Three-component reaction of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with aromatic aldehydes and propane-1,2-diamine and chemical properties of the products

Article abstract of DOI:10.1134/S1070428010060163

The reactions of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with a mixture of an aromatic aldehyde and propane-1,2-diamine, depending on the initial reactant ratio, gave 4-acyl-1-(2-aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones and 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-hydroxy-5-phenyl-2, 5-dihydro-1H-pyrrol-2-one). Reactions of substituted 1-(2-aminopropyl)-2,5- dihydro-1H-pyrrol-2-ones with aromatic amines and hydrazines were studied, and the structure of one of the products, 5-(2-aminopropyl)-3,4-diphenylpyrrolo[3,4- c]pyrazol-6-one, was proved by X-ray analysis.

Full text of DOI:10.1134/S1070428010060163

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 6, pp. 875–883. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.L. Gein, N.N. Kasimova, Z.G. Aliev, M.I. Vakhrin, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 6,
pp. 879–887.
Three-Component Reaction of Methyl 2,4-Dioxo-4-phenyl-
butanoate and Methyl 2,4-Dioxopentanoate with Aromatic
Aldehydes and Propane-1,2-diamine and Chemical Properties
of the Products
V. L. Geina, N. N. Kasimovaa, Z. G. Alievb, and M. I. Vakhrina
a Perm State Pharmaceutical Academy, ul. Polevaya 2, Perm, 614990 Russia
e-mail: geinvl48@mail.ru
b Institute of Chemical Physics Problems, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, Russia
Received October 10, 2009
Abstract—The reactions of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with a mix-
ture of an aromatic aldehyde and propane-1,2-diamine, depending on the initial reactant ratio, gave 4-acyl-1-(2-
aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones and 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-hy-
droxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one). Reactions of substituted 1-(2-aminopropyl)-2,5-dihydro-1H-
pyrrol-2-ones with aromatic amines and hydrazines were studied, and the structure of one of the products,
5-(2-aminopropyl)-3,4-diphenylpyrrolo[3,4-c]pyrazol-6-one, was proved by X-ray analysis.
DOI: 10.1134/S1070428010060163
We previously showed that reactions of 2,4-dioxo-
alkanoic acid esters with aromatic aldehydes and ethyl-
enediamine, depending on the initial reactant ratio,
lead to the formation of 1-(2-aminoethyl)-3-hydroxy-
2,5-dihydro-1H-pyrrol-2-ones or 1,1′-(ethane-1,2-diyl)-
bis(3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones) [1]. It
was interesting to elucidate whether analogous relation
is observed in reactions of the same compounds with
alkanediamines having a different structure.
less crystalline substances, which are soluble in di-
methylformamide and dimethyl sulfoxide and insol-
uble or poorly soluble in alcohols. Hydrochlorides IIa
and IIb are soluble in common organic solvents. Com-
pound IIa is soluble in water, and it shows a positive
test for chloride ion (treatment with a solution of silver
nitrate); compound IIb is poorly soluble in water.
The spectral parameters of free bases I and hydro-
chlorides II are similar. In the IR spectra of Ia–Il, IIa,
and IIb we observed absorption bands corresponding to
stretching vibrations of the ketone (1610–1651 cm–1)
and lactam carbonyl groups (1655–1718 cm–1), prima-
ry amino group (3300–3503 cm–1) and enol hydroxy
group (3158–3240 cm–1). Some compounds displayed
no absorption bands of amino group and enol hydroxy
group because of strong broadening due to exchange
processes.
For this purpose, we examined the reaction of
methyl 2,4-dioxo-4-phenylbutanoate and methyl
2,4-dioxopentanoate with a mixture of aromatic alde-
hyde and propane-1,2-diamine at molar ratios of 1:1:1
and 2:2:1. The results of our experiments showed that
mixing of the initial reactants in 1,4-dioxane or ethanol
at a ratio of 1:1:1 gives the corresponding 4-acyl-1-(2-
aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyr-
rol-2-oes Ia–Il (Scheme 1). Compounds Ia and Ih
were converted into the corresponding hydrochlorides
IIa and IIb by treatment with concentrated hydro-
chloric acid.
1
The H NMR spectra of I and II contained a dou-
blet signal with a coupling constant J of 5.7–6.6 Hz or
a multiplet signal belonging to three protons in the
methyl group of the aminoalkyl residue (δ 0.98–
1.31 ppm), multiplets from two methylene protons at
δ 2.33–3.24 (1′-HA) and 3.35–4.09 ppm (1′-HB) and
CH proton in the aminoalkyl residue at δ 3.22–
The mechanism of formation of compounds Ia–Il is
likely to be similar to the mechanism of analogous
reactions described in [1]. Compounds Ia–Il are color-
875

GEIN et al.
876
Scheme 1.
HO
O
HO
O
Me
Me
R1
R1
NH2
NH2 ·HCl
N
N
H2NCH2CH(Me)NH2
Concd. HCl
O
O
O
O
+
OMe
R1
R2
R2
O
Ia–Il
IIa, IIb
CHO
HO
O
Ph
Me
Me
Me
R2
N
N
1/2H2NCH2CH(Me)NH2
O
O
Ph
O
OH
III
I, R1 = Me (a–g), Ph (h–l); R2 = H (a, h), 4-F (b), 4-Cl (c, i), 4-MeO (d, j), 3,4-(MeO)2 (e), 4-O2N (f, k), 3-O2N (g, l);
II, R2 = H, R1 = Me (a), Ph (b).
3.80 ppm, one or two singlets from 5-H in the pyrrole
ring (δ 4.98–5.95 ppm), a group of signals from
aromatic protons in the region δ 6.70–8.28 ppm, and
a broadened singlet from protons in the primary amino
group at δ 7.77–8.18 ppm. In the spectra of Ia–Ig and
IIa we also observed a signal from protons in the
acetyl residue at δ 2.04–2.34 ppm (two singlets for
most compounds).
droxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one (Ih),
while analogous reaction with methyl 2,4-dioxopen-
tanoate gave 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-
hydroxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one) (III)
(Scheme 1). Presumably, in the latter case the reaction
also involves intermediate formation of Schiff base [2]
due to higher reactivity of methyl 2,4-dioxopentanoate.
Another reason is steric shielding of position 2 in the
propane-1,2-diamine molecule. The same factor is
responsible for the structure of the aminoalkyl residue
assigned to compounds I and II.
