Synthesis and anti-hbv activity of 4-aminoanti- pyrine derivatives

Article abstract of DOI:10.1007/s10593-010-0472-7

The reactions of 4-aminoantipyrine with acetylacetone, ethyl acetoacetate, morpholine, piperazine, and ethyl cyanoacetate were studied. All structures were determined by 1H NMR and mass spectroscopy techniques.

Full text of DOI:10.1007/s10593-010-0472-7

Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010
SYNTHESIS AND ANTI-HBV
ACTIVITY OF 4-AMINOANTI-
PYRINE DERIVATIVES
A. A.-H. Abdel-Rahman1*, A. H. A. Ahmed2, M. M. M. Ramiz3
The reactions of 4-aminoantipyrine with acetylacetone, ethyl acetoacetate, morpholine, piperazine, and
1
ethyl cyanoacetate were studied. All structures were determined by H NMR and mass spectroscopy
techniques.
Keywords: acetylacetone, 4-aminoantipyrine, ethyl acetoacetate, antiviral activity, diazotization.
The syntheses of 4-aminoantipyrine derivatives have attracted the attention of several research groups
due to their potential biological activities [1]. In this context, a broad spectrum of bioactive 4-aminoantipyrine
derivatives has been investigated, and diverse bioactivities such as analgesic [2, 3], anti-inflammatory [3],
antimicrobial [4-6], and anticancer [7] have been reported.
As part of our continuing interest in the synthesis of potential bioactive compounds [8-10], we
undertook the syntheses of 4-aminoantipyrine derivatives in our search for antiviral agents. In this work we
describe our results concerning the syntheses and anti-hepatitis B activity of these substances.
In the present work, we investigated the reaction of 4-aminoantipyrine 1 with acetylacetone, ethyl
acetoacetate, morpholine, piperazine, or ethyl cyanoacetate, which afforded compounds 2–5 in 65–78% yields.
The nitrile derivative 5 [11] was treated with acetylacetone in the presence of triethylamine at reflux temperature
to afford the carbonitrile 6 in 73% yield. The reaction of compound 5 with acetylacetone started with
condensation followed by a cyclization step.
The treatment of 1,5-dimethyl-4-(4-oxopentan-2-ylideneamino)-2-phenyl-1,2-dihydropyrazol-3-one 2
with phenyl isothiocyanate, aniline, Schiff base, ethyl cyanoacetate, malononitrile, and aromatic aldehydes gave
compounds 7-12 in 55-71% yields.
_______
* To whom correspondence should be addressed, e-mail: adelnassar63@hotmail.com.
1Chemistry Dept., Faculty of Science Menoufia University, Shebin El-Koam, Egypt.
2Chemistry Dept., Faculty of Medicinal Science, University of Science and Technology,
Yemen; e-mail: god_h2006@yahoo.com.
3Faculty of Electronic Engineering, Menoufia University, Menouf, Egypt; e-mail: wdramiz@hotmail.com.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84-90, January, 2010. Original
article received November 15, 2008.
72
0009-3122/10/4601-0072©2010 Springer Science+Business Media, Inc.

Me
N
Me
O
O
Me
MeCOCH2COMe
EtOH/reflux, 5 h
Ph
Ph
N
N
Me
Me
X
N
O
Me
N
2
Me
N
Me
Me
MeCOCH2CO2Et
EtOH/reflux, 4 h
O
Ph
N
NH2
N
H
O
O
3
NaNO2/HCl
1
Me
N
H
HN
X
Me
N
N
Ph
N
EtOH/MeCO2Na
0°C
N
H
rt
NCCH2CO2Et
O
EtOH/reflux, 5 h
4 a X = O, b X= NH
Me
Me
Me
N
Me
N
O
MeCOCH2COMe
O
Ph
N
Ph
N
CN
CN
Me
N
EtOH/Et3N/reflux, 6 h
N
H
O
O
5
Me
6
Me
Me
N
Me
N
Ph
N
O
N
Me
H
S
Me
Ph
N
O
N
CNHPh
CN
O
NCCH2CO2Et
reflux,
PhN=C=S
reflux, 7h
O
10
7
PhH/
3h
Me
Me
Me
N
Me
N
O
CN
Me
N
Me
Ph
N
Ph
N
N
Me
NNHPh
NH2
O
NaNO2/HCl
O
NCCH2CN/EtOH
PhNH2/EtOH
11
2
8
reflux,
3h
MeCO2Na
rt
0°C
Me
N
Me
Me
N
Me
O
Ph
N
Me
N
O
Me
N
Me
Ph
N
O
CHC6H4R
Me
CH2Ph
12a–c
O
PhN=CHPh
RC6H4CHO/EtOH
reflux, 3–5 h
9
12 a R = H, b R = p-OMe, c R = o-OH
73

The treatment of N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-oxobutanamide 3
with phenyl isothiocyanate, malononitrile, ethyl cyanoacetate, or aromatic aldehydes afforded compounds 13-16
in 57–84% yields.
