Synthesis of some new nitrogen bridge-head pyrido[1,2,4]triazepines

Article abstract of DOI:10.1007/s10593-010-0460-y

Ring closure reactions of 1,6-diamino-4-(4-chlorophenyl)-2-oxopyridine-3,5- dicarbonitrile with various 1,3-dielectrophiles, namely, diethyl malonate, ethyl ethoxymethylenecyanoacetate, 2-cyano-3,3-bis(methylthio)acrylonitrile, dimethyl acetylenedicarboxy

Full text of DOI:10.1007/s10593-010-0460-y

Chemistry of Heterocyclic Compounds, Vol. 45, No. 12, 2009
SYNTHESIS OF SOME NEW NITROGEN
BRIDGE-HEAD PYRIDO[1,2,4]TRIAZEPINES
M. Abdel-Megid1*
Ring closure reactions of 1,6-diamino-4-(4-chlorophenyl)-2-oxopyridine-3,5-dicarbonitrile with various
1,3-dielectrophiles, namely, diethyl malonate, ethyl ethoxymethylenecyanoacetate, 2-cyano-
3,3-bis(methylthio)acrylonitrile, dimethyl acetylenedicarboxylate, dehydroacetic acid, chromone-
3-carbonitrile, and 3-formylchromone led to the formation of the target biheterocyclic 1,2,4-triaze-
pines. The reactions with 3-phenylazo-2,4-pentadione, ethyl α-cyano-α-phenylazoacetate, and 3,1-benz-
oxazin-4-one derivative are also described.
Keywords: pyridotriazepines, pyridotriazines, triazolopyridines.
It has been shown that condensed triazepines exhibit important pharmacological activities [1–4]. Most of
the reported condensed triazepines are from the types [1,2,5]-, [1,3,5]-, and [1,3,4]triazepines such as
benzo[1,2,5]triazepines [5, 6], triazolo[1,2,5]triazepines [7], benzo[1,3,5]triazepines [8], and benzo-
[1,3,4]triazepines [9]. In contrast, the biheterocyclic 1,2,4-triazepines are relativity rare. A few examples were
seen in the literature such as thiazolo[1,2,4]triazepines [10, 11], oxadiazolo- and isoxazolo[1,2,4]triazepines
[12], and pyrazolopyrimido[1,2,4]triazepines [13]. As a part of our program directed to the synthesis of new
polynuclear bioactive heterocyclic systems [14-17], the present synthetic strategy is designed to utilize
1,6-diamino-4-(4-chlorophenyl)-2-oxopyridine-3,5-dicarbonitrile (1) as a suitable starting material for the
synthesis of nitrogen bridge-head pyrido[1,2,4]triazepines of expected biological activity.
It is well known that compounds having vicinal amino groups are good precursors for building many
condensed heterocycles [18, 19]. Compound 1 as an example of such compounds was used in the synthesis of
triazolopyridines [20-22] and pyridotriazines [22, 23], but until now only a few examples of pyrido[1,2-b]-
[1,2,4]triazepines are known [22, 24]. Therefore, we used compound 1 to synthesize some novel pyrido-
[1,2-b][1,2,4]triazepines via ring closure reactions with some interesting 1,3-dielectrophiles. Thus, when 1,6-di-
amino pyridine derivative 1 was allowed to react with diethyl malonate in boiling DMF, 9-(4-chlorophenyl)-
1
2,4,7-trioxo-1,3,5-trihydropyrido[1,2-b][1,2,4]triazepine-8,10-dicarbonitrile (2) was obtained. The H NMR
spectrum of compound 2 showed a singlet signal at δ 3.35 ppm due to the CH2 protons in addition to two
exchangeable singlets at δ 5.67 and 8.52 ppm assigned to N−NH and C−NH protons, respectively. The treatment
of compound 1 with ethyl ethoxymethylenecyanoacetate may afford two possible pyridotriazepine
_______
* To whom correspondence should be addressed, e-mail: mabdelmegid@yahoo.com.
1Chemistry Department, Faculty of Education, Ain-Shams University, Roxy, Cairo, A. R. Egypt.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, 1888-1896, December, 2009.
Original article received June 15, 2009.
0009-3122/09/4512-1523©2009 Springer Science+Business Media, Inc.
1523

