Synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones by the condensation of cyclohexanone derivatives with 3-amino-1-phenyl-1h-pyrazol-5(4h)-one

Article abstract of DOI:10.1134/S1070363212020211

The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure of the 7-acetyl-2,4,6,7,8, 9-hexahydro-8-hydroxy-5,8-

Full text of DOI:10.1134/S1070363212020211

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 305–309. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.D. Dyachenko, S.M. Sukach, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 2, pp. 310–314.
Synthesis of 1H-Pyrazolo[3,4-c]isoquinolin-1-ones
by the Condensation of Cyclohexanone Derivatives
with 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one
V. D. Dyachenko and S. M. Sukach
Taras Shevchenko Lugansk National University, Oboronnaya ul. 2, Lugansk, 91011 Ukraine
e-mail: dvd_lug@online.lg.ua
Received December 28, 2010
Abstract—The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-
2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure
of the 7-acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]iso-
quinolin-1-one obtained was proved by X-ray diffraction analysis.
DOI: 10.1134/S1070363212020211
On the basis of tetrahydroisoquinoline a series of
compounds used in medicine as drugs has been
synthesized [1, 2]. Besides, the isoquinoline
framework is a part of many alkaloids exhibiting
pharmacological effect [3–5]. In turn, among the
pyrazoloizoquinolines some kinase inhibitors were
identified, which were taken as the base to develop
drugs for the treatment of osteoarthritis, rheumatoid
arthritis and asthma [6]. Therefore, the development of
the methods of synthesis and production of new
compounds of this class is relevant and promising in
terms of finding new biologically active substances.
5H-one (II). We found that at reflux in the presence of
sodium ethoxide a formation occurs of new derivatives
of the tricyclic system 6-aryl(heteryl)-7-acetyl-2,4,6,7,8,9-
hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-1H-
pyrazolo[3,4-c]isoquinolin-1-ones (IIIa–IIIg), apparently
as a result of intramolecular cyclization of inter-
mediates (A).
Structure of compounds obtained is confirmed by
spectral studies (see Experimental). However, unam-
biguous choice between the prototropic tautomers III
and IV was impossible. Therefore, the structure of 7-
acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-
2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-
1-one IIIf was studied by the X-ray diffraction
analysis (see the figure and Tables 1, 2).
In the present study, we investigated a reaction of
3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclo-
hexanones (Ia–Ig) with 3-amino-1-phenyl-1H-pyrazol-
NH2
N
O
O
R
O
N
O
R
O
R
O
R
O
O
Ph
II
NH2
NH
N
OH
N
N
Ph
N
N
NH
N
Ph
OH
OH
IVа_IVg
OH
O
O
O
Ph
IIIа_IIIg
Iа_Ig
A
I, III, IV, R = Ph (a), 4-MeC6H4 (b), 4-EtC6H4 (c), 3-MeOC6H4 (d), 3-pyridyl (e), 2-furyl (f), 5-methylfur-2-yl (g).