Me
Me
Me
N
Me
N
O
O
NH2
O
O
Ph
N
Ph
N
N
H
N
H
Me
O
O
CNHPh
S
O
O
CN
NCCH2CO2Et
reflux,
Ph–N=C=S
13
15
3h
benzene/reflux,
7h
Me
N
Me
N
Me
Me
3
O
O
O
O
Ph
N
Ph
N
N
Me
CN
N
H
Me
CHC6H4R
H
O
O
H2N
RC6H4CHO/EtOH
reflux, 3–5h
NCCH2CN/EtOH
reflux, 5h
14
16a–c
16 a R = H, b R = p-OMe, c R = o-OH
1
The structures of compounds 2-16 were confirmed by H NMR and IR spectroscopy, and mass
1
spectrometry. In the H NMR spectra of the synthesized compounds we observed all the proton signals of the
aromatic ring, heterocyclic ring, methyl groups, and proton of NH group.
A preliminary viral screening against hepatitis B virus (HBV) (Hep G2 2.2.15 cell method) [12-15]
indicated that compounds 6, 7, 10, and 11 are active against HBV replication with IC50 80-90 µM and CC50
78-88 µM, while compounds 2–5, 8, 9, and 12a–c showed moderate viral replication inhibition and moderate
cytotoxicity. The drug Lamivudine, which is a potent selective inhibitor of HBV replication [15], was used as a
standard for the comparative studies.
EXPERIMENTAL
Melting points were determined using a Kofler block instrument. IR (KBr disks) spectra were recorded
1
on a Pie-Unicam SP-1100 spectrophotometer. H NMR spectra were recorded on a Bruker AC 250 FT NMR
spectrometer at 250 MHz in DMSO-d6, with TMS as an internal standard. ES mass spectra were obtained from
an Esquire 3000 plus ion-trap mass spectrometer from Bruker Daltonics. The microanalyses were performed at
the microanalytical unit, Cairo University, Egypt. Antiviral activity against HBV of the synthesized compounds
was conducted at the National Liver Institute, Menoufia University, Shebin El-Koam, Egypt.
Compounds 2, 3, and 5 (General Method). A mixture of 4-aminoantipyrine 1 (10.15 g, 0.05 mol) in an
excess of acetylacetone, ethyl acetoacetate, or ethyl cyanoacetate was refluxed for 6 h. The reaction mixture was
cooled to room temperature, and the formed solid product was collected by filtration and recrystallized from
ethanol to afford compounds 2, 3, and 5 in 67-78% yields.
74

1,5-Dimethyl-4-(4-oxopentan-2-ylideneamino)-2-phenyl-1,2-dihydropyrazol-3-one (2). Yield 11.11 g
1
(78%); mp 138-140oC. IR spectrum, ν, cm–1: 3300 (NH), 1685, 1710 (C=O). H NMR spectrum, δ, ppm:
7.70-7.32 (5H, m, H Ar); 3.18 (3H, s, NCH3); 2.50 (2H, s, CH2); 2.45 (3H, s, CH3); 1.99 (3H, s, COCH3); 0.99
(3H, s, CH3). Mass spectrum, m/z (I, %): 285 [M]+ (75), 286 [M + H]+ (60). Found, %: C 67.21; H 6.90;
N 14.58. C16H19N3O2. Calculated, %: C 67.35; H 6.71; N 14.73.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-oxobutanamide (3). Yield 9.61 g
1
(67%); mp 130-132oC. IR spectrum, ν, cm–1: 3310 (NH), 1680, 1700 (C=O). H NMR spectrum, δ, ppm: 9.28
(1H, br. s, NH); 7.62-7.34 (5H, m, H Ar); 3.33 (2H, s, CH2); 3.10 (3H, s, NCH3); 2.19 (3H, s, CH3); 2.07 (3H, s,
COCH3). Mass spectrum, m/z (I, %): 287 [M]+ (100), 288 [M + H]+ (44). Found, %: C 62.60; H 6.11; N 14.57.
