2S. The IR spectrum of compound 5 showed characteristic
Also, treatment of diaminopyridone 4 with acetic anhydride
under reflux afforded 1-acetyl-7-(6-methyl-4-oxo-4H-chro-
men-3-yl)-2-methyl-5-oxo-1,5-dihydro-[1,2,4]triazolo [1,5-
a]pyridine-6,8-dicarbonitrile (6) (Scheme 2). The IR and 1H
NMR spectra of compound 6 confirmed the absence of the
two NH2 groups. The IR spectrum showed characteristic
absorption bands at 2225 (2 CꢀN), 1763 (C═Oacetyl), 1700
(C═Opyridone), and 1616 cmꢁ1 (C═Og-pyrone). The 1H NMR
spectrum showed the presence of three methyl groups at d
1.89 (CH3 triazole), 2.01 (CH3 chromone), and 2.35 (CH3 acetyl).
Treating compound 4 with anthranilic acid in phosphorus
oxychloride gave 2-[(2-aminophenyl)]-7-[(6-methyl-4-oxo-
4H-chromen-3-yl)]-5-oxo-3,5-dihydro-[1,2,4]triazolo [1,5-a]
pyridine-6,8-dicarbonitrile (7) (Scheme 3) [27]. The IR
spectrum of compound 7 exhibited characteristic absorption
bands at 3428, 3210 (NH, NH2), 2219 (2 CꢀN), 1677
(C═Opyridone and C═Og-pyrone), and 1589 cmꢁ1 (C═N and
Scheme 2. Cyclocondensation of 4 with CS2 and Ac2O.
O
NC
1
H
C═C). Also, its H NMR spectrum showed exchangeable
O
O
N
N
signals at 4.71 and 9.96 ppm assigned to the NH2 and NH
protons, respectively. The mass spectrum of compound 7
showed the molecular ion peak at m/z 434, which is coinci-
dent with the molecular weight (434.42).
Compound 7 was used as a precursor for the synthesis
of pyridotriazoloquinazoline derivatives via the reaction
with monoelectrophilic reagents. Thus, condensation of
compound 7 with CS2 and acetic anhydride afforded
chromenylpyridotriazoloquinazolines 8 and 9, respectively
(Scheme 3). The 1H NMR spectrum of compound
8 showed one exchangeable signal at 4.57 ppm assigned
H3C
CS2
N
H
S
pyridine
43%
CN
O
5
4
NC
O
N
N
(CH3CO)2O
53%
H3C
N
CH3
CN
COCH3
O
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DOI 10.1002/jhet

Month 2013
Triazolopyridines, Pyridotriazines, and Pyridotriazepines
Scheme 3. Formation of pyridotriazoloquinazoline derivatives 8 and 9.
O
O
NH2
NC
H
N
O
O
NH2
N
HO
H3C
N
4
CN
POCl3
36%
7
CS2
Ac2O
pyridine
44%
36%
O
O
S
CH3
NC
NC
O
O
N
N
NH
O
O
N
N
N
H3C
H3C
N
N
CN
CN
to the NH proton, whereas the 1H NMR spectrum of
compound 9 showed characteristic singlet at 1.91 ppm
attributed to the methyl protons in the quinazoline moiety.
Also, the mass spectrum of compound 9 revealed the
molecular ion peak at m/z 458 corresponding to the
molecular formula C26H14N6O3, which agrees well with
the molecular weight (458.44) and supports the identity
of the structure.
Herein, we aimed to use diaminopyridone 4 in the syn-
thesis of nitrogen bridge-head pyrido[1,2-b][1,2,4]triazines
of expected biological activity, via the reaction of 4 with
a,b-bifunctional electrophiles. Thus, cyclocondensation
of compound 4 with chloroacetyl chloride and oxalyl
chloride gave pyrido[1,2-b][1,2,4]triazines 10 and 11,
respectively (Scheme 4). The 1H NMR spectrum of
compound 10 revealed characteristic singlet for the CH2
protons at 2.78 ppm, in addition to two exchangeable
signals at 8.50 and 10.30 ppm attributable to 2NH protons.
The 1H NMR spectrum of compound 11 showed two
exchangeable signals at 9.90 and 10.30 ppm assignable to
the two NH protons.
Condensation of compound 4 with sodium pyruvate in
glacial acetic acid containing freshly fused sodium acetate
under reflux afforded 8-(6-methyl-4-oxo-4H-chromen-
3-yl)-3-methyl-2,6-dioxo-1,2,6-trihydropyrido[1,2-b][1,2,4]
triazine-7,9-dicarbonitrile (12) (Scheme 5). The 13C NMR
spectrum of compound 12 showed characteristic signals at
17.9 (CH3 triazine), 19.8 (CH3 chromone), 150.1 (C2 as C═O),
154.6 (C3 as C═N), 161.9 (C6 as C═Opyridone), and
0
192.5 ppm (C4 as C═Og-pyrone). The mass spectrum of
compound 12 showed the molecular ion peak at m/z 386
(M + 1), which agrees with the molecular weight (385.34).
Also, cyclocondensation of diaminopyridone 4 with
benzil in glacial acetic acid containing freshly fused sodium
acetate produced 2,3-diphenylpyrido[1,2-b][1,2,4]triazine
1
derivative 13 (Scheme 5). The IR and HNMR spectra of
compound 13 showed the disappearance of two amino
Scheme 5. Formation of pyrido[1,2-b][1,2,4]triazines 12 and 13.
Scheme 4. Formation of pyrido[1,2-b][1,2,4]triazines 10 and 11.
O
O
O
O
CH3
NC
N
CH3
O
H
N
O
Cl
NC
O
O
N
O
O
O
N
H3C
ONa
H3C
N
H
Cl
N
H
CN
68%
39%
CN
O
12
10
DMF/TEA
gl.AcOH/
NaOAc
O
4
4
O
O
Ph
Ph
H
N
O
Cl
O
NC
N
N
Ph
NC
O
O
O
O
N
O
O
N
H3C
H3C
Cl
N
H
Ph
45%
48%
CN
CN
13
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Abdel-megid, M. A. Ibrahim, Y. Gabr, N. M. El-Gohary, and E. A. Mohamed
Vol 000
groups that were appeared in the IR and 1H NMR spectra of
compound 4. Moreover, the mass spectrum showed the mo-
lecular ion peak at m/z 507, which agrees with the molecular
weight (507.51) and supports the structure.
compound 4 with 2-cyano-3,3-bis(methylthio)acrylonitrile
afforded 2-amino-9-(6-methyl-4-oxo-4H-chromen-3-yl)-4-
methylthio-7-oxo-5H-pyrido [1,2-b][1,2,4]triazepine-3,8,10-
tricarbonitrile (17) (Scheme 7). The reaction may proceed
via nucleophilic displacement of SCH3 group by the more
nucleophilic amino group (N-NH2) with concomitant
cycloaddition of the other amino group (C-NH2) onto nitrile
function to produce the target product 17. The IR spectrum
showed absorption bands at 3434, 3156 (NH2, NH), 2263,
2230 (3CꢀN), 1685 (C═Opyridone), 1632 (C═Og-pyrone),
and 1599 cmꢁ1 (C═N and C═C). Also, its 1H NMR
spectrum exhibited characteristic signals assigned to two
methyl groups at 2.24 (CH3 chromone) and 2.76 ppm (SCH3),
in addition to two exchangeable signals at 7.93 and
10.05 ppm attributed to NH2 and NH protons, respectively.
