Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2H- pyrazolo[3,4-d]pyridazin-7-ones

Article abstract of DOI:10.1134/S1070428010100192

Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic thiones at the sulfur atom. Reactions of the resulting

Full text of DOI:10.1134/S1070428010100192

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 10, pp. 1550–1557. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.S. Matiichuk, M.A. Potopnyk, N.D. Obushak, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 10,
pp. 1544–1551.
Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-
2H-pyrazolo[3,4-d]pyridazin-7-ones
V. S. Matiichuk, M. A. Potopnyk, and N. D. Obushak
Ivan Franko Lviv National University, ul. Kirilla i Mefodiya 6, Lviv, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received December 21, 2009
Abstract—Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-
(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic
thiones at the sulfur atom. Reactions of the resulting S-alkylation products with hydrazine or methylhydrazine
involved closure of pyridazine ring to afford 2-aryl-3-methyl-4-[phenyl(or hetaryl)sulfanylmethyl]-6,7-dihydro-
2H-pyrazolo[3,4-d]pyridazin-7-ones.
DOI: 10.1134/S1070428010100192
1-Arylpyrazoles having functional substituents at
positions 3 and 4 attract interest as reagents for the
synthesis of more complex heterocyclic assemblies,
including fused heterocyclic systems [1–3], and design
of new pharmacologically active agents [4–6], as well
as electroluminescent materials [7]. We previously re-
ported on effective procedure for the synthesis of ethyl
1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates I
by reaction of arenediazonium salts II with ethyl
2-chloroacetoacetate (Japp–Klingemann reaction), fol-
lowed by condensation of hydrazones III thus formed
with acetylacetone (Scheme 1). It was also reported
that compounds I react with hydrazine and its deriva-
tives to give products in which pyridazine ring is fused
at the c side of the pyrazole ring [2].
(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2H-pyra-
zolo[3,4-d]pyridazin-7-ones. For this purpose, in the
first step pyrazoles Ia–Ie were subjected to bromina-
tion of at the acetyl fragment on C4. The optimal
bromination procedure was treatment of solutions of
Ia–Ie in acetic acid with bromine in the presence of
a catalytic amount of sulfuric acid. We thus obtained
ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazole-3-
carboxylates IVa–IVe (Scheme 2).
α-Halo ketones are convenient reagents for the al-
kylation of various nucleophiles [8]. Such transforma-
tions of bromo ketones IV could give rise to many
polyfunctional 1-arylpyrazole derivatives. We used
compounds IVa–IVe to perform S-alkylation of ben-
zenethiol (V) and various heterocyclic thiones VI–X.
The reactions were carried out by heating the reactants
in ethanol in the presence of triethylamine. As a result,
the corresponding 4-[phenyl(hetaryl)sulfanylacetyl]-
pyrazoles XI–XVI were isolated (Scheme 2). Ethyl
1-aryl-5-methyl-4-(R-sulfanylacetyl)-1H-pyrazole-3-
carboxylates XI–XVI are polyfunctionalized com-
pounds and are therefore convenient building blocks
for the design of fused heterocyclic systems. By reac-
tion of compounds XI–XVI with hydrazine or methyl-
hydrazine we obtained previously unknown pyrazolo-
[3,4-d]pyridazin-7-ones XVII–XXVII (Scheme 3).
In the present article we report on the synthesis of
previously unknown pyrazole derivatives, 2-aryl-4-
Scheme 1.
O
O
O
AcONa
ArN2 Cl–
+
Ar
N
Me
OEt
N
OEt
H
Cl
Cl
III
II
O
O
EtO
Me
CH2(COMe)2, AcONa
To conclude, we have developed an efficient
procedure for the synthesis of functionally substituted
2-aryl-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-
7-ones.
N
Me
N
Ar
I
1550

SYNTHESIS OF 2-ARYL-4-[(R-SULFANYLMETHYL]-3-METHYL-6,7-DIHYDRO-2H-...
1551
Scheme 2.
O
O
O
O
O
O
Br
S
Ph(Ht)
EtO
Me
EtO
EtO
PhSH (V) or
XYC=S (VI–X)
Et3N, EtOH
Br2, H2SO4, AcOH
N
N
N
Me
Me
Me
N
N
N
R
R
R
Ia–Ie
IVa–IVe
XIa–XIc, XIIa–XIIc, XIIIa–XIIIc
XIVa–XIVd, XVa–XVe, XVIa–XVId
Me
N
C6H4Cl-4
H
N
N
NH
N
NH
HN
N
N
NH
S
Ph
S
Ph
S
S
O
N
N
S
Me
S
Ph
IX
VI
VII
VIII
X
I, IV, R = 2-Cl (a), 3-Cl (b), 4-Cl (c), 2,4-Cl2 (d), 2,5-Cl2 (e); XI, Ph, R = 3-Cl (a), 4-Cl (b), 2,5-Cl2 (c); XII, Ht = 4,6-dimethylpyri-
midin-2-yl, R = 2-Cl (a), 4-Cl (b), 2,5-Cl2 (c); XIII, Ht = 1,3-benzothiazol-2-yl, R = 4-Cl (a), 2,4-Cl2 (b), 2,5-Cl2 (c); XIV, Ht =
5-phenyl-1,3,4-oxadiazol-2-yl, R = 3-Cl (a), 4-Cl (b), 2,4-Cl2 (c), 2,5-Cl2 (d); XV, Ht = 4,5-diphenyl-4H-1,2,4-triazol-3-yl, R =
2-Cl (a), 3-Cl (b), 4-Cl (c), 2,4-Cl2 (d), 2,5-Cl2 (e); XVI, Ht = 1-(4-chlorophenyl)-1H-tetrazol-5-yl, R = 2-Cl (a), 4-Cl (b),
2,4-Cl2 (c), 2,5-Cl2 (d).
Scheme 3.