derivatives 3 and 4. Compound 4 was ruled out due to the absence of triplet and quartet signals attributed to the
1
ethoxy group in the H NMR spectrum. Compound 3 showed a characteristic singlet signal at δ 7.79 ppm
attributed to H-3 proton. The formation of compound 3 proceeds via nucleophilic replacement of the ethoxy
group followed by cyclocondensation losing one ethanol molecule.
Ketene dithioacetals are very useful building blocks to incorporate two or three carbon units in the
construction of a variety of heterocyclic compounds. Thus, the treatment of compound 1 with 2-cyano-3,3-bis-
(methylthio)acrylonitrile afforded 2-amino-9-(4-chlorophenyl)-4-methylthio-7-oxo-5H-pyrido[1,2-b][1,2,4]tri-
azepine-3,8,10-tricarbonitrile (5). The reaction proceeds through an addition−elimination mechanism, which
starts with nucleophilic addition at the sp2 sulfur-substituted carbon atom of ketene dithioacetal followed by
elimination of the methanethiol molecule with a cascade addition to the nitrile function to produce the target
product 5.
On the other hand, a new derivative of pyridotriazepine 6 was obtained from the reaction of the starting
diamino compound 1 with dimethyl acetylenedicarboxylate. The IR spectrum of compound 6 showed absorption
1
bands at 3412, 3344 (2NH), and 1710 cm–1 (C=O ester). Its H NMR spectrum showed a characteristic singlet
signals at δ 2.90 and 7.95 ppm assigned to CH3 and H-3 protons, respectively, in addition to two exchangeable
signals at δ 5.67 and 8.53 ppm corresponding to 2NH protons.
Scheme 1
O
O
O
O
SMe
CN
H
N
H
N
NC
NC
N
N
N
H
N
NH2
CN
CN
Cl
Cl
2
5
CH2(COOEt)2
(NC)2C=C(SMe)2
O
O
COOMe
H
N
NC
NH2
NC
N
MeOOCC
CCOOMe
Cl
N
NH2
N
H
O
CN
CN
Cl
6
1
EtOCH=C(CN)COOEt
O
O
COOEt
CN
O
H
N
H
N
NC
NC
N
N
N
N
H
NH2
CN
CN
Cl
Cl
3
4
Herein, the chemical reactivity of compound 1 was studied towards 3-phenylazo-2,4-pentanedione (7) and
ethyl α-cyano-α-phenylazoacetate (10) [19]. Thus, the treatment of compound 1 with 7 afforded 9-(4-chloro-
phenyl)-2,4-dimethyl-7-oxo-3-phenylhydrazono-1H-pyrido[1,2-b][1,2,4]triazepine-8,10-tricarbonitrile (9).
1524

Scheme 2
O
Me
N
N
NC
N
1
+
CH2(COMe)2
Me
_
CN
Cl
8
+
PhN N Cl
O
MeC
O
O
Me
NNHPh
N
N
NC
NC
NH2
MeC
O
N
N
NNHPh
7
NH2
Me
CN
CN
Cl
Cl
1
9
CN
PhNHN
COOEt
10
O
H
O
H
NHNHPh
COOEt
NH2
NHNHPh
NC
N
NC
N
N
N
CN
O
N
H
N
CN
CN
Cl
Cl
–PhNHNH2
–PhNHNH2
O
O
NC
N
CN
N
N
NC
COOEt
NH2
N
N
H
O
N
CN
CN
Cl
Cl
NH2
11
12
O
N
NC
N
NNHPh
N
H
O
CN
Cl
13
The latter compound 9 was also obtained authentically from the coupling of phenyldiazonium chloride
with compound 8, which was prepared from the condensation of the starting material 1 with acetyl acetone [24]
in glacial acetic acid. The structure of compound 9 was deduced from elemental analysis and spectral data. Its 1H
NMR spectrum showed only one exchangeable signal at δ 8.52 ppm assigned to the NH proton, in addition to two
singlet signals at δ 2.31 and 2.47 ppm attributed to 2- and 4-CH3 protons.
1525