Similarly, condensation of compound 4 with 2-
cyano-3,3-bis(methylthio)prop-2-enamide under similar
conditions gave 2-amino-8,10-dicyano-9-(6-methyl-4-oxo-
4H-chromen-3-yl)-4-(methylthio)-7-oxo-1,7-dihydropyrido
[1,2-b][1,2,4]triazepine-3-carboxamide (18).
The study was extended to investigate the behavior
of diaminopyridone 4 toward some heterocyclic o-chloroal-
dehydes [30]. Thus, condensation of 4 with 5-chloro-
3-methyl-1-phenylpyrazole-4-carboxaldehyde [31] and
2-chloro-3-formylquinoline [32] in DMF containing few
drops in triethylamine afforded the heteroannulated
pyrido[1,2-b][1,2,4]triazepines 19 and 20, respectively
(Scheme 7). The 1H NMR spectra of compounds 19 and 20
showed characteristic singlet signals because of H-7triazepine
at 8.56 and 8.55ppm, respectively. Also, the spectrum of
compound 20 showed characteristic singlet at 8.90ppm
attributed to the H-4 of the quinoline nucleus. Further, the
mass spectrum of compound 20 revealed the molecular ion
peak at m/z 469 (M-1) corresponding to the molecular
formula C27H14N6O3, which is coincident with the formula
weight (470.45) and supports the identity of the structure.
Further, condensation of diaminopyridone 4 with cyclic
a-dicarbonyl compounds was studied. Thus, refluxing
compound 4 with indol-2,3-dione (isatin) in glacial acetic
acid containing freshly fused sodium acetate afforded
chromenylindolopyridotriazine derivative 14 (Scheme 6).
1
The H NMR spectrum of compound 14 showed one ex-
changeable signal at 10.85 ppm because of NHindole proton.
N-Acetylisatin showed a different behavior [28]. Thus,
reaction of diaminopyridone 4 with N-acetylisatin in
glacial acetic acid led to 2-(2-acetanilido)-8-(6-methyl-4-
oxo-4H-chromen-3-yl)-3,6-dioxo-3,6-dihydro-4H-pyrido
[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (16) (Scheme 6).
This reaction can be explained by an increase in the positive
charge on the a-carbon atom in comparison with isatine
itself because of the electron-withdrawing acetyl group that
facilitates the nucleophilic attack of more nucleophilic
amino group (N-NH2) at this position with concomitant
opening of five-membered ring. Apparently, the reaction
can be claimed to proceed via intermediate 15, as also
observed by previous workers in reaction with other
diamines [29]. However, this type of intermediate was
1
reported to be unstable and not isolated. The H NMR
of compound 16 showed characteristic signals at 1.92
(CH3 in CH3CONH-), 10.19 (NH in CH3CONH-), and
11.01 ppm (NH in triazine). Also, the IR spectrum showed
characteristic absorption bands at 3310, 3121 (2 NH), 2219
(2 CꢀN), 1720 (C═Oacetanilido), 1680 (C═Opyridone), 1660
(C═Otriazine), 1639 (C═Og-pyrone), and 1601 cmꢁ1 (C═N).
On the other hand, diaminopyridone 4 is a useful
building block for nitrogen bridge-head pyrido[1,2-b]
[1,2,4]triazepine derivatives via the reaction with
some a,g-bifunctional electrophiles. Thus, treatment of
Scheme 6. Condensation of 4 with isatin and N-acetylisatin.
O
O
O
H
N
NC
N
O
O
O
N
COCH3
H3C
4
O
NH2
gl. AcOH
44%
NHCOCH3
CN
15
O
gl.AcOH/
NaOAc
57%
N
H
O
O
O
NC
O
H
N
N
NC
O
N
O
N
NHCOCH3
H3C
H3C
N
N
H
N
CN
CN
O
O
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Month 2013
Triazolopyridines, Pyridotriazines, and Pyridotriazepines
Scheme 7. Formation of pyrido[1,2-b][1,2,4]triazepine derivatives 17–20.
O
SCH3
CH3S
CH3S
CN
CN
NC
N
O
O
N
CN
NH2
H3C
N
H
52%
CN
O
17
SCH3
CONH2
NH2
NC
N
CH3S
CH3S
CONH2
CN
O
O
N
H3C
N
H
41%
CN
18
DMF/TEA
4
CH3
N
O
O
NC
N
O
N
N
Cl
H3C
CH3
Ph
56%
N
H
N
N
CN
19
O
Ph
N
O
NC
N
O
O
H3C
Cl
N
N
H
N
CN
54%
O
20
Next, we aimed to study the reactivity of compound 4
toward some arylidenenitriles. Thus, treating diaminopyri-
to the nitrile function with concomitant dehydrogenation to
produce the target compound 22. The H NMR spectrum
1
done
4
with p-methoxybenzylidene-malononitrile in
showed triplet and quartet signals at 1.28 and 4.28 ppm attrib-
uted to the ethoxy protons, the spectrum also revealed charac-
teristic singlet at 3.85 ppm assigned to the methoxy protons.
