β-oxoanilides in heterocyclic synthesis: An expeditious synthesis of new polyfunctionally substituted pyridine and pyrazole derivatives

Article abstract of DOI:10.1002/jhet.5570450641

(Chemical Equation Presented) 3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl] phenyl}butanamide 3 was condensed with (DMF-DMA) in refluxing dry dioxane to yield branched structure 4 not its linear isomeric 5. Compound 4 readily reacted with active methylene to

Full text of DOI:10.1002/jhet.5570450641

Nov-Dec 2008
1819
ꢀ-Oxoanilides in Heterocyclic Synthesis: An Expeditious Synthesis
of New Polyfunctionally Substituted Pyridine and Pyrazole
Derivatives
A. M. Hussein1, A. A. Harb2, and I. A. Mousa2
1- Chemistry Department, Faculty of Science, Al-Azhar University, Assiut, 71524 Egypt
2- Chemistry Department, Faculty of Science, South Valley University, Qena, Egypt
E-mail: abdelhaleemmh@yahoo.com
Received June 25, 2007
O
O
X
Y
O
O
O
O
Ar
DMF-DMA
N
Ar
Ar
N
N
H
H
Y
NMe2
X
N
O
Ar =
S
X = CN,
Y = NH2
N
N
X = CONH2, Y = NH2
X = COOEt, Y = NH2
X = COCH3, Y = CH3
O
H
3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}butanamide 3 was condensed with (DMF-DMA) in
refluxing dry dioxane to yield branched structure 4 not its linear isomeric 5. Compound 4 readily reacted
with active methylene to yield compounds 8a-c, 14, 17 and 20 respectively. Also enaminone 4 reacted with
phenyl hydrazine giving 24 and 25. In contrast, when compound 4 reacted with hydrazine hydrate in the
same experimental conditions pyrazole derivative 27 was obtained. Furthermore, condensation of anilide 3
with triethylorthoformate in refluxing acetic anhydride afforded the ethoxy methylene derivative 28. On
the other hand, compound 28 was reacted with active methylene reagents, and hydrazines to afford the
products identical in all respects (mp., mixed mp., and spectral data) with those corresponding to
compounds 6-27 respectively. Similarly, compound 3 was reacted with hydrazine hydrate to afford the
reaction product 29. Also, compound 3 reacted with cyanoacetamide in refluxing ethanolic pipridine
solution to yield the pyridine derivative 30. Finally, 3 reacted with hydroxylamine hydrochloride in
refluxing ethanol/sodium acetate solution to yield the acyclic oxime derivative 31.
J. Heterocyclic Chem., 45, 1819 (2008).
INTRODUCTION
RESULTS AND DISCUSSION
It has been found that 3-oxo-N-{4-[(pyrimidin-2-
ylamino)sulfonyl]phenyl}butanamide 3 was condensed
with N,N-dimethylformamide-dimethylacetal (DMF-
DMA) in refluxing dry dioxane to yield a product that
may be either structure 4 or its isomeric 5. Establishing
the exact structure of the reaction product as structure 4
rather than 5 was based on elemental analysis and spectral
Literature survey revealed that polyfunctionally
substituted pyridones have played an important role in the
development of bioactive compounds for the inhibition of
enzymatic processes [1-3]. A number of representative
pyridone derivative 1 are effective inhibitors of HIV
reverse transcriptase. Pyridone 2 is a potent (4.5 nm),
reversible nonpeptidic inhibitor of human leukocyte
elastase (HLE) [4,5]. In view of our continued interest in
developing efficient synthesis of polyfunctionally
substituted heteroaromatics utilizing the readily
obtainable starting materials [6-9], we report here the
results of our investigations aiming to explore the
synthetic potential of 3-Oxo-N-{4-[(pyrimidin-2-yl-
amino)sulphonyl]phenyl}butanamide 3 to synthesis of
substituted pyridones from enaminone using active
methylene reagents.
1
data. H nmr spectra revealed the presence of a singlet
signal at ꢀ = 1.2 ppm assigned to the acetyl functional
group and absence of olefinic doublet-doublet which
would be observed for structure 5.