R2
O
O
N
N
S
Ph(Ht)
O
EtO
NH2NH2 or
MeNHNH2
S
Ph(Ht)
N
N
Me
Me
N
N
R1
R1
XIa–XIc, XIIa–XIIc, XIIIa–XIIIc
XIVa–XIVd, XVa–XVe, XVIa–XVId
XVIIa–XVIIc, XVIIIa–XVIIIc, XIXa, XIXb, XXa–XXd
XXIa–XXIe, XXIIa–XXIIc, XXIII, XXIVa, XXIVb, XXV
XXVIa, XXVIb, XXVIIa, XXVIIb
XVII, Ph, R = 2-Cl (a), 4-Cl (b), 2,5-Cl2 (c); XVIII, Ht = 4,6-dimethylpyrimidin-2-yl, R = 2-Cl (a), 4-Cl (b), 2,5-Cl2 (c); XIX, Ht =
1,3-benzothiazol-2-yl, R = 2,4-Cl2 (a), 2,5-Cl2 (b); XX, Ht = 5-phenyl-1,3,4-oxadiazol-2-yl, R = 3-Cl (a), 4-Cl (b), 2,4-Cl2 (c),
2,5-Cl2 (d); XXI, Ht = 4,5-diphenyl-4H-1,2,4-triazol-3-yl, R = 2-Cl (a), 3-Cl (b), 4-Cl (c), 2,4-Cl2 (d), 2,5-Cl2 (e); XXII, Ht =
1-(4-chlorophenyl)-1H-tetrazol-5-yl, R = 2-Cl (a), 2,4-Cl2 (b), 2,5-Cl2 (c); XXIII, Ph, R1 = 2,5-Cl2, R2 = Me; XXIV, Ht =
4,6-dimethylpyrimidin-2-yl, R1 = 2-Cl (a), 4-Cl (b), R2 = Me; XXV, Ht = 1,3-benzothiazol-2-yl, R1 = 4-Cl, R2 = Me; XXVI, Ht =
4,5-diphenyl-4H-1,2,4-triazol-3-yl, R1 = 2,4-Cl2 (a), 2,5-Cl2 (b), R2 = Me; XXVII, Ht = 1-(4-chlorophenyl)-1H-tetrazol-5-yl, R1 =
4-Cl (a), 2,4-Cl2 (b), R2 = Me.
EXPERIMENTAL
were reported previously [2]. Compounds Id and Ie
were synthesized in a similar way.
1
The H NMR spectra were recorded on Varian
Mercury spectrometers operating at 200 and 400 MHz;
the chemical shifts were measured relative to tetra-
methylsilane as internal reference.
Ethyl 4-acetyl-1-(2,4-dichlorophenyl)-5-methyl-
1H-pyrazole-3-carboxylate (Id). Yield 89%, mp 92°C.
1H NMR spectrum (200 MHz, CDCl3), δ, ppm: 1.42 t
(3H, CH3, J = 7.2 Hz), 2.29 s (3H, CH3), 2.61 s (3H,
CH3), 4.46 q (2H, CH2O, J = 7.2 Hz), 7.35 d (1H,
Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazol-3-car-
boxylates Ia–Ic and the procedure for their synthesis
3
3
4
H
arom, J = 8.6 Hz), 7.43 d.d (1H, Harom, J = 8.6, J =
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

MATIICHUK et al.
1552
4
2.0 Hz), 7.35 d (1H, Harom, J = 2.0 Hz). Found, %:
C 52.62; H 4.03; N 8.27. C15H14Cl2N2O3. Calculated,
%: C 52.80; H 4.14; N 8.21.
N 6.54. C15H13BrCl2N2O3. Calculated, %: C 42.89;
H 3.12; N 6.67.
Ethyl 4-(bromoacetyl)-1-(2,5-dichlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (IVe). Yield 78%,
mp 99°C. 1H NMR spectrum (200 Hz, CDCl3), δ, ppm:
1.44 t (3H, CH3, J = 7.2 Hz), 2.32 s (3H, CH3), 4.48 q
(2H, CH2O, J = 7.2 Hz), 4.61 s (2H, CH2Br), 7.48–
7.52 m (3H, Harom). Found, %: C 42.96; H 3.19;
N 6.45. C15H13BrCl2N2O3. Calculated, %: C 42.89;
H 3.12; N 6.67.
Ethyl 4-acetyl-1-(2,5-dichlorophenyl)-5-methyl-
1H-pyrazole-3-carboxylate (Ie). Yield 85%,
mp 110°C. H NMR spectrum (200 Hz, CDCl3), δ,
ppm: 1.43 t (3H, CH3, J = 7.2 Hz), 2.31 s (3H, CH3),
2.62 s (3H, CH3), 4.46 q (2H, CH2O, J = 7.2 Hz),
7.43–7.53 m (3H, Harom). Found, %: C 52.73; H 4.26;
N 8.05. C15H14Cl2N2O3. Calculated, %: C 52.80;
H 4.14; N 8.21.
1
S-Alkylation of benzenethiol (V) and hetero-
cyclic thiones V–X with 4-(bromoacetyl)pyrazoles
IVa–IVe (general procedure). Triethylamine, 1.16 ml
(8.25 mmol), was added to a solution of 7.5 mmol of
compound V–X in 5 ml of ethanol, the mixture was
stirred for 0.5 h, a solution of 7.5 mmol of bromo-
acetylpyrazole IVa–IVe in 30 ml of ethanol was added,
and the mixture was heated for 3 h under reflux. After
cooling, the mixture was diluted with 40 ml of water,
and the precipitate was filtered off, dried, and recrys-
tallized from ethanol.
Ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyra-
zole-3-carboxylates IVa–IVe (general procedure).
Concentrated sulfuric acid, 2–3 drops, was added to
a solution of 30 mmol of acetylpyrazole Ia–Ie in 80 ml
of glacial acetic acid, a solution of 1.55 ml (30 mmol)
of bromine in 20 ml of glacial acetic acid was slowly
added dropwise, and the mixture was stirred for 7 h
and poured into 500 ml of water. The precipitate was
filtered off, dried, and recrystallized from ethanol.
Ethyl 4-(bromoacetyl)-1-(2-chlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (IVa). Yield 81%,
mp 59°C. H NMR spectrum (400 Hz, DMSO-d6), δ,
Ethyl 1-(3-chlorophenyl)-5-methyl-4-(2-phenyl-
sulfanyl-1-oxoethyl)-1H-pyrazole-3-carboxylate
(XIa). Yield 78%, oily substance. 1H NMR spectrum
(200 Hz, DMSO-d6), δ, ppm: 1.42 t (3H, CH3, J =
7.2 Hz), 2.29 s (3H, CH3), 4.45 q (2H, CH2O, J =
7.2 Hz), 4.55 s (2H, CH2S), 7.25–7.49 m (5H, Harom),
7.53–7.64 m (4H, Harom). Found, %: C 60.54; H 4.69;
N 6.57. C21H19ClN2O3S. Calculated, %: C 60.79;
H 4.62; N 6.75.
1
ppm: 1.38 t (3H, CH3, J = 7.2 Hz), 2.24 s (3H, CH3),
4.37 q (2H, CH2O, J = 7.2 Hz), 4.63 s (2H, CH2Br),
7.55–7.72 m (4H, Harom). Found, %: C 46.47; H 3.60;
N 7.32. C15H14BrClN2O3. Calculated, %: C 46.72;
H 3.66; N 7.26.
