Transformations of alkyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetates into 5-heteroaryl-3-oxo-2-phenyl-3,5-dihydro-2H-pyrazolo[4,3-c] pyridine-7-carboxylates

Article abstract of DOI:10.3987/com-03-s20

Alkyl [(Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl] acetate (4) was transformed with N- and C-nucleophiles into alkyl [4-(substituted amino)methylidene-4,5-dihydro-1H-pyrazol-3- yl] acetates (7) and alkyl (4-heteroarylmethylidene-4,5-dihydro-1H -pyrazol-3-yl)acetates (8), respectively. Compounds (7) cyclize by heating with DMFDMA in DMF into 2H-pyrazolo[4,3-c]pyridine-7-carboxylates (9).

Full text of DOI:10.3987/com-03-s20

HETEROCYCLES, Vol. 61, 2003
197
HETEROCYCLES, Vol. 61, 2003, pp. 197 - 223
Received, 26th May, 2003, Accepted, 28th July, 2003, Published online, 4th August, 2003
TRANSFORMATIONS OF ALKYL (5-OXO-1-PHENYL-4,5-DIHYDRO-
1H-PYRAZOL-3-YL)ACETATES INTO 5-HETEROARYL-3-OXO-2-
PHENYL-3,5-DIHYDRO-2H-PYRAZOLO[4,3–c]PYRIDINE-7-CARBOXY-
LATES
David Bevk, Renata Jakše, Jurij Svete,* Amalija Golobič, Ljubo Golič, and
Branko Stanovnik*
Faculty of Chemistry and Chemical Technology, University of Ljubljana,
Aškerčeva 5, 1000 Ljubljana, Slovenia
On the occasion of the 30th Anniversary of HETEROCYCLES.
Abstract – Alkyl [(Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-
1H-pyrazol-3-yl]acetate (4) was transformed with N- and C-nucleophiles into
alkyl [4-(substituted amino)methylidene-4,5-dihydro-1H-pyrazol-3-yl]acetates (7)
and alkyl (4-heteroarylmethylidene-4,5-dihydro-1H-pyrazol-3-yl)acetates (8),
respectively. Compounds (7) cyclize by heating with DMFDMA in DMF into 2H-
pyrazolo[4,3–c]pyridine-7-carboxylates (9).
Pyrazolo[4,3–c]pyridines and their [3,4–c] analogues are structurally related to some biologically active
compounds, like the nucleotide antibiotics formycin1,2 and allopurinol.3 Some of pyrazolo[4,3–c]pyridine
derivatives exhibit a broad spectrum of antitumor activity.4 There are only few methods starting from
substituted pyrazoles described in the literature.5 Other methods for the preparation of pyrazolo-[4,3–c]-
pyridines involve an aza Wittig-type reaction starting from 5-formyl-1-phenylpyrazole,6 intramolecular
cycloaddition of azomethine imines,7 ring opening of pyrido[4,3–d]pyrimidine derivatives with sodium
methoxide followed by rearrangement and cyclization,8 photochemical irradiation of 4-hydrazino-
isoxazolo[5,4–b]pyridines,9 cyclization of diazonium salts, generated from 5-alkyl-4-amino-2-trifluoro-
methylpyridines,10 nitrosation of N-acylated 4-amino-3-methylpyridines,11 treatment of piperidones with
hydrazines which afforded 1,4,5,6-tetrahydropyrazolo[4,3–c]pyridines,12 treatment of (E)-1-methyl-3,5-

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HETEROCYCLES, Vol. 61, 2003
bis(4-methylbenzylidene)-4-piperidone and analogues with hyrazines,4 from 4-amino-5-methylnicotic
acid,13 and from N-substituted 4-pyridone benzoylhydrazones.14 5-Alkoxy-3-(N-substituted carbamoyl)-1-
phenylpyrazoles were prepared and tested for antiinflamatory and hypnotic activity.15
In continuation of our research, we describe in this paper the synthesis of 5-heteroaryl-3-oxo-2-phenyl-
3,5-dihydro-2H-pyrazolo[4,3–c]pyridine-7-carboxylates (9) from alkyl (5-oxo-1-phenyl-4,5-dihydro-1H-
pyrazol-3-yl)acetates (3). Ethyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetate16a,b (3a) and its
corresponding methyl ester16c (3b) have been prepared according to the methods described in the
literature.
Compounds (3a,b) were transformed with N,N-dimethylformamide dimethylacetal (DMFDMA) in
toluene at room temperature into ethyl [(Z)-4-(dimethylamino)methylidene-5-oxo-1-phenyl-4,5-dihydro-
1H-pyrazol-3-yl]acetate (4a) and the corresponding methyl ester (4b). They reacted with N- and C-
nucleophiles in ethanol in the presence of small amounts of hydrochloric acid at room temperature to give
the corresponding dimethylamine substitution products (7) and (8). In the N-nucleophile series, aromatic
and heterocyclic amines (5a–s) were used. The corresponding methyl and ethyl (Z)-[5-oxo-1-phenyl-4-
(hetero)arylaminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetates (7a–s) were produced. In IR spectra
of 7q and 7r, obtained from 3a,b and aminoacetonitrile (5q), we did not observe any absorption in the
region between 2100cm-1 and 2200cm-1, characteristic for the C≡N group. We thought at first that
cyclization occured to give alkyl (7-imino-1-phenyl-6,7-dihydro-1H-pyrazolo[4,3–f][1,4]oxazepin-3-
yl)acetates. However, the X-Ray analysis shows, that compounds (7q) and (7r) in fact exist in the cyano
form. Reactions with C-nucleophiles proceeded under the same conditions to form 8a–l in 57–98% yield
(Scheme 1).
Ph
N
Ph
N
Ph
N
O
HO
O
ROOC
O
i
ii
N
N
N
COOR
Me2N
COOR
COOR
COOR
1a,b
4a,b
3a,b
Ph
Ph
N
Ph
N
N
N
O
O
O
iii
iii
N
N
R2
R1-HN
Me2N
R1-NH2
5a-s
R2R3CH2
COOR
COOR
COOR
R3
7a-s
4a,b
6a-k
8a-l
Scheme 1. (i) Ph–NHNH2 (2), rt–70 °C; (ii) DMFDMA, toluene, rt; (iii) R1–NH2 (5a–s, 5→7) or
R2R3CH2 (6a–k, 6→8), EtOH, 37% HCl–H2O (1 equiv.), rt

HETEROCYCLES, Vol. 61, 2003
199
Reaction R
R1
Reaction R
R1
5a→7a
5a→7b
5c→7c
5d→7d
Et
phenyl
5q→7q
5q→7r
5s→7s
Et
cyanomethyl
cyanomethyl
phenylamino
R2R3CH
Me phenyl
Me
Et
Et
Et
4-methylphenyl
4-hydroxyphenyl
Reaction R
6-hydroxy-2,2-dimethyl-4-oxo-4H-[1,3]-
dioxin-5-yl
5e→7e
5f→7f
5f→7g
5h→7h
5i→7i
5i→7j
Me 4-methoxyphenyl
6a→8a
6b→8b
6b→8c
6d→8d
6e→8e
6e→8f
Et
6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-
pyrimidin-5-yl
Et
pyridin-2-yl
Et
6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-
pyrimidin-5-yl
Me pyridin-2-yl
Me
Et
6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetra-
hydropyrimidin-5-yl
Et
Et
quinolin-3-yl
2,4-dihydroxypyri-
midin-5-yl
6-hydroxy-1,3-dimethyl-2,4-dioxo-
1,2,3,4-tetrahydropyrimidin-5-yl
6-hydroxy-1,3-dimethyl-2,4-dioxo-
1,2,3,4-tetrahydropyrimidin-5-yl
3-hydroxy-1-oxo-1H-inden-2-yl
3-hydroxy-1-oxo-1H-inden-2-yl
3-ethoxycarbonylmethyl-5-oxo-1-phenyl-
1,5-dihydro-1H-pyrazol-4-yl
3-ethoxycarbonylmethyl-5-oxo-1-phenyl-
1,5-dihydro-1H-pyrazol-4-yl
5-hydroxy-3-methyl-1-phenyl-1H-
pyrazol-4-yl
Et
2,4-dihydroxypyri-
midin-5-yl
Me
Et
Me
5k→7k
5k→7l
pyrazinyl
6g→8g
6g→8h
Et
Me pyrazinyl
1H-pyrazol-3-yl
Me 1H-indazol-3-yl
Me
5m→7m Et
6i→8i
6i→8j
Et
5n→7n
Me
5o→7o
5p→7p
Et
Et
benzothiazol-3-yl
hydroxy
6k→8k
6l→8l
Et
Et
5-hydroxy-1,3-diphenyl-1H-pyrazol-4-yl
Scheme 1 (Continued).
When compound (4a) was heated in ethanol under reflux in the presence of hydrochloric acid (Z)-[4-(5-
hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-ylmethylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (8i) was obtained in 75%. This compound was identical with the compound (8i) prepared from 4a
and 6i in 90% yield. Apparently, partial hydrolysis of enamine (4a) took place to furnish in situ the

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HETEROCYCLES, Vol. 61, 2003
pyrazole derivative (6i) as the C-nucleophile, which reacted with the non-hydrolysed enaminone (4a) to
afford 8i. Preparation of analogous compound from 3-ethoxycarbonyl-5-oxo-1-phenyl-1H-pyrazole and
1,3,5-triazine has been reported previously.17 Compounds (7c,d,k) were heated with 2 equivalents of
DMFDMA in DMF at reflux temperature to give pyrazolo[4,3–c]pyridines (9c,d,k) in moderate yields.
Cyclisation proceeds by incorporation of DMFDMA as C1 synthon between the nucleophilic NH and CH2
groups. In the reaction of 7d with DMFDMA, also methylation of the phenolic hydroxy group took place
to give the 5-(4-methoxyphenyl)pyrazolo[4,3–c]pyridine derivative (9d) (Scheme 2).
Ph
N
H
O
O
Ph
Ph
O
N
EtOH, 37% HCl-H2O (1 equiv.), rt
N
N
N
N
Me2N
COOEt
4a
COOEt
EtOOC
8i
H+, H2O
(partial hydrolysis)
4a
Ph
Ph
N
Ph
N
N
N
N
O
OH
O
-DMF
N
Me2N
COOEt
EtOOC
EtOOC
O
6i
H
COOEt
Ph
N
7
N1
N
6
O
DMFDMA, DMF, reflux
N
Ph
2
N
R1
R1-HN
3
5
COOEt
4
O
7c (R1 = 4-methylphenyl)
7d (R1 = 4-hydroxyphenyl)
7k (R1 = pyrazinyl)
9c (R1 = 4-methylphenyl)
9d (R1 = 4-methoxyphenyl)
9k (R1 = pyrazinyl)
Scheme 2
Structure determination
The structures of all compounds were established on the basis of elemental analysis for C H N, IR, MS
and NMR spectra. The orientation around the exocyclic double bond in compounds (4a) and (7c) was

HETEROCYCLES, Vol. 61, 2003
201
established on the basis of 2D-HMBC NMR technique. Namely, the magnitude of the coupling constants,
3J1H-13C, for nuclei with (Z)-orientation around the C=C double bond are smaller (2–6 Hz) than those for
the (E)-oriented ones (8-12 Hz).18 The HMBC correlation technique has been found the most suitable for
the determination of the orientation around the C=C double bond in analogous compounds.19
3
Accordingly, for compound (4a) the heteronuclear coupling constant, J1H–13C = 8 Hz, indicates the (Z)-
orientation and similarly for compound (7c), 3J1H–13C = 11 Hz, clearly indicates the (Z)-orientation, while
for compounds (8b) and (8i) the (Z)-orientation was established on the basis of the NOE effect between
methylidene proton and CH2 group of the ethoxycarbonylmethyl group. Compound (8i) exhibits only one
singlet for both CH2 groups of ethoxymethyl groups at δ = 3.803 ppm and only one singlet for the
methylidene proton at δ = 7.657 ppm. This means that fast tautomerisation between two identical
structures is taking place. Since the NOE effect was observed between the methylidene proton and both
CH2 groups the compound is best represented by structure (8i’) (Scheme 3).
Ph
N
Ph
N
Ph
N
H
O
O
Ph
Ph
O
O
O
N
N
N
N
N
OH
H
N
N
COOEt
COOEt
COOEt
HN
Me2N
N
H
H
H
O
COOEt
EtOOC
N
NOE
3JC-H = 8 Hz
3JC-H = 11Hz
NOE
O
H
4a
8b
8i'
Me
7c
Scheme 3
1
The H NMR spectra of compounds (9) exhibit beside the signals characteristic for ethoxy groups and
groups attached to nitrogen atoms at 2- and 5-positions, a doublet in the range at δ = 8.15–8.76 ppm for
4–H and at δ = 8.32–8.97 ppm for 6-H with a coupling constant J4H–6H= 1.5 Hz.
The structures for compounds (4a), (7f), (7r) and (8g) in the solid state were confirmed by the X-Ray
analysis.
X-Ray structure analysis
Diffraction data for compounds (4a), (7f), (7r) and (8g) were collected on a Nonius Kappa CCD
diffractometer with graphite monochromated MoKα radiation. The data were processed using DENZO20
program. Structures were solved by direct methods using SIR97.21 We employed full-matrix least-squares