Scheme 2
O
O
Ar
N
H
O
O
DMF-DMA
dry dioxan
4
Ar
NMe2
O
N
H
O
Scheme 1
3
Ar
H3C
N
H
NMe2
Y
5
N
H3C
O
CH3
CF3
Ph
X
CH3
N
O
O
O
NH
Ar =
N
S
Ph
O
N
N
O
N
N
H
Y
H
H
O
1
O
O
2

1820
A. M. Hussein, A. A. Harb, and I. A. Mousa
Vol 45
Compound 4 readily reacted with malononitrile in
reacted with enaminone 4 in ethanolic piperidine solution
to yield compound 14. Assignment of structure 14 for the
reaction product was based on its correct elemental
refluxing ethanolic piperidine solution to yield the product
which may be formulated as structures 8a or 11a.
Structure 11a was ruled out and structure 8a was
considered to be only the reaction product based on
spectroscopic data. Thus, the 1H nmr spectrum of
compound 8a showed a singlet signal (3H) at ꢀ = 3.56
ppm assigned for acetyl protons, a broad signal at ꢀ =
5.75 ppm assigned for NH2 protons, multiplet at ꢀ = 6.51 -
7.58 ppm assigned for CH aromatic and 2 NH, and a
singlet at ꢀ = 8.35 ppm assigned for CH-pyridine. Also,
its mass spectrum revealed a molecular ion peak at m/z =
411(M+1) corresponding to the molecular formula
1
analysis and compatible spectroscopic data. Thus, the H
nmr spectrum showed, the presence of singlet signals at ꢀ
= 1.70, 2.05 ppm assigned for 2 COCH3 protons besides
the expected signals. Compound 14 is assumed to be
formed by condensing acetyl acetone to enaminone 4 with
elimination of dimethyl amine which would afford
intermediate 13 which on cyclization via water
elimination gives 14 (Scheme 4).
Similarly, ethyl acetoacetate was reacted with
enaminone 4 at the same conditions to yield compound 17
(Scheme 5).
C18H14N6O4S. Similarly, compound
4 reacted with
cyanoacetamide and ethyl cyanoacetate to yield the
pyridone derivatives 8b,c rather than 11b,c respectively.
In contrast to the behavior of active methylene reagents
to enaminone 4, compound 4 readily reacted with
Scheme 3
O
X
O
O
X
O
O
X
O
Ar
Ar
X
CN
O
Ar
N
CH3
N
N
4
H
NC
H2N
HN
6
8a-c
7
O
O
Ar
X
Ar
X
Ar
X
N
N
H
N
H
H
CN
H3C
OH
H3C
N
O
H3C
O
NH
H
11a-c
9
10
8 a, X = CN
b, X = CONH2
c, X = COOEt
Formation of 8a-c is believed to proceed via initial
addition of active methylene moiety in malononitrile to
afford the Michael adduct 6 via elimination of dimethyl
amine, which cyclizes into 7 and aromatized to the
pyridone derivatives 8a-c.
cyanothioacetamide in refluxing ethanolic pipridine
solution to yield the product which may be formulated as
pyridinethione 20 neither 22 nor 23. Structure 20 was
considered to be the reaction product based on its
spectroscopic data and further confirmed on the bases of
its chemical behavior towards different chemical reagents
(Scheme 6).