The chemical behavior of diaminopyridone 4 was
studied toward chromone-3-carboxylic acid [33] and
chromone-3-carbonitrile [34]. Thus, treatment of
compound 4 with chromon-3-carboxylic acid in POCl3
produced 7-(6-methyl-4-oxo-4H-chromene-3-yl)-2-(4-oxo-
4H-chromene-3-yl)-5-oxo-3,5-dihydro-1,2,4-triazolo[1,5-
a]pyridine-6,8-dicarbonitrile (24) (Scheme 9). The IR
spectrum recorded characteristic absorption bands at
3402 (NH), 2219 (2 CꢀN), 1670 (C═Opyridone), 1650 (2
C═Og-pyrone), and 1601 cmꢁ1 (C═N and C═C). Also, its
1H NMR spectrum showed characteristic signals at 9.23
(H–20chromone), 9.44 (H–2chromone), in addition to an
DMF containing two drops of triethylamine gave 2-
amino-4-(4-methoxyphenyl)-7-oxo-5,7-dihydro-9-(6-
methyl-4-oxo-4H-chromen-3-yl)-pyrido[1,2-b][1,2,4]
triazepine-3,8,10-tricarbonitrile (21) (Scheme 8). The 1H
NMR spectrum of compounds 21 showed characteristic
singlet signals at 3.87 ppm attributed to methoxy protons.
The mass spectrum of compound 21 did not recorded the
molecular ion peak at m/z 515 but record a peak at m/e 484
(M-31) corresponding to the molecular weight after
loss of the methoxy group. Also, condensation of 4 with
ethyl 2-cyano-3-(4-methoxyphenyl)prop-2-enoate under
the same reaction conditions yielded ethyl 2-amino-8,
10-dicyano-4-(4-methoxyphenyl)-9-(6-methyl-4-oxo-4H-
chromen-3-yl)-7-oxo-5,7-dihydropyrido[1,2-b][1,2,4]
triazepine-3-carboxylate (22) and not the other possible
product 23 (Scheme 8); the reaction may proceed nucleophilic
addition of amino group (N-NH2) to the activate double bond
followed by cycloaddition of the other amino group (C-NH2)
exchangeable signal at 10.20 ppm attributed to NHtriazole
.
Finally, treatment of 4 with chromone-3-carbonitrile
gave pyridotriazepine derivative 25 (Scheme 9). The reac-
tion may proceed via ring opening of the g-pyrone ring by
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Abdel-megid, M. A. Ibrahim, Y. Gabr, N. M. El-Gohary, and E. A. Mohamed
Vol 000
Scheme 8. Reaction of 4 with arylidinenitriles.
O
Ar
NC
N
CN
H3C
O
O
N
CN
NH2
CN
CH3O
N
H
CN
21
56%
Ar = 4-CH3O-C6H4
O
Ar
DMF/TEA
NC
O
N
4
N
COOEt
H3C
N
H
35%
NH2
CN
22
O
COOEt
CN
Ar = 4-CH3O-C6H4
CH3O
O
H
Ar
O
NC
N
O
O
N
CN
H3C
N
H
CN
23
Ar = 4-CH3O-C6H4
Scheme 9. Reaction of 4 with chromone-3-carboxylic acid and chromone-3-carbonitrile.
O
O
O
NC
O
O
O
O
N
N
HO
H3C
N
H
O
CN
POCl3
54%
24
O
O
4
NC
NC
N
O
O
N
OH
H3C
O
O
N
H
NH2
CN
DMF
39%
EXPERIMENTAL
the more nucleophilic amino group with concomitant
cycloaddition of the other amino group to the nitrile
function. The IR spectrum of compound 25 showed
characteristic absorption bands at 3405, 3315, 3211 (OH,
NH2, NH), 2259, 2220 (2 CꢀN), 1684 (C═Opyridone),
1629 (C═Og-pyrone and C═Oh1ydrogen bonded), and
1600 cmꢁ1 (C═C and C═N). The H NMR spectrum of
compound 25 showed characteristic singlet at 8.46 ppm
because of the H-7triazepine [35].
Melting points were determined on a digital Stuart SMP3
apparatus. Infrared spectra were measured on Perkin-Elmer 293
spectrophotometer (cmꢁ1), using KBr disks. 1H NMR
(300 MHz) and 13C NMR (75 MHz) spectra were measured on
Mercury-300BB, using DMSO-d6 as a solvent and TMS (d) as
the internal standard. Mass spectra were obtained using Jeol-
AMS-AX-500 instrument mass spectrometer (70 eV). Elemental
microanalyses were performed at microanalysis unit in National
Research Center, Dokki, Giza, Egypt.
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Month 2013
Triazolopyridines, Pyridotriazines, and Pyridotriazepines
1,6-Diamino-4-(6-methyl-4-oxo-4H-chromen-3-yl)-2-oxo-
1,2-dihydropyridine-3,5-dicarbonitrile (4).
C21H13N5O4 (399.37): C, 63.16; H, 3.28; N, 17.54%. Found: C,
63.39; H, 3.30; N, 17.63%.
2-[(2-Aminophenyl)]-7-[(6-methyl-4-oxo-4H-chromen-3-yl)]-5-
oxo-3,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitrile
(7). A mixture of compound 4 (0.67 g, 2 mmol) and anthranilic
acid (0.27 g, 2 mmol) in POCl3 (10 mL) was heated under reflux
on a water bath for 4 h. After cooling, the reaction mixture was
poured onto ice/water. The precipitated solid was filtered,
washed with water, air dried, and crystallized from DMF to give
7 as pale brown crystals, yield (0.32 g, 36%), mp 274ꢂC. IR
(KBr, cmꢁ1): 3428, 3210 (NH2, NH), 3059 (CHarom.), 2987,
2928 (CHaliph.), 2219 (2CꢀN), 1677 (C═Opyridone, C═Og-pyrone),
Method A. A mixture of (6-methyl-4-oxo-4H-chromen-3-yl)
methylenemalononitrile (2) (2.36 g, 10 mmol) and cyano-
acetohydrazide (0.99g, 10mmol), in absolute ethanol (50 mL)
containing two drops of piperidine, was heated under reflux for
3 h. The orange-yellow precipitate obtained during heating was
filtered and crystallized from ethanol to give 4 as orange-yellow
crystals, yield (2.33g, 70%), mp 242–243ꢂC.
Method B. A mixture of N`-[(6-methyl-4-oxo-4H-chromen-
3-yl)methylene]-2-cyano acetohydrazide (3) (1.35, 5 mmol) and
malononitrile (0.33 g, 5 mmol), in absolute ethanol (50 mL)
containing two drops of piperidine, was heated under reflux for
3 h. The orange-yellow precipitate obtained during heating was
filtered and crystallized from ethanol to give 4 as orange-yellow
crystals, yield (1.1 g, 68%), mp 242–243ꢂC. IR (KBr, cmꢁ1):
3418, 3313 (2 NH2), 3050 (CHarom.), 2924 (CHaliph.), 2262
(2CꢀN), 1680 (C═Opyridone), 1634 (C═Og-pyrone), 1591 (C═C).