C15H17N3O3. Calculated, %: C 62.71; H 5.96; N 14.63.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-cyanoacetamide (5). Yield 9.45 g
(70%), lit. [11] 57%.
Compounds 4a,b (General Method). A mixture of 4-aminoantipyrine 1 (2.03 g, 0.01 mol) in the
appropriate amounts of cold HCl and NaNO2 was added to a solution of the appropriate active methylene
compound (0.01 mol) dissolved in ethanol (20 ml) and sodium acetate (1.5 g). The reaction mixture was left for
3 h at room temperature and the formed solid product was filtered off, washed several times with water, and
recrystallized from ethanol to give compounds 4a,b.
1,5-Dimethyl-4-[2-(morpholin-3-ylidene)hydrazinyl]-2-phenyl-1,2-dihydropyrazol-3-one (4a). Yield
1
2.31 g (77%); mp 255-256oC. IR spectrum, ν, cm–1: 3300 (NH), 1675 (C=O). H NMR spectrum, δ, ppm:
7.52-7.31 (5H, m, H Ar); 7.02 (1H, br. s, NH); 3.63 (2H, m, CH2); 3.40 (2H, m, CH2); 3.12 (3H, s, NCH3); 2.81
(2H, m, CH2); 2.09-1.98 (4H, m, CH3, NH). Mass spectrum, m/z (I, %): 301 [M]+ (100), 302 [M + H]+ (71).
Found, %: C 59.63; H 6.20; N 23.11. C15H19N5O2. Calculated, %: C 59.79; H 6.36; N 23.24.
1,5-Dimethyl-2-phenyl-4-[2-(piperazin-2-ylidene)hydrazinyl]-1,2-dihydropyrazol-3-one (4b). Yield
1
1.95 g (65%); mp 243-246oC. IR spectrum, ν, cm–1: 3300 (NH), 1665 (C=O). H NMR spectrum, δ, ppm:
7.50-7.32 (5H, m, H Ar); 7.05 (1H, br. s, NH); 3.10 (3H, s, NCH3); 2.84 (2H, m, CH2); 2.79 (2H, m, CH2); 2.61
(2H, m, CH2); 2.15–1.97 (4H, m, CH3, NH). Mass spectrum, m/z (I, %): 300 [M]+ (100), 301 [M + H]+ (28).
Found, %: C 59.90; H 6.60; N 27.88. C15H20N6O. Calculated, %: C 59.98; H 6.71; N 27.98.
1-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4,6-dimethyl-2-oxo-1,2-dihydropyri-
dine-3-carbonitrile (6). A mixture of compound 5 (2.70 g, 0.01 mol), absolute ethanol (20 ml), acetylacetone
(0.01 mol), and triethylamine (0.5 ml) was refluxed for 6 h. The reaction mixture was allowed to cool to room
temperature and the formed solid product was filtered off and recrystallized from ethanol to afford compound 6
(2.43 g, 73%); mp 230–232oC. IR spectrum, ν, cm–1: 3300 (NH), 2200 (CN), 1690 (C=O). 1H NMR spectrum, δ,
ppm: 7.52-7.33 (5H, m, H Ar); 6.50 (1H, s, pyridinone); 3.17 (3H, s, NCH3); 2.21 (3H, s, CH3); 1.84 (3H, s,
CH3); 1.74 (3H, s, CH3). Mass spectrum, m/z (I, %): 334 [M]+ (100). Found, %: C 68.19; H 5.33; N 16.65.
C19H18N4O2. Calculated, %: C 68.25; H 5.43; N 16.76.
