Cyanoacetanilides intermediates in heterocyclic synthesis. Part 1: A facile synthesis of polysubstituted and condensed pyridones

Article abstract of DOI:10.1002/jccs.200400145

Polysubstituted pyridone derivatives were obtained through interaction of cyanoacetanilides with different reagents such as chalcones, 1,1,3-tricyano-2-aminopropene, and arylidenemalononitrile and acetyl-acetone.

Full text of DOI:10.1002/jccs.200400145

Journal of the Chinese Chemical Society, 2004, 51, 975-981
975
Cyanoacetanilides Intermediates in Heterocyclic Synthesis. Part 1: A
Facile Synthesis of Polysubstituted and Condensed Pyridones
Y. A. Ammar,a A. M. Sh. El-Sharief,a Y. A. Mohamed,a M. A. Salem,a
A. G. Al-Sehemib and M. S. A. El-Gabyc*
aDepartment of Chemistry, Faculty of Science, Al-Azhar University, Nasr City 11884 Cairo, Egypt
bChemistry Department, Teachers Colleges, Abha, Saudia
cDepartment of Chemistry, Faculty of Science, Al-Azhar University at Assiut , Assiut 71524, Egypt
Polysubstituted pyridone derivatives were obtained through interaction of cyanoacetanilides with differ-
ent reagents such as chalcones, 1,1,3-tricyano-2-aminopropene, and arylidenemalononitrile and acetyl-
acetone.
Keywords: Acetanilide; Pyridine and pyrido[2,3-d]pyrimidine derivatives.
INTRODUCTION
Pyridone and their fused derivatives play an essential
5 assumed to proceed via Michael addition of the active
methylene to the a,b-unsaturated ketone to yield the Michael
adduct 3 followed by intramolecular cyclization to form 4
and subsequent Dimrouth rearrangement16 to yield 5 (Scheme
I). Also, interaction of 1b with 1,1,3-tricyano-2-aminopro-
pene 6 in the presence of piperidine yielded a single product
that analysed as C15H8ClN5O. This product was formulated as
1-(4-chlorophenyl)-6-amino-4-cyano-methyl-2-pyridon-
3,5-dicarbonitrile 8. Structure 8 was readily demonstrated on
the basis of spectral data. Its infrared spectrum afforded
role in several biological processes and have considerable
chemical and pharmacological importance.1-3 Particularly the
pyridine ring can be found in a broad variety of drugs such as
milirinone,4 which is useful for the treatment of the heart;
acetylcholine5 enhancement is useful in the treatment of
Alzheimer’s disease and 4-aminopyridine derivatives were
reported to have antiamnesic activity.6 As a part of our pro-
gram directed for the development of a new, simple and effi-
cient procedure for the synthesis of biologically active het-
erocyclic nitrogenous compounds utilizing readily obtain-
able intermediates,7-14 we have investigated the reaction of
cyanoacetanilides 1a,b with different reagents for the synthe-
sis of polysubstituted and condensed pyridones. These com-
pounds seem promising for further chemical transformation
and biological evaluation studies.
1
bands at 3271, 3201 (NH2), 2198 cm-1 (CºN) and H NMR
showed a singlet at d = 3.87 ppm (CH2) and at d = 7.2-7.5 ppm
(AB system, 4H, Ar-H). The reaction proceeds through the
formation of 7 as intermediate followed by cyclization, and
the ammonia molecule was eliminated. Dimerization of 1a,b
in ethanol in the presence of sodium ethoxide under reflux
produced the pyridone derivatives 10a,b via the intermediate
9. The structure of 10 could be established for the reaction
product based on the absence of CºN absorption band in the
infrared spectrum, and 1H NMR of 10a revealed a singlet at d
= 2.26 ppm (2CH3), 3.2, 3.7, 9.9 (2NH2, NH; cancelled with
D2O). Also, the mass spectrum of 10b exhibited a molecular
ion peak at m/z 388 (1.3%) and a base peak at m/z 127.