High signal multiplicity originates from the pres-
ence of two chiral centers in molecules I and II, so that
the products are formed as mixtures of diastereoiso-
mers. The ratio of diastereoisomers was determined
from the intensity ratio of the 5-H signals; it ranged
from 1:1 to 1:2. The observed broadening of the melt-
ing temperature range of compounds Ia, Ic, Id, and Ij
is also explained by the presence of different diastereo-
isomers. Compounds Ib, Ih, and Ik displayed in the
mass spectra the molecular ion peaks and peaks of
fragment ions with m/z 57 [CH2=C(Me)NH2]+, 44
[CH2=CHNH3]+ (Ih), 77 [C6H5]+, 105 [C6H5CO]+ (Ih,
Ik), as well as [R2C6H4CH=CHCOR1]+ and [M –
CH2=CHNH2]+ ion peaks.
Compound III is a colorless crystalline substance
which is soluble in common organic solvents. Its struc-
1
ture was confirmed by the data of IR, H NMR, and
mass spectra. It showed a positive test for enol
hydroxy group with iron(III) chloride.
Taking into account that molecules I and II possess
two reactive carbonyl groups, it was interesting to
examine their reactions with nucleophilic reagents. As
the latter we used aromatic amines and hydrazines. It
was shown previously [1] that 4,5-disubstituted
1-aminoethyl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-one
hydrochlorides react with aromatic amines and hydra-
zine. Reactions of compounds having a 2-aminopropyl
substituent in position 1 of the heteroring successfully
occurred with participation of bases. 4-Acyl-1-(2-
aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyr-
rol-2-ones and their hydrochlorides reacted with
p-anisidine, p-phenetidine, and p-(dimethylamino)ani-
line to give the corresponding arylamino derivatives
All compounds I and II showed a positive test
(intense cherry color) for enol hydroxy group upon
treatment with an alcoholic solution of iron(III) chlo-
ride, which, in combination with the spectral data,
indicates that these compounds exist in the enol form.
The reaction of methyl 2,4-dioxo-4-phenylbutano-
ate with benzaldehyde and 0.5 equiv of propane-1,2-
diamine afforded 1-(2-aminopropyl)-4-benzoyl-3-hy-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

THREE-COMPONENT REACTION OF METHYL 2,4-DIOXO-4-PHENYLBUTANOATE
877
Scheme 2.
Me2N
O
O
Me
Ph
NH2 ·HCl
N
O
IV
R3C6H4NH2
O
O
Me
H
R3
N
NH2 (· HCl)
N
Me
HO
O
Me
Va–Vc
R1
NH2
N
O
O
N
O
Me
Me
NH2 ·HCl
Ph
R2
N
N
H
Ph
I, II
VI
R3
O
N
Me
N
NH2 (· HCl)
N
R3NHNH2
R1
R2
VIIa–VIIi
O
N
Me
Ph
N
NH2 ·HCl
N
Ph
Ph
VIII
V, R3 = 4-MeO (·HCl) (a), 4-EtO (b), 4-EtO (·HCl) (c); VII, R1 = Me: R3 = H, R2 = 4-Cl (a), 4-MeO (b); R3 = Ph, R2 = H (c),
H (·HCl) (d); R1 = Ph, R3 = H, R2 = H (e), H (·HCl) (f), 4-Cl (g), 4-MeO (h), 3-O2N (i).
whose structure depended on the substituent in posi-
tion 4 of the heteroring. Compounds having a benzoyl
group reacted at the enolized carbonyl group in the
3-position, while 4-acetyl derivatives reacted at the
side-chain carbonyl group (Scheme 2). Analogous rela-
tions were observed in the reactions with hydrazine
and phenylhydrazine, which is consistent with pub-
lished data [3]. Arylamino derivatives IV and V and
pyrrolo[3,4-c]pyrazoles VII and VIII were formed in
boiling glacial acetic acid. Phenylhydrazone VI was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

GEIN et al.
The IR spectra of IV and V contained absorption
878
C12
C13
bands belonging to stretching vibrations of the lactam
(1688–1710 cm–1) and ketone carbonyl group (1630–
1650 cm–1), secondary amino group (3200–3310 cm–1),
and primary amino group in the side chain (3400–
3500 cm–1). Compounds IV and V displayed in the
1H NMR spectra a multiplet or doublet from the side-
chain methyl group (δ 0.83–1.07 ppm), multiplets from
two methylene protons at δ 2.34–2.82 (1′-HA) and
3.32–3.70 ppm (1′-HB) and side-chain CH proton at
δ 2.97–3.30 ppm, one or two singlets from 5-H at
δ 5.42–5.69 ppm, multiplets from aromatic protons in
the region δ 6.39–7.34 ppm, a singlet from the primary
amino group at δ 8.02–8.10 ppm, and a singlet from
the NH proton at δ 9.23–12.44 ppm (the spectrum of
Vb lacked the two latter signals). In the mass spectrum
of Vb the molecular ion peak with m/z 393 was ob-
served together with fragment ion peaks in support of
the assumed structure.
C11
C18
C19
C20
C17
C16
C10
C14
C9
N1
C15
C5
C1
C2
N3
C6
C7
N4
C3
C8
N2
C4
O
Fig. 1. Structure of the molecule of 5-(2-aminopropyl)-3,4-
diphenyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (VIIe)
according to the X-ray diffraction data.
Compounds VI–VIII were characterized by IR ab-
sorption bands due to stretching vibrations of the
lactam carbonyl group (1675–1710 cm–1), secondary
amino group (3200–3290 cm–1; except for VIIc,
VIId, and VIII), and primary amino group (3350–
obtained by heating for a short time in ethanol. Com-
pounds VI–VIII are colorless while IV and V are yel-
low or orange crystalline substances which are soluble
in ethanol, DMF, and DMSO. The corresponding
hydrochlorides were better soluble than the free bases.
All hydrochlorides, except for compound IV, are
soluble in water, and they show a positive test for
chloride ion with a solution of silver nitrate.
1
3500 cm–1). In the H NMR spectra of VII and VIII
alkyl protons resonated in the region δ 0.85–3.84 ppm,
the 5-H signal appeared at δ 5.50–6.25 ppm, aromatic
protons gave a multiplet in the region δ 6.82–
8.31 ppm, and the NH2 signal was located at δ 7.61–
8.29 ppm (cf. the spectra of initial compounds I and
II). In addition, a broadened singlet from the NH
proton in the pyrazole ring was observed (δ 14.08 ppm
a
c
0
1
for VIIf). The H NMR spectra of the free bases in
DMSO-d6 contained no signal from the primary amino
group, but the corresponding signal was observed in
the spectra recorded in the presence of trifluoroacetic
acid (VIIh, VIIi), as well as in the spectra of hydro-
chlorides VIId, VIIf, and VIII, indicating that these
protons are exchangeable. The mass spectra of VIIe,
VIIi, and VIII contained the molecular ion peaks and
peaks from fragment ions, which confirmed the as-
sumed structures.