N-Phenyl-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-methyl-4-oxopyrrolidine-
3-carbothioamide (7). A mixture of compound 2 (2.85 g, 0.01 mol), dry benzene (15 ml), and phenyl
isothiocyanate (0.01 mol) was refluxed for 7 h. The reaction mixture was allowed to cool to room temperature
and the formed solid product was filtered off and recrystallized from methanol to afford compound 7 (2.73 g,
65%); mp 207-209oC. IR spectrum, ν, cm–1: 3440 (NH), 1665 (C=O). 1H NMR spectrum, δ, ppm: 7.35-7.29 (5H,
m, H Ar); 7.19-6.92 (5H, m, H Ar); 4.00 (1H, br. s, NH); 3.80 (2H, s, CH2); 3.13 (3H, s, NCH3); 3.00 (1H, m,
CH); 2.61 (1H, m, CH); 1.80 (3H, s, CH3); 1.14 (3H, s, CH3). Mass spectrum, m/z (I, %): 420 [M]+ (65). Found,
%: C 65.53; H 5.66; N 13.16. C23H24N4O2S. Calculated, %: C 65.69; H 5.75; N 13.33.
1,5-Dimethyl-4-[4-oxo-3-(2-phenylhydrazono)pentan-2-ylideneamino]-2-phenyl-1,2-dihydropyrazol-
3-one (8). As mentioned before for compounds 4a,b (2.72 g, 70%); mp 180-182oC. IR spectrum, ν, cm–1: 3435
(NH), 1669 (C=O). 1H NMR spectrum, δ, ppm: 11.00 (1H, br. s, NH); 7.42-7.32 (5H, m, H Ar); 7.04-6.94 (5H,
m, H Ar); 3.19 (3H, s, NCH3); 2.50 (3H, s, CH3); 2.20 (3H, s, COCH3); 0.99 (3H, s, CH3). Mass spectrum, m/z
75

(I, %): 389 [M]+ (54), 390 [M + H]+ (60). Found, %: C 67.60; H 5.81; N 17.80. C22H23N5O2. Calculated, %:
C 67.85; H 5.95; N 17.98.
4-(3-Benzyl-4-oxopentan-2-ylideneamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one (9). A
mixture of compound 2 (2.85 g, 0.01 mol), (E)-N-benzyli- denebenzeneamine (0.01 mol), and absolute ethanol
(15 ml) was refluxed for 6 h. The reaction mixture was cooled to room temperature and the formed solid product
was filtered off and recrystallized from ethanol to afford compound 9 (2.47 g, 66%); mp 171-173oC. IR
spectrum, ν, cm–1: 3400 (NH), 1660 (C=O). 1H NMR spectrum, δ, ppm: 7.52-7.37 (5H, m, H Ar); 7.25-7.11 (5H,
m, H Ar); 3.18 (3H, s, NCH3); 3.04 (2H, m, CH2); 2.70 (1H, m, CH); 2.44 (3H, s, CH3); 2.07 (3H, s, COCH3);
0.92 (3H, s, CH3). Mass spectrum, m/z (I, %): 375 [M]+ (88), 376 [M + H]+ (12). Found, %: C 73.44; H 6.60; N
11.08. C23H25N3O2. Calculated, %: C 73.57; H 6.71; N 11.19.
[5-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylamino)-3-oxo-cyclohexa-1,4-dienyl]-
acetonitrile (10). A mixture of compound 2 (2.85 g, 0.01 mol) in an excess of ethyl cyanoacetate was refluxed
for 3 h. The reaction mixture was cooled to room temperature and the formed solid product was filtered off and
recrystallized from ethanol to afford compound 10 (2.17 g, 65%); mp 230-232oC. IR spectrum, ν, cm–1: 3500
(NH), 2200 (CN), 1670 (C=O). 1H NMR spectrum, δ, ppm: 7.30-7.09 (5H, m, H Ar); 6.32 (1H, s, CH); 5.83 (1H, s,
CH); 3.13 (3H, s, NCH3); 3.02 (2H, m, CH2); 2.62 (2H, m, CH2); 2.17 (3H, s, CH3); 2.02 (1H, br. s, NH). Mass
spectrum, m/z (I, %): 334 [M]+ (45), 335 [M + H]+ (78). Found, %: C 68.18; H 5.34; N 16.59. C19H28N4O2.
Calculated, %: C 68.25; H 5.43; N 16.76.