Ethyl 4-(bromoacetyl)-1-(3-chlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (IVb). Yield 93%,
1
mp 104°C. H NMR spectrum (400Hz, DMSO-d6), δ,
Ethyl 1-(4-chlorophenyl)-5-methyl-4-(2-phenyl-
ppm: 1.39 t (3H, CH3, J = 7.2 Hz), 2.43 s (3H, CH3),
4.38 q (2H, CH2O, J = 7.2 Hz), 4.60 s (2H, CH2Br),
7.53–7.69 m (4H, Harom). Found, %: C 46.80; H 3.78;
N 7.07. C15H14BrClN2O3. Calculated, %: C 46.72;
H 3.66; N 7.26.
sulfanyl-1-oxoethyl)-1H-pyrazole-3-carboxylate
(XIb). Yield 86%, oily substance. H NMR spectrum
1
(200 MHz, DMSO-d6), δ, ppm: 1.43 t (3H, CH3, J =
7.2 Hz), 2.31 s (3H, CH3), 4.47 q (2H, CH2O, J =
7.2 Hz), 4.58 s (2H, CH2S), 7.35 t (1H, Ph, J =
7.6 Hz), 7.43 t (2H, Ph, J = 7.6 Hz), 7.48 d (2H, Ph,
J = 7.6 Hz), 7.60 d (2H, C6H4, J = 8.0 Hz), 7.65 d (2H,
C6H4, J = 8.0 Hz). Found, %: C 60.61; H 4.47; N 6.69.
C21H19ClN2O3S. Calculated, %: C 60.79; H 4.62;
N 6.75.
Ethyl 4-(bromoacetyl)-1-(4-chlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (IVc). Yield 95%,
1
mp 138°C. H NMR spectrum (400 Hz, DMSO-d6), δ,
ppm: 1.38 t (3H, CH3, J = 7.2 Hz), 2.41 s (3H, CH3),
4.38 q (2H, CH2O, J = 7.2 Hz), 4.60 s (2H, CH2Br),
7.60 s (4H, Harom). Found, %: C 46.33; H 3.72; N 7.34.
C15H14BrClN2O3. Calculated, %: C 46.72; H 3.66;
N 7.26.
Ethyl 1-(2,5-dichlorophenyl)-5-methyl-4-(2-
phenylsulfanyl-1-oxoethyl)-1H-pyrazole-3-carbox-
1
ylate (XIc). Yield 75%, mp 97°C. H NMR spectrum
Ethyl 4-(bromoacetyl)-1-(2,4-dichlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (IVd). Yield 77%,
mp 77°C. 1H NMR spectrum (200 Hz, CDCl3), δ, ppm:
1.43 t (3H, CH3, J = 7.2 Hz), 2.22 s (3H, CH3), 4.40 s
(2H, CH2Br), 4.45 q (2H, CH2O, J = 7.2 Hz), 7.12–
7.48 m (3H, Harom). Found, %: C 42.72; H 3.24;
(200 MHz, CDCl3), δ, ppm: 1.43 t (3H, CH3CH2, J =
7.2 Hz), 2.30 s (3H, CH3), 4.47 q (2H, CH2O, J =
7.2 Hz), 4.60 s (2H, CH2S), 7.35–7.49 m (6H, Harom),
7.57–7.63 m (2H, Harom). Found, %: C 56.08; H 4.27;
N 6.09. C21H18Cl2N2O3S. Calculated, %: C 56.13;
H 4.04; N 6.23.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

SYNTHESIS OF 2-ARYL-4-[(R-SULFANYLMETHYL]-3-METHYL-6,7-DIHYDRO-2H-...
1553
Ethyl 1-(2-chlorophenyl)-4-[2-(4,6-dimethylpy-
rimidin-2-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-pyr-
azole-3-carboxylate (XIIa). Yield 67%, mp 48°C.
1H NMR spectrum (400 Hz, DMSO-d6), δ, ppm: 1.37 t
(3H, CH3CH2, J = 7.2 Hz), 2.29 s (6H, CH3), 2.31 s
(3H, CH3), 4.35 s (2H, CH2S), 4.37 q (2H, CH2O, J =
7.2 Hz), 6.83 s (1H, 5′-H), 7.55–7.71 m (4H, Harom).
Found, %: C 56.55; H 4.49; N 12.52. C21H21ClN4O3S.
Calculated, %: C 56.69; H 4.76; N 12.59.
(3H, CH3CH2, J = 7.2 Hz), 2.18 s (3H, CH3), 4.50 q
(2H, CH2O, J = 7.2 Hz), 4.75 s (2H, CH2S), 7.21–
7.44 m (5H, Harom), 7.69–7.79 m (2H, Harom). Found,
%: C 52.34; H 3.25; N 8.34. C22H17Cl2N3O3S2. Calcu-
lated, %: C 52.18; H 3.38; N 8.30.
Ethyl 1-(3-chlorophenyl)-5-methyl-4-[1-oxo-2-(5-
phenyl-1,3,4-oxadiazol-2-ylsulfanyl)ethyl]-1H-pyra-
zole-3-carboxylate (XIVa). Yield 83%, mp 103°C.
1H NMR spectrum (200 Hz, CDCl3), δ, ppm: 1.45 t
(3H, CH3CH2, J = 7.2 Hz), 2.33 s (3H, CH3), 4.49 q
(2H, CH2O, J = 7.2 Hz), 4.82 s (2H, CH2S), 7.29–
7.58 m (7H, Harom), 7.94–8.06 m (2H, Harom). Found,
%: C 57.11; H 3.85; N 11.54. C23H19ClN4O4S. Calcu-
lated, %: C 57.20; H 3.97; N 11.60.
Ethyl 1-(4-chlorophenyl)-4-[2-(4,6-dimethylpy-
rimidin-2-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-pyr-
azole-3-carboxylate (XIIb). Yield 82%, mp 74°C.
1H NMR spectrum (400 Hz, DMSO-d6), δ, ppm: 1.39 t
(3H, CH3CH2, J = 7.2 Hz), 2.28 s (6H, CH3), 2.33 s
(3H, CH3), 4.36 s (2H, CH2S), 4.37 q (2H, CH2O, J =
7.2 Hz), 6.83 s (1H, 5′-H), 7.56 br.s (4H, Harom).
Found, %: C 56.52; H 4.85; N 12.70. C21H21ClN4O3S.
Calculated, %: C 56.69; H 4.76; N 12.59.
Ethyl 1-(4-chlorophenyl)-5-methyl-4-[1-oxo-2-(5-
phenyl-1,3,4-oxadiazol-2-ylsulfanyl)ethyl]-1H-pyra-
zole-3-carboxylate (XIVb). Yield 88%, mp 127°C.