1H NMR (DMSO-d6, d): 2.26 (s, 3H, CH3), 4.59 (bs, 2H,
N-NH2 exchangeable with D2O), 6.92 (d, 1H, J = 8.4 Hz,
H-8chromone), 7.31 (d, 1H, J = 8.4 Hz, H-7chromone), 8.50 (s, 1H,
H-5chromone), 9.40 (s, 1H, H-2chromone), 10.22 (bs, 2H, C-NH2
exchangeable with D2O). m/z (I%): 333 (4), 319 (4), 298 (12),
280 (2), 209 (3), 184 (6), 170 (7), 157 (30), 134 (45), 130 (7),
116 (12), 108 (19), 88 (100), 68 (76). Anal. Calcd for
C17H11N5O3 (333.31); C, 61.26; H, 3.33; N, 21.01%. Found: C,
60.90; H, 3.40; N, 20.70%.
1
1589 (C═N and C═C). H NMR (DMSO-d6, d): 2.22 (s, 3H,
CH3), 4.71 (bs, 2H, NH2 exchangeable with D2O), 6.96–7.88 (m,
6H, Ar-H), 8.46 (s, 1H, H-5chromone), 9.20 (s, 1H, H-2chromone), 9.95
(br, 1H, NH exchangeable with D2O). m/z (I%): 434 (1), 301 (3),
285 (2), 261 (3), 232 (2), 186 (3), 159 (2), 133 (6), 119 (5), 106
(5), 92 (3), 78 (8), 63 (100). Anal. Calcd for C24H14N6O3 (434.42):
C, 66.36; H, 3.25; N, 19.35%. Found: C, 66.10; H, 3.30; N, 19.40%.
2-(6-Methyl-4-oxo-4H-chromen-3-yl)-4-oxo-7-thioxo-4,7-
dihydro-8H-pyrido[10,20:2,3][1,2,4]triazolo[1,5-c]quinazoline-1,3-
dicarbonitrile (8). A mixture of compound 7 (0.86 g, 2 mmol) and
carbon disulfide (0.16 mL, 2 mmol) in pyridine (25mL) was heated
under reflux for 8 h. After cooling, the reaction mixture was poured
onto ice/water and neutralized with conc. HCl. The precipitated
solid was filtered, washed with water, air dried, and crystallized
from dioxane to give 8 as brownish crystals, yield (0.42 g, 44%),
mp 259ꢂC. IR (KBr, cmꢁ1): 3317 (NH), 3071 (CHarom.), 2956,
2925 (CHaliph.), 2235 (2CꢀN), 1660 (C═Opyridone, C═Og-pyrone),
7-(6-Methyl-4-oxo-4H-chromen-3-yl)-5-oxo-2-thioxo-1H-
2,3,4,5-tetrahydro[1,2,4] triazolo[1,5-a]pyridine-6,8-dicarbonitrile
(5). A mixture of compound 4 (0.67 g, 2 mmol) and carbon
disulfide (0.16 mL, 2 mmol) in pyridine (20mL) was heated under
reflux for 8 h. After cooling, the reaction mixture was poured onto
ice/water and neutralized with conc. HCl. The precipitated solid
was filtered, washed with water, air dried, and crystallized from
methanol to give 5 as yellow crystals, yield (0.32 g, 43%), mp
195ꢂC. IR (KBr, cmꢁ1): 3396, 3185 (2 NH), 3067 (CHarom.),
2970, 2940 (CHaliph.), 2216 (2CꢀN), 1680 (C═Opyridone), 1630
1
1611 (C═N and C═C), 1301 (C═S). H NMR (DMSO-d6, d):
2.26 (s, 3H, CH3), 4.57 (bs, 1H, NH exchangeable with D2O),
6.94 (d, 1H, H-8chromone), 7.33–7.80 (m, 5H, Ar-H), 7.95 (s, 1H,
H-5chromone), 8.58 (s, 1H, H-2chromone). Anal. Calcd for
C25H12N6O3S (476.48): C, 63.02; H, 2.54; N, 17.64; S, 6.73%.
Found: 62.80; H, 2.40; N, 17.50; S, 6.80%.
2-(6-Methyl-4-oxo-4H-chromen-3-yl)-7-methyl-4-oxo-4H-pyrido
[10,20:2,3][1,2,4]triazolo[1,5-c]quinazoline-1,3-dicarbonitrile (9). A
mixture of compound 8 (0.86 g, 2 mmol) and acetic anhydride
(10 mL) was heated under reflux for 3 h. After cooling, the reaction
mixture was poured onto ice/water. The precipitated solid was
filtered, washed with water, air dried, and crystallized from DMF to
give 9 as yellow crystals, yield (0.33 g, 36%), mp >300ꢂC. IR
(KBr, cmꢁ1): 3073 (CHarom.), 2925 (CHaliph.), 2237 (2CꢀN), 1672
(C═Opyridone, C═Og-pyrone), 1613 (C═N and C═C). 1H NMR
(DMSO-d6, d): 1.91 (s, 3H, CH3 pyrimidine), 2.26 (s, 3H,
CH3chromone), 6.94 (d, 1H, H-8chromone), 7.34–7.72 (m, 5H, Ar-H),
8.20 (s, 1H, H-5chromone), 9.25 (s, 1H, H-2chromone). m/z (I%): 458
(41), 443 (8), 429 (17), 415 (12), 209 (12), 184 (16), 160 (10), 135
(24), 121 (56), 107 (16), 91 (14), 78 (65), 63 (100). Anal. Calcd for
C26H14N6O3 (458.44); C, 68.12; H, 3.08; N, 18.33%. Found: C,
68.00; H, 3.20; N, 18.30%.
1
(C═Og-pyrone), 1604 (C═C), 1300 (C═S). H NMR (DMSO-d6,
d): 2.25 (s, 3H, CH3), 6.92 (d, 1H, J = 7.8 Hz, H-8chromone), 7.29
(d, 1H, J = 7.5 Hz, H-7chromone), 7.88 (s, 1H, NH exchangeable
with D2O), 8.27 (s, 1H, H-5chromone), 8.85 (s, 1H, NH
exchangeable with D2O), 9.36 (s, 1H, H-2chromone). 13C NMR
(DMSO-d6, d): 19.8 (CH3), 116.3 (C-9), 116.9 (C-7), 119.6
(CꢀN), 123.5 (CꢀN), 125.4 (C-30), 126.6 (C-40a), 128.2 (C-80),
130.9 (C-50), 132.3 (C-60), 134.3 (C-70), 143.2 (C-8), 154.6 (C-
8`a), 159.4 (C-9a), 160.5 (C6 as C═O), 161.9 (C-2`), 187.0 (C2 as
0
C═S), 192.5 (C4 as C═Og-pyrone). Anal. Calcd for C18H9N5O3S
(375.37); C, 57.60; H, 2.42; N, 18.66; S, 8.54%. Found: C, 57.80;
H, 2.60; N, 18.30; S, 8.20%.