6-Amino-4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)-2-methylcyclohexa-
1,5-dienecarbonitrile (11). A mixture of compound 2 (2.85 g, 0.01 mol), malononitrile (0.01 mol), and absolute
ethanol (15 ml) was refluxed for 3 h. The reaction mixture was cooled to room temperature, and the formed
solid product was filtered off and recrystallized from ethanol to afford compound 11 (1.83 g, 55%); mp 250-
252oC. IR spectrum, ν, cm–1: 3300 (NH), 2200 (CN), 1675 (C=O). 1H NMR spectrum, δ, ppm: 7.40-7.22 (5H, m,
H Ar); 4.85 (2H, br. s, NH2); 3.95 (1H, s, CH); 3.17 (3H, s, NCH3); 2.37 (3H, s, CH3); 2.00 (2H, s, CH2); 1.75
(3H, s, CH3). Mass spectrum, m/z (I, %): 333 [M]+ (77), 334 [M + H]+ (48). Found, %: C 68.34; H 5.66;
N 21.11. C19H19N5O. Calculated, %: C 68.45; H 5.74; N 21.01.
Compounds 12a-c (General Method). A mixture of compound 2 (2.85 g, 0.01 mol), the appropriate
aldehyde (0.01 mol), and ethanol (25 ml) was heated under reflux for 3–5 h. The reaction mixture was cooled to
room temperature and the formed solid product was filtered off and recrystallized from ethanol to afford
compounds 12a-c.
4-(3-Benzylidene-4-oxopentan-2-ylideneamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one (12a).
Yield 2.23 g (60%); mp 160-162oC. IR spectrum, ν, cm–1: 3300 (NH), 1660 (C=O). 1H NMR spectrum, δ, ppm:
7.50-7.34 (6H, m, H Ar, CH); 7.25-7.04 (5H, m, H Ar); 3.16 (3H, s, NCH3); 2.44 (3H, s, CH3); 2.39 (3H, s,
COCH3); 0.96 (3H, s, CH3). Mass spectrum, m/z (I, %): 373 [M]+ (100), 374 [M + H]+ (58). Found, %: C 73.85;
H 6.09; N 11.15. C23H23N3O2. Calculated, %: C 73.97; H 6.21; N 11.25.
4-[3-(4-Methoxybenzylidene)-4-oxopentan-2-ylideneamino]-1,5-dimethyl-2-phenyl-1,2-dihydro-
pyrazol-3-one (12b). Yield 2.86 g (71%); mp 171-173oC. IR spectrum, ν, cm–1: 3250 (NH), 1668 (C=O).
1H NMR spectrum, δ, ppm: 8.34-8.22 (2H, m, H Ar); 7.50-7.22 (6H, m, H Ar, CH); 7.19-7.04 (2H, m, H Ar);
3.85 (3H, s, OCH3); 3.19 (3H, s, NCH3); 2.40 (3H, s, CH3); 2.30 (3H, s, COCH3); 0.92 (3H, s, CH3). Mass
spectrum, m/z (I, %): 373 [M]+ (100), 403 [M + H]+ (44). Found, %: C 71.34; H 6.12; N 10.22. C24H25N3O3.
Calculated, %: C 71.44; H 6.25; N 10.41.
4-[3-(4-Hydroxybenzylidene)-4-oxopentan-2-ylideneamino]-1,5-dimethyl-2-phenyl-1,2-dihydro-
pyrazol-3-one (12c). Yield 2.45 g (63%); mp 198–200oC. IR spectrum, ν, cm–1: 3230 (NH), 1665 (C=O).
1H NMR spectrum, δ, ppm: 9.80 (1H, br. s, OH); 7.50-7.22 (6H, m, H Ar, CH); 7.19-6.97 (4H, m, H Ar); 3.16
(3H, s, NCH3); 2.43 (3H, s, CH3); 2.33 (3H, s, COCH3); 0.92 (3H, s, CH3). Mass spectrum, m/z (I, %): 389 [M]+.
Found, %: C 70.80; H 5.81; N 10.60. C23H23N3O3. Calculated, %: C 70.93; H 5.95; N 10.79.
76

N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-oxo-2-(phenylcarbamothioyl)-
butanamide (13). As mentioned before for compound 7 (3.12 g, 74%); mp 195-197oC. IR spectrum, ν, cm–1:
1
3200 (NH), 1685 (C=O). H NMR spectrum, δ, ppm: 9.30 (1H, br. s, NH); 7.30-7.20 (5H, m, H Ar); 7.10-6.95
(5H, m, H Ar); 4.09 (1H, br. s, NH); 3.30 (1H, s, CH); 3.11 (3H, s, NCH3); 2.18 (3H, s, CH3); 2.06 (3H, s,
COCH3). Mass spectrum, m/z (I, %): 422 [M]+ (45). Found, %: C 62.39; H 5.19; N 13.18. C22H22N4O3S.