305

306
DYACHENKO, SUKACH
Table 2. Bond angles (ω, deg) in the structure IIIf
Table 1. Bond lengths (d, Å) in structure IIIf
Angle
C21O4C24
C1N1C11
C1N1N2
C11N1N2
C3N2N1
C4N3C3
O1C1N1
O1C1C2
N1C1C2
C6C2C3
C6C2C1
C3C2C1
N2C3N3
N2C3C2
N3C3C2
N3C4C5
N3C4C17
C5C4C17
C4C5C6
C4C5C10
C6C5C10
C2C6C5
C2C6C7
C5C6C7
C6C7C8
O2C8C7
O2C8C18
ω
Angle
C7C8C18
O2C8C9
C7C8C9
ω
Bond
O1–C1
d
Bond
C6–C7
d
106.0(3)
129.4(3)
113.0(3)
116.6(3)
102.2(2)
121.3(3)
125.1(3)
130.9(3)
104.1(3)
121.3(3)
134.3(3)
104.4(3)
125.0(3)
116.2(3)
118.7(3)
121.1(3)
114.3(3)
124.5(3)
118.8(3)
119.8(3)
121.4(3)
118.6(3)
120.6(3)
120.8(3)
114.3(2)
109.3(2)
110.3(2)
110.1(2)
106.6(2)
108.0(3)
112.5(3)
113.3(3)
110.5(3)
111.9(2)
112.2(2)
108.6(2)
113.9(2)
118.9(3)
120.0(3)
121.1(3)
119.5(3)
121.6(4)
118.8(4)
120.4(4)
120.6(4)
120.0(3)
121.3(3)
118.7(3)
110.0(3)
134.3(3)
115.6(3)
107.3(3)
106.1(3)
110.6(3)
1.255(3)
1.498(4)
O2–C8
O3–C19
O4–C21
O4–C24
N1–C1
N1–C11
N1–N2
N2–C3
N3–C4
N3–C3
C1–C2
C2–C6
C2–C3
C4–C5
C4–C17
C5–C6
C5–C10
1.439(3)
1.213(4)
1.371(3)
1.372(4)
1.402(4)
1.411(4)
1.423(3)
1.311(4)
1.353(4)
1.370(4)
1.437(4)
1.378(4)
1.410(4)
1.401(4)
1.498(4)
1.419(4)
1.521(4)
C7–C8
1.519(4)
1.520(4)
1.541(4)
1.524(4)
1.541(4)
1.504(4)
1.383(4)
1.396(4)
1.375(4)
1.370(5)
1.384(5)
1.378(5)
1.500(4)
1.331(4)
1.426(5)
1.333(5)
C8–C18
C8–C9
C18C8C9
C19C9C8
C19C9C10
C8C9C10
C21C10C5
C21C10C9
C5C10C9
C16C11C12
C16C11N1
C12C11N1
C13C12C11
C14C13C12
C13C14C15
C16C15C14
C15C16C11
O3C19C20
O3C19C9
C20C19C9
C22C21O4
C22C21C10
O4C21C10
C21C22C23
C24C23C22
C23C24O4
C9–C19
C9–C10
C10–C21
C11–C16
C11–C12
C12–C13
C13–C14
C14–C15
C15–C16
C19–C20
C21–C22
C22–C23
C23–C24
The molecule IIIf has three chiral centers, the
atoms C8, C9 and C10, with relative configuration
(S*,R*,R*). The cyclohexene ring conformation is a
distorted sofa. The fragment C9C10C5C6C7 is almost
flat [the torsion angles C9C10C5C6 and C10C5C6C7 are
4.0(4)° and 6.2(4)°, respectively], the C8 atom is
deviated from this plane by 0.697(4) Å. Hydroxy
group has the axial orientation [the torsion angle
C6C7C8O2 is 63.5(3)°], and the methyl group C18 and
acetyl are in equatorial positions [the torsion angles
C6C7C8C18 and C7C8C9C19 are –175.2(3)° and –171.9(2)°,
respectively]. This leads to an appearance of a
shortened intramolecular contact H18b···C19 2.66 Å
(sum of the van der Waals radii is 2.87 Å [7]). Furyl
group is so oriented that the C21–O4 bond has ap-
orientation relative to the C10H10 (torsion angle
O4C21C10H10 is –158°). The nitrogen atom N1 has a
slightly non-planar configuration [the deviation of the
N1 atom from the plane of the atoms bound to it is
–0.080(3) Å]. The phenyl substituent is somewhat
turned relative to the plane of the bicyclic fragment
Structure of compound IIIf by the data of XRD analysis.
Thermal ellipsoids of nonhydrogen atoms are shown at
50% probability.
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SYNTHESIS OF 1H-PYRAZOLO[3,4-c]ISOQUINOLIN-1-ONES
307
[the torsion angle C1N1C11C12 is –15.6(5)°]. This
orientation of the substituent is stabilized by the
formation of an additional intramolecular hydrogen
bond C12–H12···O1 (H···O 2.32 Å, C–H···O 122°) and a
shotened attractive contact N2···H16 2.39 Å (the sum of
the van der Waals radii is 2.66 Å [7]), which cannot be
classified as a hydrogen bond because the C16–H16···N2
angle is too small, 102°.