Also, the behavior of enaminone 4 towards active
diketone reagents was investigated. Thus, acetyl acetone
Scheme 4
O
O
O
O
O
O
Ar
Ar
Ar
CH3COCH2COCH3
EtOH/pip
N
CH3
N
N
CH3
4
H
H
H3C
H3C
H3C
COCH3
COCH3
14
COCH3
O
HO
13
12
Scheme 5
O
O
O
O
O
O
Ar
Ar
CH3COCH2COOEt
N
Ar
CH3
N
4
-EtOH
N
H
EtOH/pip
EtO2C
O
HO
COCH3
COCH3
COCH3
15
16
17

Nov-Dec 2008
ꢀ-Oxoanilides in Heterocyclic Synthesis: An Expeditious Synthesis of New Polyfunctionally
1821
Scheme 6
O
CH3
O
Ar
CN
S
Ar
N
CN
N
NMe2
-NMe2H
H
H
4
+
CSNH2
N
H
H3C
CSNH2
CN
20
19
O
O
O
O
O
O
Ar
Ar
N
H
Ar
CN
Ar
CN
S
N
CH3
-H2O
N
N
H
H
NC
H2N
S
NH2
H3C
N
H
22
OH
CSNH2
S
NH2
21
23
Furthermore, the behavior of enaminone 4 towards
phenyl hydrazine and hydrazine hydrate was also
investigated. Thus, enaminone 4 reacted with phenyl
hydrazine giving products depending on the ratio between
the reactants. Thus, the reaction between 4 and phenyl
hydrazine in equimolar ratio yielded two products 24 and
25. However, when the reaction is carried out using one
mole of 4 with two moles of phenyl hydrazine, product 25
was isolated as the only reaction product. The exact
structure of such reaction product is based on its
elemental analysis and spectroscopic data. Thus, the mass
spectrum of compound 24 revealed a molecular ion peak
at m/z = 452 (M+) corresponding to the molecular formula
C21H20N6O4S. Compound 25 was confirmed based on its
spectroscopic data (Scheme 7).
other hand, compound 28 was reacted with the active
methylene reagents, and hydrazines to afford products
identical in all respects (mp., mixed mp., and spectral
data) with those corresponding to compounds 6-27
respectively (Scheme 9).
Scheme 9
X
O
O
O
O
CH(OEt)3
Ar
Ar
Y
N
N
6-23
H
H
OEt
28
RNHNH2
24-27
O
O
Scheme 7
Ar
N
H
+ 25
Ph
HN
N
24
NH
1 mole
2 mole
CH3
N Ph
Ar
PhNHNH2
4 +
HN
N
H
Ph
O
N
CH3
Ar
N
H
25
N
Ph
N
26
In contrast, when compound 4 reacted with hydrazine
hydrate under the same experimental conditions the
pyrazole derivative 27 was afforded (Scheme 8).
On the other hand, the reactivity of anilide 3 towards
hydrazine hydrate, cyanoacetamide, and hydroxyl amine
hydrochloride was investigated. Thus, acetoacetanilide 3
was reacted with hydrazine hydrate to afford the reaction
product 29. Assignment of structure 29 for the reaction
product was based on its correct elemental analysis and
spectroscopic data. Also, anilide 3 reacted with cyano-
acetamide in refluxing ethanolic pipridine solution to
yield the product which may be formulated as pyridine
derivative 30. Furthermore, anilide 3 reacted with
hydroxylamine hydrochloride in refluxing ethanol/sodium
acetate solution to yield the acyclic oxime derivative 31.
Structure 31 was established based on its elemental
analysis and spectroscopic data. Thus, its 1H NMR
Scheme 8
O
CH3
Ar
4
+ PhNHNH2
N
H
NH
N
27
Also, condensation of anilide 3 with triethylortho-
formate in refluxing acetic anhydride afforded the ethoxy
methylene derivative 28. Establishing of the structure 28
was based on elemental analysis and spectral data. On the

1822
A. M. Hussein, A. A. Harb, and I. A. Mousa
Vol 45
4-(3-Acetyl-6-amino-5-cyano-2-oxo-2H-pyridin-1-yl)-N-
pyrimidin-2-ylbenzene-sulfonamide (8a). Compound 8a was
obtained as colorless crystals from ethanol; yield 40%; mp 210º;
ir: 3400 (NH2), 3200 (NH), 2240 (CN), 1700 (CO), 1650 (CO)
cm-1; 1H nmr (DMSO-d6) ꢀ: 1.55 (s, 3H, CH3), 3.56 (s, 1H, NH),
5.75 (s, 2H, NH2), 6.6 (d, 2H, CH-pyrimidine-ꢁ-protons), 6.8-7.6
(m, 5H, Ar-H), 8.4 (s, 1H, CH-C-4-pyridine ring); MS: m/z 410
(411 M+1). Anal. Calcd. for C18H14N6O4S: C, 52.66; H, 3.43; N,
20.47; S, 7.80. Found: C, 52.71; H, 3.49; N, 20.52; S, 7.91.