On the other hand, ethyl α-cyano-α-phenylazoacetate showed a different behavior towards compound 1,
producing 8-(4-chlorophenyl)-2,6-dioxo-1H-pyrido[1,2-b][1,2,4]triazine-3,7,9-tricarbonitrile (11). The reaction
may proceed through nucleophilic addition of the amino (N−NH2) group to the highly activated carbon atom
(N=C) followed by cyclization with losing one molecule of ethanol and subsequent elimination of one molecule
of phenylhydrazine to produce compound 11. The other possible products 12 and 13 were excluded on the basis
1
of elemental analysis and spectral data. The H NMR spectrum of the product did not show the ethoxy protons
that appeared in 12 and the phenyl protons present in compound 13 (Scheme 2).
Moreover, the reaction of diamino compound 1 with some cyclic oxygenated compounds such as
benzoxazinone and dehydroacetic acid was deduced. Thus, when compound 1 reacted with 2-phenyl-4H-3,1-
benzoxazin-4-one [25] in dry pyridine, [1,2,4]triazolo[2,3-a]pyridinedicarbonitrile 15 was obtained through the
formation of intermediate 14, which on dehydration yielded compound 15 and not compounds 16 or 17. The 1H
NMR spectrum of compound 15 revealed the presence of two deshielded protons at δ 12.18 and 8.56 ppm due to
the two NH protons in addition to the aromatic protons, which were observed in the range of δ 7.22-8.09 ppm.
On the other hand, the treatment of compound 1 with dehydroacetic acid in glacial acetic acid afforded
pyrano[2,3-e]pyrido[1,2-b][1,2,4]triazepine 19 via intermediate 18. The structure of compound 19 was elucidated
Scheme 3
Ph
N
O
NHCOPh
O
NC
N
N
NC
N
N
N
H
O
NH2
CN
Cl
15
CN
Cl
16
–H2O
–H2O
O
N
O
O
H
–H2O
N
NC
Ph
N
1
O
NHCOPh
NH2
CN
14
Ph
Cl
O
NC
Me
O
Me
N
N
N
O
N
O
Me
CN
17
Cl
HO
Me
O
O
O
Me
O
H
N
N
NC
OH
Me
–2H2O
Cl
Me
NC
N
N
Me
N
NH2
O
CN
CN
Cl
18
19
1526

from its elemental analysis and spectral data. The IR spectrum exhibited one absorption band at 1655 cm–1
1
corresponding to C=O of the pyridone system. The H NMR spectrum showed two singlets at δ 2.56 and 3.34
ppm assigned to the two methyl groups in addition to a characteristic signal at δ 7.95 ppm attributed to the H-3
proton; the replaceable signal at δ 8.50 ppm was assigned to the OH proton (Scheme 3).
Also, the research was extended to study the effect of 1,6-diaminopyridone 1 towards very active
substrates named chromone-3-carbonitrile (20) and chromone-3-carboxaldehyde (21) with the aim to prepare
some novel 1,2,4-triazepine derivatives. Thus, the treatment of compound 1 with compounds 20 and 21 afforded
pyrido[1,2-b][1,2,4]triazepines 23 and 26, respectively. The latter two products gave a positive coloration with
iron(III) chloride solution due to the presence of phenolic OH group. Formation of compound 23 proceeds via
ring opening at C-2 of γ-pyrone to give compound 22, then addition to the cyano group, while formation of
Scheme 4
HO
CN
O
O
H
N
H
N
NC
NC
N
N
OH
NH2
O
N
NH2
CN
CN
Cl
Cl
23
22
O
O
NC
20
1
O
OHC
O
21
–H2O
O
O
HO
O
H
N
NC
N
NC
N
N
CHO
NH2
NH2
O
CN
CN
24
Cl
Cl
25
–H2O
HO
O
O
H
N
NC
N
NC
N
N
OH
O
O
N
N
H
CN
CN
26b
Cl
Cl
26a
1527