In the molecule a lengthening of the C1–O1 bond
[1.255(3) Å] is observed to the value characteristic of
carboxy groups (1.25 Å [8]) indicating the localization
of a significant negative charge on the carbonyl group.
The positive charge is apparently delocalized over the
pyridine ring, as evidenced by the leveling of the C–C
bonds in it (bond lengths are in the range 1.378(4)–
1.419(4) Å, while the average values of double and
single bond lengths are 1.35 and 1.455 Å, respectively
[8]). On this basis, we can assume a significant
contribution of zwitterionic resonance structure into
the molecular structure of IIIf.
Mr = 417.45, Z = 4, space group P21/c, dcalc = 1.357 g cm–3,
μ(MoKα) = 0.094 mm–1, F(000 ) = 880. The unit cell
parameters and intensities of 19292 reflections (3588
independent, Rint = 0.065) were measured on an auto-
matic four-circle diffractometer Xcalibur 3 (MKα,
graphite monochromator, CCD detector, ω-scanning,
2θ max = 50°).
The structure was solved by direct method with a
SHELX-97 software [9]. The positions of the hydrogen
atoms were calculated geometrically and refined using
rider model with Uiso = nUeq of a carrier atom (n = 1.5
for CH3 and OH groups and n = 1.2 for the other
hydrogen atoms). The structure was refined with
respect to F2 by a full-matrix least-squares method in
the anisotropic approximation for nonhydrogen atoms
to wR2 = 0.182 for 3588 reflections [R1 = 0.066 for
2109 reflections with F > 4σ(F), S = 0.99]. The final
atomic coordinates are listed in Table 1, bond lengths
and angles, in Tables 1 and 2, respectively.
The IR spectra of the synthesized compounds were
recorded on a Pelkin Elmer SPECTRUM ONE FTIR-
1
O
O
spectrometer from the mulls in mineral oil. The H
O
O
NMR spectra were recorded on a Bruker AVANCE
400 instrument, solvent DMSO-d6, internal reference
TMS. The mass spectra were recorded on a Crommas
GC/MS-Hewlett-Packard 5890/5972 spectrometer,
column HP-5 MS (70 eV), from a solution in CH2Cl2
(compound ІІІg) and MX-1321 (70 eV) spectrometer
with direct inlet of the substance to the ion source
(other compounds). Melting points were determined on
a Koeffler block. Monitoring the progress of the
reaction and the purity of compounds obtained was
carried out by TLC on Silufol UV-254 plates, eluent
acetone-hexane mixture, 3:5, developers iodine vapor
and UV radiation.
NH
NH
N
N
OH
OH
N
N
O
O
Ph
Ph
Such a redistribution of electron density is
stabilized by the formation of intermolecular hydrogen
bonds O2–H2···O1i [i: 1 – x , 1 – y, –z] (H···O 1.93 Å,
OH···O 173°) and N3–H3···O2ii [ii: 1 – x, –1/2 + y, 1/2 –
z] (H···O 2.06 Å, NH···O 167°). Due to these hydrogen
bonds the molecules in the crystal form layers parallel
to the [001] plane. Also, in the crystal a series of weak
CH···O, CH···N, and CH···π bonds is formed: C17–
H17···O1iii [iii: x, 1/2–y, 1/2+z], (H···O 2.54 Å, CH .... O
161°), C24–H24···O3iv [iv: x, –1+y, z], (H···O 2.50 Å,
CH···O 152°), C10–H10···N2v [v: 1 – x, 1/2 + y, 1/2 – z],
(H···N 2.50 Å, CH···N 166°), C9–H9···C12vi [vi: 1 – x,
–y, –z] (H···C 2.78 Å, CH···C 170°) and C13–H13···C24vi
(H···C 2.83 Å, CH···C 142°).