202
HETEROCYCLES, Vol. 61, 2003
refinements on F magnitudes with anisotropic displacement factors for all non-hydrogen atoms using
Xtal3.6.22 The positions of hydrogen atoms were obtained from the difference Fourier maps, only the
positions of some of H atoms of ethyl group in 8g were calculated according to expected geometry. For
4a H-atoms parameters were not refined, for 7f and 8g only positional parameters of H atoms were
refined (the exception were H atoms of ethyl group in 8g, which were not refined) and for 7s the
positional parameters of H atoms together with their isotropic displacement factors were refined (the
exception were H atoms bonded to C8a and C8b, which were not refined). In the final cycle of the
refinement we used 2945, 2931, 5825 and 3068 reflections and 199, 290, 485 and 311 parameters for 4a,
7f, 7r and 8g, respectively. The resulting crystal data and details concerning data collection and
refinement for all four compounds are quoted in Table 1. Final atomic coordinates and equivalent
isotropic displacement parameters with their e.s.d.'s are reported in Tables 2, 3, 4 and 5. Bond lengths and
bond angles for nonhydrogen atoms are listed in Tables 6, 7, 8 and 9 for 4a, 7f, 7r and 8g, respectively.
ORTEP23 drawings of the content of asymmetric units of all four compounds showing the atom-labeling
scheme are presented in Figures 1, 2, 3 and 4.
Figure 1. ORTEP view of the asymmetric unit of compound (4a) with labeling of nonhydrogen atoms.
(Ellipsoids are drawn at 50% probability level.)

HETEROCYCLES, Vol. 61, 2003
203
Figure 2. ORTEP view of the asymmetric unit of compound (7f) with labeling of nonhydrogen atoms.
(Ellipsoids are drawn at 50% probability level.)
Figure 3. ORTEP view of the asymmetric unit of compound (7r) with labeling of nonhydrogen atoms.
(Ellipsoids are drawn at 50% probability level.)

204
HETEROCYCLES, Vol. 61, 2003
Figure 4. ORTEP view of the asymmetric unit of compound (8g) with labeling of nonhydrogen atoms.
(Ellipsoids are drawn at 50% probability level.)
Table 1. Crystal data, data collection and structure refinement for compounds (4a), (7f), (7r), and (8g).
compound (4a)
C16H19N3O3
301.35
compound (7f)
C19H18N4O3
350.38
compound (7r)
C15H14N4O3
298.30
compound (8g)
C23H18N2O5
402.41
Formula
Rel. formula weight
Crystal System
Space group
a (Å)
triclinic
P-1, No. 2
7.0295(2)
10.7698(3)
11.6596(3)
102.445(1)
105.817(1)
105.791(1)
776.20(4)
2
1.289
0.091
colorless
prism
triclinic
P-1, No. 2
7.5228(2)
10.6141(2)
11.2966(2)
87.576(1)
78.894(1)
76.511(1)
860.70(3)
2
triclinic
triclinic
P-1, No. 2
11.2154(2)
11.4495(2)
13.0384(2)
69.463(1)
71.304(1)
78.807(1)
1478.82(4)
4
P-1, No. 2
8.3447(2)
10.6533(2)
12.5502(3)
103.267(1)
109.266(1)
103.557(1)
b (Å)
c (Å)
α (˚)
β (˚)
γ (˚)
V (Å3)
964.94(4)
Z
2
ρ (Mg m-3)
µ (mm-1)
1.340
1.385
1.352
0.094
0.097
0.099
yellow
Color of crystal
Shape of crystal
Dimensions (mm)
Temperature (K)
Wavelength (Å)
yellow
orange-red
prism
prism
prism
0.40×0.20×0.20
293
0.71073
0.30×0.20×0.10
0.40×0.40×0.20
0.35×0.30×0.20
293
293
293
0.71073
0.71073
0.71073

HETEROCYCLES, Vol. 61, 2003
205
27.5
27.5
27.5
27.5
θmax (°)
13480
3536
0.052
2093
19287
3918
0.042
2931
No. of integr. refl.
No. of indep. refl.
Rint
24317
16592
6714
4343
0.036
0.038
No. of observed refl.
Threshold criterion
Final R and Rw
(∆/σ)max
4572
3068
F2 > 2.0σ(F2)
0.067, 0.048
0.0003
F2 > 2.5σ(F2)
0.058, 0.060
0.136
F2 > 2.0σ(F2)
0.057, 0.044
0.0004
F2 > 3.0σ(F2)
0.072, 0.075
0.203
∆ρmax, ∆ρmin (e Å-3)
0.32, -0.38
0.38, -0.24
0.42, -0.38
0.34, -0.24
2
Table 2. Fractional Coordinates and Equivalent Temperature Factors (Å ) for compound (4a). U is
eq
defined as one third of the trace of the orthogonalized U tensor.
ij
x/a
y/b
0.8120(2)
z/c
U
eq
N(1)
0.0987(3)
0.1103(2)
0.4577(3)
0.5926(3)
0.5342(2)
0.1995(2)
0.2122(3)
0.2739(3)
0.1944(3)
0.0001(3)
-0.0316(4)
-0.1293(5)
-0.1919(4)
-0.1598(4)
-0.0658(3)
0.2484(3)
0.4770(3)
0.7518(3)
0.7745(5)
0.3846(3)
0.4349(4)
0.5641(4)
0.4318(2)
0.5516(1)
0.5997(2)
0.9127(2)
0.8253(1)
0.3353(1)
0.6268(2)
0.5631(2)
0.4313(2)
0.3310(2)
0.2077(2)
0.1129(2)
0.1384(2)
0.2609(3)
0.3569(2)
0.7639(2)
0.8422(2)
0.8945(2)
0.8811(4)
0.6309(2)
0.4740(3)
0.6969(3)
0.041(1)
0.044(1)
0.054(1)
0.071(1)
0.049(1)
0.055(1)
0.042(1)
0.041(1)
0.041(1)
0.043(1)
0.060(2)
0.075(2)
0.070(2)
0.064(2)
0.052(1)
0.051(1)
0.046(1)
0.053(1)
0.091(2)
0.046(1)
0.066(2)
0.069(2)
N(2)
0.8060(2)
1.2703(2)
1.1037(2)
0.8841(1)
0.9733(1)
0.9292(2)
1.0249(2)
0.9440(2)
0.6904(2)
0.6875(2)
0.5628(3)
0.4423(2)
0.4463(2)
0.5680(2)
0.9575(2)
0.9920(2)
0.9057(2)
0.7716(3)
1.1620(2)
1.2732(2)
1.4026(2)
N(3)
O(1)
O(2)
O(3)
C(3)
C(4)
C(5)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(31)
C(32)
C(33)
C(34)
C(41)
C(42)
C(43)
2
Table 3. Fractional Coordinates and Equivalent Temperature Factors (Å ) for compound (7f). U is
eq
defined as one third of the trace of the orthogonalized U tensor.
ij
x/a
y/b
z/c
0.71094(16)
U
eq
0.0686(7)
O(31)
O(32)
O(5)
0.6850(3)
0.6359(3)
0.67952(25)
0.86953(24)
0.91557(24)
0.50546(25)
0.4560(3)
0.9399(3)
1.0402(4)
1.1021(5)
1.0656(5)
0.21256(17)
0.34658(18)
0.57897(16)
0.38792(16)
0.33352(16)
0.73704(16)
0.86994(19)
0.31370(21)
0.18757(23)
0.1118(3)
0.86560(14)
0.31008(14)
0.37000(15)
0.47880(15)
0.52501(17)
0.69128(17)
0.26292(19)
0.26887(23)
0.16536(25)
0.0563(3)
0.0655(7)
0.0610(6)
0.0442(6)
0.0446(6)
0.0450(6)
0.0575(7)
0.0466(7)
0.0615(9)
N(1)
N(2)
N(4)
N(41)
C(11)
C(12)
C(13)
C(14)
0.0768(12)
0.0797(12)
0.1613(3)

206
HETEROCYCLES, Vol. 61, 2003
C(15)
C(16)
C(3)
0.9708(5)
0.9067(4)
0.82396(25)
0.8390(3)
0.7118(3)
0.5120(6)
0.4412(6)
0.71268(25)
0.6071(3)
0.3753(4)
0.2535(4)
0.2083(4)
0.2885(3)
0.4124(3)
0.7443(3)
0.2878(4)
0.04979(25)
0.0830(13)
0.0675(10)
0.0411(6)
0.0468(7)
0.0463(7)
0.0875(15)
0.0920(16)
0.0415(6)
0.0425(7)
0.0681(10)
0.0647(9)
0.0568(8)
0.0489(7)
0.0431(6)
0.0445(7)
0.3656(3)
0.15231(22)
0.56323(18)
0.69257(19)
0.75467(18)
0.9358(3)
0.41604(18)
0.38927(22)
0.30586(20)
0.2717(4)
C(31)
C(32)
C(33)
C(34)
C(4)
0.3324(5)
1.0538(3)
0.52868(19)
0.63828(19)
0.98296(25)
1.08057(24)
1.06181(22)
0.94688(21)
0.85467(19)
0.50755(20)
0.51661(18)
0.57660(19)
0.74813(24)
0.70255(23)
0.59347(22)
0.53263(20)
0.58563(18)
0.38796(18)
C(41)
C(42)
C(43)
C(44)
C(45)
C(46)
C(5)
2
Table 4. Fractional Coordinates and Equivalent Temperature Factors (Å ) for compound (7r). U is
eq
defined as one third of the trace of the orthogonalized U tensor.
ij
x/a
y/b
z/c
U
eq
O(1a)
O(1b)
O(2a)
O(2b)
O(3a)
O(3b)
N(1a)
N(1b)
N(2a)
N(2b)
N(3a)
N(3b)
N(4a)
N(4b)
C(3a)
C(3b)
C(4a)
C(4b)
C(5a)
C(5b)
C(6a)
C(6b)
C(7a)
C(7b)
C(8a)
C(8b)
C(9a)
C(9b)
C(10a)
C(10b)
C(11a)
C(11b)
C(12a)
C(12b)
C(13a)
C(13b)
C(14a)
C(14b)
0.7716(1)
0.7002(1)
1.1582(2)
0.1885(2)
1.3566(1)
0.0835(1)
0.8842(1)
0.5927(1)
1.0075(1)
0.4769(1)
0.9470(1)
0.5358(1)
0.8371(2)
0.3054(3)
1.0692(2)
0.4173(1)
0.9913(1)
0.4895(1)
0.8692(1)
0.6065(1)
1.2061(2)
0.2891(2)
1.2346(2)
0.1839(2)
1.3987(3)
-0.0243(2)
1.0234(1)
0.4606(1)
0.9886(2)
0.5086(2)
0.9051(2)
0.3949(2)
0.7931(2)
0.6774(1)
0.8185(3)
0.7793(2)
0.7292(4)
0.8592(2)
-0.0565(1)
0.1584(1)
-0.3855(2)
0.2388(4)
-0.3839(2)
0.2655(2)
-0.1950(1)
0.2825(1)
-0.2535(1)
0.2847(1)
0.0139(1)
-0.0368(1)
0.0793(3)
-0.1353(3)
-0.2155(1)
0.1953(1)
-0.1317(1)
0.1284(1)
-0.1195(1)
0.1866(1)
-0.2571(2)
0.1727(2)
-0.3480(2)
0.2304(2)
-0.4692(3)
0.3269(3)
-0.0691(2)
0.0241(1)
0.0864(2)
-0.1544(2)
0.0810(2)
-0.1435(2)
-0.2217(2)
0.3704(1)
-0.3225(2)
0.3942(2)
-0.3464(3)
0.4819(2)
0.6351(1)
0.74241(9)
0.7437(1)
0.8800(2)
0.6360(2)
1.0459(1)
0.5340(1)
0.8599(1)
0.5101(1)
0.9433(1)
0.7233(1)
0.7881(1)
0.9752(2)
0.7268(4)
0.5601(1)
0.9475(1)
0.6193(1)
0.8711(1)
0.6008(1)
0.8144(1)
0.5480(2)
1.0300(1)
0.6539(2)
0.9744(1)
0.7314(3)
1.0026(3)
0.6782(1)
0.8575(1)
0.7748(2)
0.7860(2)
0.8875(2)
0.7531(2)
0.4933(1)
0.8385(1)
0.4524(2)
0.7411(2)
0.4104(3)
0.7236(2)
0.0577(8)
0.0530(7)
0.087(1)
0.132(2)
0.078(1)
0.080(1)
0.0488(8)
0.0451(8)
0.0518(8)
0.0458(8)
0.0505(9)
0.0466(9)
0.093(2)
0.130(3)
0.0483(9)
0.0440(9)
0.0469(9)
0.0428(9)
0.0450(9)
0.0424(9)
0.058(1)
0.048(1)
0.054(1)
0.052(1)
0.102(2)
0.095(2)
0.048(1)
0.0450(9)
0.062(1)
0.055(1)
0.064(1)
0.068(1)
0.051(1)
0.0443(9)
0.075(2)
0.057(1)
0.102(3)
0.065(1)