RESULTS AND DISCUSSION
When equimolecular amounts of cyanoacetanilides
1a,b15 and chalcones 2 were reacted in the presence of a cata-
lytic amount of piperidine, pyridones of type 5a,b were ob-
tained. The structure 5 was confirmed for the reaction prod-
uct on the basis of their elemental and spectral data. The in-
frared spectrum of 5a showed the disappearance of CºN
Condensation of 1b with p-anisaldehyde in the pres-
ence of piperidine produced a-cyano-4-methoxy-N-(4-chlo-
rophenyl)cinnamide 11. This compound was utilized in syn-
thesis of several new pyridone derivatives of potential and
synthetic intermediates. Thus, interaction of compound 11
with cyanoacetamide 12a and cyanoacetic acid hydrazide
12b in the presence of piperidine affected cyclization to af-
ford products with analytical and spectral data in complete
1
band. H NMR of 5a revealed two singlets at d = 8.1, 10.2
ppm assignable to two NH groups and a multiplet at d =
7.3-7.8 ppm assigned for aromatic protons. The formation of

976 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ammar et al.
Scheme I
Ar`
Ar`
O
Ar`
O
O
C
O
O
H
H
H
ArNH C
ArNH
ArNH C
Ar`CH CHCOAr``
N
C
(2)
Ar``
O
N
H
Ar``
Ar``
HN
(4)
(5a,b)
(3)
Ar
Ar`
Ar``
5a: C6H4CH3-p
5b: C6H4Cl-p
C6H4Br-p
C6H4Cl-o
C6H4Br-p
C6H4Cl-p
NC
NC
CH2CN
NH2
C
C
CH2CN
H2N
NC
CH2CN
CN
NC
O
CN
-NH3
(6)
H
ArNHCOCH2CN
1a; Ar = C6H4CH3-p
1b; Ar = C6H4Cl-p
(1b)
C
N
O
NH
Ar
N
NH2
Ar
(8; Ar = C6H4Cl-p)
(7)
NH2
NH2
CONHAr
NH2
H
O
CONHAr
N
EtOH/EtONa
C
O
N
NH
Ar
Ar
10a; Ar = C6H4CH3-p
10b; Ar = C6H4Cl-p
(9)
agreement with structures 14a and 14b, respectively. The 1H
NMR spectrum of 14a revealed a singlet at d = 3.8 ppm for
OCH3 and a broad signal at d = 7.99 for NH2. It seems that 14
was formed via Michael type addition of the methylene func-
tion in 12 to the active double bond in 11 to yield acyclic Mi-
chael adduct 13 which cyclizes followed by oxidation to form
14. When enaminonitriles 15a,b17 were reacted with an
equimolecular quantity of 11 in ethanol, excellent yield from
the corresponding dihydropyridine derivatives 17a,b were
formed. The structure of 17 was supported on the basis of ele-
mental analysis and spectral data. The infrared spectrum of
17a showed bands at 3349, 3197, 3119 (NH2, NH), 2192 cm-1
(CºN). Also, 1H NMR spectrum of 17a exhibited signals at d
= 1.5, 3.1 ppm (m, 8H, piperidyl), 3.79 (s, 3H, OCH3), 5.27,
5.89 ppm (2d, 2H, Pyridine H-3, H-4). It can be postulated
that the reaction initially proceeds via a nucleophilic addition
to the double bond to form Michael type adduct 16 that subse-
quently cyclize intramolecularly. In addition, compound 11
was reacted with acetylacetone in boiling ethanol containing
piperidine as catalyst and the pyridone derivative 21 was ob-
tained, and the other possible structure 19 was excluded on
the basis of analytical and spectral data. The structure of 21
was identified on the basis of satisfactory elemental analysis
and spectral data. The infrared spectrum exhibited bands at
2217 (CºN) and 1660 cm-1 (C=O), while its 1H NMR spec-
trum showed signals at d = 1.9, 2.41 (2s, 6H, 2CH3), 6.4 ppm
(s, 1H, CH-pyridone). The reaction was assumed to proceed
via the formation of the Michael adduct 18 as intermediate
which split into p-methoxybenzylideneacetylacetone 20 and
cyanoacetanilide 1b, the latter underwent cyclocondensation
with acetylacetone to form 21. Compound 21 could also be
obtained in good yield via the reaction of 1b with acetylace-
tone in the presence of piperidine (Scheme II).