5-Acetyl-2-amino-6-oxo-1-{4-[(pyrimidin-2ylamino)sulfonyl]-
phenyl}-1,6-dihydropyridine-3-carboxamide (8b). Compound
8b was obtained as colorless crystals from ethanol; yield 35%;
mp 180º; ir: 3450 (NH2), 3200 (NH2), 1700 (CO), 1650 (CO)
spectrum showed absorption peaks at ꢀ = 2.5 ppm (CH3)
protons, at ꢀ = 3.32 ppm assigned for (OH) proton, at ꢀ =
5.97 ppm (CH2) protons, and at ꢀ = 11.22 ppm a broad
signal assumed for (NH) proton beside the expected
signals (Scheme 10).
Scheme 10
H
N
O
Ar
NH2NH2H2O
Ar
N
CNCH2CONH2
N
3
CH3
N
H
H2N
CH3
CONH2
29
NH2OH.HCl
1
cm-1 ; H nmr (DMSO-d6) ꢀ: 1.78 (s, 3H, CH3), 7.0-8.0 (m, 8H,
30
Ar-H), 8.4 (s, 2H, NH2), 10.33 (s, 1H, NH), 11.87 (s, 2H, NH2);
MS: m/z 428 (423 M-5). Anal. Calcd. for C18H16N6O5S: C, 50.46;
H, 3.76; N, 19.62; S, 7.48. Found: C, 50.49; H, 3.80; N, 19.68;
S, 7.52.
HO
O
N
Ar
N
CH3
5-Acetyl-2-amino-6-oxo-1-{4-[(pyrimidin-2ylamino)sulfonyl]-
phenyl}-1,6-dihydropyridine-3-caroxylic acid ethyl ester (8c).
Compound 8c was obtained as brown crystals from toluene/
ethanol; yield 30%; mp 170º; ir: 3400 (NH2), 3200 (NH), 1730
(CO), 1670 (CO) cm-1; 1H nmr (DMSO-d6) ꢀ: 1.03 (t, 3H,
CH3), 1.24 (s, 3H, acetyl-CH3), 2.52 (s, 2H, NH2), 4.025 (q, 2H,
CH2), 7.0-8.0 (m, 7H, Ar-H), 8.4 (s, 1H, CH-C-4-pyridine ring),
10.34 (s, 1H, NH); MS: m/z 457. Anal. Calcd. for C20H19N5O6S:
C, 52.51; H, 4.19; N, 15.31; S, 7.01. Found: C, 52.58; H, 4.22;
N, 15.36; S, 7.10.
H
31
EXPERIMENTAL
All melting points are uncorrected and were determined on a
Gallenkamp apparatus; IR spectra were recorded on Schimadzu
470 spectrophotometer in potassium bromide discs; H NMR
1
spectra were recorded on
a Varian EM-390 (90 MHz)
spectrophotometer using TMS as internal standard, Mass
spectrometer MS 30(AEL) at 70eV. Analytical data were
obtained from the micro analytical data center at Cairo
University.
4-(3,5-Diacetyl-6-methyl-2-oxo-2H-pyridin-1-yl)-N-pyrim-
idin-2-ylbenzene-sulfonamide (14). Compound 14 was
obtained as colorless crystals from methanol; yield 30%; mp
1
205º; ir: 3200 (NH), 1700 (CO) cm-1; H nmr (DMSO-d6) ꢀ:
3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulphonyl]phenyl}-
butanamide (3). Compound 3 was prepared as literature
procedure [10].