HETEROCYCLES, Vol. 61, 2003
207
C(15a)
C(15b)
C(16a)
C(16b)
C(17a)
C(17b)
0.6161(3)
0.8402(2)
0.5928(2)
0.7395(2)
0.6816(2)
0.6582(2)
-0.2751(3)
0.4120(2)
0.7989(2)
0.4507(2)
0.8959(2)
0.4898(2)
0.9156(2)
0.093(2)
0.063(1)
0.084(2)
0.065(1)
0.066(1)
0.056(1)
0.5462(2)
-0.1746(3)
0.5224(2)
-0.1457(2)
0.4351(2)
2
Table 5. Fractional Coordinates and Equivalent Temperature Factors (Å ) for compound (8g). U is
eq
defined as one third of the trace of the orthogonalized U tensor.
ij
x/a
y/b
z/c
U
eq
O(31)
O(32)
O(5)
0.779(1)
0.1666(4)
0.0521(4)
0.6353(2)
0.6020(2)
0.1256(2)
0.5324(2)
0.4029(2)
0.6484(3)
0.6256(3)
0.7331(4)
0.8626(3)
0.8851(4)
0.7781(3)
0.3179(3)
0.1688(3)
0.1313(3)
0.001(1)
0.8225(3) 0.205(4)
0.6412(3) 0.132(2)
0.6436(2) 0.070(1)
0.4692(2) 0.075(1)
0.3151(2) 0.087(1)
0.7637(2) 0.060(1)
0.7725(2) 0.069(1)
0.8552(2) 0.058(1)
0.9484(3) 0.080(2)
1.0366(3) 0.094(2)
1.0343(3) 0.085(2)
0.9402(4) 0.103(2)
0.8494(3) 0.095(2)
0.6812(2) 0.064(1)
0.6659(3) 0.078(2)
0.7200(3) 0.095(2)
0.7211(5)
0.7291(3)
0.8061(3)
0.6904(4)
0.6320(3)
0.5729(4)
0.6461(4)
0.6087(5)
0.6127(6)
0.6576(6)
0.6929(7)
0.6861(7)
0.5772(4)
0.5262(5)
0.6911(7)
0.877(1)
O(1')
O(3')
N(1)
N(2)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(3)
C(31)
C(32)
C(33)
C(34)
C(4)
0.682(1)
0.631(2)
0.216(8)
0.27(1)
0.973(2)
0.024(2)
0.6403(3)
0.6637(4)
0.6727(3)
0.7873(4)
0.7237(4)
0.7322(4)
0.8305(5)
0.8918(5)
0.9224(5)
0.8935(5)
0.8312(4)
0.7997(4)
0.3856(3)
0.3171(3)
0.5253(3)
0.4844(3)
0.3550(3)
0.2477(3)
0.2680(4)
0.3587(4)
0.4959(4)
0.5487(4)
0.4575(3)
0.3191(3)
0.6088(2) 0.057(1)
0.5077(2) 0.057(1)
0.6674(2) 0.055(1)
0.4096(2) 0.058(1)
0.4262(2) 0.057(1)
0.3301(2) 0.064(1)
0.1559(3) 0.079(2)
0.1037(3) 0.086(2)
0.1507(3) 0.087(2)
0.2520(3) 0.076(1)
0.3034(2) 0.061(1)
0.2565(2) 0.065(1)
C(41)
C(5)
C(1')
C(2')
C(3')
C(4')
C(5')
C(6')
C(7')
C(8')
C(9')
Table 6. Bond Distances (Å) and Bond Angles (°) with e.s.d.’s in parentheses for compound (4a).
N(1)-N(2)
N(1)-C(5)
N(1)-C(11)
N(2)-C(3)
N(3)-C(41)
N(3)-C(42)
N(3)-C(43)
O(1)-C(32)
O(2)-C(32)
O(2)-C(33)
O(3)-C(5)
C(3)-C(4)
1.394(3)
1.399(3)
1.406(2)
1.297(2)
1.309(3)
1.439(4)
1.461(3)
1.208(2)
1.322(3)
1.448(2)
1.233(3)
1.437(3)
C(3)-C(31)
C(4)-C(5)
1.497(3)
1.457(3)
1.396(2)
1.385(3)
1.401(3)
1.393(3)
1.376(4)
1.373(4)
1.379(3)
1.511(3)
1.475(5)
C(4)-C(41)
C(11)-C(12)
C(11)-C(16)
C(12)-C(13)
C(13)-C(14)
C(14)-C(15)
C(15)-C(16)
C(31)-C(32)
C(33)-C(34)

208
HETEROCYCLES, Vol. 61, 2003
N(2)-N(1)-C(5)
N(2)-N(1)-C(11)
C(5)-N(1)-C(11)
N(1)-N(2)-C(3)
C(41)-N(3)-C(42)
C(41)-N(3)-C(43)
C(42)-N(3)-C(43)
C(32)-O(2)-C(33)
N(2)-C(3)-C(4)
N(2)-C(3)-C(31)
C(4)-C(3)-C(31)
C(3)-C(4)-C(5)
C(3)-C(4)-C(41)
C(5)-C(4)-C(41)
N(1)-C(5)-O(3)
112.6(1)
118.3(2)
129.1(2)
106.1(2)
125.5(2)
119.4(2)
115.1(2)
116.3(1)
113.0(2)
119.3(2)
127.7(2)
104.7(2)
120.1(2)
135.2(2)
123.6(2)
N(1)-C(5)-C(4)
103.6(2)
132.8(2)
122.4(2)
118.5(2)
119.1(2)
119.1(2)
121.9(2)
118.6(2)
121.0(2)
120.3(2)
112.6(2)
124.1(2)
124.4(2)
111.5(1)
108.1(2)
O(3)-C(5)-C(4)
N(1)-C(11)-C(12)
N(1)-C(11)-C(16)
C(12)-C(11)-C(16)
C(11)-C(12)-C(13)
C(12)-C(13)-C(14)
C(13)-C(14)-C(15)
C(14)-C(15)-C(16)
C(11)-C(16)-C(15)
C(3)-C(31)-C(32)
O(1)-C(32)-O(2)
O(1)-C(32)-C(31)
O(2)-C(32)-C(31)
O(2)-C(33)-C(34)
Table 7. Bond Distances (Å) and Bond Angles (°) with e.s.d.’s in parentheses for compound (7f).
O(31)-C(32)
O(32)-C(32)
O(32)-C(33)
O(5)-C(5)
1.199(3)
1.3183(24)
1.462(5)
1.2339(2)
1.3898(2)
1.4053(2)
1.4155(2)
1.2991(2)
1.3301(2)
1.4134(2)
1.323(3)
1.340(3)
1.381(3)
1.387(3)
C(12)-C(13)
C(13)-C(14)
C(14)-C(15)
C(15)-C(16)
C(3)-C(4)
1.388(4)
1.371(5)
1.371(5)
1.391(4)
1.4344(25)
1.497(3)
1.509(3)
1.455(5)
1.3681(25)
1.445(3)
1.368(4)
1.374(4)
1.376(3)
1.387(3)
N(1)-C(5)
N(1)-N(2)
C(3)-C(31)
C(31)-C(32)
C(33)-C(34)
C(4)-C(41)
C(4)-C(5)
N(1)-C(11)
N(2)-C(3)
N(4)-C(41)
N(4)-C(46)
N(41)-C(46)
N(41)-C(42)
C(11)-C(12)
C(11)-C(16)
C(42)-C(43)
C(43)-C(44)
C(44)-C(45)
C(45)-C(46)
C(32)-O(32)-C(33)
C(5)-N(1)-N(2)
116.29(23)
C(3)-C(31)-C(32)
O(31)-C(32)-O(32)
O(31)-C(32)-C(31)
O(32)-C(32)-C(31)
C(34)-C(33)-O(32)
C(41)-C(4)-C(3)
C(41)-C(4)-C(5)
C(3)-C(4)-C(5)
113.23(21)
111.92(15)
129.31(18)
118.54(15)
106.36(15)
123.16(19)
116.72(21)
119.63(22)
119.62(20)
120.74(20)
120.15(25)
120.52(25)
119.3(3)
123.68(22)
125.03(19)
111.27(20)
108.0(4)
C(5)-N(1)-C(11)
N(2)-N(1)-C(11)
C(3)-N(2)-N(1)
C(41)-N(4)-C(46)
C(46)-N(41)-C(42)
C(12)-C(11)-C(16)
C(12)-C(11)-N(1)
C(16)-C(11)-N(1)
C(11)-C(12)-C(13)
C(14)-C(13)-C(12)
C(13)-C(14)-C(15)
C(14)-C(15)-C(16)
C(11)-C(16)-C(15)
N(2)-C(3)-C(4)
128.81(19)
125.68(18)
105.39(15)
124.12(20)
123.59(25)
118.66(23)
119.30(22)
117.64(22)
124.08(18)
115.65(18)
120.24(20)
127.00(19)
128.84(18)
N(4)-C(41)-C(4)
N(41)-C(42)-C(43)
C(42)-C(43)-C(44)
C(43)-C(44)-C(45)
C(44)-C(45)-C(46)
N(41)-C(46)-C(45)
N(41)-C(46)-N(4)
C(45)-C(46)-N(4)
O(5)-C(5)-N(1)
121.3(3)
119.08(25)
112.18(18)
121.11(17)
126.71(16)
104.15(17)
N(2)-C(3)-C(31)
C(4)-C(3)-C(31)
N(1)-C(5)-C(4)
O(5)-C(5)-C(4)
Table 8. Bond Distances (Å) and Bond Angles (°) with e.s.d.’s in parentheses for compound (7r).
O(1a)-C(5a)
O(2a)-C(7a)
O(3a)-C(7a)
O(3a)-C(8a)
1.235(2)
1.198(2)
1.319(2)
1.438(4)
O(1b)-C(5b)
O(2b)-C(7b)
O(3b)-C(7b)
O(3b)-C(8b)
1.240(2)
1.186(3)
1.309(2)
1.450(3)