As a part of this research, the reaction of cyanoacetani-
lide with unsaturated nitriles was investigated. Thus, it has
been found that compound 1b was reacted with a-cinnamo-
nitriles to yield 1:1 Michael adduct 22 as intermediate which
underwent cyclization and oxidation, affording the pyridone
derivatives 23a-c as the final products. IR and 1H NMR spec-
tra were utilized to establish structure 23. IR spectrum of 23a
exhibited bands at 3397, 3295 (NH2) and 2214 cm-1 (CºN).
1H NMR spectrum of 23a showed a singlet at d = 7.9 ppm as-
signable for NH2 and multiplet at d = 7.4-7.8 ppm assigned to
aromatic protons. The proposed structure of 23c was also
confirmed through their synthesis from the reaction of 11
with malononitrile. The behavior of 23a towards some re-

Cyanoacetanilides in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 977
Scheme II
(1b)
CHO
C6H4OCH3-p
C6H4OCH3-p
CONHC6H4Cl-p
CH2CONHY
CN
NC
O
CONHC6H4Cl-p
NC
O
C
N
N
Y
NH2
(12a,b)
NH
OCH3
Y
(14a,b)
CONHC6H4Cl-p
(13)
H3CO
CH
C
12 and 14a; Y = H
b; Y = NH2
CN
(11)
H2N
CN
C6H4OCH3-p
CONHC6H4Cl-p
C6H4OCH3-p
NC
X
NC
X
CONHC6H4Cl-p
X
CH2(COCH3)2
C
N
(15a,b)
N
NH2
NH2
C6H4OCH3-p
(17a,b)
(16)
H
C6H4OCH3-p
COCH3
CN
CH3CO
H3C
NC
O
15 and 17a, X = piperidyl
b; X = morpholinyl
O
O
NH
N
CH3
C6H4Cl-p
C6H4Cl-p
(18)
(19)
CH3
NC
O
CH2(COCH3)2
CH2CONHC6H4Cl-p
CN
N
CH3
(1b)
C6H4Cl-p
COCH3
p-CH3OC6H4CH
(20)
(21)
COCH3
agents was discussed. Thus treatment of 23a with acetic an-
hydride affected cyclization to afford pyrido[2,3-d]pyrimi-
dine derivative 24. Both elemental analysis and spectro-
scopic data are compatible with the assigned structure. Its in-
frared spectrum exhibited bands at 3340 (NH), 2221 cm-1
(CºN). Also, pyridopyrimidine derivative 25 was obtained
upon treatment of 23a with formamide. The structure of 25
was confirmed via inspection of elemental analysis and spec-
CONCLUSION
These results indicate that cyanoacetanilides can be uti-
lized as excellent intermediates for the synthesis of several
polysubstituted pyridin-2-ones and their condensed deriva-
tives. The synthesized compounds appear promising for fur-
ther chemical transformations and for biological testing.
1
tral data. Its H NMR spectrum revealed a multiplet at d =
7.3-7.8 ppm assigned for 8H, a singlet at d = 8.6 ppm (CH-
pyrimidine) and a singlet at d = 9.1 ppm (NH2). In addition,
interaction of 23a with phenyl isocyanate consumed two
moles of the reagent to furnish pyrido[2,3-d]pyrimidine de-
rivative 26 (Scheme III). Finally, condensation of 23a with
hydrazine hydrate caused cyclization to yield pyrazolo[3,4-
b]pyridine derivative 27. Its infrared spectrum exhibited
bands at 3425, 3325 (NH2), 2206 cm-1 (CºN). The formation
of 27 is assumed to proceed via the addition of amino func-
tion of hydrazine to the cyano group followed by an intra-
molecular cyclization through NH3 elimination.
EXPERIMENTAL
Melting points were determined on a stuart apparatus
and are uncorrected. The infrared spectra were recorded on a
1
FT/IR 5300 spectrometer. The H NMR spectra were mea-
sured with a Varian Gemini 200 (200 MHz) spectrometer us-
ing TMS as an internal standard; chemical shifts are reported
as d units. Mass spectra were obtained on a GC-MS-QP 100
EX mass spectrometer at 70 ev. Elemental analyses were car-
ried out at the Microanalytical Center, Cairo University.