1.59 (s, 6H, 2CH3), 2.05 (s, 3H, CH3), 6.4 (d, 2H, CH-
pyrimidine-ꢁ-protons); 7.4-7.9 (m, 5H, Ar-H), 8.2 (s, 1H, CH-C-
4-pyridine ring), 10.11 (s, 1H, NH); MS: m/z 426. Anal. Calcd.
for C20H18N4O5S: C, 56.33; H, 4.25; N, 13.14; S, 7.52. Found: C,
56.39; H, 4.28; N, 13.18; S, 7.58.
4-(3,5-Diacetyl-6-hydroxy-2-oxo-2H-pyridin-1-yl)-N-
pyrimidin-2-ylbenzene-sulfonamide (17). Compound 17 was
obtained as yellow crystals from ethanol/acetic acid; yield 45%;
mp 235º; ir: 3500 (OH), 3200 (NH), 1700 (CO), 1650 (CO)
cm-1; 1H nmr (DMSO-d6) ꢀ: 1.65 (s, 6H, 2CH3), 5.6 (s, 1H, OH),
6.6 (d, 2H, CH-pyrimidine-ꢁ-protons), 7.4-7.8 (m, 5H, Ar-H),
8.2 (s, 1H, CH-C-4-pyridine ring), 9.63 (s, 1H, NH); MS: m/z
428. Anal. Calcd. for C19H16N4O6S: C, 53.27; H, 3.76; N, 13.08;
S, 7.48. Found: C, 53.31; H, 3.80; N, 13.10; S, 7.51.
2-Acetyl-3-(dimethylamino)-N-{4-[(pyrimidin-2-ylamino)-
sulfonyl] phenyl}acrylamide (4). A mixture of anilide (3) (3.34
gm, 10.0 mmoles) and DMF/DMA (Dimethylformamide/
Dimethylacetal) (1.32 mL, 10.0 mmoles) in dry dioxane was
heated under reflux for 3 hrs, then the solvent was evaporated
under vacium. The solid product formed was collected by
filtration and crystallized from ethanol as yellow crystals; yield
42%; mp 230˚; ir: 3300 (NH), 3200 (NH), 1710 (CO), 1660
1
(CO) cm-1; H nmr (DMSO-d6) ꢀ: 1.2 (s, 3H, CH3), 2.47 (s, 6H,
2CH3), 7-7.7 (m, 8H, aromatic protons and 1H CH), 12.2 (br,
1H, NH); MS: m/z 389 (386 M-3), 389 (387 M-2). Anal. Calcd.
for C17H19N5O4S: C, 52.42; H, 4.93; N, 17.97; S, 8.22. Found: C,
52.47; H, 5.12; N, 18.38; S, 8.33.
5-Cyano-2-methyl-N-{4-[(pyrimidin-2-ylamino)sulfonyl]-
phenyl}-6-thioxo-1,6-dihydropyridine-3-carboxamide (20).
Compound 20 was obtained as colorless crystals from ethanol;
yield 48%; mp 248-250º; ir: 3300 (NH), 3200 (NH), 2220 (CN),
General procedure for preparation of 4-(3-Acetyl-6-amino-5-
substituted-2-oxo-2H-pyridin-1-yl)-N-pyrimidin-2-ylbenzene-
sulfonamide (8a-c, 14, 17, 20).
1
1650 (CO) cm-1; H nmr (DMSO-d6) ꢀ: 2.06 (s, 3H, CH3), 7.0-
8.0 (m, 8H, Ar-H), 8.47 (s, 1H, NH), 10.27 (s, 1H, NH), 11.61
(s, 1H, NH); MS: m/z 426 (424 M-2). Anal. Calcd. for
C18H14N6O3S2: C, 50.69; H, 3.31; N, 19.71; S, 15.04. Found: C,
50.72; H, 3.36; N, 19.76; S, 15.13.
Method (A). A mixture of enaminone (4) (0.01 mole) and
active methylene reagents (0.01 mole) in ethanol (30 mL)
containing a catalytic amount of pipridine (0.1 mL) was heated
under reflux for 6 hrs. The solid product formed was collected
by filtration and crystallized from the proper solvent.