C8
C8′
C6
C7
N4
C7′
The molecular and crystalline structure of pyrrolo-
pyrazole VIIe was determined by X-ray analysis of its
single crystal obtained by slow crystallization from
alcohol (Fig. 1). The pyrrolopyrazole bicyclic system
is planar, and the double bonds therein are completely
delocalized. The benzene ring on C5 lies almost in the
plane of the bicyclic fragment (the dihedral angle
between the corresponding planes is 11.2°), whereas
the benzene ring on C1 is almost orthogonal to the
b
Fig. 2. Packing of molecules VIIe in crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

THREE-COMPONENT REACTION OF METHYL 2,4-DIOXO-4-PHENYLBUTANOATE
879
pyrrolopyrazole skeleton (the corresponding dihedral
angle is 88.9°, and the torsion angle N1C1C9C10 is
69.7°). The C7 and C8 atoms in the aminopropyl frag-
ment are disordered by two positions with almost equal
probabilities, the distance between the disordered posi-
tions being 1 Å. These positions are related to each
other through a symmetry plane passing through the
N1, C6, and N4 atoms. Each crystallographic position is
statistically occupied by two diastereoisomers (Fig. 2).
Thus, there are two enantiomers and two diastereoiso-
mers, which is very consistent with the spectral data.
C 65.59; H 6.58; N 10.17. C15H18N2O3. Calculated, %:
C 65.67; H 6.61; N 10.21.
Compounds Ib–Il were synthesized in a similar
way.
4-Acetyl-1-(2-aminopropyl)-5-(4-fluorophenyl)-
3-hydroxy-2,5-dihydro-1H-pyrrol-2-one (Ib). Yield
0.91 g (31%), mp >300°C (from ethanol). IR spectrum,
ν, cm–1: 3400 (NH2), 1684 (NC=O), 1651 (C=O).
1H NMR spectrum (CD3COOD), δ, ppm: 1.27 m (3H,
Me), 2.34 s (3H, MeCO), 2.89 m and 2.93 m (1H,
1′-HA), 3.92 m and 3.96 m (1H, 1′-HB), 3.71 m (1H,
The aminopropyl groups in crystal reside in a plane
parallel to the crystallographic a axis, they are not
involved in intermolecular hydrogen bonds, and no
shortened contacts (relative to the corresponding van
der Waals contacts) were observed. In combination
with large thermal vibration parameters of the C7, C8
and C7′, C8′ atoms, these findings suggest that dia-
stereoisomers of VIIe in crystal exist in dynamic
equilibrium.
2′-H), 5.42 s and 5.47 s (1H, 5-H), 7.10 t (2H, Harom
,
J = 8.8 Hz), 7.30 m (2H, Harom). Mass spectrum, m/z
(Irel, %): 292 (10.68) [M]+, 249 (100) [M –
CH2=CHNH2]+, 164 (11.67) [4-FC6H4CH=CHCOMe]+,
149 (63.31) [4-FC6H4CH=CHCO]+, 57 (19.22)
[CH2=C(Me)NH2]+. Found, %: C 61.59; H 5.87;
N 9.50. C15H17FN2O3. Calculated, %: C 61.63; H 5.86;
N 9.59.
4-Acetyl-1-(2-aminopropyl)-5-(4-chlorophenyl)-
3-hydroxy-2,5-dihydro-1H-pyrrol-2-one (Ic). Yield
2.01 g (65%), mp 275–286°C (the product was recrys-
tallized from ethanol and then treated with hot
acetone). IR spectrum, ν, cm–1: 3340 (NH2), 1700
EXPERIMENTAL
The IR spectra were recorded on UR-20 and
Specord M-80 spectrometers from samples dispersed
in mineral oil. The 1H NMR spectra were measured on
Bruker DRX-500 (500.13 MHz), Bruker DRX-400
(400.13 MHz), and Varian Mercury-300 (300.05 MHz)
instruments using hexamethyldisiloxane as internal
reference. The mass spectra (electron impact, 70 eV)
were obtained on a Finnigan MAT Incos 50 mass spec-
trometer. The progress of reactions was monitored, and
the purity of compound VIII was checked, by TLC on
Silufol plates using acetonitrile–water–ethanol (1:1:1)
as eluent.
1
(NC=O), 1613 (C=O). H NMR spectrum (DMSO-d6–
CF3COOH), δ, ppm: 1.02 m (3H, Me), 2.24 s (3H,
MeCO), 2.51 m and 2.71 m (1H, 1′-HA), 3.50 m and
3.64 m (1H, 1′-HB), 3.33 m (1H, 2′-H), 5.23 s and
5.27 s (1H, 5-H), 7.34 m (2H, Harom), 7.20 d (2H,
H
arom, J = 8.1 Hz), 7.82 br.s (2H, NH2). Found, %:
C 58.33; H 5.50; N 9.01. C15H17ClN2O3. Calculated,
%: C 58.35; H 5.55; N 9.07.
4-Acetyl-1-(2-aminopropyl)-3-hydroxy-5-(4-me-
thoxyphenyl)-2,5-dihydro-1H-pyrrol-2-one (Id).
Yield 1.40 g (46%), mp 255–266°C (the product was
recrystallized from ethanol and then treated with hot
acetone). IR spectrum, ν, cm–1: 3440 (NH2), 3200
4-Acetyl-1-(2-aminopropyl)-3-hydroxy-5-phenyl-
2,5-dihydro-1H-pyrrol-2-one (Ia). A solution of
0.01 mol of methyl 2,4-dioxopentanoate in 15 ml of
1,4-dioxane was added at room temperature to a solu-
tion of 0.01 mol of propane-1,2-diamine and 0.01 mol
of benzaldehyde in 5 ml of 1,4-dioxane. The mixture
was kept for 24 h at room temperature, and the precip-
itate was filtered off and recrystallized from appropri-
ate solvent. Yield 1.21 g (44%), mp 290–300°C (from
ethanol). IR spectrum, ν, cm–1: 3503 (NH2), 3158
1
(OH), 1655 (NC=O), 1620 (C=O). H NMR spectrum
(DMSO-d6–CF3COOH), δ, ppm: 1.01 m (3H, Me),
2.23 s and 2.24 s (3H, MeCO), 2.50 m and 2.73 m (1H,
1′-HA), 3.46 m and 3.60 m (1H, 1′-HB), 3.33 m (1H,
2′-H), 3.68 s (3H, MeO), 5.16 s and 5.20 s (1H, 5-H),
6.83 d (2H, Harom, J = 7.5 Hz), 7.09 m (2H, Harom),
7.82 br.s (2H, NH2). Found, %: C 63.15; H 6.57;
N 9.15. C16H20N2O4. Calculated, %: C 63.14; H 6.62;
N 9.21.