1H NMR spectrum (200 Hz, CDCl3), δ, ppm: 1.42 t
(3H, CH3CH2, J = 7.2 Hz), 2.31 s (3H, CH3), 4.45 q
(2H, CH2O, J = 7.2 Hz), 4.80 s (2H, CH2S), 7.45–
7.71 m (7H, Harom), 7.86–7.91 m (2H, Harom). Found,
%: C 57.45; H 3.98; N 11.63. C23H19ClN4O4S. Calcu-
lated, %: C 57.20; H 3.97; N 11.60.
Ethyl 1-(2,5-dichlorophenyl)-4-[2-(4,6-dimethyl-
pyrimidin-2-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-
pyrazole-3-carboxylate (XIIc). Yield 75%, oily sub-
1
stance. H NMR spectrum (400 Hz, DMSO-d6), δ,
ppm: 1.39 t (3H, CH3CH2, J = 7.2 Hz), 2.32 s (6H,
CH3), 2.34 s (3H, CH3), 4.35 s (2H, CH2S), 4.38 q (2H,
CH2O, J = 7.2 Hz), 6.87 s (1H, 5′-H), 7.67–7.90 m
(3H, Harom). Found, %: C 52.74; H 4.30; N 11.53.
C21H20Cl2N4O3S. Calculated, %: C 52.61; H 4.21;
N 11.69.
Ethyl 1-(2,4-dichlorophenyl)-5-methyl-4-[1-
oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylsulfanyl)ethyl]-
1H-pyrazole-3-carboxylate (XIVc). Yield 83%,
1
mp 121°C. H NMR spectrum (200 Hz, CDCl3), δ,
ppm: 1.44 t (3H, CH3CH2, J = 7.2 Hz), 2.27 s (3H,
CH3), 4.48 q (2H, CH2O, J = 7.2 Hz), 4.83 s (2H,
CH2S), 7.33–7.59 m (6H, Harom), 7.95–8.06 m (2H,
Ethyl 4-[2-(1,3-benzothiazol-2-ylsulfanyl)-1-oxo-
ethyl]-1-(4-chlorophenyl)-5-methyl-1H-pyrazole-3-
carboxylate (XIIIa). Yield 73%, mp 69°C. 1H NMR
spectrum (200 Hz, CDCl3), δ, ppm: 1.45 t (3H,
CH3CH2, J = 7.2 Hz), 2.32 s (3H, CH3), 4.49 q (2H,
CH2O, J = 7.2 Hz), 4.76 s (2H, CH2S), 7.18–7.58 m
(6H, Harom), 7.64–7.85 m (2H, Harom). Found, %:
C 55.74; H 3.76; N 8.98. C22H18ClN3O3S2. Calculated,
%: C 55.98; H 3.84; N 8.90.
H
arom). Found, %: C 53.32; H 3.48; N 10.79.
C23H18Cl2N4O4S. Calculated, %: C 53.39; H 3.51;
N 10.83.
Ethyl 1-(2,5-dichlorophenyl)-5-methyl-4-[1-
oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylsulfanyl)ethyl]-
1H-pyrazole-3-carboxylate (XIVd). Yield 72%,
1
mp 139°C. H NMR spectrum (200 Hz, CDCl3), δ,
Ethyl 4-[2-(1,3-benzothiazol-2-ylsulfanyl)-1-oxo-
ethyl]-1-(2,4-dichlorophenyl)-5-methyl-1H-pyra-
zole-3-carboxylate (XIIIb). Yield 82%, mp 83°C.
1H NMR spectrum (200 Hz, CDCl3), δ, ppm: 1.46 t
(3H, CH3CH2, J = 7.2 Hz), 2.16 s (3H, CH3), 4.50 q
(2H, CH2O, J = 7.2 Hz), 4.74 s (2H, CH2S), 7.22–
7.56 m (5H, Harom), 7.69–7.81 m (2H, Harom). Found,
%: C 52.02; H 3.27; N 8.54. C22H17Cl2N3O3S2. Calcu-
lated, %: C 52.18; H 3.38; N 8.30.
ppm: 1.45 t (3H, CH3CH2, J = 7.2 Hz), 2.29 s (3H,
CH3), 4.49 q (2H, CH2O, J = 7.2 Hz), 4.83 s (2H,
CH2S), 7.42–7.58 m (6H, Harom), 7.94–8.03 m (2H,
H
arom). Found, %: C 53.45; H 3.63; N 10.70.
C23H18Cl2N4O4S. Calculated, %: C 53.39; H 3.51;
N 10.83.
Ethyl 1-(2-chlorophenyl)-4-[2-(4,5-diphenyl-4H-
1,2,4-triazol-3-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-
pyrazole-3-carboxylate (XVa). Yield 60%, mp 188°C.
1H NMR spectrum (400 Hz, DMSO-d6), δ, ppm: 1.36 t
(3H, CH3CH2, J = 7.2 Hz), 2.22 s (3H, CH3), 4.36 q
(2H, CH2O, J = 7.2 Hz), 4.58 s (2H, CH2S), 7.27–
7.38 m (7H, Harom), 7.54–7.69 m (7H, Harom). Found,
Ethyl 4-[2-(1,3-benzothiazol-2-ylsulfanyl)-1-oxo-
ethyl]-1-(2,5-dichlorophenyl)-5-methyl-1H-pyra-
zole-3-carboxylate (XIIIc). Yield 90%, mp 104°C.
1H NMR spectrum (200 Hz, CDCl3), δ, ppm: 1.46 t
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

MATIICHUK et al.
1554
%: C 62.49; H 4.15; N 12.67. C29H24ClN5O3S. Calcu-
lated, %: C 62.42; H 4.33; N 12.55.
Ethyl 5-methyl-1-(4-chlorophenyl)-4-{2-[1-
(4-chlorophenyl)-1H-tetrazol-5-ylsulfanyl]-1-oxo-
ethyl}-1H-pyrazole-3-carboxylate (XVIb). Yield 76%,
Ethyl 1-(3-chlorophenyl)-4-[2-(4,5-diphenyl-4H-
1,2,4-triazol-3-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-
pyrazole-3-carboxylate (XVb). Yield 63%, mp 163°C.
1H NMR spectrum (200 Hz, DMSO-d6), δ, ppm: 1.29 t
(3H, CH3CH2, J = 7.0 Hz), 2.39 s (3H, CH3), 4.35 q
(2H, CH2O, J = 7.0 Hz), 4.66 s (2H, CH2S), 7.27–
7.44 m (7H, Harom), 7.50–7.76 m (7H, Harom). Found,
%: C 62.49; H 4.35; N 12.49. C29H24ClN5O3S. Calcu-
lated, %: C 62.42; H 4.33; N 12.55.