3-Aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methyl-
cyclohexanones Ia–Ig were obtained by the known
procedure [10].
2,4-Diacetyl-5-hydroxy-5-methyl-3-(3-methoxy-
phenyl)cyclohexanone (Id). Yield 2.5 g (87%), white
powder, mp 107–110°C. IR spectrum, ν, cm–1: 3415
1
(OH), 1717, 1696 (C=O). H NMR spectrum, δ, ppm:
1.17 s (3H, Me), 1.91 s (3H, Me), 1.92 s (3H, Me),
2
2
2.33 d (1H, C6 H, J 13.72 Hz) , 2.91 d (1H, C6H, J
13.72 Hz), 3.28 d (1H, C4H, J 12.0 Hz), 3.71 s (3H,
MeO), 3.95 t (1H, C3H, J 12.0 Hz ), 8.4 d (1H, C2H, J
EXPERIMENTAL
12.0 Hz), 5.21 br.s (1H, OH), 6.73 d (1H, Harom
J 8.0 Hz), 6.86 d (1H, Harom, J 7.6 Hz ), 7.18 m (1H,
arom, J 8.0 Hz). Mass spectrum, m/z (Irel, %): 300 (0.6)
,
Crystals of compound IIIf are monoclinic,
C24H23N3O4, at 298 K a = 15.802(3) Å, b = 8.1219(10) Å,
c = 17.147(3) Å, β = 111.761(18), V = 2043.9(5) Å3,
H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012

308
DYACHENKO, SUKACH
2
[M – H2O]+, 257 (27.8) [M – CH3CO – H2O]+, 215
(22.2), 43 (100) [CH3C=O]+. Found, %: C 67.79; H
6.83. C18H22O5. Calculated, %: C 67.91; H 6.97.
C9H, J 17.6 Hz), 4.45 d (1H, C6H, J 10.0 Hz), 4.75
br.s (1H, OH), 6.92 d (2H, Harom, J 7.2 Hz), 6.7 d (2H,
arom, J 7.6 Hz), 7.20 d (1H, Harom, J 6.8 Hz), 7.46 t
H
(2H , Harom, J 7.2 Hz), 7.97 m (2H, Harom), 11.24 br.s
(1H, NH). Mass spectrum, m/z (Irel, %): 441 (9.5) [M]+,
380 (100) [M – CH3CO – H2O]+, 290 (5.2), 235 (4.4)
193 (3.6), 105 (2.1), 43 (14.6) [CH3C=O]+. Found, %:
C 73.38; H 6.01; N 9.40. C27H27N3O3. Calculated, %:
C 73.45; H 6.16; N 9.52.
2,4-Diacetyl-5-hydroxy-5-methyl-3-(4-ethyl-
phenyl)cyclohexanone (Ic). Yield 2.0 g (90%), white
powder, mp 135–138°C. IR spectrum, ν, cm–1: 3437
1
(OH), 1720, 1695 (C=O). H NMR spectrum, δ, ppm:
1.14 m (3H, Me, J 7.6 Hz), 1.16 s (3H, Me), 1.88 s
2
(3H, Me), 1.89 s (3H, Me), 2.33 d (1H, C6 H, J 13.7
2
Hz), 2.53 q (2H, CH2, J 7.6 Hz), 2.91 d (1H, C6 H, J
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-
dimethyl-2-phenyl-6-(4-ethylphenyl)-1H-pyrazolo-
[3,4-c] isoquinolin-1-one (IIIc) was prepared
analogously to compound IIIa with an appropriate
cyclohexanone derivative Ic. Yield 2.8 g (88%), red
powder, mp 265–270°C. IR spectrum, ν, cm–1: 3430
13.7 Hz), 3.26 d (1H, C4H, J 12.0 Hz), 3.91 t (1H,
C3H, J 12.0 Hz), 4.4 d (1H, C2H, J 12.0 Hz), 5.20 br.s
(1H, OH), 07.09 d (2H, Harom, J 7.92 Hz), 7.22 d (2H,
H
arom, J 7.92 Hz). Mass spectrum, m/z (Irel, %): 298
(0.3) [M – H2O]+, 255 (32.8) [M – CH3CO – H2O]+,
213 (22.2), 43 (100) [CH3C=O]+. Found, %: C 72.01;
H 7.55. C19H24O4. Calculated, %: C 72.13; H 7.65.