1-Acetyl-7-(6-methyl-4-oxo-4H-chromen-3-yl)-2-methyl-5-oxo-
1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitrile (6). A
mixture of compound 4 (0.67 g, 2 mmol) and acetic anhydride
(10 mL) was heated under reflux for 2 h. After cooling, the reaction
mixture was poured onto ice/water. The precipitated solid was
filtered, washed with water, air dried, and crystallized from acetic
acid to give 6 as brown crystals (0.42 g, 53%), mp 290ꢂC. IR
(KBr, cmꢁ1): 3070 (CHarom.), 2960, 2927 (CHaliph.), 2225
(2CꢀN), 1763 (C═Oacetyl), 1700 (C═Opyridone), 1616 (C═Og-
8-(6-Methyl-4-oxo-4H-chromen-3-yl)-3,6-dioxo-1,3,4,6-tetrahydro-
2H-pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (10). A mixture of
compound 4 (0.67 g, 2 mmol) and chloroacetyl chloride (0.16 mL,
2 mmol) in DMF (10 mL) containing few drops of triethylamine
was heated under reflux for 4 h. After cooling, the reaction
mixture was poured onto ice/water. The formed solid was
filtered, washed with water, air dried, and crystallized from
ethanol to give 10 as pale yellow crystals, yield (0.29g, 39%),
mp 244ꢂC. IR (KBr, cmꢁ1): 3404 (2 NH), 2970 (CHaliph.), 2261
(2CꢀN), 1682 (C═Opyridone, C═Otriazinone), 1633 (C═Og-pyrone).
1
pyrone), 1589 (C═N and C═C). H NMR (DMSO-d6, d): 1.89 (s,
3H, CH3 triazole), 2.01 (s, 3H, CH3 chromone), 2.35 (s, 3H, CH3
acetyl), 7.23 (d, 1H, H-8chromone), 7.50 (d, 1H, H-7chromone), 8.51 (s,
1H, H-5chromone), 9.44 (s, 1H, H-2chromone). Anal. Calcd for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Abdel-megid, M. A. Ibrahim, Y. Gabr, N. M. El-Gohary, and E. A. Mohamed
Vol 000
1H NMR (DMSO-d6, d): 2.26 (s, 3H, CH3), 2.78 (s, 2H, CH2CO),
6.92 (d, 1H, J = 7.8Hz, H-8chromone), 7.28 (d, 1H, J = 8.1 Hz, H-
7chromone), 8.29 (s, 1H, H-5chromone), 8.50 (s, 1H, NH
exchangeable with D2O), 9.38 (s, 1H, H-2chromone), 10.30 (bs,
1H, NH exchangeable with D2O). Anal. Calcd C19H11N5O4
(373.33); C, 61.13; H, 2.97; N, 18.76%. Found: C, 60.90; H,
2.80; N, 18.80%.
8-(6-Methyl-4-oxo-4H-chromen-3-yl)-2,3,6-trioxo-1,2,3,4,6-
pentahydro-2H-pyrido[1,2-b][1,2,4[triazine-7,9-dicarbonitrile
(11). A mixture of compound 4 (0.67 g, 2 mmol) and oxalyl
chloride (0.2 mL, 2 mmol) in DMF (15 mL) was heated under
reflux for 2 h. After cooling, the reaction mixture was
concentrated to one-third its original volume. The formed
precipitate was filtered and crystallized from dioxane to give
11 as yellow crystals, yield (0.37 g, 48%), mp 268ꢂC. IR (KBr,
cmꢁ1): 3383, 3250 (2 NH), 3050 (CHarom.), 2924 (CHaliph.),
2218 (2CꢀN), 1680 (C═Opyridone), 1650 (2C═Otriazine), 1622
(C═Og-pyrone). 1H NMR (DMSO-d6, d): 2.26 (s, 3H, CH3),
6.92 (d, 1H, J = 8.7 Hz, H-8chromone), 7.33 (d, 1H, H-7chromone),
8.63 (s, 1H, H-5chromone), 9.49 (s, 1H, H-2chromone), 9.90 (br,
1H, NH exchangeable with D2O), 10.30 (br, 1H, NH
exchangeable with D2O). Anal. Calcd for C19H9N5O5 (387.31):
C, 58.92; H, 2.34; N, 18.08%. Found: C, 58.80; H, 2.40; N,
18.00%.
8-(6-Methyl-4-oxo-4H-chromen-3-yl)--10-oxo-11-hydroindolo
[2,3-e]pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (14).
A
mixture of compound 4 (0.67 g, 2 mmol) and indol-2,3-dione
(0.30 g, 2 mmol), in glacial acetic acid containing freshly fused
sodium acetate, was heated under reflux for 4 h. the solid
obtained during heating was filtered and crystallized from DMF
to give 14 as pale red crystals, yield (0.51 g, 57%), mp 275ꢂC.
IR (KBr, cmꢁ1): 3387 (NH), 2231 (2CꢀN), 1728 (C═Opyridone),
1672 (C═Og-pyrone), 1619 (C═N), 1570 (C═C). 1H NMR
(DMSO-d6, d): 2.27 (s, 3H, CH3), 6.91 (d, 1H, H-8chromone),
7.30–7.85 (m, 5H, Ar-H), 8.25 (s, 1H, H-5chromone), 9.30 (s, 1H,
H-2chromone), 10.85 (s, 1H, NH exchangeable with D2O). m/z (I
%): 443 (M-1; 3), 313 (42), 285 (5), 239 (15), 210 (10), 134 (55),
119 (27), 106 (11), 91 (27), 78 (28). Anal. Calcd for C25H12N6O3
(444.41): C, 67.57; H, 2.72; N, 18.91%. Found: C, 67.70; H,
2.60; N, 18.70%.
2-(2-Acetanilido)-8-(6-methyl-4-oxo-4H-chromen-3-yl)-3,6-dioxo-
3,6-dihydro-4H-pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (16). A
mixture of compound 4 (0.67 g, 2 mmol) and N-acetylisatin (0.38 g,
2 mmol) in glacial acetic acid (30 mL) was heated under reflux for 4 h.