Physical data for the synthesized compounds are given in Ta-

978 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ammar et al.
Scheme III
Ar`
O
NC
O
Ac O
2
NH
CH
(23a)
N
N
3
Ar
(24)
(1b)
CN
Ar` NH
2
Ar`CH
X
NC
O
HCONH
2
N
(23a)
N
N
Ar`
Ar`
Ar
NC
O
X
N
NC
O
X
(25)
C
NH
N
NH
2
Ar` NCONHPh
NPh
Ar
Ar
NC
O
PhNCO
(22)
(23a-c)
(23a)
N
N
H
O
CN
CN
H C
2
Ar
(26)
Ar`
(11)
NC
O
NH
2
NH NH
2
2
N
(23a)
N
N
H
23a; Ar = C H Cl-p, Ar` = C H Cl-o, X = CN
6
4
6 4
Ar
23b; Ar = C H Cl-p, Ar` = C H Cl-o, X = COOEt
6
4
6 4
(27)
23c; Ar = C H Cl-p, Ar` = C H OCH -p, X = CN
6
4
6
4
3
ble 1, and the spectral data are collected in Table 2.
precipitate filtered off to give (10a,b). Mass spectrum of 10b
exhibited a molecular ion peak at m/z 388 (M, 1.3%) and a
base peak at m/z 127 (100%).
4,6-Diaryl-2-oxo-1,2-dihydropyridin-3-(N-substituted-
phenyl)carboxamides (5a,b): General procedure
A mixture of 1 (0.01 mol), the chalcone derivatives 2
(0.01 mol) and piperidine (0.5 mL) in ethanol (30 mL) was
refluxed for 3 h. The reaction was cooled and poured into
crushed ice acidified with HCl. The solid product was filtered
off and recrystallized from the proper solvent to give (5a,b).
a-Cyano-4-methoxy-N-(4-chlorophenyl)cinnamide (11)
Equimolar amounts of 1b (0.01 mol) and the appropri-
ate p-anisaldehyde (0.01 mol) in ethanol (30 mL) were
treated with a few drops of piperidine and refluxed for 1 h.
The solid product formed was filtered off and recrystallized
from the appropriate solvent to give (11).
6-Amino-1-(4-chlorophenyl)-4-cyanomethyl-2-oxo-1,2-di-
hydropyridin-3,5-dicarbonitrile (8)
2-Amino-5-cyano-6-oxo-4-(4-methoxyphenyl)-1,6-dihydro-
pyridine-3-(N-4-chlorophenyl)carboxamides (14a,b): Gen-
eral procedure
To a solution of 1b (0.01 mol) in ethanol (30 mL),
1,1,3-tricyano-2-aminopropene 6 (0.01 mol) and piperidine
(0.5 mL) were added. The mixture was refluxed for 3 h,
cooled and poured into crushed ice acidified with drops of
HCl where the solid was filtered off and recrystallized from
suitable solvent to give (8).
A mixture of 11 (0.01 mol), cyanoacetamide or cyano-
acetohydrazide (0.01 mol) and piperidine (0.5 mL) was
refluxed for 3 h. cooled, poured into crushed ice and the re-
sulting solid was filtered off and then recrystallized from the
proper solvent to give (14a,b).
1-Aryl-2,4-diamino-6-oxo-1,6-dihydropyridin-3-(N-substi-
tutedphenyl)carboxamides (10a,b): General procedure
To a solution of sodium ethoxide prepared from sodium
(2.5 g) and ethanol (20 mL), a solution of 1 (0.01 mol) in etha-
nol (20 mL) was added. The reaction mixture was refluxed
for 3 hr, cooled, poured into ice acidified with HCl and the
2-Amino-5-cyano-4-(4-methoxyphenyl)-6-(piperidin-1-yl
or morpholin-4-yl)pyridin-3-(N-4-chlorophenyl)carbox-
amides (17a,b): General procedure
A solution of 11 (0.01 mol) in ethanol (30 mL) was
treated with enaminonitriles 15a,b (0.01 mol) and piperidine

Cyanoacetanilides in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 979
Table 1. Physical data of synthesized compounds
Elemental analyses
Calcd./Found [%]
Compd. Yield
Solvent
Cryst.