1
(OH), 2921 (NH), 1701 (C=O). H NMR spectrum, δ,
ppm: 1.14 m (3H, Me, J 7.5 Hz), 1.21 s (3H, Me), 1.84
s (3H, Me), 2.12 s (3H, Me), 2.54 q (2H, CH2, J 7.5
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-2,6-diphenyl-1H-pyrazolo[3,4-c]isoquinolin-
1-one (IIIa). To a suspension of 2 g (7 mmol) of
cyclohexanone (Ia) in 30 ml of anhydrous ethanol was
added 1.23 g (7 mmol) of pyrazole II and a solution of
0.16 g (7 mmol) of sodium in 5 ml of anhydrous
ethanol. The reaction mixture was refluxed for 1 h and
then cooled. The resulting precipitate was filtered off
and washed with ethanol. Yield 2.55 g (85%), red
powder, mp 260°C. IR spectrum, ν, cm–1: 3421 (OH),
2
Hz), 2.83 d (1H, C7H, J 9.8 Hz), 3.7 d (1H, C9H, J
2
17.7 Hz), 3.60 d (1H, C9H, J 17.7 Hz), 4.39 d (1H,
C6H, J 9.8 Hz), 4.60 br.s (1H, OH), 6.93 d (2H, Harom
,
J 7.6 Hz), 7.7 m (3H, Harom), 7.36–7.40 m (2H, Harom),
8.11 d (2H, Harom, J 6.8 Hz). The NH proton signal is
not observed, apparently due to rapid deuterium
exchange. Mass spectrum, m/z (Irel, %): 455 (17.5) [M]+,
394 (100) [M – CH3CO – H2O]+, 290 (15.4), 206 (8.2)
119 (7.6), 43 (27) [CH3C=O]+, 31 (76). Found, %: C
73.69; H 6.30; N 9.15. C28H29N3O3. Calculated, %: C
73.82; H 6.42; N 9.22.
1
3057 (NH), 1714 (C=O), 1673 (NC=O). H NMR
spectrum, δ, ppm: 1.25 s (3H, Me), 1.93 s (3H, Me),
2.12 s (3H, Me), 2.93 d (1H, C7H, J 10.4 Hz), 3.18 d
2
2
(1H, C9H, J 18.0 Hz), 3.65 d (1H, C9H, J 18.0 Hz),
4.50 d (1H, C6H, J 10.4 Hz), 4.76 br.s (1H, OH), 7.04
d (2H, Harom, J 7.2 Hz), 7.18–7.27 m (4H, Harom), 7.45 t
(2H, Harom, J 7.6 Hz), 7.96 m (2H, Harom). The NH
proton signal is not observed, apparently due to rapid
deuterium exchange. Mass spectrum, m/z (Irel, %): 427
(21.6) [M]+, 366 (100) [M – CH3CO – H2O]+, 290
(25.1) 235 (4.2) 178 (3.3), 105 (2.7), 43 (18.7)
[CH3C=O]+. Found, %: C 73.00; H 5.79; N 9.75.
C26H25N3O3. Calculated, %: C 73.05; H 5.89; N 9.83.