HETEROCYCLES, Vol. 61, 2003
209
N(1a)-N(2a)
1.403(2)
1.384(2)
1.414(3)
1.304(3)
1.317(2)
1.450(3)
1.149(3)
1.428(2)
1.491(2)
1.437(2)
1.378(3)
1.495(2)
1.455(3)
1.380(3)
1.382(3)
1.394(6)
1.367(5)
1.362(5)
117.3(2)
111.9(1)
119.2(1)
128.9(1)
106.2(1)
122.6(2)
112.0(1)
120.0(2)
128.0(2)
105.6(2)
128.9(2)
125.4(1)
126.4(2)
129.2(2)
104.4(1)
114.3(1)
123.4(2)
125.5(2)
111.0(1)
124.6(2)
111.5(2)
178.2(2)
119.2(2)
121.1(2)
119.6(2)
118.7(3)
121.8(4)
119.0(4)
120.7(3)
120.1(2)
N(1b)-N(2b)
1.403(1)
1.383(2)
1.414(2)
1.304(2)
1.319(2)
1.449(3)
1.138(5)
1.419(2)
1.499(2)
1.444(2)
1.379(3)
1.505(2)
1.441(4)
1.393(2)
1.389(3)
1.385(3)
1.366(3)
1.382(3)
117.1(2)
111.8(1)
118.0(1)
130.1(1)
106.2(1)
123.0(1)
112.1(1)
119.4(2)
128.5(2)
105.7(1)
128.3(1)
125.9(1)
126.6(1)
129.2(2)
104.2(1)
112.5(1)
123.9(2)
125.0(2)
111.0(2)
124.7(1)
112.9(2)
179.7(3)
121.3(2)
119.4(1)
119.3(2)
119.1(2)
121.7(2)
119.3(2)
120.2(2)
120.4(1)
N(1a)-C(5a)
N(1b)-C(5b)
N(1a)-C(12a)
N(1b)-C(12b)
N(2a)-C(3a)
N(2b)-C(3b)
N(3a)-C(9a)
N(3b)-C(9b)
N(3a)-C(10a)
N(3b)-C(10b)
N(4a)-C(11a)
N(4b)-C(11b)
C(3a)-C(4a)
C(3b)-C(4b)
C(3a)-C(6a)
C(3b)-C(6b)
C(4a)-C(5a)
C(4b)-C(5b)
C(4a)-C(9a)
C(4b)-C(9b)
C(6a)-C(7a)
C(6b)-C(7b)
C(10a)-C(11a)
C(10b)-C(11b)
C(12a)-C(13a)
C(12b)-C(13b)
C(12a)-C(17a)
C(12b)-C(17b)
C(13a)-C(14a)
C(13b)-C(14b)
C(14a)-C(15a)
C(14b)-C(15b)
C(15a)-C(16a)
C(15b)-C(16b)
C(7a)-O(3a)-C(8a)
N(2a)-N(1a)-C(5a)
N(2a)-N(1a)-C(12a)
C(5a)-N(1a)-C(12a)
N(1a)-N(2a)-C(3a)
C(9a)-N(3a)-C(10a)
N(2a)-C(3a)-C(4a)
N(2a)-C(3a)-C(6a)
C(4a)-C(3a)-C(6a)
C(3a)-C(4a)-C(5a)
C(3a)-C(4a)-C(9a)
C(5a)-C(4a)-C(9a)
O(1a)-C(5a)-N(1a)
O(1a)-C(5a)-C(4a)
N(1a)-C(5a)-C(4a)
C(3a)-C(6a)-C(7a)
O(2a)-C(7a)-O(3a)
O(2a)-C(7a)-C(6a)
O(3a)-C(7a)-C(6a)
N(3a)-C(9a)-C(4a)
N(3a)-C(10a)-C(11a)
N(4a)-C(11a)-C(10a)
N(1a)-C(12a)-C(13a)
N(1a)-C(12a)-C(17a)
C(13a)-C(12a)-C(17a)
C(12a)-C(13a)-C(14a)
C(13a)-C(14a)-C(15a)
C(14a)-C(15a)-C(16a)
C(15a)-C(16a)-C(17a)
C(12a)-C(17a)-C(16a)
C(7b)-O(3b)-C(8b)
N(2b)-N(1b)-C(5b)
N(2b)-N(1b)-C(12b)
C(5b)-N(1b)-C(12b)
N(1b)-N(2b)-C(3b)
C(9b)-N(3b)-C(10b)
N(2b)-C(3b)-C(4b)
N(2b)-C(3b)-C(6b)
C(4b)-C(3b)-C(6b)
C(3b)-C(4b)-C(5b)
C(3b)-C(4b)-C(9b)
C(5b)-C(4b)-C(9b)
O(1b)-C(5b)-N(1b)
O(1b)-C(5b)-C(4b)
N(1b)-C(5b)-C(4b)
C(3b)-C(6b)-C(7b)
O(2b)-C(7b)-O(3b)
O(2b)-C(7b)-C(6b)
O(3b)-C(7b)-C(6b)
N(3b)-C(9b)-C(4b)
N(3b)-C(10b)-C(11b)
N(4b)-C(11b)-C(10b)
N(1b)-C(12b)-C(13b)
N(1b)-C(12b)-C(17b)
C(13b)-C(12b)-C(17b)
C(12b)-C(13b)-C(14b)
C(13b)-C(14b)-C(15b)
C(14b)-C(15b)-C(16b)
C(15b)-C(16b)-C(17b)
C(12b)-C(17b)-C(16b)
Table 9. Bond Distances (Å) and Bond Angles (°) with e.s.d.’s in parentheses for compound (8g).
O(31)-C(32)
O(32)-C(32)
O(32)-C(33)
O(5)-C(5)
1.167(5)
1.278(6)
1.51(1)
C(3)-C(31)
C(31)-C(32)
C(33)-C(34)
C(4)-C(41)
C(4)-C(5)
1.494(4)
1.510(6)
1.19(3)
1.296(4)
1.245(3)
1.217(4)
1.350(4)
1.395(3)
1.433(4)
1.408(4)
1.416(4)
1.376(4)
1.445(4)
1.480(4)
1.492(4)
O(1')-C(1')
O(3')-C(3')
N(1)-C(5)
C(41)-C(2')
C(1')-C(2')
C(1')-C(8')
C(2')-C(3')
N(1)-N(2)
N(1)-C(11)

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N(2)-C(3)
1.304(4)
1.364(5)
1.368(5)
1.383(6)
1.352(5)
1.367(7)
1.390(6)
1.436(5)
C(3')-C(9')
C(4')-C(5')
C(4')-C(9')
C(5')-C(6')
C(6')-C(7')
C(7')-C(8')
C(8')-C(9')
1.489(5)
1.380(6)
1.385(5)
1.371(6)
1.389(6)
1.379(5)
1.381(4)
C(11)-C(12)
C(11)-C(16)
C(12)-C(13)
C(13)-C(14)
C(14)-C(15)
C(15)-C(16)
C(3)-C(4)
C(32)-O(32)-C(33)
C(5)-N(1)-N(2)
118.6(6)
C(2')-C(41)-C(4)
O(5)-C(5)-N(1)
O(5)-C(5)-C(4)
N(1)-C(5)-C(4)
O(1')-C(1')-C(2')
O(1')-C(1')-C(8')
C(2')-C(1')-C(8')
C(41)-C(2')-C(1')
C(41)-C(2')-C(3')
C(1')-C(2')-C(3')
O(3')-C(3')-C(9')
O(3')-C(3')-C(2')
C(9')-C(3')-C(2')
C(5')-C(4')-C(9')
C(6')-C(5')-C(4')
C(5')-C(6')-C(7')
C(8')-C(7')-C(6')
C(7')-C(8')-C(9')
C(7')-C(8')-C(1')
C(9')-C(8')-C(1')
C(8')-C(9')-C(4')
C(8')-C(9')-C(3')
C(4')-C(9')-C(3')
135.8(3)
111.4(2)
130.5(2)
118.1(3)
105.4(3)
119.4(3)
117.7(3)
122.8(3)
120.1(3)
121.3(4)
118.5(4)
121.1(4)
119.5(4)
112.7(3)
119.2(3)
128.0(3)
110.9(3)
123.3(6)
124.1(6)
112.6(3)
111(2)
120.6(2)
132.0(3)
107.4(2)
129.8(3)
122.3(3)
108.0(2)
133.9(3)
119.2(3)
106.9(3)
127.1(3)
126.3(3)
106.7(3)
118.3(4)
120.8(4)
121.6(4)
117.4(4)
121.4(3)
129.0(3)
109.6(3)
120.6(3)
108.8(3)
130.5(3)
C(5)-N(1)-C(11)
N(2)-N(1)-C(11)
C(3)-N(2)-N(1)
C(12)-C(11)-C(16)
C(12)-C(11)-N(1)
C(16)-C(11)-N(1)
C(11)-C(12)-C(13)
C(14)-C(13)-C(12)
C(13)-C(14)-C(15)
C(14)-C(15)-C(16)
C(11)-C(16)-C(15)
N(2)-C(3)-C(4)
N(2)-C(3)-C(31)
C(4)-C(3)-C(31)
C(3)-C(31)-C(32)
O(31)-C(32)-O(32)
O(31)-C(32)-C(31)
O(32)-C(32)-C(31)
C(34)-C(33)-O(32)
C(41)-C(4)-C(5)
C(41)-C(4)-C(3)
C(5)-C(4)-C(3)
133.2(3)
123.7(3)
103.0(2)
EXPERIMENTAL
1
13
Melting points were taken on a Kofler micro hot stage. The H NMR, C NMR and 2D NMR HMBC,
NOESY spectra were obtained on a Bruker Avance DPX 300 (300 MHz) spectrometer with DMSO-d6 or
CDCl3 as solvent and TMS as internal standard (δ in ppm, J in Hz). IR spectra were recorded with Perkin–
Elmer Spectrum BX FTIR spectrophotometer (KBr discs, ν in cm-1). MS spectra were obtained on an
Autospeck Q spectrometer. The microanalyses for C, H, and N were obtained on a Perkin Elmer CHN
Analyser 2400.
Ethyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetate (3a).16a,b
Phenylhydrazine (2) (9.9 mL, 100 mmol) was added at a rapid dropwise rate to diethyl acetone-1,3-
dicarboxylate (1) (18.1 mL, 100 mmol), stirred vigorously. Temperature rose to 70 °C, mixture was then
heated on steam bath for 1.5 h. The glassy product obtained on cooling was dissolved in a boiling mixture
of methanol (50 mL) and water (50 mL), filtered hot, and the filtrate was cooled to –20 °C. The

HETEROCYCLES, Vol. 61, 2003
211
precipitate was collected by filtration, to give 3a. White solid. Yield: 56% (14.6 g) mp 75−76 °C
(methanol/water) (lit.,16a 85 °C). IR (cm–1): 1740, 1600, 1560, 1400, 1340, 1190, 760. 1H NMR (CDCl3):
δ 1.31 (t, 3H, J = 7.2, OCH2CH3); 3.59 (s, 2H, CH2); 3.64 (s, 2H, CH2); 4.23 (q, 2H, J = 7.2, OCH2CH3);
7.17–7.22 (m, 1H, Ph); 7.37–7.42 (m, 2H, Ph); 7.83–7.84 (m, 2H, Ph). (DMSO-d6): δ 1.20 (t, 3H, J = 7.0,
OCH2CH3); 3.54 (s, 2H, CH2); 4.10 (q, 2H, J = 7.2, OCH2CH3); 5.50 (s, 1H, 4–H); 7.21–7.27 (m, 1H,
Ph); 7.40–7.46 (m, 2H, Ph); 7.68–7.72 (m, 2H, Ph); 11.58 (br s, 1H, OH).
Methyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetate (3b).16c
Phenylhydrazine (2) (9.9 mL, 100 mmol) was added at a rapid dropwise rate to dimethyl acetone-1,3-
dicarboxylate (1) (17.4 mL, 100 mmol), stirred vigorously. Temperature rose to 70 °C, mixture was then
heated on steam bath for 1.5 h. The glassy product obtained on cooling was crystallized from a mixture of
methanol (100 mL) and water (100 mL). The precipitate was collected by filtration to give 3b. White
solid. Yield: 62% (14.4 g), mp 89−92 °C (methanol/water) (lit.,16c 86–89 °C). IR (cm–1): 1740, 1590,
1550, 1530, 1410, 1330, 1200, 1150, 760, 690. 1H NMR (CDCl3): δ 3.60 (s, 2H, CH2); 3.63 (s, 2H, CH2);
3.78 (s, 3H, OCH3); 7.16–7.22 (m, 1H, Ph); 7.36–7.43 (m, 2H, Ph); 7.83–7.86 (m, 2H, Ph).
General Procedure for the Preparation of Alkyl [(Z)-4-Dimethylaminomethylidene-5-oxo-1-phenyl-
4,5-dihydro-1H-pyrazol-3-yl]acetates (4a,b). DMFDMA (3 mL, 20 mmol) was added to a solution of
3a,b (10 mmol) in toluene (30 mL) and the mixture was left at rt overnight (~12 h). The precipitate was
collected by filtration, and recrystallized from mixture of ethanol and toluene to give 4a,b.
The following compounds were prepared in this manner:
Ethyl [(Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (4a).
This compound was prepared from 3a (2.46 g, 10 mmol) and DMFDMA. White crystals. Yield: 78%
(2.36 g), mp 106−110 °C (ethanol/toluene). Anal. Calcd for C16H19N3O3: C 63.77; H 6.36; N 13.94.
Found, C 64.03; H 6.52; N 13.80. MS: m/z (M+, 301; MH+, 302). IR (cm–1): 1730, 1680, 1620, 1560,
1490, 1430, 1290, 770. 1H NMR (CDCl3): δ 1.21 (t, 3H, J = 7.2, OCH2CH3); 3.35 (s, 3H, NMe); 3.67 (s,
2H, CH2); 3.79 (s, 3H, NMe); 4.11 (q, 2H, J = 7.2, OCH2CH3); 7.05−7.10 (m, 1H, Ph); 7.31−7.37 (m, 2H,
13
Ph); 7.91−7.95 (m, 2H, Ph); 7.59 (s, 1H, =CH). C NMR (CDCl3): δ 14.5; 35.7; 43.9; 48.6; 61.8; 99.0;
120.0; 124.6; 128.9; 139.8; 147.2; 153.8; 162.5; 170.3.
Methyl [(Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (4b).
This compound was prepared from 3b (2.32 g, 10 mmol) and DMFDMA. White crystals. Yield: 53%