The solid obtained after cooling was filtered and crystallized from
ethanol to give 16 as yellow crystals, yield (0.48 g, 44%), mp. 201ꢂC.
IR (KBr, cmꢁ1): 3310, 3121 (2 NH), 3039 (CHarom.), 2931 (CHaliph.),
2219 (2CꢀN), 1720 (C═Oacetanilido), 1680 (C═Opyridone), 1660
(C═Otriazine), 1639 (C═Og-pyrone), 1601 (C═N), 1598 (C═C). 1H
NMR (DMSO-d6, d): 1.92 (s, 3H, CH3 acetanilido), 2.24 (s, 3H, CH3
chromone), 6.89–8.30 (m, 6H, Ar-H), 8.46 (s, 1H, H-5chromone), 9.37 (s,
1H, H-2chromone), 10.19 (bs, 1H, NH exchangeable with D2O), 11.01
(bs, 1H, NH exchangeable with D2O). Anal. Calcd for C27H16N6O5
(504.43) C, 64.28; H, 3.17; N, 16.66%. Found: C, 64.10; H, 3.00; N,
16.50%.
2-Amino-9-(6-methyl-4-oxo-4H-chromen-3-yl)-4-methylthio-
7-oxo-5H-pyrido[1,2-b][1,2,4]triazepine-3,8,10-tricarbonitrile (17). A
mixture of compound 4 (0.67 g, 2 mmol) and 2-cyano-3,3-bis
(methylthio) acrylonitrile (0.34 g, 2 mmol) in DMF (30 mL) containing
two drops of triethylamine was heated under reflux for 4 h. The solid
obtained after cooling was filtered, washed with ethanol, and
crystallized from DMF/EtOH to give 17 as yellow crystals, yield
(0.47 g, 52%), mp 242ꢂC. IR (KBr, cmꢁ1): 3434, 3156 (NH2, NH),
3049 (CHarom.), 2926 (CHaliph), 2263, 2230 (3CꢀN), 1685
(C═Opyridone), 1632 (C═Og-pyrone), 1599 (C═N and C═C). 1H NMR
(DMSO-d6, d): 2.24 (s, 3H, CH3 chromone), 2.76 (s, 3H, SCH3), 6.90
(d, 1H, J=8.4Hz, H-8chromone), 7.22 (d, 1H, J=8.1Hz, H-7chromone),
7.93 (bs, 2H, NH2 exchangeable with D2O), 8.49 (s, 1H, H-5chromone),
9.31 (s, 1H, H-2chromone), 10.05 (bs, 1H, NH exchangeable with D2O).
m/z (I%): 453 (M-2; 4), 439 (3), 409 (2), 390 (5), 317 (9), 302 (4),
289 (15), 274 (3), 263 (6), 237 (6), 209 (5), 159 (4), 134 (12), 116 (6),
107 (13), 91 (5), 78 (45), 73 (100), 50 (12). Anal. Calcd for
C22H13N7O3S (455.46): C, 58.02; H, 2.88; N, 21.53; S, 7.04%.
Found: C, 57.80; H, 2.80; N, 21.30; S, 6.90%.
2-Amino-8,10-dicyano-9-(6-methyl-4-oxo-4H-chromen-3-yl)-
4-(methylthio)-7-oxo-1,7-dihydropyrido[1,2-b][1,2,4]triazepine-
3-carboxamide (18). A mixture of compound 4 (0.67 g, 2 mmol)
and 2-cyano-3,3-bis(methylthio)prop-2-enamide (0.38 g, 2 mmol)
in DMF (30 mL) containing two drops of triethylamine was
heated under reflux for 4 h. The solid obtained after cooling was
filtered, washed with ethanol, and crystallized from DMF to give
18 as yellow crystals, yield (0.39 g, 41%), mp 142ꢂC. IR (KBr,
cmꢁ1): 3428, 3200 (2NH2, NH), 2925 (CHaliph), 2194 (2CꢀN),
1695 (C═Ocarboxamide), 1682 (C═Opyridone), 1652 (C═Og-pyrone),
1600 (C═N and C═C). 1H NMR (DMSO-d6, d): 2.23 (s, 3H,
CH3 chromone), 2.72 (s, 3H, SCH3), 6.87 (d, 1H, J = 7.2Hz, H-
8-(6-Methyl-4-oxo-4H-chromen-3-yl)-3-methyl-2,6-dioxo-
1,2,6-trihydropyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (12). A
mixture of compound 4 (0.67 g, 2 mmol) and sodium pyruvate
(0.22 g, 2 mmol), in glacial acetic acid containing freshly fused
sodium acetate, was heated under reflux for 3 h. After cooling,
the reaction mixture was poured onto ice/water. The formed
precipitate was filtered, washed with water, air dried, and
crystallized from ethanol to give 12 as yellow crystals, yield
(0.52 g, 68%), mp 283ꢂC. IR (KBr, cmꢁ1): 3432 (NH), 3064
(CHarom.), 2231 (2CꢀN), 1728 (C═Opyridone and C═Otriazinone),
1
1633 (C═Og-pyrone), 1610 (C═N and C═C). H NMR (DMSO-
d6, d): 1.90 (s, 3H, CH3triazine), 2.25 (s, 3H, CH3 chromone), 6.92 (d,
1H, H-8 chromone), 7.28 (d, 1H, H-7chromone), 8.29 (s, 1H, H-
5chromone), 8.50 (s, 1H, NH exchangeable with D2O), 9.38 (s, 1H,
H-2chromone). 13C NMR (DMSO-d6, d): 17.9 (CH3), 19.8
(CH3), 116.4 (C-9), 116.9 (C-7), 119.6 (CꢀN), 120.9 (CꢀN),
123.5 (C-30), 125.4 (C-40a), 128.3 (C-8`), 130.6 (C-50), 132.4
(C-6`), 134.3 (C-70), 144.4 (C-8), 150.1 (C2 as C═O), 154.6 (C3
as C═N), 156.5 (C-80a), 159.4 (C-9a), 161.9 (C6 as C═O), 163.0
0
(C-2`), 192.5 (C4 as C═Og-pyrone). m/z (I%): 386 (M + 1; 5), 317
(62), 302 (11), 289 (21), 274 (9), 261 (5), 246 (5), 134 (100), 106
(22), 79 (20), 66 (15). Anal. Calcd for C20H11N5O4 (385.34); C,
62.34; H, 2.88; N, 18.17%. Found: C, 62.45; H, 2.49; N, 18.23%.