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-6-(3-methoxyphenyl)-2-phenyl-1H-pyrazolo-
[3,4-c] isoquinolin-1-one (IIId) is obtained similarly
to compound IIIa with an appropriate cyclohexanone
derivative Id. Yield 2.7 g (84%), red powder, mp 242–
245°C. IR spectrum, ν, cm–1: 3415 (OH), 3235 (NH),
1
1717, 1655 (C=O). H NMR spectrum, δ, ppm: 1.25 s
(3H, Me), 1.97 s (3H, Me), 2.14 s (3H, Me), 2.93 d
2
(1H, C7H, J 10.0 Hz), 3.18 d (1H, C9H, J 18.1 Hz),
3.64 d (1H, C9H, 2J 18.1 Hz), 3.67 s (3H, OMe), 4.47 d
(1H, C6H, J 10.0 Hz ), 4.74 br.s (1H, OH), 6.60 m (2H,
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-6-(p-tolyl)-2-phenyl-1H-pyrazolo[3,4-c]iso-
quinolin-1-one (IIIb) was prepared analogously to
compound IIIa using cyclohexanone Ib. Yield 2.4 g
(78%), red powder, mp 265–270°C. IR spectrum, ν,
H
H
arom), 6.76 d (1H, Harom, J 7.7 Hz), 7.16–7.19 m (2H,
arom), 7.44 t (2H, Harom, J 7.2 Hz), 7.97 d (2H, Harom, J
6.1 Hz). The NH proton signal is not observed,
apparently due to rapid deuterium exchange. Mass
spectrum, m/z (Irel, %): 457 (21) [M]+, 396 (100) [M –
CH3CO – H2O]+, 326 (12.1), 290 (15.5) 202 (10.0),
133 (8.4), 77 (38.9) [Ph]+, 43 (14.6) [CH3C=O]+.
Found, %: C 70.42; H 5.81; N 9.05. C27H27N3O4.
Calculated, %: C 70.88; H 5.95; N 9.18.
1
cm–1: 3372 (OH), 3105 (NH), 1686 (C=O). H NMR
spectrum, δ, ppm: 1.24 s (3H, Me), 1.94 s (3H, Me),
2.13 s (3H, Me), 2.24 (3H, Me), 2.90 d (1H, C7 N, J
2
10.0 Hz), 3.17 d (1H, C9H, J 17.6 Hz), 3.64 d (1H,
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SYNTHESIS OF 1H-PYRAZOLO[3,4-c]ISOQUINOLIN-1-ONES
309
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-6-(pyridin-3-yl)-2-phenyl-1H-pyrazolo[3,4-c]-
isoquinolin-1-one (IIIe) was prepared analogously to
compound IIIa with an appropriate cyclohexanone
derivative Ie. Yield 2.6 g (87%), red powder, mp 245–
248°C. IR spectrum, ν, cm–1: 3435 (OH), 2923 (NH),
[3,4-c] isoquinolin-1-one (IIIg) was prepared like the
compound IIIa with an appropriate cyclohexanone
derivative Ig. Yield 2.6 g (86%), red powder, mp 230–
233°C. IR spectrum, ν, cm–1: 3430 (OH), 2967 (NH),
1
1725, 1660 (C=O). H NMR spectrum, δ, ppm: 1.25 s
(3H, Me), 2.16 s (3H, Me), 2.17 s (3H, Me), 2.22 s
(3H, Me), 3.08 d (1H, C7H, J 8.1 Hz), 3.11 d (1H,
C9H, 2J 18.0 Hz), 3.53 d (1H, C9H, 2J 18.0 Hz), 4.56 d
(1H, C6 H, J 8.1 Hz ), 4.88 br.s (1H, OH), 5.87 d (1H,
C4H furan J 2.7 Hz), 5.93 d (1H, furan C3H, J 2.7 Hz),
7.19 t (1H, HPh, J 7.3 Hz), 7.45 m (2H, HPh, J 7.7 Hz),
7.96 d (2H , HPh, J 6.6 Hz). Mass spectrum, m/z (Irel,
%): 432 [M + 1]+. Found, %: C 69.49; H 5.69; N 9.61.
C25H25N3O4. Calculated, %: C 69.59; H 5.84; N 9.74.