1
mp 108°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 1.31 t (3H, CH3CH2, J = 7.2 Hz), 2.37 s (3H,
CH3), 4.36 q (2H, CH2O, J = 7.2 Hz), 4.94 s (2H,
CH2S), 7.45–7.83 m (8H, Harom). Found, %: C 50.80;
H 3.44; N 16.35. C22H18Cl2N6O3S. Calculated, %:
C 51.07; H 3.51; N 16.24.
Ethyl 4-{2-[1-(4-chlorophenyl)-1H-tetrazol-5-yl-
sulfanyl]-1-oxoethyl}-1-(2,4-dichlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (XVIc). Yield
Ethyl 1-(4-chlorophenyl)-4-[2-(4,5-diphenyl-4H-
1,2,4-triazol-3-ylsulfanyl)-1-oxoethyl]-5-methyl-1H-
pyrazole-3-carboxylate (XVc). Yield 67%, mp 175–
1
67%, mp 158°C. H NMR spectrum (200 Hz,
DMSO-d6), δ, ppm: 1.30 t (3H, CH3CH2, J = 7.0 Hz),
2.21 s (3H, CH3), 4.35 q (2H, CH2O, J = 7.0 Hz),
4.93 s (2H, CH2S), 7.66–7.83 m (6H, Harom), 8.02 d
1
176°C. H NMR spectrum (400 Hz, DMSO-d6), δ,
ppm: 1.36 t (3H, CH3CH2, J = 7.2 Hz), 2.41 s (3H,
CH3), 4.37 q (2H, CH2O, J = 7.2 Hz), 4.59 s (2H,
CH2S), 7.26–7.36 m (7H, Harom), 7.53–7.60 m (7H,
4
(1H, Harom, J = 2.0 Hz). Found, %: C 47.79; H 3.23;
N 15.45. C22H17Cl3N6O3S. Calculated, %: C 47.88;
H 3.11; N 15.23.
H
arom). Found, %: C 62.26; H 4.30; N 12.43.
C29H24ClN5O3S. Calculated, %: C 62.42; H 4.33;
N 12.55.
Ethyl 4-{2-[1-(4-chlorophenyl)-1H-tetrazol-5-yl-
sulfanyl]-1-oxoethyl}-1-(2,5-dichlorophenyl)-5-
methyl-1H-pyrazole-3-carboxylate (XVId). Yield
Ethyl 1-(2,4-dichlorophenyl)-4-[2-(4,5-diphenyl-
4H-1,2,4-triazol-3-ylsulfanyl)-1-oxoethyl]-5-methyl-
1H-pyrazole-3-carboxylate (XVd). Yield 63%,
1
78%, mp 117°C. H NMR spectrum (200 Hz,
DMSO-d6), δ, ppm: 1.30 t (3H, CH3CH2, J = 7.0 Hz),
2.23 s (3H, CH3), 4.36 q (2H, CH2O, J = 7.0 Hz),
4.93 s (2H, CH2S), 7.56–7.87 m (6H, Harom), 7.95 d
1
mp 216°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 1.28 t (3H, CH3CH2, J = 7.2 Hz), 2.20 s (3H,
CH3), 4.33 q (2H, CH2O, J = 7.2 Hz), 4.64 s (2H,
CH2S), 7.23–7.62 m (10H, Harom), 7.65–7.77 m (2H,
4
(1H, Harom, J = 1.8 Hz). Found, %: C 47.71; H 3.02;
N 15.10. C22H17Cl3N6O3S. Calculated, %: C 47.88;
H 3.11; N 15.23.
H
arom), 8.00 d (1H, Harom, J = 1.4 Hz). Found, %:
C 58.69; H 3.78; N 11.97. C29H23Cl2N5O3S. Calculat-
ed, %: C 58.79; H 3.91; N 11.82.
Pyrazolo[3,4-d]pyridazin-7-ones XVII–XXVII
(general procedure). A mixture of 0.01 mol of pyrazole
XI–XVI dissolved in 20 ml of ethanol and 1.46 ml
(0.03 mol) of hydrazine hydrate or 0.80 ml (0.015 mol)
of methylhydrazine was heated for 5 h under reflux.
The mixture was cooled, and the precipitate was fil-
tered off, dried, and recrystallized from dimethyl-
formamide.
Ethyl 1-(2,5-dichlorophenyl)-4-[2-(4,5-diphenyl-
4H-1,2,4-triazol-3-ylsulfanyl)-1-oxoethyl]-5-methyl-
1H-pyrazole-3-carboxylate (XVe). Yield 68%,
1
mp 191°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 1.28 t (3H, CH3CH2, J = 7.2 Hz), 2.22 s (3H,
CH3), 4.33 q (2H, CH2O, J = 7.2 Hz), 4.63 s (2H,
CH2S), 7.16–7.93 m (13H, Harom). Found, %: C 58.57;
H 3.80; N 11.74. C29H23Cl2N5O3S. Calculated, %:
C 58.79; H 3.91; N 11.82.
2-(3-Chlorophenyl)-3-methyl-4-(phenylsulfanyl-
methyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-
7-one (XVIIa). Yield 66%, mp 202°C. 1H NMR spec-
trum (200 Hz, DMSO-d6), δ, ppm: 2.69 s (3H, CH3),
4.42 s (2H, CH2S), 7.18–7.47 m (5H, Harom), 7.64–
Ethyl 1-(2-chlorophenyl)-4-{2-[1-(4-chlorophen-
yl)-1H-tetrazol-5-ylsulfanyl]-1-oxoethyl}-5-methyl-
1H-pyrazole-3-carboxylate (XVIa). Yield 73%,
4
7.76 m (3H, Harom), 7.84 d (1H, Harom, J = 1.2 Hz),
1
12.22 s (1H, NH). Found, %: C 59.51; H 3.82;
N 14.74. C19H15ClN4OS. Calculated, %: C 59.60;
H 3.95; N 14.63.
mp 124°C. H NMR spectrum (200 Hz, CDCl3), δ,
ppm: 1.43 t (3H, CH3CH2, J = 7.2 Hz), 2.27 s (3H,
CH3), 4.48 q (2H, CH2O, J = 7.2 Hz), 4.96 s (2H,
CH2S), 7.40–7.63 m (8H, Harom). Found, %: C 51.14;
H 3.73; N 16.17. C22H18Cl2N6O3S. Calculated, %:
C 51.07; H 3.51; N 16.24.
2-(4-Chlorophenyl)-3-methyl-4-(phenylsulfanyl-
methyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-
7-one (XVIIb). Yield 70%, mp 277°C. 1H NMR spec-
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SYNTHESIS OF 2-ARYL-4-[(R-SULFANYLMETHYL]-3-METHYL-6,7-DIHYDRO-2H-...