compound 26a may proceed via ring opening at C-2 of γ-pyrone to yield compound 24, then cyclocondensation
with the formyl group, while the isomeric form of compound 26b is formed initially via condensation with the
formyl group to afford compound 25, then ring opening at C-2 of γ-pyrone.
EXPERIMENTAL
Melting points are uncorrected and were recorded in open capillary tubes on a Stuart SMP3 melting point
apparatus. IR spectra were recorded on an FT-IR Bruker Vector 22 spectrophotometer using the KBr wafer
1
technique. H NMR spectra were measured on a Gemini (200 MHz) spectrometer using DMSO-d6 as solvent
and TMS as an internal standard. Mass spectra were obtained using a Shimadzu GC-MS qp 1000 ex instrument
mass spectrometer (70 eV). Elemental microanalyses were performed at the Cairo University Micro Analytical
Center.
1,6-Diamino-4-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (1) was prepared
according to the reported method [26].
9-(4-Chlorophenyl)-2,4,7-trioxo-1,3,5,-trihydropyrido[1,2-b][1,2,4]triazepine-8,10-dicarbonitrile (2).
A mixture of compound 1 (1.46 g, 5 mmol) and diethyl malonate (0.8 ml, 5 mmol) in DMF (20 ml) was refluxed
for 6 h; after cooling, the reaction mixture was poured onto ice. The solid obtained was filtered off, washed with
water and recrystallized from DMF/H2O to give compound 2 as white crystals, yield 0.92 g (63%); mp > 300ºC.
IR spectrum, ν, cm–1: 3415, 3343 (2NH); 2216, 2210 (2C≡N); 1668 (C=O pyridone); 1655-1645 (2C=O amide).
1H NMR spectrum, δ, ppm (J, Hz): 3.35 (2H, s, CH2); 5.67 (1H, s, NH); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62,
7.66 (2H, d, J = 8.2, Ar); 8.52 (1H, s, NH). Mass spectrum, m/z (I, %): 354 [M] (4.8), 321 (100). Found, %: C
54.85; H 2.42; Cl 10.3; N 19.55. C16H8ClN5O3. Calculated, %: C 54.43; H 2.26; Cl 10.02; N 19.80.
9-(4-Chlorophenyl)-2,7-dioxo-2,5-dihydropyrido[1,2-b][1,2,4]triazepine-4,8,10-tricarbonitrile (3).
A mixture of compound 1 (1.46 g, 5 mmol) and ethyl ethoxymethylenecyanoacetate (0.56 g, 5 mmol) in DMF
(20 ml) was refluxed for 6 h; after cooling, the reaction mixture was poured onto ice. The solid obtained was
filtered off, washed with water, and crystallized from ethanol to give compound 3 as pale-yellow crystals, yield
0.85 g (58%); mp 280–282ºC. IR spectrum, ν, cm–1: 3410, 3334 (2NH), 2226, 2220, 2218 (3C≡N); 1686 (C=O
pyridone); 1655 (C=O amide). 1H NMR, δ, ppm (J, Hz): 5.67 (1H, s, NH); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62,
7.66 (2H, d, J = 8.2, Ar); 7.79 (1H, s, H-3); 8.52 (1H, br. s, NH); Mass spectrum, m/z (I, %): 363 [M] (2.4). Found,
%: C 56.65; H 3.42; Cl 9.57; N 21.35. C17H7ClN6O2. Calculated, %: C 56.27; H 1.93; Cl 9.79; N 23.17.
2-Amino-9-(4-chlorophenyl)-4-methylthio-7-oxo-5H-pyrido[1,2-b][1,2,4]triazepine-3,8,10-tricarbo-
nitrile (5). A mixture of compound 1 (1.46 g, 5 mmol) and 2-cyano-3,3-bis(methylthio)acrylonitrile (0.85 g,
5 mmol) in DMF (20 ml) was refluxed for 4 h. The solid obtained after cooling was filtered off and
recrystallized from DMF/EtOH to give compound 5 as yellow crystals, yield 1.2 g (82%); mp 210-212ºC. IR
spectrum, ν, cm–1: 3416, 3340, 3305 (NH, NH2); 2978 (CH aliphatic); 2220, 2216, 2215 (3 C≡N); 1669 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.66 (3H, s, SCH3); 5.66 (1H, s, NH); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62,
7.66 (2H, d, J = 8.2, Ar); 8.51 (2H, s, NH2). Found %: C 57.85; H 2.42; N 26.35; Cl 9.65. C18H10ClN7O.
Calculated, %: C 57.52; H 2.66; N 26.09; Cl 9.45.
Methyl 9-(4-chlorophenyl)-8,10-dicyano-2,7-dioxo-1,5-dihydropyrido[1,2-b][1,2,4]triazepine-4-carb-
oxylate (6). A mixture of compound 1 (1.46 g, 5 mmol) and dimethyl acetylenedicarboxylate (0.83 ml, 5 mmol)
in DMF (20 ml) was refluxed for 8 h. The solid obtained after cooling was filtered off and recrystallized from
methanol to give compound 6 as brown crystals, yield 1.12 g (76%); mp 296–298ºC. IR spectrum, ν, cm–1: 3412,
3344 (2NH); 2974 (CH aliphatic); 2220, 2216 (2C≡N); 1710 (CO ester); 1670 (C=O pyridone);
1528