8-(6-Methyl-4-oxo-4H-chromen-3-yl)-2,3-diphenyl-6-oxo-pyrido
[1,2-b][1,2,4]triazine-7,9-dicarbonitrile (13). A mixture of
compound 4 (0.67 g, 2 mmol) and benzil (0.42 g, 2 mmol), in
glacial acetic acid containing freshly fused sodium acetate, was
heated under reflux for 4 h. The solid obtained after cooling was
filtered and crystallized from acetic acid to give 13 as yellow
crystals, yield (0.46 g, 45%), mp 285ꢂC. IR (KBr, cmꢁ1): 2924,
2853 (CH3), 2219 (2CꢀN), 1655 (C═Opyridone and C═Og-pyrone),
1580 (C═N), 1541 (C═C). 1H NMR (DMSO-d6, d): 2.25 (s, 3H,
CH3), 6.92 (d, 1H, H-8chromone), 7.27 (d, 1H, H-7chromone), 7.62–
7.93 (m, 10H, Ar-H), 8.40 (s, 1H, H-5chromone), 9.10 (s, 1H, H-
2chromone). m/z (I%): 507 (2), 238 (3), 210 (11), 179 (11), 134 (5),
106 (49), 93 (5), 77 (17), 65 (73), 51 (100). Anal. Calcd for
C31H17N5O3 (507.51); C, 73.37; H, 3.38; N, 13.80%. Found: C,
73.20; H, 3.40; N, 13.60%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Triazolopyridines, Pyridotriazines, and Pyridotriazepines
8chromone), 7.15 (d, 1H, J = 7.8Hz, H-7chromone), 7.60 (bs, 2H, NH2),
7.94 (bs, 2H, NH2), 8.55 (s, 1H, H-5chromone), 8.74 (s, 1H, H-
2chromone), 10.02 (bs, 1H, NH). Anal. Calcd for C22H15N7O4S
(473.46): C, 55.81; H, 3.19; N, 20.71; S, 6.77%. Found: C, 55.81;
H, 3.19; N, 20.71; S, 6.77%.
Ethyl 2-amino-8,10-dicyano-4-(4-methoxyphenyl)-9-(6-methyl-
4-oxo-4H-chromen-3-yl) -7-oxo-5, 7-dihydropyrido[1,2-b][1,2,4]
triazepine-3-carboxylate (22). A mixture of compound 4 (0.67 g,
2 mmol) and ethyl 2-cyano-3-(4-methoxyphenyl)prop-2-enoate
(0.46 g, 2 mmol) in DMF (30 mL) containing two drops of
triethylamine was heated under reflux for 4 h. The solid obtained
during heating was filtered and crystallized from DMF/H2O to give
22 as reddish orange crystals, yield (0.39 g, 35%), mp 285ꢂC. IR
(KBr, cmꢁ1): 3377, 3200 (NH2, NH), 3032 (CHarom.), 2933, 2841
(CHaliph.), 2220 (2CꢀN), 1710 (C═Oester), 1685 (C═Opyridone),
1634 (C═Og-pyrone), 1593 (C═N and C═C). 1H NMR (DMSO-d6,
d): 1.28 (t, 3 H, J =7.2Hz, CH2CH3), 2.26 (s, 3H, CH3 chromone),
3.85 (s, 3H, OCH3), 4.28 (q, 2H, J=7.2Hz, CH2CH3), 6.93 (d,
1H, J= 8.7Hz, H-8chromone), 7.12 (d, 2H, Ar-H), 7.33 (d, 1H,
J=8.7Hz, H-7chromone), 8.05 (d, 2H, Ar-H), 8.26 (s, 1H, H-
5chromone), 8.44 (bs, 1H, NH exchangeable with D2O), 8.52 (bs,
1H, NH exchangeable with D2O), 9.32 (s, 1H, H-2chromone), 10.24
(bs, 1H, NH exchangeable with D2O). Anal. Calcd for
C30H22N6O6 (562.55): C, 64.05; H, 3.94; N, 14.94%. Found: C,
64.09; H, 4.05; N, 14.72%.
3-Methyl-9-(6-methyl-4-oxo-4H-chromen-3-yl)-7-oxo-7,11-dihydro-
1-phenyl-1H-pyrazolo[3,4-e]pyrido[1,2-b][1,2,4]triazepine-
8,10-dicarbonitrile (19). A mixture of compound 4 (0.67 g,
2 mmol) and 5-chloro-3-methyl-1-phenylpyrazole-4-carbaldehyde
(0.44 g, 2 mmol) in DMF (20mL) containing two drops of
triethylamine was heated under reflux for 4 h. The solid obtained
during heating was filtered and crystallized from DMF to give 19
as yellow crystals, yield (0.56 g, 56%), mp 281ꢂC. IR (KBr,
cmꢁ1): 3332 (NH,), 3063 (CHarom.), 2933 (CHaliph.), 2226
(2CꢀN), 1681 (C═Opyridone), 1633 (C═Og-pyrone), 1589 (C═N
1
and C═C). H NMR (DMSO-d6, d): 2.07 (s, 3H, CH3 pyrazole),
2.38 (s, 3H, CH3 chromone), 6.90–7.80 (m, 7H, Ar-H), 8.15 (s, 1H,
H-5chromone), 8.56 (s, 1H, H-7triazepine), 9.35 (s, 1H, H-2chromone),
11.41 (bs, 1H, NH exchangeable with D2O). Anal. Calcd for
C28H17N7O3 (499.49): C, 67.33; H, 3.43; N, 19.63%. Found: C,
67.10; H, 3.30; N, 19.40%.
7-(6-Methyl-4-oxo-4H-chromen-3-yl)-2-(4-oxo-4H-chromen-
3-yl)-5-oxo-3,5-dihydro[1,2,4]triazolo[1,5-a]pyridine-6,8-
dicarbonitrile (24). A mixture of compound 4 (0.67 g, 2 mmol) and
chromone-3-carboxylic acid (0.38 g, 2 mmol) in phosphorus
oxychloride (30mL) was heated under reflux on a water bath for
4 h. After cooling, the reaction mixture was poured onto ice/water.
The precipitated solid was filtered, washed with water, air dried,
and crystallized from ethanol to give 24 as yellow crystals, yield
(0.53 g, 54%), mp >300ꢂC. IR (KBr, cmꢁ1): 3402 (NH), 3039
(CHarom.), 2925 (CHaliph.), 2219 (2CꢀN), 1670 (C═Opyridone),
2-(6-Methyl-4-oxo-4H-chromen-3-yl)-4-oxo-4H-quinolino
[2,3-e]pyrido[1,2-b][1,2,4]triazepine-1,3-dicarbonitrile (20).