1
1707, 1659 (C=O). H NMR spectrum, δ, ppm: 1.26 s
(3H, Me), 1.94 s (3H, Me), 2.18 s (3H, Me), 2.95 d
2
(1H, C7 H, J 10.0 Hz), 3.24 d (1H, C9H, J 18.1 Hz),
2
3.66 d (1H, C9H, J 18.1 Hz), 4.59 d (1H, C6H, J
10.0 Hz), 4.88 br.s (1H, OH), 7.18–7.29 m (2H, Harom),
7.44–7.48 m (3H, Harom), 7.96 d (2H, Harom, J 5.2 Hz),
8.35 s (1H, Harom) , 8.41 d (1H, Harom, J 3.6 Hz), 11.49
br.s (1H, NH). Mass spectrum, m/z (Irel, %): 428 (19.7)
[M]+, 367 (100) [M – CH3CO – H2O]+, 290 (18.5) 248
(11.3) 180 (2.5), 93 (11.1) 43 (70.1) [CH3C=O]+.
Found, %: C 79.89; H 5.54; N 12.87. C25H24N4O3.
Calculated, %: C 70.08; H 5.65; N 13.08.
REFERENCES
1. Shi, C. and Ojima, I., Tetrahedron, 2007, vol. 63,
no. 35, p. 8563.
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]iso-
quinolin-1-one (IIIf) was prepared analogously to
compound IIIa with an appropriate cyclohexanone
derivative If. Yield 2.4 g (82%), red powder, mp. 230–
232°C. IR spectrum, ν, cm–1: 3438 (OH), 2927 (NH),
2. Siengalewicz, P., Brecker, L., and Mulzer, J., Synlett.,
2008, no. 16, p. 2443.
3. Aubry, S., Razafindrabe, C.R., Bourdon, B., Pellet-
Rostaing, S., and Lemaire, M., Tetrahedron Lett., 2007,
vol. 48, no. 52, p. 9163.
1
4. Wu,Y.-Ch., Liron, M., and Zhu, J., J. Amer. Chem. Soc.,
1719, 1661 (C=O). H NMR spectrum, δ, ppm: 1.25 s
2008, vol. 130, no. 22, p. 7148.
(3H, Me), 2.12 s (3H, Me), 2.20 (3H, Me), 3.08 d (1H,
2
C7H, J 8.4 Hz); 3.15 d (1H, C9H, J 18.4 Hz), 3.54 d
5. Quirante, J., Paloma, L., Diaba, F., Vila, X., and Bon-
2
(1H, C9H, J 18.4 Hz), 4.64 d (1H, C6H, J 8.4 Hz),
joch, J., J. Org. Chem., 2008, vol. 73, no. 2, p. 768.
4.91 br.s (1H, OH), 6.05 d (1H, furan C3H, J 2.8 Hz),
6.35 d.d (1H, C4H furan, J 2.38 Hz), 7.20 t (1H, HPh, J
7.2 Hz), 7.45 m (2H, HPh, J 7.6 Hz), 7.52 d (1H, C5H
furan, J 1.21 Hz), 7.96 d (2H, HPh, J 7.6 Hz), 11.21
br.s (1H, NH). Mass spectrum, m/z (Irel, %): 417 (11.6)
[M]+, 356 (100) [M – CH3CO – H2O]+, 328 (3.0), 265
(1.7) 209 (1.0), 93 (1.0), 43 (16.3) [CH3C=O]+. Found,
%: C 68.89; H 5.44; N 9.87. C24H23N3O4. Calculated,
%: C 69.05; H 5.55; N 10.07.
6. USA Patent no. 7132428, 2006; Ref. Zh. Khim., 2007,
19O.83P
7. Zefirov, Yu.V. and Zorkii, P.M., Usp. Khim., 1989,
vol. 58, no. 5, p. 713.
8. Burgi, H.-B. and Dunitz, J.D., Structure Correlation,
Weinheim: VCH, 1994, vol. 2, p. 741.
9. Sheldrick, G., Acta Cryst., Sect., A, 2008, vol. 64,
p. 112.
10. Kriven’ko, A.P. and Sorokin, V.V., Zameshchennye
tsyklogeksanolony (Substituted Cyclohexanones), Saratov:
Saratov. Gos. Univ., 1999, p. 38.
7-Acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-di-
methyl-6-(5-methylfur-2-yl)-2-phenyl-1H-pyrazolo-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012