1646 (C=O amide). 1H NMR spectrum, δ, ppm (J, Hz): 2.90 (3H, s, OCH3); 5.67 (1H, s, NH); 7.51, 7.55 (2H, d,
J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar); 7.95 (1H, s, H-3); 8.53 (1H, s, NH). Found %: C 54.85; H 2.42;
Cl 9.16; N 17.35. C18H10ClN5O4 (375.5). Calculated, %: C 54.61; H 2.52; Cl 8.97; N 17.69.
9-(4-Chlorophenyl)-2,4-dimethyl-7-oxo-3,7-dihydropyrido[1,2-b][1,2,4]triazepine-8,10-dicarbo-
nitrile (8). A mixture of compound 1 (1.46 g, 5 mmol) and acetylacetone (0.5 ml, 5 mmol) in glacial acetic acid
(30 ml) was refluxed for 6 h; after cooling the reaction mixture was poured onto ice. The solid obtained was
filtered off, washed with water, and crystallized from methanol to give compound 8 as white crystals, yield 1.0 g
(68%); mp 290–291ºC. Reported mp 298ºC [24].
9-(4-Chlorophenyl)-2,4-dimethyl-7-oxo-3-phenylhydrazono-1H-pyrido[1,2-b][1,2,4]triazepine-
8,10-tricarbonitrile (9). A. A mixture of compound 1 (1.46 g, 5 mmol) and 3-phenylazo-2,4-pentanedione (7)
(1.02 g, 5 mmol) in acetic acid (20 ml) was refluxed for 8 h. The solid obtained after cooling was filtered off and
recrystallized from methanol to give compound 9 as orange crystals, yield 1.10 g (75%); mp 275-276ºC.
B: A mixture of compound 8 (0.57 g, 7 mmol) in ethanol (25 ml) and sodium acetate (1 g) was added
gradually to a solution of benzene diazonium chloride (0.51 g, 4 mmol); the temperature was kept lower than
5ºC. The solid obtained was filtered off and recrystallized from DMF/MeOH to give compound 9 as orange
crystals, yield 1.22 g (83%); mp 275–276oC. IR spectrum, ν, cm–1: 3304 (NH); 2987 (CH aliphatic); 2220, 2216
1
(2C≡N); 1670 (C=O); 1520 (N=N). H NMR spectrum, δ, ppm (J, Hz): 2.31 (3H, s, CH3); 2.47 (3H, s, CH3);
7.22, 7.24 (2H, d, J = 8.2, Ar); 7.46–7.59 (5H, m, C6H5); 7.61, 7.66 (2H, d, J = 8.2, Ar); 8.52 (1H, s, NH).
Found, %: C 63.85; H 3.42; Cl 7.61; N 21.35. C24H16ClN7O. Calculated, %: C 63.50; H 3.52; Cl 7. 82; N 21.60.
8-(4-Chlorophenyl)-2,6-dioxo-1H-pyrido[1,2-b][1,2,4]triazine-3,7,9-tricarbonitrile (11). A mixture
of compound 1 (1.46 g, 5 mmol) and ethyl α-cyano-α-phenylazoacetate (1.08 g, 5 mmol) in acetic acid (20 ml)
was refluxed for 4 h; after cooling, the reaction mixture was poured onto ice. The solid obtained was filtered off
and recrystallized from DMF/H2O to give compound 11 as yellow crystals, yield 1.25 g (85%); mp 311-312ºC.
1
IR spectrum, ν, cm–1: 3415 (NH); 2220, 2215, 2210 (3C≡N); 1669 (C=O pyridone); 1653 (C=O amide). H
NMR spectrum, δ, ppm (J, Hz): 7.22 (1H, s, H-3); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar);
8.51 (1H, s, NH). Mass spectrum, m/z (I, %): 348 (13.0), 63 (100). Found %: C 54.85; H 1.42; Cl 10.37; N 24.35.
C16H5ClN6O2. Calculated, %: C 55.09; H 1.43; Cl 10.18; N 24.10.
2-(2-Benzoylaminophenyl)-7-(4-chlorophenyl)-5-oxo-1H-[1,2,4]triazolo[2,3-a]pyridine-6,8-dicarbo-
nitrile (15). A mixture of compound 1 (1.46 g, 5 mmol) and 2-phenyl-4H-3,1-benzoxazin-4-one (0.56 g,
5 mmol) in dry pyridine (30 ml) was refluxed for 6 h; after cooling, the reaction mixture was poured onto ice-
HCl. The solid obtained was filtered off, washed with water, and recrystallized from DMF/H2O to give
compound 15 as yellow crystals, yield 0.96 g (61%); mp 250-252ºC. IR spectrum, ν, cm–1: 3410, 3315 (2NH);
1
2222, 2216 (2 C≡N); 1668 (C=O pyridone); 1345 (C=O amide). H NMR spectrum, δ, ppm (J, Hz): 7.22-7.26
(4H, m, C6H4); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar); 7.95–8.09 (5H, m, C6H5); 8.56
(1H, s, NH); 12.18 (1H, s, NH). Found, %: C 65.85; H 3.12; Cl 7.39; N 17.35. C27H15ClN6O2. Calculated, %:
C 66.05; H 3.05; Cl 7.23; N 17.12.
10-(4-Chlorophenyl)-4-hydroxy-2,6-dimethyl-8-oxopyrano[2,3-e]pyrido[1,2-b][1,2,4]triazepine-
9,11-dicarbonitrile (19). A mixture of compound 1 (1.46 g, 5 mmol) and dehydroacetic acid (0.84 ml, 5 mmol)
in glacial acetic acid (40 ml) was refluxed for 8 h; after cooling, the reaction mixture was poured onto ice. The
solid obtained was filtered off, washed with water and recrystallized from DMF to give compound 19 as brown
crystals, yield 1.24 g (85%); mp 308–309ºC. IR spectrum, ν, cm–1: 3535 (OH); 3395, 3325 (2NH); 2987 (CH
aliphatic); 2221, 2216 (2 C≡N); 1655 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.56 (3H, s, CH3); 3.34 (3H, s,
CH3); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar); 7.95 (1H, s, H-3); 8.50 (1H, s, OH). Mass
spectrum, m/z (I, %): 417 [M] (17.9), 77 (100). Found, %: C 60.65; H 2.62; Cl 8.79; N 16.55. C21H12ClN5O3.
Calculated, %: C 60.35; H 2.87; Cl 8.50; N 16.76.
2-Amino-9-(4-chlorophenyl)-3-(2-hydroxybenzoyl)-7-oxo-6H-pyrido[1,2-b][1,2,4]triazepine-8,10-di-
carbonitrile (23). A mixture of compound 1 (1.46 g, 5 mmol) and chromone-3-carbonitrile (20) (0.85 g,
1529