M.P.
[°C]
Mol. Formula
(Mol. Wt.)
No.
(%)
C
H
N
5a
60
Benzene
140
C25H18Br2N2O2
(538)
55.76
55.67
3.34
3.29
5.20
5.16
5b
67
70
75
73
80
50
52
60
65
80
70
70
80
50
80
60
65
Benzene
MeOH
Benzene
Benzene
Dioxane
Benzene
Benzene
MeOH
MeOH
AcOH
90
170
C24H15Cl3N2O2
(469.5)
C15H8ClN5O
(309.5)
C20H20N4O2
(348)
C18H14Cl2N4O2
(389)
C17H13ClN2O2
(312.5)
C20H15ClN4O3
(394.5)
C20H16ClN5O3
(409.5)
C25H26ClN5O2
(463.5)
C24H24ClN5O3
(465.5)
C14H11ClN2O
(258.5)
C19H10Cl2N4O
(381)
C21H15Cl2N3O3
(428)
C20H13ClN4O2
(376.5)
C21H12Cl2N4O2
(423)
C20H11Cl2N5O
(408)
C33H20Cl2N6O3
(619)
61.34
61.20
58.15
58.40
68.96
68.70
55.52
55.65
65.28
65.35
60.83
60.70
58.60
58. 70
64.72
64.90
61.86
61.90
64.99
65.05
59.84
59.70
58.87
58.90
63.74
63.80
59.57
59.70
58.82
58.90
63.97
63.70
57.57
57.70
3.19
3.15
2.58
2.70
5.74
5.90
3.59
3.70
4.16
4.10
3.80
3.85
3.91
3.80
5.60
5.60
5.15
5.26
4.25
4.30
2.62
2.70
3.50
3.50
3.45
3.30
2.83
2.70
2.69
2.70
3.23
3.20
2.77
2.70
5.96
5.80
2.61
8
2.70
10a
10b
11
160
16.09
16.30
14.40
14.50
8.96
140
220
8.90
14a
14b
17a
17b
21
110
14.19
14.30
17.09
17.17
15.10
15.20
15.03
15.13
10.83
10.90
14.69
14.70
9.81
200
130
250
275
23a
23b
23c
24
DMF
> 300
300
AcOH
9.90
DMF
> 300
> 300
> 300
120
14.87
14.70
13.23
13.40
17.15
17.30
13.57
13.80
17.67
17.60
DMF
25
DMF
26
Benzene
Benzene
27
200
C19H11Cl2N5O
(396)
(0.5 mL). The mixture was refluxed for 3 h, cooled and the re-
sulting solid was filtered off and recrystallized from the
proper solvent to give (17a,b).
(21).
Method B
A mixture of 1b (0.01 mol), acetylacetone (0.01 mol)
and piperidine (0.5 mL) was fused in an oil bath at 150 °C for
1/2 hr to give (21; m.p. and mixed m.p.).
4,6-Dimethyl-2-oxo-1-(4-chlorophenyl)-1,2-dihydro-
pyridin-3-carbonitrile (21)
Method A
6-Amino-2-oxo-1,4-diaryl-5-cyano or ethoxycarbonyl-
1,2-dihydropyridin-3-carbonitriles (23a-c): General pro-
cedure
To a solution of 11 (0.01 mol) in ethanol (30 mL),
acetylacetone (0.01 mol) and piperidine (0.5 mL) were added
and the mixture was refluxed for 3 h, cooled and the solid was
filtered off and crystallized from the proper solvent to give
Method A
Equimolar amounts of 1b (0.01 mol) and the appropri-

980 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ammar et al.
Table 2. Spectroscopic data of the synthesized compounds
Compd.
No.
IR (n, cm-1)
1H NMR (d, ppm) (DMSO-d6)
5a
5b
8
3267, 3187 (2NH), 2935 (CH-aliph), 1682
(C=O).
3293 (NH), 2931 (CH-aliph), 1685, 1659
(C=O).