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HETEROCYCLES, Vol. 61, 2003
(1.87 g), mp 138−140 °C (ethanol/toluene). Anal. Calcd for C15H17N3O3: C 62.71; H 5.96; N 14.63.
1
Found, C 62.52; H 5.88; N 14.60. IR (cm–1): 1740, 1670, 1610, 1550, 1490, 1430, 1400, 1260, 770. H
NMR (CDCl3): δ 3.32 (s, 3H, NMe); 3.62 (s, 2H, CH2); 3.73 (s, 3H, OCH3); 3.88 (s, 3H, NMe);
13
7.09−7.14 (m, 1H, Ph); 7.28 (s, 1H, =CH); 7.33−7.38 (m, 2H, Ph); 7.42−7.59 (m, 2H, Ph). C NMR
(CDCl3): δ 35.3; 43.9; 48.6; 52.8; 99.0; 120.0; 124.6; 128.9; 139.8; 147.0; 153.7; 162.4; 170.8.
General Procedures for the Preparation of Alkyl {5-oxo-1-phenyl-4-[(Z)-(substituted methylidene)]-
4,5-dihydro-1H-pyrazol-3-yl}acetates (7a–s) and (8a–l).
Procedure A. Hydrochloric acid (37%, 2 drops, ~0.6 mmol) was added to a mixture of 4a,b (0.5 mmol)
and nucleophile (5) or (6) (0.5 mmol) in anhydrous ethanol (5 mL), and the mixture was left at rt
overnight (~12 h). The precipitate was collected by filtration, washed with anhydrous ethanol, crystallized
from anhydrous ethanol, to give 7 and 8.
Procedure B. A mixture of 4a,b (0.5 mmol) and amine hydrochloride (5) (0.5 mmol) in anhydrous
ethanol (5 mL) was left at rt overnight (~12 h). The precipitate was collected by filtration, washed with
anhydrous ethanol, crystallized from anhydrous ethanol, to give 7 and 8.
Procedure C. A mixture of 4a (80 mg, 0.265 mmol), ethanol (3 mL), and hydrochloric acid (37%, 1
drop, ~0.3 mmol), was heated at reflux temperature for 4 h. After cooling, the precipitate was collected by
filtration to give 8i.
The following compounds were prepared in this manner:
Ethyl [(Z)-5-oxo-1-phenyl-4-phenylaminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate (7a).
This compound was prepared from 4a (151 mg, 0.5 mmol) and aniline hydrochloride (5a) (65 mg, 0.5
mmol), Procedure B. Yellow solid. Yield: 83% (145 mg), mp 138−140 °C (ethanol). Anal. Calcd for
C20H19N3O3: C 68.75; H 5.48; N 12.03. Found, C 68.79; H 5.61; N 12.32. MS: m/z (M+, 349; MH+, 350).
IR (cm–1): 1730, 1680, 1630, 1590, 1500, 1320, 1200, 750, 690. 1H NMR (CDCl3): δ 1.30 (t, 3H, J = 7.2,
OCH2CH3); 3.74 (s, 2H, CH2); 4.22 (q, 2H, J = 7.2, OCH2CH3); 7.15−7.72 (m, 4H, Ph); 7.39−7.46 (m,
13
4H, Ph); 7.98−8.02 (m, 2H, Ph); 8.29 (s, 1H, =CH); 11.68 (br s, 1H, NH). C NMR (CDCl3): δ 14.6;
35.6; 62.0; 102.3; 117.8; 119.1; 125.1; 126.4; 129.4; 130.4; 138.8; 139.2; 144.8; 145.3 164.7; 170.1.
Methyl [(Z)-5-oxo-1-phenyl-4-phenylaminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate (7b).
This compound was prepared from 4b (144 mg, 0.5 mmol) and aniline hydrochloride (5a) (65 mg, 0.5
mmol), Procedure B. Yellow solid. Yield: 50% (84 mg), mp 142–143 °C (ethanol). Anal. Calcd for
C19H17N3O3: C 68.05; H 5.11; N 12.53. Found, C 68.16; H 5.38; N 12.75. IR (cm–1): 1730, 1670, 1630,

HETEROCYCLES, Vol. 61, 2003
213
1
1590, 1500, 1320, 1210, 750. H NMR (CDCl3): δ 3.76 (s, 2H, CH2); 3.77 (s, 3H, OMe); 7.15–7.24 (m,
4H, Ph); 7.38–7.46 (m, 4H, Ph); 7.99–8.01 (m, 2H, Ph); 8.27 (br s, 1H, =CH);11.71 (br s, 1H, NH).
Ethyl [(Z)-5-oxo-1-phenyl-4-(4-methylphenyl)aminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7c). This compound was prepared from 4a (151 mg, 0.5 mmol) and 4-methylaniline hydrochloride (5c) (72
mg, 0.5 mmol), Procedure B. Yellow solid. Yield: 96% (175 mg), mp 128−140 °C (ethanol). Anal. Calcd
for C21H21N3O3: C 69.41; H 5.82; N 11.56. Found, 69.74; H 5.92; N 11.64. MS: m/z (M+, 363). IR (cm–1):
1730, 1670, 1630, 1400. 1H NMR (CDCl3): δ 1.32 (t, 3H, J = 7.2, OCH2CH3); 2.39 (s, 3H, Ph-Me); 3.76 (s,
2H, CH2); 4.24 (q, 2H, J = 7.2, OCH2CH3); 7.14−7.23 (m, 5H, Ph); 7.40−7.46 (m, 2H, Ph); 8.01−8.04 (m, 2H,
13
Ph); 8.26 (s, 1H, =CH); 11.70 (br s, 1H, NH). C NMR (CDCl3): δ 14.6; 21.3; 35.6; 62.0; 101.9; 117.8;
119.5; 125.1; 129.2; 130.9; 136.4; 139.2; 144.7; 145.4; 160.7; 166.1; 170.1.
Ethyl
[(Z)-4-(4-hydroxyphenyl)aminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (7d). This compound was prepared from 4a (151 mg, 0.5 mmol) and 4-hydroxyaniline (5d) (55
mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 67% (122 mg), mp 220−224 °C (ethanol). Anal. Calcd
for C20H19N3O4: C 65.74; H 5.24; N 11.50. Found, C 65.70; H 5.48; N 11.53. MS: m/z (M+, 365; MH+,
366). IR (cm–1): 3310, 1730, 1670, 1600, 1520, 1490, 1340, 1270, 1200, 830, 750. 1H NMR (DMSO-d6):
δ 1.21 (t, 3H, J = 7.2, OCH2CH3); 3.82 (s, 2H, CH2); 4.14 (q, 2H, J = 7.0, OCH2CH3); 6.83−6.86 (m, 2H,
Ph); 7.12−7.18 (m, 1H, Ph); 7.36−7.44 (m, 4H, Ph); 7.98−8.01 (m, 2H, Ph); 8.54 (s, 1H, =CH); 9.64 (s,
13
1H, NH); 11.41 (br s, 1H, OH). C NMR (DMSO-d6): δ 14.9; 34.2; 61.5; 101.0; 117.0; 118.6; 120.5;
124.8; 129.6; 131.4; 139.9; 146.7; 147.6; 156.6; 165.6; 170.3.
Methyl [(Z)-4-(4-methoxyphenyl)aminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (7e). This compound was prepared from 4b (144 mg, 0.5 mmol) and 4-methoxyaniline (5e) (62
mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 76% (138 mg), mp 131−133 °C (ethanol). Anal. Calcd
for C20H19N3O4: C 65.74; H 5.24; N 11.50. Found, C 65.83; H 5.43; N 11.60. IR (cm–1): 1730, 1670,
1
1230, 1500, 1390, 1250, 830, 750. H NMR (CDCl3): δ 3.75 (s, 2H, CH2); 3.76 (s, 3H, OCH3); 3.83 (s,
3H, PhOCH3); 6.93−6.97 (m, 2H, Ph); 7.17−7.20 (m, 3H, Ph); 7.38−7.43 (m, 2H, Ph); 7.98−8.02 (m, 2H,
Ph); 8.16 (br s, 1H, =CH); 11.72 (br s, 1H, NH). 13C NMR (DMSO-d6): δ 33.9; 52.9; 56.3; 101.4; 115.7;
118.6; 120.4; 124.8; 129.6; 132.8; 139.9; 146.6; 147.6; 158.2; 165.5; 170.8.
Ethyl [(Z)-5-oxo-1-phenyl-4-(pyridin-2-yl)aminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7f). This compound was prepared from 4a (151 mg, 0.5 mmol) and 2-aminopyridine (5f) (47 mg, 0.5

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mmol), Procedure A. Yellow crystals. Yield: 58% (102 mg), mp 126−127 °C (ethanol). Anal. Calcd for
C19H18N4O3: C 65.15; H 5.18; N 15.99. Found, C 65.34; H 5.24; N 16.09. MS: m/z (M+, 350). IR (cm–1):
1
3270, 1730, 1670, 1630, 1600, 1570, 1500, 1480, 1320, 1280, 1030, 760, 680. H NMR (CDCl3): δ 1.30
(t, 3H, J = 7.2, OCH2CH3); 3.72 (s, 2H, CH2); 4.23 (q, 2H, J = 7.2, OCH2CH3); 6.99 (ddd, 1H, J = 8.3,
1.8, 0.9, 3’−H); 7.12 (ddd, 1H, J = 7.5, 4.9, 1.0, 5’−H); 7.16−7.21 (m, 1H, Ph); 7.39−7.45 (m, 2H, Ph);
7.72 (ddd, 1H, J = 8.2, 7.4, 1.9, 4’–H); 7.98−8.02 (m, 2H, Ph); 8.40 (ddd, 1H, J = 4.9, 1.9, 0.9, 6’–H);
13
8.94 (bd, 1H, J = 8.5, =CH); 11.76 (br s, 1H, NH). C NMR (CDCl3): δ 14.5; 35.2; 61.9; 103.9; 113.7;
113.1; 119.4; 121.0; 125.2; 129.2; 139.1; 139.3; 143.4; 145.6; 149.3; 150.3; 166.2; 169.7.
Methyl [(Z)-5-oxo-1-phenyl-4-(pyridin-2-yl)aminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7g). This compound was prepared from 4b (144 mg, 0.5 mmol) and 2-aminopyridine (5f) (47 mg, 0.5
mmol), Procedure A. Yellow solid. Yield: 48% (80 mg), mp 132−134 °C (ethanol). Anal. Calcd for
C18H16N4O3: C 64.28; H 4.79; N 16.66. Found, C 64.38; H 4.84; N 16.76. IR (cm–1): 3280, 1730, 1670,
1630, 1480, 1280, 1150, 760. 1H NMR (CDCl3): δ 3.77 (s, 3H, OCH3); 3.78 (s, 2H, CH2); 6.99 (d, 1H, J =
7.9, 3’−H); 7.12 (ddd, 1H, J = 7.2, 4.9, 0.8, 5’−H); 7.16−7.21 (m, 1H, Ph); 7.39−7.44 (m, 2H, Ph); 7.72
(ddd, 1H, J = 7.9, 7.5, 1.9, 4’–H); 7.98−8.01 (m, 2H, Ph); 8.40 (dd, 1H, J = 4.9, 0.8, 6’–H); 8.94 (bd, 1H,
J = 7.2, =CH); 11.76 (br s, 1H, NH).
Ethyl (Z)-[5-oxo-1-phenyl-4-(quinolin-3-yl)aminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7h). This compound was prepared from 4a (151 mg, 0.5 mmol) and 3-aminoquinoline (5h) (72 mg, 0.5
mmol), Procedure A. Yellow solid. Yield: 92% (185 mg), mp 203−206 °C (ethanol). Anal. Calcd for
C23H20N4O3: C 68.99; H 5.03; N 13.99. Found, C 68.77; H 5.15; N 13.96. MS: m/z (M+, 400; MH+, 401).
1
IR (cm–1): 1720, 1670, 1630, 1600, 1550, 1500, 1400, 1340, 1300, 1200, 750. H NMR (CDCl3): δ 1.33
(t, 3H, J = 7.2, OCH2CH3); 3.80 (s, 2H, CH2); 4.25 (q, 2H, J = 7.2, OCH2CH3); 7.18−7.24 (m, 1H, Ph);
7.40−7.46 (m, 2H, Ph); 7.59–7.65 (m, 1H, 1H of quinoline); 7.69–7.74 (m, 1H, 1H of quinoline); 7.85
(dd, 1H, J = 8.3, 1.5, 1H of quinoline); 7.95 (d, 1H, J = 2.6, 4–H of quinoline); 8.00−8.03 (m, 2H, Ph);
13
8.13 (d, 1H, J = 8.7, 1H of quinoline); 8.43 (s, 1H, =CH); 8.92 (d, 1H, J = 2.6, 2–H of quinoline). C
NMR (CDCl3): δ 14.6; 35.6; 62.0; 102.3; 117.8; 119.1; 125.1; 126.4; 129.4; 130.4; 138.8; 139.2; 144.8;
145.3 164.7; 170.1.
Ethyl [(Z)-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)aminomethylidene-5-oxo-1-phenyl-4,5-di-
hydro-1H-pyrazol-3-yl]acetate (7i). This compound was prepared from 4a (151 mg, 0.5 mmol) and 4-
aminouracil (5i) (64 mg, 0.5 mmol), Procedure A. Pale orange solid. Yield: 84% (160 mg), mp 244−246