1
(OH), 1700 (NC=O), 1625 (C=O). H NMR spectrum
(DMSO-d6), δ, ppm: 1.00 d (3H, Me, J = 6.3 Hz),
2.04 s and 2.07 s (3H, MeCO), 2.33 m and 2.56 m (1H,
1′-HA), 3.51 m and 3.59 m (1H, 1′-HB), 3.32 m (1H,
2′-H), 5.01 s and 5.02 s (1H, 5-H), 7.02 m (2H, Harom),
7.17 m (3H, Harom), 8.14 br.s (2H, NH2). Found, %:
4-Acetyl-1-(2-aminopropyl)-5-(3,4-dimethoxy-
phenyl)-3-hydroxy-2,5-dihydro-1H-pyrrol-2-one
(Ie). Yield 1.00 g (30%), mp >300°C (the product was
recrystallized from DMF and then treated with hot
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

GEIN et al.
880
ethanol). IR spectrum, ν, cm–1: 3300 (NH2), 1694
(NC=O), 1646 (C=O). 1H NMR spectrum (DMSO-d6),
δ, ppm: 1.09 m (3H, Me), 2.13 s and 2.14 s (3H,
MeCO), 2.80 m (1H, 1′-HA), 3.35 m and 3.64 m (1H,
1′-HB), 3.41 m (1H, 2′-H), 3.71 s and 3.74 s (3H each,
MeO), 4.98 s and 5.02 s (1H, 5-H), 6.70 m (2H, Harom),
6.80 m (1H, Harom), 8.11 br.s (2H, NH2). Found, %:
C 61.00; H 6.60; N 8.33. C17H22N2O5. Calculated, %:
C 61.06; H 6.63; N 8.38.
spectrum, ν, cm–1: 3450 (NH2), 3230 (OH), 1688
(NC=O), 1620 (C=O). 1H NMR spectrum (DMSO-d6),
δ, ppm: 0.98 m (3H, Me), 2.50 m and 2.78 m (1H,
1′-HA), 3.41 m and 3.59 m (1H, 1′-HB), 3.24 m (1H,
2′-H), 5.18 s and 5.24 s (1H, 5-H), 7.23 m (7H, Harom),
7.65 m (2H, Harom), 7.85 br.s (2H, NH2). Found, %:
C 64.76; H 5.10; N 7.52. C20H19ClN2O3. Calculated,
%: C 64.78; H 5.16; N 7.56.
1-(2-Aminopropyl)-4-benzoyl-3-hydroxy-5-(4-
methoxyphenyl)-2,5-dihydro-1H-pyrrol-2-one (Ij).
Yield 2.97 g (81%), mp 235–241°C (the product was
recrystallized from DMF and then treated with hot
ethanol). IR spectrum, ν, cm–1: 3330 (NH2), 3240
4-Acetyl-1-(2-aminopropyl)-3-hydroxy-5-(4-ni-
trophenyl)-2,5-dihydro-1H-pyrrol-2-one (If). Yield
2.17 g (68%), mp >300°C (from propan-2-ol). IR spec-
1
trum, ν, cm–1: 1682 (NC=O), 1646 (C=O). H NMR
1
(OH), 1679 (NC=O), 1620 (C=O). H NMR spectrum
spectrum (DMSO-d6), δ, ppm: 1.10 m (3H, Me), 2.10 s
and 2.11 s (3H, MeCO), 2.52 m and 2.64 m (1H,
1′-HA), 3.60 m and 3.73 m (1H, 1′-HB), 3.44 m (1H,
2′-H), 5.20 s and 5.23 s (1H, 5-H), 7.41 m (2H, Harom),
8.10 m (2H, Harom), 8.16 br.s (2H, NH2). Found, %:
C 56.41; H 5.31; N 13.17. C15H17N3O5. Calculated, %:
C 56.42; H 5.37; N 13.16.
(DMSO-d6–CF3COOH), δ, ppm: 1.04 m (3H, Me),
2.60 m and 2.86 m (1H, 1′-HA), 3.53 m and 3.68 m
(1H, 1′-HB), 3.35 m (1H, 2′-H), 3.65 s (3H, 4-MeO),
5.45 s and 5.49 s (1H, 5-H), 6.83 d (2H, Harom, J =
8.7 Hz), 7.25 m (2H, Harom), 7.40 t (2H, Harom, J =
7.8 Hz), 7.58 m (3H, Harom), 7.80 br.s (2H, NH2).
Found, %: C 68.82; H 6.03; N 7.63. C21H22N2O4. Cal-
culated, %: C 68.83; H 6.05; N 7.65.
4-Acetyl-1-(2-aminopropyl)-3-hydroxy-5-(3-ni-
trophenyl)-2,5-dihydro-1H-pyrrol-2-one (Ig). Yield
2.14 g (67%), mp >300°C (the product was recrystal-
lized from DMF and then treated with hot ethanol). IR
spectrum, ν, cm–1: 3450 (NH2), 3160 (OH), 1700
1-(2-Aminopropyl)-4-benzoyl-3-hydroxy-5-(4-ni-
trophenyl)-2,5-dihydro-1H-pyrrol-2-one (Ik). Yield
3.17 g (83%), mp 250–252°C (from ethanol). IR spec-
trum, ν, cm–1: 3380 (NH2), 3240 (OH), 1702 (NC=O),
1633 (C=O). 1H NMR spectrum (CD3COOD), δ, ppm:
1.31 m (3H, Me), 3.00 m and 3.24 m (1H, 1′-HA),
3.88 m and 4.09 m (1H, 1′-HB), 3.80 m (1H, 2′-H),
5.89 s and 5.95 s (1H, 5-H), 7.41 m (2H, Harom),
7.58 m (3H, Harom), 7.75 d (2H, Harom, J = 7.2 Hz),
8.19 m (2H, Harom). Mass spectrum, m/z (Irel, %): 381
(3.69) [M]+, 338 (49.06) [M – CH2=CHNH2]+, 253
(11.84) [4-O2NC6H4CH=CHCOPh]+, 105 (100)
[PhCO]+, 77 (38.48) [Ph]+, 57 (17.60) [CH2=C(Me)-
NH2]+. Found, %: C 62.89; H 5.00; N 10.96.