1555
trum (400 Hz, DMSO-d6), δ, ppm: 2.70 s (3H, CH3),
4.32 s (2H, CH2S), 7.20 t (1H, Ph, J = 7.6 Hz), 7.29 t
(2H, Ph, J = 7.6 Hz), 7.38 d (2H, Ph, J = 7.6 Hz),
7.62 d (2H, C6H4, J = 8.4 Hz), 7.66 d (2H, C6H4, J =
8.4 Hz), 12.05 s (1H, NH). Found, %: C 59.78; H 3.90;
N 14.71. C19H15ClN4OS. Calculated, %: C 59.60;
H 3.95; N 14.63.
7.52 m (2H, Harom), 7.69–7.90 m (3H, Harom), 7.99–
8.03 m (2H, Harom), 12.40 s (1H, NH). Found, %:
C 50.48; H 2.63; N 14.89. C20H13Cl2N5OS2. Calculat-
ed, %: C 50.64; H 2.76; N 14.76.
4-(1,3-Benzothiazol-2-ylsulfanylmethyl)-2-
(2,5-dichlorophenyl)-3-methyl-6,7-dihydro-2H-pyr-
azolo[3,4-d]pyridazin-7-one (XIXb). Yield 70%,
1
2-(2,5-Dichlorophenyl)-3-methyl-4-(phenylsul-
mp 291°C. H NMR spectrum (200 MHz, DMSO-d6),
fanylmethyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyrid-
azin-7-one (XVIIc). Yield 70%, mp 249°C. H NMR
δ, ppm: 2.56 s (3H, CH3), 4.95 s (2H, CH2S), 7.33–
7.54 m (2H, Harom), 7.78–7.93 m (3H, Harom), 8.04 d
(2H, Harom, J = 8.4 Hz), 12.43 s (1H, NH). Found, %:
C 50.89; H 2.70; N 14.54. C20H13Cl2N5OS2. Calculat-
ed, %: C 50.64; H 2.76; N 14.76.
1
spectrum (200 Hz, DMSO-d6), δ, ppm: 2.53 s (3H,
CH3), 4.44 s (2H, CH2S), 7.17–7.46 m (5H, Harom),
7.77–7.92 m (2H, Harom), 8.03 br.s (1H, Harom), 12.24 s
(1H, NH). Found, %: C 54.96; H 3.47; N 13.38.
C19H14Cl2N4OS. Calculated, %: C 54.68; H 3.38;
N 13.43.
2-(3-Chlorophenyl)-3-methyl-4-(5-phenyl-1,3,4-
oxadiazol-2-ylsulfanylmethyl)-6,7-dihydro-2H-pyr-
azolo[3,4-d]pyridazin-7-one (XXa). Yield 63%,
1
2-(2-Chlorophenyl)-4-(4,6-dimethylpymiridin-
2-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-pyra-
zolo[3,4-d]pyridazin-7-one (XVIIIa). Yield 55%,
mp 254°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 2.72 s (3H, CH3), 4.89 s (2H, CH2S), 7.54–
7.76 m (5H, Harom), 7.83 br.s (1H, Harom), 7.93–8.05 m
(3H, Harom), 12.40 s (1H, NH). Found, %: C 55.83;
H 3.20; N 18.79. C21H15ClN6O2S. Calculated, %:
C 55.94; H 3.35; N 18.64.
1
mp 246–247°C. H NMR spectrum (400 Hz,
DMSO-d6), δ, ppm: 2.38 s (6H, CH3), 2.47 s (3H,
CH3), 4.61 s (2H, CH2S), 6.90 s (1H, 5′-H), 7.59–
7.76 m (4H, Harom), 12.23 s (1H, NH). Found, %:
C 55.19; H 4.01; N 20.18. C19H17ClN6OS. Calculated,
%: C 55.27; H 4.15; N 20.35.
2-(4-Chlorophenyl)-3-methyl-4-(5-phenyl-1,3,4-
oxadiazol-2-ylsulfanylmethyl)-6,7-dihydro-2H-pyr-
azolo[3,4-d]pyridazin-7-one (XXb). Yield 68%,
1
2-(4-Chlorophenyl)-4-(4,6-dimethylpymiridin-
2-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-pyra-
zolo[3,4-d]pyridazin-7-one (XVIIIb). Yield 60%,
mp 245–246°C. H NMR spectrum (400 Hz,
DMSO-d6), δ, ppm: 2.74 s (3H, CH3), 4.83 s (2H,
CH2S), 7.55–7.70 m (7H, Harom), 7.96–8.01 m (2H,
1
mp 279°C. H NMR spectrum (400 Hz, DMSO-d6),
Harom), 12.23 s (1H, NH). Found, %: C 56.19; H 3.19;
δ, ppm: 2.39 s (6H, CH3), 2.65 s (3H, CH3), 4.60 s
(2H, CH2S), 6.90 s (1H, 5′-H), 7.61 d (2H, Harom, J =
8.8 Hz), 7.65 d (2H, Harom, J = 8.8 Hz), 12.17 s
(1H, NH). Found, %: C 55.55; H 4.03; N 20.48.
C19H17ClN6OS. Calculated, %: C 55.27; H 4.15;
N 20.35.
N 18.72. C21H15ClN6O2S. Calculated, %: C 55.94;
H 3.35; N 18.64.
2-(2,4-Dichlorophenyl)-3-methyl-4-(5-phenyl-
1,3,4-oxadiazol-2-ylsulfanylmethyl)-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXc). Yield 72%,
1
mp 236°C. H NMR spectrum (200 MHz, DMSO-d6),
2-(2,5-Dichlorophenyl)-4-(4,6-dimethylpyrimi-
din-2-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XVIIIc). Yield 67%,
mp 245°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 2.36 s (6H, CH3), 2.55 s (3H, CH3), 4.68 s (2H,
δ, ppm: 2.55 s (3H, CH3), 4.90 s (2H, CH2S), 7.54–
7.86 m (5H, Harom), 7.93–8.03 m (2H, Harom), 8.06 d
4
(1H, Harom, J = 2.0 Hz), 12.42 s (1H, NH). Found, %:
1
C 51.86; H 3.06; N 17.49. C21H14Cl2N6O2S. Calculat-
ed, %: C 51.97; H 2.91; N 17.32.
CH2S), 7.01 s (1H, 5′-H), 7.77–7.90 m (2H, Harom),
8.00 d (1H, Harom, J = 2.0 Hz), 12.36 s (1H, NH).
Found, %: C 51.19; H 3.56; N 18.50. C19H16Cl2N6OS.