HETEROCYCLES, Vol. 61, 2003
215
°C (ethanol). Anal. Calcd for C18H17N5O5: C 56.39; H 4.47; N 18.27. Found, C 56.11; H 4.70; N 18.21.
MS: m/z (M+, 383; MH+, 384). IR (cm–1): 3390, 3340, 3200, 1750, 1730, 1640, 1590, 1500, 1420, 1350,
1250, 760. 1H NMR (DMSO-d6): δ 1.20 (t, 3H, J = 7.0, OCH2CH3); 3.77 (s, 2H, CH2); 4.13 (q, 2H, J = 7.2,
OCH2CH3); 6.15 (br s, 1H, NH); 7.18−7.23 (m, 1H, Ph); 7.41−7.46 (m, 2H, Ph); 7.89−7.91 (m, 2H,
13
Ph); 7.99 (s, 1H, =CH); 10.03 (br s, 1H, NH); 11.12 (br s, 1H, NH); 11.22 (s, 1H, 6’−H). C NMR
(DMSO-d6): δ 14.8; 34.8; 61.7; 94.0; 110.8; 119.9; 125.8; 129.6; 139.2; 142.2; 149.3; 150.7; 158.2;
164.0; 164.4; 169.9.
Methyl [(Z)-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)aminomethylidene-5-oxo-1-phenyl-4,5-
dihydro-1H-pyrazol-3-yl]acetate (7j). This compound was prepared from 4b (144 mg, 0.5 mmol) and 4-
aminouracil (5i) (64 mg, 0.5 mmol), Procedure A. Pale orange solid. Yield: 70% (129 mg), mp 265−266
°C (ethanol). Anal. Calcd for C17H15N5O5: C 55.28; H 4.09; N 18.96. Found, C 55.14; H 4.32; N 18.84.
1
IR (cm–1): 3360, 1740, 1660, 1590, 1440, 1390, 1260, 940, 760. H NMR (DMSO-d6): δ 3.66 (s, 3H,
OCH3); 3.79 (s, 2H, CH2); 7.19−7.23 (m, 1H, Ph); 7.41−7.46 (m, 2H, Ph); 7.89−7.91 (m, 2H, Ph); 7.97 (s,
1H, =CH); 11.08 (br s, 1H, NH); 11.23 (s, 1H, 6’–H).
Ethyl [(Z)-5-oxo-1-phenyl-4-pyrazinylaminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]acetate (7k).
This compound was prepared from 4a (151 mg, 0.5 mmol) and aminopyrazine (5k) (48 mg, 0.5 mmol),
Procedure A. Yellow solid. Yield: 84% (148 mg), mp 164−166 °C (ethanol). Anal. Calcd for C18H17N5O3:
C 61.53; H 4.88; N 19.93. Found, C 61.78; H 5.09; N 19.89. MS: m/z (M+, 351). IR (cm–1): 1720, 1670,
1
1630, 1500, 1400, 1340, 1280, 1210, 750. H NMR (CDCl3): δ 1.31 (t, 3H, J = 7.2, OCH2CH3); 3.77 (s,
2H, CH2); 4.23 (q, 2H, J = 7.2, OCH2CH3); 7.17−7.23 (m, 1H, Ph); 7.40−7.45 (m, 2H, Ph); 7.96−8.00 (m,
2H, Ph); 8.34 (dd, 1H, J = 2.6, 1.5, 5’−H); 8.39 (d, 1H, J = 2.6, 6’−H); 8.44 (d, 1H, J = 1.5, 3’–H); 8.85
13
(s, 1H, =CH); 11.89 (br s, 1H, NH). C NMR (CDCl3): δ 14.5; 35.2; 62.0; 105.5; 119.2; 125.4; 129.2;
135.8; 138.8; 141.3; 142.5; 143.0; 145.4; 147.2; 166.1; 169.5.
Methyl (Z)-[5-oxo-1-phenyl-4-(pyrazin-2-ylaminomethylidene)-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7l). This compound was prepared from 4b (144 mg, 0.5 mmol) and aminopyrazine (5k) (48 mg, 0.5
mmol), Procedure A. Yellow crystals. Yield: 81% (136 mg), mp 192−195 °C (ethanol). Anal. Calcd for
C17H15N5O3: C 60.53; H 4.48; N 20.76. Found, C 60.48; H 4.64; N 20.72. IR (cm–1): 1740, 1680, 1630,
1500, 1390, 1270, 1050, 770. 1H NMR (CDCl3): δ 3.77 (s, 3H, OCH3); 3.78 (s, 2H, CH2); 7.18−7.23 (m,
1H, Ph); 7.40−7.45 (m, 2H, Ph); 7.97−8.00 (m, 2H, Ph); 8.35 (dd, 1H, J = 2.6, 1.5, 5’−H); 8.39 (d, 1H, J
= 2.6, 6’−H); 8.44 (d, 1H, J = 1.1, 3’H); 8.82 (s, 1H, =CH); 11.89 (br s, 1H, NH).

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Ethyl
[(Z)-5-oxo-1-phenyl-4-(1H-pyrazol-3-yl)aminomethylidene-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (7m). This compound was prepared from 4a (151 mg, 0.5 mmol) and 3-aminopyrazole (5m) (42
mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 91% (155 mg), mp 172−175 °C (ethanol). Anal. Calcd
for C17H17N5O3: C 60.17; H 5.05; N 20.64. Found, C 60.38; H 5.28; N 20.75. MS: m/z (M+, 339; MH+,
1
340). IR (cm–1): 3420, 1720, 1670, 1630, 1540, 1320, 1260, 1030, 750. H NMR (DMSO-d6): δ 1.22 (t,
3H, J = 7.2, OCH2CH3); 3.83 (s, 2H, CH2); 4.14 (q, 2H, J = 7.2, OCH2CH3); 6.46 (br s, 1H, 4’−H);
7.13−7.19 (m, 1H, Ph); 7.40−7.45 (m, 2H, Ph); 7.78 (br s, 1H, 1H, 5’−H); 7.96−8.00 (m, 2H, Ph); 8.57 (s,
13
1H, =CH); 11.48 (br s, 1H, NH); 12.79 (br s, 1H, 1’−NH). C NMR (CDCl3): δ 14.6; 35.5; 62.0; 94.6;
102.2; 119.8; 125.3; 129.2; 130.6; 139.1; 145.5; 146.0; 149.4; 165.5; 170.1.
Ethyl
[(Z)-4-(1H-indazol-3-yl)aminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (7n). This compound was prepared from 4a (151 mg, 0.5 mmol) and 3-aminoindazole (5n) (67
mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 90% (175 mg), mp 187−189 °C (ethanol). Anal. Calcd
for C21H19N5O3: C 64.77; H 4.92; N 17.98. Found, C 64.33; H 5.13; N 18.06. MS: m/z (M+, 389; MH+,
1
390). IR (cm–1): 3460, 1730, 1680, 1620, 1540, 1500, 1350, 1280, 750. H NMR (DMSO-d6): δ 1.23 (t,
3H, J = 7.2, OCH2CH3); 3.90 (s, 2H, CH2); 4.16 (q, 2H, J = 7.2, OCH2CH3); 7.16−7.26 (m, 2H, Ph);
7.42−7.49 (m, 3H, Ph); 7.55−7.58 (m, 1H, Ph); 7.91−7.94 (m, 1H, Ph); 7.99−8.02 (m, 2H, Ph); 8.75 (s,
13
1H, =CH); 11.78 (br s, 1H, NH); 13.07 (s, 1H, NH). C NMR (DMSO-d6): δ 14.5; 35.2; 62.1; 103.1;
110.8; 114.2; 118.8; 119.7; 122.0; 125.3; 128.3; 129.3; 139.0; 141.7; 142.1; 145.2; 166.2; 170.1.
Ethyl
[(Z)-4-(benzothiazol-2-yl)aminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-
acetate (7o). This compound was prepared from 4a (151 mg, 0.5 mmol) and 2-aminobenzothiazole (5o)
(75 mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 70% (142 mg), mp 150−153 °C (ethanol). Anal.
Calcd for C21H18N4O3S: C 62.05; H 4.46; N 13.78. Found, C 62.12; H 4.64; N 13.86. MS: m/z (M+, 406;
MH+, 407). IR (cm–1): 1720, 1670, 1630, 1520, 1500, 1350, 1260, 750. 1H NMR (CDCl3): δ 1.33 (t, 3H, J
= 7.2, OCH2CH3); 3.78 (s, 2H, CH2); 4.26 (q, 2H, J = 7.2, OCH2CH3); 7.18−7.24 (m, 1H, Ph); 7.35−7.51
(m, 4H, Ph); 7.78 (dd, 1H, J = 7.9, 0.8, Ph’); 7.84 ( dd, 1H, J = 8.3, 0.8, Ph’); 7.97−8.00 (m, 2H, Ph); 8.67
13
(s, 1H, =CH). C NMR (CDCl3): δ 14.6; 19.3; 35.2; 62.1; 106.0; 119.3; 121.9; 122.2; 125.2; 125.5;
127.3; 129.3; 138.7; 142.7; 145.7; 151.3; 159.2; 165.8; 169.4.
Ethyl [(Z)-4-hydroxyaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (7p).
This compound was prepared from 4a (151 mg, 0.5 mmol) and hydroxylamine hydrochloride (5p) (35
mg, 0.5 mmol), Procedure B. Light yellow crystals. Yield: 45% (65 mg), mp 140−143 °C (ethanol). Anal.

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Calcd for C14H15N3O4: C 58.13; H 5.23. N 14.53. Found, C 58.08; H 5.21; N 14.56. MS: m/z (M+, 289).
1
IR (cm–1): 1780, 1630, 1410, 1210, 1030, 760. H NMR (DMSO-d6): δ 1.20 (t, 3H, J = 7.0, OCH2CH3);
3.71 (s, 2H, CH2); 4.11 (q, 2H, J = 7.2, OCH2CH3); 7.18−7.23 (m, 1H, Ph); 7.39−7.44 (m, 2H, Ph);
7.80−7.87 (m, 2H, Ph); 8.08 (s, 1H, =CH); 10.62 (br s, 1H, NH); 12.82 (br s, 1H, OH).
Ethyl
[(Z)-4-cyanomethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7q). This compound was prepared from 4a (151 mg, 0.5 mmol) and aminoacetonitrile hydrochloride (5q)
(46 mg, 0.5 mmol), Procedure B. Pale yellow solid. Yield: 74% (115 mg), mp 131−134 °C (ethanol). Anal.
Calcd for C16H16N4O3: C 61.53; H 5.16; N 17.94. Found, C 61.56; H 5.22; N 18.03. MS: m/z (M+, 312). IR
(cm–1): 3250, 2980, 1720, 1670, 1620, 1600, 1340, 1210, 750. 1H NMR (DMSO-d6): δ 1.22 (t, 3H, J = 7.2,
OCH2CH3); 3.69 (s, 2H, CH2); 4.13 (q, 2H, J = 7.2, OCH2CH3); 4.59 (s, 2H, 6–H); 7.11−7.16 (m, 1H, Ph);
13
7.37−7.42 (m, 2H, Ph); 7.93−7.97 (m, 2H, Ph); 8.07 (br s, 1H, =CH); 9.80 (br s, 1H, NH). C NMR
(CDCl3): δ 14.5; 35.4; 36.9; 62.1; 102.6; 114.7; 120.0; 125.5; 129.3; 138.9; 144.7; 152.1; 166.0; 170.0.
Methyl
[(Z)-cyanomethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate
(7r). This compound was prepared from 4b (144 mg, 0.5 mmol) and aminoacetonitrile hydrochloride (5q)
(46 mg, 0.5 mmol), Procedure B. Pale yellow solid. Yield: 78% (116 mg), mp 143−146 °C (ethanol).
Anal. Calcd for C15H14N4O3: C 60.40; H 4.73; N 18.78. Found, C 60.68; H 4.79; N 19.00. IR (cm–1):
3260, 1730, 1670, 1620, 1600, 1340, 1220, 750. 1H NMR (DMSO-d6): δ 3.67 (s, 3H, OCH3); 3.71 (s, 2H,
CH2); 4.59 (s, 2H, 6–H); 7.11−7.16 (m, 1H, Ph); 7.37−7.42 (m, 2H, Ph); 7.93−7.96 (m, 2H, Ph); 8.06 (s,
1H, =CH); 9.79 (br s, 1H, NH).
Ethyl [5-hydroxy-1-phenyl-4-phenylhydrazonomethylidene-1H-pyrazol-3-yl]acetate (7s). This
compound was prepared from 4a (151 mg, 0.5 mmol) and phenylhyrazine hydrochloride (5s) (72 mg, 0.5
mmol), Procedure B. White crystals. Yield: 82% (150 mg), mp 135−136 °C (ethanol). Anal. Calcd for
C20H20N4O3: C 65.92; H 5.53; N 15.38. Found, C 66.10; H 5.72; N 15.38. MS: m/z (M+, 364; MH+, 365).
1
IR (cm–1): 3200, 3180, 1730, 1670, 1620, 1560, 1540, 1500, 1310, 1260, 1030, 690. H NMR (DMSO-
d6): δ 1.19 (t, 3H, J = 7.2, OCH2CH3); 3.78 (s, 2H, CH2); 4.09 (q, 2H, J = 7.0, OCH2CH3); 6.81−6.86 (m,
3H, Ph); 7.14−7.27 (m, 3H, Ph); 7.39−7.44 (m, 2H, Ph); 7.91−7.93 (m, 2H, Ph); 8.09 (s, 1H, =CH); 8.99
(br s, 1H, NH). 13C NMR (DMSO-d6): δ 14.9; 34.7; 61.4; 113.6; 119.3; 119.7; 120.9; 125.1; 129.5; 129.7;
129.9; 139.8; 146.0; 148.4; 162.4; 170.3.
Ethyl [(Z)-4-(6-hydroxy-2,2-dimethyl-4-oxo-4H-[1,3]dioxin-5-yl)methylidene-5-oxo-1-phenyl-4,5-