C20H19N3O5. Calculated, %: C 62.98; H 5.02; N 11.02.
1
(NC=O), 1610 (C=O). H NMR spectrum (DMSO-d6–
CF3COOH), δ, ppm: 1.01 m (3H, Me), 2.26 s (3H,
MeCO), 2.52 m and 2.72 m (1H, 1′-HA), 3.54 m and
3.67 m (1H, 1′-HB), 3.27 m and 3.46 m (1H, 2′-H),
5.41 s and 5.47 s (1H, 5-H), 7.58 m (2H, Harom),
8.23 m (2H, Harom), 7.77 br.s (2H, NH2). Found, %:
C 56.42; H 5.31; N 13.10. C15H17N3O5. Calculated, %:
C 56.42; H 5.37; N 13.16.
1-(2-Aminopropyl)-4-benzoyl-3-hydroxy-5-phen-
yl-2,5-dihydro-1H-pyrrol-2-one (Ih). Yield 1.41 g
(42%), mp 254–257°C (from ethanol). IR spectrum, ν,
cm–1: 3236 (OH), 1697 (NC=O), 1635 (C=O). 1H NMR
spectrum (DMSO-d6), δ, ppm: 1.08 m (3H, Me),
2.62 m and 2.90 m (1H, 1′-HA), 3.40 m and 3.64 m
(1H, 1′-HB), 3.22 m (1H, 2′-H), 5.27 s and 5.32 s (1H,
5-H), 7.24 m (2H, Harom), 7.77 m (8H, Harom), 8.18 br.s
(2H, NH2). Mass spectrum, m/z (Irel, %): 336 (2)
[M]+, 293 (28) [M – CH2=CHNH2]+, 208 (9.50)
[PhCH=CHCOPh]+, 105 (50) [PhCO]+, 77 (30.50)
[Ph]+, 57 (6.50) [CH2=C(Me)NH2]+, 44 (100)
[CH2=CHNH3]+. Found, %: C 71.37; H 5.95; N 8.30.
C20H20N2O3. Calculated, %: C 71.41; H 5.99; N 8.33.
1-(2-Aminopropyl)-4-benzoyl-3-hydroxy-5-(3-ni-
trophenyl)-2,5-dihydro-1H-pyrrol-2-one (Il). Yield
1.41 g (37%), mp 240–242°C (the product was recrys-
tallized from ethanol and then treated with hot ace-
tone). IR spectrum, ν, cm–1: 3240 (OH), 1718 (NC=O),
1
1620 (C=O). H NMR spectrum (DMSO-d6–
CF3COOH), δ, ppm: 1.05 m (3H, Me), 2.63 m and
2.84 m (1H, 1′-HA), 3.60 m and 3.75 m (1H, 1′-HB),
3.36 m and 3.51 m (1H, 2′-H), 5.69 s and 5.73 s (1H,
5-H), 7.39 m (2H, Harom), 7.56 m (4H, Harom), 7.79 m
(1H, Harom), 8.11 m (1H, Harom), 8.28 s (1H, Harom),
7.84 br.s (2H, NH2). Found, %: C 62.89; H 4.98;
N 11.00. C20H19N3O5. Calculated, %: C 62.98; H 5.02;
N 11.02.
1-(2-Aminopropyl)-4-benzoyl-5-(4-chlorophen-
yl)-3-hydroxy-2,5-dihydro-1H-pyrrol-2-one (Ii).
Yield 1.52 g (41%), mp 240–242°C (from ethanol). IR
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THREE-COMPONENT REACTION OF METHYL 2,4-DIOXO-4-PHENYLBUTANOATE
881
4-Acetyl-1-(2-aminopropyl)-3-hydroxy-5-phenyl-
2,5-dihydro-1H-pyrrol-2-one hydrochloride (IIa).
Compound Ia, 0.01 mol, was dissolved in 40 ml of
concentrated hydrochloric acid on heating on a boiling
water bath, the solution was evaporated to dryness, and
the residue was recrystallized. Yield 1.77 g (57%),
mp 219–223°C (from ethanol). IR spectrum, ν, cm–1:
3500, 3390 (+NH3), 3180 (OH), 1686 (NC=O), 1630
(C=O). 1H NMR spectrum (DMSO-d6), δ, ppm: 1.03 d
(3H, Me, J = 5.7 Hz), 2.22 s (3H, MeCO), 2.51 m (1H,
1′-H), 3.63 m (1H, 1′-HB), 3.28 m (1H, 2′-H), 5.22 s
rol-2-one hydrochloride (IV). A mixture of 5 mmol of
compound II and 5 mmol of p-dimethylaminoaniline
in 12 ml of glacial acetic acid was heated for 1.5 h
under reflux. The mixture was cooled and evaporated,
and the residue was treated with hexane and recrystal-
lized. Yield 0.52 g (21%), mp 232–236°C (the product
was recrystallized from propan-2-ol and then treated
with hot chloroform). IR spectrum, ν, cm–1: 3470
(+NH3), 3310 (NH), 1688 (NC=O), 1642 (C=O).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.06 m (3H,
Me), 2.55 m and 2.82 m (1H, 1′-HA), 2.73 s (6H,
NMe2), 3.37 m and 3.70 m (1H, 1′-HB), 3.30 m (1H,
2′-H), 5.69 s (1H, 5-H), 6.39 m (2H, Harom), 6.83 d
(2H, Harom, J = 8.4 Hz), 7.16 m (10H, Harom), 8.09 s
+
(1H, 5-H), 7.22 m (5H, Harom), 8.05 br.s (3H, NH3).
Found, %: C 57.94; H 6.12; N 9.02. C15H18N2O3·HCl.
Calculated, %: C 57.97; H 6.16; N 9.02.
+
(3H, NH3), 9.23 s (1H, NH). Found, %: C 68.50;
H 6.30; N 11.38. C28H30N4O2·HCl. Calculated, %:
C 68.49; H 6.36; N 11.41.
1-(2-Aminopropyl)-4-benzoyl-3-hydroxy-5-phen-
yl-2,5-dihydro-1H-pyrrol-2-one hydrochloride (IIb)
was synthesized in a similar way. Yield 2.78 g (75%),
mp 246–249°C (from ethanol). IR spectrum, ν, cm–1:
3440 (+NH3), 3160 (OH), 1695 (NC=O), 1626 (C=O).