3271, 3201 (NH2), 2954 (CH-aliph), 2198
(C= N), 1666 (C=O).
6.4 (s, 1H, CH), 7.3-7.8 (m, 12H, Ar-H), 8.1,
10.2 (2s, 2H, 2NH).
3.87 (s, 2H, CH2), 7.2-7.5 (AB-system), 10.3 (s,
2H, NH2).
10a
3290, 3199 (NH2), 3132 (NH), 1666 (C=O).
2.26 (s, 6H, 2CH3), 3.2, 3.7 (s, 4H, 2NH2), 7.0-
7.4 (m, 9H, Ar-H+CH pyridine), 9.9 (s, 1H,
NH).
10b
11
3275, 3205 (NH2), 3137 (NH), 1663 (C=O).
3317 (NH), 2923 (CH-aliph), 2221 (CºN),
1674 (C=O).
14a
14b
17a
3323 broad (NH2, NH), 2945 (CH-aliph), 2199 3.8 (s, 3H, OCH3), 6.9-7.2 (m, 8H, Ar-H) 7.99
(CºN).
(broad, 2H, NH2), 9.3 (s, 2H, 2NH).
3347, 3171 (NH2 + NH), 2979 (CH-aliph),
2260 (CºN), 1688 (C=O).
3349, 3197 (NH2), 3119 (NH), 2192 (CºN),
1640 (CO).
1.5, 3.1 (m, 10H, piperidyl), 3.79 (s, 3H, OCH3),
3.8 (s, 2H, NH2), 5.27, 5.8 (2d, 2H, H-3, H-4-
pyridyl), 6.8-7.9 (m, 8H, Ar-H), 10.2 (s, NH).
17b
21
3422, 3229 (NH2 + NH), 2965 (CH-aliph),
2209 (CºN), 1638 (C=O).
2217 (CºN), 1660 (C=O).
1.9, 2.4 (2s, 6H, 2CH3), 6.4 (s, 1H, CH), 7.3-7.6
(m, 4H, Ar-H).
23a
23b
3397, 3295 (NH2), 2214 (CºN), 1660 (C=O).
3349, 3281 (NH2), 2220 (CºN), 1699, 1667
(C=O).
7.4-7.6 (m, 8H, Ar-H), 7.98 (s , 2H, NH2).
0.6 (t, 3H, CH3-ester), 3.8 (q, 2H, CH2-ester),
7.2-7.6 (m, 8H, Ar-H), 7.7 (s, 2H, NH2).
2.8 (s, 2H, NH2), 3.8 (s, 3H, OCH3), 7.0-7.3-7.8
(m, 8H, Ar-H), 8.5 (s, 1H, CH), 9.1 (s, 2H,
NH2).
23c
3319, 3102 (NH2), 2212 (CºN), 1661 (C=O).
24
25
3340, (NH), 2221 (CºN), 1666 (C=O).
3448, 3255 (NH2), 2198 (CºN), 1650 (C=O).
7.3-7.8 (m, 8H, Ar-H), 8.6 (s, 1H, CH), 9.1 (s,
2H, NH2).
26
27
3379, 3247 (NH), 2221 (CºN), 1735, 1689
(C=O).
3425, 3325 (NH2 + NH), 2206 (CºN), 1651
(C=O).
ate cinnamonitrile (0.01 mol) in ethanol (30 mL) was treated
with piperidine (0.5 mL) and the reaction mixture was
refluxed for 3 hr. The resulting solid was filtered off and
recrystallized from the suitable solvent. The mass spectrum
of 23a showed a molecular ion peak at 380 (100%) and other
peaks such as 354 (12.5%), 354 (44.2%), 282 (16.9%), 180
(8.0%) and 75 (35.9%) were observed.
2-Methyl-4,7-dioxo-5-(2-chlorophenyl)-8-(4-chlorophenyl)-
3,4,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-carbonitrile
(24)
A suspension of 23a (0.01 mol) in acetic anhydride (15
mL) was refluxed for 6 h, cooled and the resulting precipitate
was filtered off and recrystallized from the proper solvent to
give 24.