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dihydro-1H-pyrazol-3-yl]acetate (8a). This compound was prepared from 4a (151 mg, 0.5 mmol) and
Meldrum’s acid (6a) (72 mg, 0.5 mmol), Procedure A. Yellow crystals. Yield: 67% (135 mg), mp 79−81
°C (ethanol). Anal. Calcd for C20H20N2O7: C 60.00; H 5.03; N 7.00. Found, C 59.68; H 5.20; N 6.61. MS:
1
m/z (M+, 400; MH+, 401). IR (cm–1): 1730, 1650, 1580, 1290, 760. H NMR (CDCl3): δ 1.32 (t, 3H, J =
7.2, OCH2CH3); 1.82 (s, 6H, 2CH3); 3.87 (s, 2H, CH2); 4.25 (q, 2H, J = 7.2, OCH2CH3); 7.36−7.41 (m,
1H, Ph); 7.47−7.53 (m, 2H, Ph); 7.80−7.83 (m, 2H, Ph); 8.43 (s, 1H, =CH); 14.51 (s, 1H, OH). 13C NMR
(CDCl3): δ 14.5; 27.5; 34.1; 62.1; 100.2; 103.7; 105.3; 122.8; 128.3; 129.5; 137.2; 148.7; 151.9; 157.4;
163.6; 168.2; 169.3.
Ethyl
[(Z)-4-(6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methylidene-5-oxo-1-phenyl-
4,5-dihydro-1H-pyrazol-3-yl]acetate (8b). This compound was prepared from 4a (151 mg, 0.5 mmol)
and barbituric acid (6b) (64 mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 60% (116 mg), mp
213−215 °C (ethanol). Anal. Calcd for C18H16N4O6: C 56.25; H 4.20; N 14.58. Found, C 56.38; H 4.31; N
14.61. MS: m/z (M+, 384; MH+, 385). IR (cm–1): 3480, 3190, 1740, 1690, 1630, 1580, 1490, 1380, 1250,
1
760. H NMR (CDCl3): δ 1.29 (t, 3H, J = 7.2, OCH2CH3); 3.87 (s, 2H, CH2); 4.23 (q, 2H, J = 7.0,
OCH2CH3); 7.34−7.39 (m, 1H, Ph); 7.45−7.51 (m, 2H, Ph); 7.80−7.83 (m, 2H, Ph); 8.05 (br s, 1H, NH);
13
8.14 (br s, 1H, NH); 8.42 (s, 1H, =CH); 15.70 (s, 1H, OH). C NMR (DMSO-d6): δ 14.8; 34.6; 61.7;
104.1; 106.1; 121.9; 122.4; 128.1; 130.1; 137.8; 145.6; 150.3; 151.8; 158.5; 170.0.
Methyl [(Z)-4-(6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methylidene-5-oxo-1-phenyl-
4,5-dihydro-1H-pyrazol-3-yl]acetate (8c). This compound was prepared from 4b (144 mg, 0.5 mmol)
and barbituric acid (6b) (64 mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 85% (158 mg), mp
269−272 °C (ethanol). Anal. Calcd for C17H14N4O6: C 55.14; H 3.81; N 15.13. Found, C 54.86; H 4.04; N
1
14.97. IR (cm–1): 3180, 3050, 1730, 1690, 1570, 1380, 760. H NMR (DMSO-d6): δ 3.63 (s, 3H, OMe);
3.91 (s, 2H, CH2); 7.31–7.36 (m, 1H, Ph); 7.48–7.53 (m, 2H, Ph); 7.80–7.83 (m, 2H, Ph); 8.13 (s, 1H,
=CH);11.41 (br s, 2H, 2 × NH).
Ethyl
[(Z)-4-(6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methylidene-5-oxo-1-
phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (8d). This compound was prepared from 4a (151 mg, 0.5
mmol) and thiobarbituric acid (6d) (72 mg, 0.5 mmol), Procedure A. Yellow solid. Yield: 97% (195 mg),
mp 224−230 °C (ethanol). Anal. Calcd for C18H16N4O5S: C 53.99; H 4.03; N 13.99. Found, C 53.91; H
4.12; N 13.99. MS: m/z (M+, 400). IR (cm–1): 3120, 1740, 1680, 1620, 1570, 1540, 1450, 1360, 1300,
1150, 760, 680, 540. 1H NMR (CDCl3): δ 1.32 (t, 3H, J = 7.2, OCH2CH3); 3.88 (s, 2H, CH2); 4.25 (q, 2H,

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J = 7.2, OCH2CH3); 7.37−7.42 (m, 1H, Ph); 7.48−7.53 (m, 2H, Ph); 7.83−7.85 (m, 2H, Ph); 8.41 (s, 1H,
13
=CH); 9.08 (br s, 2H, 2 × NH); 14.51 (s, 1H, OH). C NMR (DMSO-d6): δ 14.8; 35.3; 61.6; 105.2;
107.0; 121.6; 122.0; 129.9; 130.0; 138.2; 145.4; 151.2; 161.8; 163.9; 170.0; 177.6.
Ethyl [(Z)-4-(6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methylidene-5-oxo-
1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (8e). This compound was prepared from 4a (151 mg, 0.5
mmol) and 1,3-dimethylbarbituric acid (6e) (78 mg, 0.5 mmol), Procedure A. Yellow needles. Yield: 98%
(203 mg), mp 153−155 °C (ethanol). Anal. Calcd for C20H20N4O6: C 58.25; H 4.89; N 13.59. Found, C
58.40; H 5.11; N 13.71. MS: m/z (M+, 412; MH+, 413). IR (cm–1): 1740, 1670, 1580, 1370, 790, 770. 1H
NMR (CDCl3): δ 1.29 (t, 3H, J = 7.2, OCH2CH3); 3.42 (s, 3H, NMe); 3.45 (s, 3H, NMe); 3.86 (s, 2H,
CH2); 4.22 (q, 2H, J = 7.2, OCH2CH3); 7.35−7.40 (m, 1H, Ph); 7.47−7.52 (m, 2H, Ph); 7.84−7.87 (m, 2H,
13
Ph); 8.50 (s, 1H, =CH); 15.59 (s, 1H, OH). C NMR (CDCl3): δ 14.5; 29.5; 29.5; 34.2; 62.1; 104.8;
104.9; 116.4; 122.5; 128.0; 129.4; 137.5; 148.3; 152.0; 158.1; 163.0; 166.6; 169.4.
Methyl [(Z)-4-(6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methylidene-5-
oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]acetate (8f). This compound was prepared from 4b (144
mg, 0.5 mmol) and 1,3-dimethylbarbituric acid (6e) (78 mg, 0.5 mmol), Procedure A. Yellow solid.
Yield: 75% (149 mg), mp 176−179 °C (ethanol). Anal. Calcd for C19H18N4O6: C 57.28; H 4.55; N 14.06.
1
Found, C 57.36; H 4.65; N 14.10. IR (cm–1): 1750, 1670, 1580, 1370, 790. H NMR (DMSO-d6): δ 3.58
(s, 3H, OCH3); 3.87 (s, 2H, CH2); 4.53 (br s, 6H, 2 × NMe); 7.24−7.29 (m, 1H, Ph); 7.44−7.49 (m, 2H,
Ph); 7.86−7.89 (m, 2H, Ph); 8.15 (s, 1H, =CH).
Ethyl [(Z)-4-(3-hydroxy-1-oxo-1H-inden-2-yl)methylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-
3-yl]acetate (8g). This compound was prepared from 4a (151 mg, 0.5 mmol) and 1,3-indandione (6g) (73
mg, 0.5 mmol), Procedure A. Dark red needles. Yield: 59% (119 mg), mp 155−157 °C (ethanol). Anal.
Calcd for C23H18N2O5: C 68.65; H 4.51. N 6.96. Found, C 68.66; H 4.81; N 7.01. MS: m/z (M+, 402;
MH+, 403). IR (cm–1): 1740, 1710, 1640, 1610, 1580, 1490, 1370, 1220, 740. 1H NMR (CDCl3): δ 1.31 (t,
3H, J = 7.2, OCH2CH3); 3.87 (s, 2H, CH2); 4.23 (q, 2H, J = 7.2, OCH2CH3); 7.32−7.38 (m, 1H, Ph);
7.46−7.51 (m, 2H, Ph); 7.71 (s, 1H, =CH); 7.76−7.81 (m, 2H, Ph); 7.85−7.88 (m, 2H, Ph); 7.92−7.96 (m,
13
2H, Ph); 16.40 (s, 1H, OH). C NMR (CDCl3): δ 14.5; 34.2; 62.0; 105.0; 117.5; 122.5; 123.3; 123.8;
127.8; 129.4; 134.9; 136.2; 136.6; 137.7; 139.7; 141.1; 151.1; 157.7; 169.5; 190.0; 195.2.
Methyl [(Z)-4-(3-hydroxy-1-oxo-1H-inden-2-yl)methylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-

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3-yl]acetate (8h). This compound was prepared from 4b (144 mg, 0.5 mmol) and 1,3-indandione (6g) (73
mg, 0.5 mmol), Procedure A. Dark red needles. Yield: 57% (111 mg), mp 185−188 °C (ethanol). Anal.
Calcd for C22H16N2O5: C 68.04; H 4.15; N 7.21. Found, C 67.94; H 4.30; N 7.34. IR (cm–1): 1740, 1590,
1
1360, 740. H NMR (DMSO-d6): δ 3.59 (s, 3H, OMe); 4.09 (s, 2H, CH2); 7.26–7.31 (m, 1H, Ph); 7.46–
7.51 (m, 2H, Ph); 7.61 (s, 1H, =CH); 7.82 (br s, 4H, Ph); 7.87–7.90 (m, 2H, Ph).
Ethyl
[(Z)-4-(3-ethoxycarbonylmethyl-5-oxo-1-phenyl-1,5-dihydro-pyrazol-4-ylidene)methyl-5-
hydroxy-1-phenyl-1H-pyrazol-3-yl]acetate (8i). This compound was prepared in two ways: a) from 4a
(151 mg, 0.5 mmol) and ethyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)carboxylate (3a) (123 mg,
0.5 mmol) (Procedure A) and b) from 4a (151 mg, 0.5 mmol) (Procedure C). Yellow solid. Yield: 90%
(226 mg, Procedure A), 75% (50 mg, Procedure C), mp 172−174 °C (ethanol). Anal. Calcd for
C27H26N4O6: C 64.53; H 5.22; N 11.15. Found, C 64.90; H 5.28; N 11.47. MS: m/z (M+, 502; MH+, 503).
IR (cm–1): 1720, 1620, 1590, 1540, 1490, 1360, 1200, 1100, 1010, 760. 1H NMR (CDCl3): δ 1.32 (t, 6H,
J = 7.2, OCH2CH3); 3.80 (s, 4H, CH2); 4.25 (q, 4H, J = 7.2, OCH2CH3); 7.29−7.34 (m, 2H, Ph);
7.44−7.49 (m, 4H, Ph); 7.66 (s, 1H, =CH); 7.91−7.93 (m, 4H, Ph). 13C NMR (CDCl3): δ 14.6; 34.7; 62.1;
109.7; 121.7; 127.2; 129.3; 137.9; 140.7; 149.7; 161.8; 169.4.
Methyl [(Z)-4-(3-methoxycarbonylmethyl-5-oxo-1-phenyl-1,5-dihydro-1H-pyrazol-4-ylidene)methyl-
5-hydroxy-1-phenyl-1H-pyrazol-3-yl]acetate (8j). This compound was prepared from 4b (144 mg, 0.5
mmol) and methyl (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetate (3b) (116 mg, 0.5 mmol),
Procedure A. Yellow solid. Yield: 59% (140 mg), mp 179−180 °C (ethanol). Anal. Calcd for C25H22N4O6:
C 63.29; H 4.67; N 11.81. Found, C 63.03; H 4.88; N 11.83. IR (cm–1): 1730, 1610, 1590, 1360, 760. 1H
NMR (DMSO-d6): δ 3.67 (s, 6H, OCH3); 4.03 (s, 4H, CH2); 7.31−7.36 (m, 2H, Ph); 7.48−7.54 (m, 4H,
Ph); 7.66 (s, 1H, =CH); 7.84−7.87 (m, 4H, Ph). 13C (DMSO-d6): δ 19.3; 52.9; 109.6; 121.8; 127.7; 129.9;
137.9; 142.5; 151.3; 161.7; 170.2.
Ethyl [(Z)-4-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylidene-5-oxo-1-phenyl-4,5-dihydro-
1H-pyrazol-3-yl]acetate (8k). This compound was prepared from 4a (151 mg, 0.5 mmol) and 3-methyl-
5-oxo-1-phenyl-4,5-dihydro-1H-pyrazole (6k) (87 mg, 0.5 mmol), Procedure A. Yellow solid. Yield:
58% (125 mg), mp 165−167 °C (ethanol). Anal. Calcd for C24H22N4O4: C 66.97; H 5.15; N 13.02. Found,
C 66.89; H 5.19; N 13.16. MS: m/z (M+, 430; MH+, 431). IR (cm–1): 1720, 1610, 1540, 1500, 1340, 1200,
1000, 820, 750, 690, 670. 1H NMR (CDCl3): δ 1.30 (t, 3H, J = 7.0, OCH2CH3); 2.37 (s, 3H, Me); 3.79 (s,
2H, CH2); 4.23 (q, 2H, J = 7.2, OCH2CH3); 7.25−7.32 (m, 2H, Ph); 7.42−7.48 (m, 4H, Ph); 7.50 (s, 1H,