1H NMR spectrum (DMSO-d6–CF3COOH), δ, ppm:
1.09 d (3H, Me, J = 6.6 Hz), 2.66 m and 2.92 m (1H,
1′-HA), 3.59 m and 3.75 m (1H, 1′-HB), 3.38 m (1H,
2′-H), 5.54 s and 5.56 s (1H, 5-H), 7.32 m (5H, Harom),
7.41 m (2H, Harom), 7.53 m (1H, Harom), 7.68 m (2H,
Compounds Va–Vc were synthesized in a similar
way.
1-(2-Aminopropyl)-4-[1-(4-metoxyphenylamino)-
ethylidene]-5-phenyltetrahydropyrrole-2,3-dione
hydrochloride (Va). Yield 1.19 g (57%), mp 198–
202°C (from toluene). IR spectrum, ν, cm–1: 3400 br
+
1
+
(NH, NH3), 1700 (NC=O), 1650 (C=O). H NMR
spectrum (DMSO-d6), δ, ppm: 1.07 m (3H, Me), 1.71 s
and 1.72 s (3H, MeC=C), 2.53 m and 2.80 m (1H,
1′-HA), 3.49 m and 3.65 m (1H, 1′-HB), 3.26 m (1H,
2′-H), 3.70 s (3H, MeO), 5.47 s and 5.48 s (1H, 5-H),
Harom), 8.00 br.s (3H, NH3). Found, %: C 64.35;
H 5.65; N 7.44. C20H20 N2O3 ·HCl. Calculated, %:
C 64.42; H 5.68; N 7.52.
1,1′-(Propane-1,2-diyl)bis(4-acetyl-3-hydroxy-5-
phenyl-2,5-dihydro-1H-pyrrol-2-one) (III). A solu-
tion of 0.01 mol of methyl 2,4-dioxopentanoate in
10 ml of 1,4-dioxane was added at room temperature
to a solution of 0.01 mol of benzaldehyde and
0.005 mol of propane-1,2-diamine in 10 ml of 1,4-di-
oxane. The mixture was kept for 24 h at room tempera-
ture, and the precipitate was filtered off and purified by
recrystallization. Yield 0.67 g (28%), mp >300°C
(from glacial acetic acid). IR spectrum, ν, cm–1: 3160
6.91 m (2H, Harom), 7.14 m (2H, Harom), 7.34 m (5H,
+
H
arom), 8.10 s (3H, NH3), 12.44 s (1H, NH). Found,
%: C 63.50; H 6.28; N 10.04. C22H25N3O3·HCl. Cal-
culated, %: C 63.53; H 6.30; N 10.10.
1-(2-Aminopropyl)-4-[1-(4-ethoxyphenylamino)-
ethylidene]-5-phenyltetrahydropyrrole-2,3-dione
(Vb). Yield 0.24 g (12%), mp 151–155°C (the product
was recrystallized from acetonitrile and then treated
with hot toluene). IR spectrum, ν, cm–1: 3500 (NH2),
1
(OH), 1685 (NC=O), 1650 (C=O). H NMR spectrum
1
3300 (NH), 1700 (NC=O), 1640 (C=O). H NMR
(DMSO-d6), δ, ppm: 1.02 d (3H, Me, J = 7.0 Hz),
2.22 s and 2.24 s (3H, MeCO), 2.26 s and 2.28 s (3H,
MeCO), 2.73 m and 3.49 m (1H each, CH2), 3.71 m
(1H, CHMe), 4.68 s and 4.79 s (1H, 5-H), 5.15 s and
5.23 s (1H, 5-H), 7.12 m (4H, Harom), 7.21 m (6H,
spectrum (DMSO-d6), δ, ppm: 0.83 d (3H, Me, J =
6.0 Hz), 1.25 m (3H, CH3CH2), 1.70 s (3H, MeC=C),
2.34 m (1H, 1′-HA), 3.32 m (1H, 1′-HB), 2.97 m (1H,
2′-H), 3.95 m (2H, OCH2), 5.42 s (1H, 5-H), 6.87 d
(2H, Harom, J = 7.5 Hz), 7.22 m (7H, Harom). Mass spec-
trum, m/z (Irel, %): 393 (19.90) [M]+, 350 (28.68) [M –
CH2=CHNH2]+, 137 (56.09) [4-EtOC6H4NH2]+, 108
(100) [p-O=C6H4=NH2]+. Found, %: C 70.18; H 6.89;
N 10.64. C23H27N3O3. Calculated, %: C 70.20; H 6.92;
N 10.68.
H
arom). Mass spectrum, m/z (Irel, %): 474 (9.68) [M]+,
244 (38. 80) [AcC4NO2(Ph)Et]+, 173 (100)
[M e C H = N C H ( P h ) C H = C O ] + , 1 3 1 ( 6 8 . 0 6)
[PhCH=CHCO]+, 77 (5.61) [Ph]+, 56 (8.08) [CH2=C-
(Me)N]+. Found, %: C 68.30; H 5.46; N 5.90.
C27H26N2O6. Calculated, %: C 68.34; H 5.52; N 5.91.
1-(2-Aminopropyl)-4-benzoyl-3-[4-(dimethyl-
amino)phenylamino]-5-phenyl-2,5-dihydro-1H-pyr-
1-(2-Aminopropyl)-4-[1-(4-ethoxyphenylamino)-
ethylidene]-5-phenyltetrahydropyrrole-2,3-dione
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

GEIN et al.
882
1
hydrochloride (Vc). Yield 1.59 g (74%), mp 242–
244°C (from propan-2-ol). IR spectrum, ν, cm–1: 3400
(+NH3), 3200 (NH), 1710 (NC=O), 1630 (C=O).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.05 m (3H,
Me), 1.26 m (3H, CH3CH2), 1.71 s and 1.72 s (3H,
MeC=C), 2.52 m (1H, 1′-HA), 3.65 m (1H, 1′-HB),
3.30 m (1H, 2′-H), 3.96 m (2H, OCH2), 5.45 s and
treated with hot ethanol). H NMR spectrum
(DMSO-d6), δ, ppm: 0.91 m (3H, Me), 1.97 s (3H,
MeC=N), 2.59 m and 3.41 m (1H each, 5-CH2), 2.98 m
(1H, CH2CH), 3.70 s (3H, MeO), 5.50 d (1H, 4-H),
6.82 m (2H, Harom), 7.01 m (2H, Harom), 7.61 br.s (2H,
NH2). Found, %: C 63.93; H 6.70; N 18.59.
C16H20N4O2. Calculated, %: C 63.98; H 6.71; N 18.65.