Calculated, %: C 51.01; H 3.61; N 18.79.
2-(2,5-Dichlorophenyl)-3-methyl-4-(5-phenyl-
1,3,4-oxadiazol-2-ylsulfanylmethyl)-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXd). Yield 73%,
4
1
mp 281°C. H NMR spectrum (200 MHz, DMSO-d6),
δ, ppm: 2.56 s (3H, CH3), 4.90 s (2H, CH2S), 7.55–
7.70 m (3H, Harom), 7.78–7.93 m (2H, Harom), 7.96–
8.04 m (3H, Harom), 12.43 s (1H, NH). Found, %:
C 52.19; H 2.95; N 17.14. C21H14Cl2N6O2S. Calculat-
ed, %: C 51.97; H 2.91; N 17.32.
4-(1,3-Benzothiazol-2-ylsulfanylmethyl)-2-
(2,4-dichlorophenyl)-3-methyl-6,7-dihydro-2H-pyr-
azolo[3,4-d]pyridazin-7-one (XIXa). Yield 63%,
mp 206°C. H NMR spectrum (200 MHz, DMSO-d6),
δ, ppm: 2.48 s (3H, CH3), 4.93 s (2H, CH2S), 7.29–
1
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MATIICHUK et al.
1556
2-(2-Chlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-tri-
Found, %: C 49.66; H 2.79; N 22.84. C20H14Cl2N8OS.
Calculated, %: C 49.49; H 2.91; N 23.09.
azol-3-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXIa). Yield 63%,
4-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanyl-
methyl]-2-(2,4-dichlorophenyl)-3-methyl-6,7-dihy-
dro-2H-pyrazolo[3,4-d]pyridazin-7-one (XXIIb).
1
mp 298°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
ppm: 2.42 s (3H, CH3), 4.55 s (2H, CH2S), 7.28–
7.97 m (14H, Harom), 12.28 s (1H, NH). Found, %:
C 61.47; H 3.75; N 18.89. C27H20ClN7OS. Calculated,
%: C 61.65; H 3.83; N 18.64.
1
Yield 79%, mp 243°C. H NMR spectrum (200 Hz,
DMSO-d6), δ, ppm: 2.49 s (3H, CH3), 4.83 s (2H,
CH2S), 7.68–7.76 m (6H, Harom), 8.06 d (1H, Harom
,
4J = 2.0 Hz), 12.35 s (1H, NH). Found, %: C 46.06;
H 2.40; N 21.33. C20H13Cl3N8OS. Calculated, %:
C 46.21; H 2.52; N 21.56.
2-(3-Chlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-tri-
azol-3-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXIb). Yield 83%,
1
mp 256°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
4-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanyl-
methyl]-2-(2,5-dichlorophenyl)-3-methyl-6,7-dihy-
dro-2H-pyrazolo[3,4-d]pyridazin-7-one (XXIIc).
ppm: 2.60 s (3H, CH3), 4.53 s (2H, CH2S), 7.27–
7.52 m (10H, Harom), 7.58–7.80 m (4H, Harom), 12.26 s
(1H, NH). Found, %: C 61.54; H 3.61; N 18.50.
C27H20ClN7OS. Calculated, %: C 61.65; H 3.83;
N 18.64.
1
Yield 62%, decomposition point 247°C. H NMR
spectrum (200 Hz, DMSO-d6), δ, ppm: 2.50 s (3H,
CH3), 4.83 s (2H, CH2), 7.67–7.98 m (7H, Harom),
12.36 s (1H, NH). Found, %: C 46.10; H 2.38; N 21.70.
C20H13Cl3N8OS. Calculated, %: C 46.21; H 2.52;
N 21.56.
2-(4-Chlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-tri-
azol-3-ylsulfanylmethyl)-3-methyl-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXIc). Yield 74%,
1
mp > 300°C. H NMR spectrum (400 Hz, DMSO-d6),
2-(2,5-Dichlorophenyl)-3,6-dimethyl-4-(phenyl-
sulfanylmethyl)-6,7-dihydro-2H-pyrazolo[3,4-d]-
pyridazin-7-one (XXIII). Yield 60%, mp 198°C.
1H NMR spectrum (200Hz, DMSO-d6), δ, ppm: 2.49 s
(3H, CH3), 3.53 s (3H, CH3N), 4.40 s (2H, CH2S),
7.20–7.48 m (5H, Harom), 7.72–8.05 m (3H, Harom).
Found, %: C 55.54; H 3.63; N 13.14. C20H16Cl2N4OS.
Calculated, %: C 55.69; H 3.74; N 12.99.
δ, ppm: 2.63 s (3H, CH3), 4.52 s (2H, CH2S), 7.20–
7.47 m (10H, Harom), 7.63 br.s (4H, Harom), 12.13 s
(1H, NH). Found, %: C 61.81; H 3.70; N 18.75.
C27H20ClN7OS. Calculated, %: C 61.65; H 3.83;
N 18.64.
2-(2,4-Dichlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-
triazol-3-ylsulfanylmethyl)-3-methyl-6,7-dihydro-
2H-pyrazolo[3,4-d]pyridazin-7-one (XXId). Yield
2-(2-Chlorophenyl)-4-(4,6-dimethylpyrimidin-
2-ylsulfanylmethyl)-3,6-dimethyl-6,7-dihydro-2H-
pyrazolo[3,4-d]pyridazin-7-one (XXIVa). Yield 43%,
1
85%, mp 293°C. H NMR spectrum (200 MHz,
DMSO-d6), δ, ppm: 2.44 s (3H, CH3), 4.55 s (2H,
CH2S), 7.28–7.64 m (10H, Harom), 7.75 br.s (2H, Harom),
8.05 br.s (1H, Harom), 12.30 s (1H, NH). Found, %:
C 57.65; H 3.35; N 17.25. C27H19Cl2N7OS. Calculated,
%: C 57.86; H 3.42; N 17.49.
1
mp 160°C. H NMR spectrum (400 Hz, DMSO-d6), δ,
ppm: 2.39 s (6H, CH3), 2.47 s (3H, CH3), 3.70 s (3H,
CH3N), 4.60 s (2H, CH2S), 6.91 s (1H, 5′-H), 7.58–
7.74 m (4H, Harom). Found, %: C 56.19; H 4.36;
N 19.84. C20H19ClN6OS. Calculated, %: C 56.27;
H 4.49; N 19.69.