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=CH); 7.88−7.92 (m, 4H, Ph).
Ethyl [(Z)-4-(5-hydroxy-1,3-diphenyl-1H-pyrazol-4-yl)methylidene-5-oxo-1-phenyl-4,5-dihydro-1H-
pyrazol-3-yl]acetate (8l). This compound was prepared from 4a (151 mg, 0.5 mmol) and 1,3-diphenyl-5-
oxo-4,5-dihydro-1H- pyrazole (6l) (118 mg, 0.5 mmol), Procedure A. Pale orange solid. Yield: 73% (180
mg), mp 168−169 °C (ethanol). Anal. Calcd for C29H24N4O4: C 70.72; H 4.91; N 11.38. Found, C 70.33;
H 5.11; N 11.46. MS: m/z (M+, 492; MH+, 493). IR (cm–1): 1720, 1610, 1590, 1520, 1490, 1350, 1240,
1
760. H NMR (CDCl3): δ 1.20 (t, 3H, J = 7.2, OCH2CH3); 3.66 (s, 2H, CH2); 4.14 (q, 2H, J = 7.2,
OCH2CH3); 7.27−7.35 (m, 2H, Ph); 7.43−7.55 (m, 7H, Ph); 7.60 (s, 1H, =CH); 7.65−7.68 (m, 2H, Ph);
13
7.91−7.94 (m, 2H, Ph); 7.99−8.03 (m, 2H, Ph). C NMR (DMSO-d6): δ 14.7; 34.2; 61.8; 108.6; 110.1;
121.8; 122.2; 127.8; 127.9; 129.8; 129.8; 129.9; 130.0; 130.7; 131.3; 137.8; 138.0; 143.3; 151.3; 155.6;
161.7; 161.8; 169.7.
General Procedure for the Preparation of Pyrazolo[4,3–c]pyridines (9c,d,k). A mixture of alkyl [(Z)-
5-oxo-1-phenyl-4-(substituted amino)methylidene-4,5-dihydro-1H-pyrazol-3-yl)acetate (7c,d,k) (0.5
mmol) and DMFDMA (0.14 mL, 1 mmol) in DMF (3 mL) was heated under reflux for 2 h. Solvent was
evaporated in vacuo, the oily residue was triturated with ethanol (2 mL), and the precipitate was collected
by filtration to afford 9c,d,k.
The following compounds were prepared in this manner:
Ethyl
3-oxo-2-phenyl-5-(4-methylphenyl)-3,5-dihydro-2H-pyrazolo[4,3–c]pyridine-7-carboxylate
(9c). This compound was prepared from 7c (182 mg, 0.5 mmol) and DMFDMA. Orange needles. Yield:
50% (100 mg), mp 233−235 °C (ethanol). Anal. Calcd for C22H19N3O3: C 70.76; H 5.13; N 11.25. Found,
C 70.44; H 5.34; N 11.26. MS: m/z (M+, 373). IR (cm–1): 1730, 1670, 1650, 1590, 1490, 1310, 1150, 790,
1
760. H NMR (CDCl3): δ 1.48 (t, 3H, J = 7.2, OCH2CH3); 2.46 (s, 3H, Me); 4.49 (q, 2H, J = 7.2,
OCH2CH3); 7.19−7.24 (m, 1H, Ph); 7.32−7.47 (m, 6H, Ph); 8.19 (d, 1H, J = 1.5, 4−H); 8.24−8.27 (m, 2H,
Ph); 8.35 (d, 1H, J = 1.5, 6−H).
Ethyl 5-(4-methoxyphenyl)-3-oxo-2-phenyl-3,5-dihydro-2H-pyrazolo[4,3–c]pyridine-7-carboxylate
(9d). This compound was prepared from 7d (183 mg, 0.5 mmol) and DMFDMA. Orange solid. Yield:
60% (63 mg), mp 235−237 °C (ethanol). Anal. Calcd for C22H19N3O4: C 67.86; H 4.92; N 10.79. Found,
C 67.62; H 5.19; N 10.80. MS: m/z (M+, 389; MH+, 390). IR (cm–1): 1730, 1670, 1650, 1590, 1510, 1480,
1250, 1160, 840, 790, 760. 1H NMR (CDCl3): δ 1.48 (t, 3H, J = 7.2, OCH2CH3); 3.89 (s, 3H, OMe); 4.49

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(q, 2H, J = 7.2, OCH2CH3); 7.05−7.08 (m, 2H, Ph); 7.18−7.24 (m, 1H, Ph); 7.35–7.46 (m, 4H, Ph); 8.15
(d, 1H, J = 1.5, 4−H); 8.32 (d, 1H, J = 1.5, 6−H); 8.24−8.27 (m, 2H, Ph).
Ethyl 3-oxo-2-phenyl-5-pyrazinyl-3,5-dihydro-2H-pyrazolo[4,3–c]pyridine-7-carboxylate (9k). This
compound was prepared from 7k (176 mg, 0.5 mmol) and DMFDMA. Red solid. Yield: 9% (16 mg), mp
215−218 °C (ethanol/DMF). Anal. Calcd for C19H15N5O3: C 63.15; H 4.18; N 19.38. Found, C 63.13; H
4.30; N 19.39. MS: m/z (M+, 361; MH+, 362). IR (cm–1): 1730, 1720, 1670, 1640, 1320, 1140, 780, 760.
1H NMR (CDCl3): δ 1.50 (t, 3H, J = 7.2, OCH2CH3); 4.53 (q, 2H, J = 7.2, OCH2CH3); 7.20−7.25 (m, 1H,
Ph); 7.42−7.47 (m, 2H, Ph); 8.21−8.24 (m, 2H, Ph); 8.60 (dd, 1H, J = 2.3, 1.5, 5’−H); 8.74 (d, 1H, J =
2.3, 6’−H); 8.76 (d, 1H, J = 1.5, 4−H); 8.97 (d, 1H, J = 1.5, 6−H); 9.01 (d, 1H, J = 1.1, 3’−H).
ACKNOWLEDGEMENTS
The financial support from the Ministry of Education, Science and Sport, Slovenia, through grant PS-502-
0103, is gratefully acknowledged.
The crystallographic data were collected on the Nonius Kappa CCD diffractometer in the Laboratory of
Inorganic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia.
We acknowledge with thanks the financial contribution of the Ministry of Education, Science and Sport,
Republic of Slovenia through grants X-2000, PS-511-103 and Z1-3246.
REFERENCES
1. J.-C. Milhavet, A. Gueiffier, L. Bernal, and J.-C. Teulade, Heterocycles, 1999, 51, 1661.
2. P. Marakos, N. Pouli, D. S. Wise, and L. B. Townsend, Synlett, 1997, 561.
3. A. Ellis, C. G. Li, and M. J. Rand, Eur. J. Pharmacol., 1998, 356, 41.
4. H. I. El-Subbagh, S. M. Abu-Zaid, M. A. Mahran, F. A. Badria, and A. M. Al-Obaid, J. Med. Chem.,
2000, 43, 2915.
5. For a review see: J. V. Greenhill, Pyrazoles with Fused Six-membered Heterocyclic Rings. In
Comprehensive Heterocyclic Chemistry; ed. by A. R. Katritzky, C. W. Rees, and K. T. Potts,
Pergamon Press, Oxford 1984, Vol. 5, pp. 305–343.
6. P. Molina, E. Aller, and A. Lorenzo, Tetrahedron, 1991, 47, 6737.
7. W. Oppolzer, Tetrahedron Lett., 1970, 3091.
8. K.-Y. Tserng and L. Bauer, J. Heterocycl. Chem., 1974, 11, 163.

HETEROCYCLES, Vol. 61, 2003
223
9. D. Donati, S. Fusi, F. Ponticelli, and P. Tedeschi, Heterocycles, 1988, 27, 1899.
10. V. I. Tyvorskii, D. N. Bobrov, O. G. Kulinkovich, K. A. Tehrani, and N. De Kimpe, Tetrahedron,
2001, 57, 2051.
11. W. J. Michaely, J. K. Curtis, and C. G. Knudsen, US Patent 5,300,478, 1994 (Chem. Abstr., 1994,
121, 57503n).
12. H. Fukui, K. Inoguchi, and J. Nakano, Heterocycles, 2002, 56, 257.
13. K. Bodendorf and P. Niemeitz, Arch. Pharm. 1957, 290, 494.
14. S. Hünig and G. Köbrich, J. Liebigs Ann. Chem., 1958, 617, 181.
15. S. Sugiura, S Ohno, O. Ohtani, K. Izumi, T. Kitamikado, H. Asai, K. Kato, M. Hori, and H.
Fujimura, J. Med. Chem., 1977, 20, 80.
16. (a) H. V. Pechmann, Liebigs Ann. Chem., 1891, 261, 171; (b) Jpn. Kokai Tokkyo Koho JP 82 40,467
1982 (Chem. Abstr., 1982, 97, 92271t); (c) F. W. Short and E. J. Schoeb, J. Heterocycl. Chem.,
1969, 6, 723.
17. A. Kreutzberger and K. Kolter, Arch. Pharm., 1986, 319, 18 (Chem. Abstr., 1986, 105, 42714c).
18. (a) S. Golič Grdadolnik and B. Stanovnik, Magn. Res. Chem., 1997, 35, 482; (b) P. Fischer, E.
Schweizer, J. Langer, and U. Schmidt, Magn. Res. Chem., 1994, 32, 567.
19. (a) U. Bratušek, S. Rečnik, J. Svete, L. Golič, and B. Stanovnik, Heterocycles, 2002, 57, 2045; (b)
M. Škof, J. Svete, B. Stanovnik, L. Golič, S. Golič Grdadolnik, and L. Selič, Helv. Chim. Acta, 1998,
81, 2332; (c) D. Bevk, M. Kmetič, S. Rečnik, J. Svete, L. Golič, A. Golobič, and B. Stanovnik,
Chemistry of Heterocyclic Compounds, 2001, 1651; (d) J. Baš, S. Rečnik, J. Svete, S. Golič
Grdadolnik, and B. Stanovnik, Arkivoc, 2001, 2, 1189; (e) S. Pirc, S. Rečnik, M. Škof, J. Svete, L.
Golič, A. Meden, and B. Stanovnik, J. Heterocycl. Chem., 2002, 39, 411; (f) U. Grošelj, S. Rečnik,
J. Svete, A. Meden, and B. Stanovnik, Tetrahedron Asymmetry, 2002, 13, 821.
20. Z. Otwinowski and W. Minor, Methods Enzymol., 1997, 276, 307.
21. A. Altomare, M. C. Burla, M. Camalli, G. Cascarano, C. Giacovazzo, A. Guagliardi, A. Moliterni,
G. Polidori, and R. Spagna, J. Appl. Cryst., 1999, 32, 115.
22. S. R. Hall, D. J. du Boulay, and R. Olthof-Hazekamp, Xtal3.6 System . University of Western
Australia, 1999.
23. C. K. Johnson, ORTEPII, Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA,
1976.