5 mmol) in dry pyridine (40 ml) was refluxed for 4 h; after cooling, the reaction mixture was poured onto ice-
HCl. The solid obtained was filtered off and recrystallized from DMF/H2O to give compound 23 as yellow
crystals, yield 1.35 g (92%); mp 262-264ºC. IR spectrum, ν, cm–1: 3527 (OH); 3453, 3397, 3304 (NH, NH2);
2220, 2219 (2 C≡N); 1668 (C=O); 1655 (C=O pyridone). 1H NMR spectrum, δ, ppm (J, Hz): 5.67 (2H, s, NH2);
7.32 (1H, s, H-4); 7.51, 7.55 (2H, d, J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar); 7.97−8.09 (4H, m, C6H4);
8.52 (1H, s, NH); 9.12 (1H, s, OH). Found, %: C 60.85; H 2.62; Cl 7.97 N 18.35. C23H13ClN6O3. Calculated, %:
C 60.46; H 2.84; Cl 7.77; N 18.40.
9-(4-Chlorophenyl)-3-(2-hydroxybenzoyl)-7-oxo-6H-pyrido[1,2-b][1,2,4]triazepine-8,10-dicarbo-
nitrile (26). A mixture of compound 1 (1.46 g, 5 mmol) and chromone-3-carbaldehyde (21) (0.87 g, 5 mmol) in
dry pyridine (40 ml) was refluxed for 4 h; after cooling, the reaction mixture was poured onto ice-HCl. The solid
obtained was filtered off and crystallized from DMF/H2O to give compound 26 as yellow crystals, yield 1.18 g
(80%); mp 157-158ºC. IR spectrum, ν, cm–1: 3527 (OH); 3305 (NH); 2221, 2216 (2 C≡N); 1668 (C=O
pyridone); 1655 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 7.06 (1H, s, H-4); 7.30 (1H, s, H-2); 7.51, 7.55 (2H, d,
J = 8.2, Ar); 7.62, 7.66 (2H, d, J = 8.2, Ar); 7.97−8.09 (4H, m, C6H4); 8.20 (1H, s, NH); 8.94 (1H, s, OH). Found
%: C 62.85; H 2.42; Cl 8.32; N 15.55. C23H12ClN5O3. Calculated, %: C 62.51; H 2.71; Cl 8.04; N 15.85.
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