2-(2,5-Dichlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-
triazol-3-ylsulfanylmethyl)-3-methyl-6,7-dihydro-
2H-pyrazolo[3,4-d]pyridazin-7-one (XXIe). Yield
2-(4-Chlorophenyl)-4-(4,6-dimethylpyrimidin-2-
ylsulfanylmethyl)-3,6-dimethyl-6,7-dihydro-2H-pyr-
azolo[3,4-d]pyridazin-7-one (XXIVb). Yield 58%,
1
59%, mp 295°C. H NMR spectrum (200 Hz,
DMSO-d6), δ, ppm: 2.47 s (3H, CH3), 4.57 s (2H,
CH2S), 7.37 br.s (6H, Harom), 7.46–7.57 m (3H, Harom),
7.76–7.98 m (4H, Harom), 12.32 s (1H, NH). Found, %:
C 57.69; H 3.30; N 17.63. C27H19Cl2N7OS. Calculated,
%: C 57.86; H 3.42; N 17.49.
1
mp 195°C. H NMR spectrum (400 MHz, DMSO-d6),
δ, ppm: 2.39 s (6H, CH3), 2.64 s (3H, CH3), 3.69 s
(3H, CH3N), 4.57 s (2H, CH2S), 6.90 s (1H, 5′-H),
7.60 d (2H, Harom, J = 8.8 Hz), 7.64 d (2H, Harom
,
J = 8.8 Hz). Found, %: C 56.01; H 4.56; N 19.53.
C20H19ClN6OS. Calculated, %: C 56.27; H 4.49;
N 19.69.
2-(2-Chlorophenyl)-4-[1-(4-chlorophenyl)-1H-
tetrazol-5-ylsulfanylmethyl]-3-methyl-6,7-dihydro-
2H-pyrazolo[3,4-d]pyridazin-7-one (XXIIa). Yield
69%, mp 236°C. H NMR spectrum (200 Hz,
DMSO-d6), δ, ppm: 2.48 s (3H, CH3), 4.85 s (2H,
1
4-(1,3-Benzothiazol-2-ylsulfanylmethyl)-2-(4-
chlorophenyl)-3,6-dimethyl-6,7-dihydro-2H-pyra-
zolo[3,4-d]pyridazin-7-one (XXV). Yield 66%,
CH2S), 7.60–7.88 m (8H, Harom), 12.35 s (1H, NH).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

SYNTHESIS OF 2-ARYL-4-[(R-SULFANYLMETHYL]-3-METHYL-6,7-DIHYDRO-2H-...
1557
1
mp 229°C. H NMR spectrum (200 Hz, DMSO-d6), δ,
Found, %: C 50.68; H 3.17; N 22.28. C21H16Cl2N8OS.
Calculated, %: C 50.51; H 3.23; N 22.44.
ppm: 2.68 s (3H, CH3), 3.64 s (3H, CH3N), 4.92 s (2H,
CH2S), 7.32–7.88 m (8H, Harom). Found, %: C 55.63;
H 3.51; N 15.48. C21H16ClN5OS2. Calculated, %:
C 55.56; H 3.55; N 15.43.
4-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanyl-
methyl]-2-(2,4-dichlorophenyl)-3,6-dimethyl-6,7-
dihydro-2H-pyrazolo[3,4-d]pyridazin-7-one
1
2-(2,4-Dichlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-
triazol-3-ylsulfanylmethyl)-3,6-dimethyl-6,7-dihy-
dro-2H-pyrazolo[3,4-d]pyridazin-7-one (XXVIa).
(XXVIIb). Yield 69%, mp 229°C. H NMR spectrum
(200 Hz, DMSO-d6), δ, ppm: 2.54 s (3H, CH3), 3.56 s
(3H, CH3N), 4.77 s (2H, CH2S), 7.65–7.78 m (6H,
1
Yield 55%, mp 154–155°C. H NMR spectrum
H
arom), 8.06 br.s (1H, Harom). Found, %: C 47.38;
(200 MHz, DMSO-d6), δ, ppm: 2.44 s (3H, CH3),
3.56 s (3H, CH3N), 4.47 s (2H, CH2S), 7.08–7.58 m
(10H, Harom), 7.75 br.s (2H, Harom), 8.06 br.s (1H, Harom).
Found, %: C 58.46; H 3.81; N 16.80. C28H21Cl2N7OS.
Calculated, %: C 58.54; H 3.68; N 17.07.
H 2.69; N 21.16. C21H15Cl3N8OS. Calculated, %:
C 47.25; H 2.83; N 20.99.
REFERENCES
1. Matiichuk, V.S., Potopnyk, M.A., and Obushak, N.D.,
Russ. J. Org. Chem., 2009, vol. 45, p. 712.
2. Matiichuk, V.S., Potopnyk, M.A., and Obushak, N.D.,
Russ. J. Org. Chem., 2008, vol. 44, p. 1352.
3. Al-Zaydi, K.M. and Hafez, E.A.A., J. Chem. Res.,
Miniprint, 1999, p. 1621.
4. Carpino, P.A. and Dow, R.L., WO Patent no. 111849,
2006.
5. Carpino, P.A. and Sakya, S.M., WO Patent no. 61504,
2005.
2-(2,5-Dichlorophenyl)-4-(4,5-diphenyl-4H-1,2,4-
triazol-3-ylsulfanylmethyl)-3,6-dimethyl-6,7-dihy-
dro-2H-pyrazolo[3,4-d]pyridazin-7-one (XXVIb).
1
Yield 60%, mp 196°C. H NMR spectrum (200 MHz,
DMSO-d6), δ, ppm: 2.47 s (3H, CH3), 3.57 s (3H,
CH3N), 4.49 s (2H, CH2S), 7.28–7.56 m (10H, Harom),
7.77–7.98 m (3H, Harom). Found, %: C 58.38; H 3.50;
N 17.19. C28H21Cl2N7OS. Calculated, %: C 58.54;
H 3.68; N 17.07.
2-(4-Chlorophenyl)-4-[1-(4-chlorophenyl)-1H-
tetrazol-5-ylsulfanylmethyl]-3,6-dimethyl-6,7-dihy-
dro-2H-pyrazolo[3,4-d]pyridazin-7-one (XXVIIa).
6. Bildirici, I., Şener, A., Atalan, E., Battal, A., and
Genz, H., Med. Chem. Res.,, 2009, vol. 18, p. 327.
7. Chang, E.-M., Lin, C.-J., Wong, F.F, and Yeh, M.-Y.,
1
Yield 65%, mp 194°C. H NMR spectrum (200 Hz,
Heterocycles, 2006, vol. 68, p. 733.
DMSO-d6), δ, ppm: 2.64 s (3H, CH3), 3.55 s (3H,
8. Erian, A.W., Sherif, M.S., and Gaber, H.M., Molecules,
CH3N), 4.73 s (2H, CH2S), 7.42–7.79 m (8H, Harom).
2003, vol. 8, p. 793.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010