Calculated, %: C 62.54; H 5.25; N 13.26.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-acetyl-3-amino-4-cyanobut-2-en-
amide (14). As mentioned before for compound 11 (2.64 g, 75%); mp 240-242oC. IR spectrum, ν, cm–1: 3320
(NH), 2210 (CN), 1655 (C=O). 1H NMR spectrum, δ, ppm: 9.74 (1H, br. s, NH); 7.30-7.22 (5H, m, H Ar); 3.14
(3H, s, NCH3); 3.06 (2H, s, CH2); 2.30 (3H, s, COCH3); 2.19 (3H, s, CH3); 2.00 (2H, br. s, NH2). Mass
spectrum, m/z (I, %): 353 [M]+ (60). Found, %: C 61.00; H 5.23; N 19.63. C18H19N5O3. Calculated, %: C 61.18;
H 5.42; N 19.82.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-6-amino-3a-cyano-1,3,4-trioxo-
1,2,3,3a,4,5-hexahydropentalene-2-carboxamide (15). As mentioned before for compound 10 (2.38 g, 57%);
mp 224-226oC. IR spectrum, ν, cm–1: 3450 (NH), 2210 (CN), 1660 (C=O). 1H NMR spectrum, δ, ppm: 9.26 (1H,
br. s, NH); 7.50-7.29 (5H, m, H Ar); 4.15 (1H, s, CH); 3.17, 3.11 (5H, 2s, NCH3, CH2); 2.17 (3H, s, CH3); 2.02
(2H, br. s, NH2). Mass spectrum, m/z (I, %): 419 [M]+ (34), 420 [M + H]+ (28). Found, %: C 60.00; H 3.93;
N 16.55. C21H17N5O5. Calculated, %: C 60.14; H 4.09; N 16.70.
Compounds 16a–c (General method). As mentioned before for compounds 12a–c.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-benzylidene-3-oxo-butanamide
(16a). Yield 3.00 g (80%); mp 170–172oC. IR spectrum, ν, cm–1: 3350 (NH), 1670 (C=O). 1H NMR spectrum, δ,
ppm: 9.70 (1H, br. s, NH); 8.25 (1H, s, CH); 7.55–7.34 (10H, m, H Ar, CH); 3.11 (3H, s, NCH3); 2.30 (3H, s,
COCH3); 2.20 (3H, s, CH3). Mass spectrum, m/z (I, %): 375 [M]+ (90), 376 [M + H]+ (54). Found, %: C 70.18;
H 5.60; N 11.25. C22H21N3O3. Calculated, %: C 70.38; H 5.64; N 11.19.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(4-methoxybenzylidene)-3-oxo-
butanamide (16b). Yield 3.16 g (78%); mp 155-157oC. IR spectrum, ν, cm–1: 3290 (NH), 1665 (C=O).
1H NMR spectrum, δ, ppm: 9.70 (1H, br. s, NH); 8.30-8.22 (3H, m, H Ar, CH); 7.50-7.22 (5H, m, H Ar);
7.18-7.00 (2H, m, H Ar); 3.80 (3H, s, OCH3); 3.13 (3H, s, NCH3); 2.30 (3H, s, COCH3); 2.20 (3H, s, CH3).
Mass spectrum, m/z (I, %): 405 [M]+ (50). Found, %: C 68.00; H 5.59; N 10.22. C23H23N3O4. Calculated, %:
C 68.13; H 5.72; N 10.36.
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(4-hydroxybenzylidene)-3-oxobutan-
amide (16c). Yield 3.28 g (84%); mp 175-177oC. IR spectrum, ν, cm–1: 3270 (NH), 1665 (C=O). 1H NMR spectrum,
δ, ppm: 9.77 (2H, br. s, OH, NH); 8.30 (1H, s, CH); 7.50–7.22 (5H, m, H Ar, CH); 7.14-6.98 (4H, m, H Ar); 3.15
(3H, s, NCH3); 2.30 (3H, s, COCH3); 2.20 (3H, s, CH3). Mass spectrum, m/z (I, %): 391 [M]+ (55). Found, %:
C 67.39; H 5.20; N 10.86. C22H21N3O4. Calculated, %: C 67.51; H 5.41; N 10.74.
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