5.46 s (1H, 5-H), 6.88 m (2H, Harom), 7.11 m (2H,
5-(2-Aminopropyl)-3-methyl-1,4-diphenyl-4,5-di-
hydropyrrolo[3,4-c]pyrazol-6(1H)-one (VIIc). Yield
0.40 g (23%), mp 143–147°C (from diethyl ether). IR
+
Harom), 7.32 m (5H, Harom), 8.02 s (3H, NH3), 12.43 s
(1H, NH). Found, %: C 64.20; H 6.53; N 9.71.
C23H27N3O3 ·HCl. Calculated, %: C 64.25; H 6.56;
N 9.77.
1
spectrum, ν, cm–1: 3460 (NH2), 1685 (C=O). H NMR
spectrum (DMSO-d6), δ, ppm: 1.01 m (3H, Me), 2.04 s
(3H, MeC=N), 2.60 m and 3.10 m (1H each, 5-CH2),
3.60 m (1H, 5-CH2CH), 5.77 d (1H, 4-H), 7.27 m
(4H, Harom), 7.38 m (4H, Harom), 7.45 m (2H, Harom),
8.29 br.s (2H, NH2). Found, %: C 72.79; H 6.35;
N 16.10. C21H22N4O. Calculated, %: C 72.80; H 6.40;
N 16.17.
1-(2-Aminopropyl)-5-phenyl-4-(1-phenylhydra-
zinoethyl)pyrrole-2,3-dione hydrochloride (VI).
A solution of 5 mmol compound IIa in 30 ml of
ethanol was heated to the boiling point, 5.5 mmol of
phenylhydrazine was added, the mixture was kept for
24 h at room temperature, and the precipitate was
filtered off and recrystallized. Yield 0.28 g (14%),
mp 299–304°C (from ethanol). IR spectrum, ν, cm–1:
3440 (+NH3), 3255 (NH), 1678 (C=O, NC=O).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.05 d (3H,
Me, J = 6.0 Hz), 1.29 s (3H, MeC=N), 2.52 m (1H,
1′-HA), 3.58 m (1H, 1′-HB), 3.30 m (1H, 2′-H), 4.04 d
(1H, 5-H, J = 9.9 Hz), 5.15 d (1H, 4-H, J = 9.3 Hz),
6.76 t (1H, Harom, J = 7.2 Hz), 7.12 m (2H, Harom),
7.30 m (5H, Harom), 7.59 d (2H, Harom, J = 7.8 Hz),
5-(2-Aminopropyl)-3-methyl-1,4-diphenyl-4,5-di-
hydropyrrolo[3,4-c]pyrazol-6(1H)-one hydrochlo-
ride (VIId). Yield 1.51 g (79%), mp >300°C (from
propan-2-ol). IR spectrum, ν, cm–1: 3460 (+NH3), 1685
(C=O). 1H NMR spectrum (DMSO-d6), δ, ppm: 1.14 d
(3H, Me), 2.01 s (3H, MeC=N), 2.80 m and 3.84 m
(1H each, 5-CH2), 3.43 m (1H, 5-CH2CH), 5.79 s (1H,
4-H), 7.34 m (3H, Harom), 7.42 m (3H, Harom), 7.53 t
(2H, Harom, J = 7.2 Hz), 8.21 d (2H, Harom, J = 7.8 Hz),
+
+
8.00 br.s (3H, NH3). Found, %: C 62.82; H 6.26;
7.92 br.s (3H, NH3). Found, %: C 65.83; H 6.07;
N 13.92. C21H24N4O2·HCl. Calculated, %: C 62.91;
H 6.29; N 13.98.
N 14.59. C21H22N4O·HCl. Calculated, %: C 65.87;
H 6.05; N 14.63.
5-(2-Aminopropyl)-4-(4-chlorophenyl)-3-methyl-
4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (VIIa).
A mixture of 5 mmol of compound Ic and 5.5 mmol of
98% hydrazine in 5 ml of glacial acetic acid was
heated for 1.5 h under reflux. The mixture was cooled
and evaporated, and the residue was treated with hex-
ane and recrystallized. Yield 0.38 g (25%), mp >300°C
5-(2-Aminopropyl)-3,4-diphenyl-4,5-dihydropyr-
rolo[3,4-c]pyrazol-6(1H)-one (VIIe). Yield 0.90 g
(54%), mp 172–177°C (from acetonitrile). IR spec-
trum, ν, cm–1: 1685 (C=O), 3280 (NH), 3350 (NH2).
1H NMR spectrum (DMSO-d6), δ, ppm: 0.85 m (3H,
Me), 2.40 m and 3.41 m (1H each, 5-CH2), 2.94 m
(1H, 5-CH2CH), 5.93 s and 5.96 s (1H, 4-H), 7.24 m
(8H, Harom), 7.42 m (2H, Harom). Mass spectrum, m/z
(Irel, %): 332 (3.84) [M]+, 289 (48.47) [M –
CH2=CHNH2]+, 260 (100) [M – CH3CH=NH2 + N2]+,
77 (13.26) [Ph]+, 57 (4.49) [CH2=C(Me)NH2]+. Found,
%: C 72.27; H 6.00; N 16.84. C20H20N4O. Calculated,
%: C 72.26; H 6.06; N 16.86.
1
(from acetonitrile). H NMR spectrum (DMSO-d6), δ,
ppm: 0.89 m (3H, Me), 1.94 s (3H, MeC=N), 2.56 m
and 3.38 m (1H each, 5-CH2), 3.04 m (1H, 5-CH2CH),
5.61 d (1H, 4-H), 7.16 m (2H, Harom), 7.38 m (2H,
H
arom). Found, %: C 59.07; H 5.60; N 18.36.
C15H16N4O·HCl. Calculated, %: C 59.11; H 5.62;
N 18.38.
5-(2-Aminopropyl)-3,4-diphenyl-4,5-dihydropyr-
rolo[3,4-c]pyrazol-6(1H)-one hydrochloride (VIIf).
Yield 0.42 g (23%), mp 230–234°C (from ethanol). IR
spectrum, ν, cm–1: 3430 (+NH3), 3210 (NH), 1710
(C=O). 1H NMR spectrum (DMSO-d6), δ, ppm: 1.08 d
(3H, Me, J = 5.7 Hz), 2.63 m and 3.73 m (1H each,
5-CH2), 3.31 m (1H, 5-CH2CH), 5.97 s (1H, 4-H),
Compounds VIIb–VIIi and VIII were synthesized
in a similar way.