3-Oxo-2-(N'-phenyl-hydrazinomethylene)-N-{4-[(pyrimidin-
2-ylamino)sulfonyl]phenyl}-butanamide (24).
Method (B). A mixture of ethoxy methylene derivative (28)
(0.01 mole) and active methylene reagents (0.01 mole) in ethanol
(30 mL) containing a catalytic amount of pipridine (0.1 mL) was
heated under reflux for 6 hrs. The solid product formed was
collected by filtration and crystallized from the proper solvent.
Method (A). A mixture of enaminone (4) (0.01 mole) and
phenyl hydrazine (0.01 mole) in ethanol (30 mL) was heated
under reflux for 8 hrs. The solid product formed during reflux
(25) was collected by filtration and another product (24) was
isolated after cooling the reaction mixture.

Nov-Dec 2008
ꢀ-Oxoanilides in Heterocyclic Synthesis: An Expeditious Synthesis of New Polyfunctionally
1823
Method (B). A mixture of ethoxy methylene derivative (28)
(0.01 mole) and phenyl hydrazine (0.01 mole) in ethanol (30
mL) was heated under reflux for 8 hrs. The solid product formed
during reflux (25) was collected by filtration and another
product (24) was isolated after cooling the reaction mixture.
Compound 24 was obtained as pale yellow crystals from
ethanol; mp 220º; ir: 3400 (NH), 3200 (NH), 1710 (CO) cm-1;
MS: m/z 452. Anal. Calcd. for C21H20N6O4S: C, 55.74; H, 4.46;
N, 18.57; S, 7.09. Found: C, 55.78; H, 4.50; N, 18.60; S, 7.12.
for 15 min., then pet. ether (60-80) was added. The solid product
that formed was collected by filtration and crystallized from
ethanol as colorless crystals; yield 40%; mp 168º; ir: 3400
(NH), 3343 (NH), 3221 (NH) cm-1 ; MS: m/z 330 (333 M+3).
Anal. Calcd. for C14H14N6O2S: C, 50.90; H, 4.27; N, 14.44; S,
7.71. Found: C, 50.94; H, 4.29; N, 14.48; S, 7.76.
2-Amino-4-methyl-6-oxo-N-{4-[(pyrimidin-2-ylamino)-
sulfonyl]phenyl}-1,6-dihydro-pyridine-3-carboxamide (30).
A mixture of anilide (3) (0.01 mole) and cyanoacetamide (0.01
mole) in ethanol (30 mL) containing a catalytic amount of
pipridine (0.1 mL) was heated under reflux for 8 hrs. The
solvent was evaporated under vacuum. The solid product that
formed was collected by filtration and crystallized from ethanol
as colorless crystals; yield 30%; mp 240º; ir: 3400 (NH2), 3100
N-{4-[(Pyrimidin-2-ylamino)sulfonyl]phenyl}-5-methyl-N,1-
diphenyl-1H-pyrazole-4-carbohydrazonamide (25).
Method (A). A mixture of enaminone (4) (0.01 mole) and
phenyl hydrazine (0.02 mole) in ethanol (30 mL) was heated
under reflux for 8 hrs. The solid product formed was collected
by filtration and crystallized from ethanol as pale yellow
crystals; yield 30%.
1
(NH), 1650 (CO) cm-1; H nmr (DMSO-d6) ꢀ: 2.5 (s, 3H, CH3),
3.18 (s, 1H, NH), 5.59 (s, 2H, NH2), 6.47-7.54 (m, 8H, Ar-H),
8.25 (s, 2H, NH2); MS: m/z
= 400. Anal. Calcd. for
C17H16N6O4S: C, 50.99; H, 4.03; N, 20.99; S, 8.01. Found: C,
51.14; H, 4.08; N, 21.14; S, 8.06.