Method B
A mixture of 11 (0.01 mol) and malononitrile (0.01
mol) in ethanol (30 mL) containing piperidine (0.5 mL) was
refluxed for 3 h. The obtained product was filtered and re-
crystallized to give (23c; m.p. and mixed m.p.).
4-Amino-7-oxo-5,8-diaryl-7,8-dihydropyrido[2,3-d]pyri-
midin-6-carbonitrile (25)
A solution of 23a in formamide (10 mL) was refluxed
for 2 h and the obtained product after cooling and filtration

Cyanoacetanilides in Heterocyclic Synthesis
was recrystallized.
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 981
R. P. J. Heterocyclic Chem. 1995, 32, 1283.
3. Oliver Kappe, C.; Kappe, T. Monatshefte fur Chemie 1989,
120, 1095.
4. Attois, A. A.; Canter, J. M.; Montanero, M. J.; Fort, D. J.;
Hood, R. A. J. Cardiova-Scular Pharmacology 1983, 303,
535.
1-(6-Cyano-2,7-dioxo-3-phenyl-5-(2-chlorophenyl)-8-(4-
chlorophenyl)-2,3,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-
ylidene)-3-phenyl urea (26)
To a solution of 23a (0.01 mol) in ethanol (20 mL),
phenyl isocyanate (0.01 mol) and triethylamine (0.5 mL)
were added. The reaction mixture was refluxed for 3 h, cooled
and the resulting solid was filtered off and recrystallized to
give (26).
5. Andreani, A.; Leani, A.; Ville, G. Eur. J. Med. Chem. 2000,
35, 77.
6. Ammar, Y. A.; Ghorab, M. M.; El-sharief, A. M. Sh.;
Mohamed, Sh. I. Heteroatom Chemistry 2002, 13, 199.
7. El-Sharief, A. M. Sh.; Ghorab, M. M.; El-Gaby, M. S. A;
Mohamed, Sh. I.; Ammar, Y. A. Heteroatom Chemistry
2002, 13, 316.
3-Amino-6-oxo-4-(2-chlorophenyl)-7-(4-chlorophenyl)-6,7-
dihydro-1H-pyrazolo[3,4-b]pyridin-5-carbonitrile (27)
A mixture of 23a (0.01 mol) and hydrazine hydrate
(0.012 mol) in ethanol (20 mL) was refluxed for 3 h. The mix-
ture was cooled and the obtained product was recrystallized
to furnish 27 (Table 1). Mass spectrum of 27 showed a molec-
ular ion peak at m/z 395 (40%) with other peaks at 375
(100%), 359 (43%), 111 (30.2%).
8. El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
El-Gaby, M. S. A. Heteroatom Chemistry 2002, 13, 291.
9. El-Gaby, M. S. A.; Ammar, Y. A.; El-Sharief, A. M. Sh.;
Zahran, M. A.; Khames, A. A. Heteroatom Chemistry 2002,
13, 611.
10. El-Sharief, A. M. Sh.; Ammar, Y. A.; Zahran, M. A.; Ali, A.
H. J. Chem. Research (S) 2002, 205.
11. Zahran, M. A.; El-Sharief, A. M. Sh.; El-Gaby, M. S. A.;
Ammar, Y. A.; El-Said, U. H. IL Farmaco 2001, 56, 277.
12. Ammar, Y. A.; El-Sharief, A. M. Sh; Ali, M. M.; Mohamed,
Y. A.; Mohamed, Sh. I. Phosphorus, Sulfur and Silicon
2000, 166, 173.
Received October 17, 2003.
13. Ammar, Y. A.; El-Sharief, A. M. Sh.; Zahran, M. A.; Ali, M.
H.; El-Gaby, M. S. A. Molecules 2001, 6, 267.
14. El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
Zahran, M. A.; Sabet, H. Kh J. Chem. Res (S) 2003, 162.
15. Sachse, B.; Ertel, H. (Hoechst A-G) Ger.Offen, 2, 546, 271
(Cl.AO1Ny 120), 28 Apr. 1977, Appl. 16 Oct. 1975.
16. Al-Arab, M. M. J. Heterocyclic Chem.1989, 26, 1665.
17. Cocco, M. T.; Congiu, C.; Onnis, V.; Maccioni, A. Synthesis
1991, 529.
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