5-(2-Aminopropyl)-4-(4-methoxyphenyl)-3-
methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one
(VIIb). Yield 0.74 g (49%), mp 59–62°C (the
product was recrystallized from acetonitrile and then
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THREE-COMPONENT REACTION OF METHYL 2,4-DIOXO-4-PHENYLBUTANOATE
883
7.27 m (8H, Harom), 7.42 d (2H, Harom, J = 6.6 Hz),
(1H each, 5-CH2), 3.43 m (1H, 5-CH2CH), 6.14 s (1H,
+
8.00 s (1H, NH3), 14.08 br.s (1H, N1H). Found, %:
4-H), 7.33 m (9H, Harom), 7.55 m (4H, Harom), 8.29 m
+
C 65.08; H 5.68; N 15.19. C20H20N4O·HCl. Calculat-
ed, %: C 65.12; H 5.74; N 15.19.
(2H, Harom), 8.07 br.s (3H, NH3). Mass spectrum, m/z
(Irel, %): 408 (6.40) [M – HCl]+, 365 (100) [M – (HCl +
CH2=CHNH2)]+, 336 (39. 67) [M – (HCl +
CH3CH=NH2 + N2)]+, 77 (33.21) [Ph]+. Found, %:
C 70.12; H 5.64; N 12.59. C26H24N4O·HCl. Calculat-
ed, %: C 70.18; H 5.66; N 12.59.
5-(2-Aminopropyl)-4-(4-chlorophenyl)-3-phenyl-
4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (VIIg).
Yield 0.94 g (51%), mp 135–139°C (from acetonitrile).
1H NMR spectrum (DMSO-d6), δ, ppm: 0.96 m (3H,
Me), 2.60 m and 3.38 m (1H each, 5-CH2), 2.98 m
(1H, 5-CH2CH), 5.98 d (1H, 4-H), 7.27 m (5H, Harom),
7.36 m (2H, Harom), 7.42 m (2H, Harom). Found, %:
C 65.46; H 5.20; N 15.21. C20H18N4O·HCl. Calculat-
ed, %: C 65.48; H 5.22; N 15.27.
X-Ray analysis of compound VIIe. Compound
VIIe crystallized as well defined extended prisms;
C20H20N4O, M 332.40; monoclinic crystal system; unit
cell parameters: a = 5.604(1), b = 17.543(4), c =
17.264(3) Å; β = 90.97(3)°; V = 1697.0(6) Å3; dcalc
=
1.301 g/cm3; Z = 4; space group P2(1)/n. Experimental
reflection intensities were measured on a KM-4 (Kuma
Diffraction) automatic four-circle diffractometer with
χ-geometry [monochromatized MoKα irradiation, ω/2Θ
scanning, 2Θmax = 50.14° (99.6%)]. Total of 3337 re-
flections were measured, 3010 of which were inde-
pendent (Rint = 0.0375). No correction for absorption
was introduced (μ = 0.083 mm–1). The structure was
solved by the direct method using SIR92 program [4],
followed by a series of calculations of electron density
maps. The positions of hydrogen atoms were set on the
basis of geometry considerations. The positions of
non-hydrogen atoms were refined by the least-squares
procedure in full-matrix anisotropic approximation
using SHELXL-97 software package [5]; the final di-
vergence factors were R1 = 0.0646 [for 1738 reflec-
tions with I ≥ 2σ(I)] and 0.1366 (for all reflections);
goodness of fit 0.968.
5-(2-Aminopropyl)-4-(4-methoxyphenyl)-3-
phenyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one
(VIIh). Yield 0.69 g (38%), mp 153–158°C (from
acetonitrile). IR spectrum, ν, cm–1: 3350 (NH2), 3200
1
(NH), 1690 (C=O). H NMR spectrum (DMSO-d6–
CF3COOH), δ, ppm: 1.05 m (3H, Me), 2.67 m and
2.87 m (1H, 5-CHA), 3.37 m and 3.60 m (1H, 5-CHB),
3.20 m (1H, 5-CH2CH), 3.67 s (3H, MeO), 5.84 s and
5.87 s (1H, 4-H), 6.86 m (2H, Harom), 7.23 m (5H,
Harom), 7.41 m (2H, Harom), 7.78 br.s (2H, NH2). Found,
%: C 69.60; H 6.08; N 15.40. C21H22N4O2. Calculated,
%: C 69.59; H 6.12; N 15.46.
5-(2-Aminopropyl)-4-(3-nitrophenyl)-3-phenyl-
4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (VIIi).
Yield 1.13 g (60%), mp 179–182°C (from acetonitrile).
IR spectrum, ν, cm–1: 3400 (NH2), 3290 (NH), 1700
1
(C=O). H NMR spectrum (DMSO-d6–CF3COOH), δ,
ppm: 1.11 m (3H, Me), 2.66 m and 2.93 m (1H,
5-CHA), 3.70 m and 3.82 m (1H, 5-CHB), 3.28 m and
3.48 d.m (1H, 5-CH2CH), 6.22 s and 6.25 s (1H, 4-H),
7.31 m (3H, Harom), 7.47 m (2H, Harom), 7.66 m (2H,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-96042).
H
arom), 8.18 m (1H, Harom), 8.31 s (1H, Harom), 7.85 br.s
REFERENCES
(2H, NH2). Mass spectrum, m/z (Irel, %): 377 (16.67)
[M]+, 359 (4.30) [M – H2O]+, 334 (100) [M –
CH2=CHNH2]+, 305 (92.55) [M – CH3CH=NH2 + N2]+,
77 (43.75) [Ph]+, 57 (27.74) [CH2C(Me)NH2]+. Found,
%: C 63.59; H 5.05; N 18.52. C20H19N5O3. Calculated,
%: C 63.65; H 5.07; N 18.56.
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2005, vol. 75, p. 254.
2. Khan, M.S.Y. and Gupta, M., Pharmazie, 2002, vol. 57,
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va, R.F., Gein, L.F., Ugrak, B.I., and Andreichikov, Yu.S.,
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5-(2-Aminopropyl)-2,3,4-triphenyl-4,5-dihydro-
pyrrolo[3,4-c]pyrazol-6(2H)-one hydrochloride
(VIII). Yield 0.67 g (30%), mp >300°C (the product
was recrystallized from DMF and was then treated
with hot ethanol). IR spectrum, ν, cm–1: 3500 (+NH3),
4. Altomare, A., Cascarano, G., Giacovazzo, C., and Gua-
lardi, A., J. Appl. Crystallogr., 1993, vol. 26, p. 343.
5. Sheldrick, G.M., SHELX97. Programs for Crystal Struc-
ture Analysis, Göttingen, Germany: Univ. Göttingen,
1998.
1
1675 (C=O). H NMR spectrum (DMSO-d6), δ, ppm:
1.12 d (3H, Me, J = 6.6 Hz), 2.67 m and 3.78 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010