A
mixture of compound 4 (0.67 g, 2 mmol) and 3-formyl-2-
chloroquinoline (0.38g, 2 mmol) in DMF (20mL) containing two
drops of triethylamine was heated under reflux for 4 h. The solid
obtained during heating was filtered and crystallized from ethanol
to give 20 as yellow crystals, yield (0.38g, 54%), mp 290ꢂC. IR
(KBr, cmꢁ1): 3401 (NH), 3063 (CHarom.), 2922, 2860 (CHaliph.),
2226 (2CꢀN), 1681 (C═Opyridone), 1630 (C═Og-pyrone), 1590
1
1
(C═N and C═C). H NMR (DMSO-d6, d): 2.27 (s, 3H, CH3),
1650 (2C═Og-pyrone), 1601 (C═N and C═C). H NMR (DMSO-
6.93 (d, 1H, J = 8.7 Hz, H-8chromone), 7.32 (d, 1H, J = 6.9 Hz, H-
7chromone), 7.76 (t, 1H, J = 7.2 Hz, H-7quinoline), 7.78 (t, 1H,
J = 7.2 Hz, H-6quinoline), 8.01 (d, 1H, J = 7.5 Hz, H-8quinoline), 8.17
(d, 1H, J = 7.8 Hz, H-5quinoline), 8.31 (s, 1H, H-5chromone), 8.55 (s,
1H, H-7triazepine), 8.90 (s, 1H, H-4quinoline), 9.12 (bs, 1H, NH
exchangeable with D2O), 9.23 (s, 1H, H-2chromone). m/z (I%): 469
(M-1; 6), 413 (5), 334 (74), 316 (33), 290 (21), 288 (84), 259
(17), 234 (15), 220 (27), 209 (18), 168 (20).152 (21), 135 (39),
107 (28), 91 (17), 88 (21), 77 (78), 73 (12), 62 (100). Anal. Calcd
for C27H14N6O3 (470.45): C, 68.93; H, 3.00; N, 17.86%. Found:
C, 68.80; H, 3.40; N, 17.90%.
d6, d): 2.28 (s, 3H, CH3), 6.92 (d, 1H, J = 8.7 Hz, H-8chromone),
7.33 (d, 1H, J = 6.6Hz, H-7chromone), 7.57 (t, 1H, J = 7.2 Hz,
H-6`chromone), 7.77 (d, 1H, J = 8.1 Hz, H-8`chromone), 7.89 (t, 1H,
J = 7.5Hz, H-7`chromone), 8.15 (d, 1H, J = 7.8 Hz, H-5`chromone),
8.34 (s, 1H, H-5chromone), 9.23 (s, 1H, H-2`chromone), 9.44 (s, 1H,
H-2chromone), 10.20 (bs, 1H, NH exchangeable with D2O). Anal.
Calcd for C27H13N5O5 (487.44): C, 66.53; H, 2.69; N, 14.37%.
Found: C, 66.20; H, 3.00; N, 14.10%.
2-Amino-3-(2-hyroxyphenyl)carbonyl-7-oxo-9-(6-methyl-4-
oxo-4H-chromen-3-yl)-5H-pyrido[1,2-b][1,2,4]triazepine-8,
10-dicarbonitrile (25). A mixture of compound 4 (0.67 g,
2 mmol) and chromone-3-carbonitrile (0.34 g, 2 mmol) in DMF
(30 mL) was heated under reflux for 4 h. The solid obtained
after cooling was filtered, washed with cold ethanol, and
crystallized from DMF to give 25 as yellow crystals, yield
(0.39 g, 39%), mp >300ꢂC. IR (KBr, cmꢁ1): 3405, 3315, 3211
(NH2, NH, OH), 3050 (CHarom.), 2968, 2922 (CHaliph.), 2259,
2220 (2CꢀN), 1684 (C═Opyridone), 1629 (C═Og-pyrone and
C═Ohydrogen bonded), 1600 (C═C). 1H NMR (DMSO-d6, d):
2.24 (s, 3H, CH3), 6.89 (d, 1H, H-8chromone), 7.26 (d, 1H, H-
7chromone), 7.40–7.90 (m, 4H, A-H), 8.24 (s, 1H, H-5chromone),
8.46 (s 1H, H-7triazepine), 8.58 (bs, 1H, NH), 9.03 (bs, 1H,
NH), 9.34 (s, 1H, H-2chromone), 10.13 (bs, 1H, NH). Anal.
Calcd for C27H16N6O5 (504.47): C, 64.29; H, 3.20; N,
16.66%. Found: C, 64.30; H, 3.10; N, 10.38%.
2-Amino-4-(4-methoxyphenyl)-7-oxo-5,7-dihydro-9-(6-methyl-
4-oxo-4H-chromen-3-yl)-pyrido[1,2-b][1,2,4]triazepine-3,8,10-
tricarbonitrile (21). A mixture of compound 4 (0.67 g, 2 mmol)
and p-methoxybenzylidene-malononitrile (0.36 g, 2 mmol) in
DMF (15 mL) containing two drops of triethylamine was
heated under reflux for 4 h. The solid obtained during heating
was filtered and crystallized from DMF/MeOH to give 21 as
orange crystals, yield (0.58 g, 56%), mp 268ꢂC. IR (KBr,
cmꢁ1): 3399, 3197 (NH2, NH), 3024 (CHarom.), 2850 (CHaliph.),
2217 (3CꢀN), 1682 (C═Opyridone), 1630 (C═Og-pyrone), 1596
1
(C═N and C═C). H NMR (DMSO-d6, d): 2.26 (s, 3H, CH3),
3.87 (s, 3H, OCH3), 6.95 (d, 1H, H-8chromone), 7.15 (d, 2H, Ar-
H), 7.31 (d, 1H, H-7chromone), 8.01 (d, 2H, Ar-H), 8.26 (s, 1H,
H-5chromone), 8.67 (bs, 2H, NH2 exchangeable with D2O), 9.32
(s, 1H, H-2chromone), 10.22 (bs, 1H, NH exchangeable with
D2O). m/z (I%): 515 (not recorded), 484 (M-OCH3; 5), 457
(42), 409 (44), 393 (10), 317 (7), 288 (4), 259 (3), 209 (3), 182
(6), 168 (6), 121 (63), 107 (19), 76 (12), 43 (100). Anal. Calcd
for C28H17N7O4 (515.49): C, 65.24; H, 3.32; N, 19.02%.
Found: C, 65.20; H, 3.4; N, 19.00%.
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