Method (B). A mixture of ethoxy methylene derivative (28)
(0.01 mole) and phenyl hydrazine (0.02 mole) in ethanol (30 mL)
was heated under reflux for 8 hrs. The solid product formed was
collected by filtration and crystallized from ethanol as pale yellow
crystals; yield 62%; mp 260-262º; ir: 3400 (NH), 3200 (NH) cm-1;
1H nmr (DMSO-d6) ꢀ: 2.5 (s, 3H, CH3), 6.01 (s, 1H, NH), 6.55 (s,
1H, NH), 7.0-8.4 (m, 17H, Ar-H), 11.4 (s, 1H, NH); MS: m/z 524
(526 M+2). Anal. Calcd. for C27H24N8O2S: C, 61.82; H, 4.61; N,
21.36; S, 6.11. Found: C, 61.86; H, 4.68; N, 21.40; S, 6.15.
3-Hydroxyimino-N-{4-[(pyrimidin-2-ylamino)sulfonyl]-
phenyl}butanamide (31). To a mixture of anilide (3) (0.01
mole) and hydroxylamine hydrochloride (0.01 mole) in ethanol
(20 mL), sodium acetate (0.01 mole) was added. The reaction
mixture was heated under reflux for 2 hrs. The solid product
formed was collected by filtration and crystallized from dioxane
as colorless crystals; yield 50%; mp 250º; ir: 3500 (OH), 3400
(NH), 3200 (NH), 1650 (CO) cm-1; 1H nmr (DMSO-d6) ꢀ: 2.5 (s,
3H, CH3), 3.32 (s, 1H, OH), 5.97 (s, 2H, CH2), 6.54-8.39 (m,
8H, Ar-H and NH proton), 11.22 (s, 1H, NH); MS: m/z 349 (345
M-4). Anal. Calcd. for C14H15N5O4S: C, 48.13; H, 4.33; N,
20.05; S, 9.18. Found: C, 48.22; H, 4.42; N, 20.08; S, 9.25.
3-Methyl-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}-1H-
pyrazole-4-carbohydrazonamide (27).
Method (A). A mixture of enaminone (4) (0.01 mole) and
excess of hydrazine hydrate in ethanol (30 mL) was heated
under reflux for 8 hrs. The solid product formed was collected
by filtration and crystallized from 1,4-dioxane as colorless
crystals.
REFERENCES
Method (B). A mixture of ethoxy methylene derivative (28)
(0.01 mole) and excess of hydrazine hydrate in ethanol (30 mL)
was heated under reflux for 8 hrs. The solid product formed was
collected by filtration and crystallized from 1,4-dioxane as
colorless crystals; yield 54%; mp 255º; ir: 3400 (NH), 3200
(NH), 1660 (CO) cm-1; 1H nmr (DMSO-d6) ꢀ: 2.08 (s, 3H, CH3),
2.52 (s, 1H, NH), 6.68-7.68 (m, 9H, Ar-H and NH proton),
10.23 (s, 1H, NH), 11.4 (s, 1H, NH); MS: m/z 358. Anal. Calcd.
for C15H14N6O3S: C, 50.27; H, 3.94; N, 23.45; S, 8.95. Found: C,
50.34; H, 4.12; N, 23.49; S, 8.99.
2-Acetyl-3-ethoxy-N-{4-[(pyrimidin-2-ylamino)sulfonyl]-
phenyl}acrylamide (28). A mixture of anilide (3) (0.01 mole)
and triethylorthoformate (0.01 mole) in acetic anhydride (20
mL) was heated under reflux for 4 hrs, then the solvent was
evaporated under vacuum. The solid product that formed was
collected by filtration and crystallized from ethanol as colorless
crystals; yield 55%; mp 240º; ir: 3300 (NH), 3100 (NH), 1700
(CO), 1650 (CO) cm-1 ; MS: m/z 390 (393 M+3). Anal. Calcd. for
C17H18N4O5S: C, 52.30; H, 4.65; N, 14.35; S, 8.21. Found: C,
52.34; H, 4.67; N, 14.38; S, 8.25.
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4-(5-Methyl-1H-pyrazol-3-ylamino)-N-pyrimidin-2-yl-
benzene-sulfonamide (29). A mixture of anilide (3) (0.01 mole)
and excess of hydrazine hydrate was fused together in sand bath
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