4,5-Dihydroxyimidazolidin-2-ones in α-ureidoalkylation of N-carboxyalkyl-, N-hydroxyalkyl-, and N-(aminoalkyl)ureas 4.* α-Ureidoalkylation of N-(2-acetylaminoethyl)ureas

Article abstract of DOI:10.1007/s11172-010-0117-0

α-Ureidoalkylation of N-(2-acetylaminoethyl)ureas with various 4,5-dihydroxyimidazoli- din-2-ones was systematically studied. Novel N-(2-acetylaminoethyl)glycolurils were obtained. Their yields were found to decrease both when moving from 1,3-H₂- to 1,3-Alk₂-4,5- dihydroxy- imidazolidin-2-ones and when increasing the size of the substituent at the second N atom in the starting acetylaminoethylurea. The higher yields were achieved with 4,5-diphenyl-4,5- dihydroxyimidazolidin-2-one as the starting compound. 2-(2-Acetylaminoethyl)-4-methylgly- coluril exhibits nootropic activity.

Full text of DOI:10.1007/s11172-010-0117-0

Russian Chemical Bulletin, International Edition, Vol. 59, No. 3, pp. 642—646, March, 2010
642
4,5ꢀDihydroxyimidazolidinꢀ2ꢀones in αꢀureidoalkylation
of Nꢀcarboxyalkylꢀ, Nꢀhydroxyalkylꢀ, and Nꢀ(aminoalkyl)ureas
4.* αꢀUreidoalkylation of Nꢀ(2ꢀacetylaminoethyl)ureas
G. A. Gazieva, P. V. Lozhkin, V. V. Baranov, A. N. Kravchenko, and N. N. Makhova
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: gaz@server.ioc.ac.ru
αꢀUreidoalkylation of Nꢀ(2ꢀacetylaminoethyl)ureas with various 4,5ꢀdihydroxyimidazoliꢀ
dinꢀ2ꢀones was systematically studied. Novel Nꢀ(2ꢀacetylaminoethyl)glycolurils were obtained.
Their yields were found to decrease both when moving from 1,3ꢀH2ꢀ to 1,3ꢀAlk2ꢀ4,5ꢀdihydroxyꢀ
imidazolidinꢀ2ꢀones and when increasing the size of the substituent at the second N atom in
the starting acetylaminoethylurea. The higher yields were achieved with 4,5ꢀdiphenylꢀ4,5ꢀ
dihydroxyimidazolidinꢀ2ꢀone as the starting compound. 2ꢀ(2ꢀAcetylaminoethyl)ꢀ4ꢀmethylglyꢀ
coluril exhibits nootropic activity.
Key words: αꢀureidoalkylation, Nꢀcarbamoylation, Nꢀ(2ꢀacetylaminoethyl)glycolurils,
4,5ꢀdihydroxyimidazolidinꢀ2ꢀones, Nꢀ(2ꢀacetylaminoethyl)ureas.
Glycolurils (2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ
3,7ꢀdiones) constitute a new class of neurotropic comꢀ
pounds.2—5 The diurnal tranquilizepr mebicar (2,4,6,8ꢀ
tetramethylꢀ2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ3,7ꢀdiꢀ
one) has been introduced into medical practice in Russia.2
The mechanism of action of mebicar remains unclear;
its effect on the GABAergic system is assumed.6 GABAerꢀ
gic effects also underlie the action of nootropics.7 The
electronic features of piracetam (nootropil) and GABA
(gammaꢀaminobutyric acid) are somewhat similar with
consideration to the zwitterionic nature of the latter.8
Ureas 3a—c were prepared by Nꢀcarbamoylation of
Nꢀacetylethylenediamine with potassium cyanate or
methyl(phenyl) isocyanate (Scheme 1) as described for
the carbamoylation of Nꢀsubstituted ethylenediamines.9,10
However, in contrast to the published procedures,9,10 all
reactions were carried out in aqueous solutions.
Scheme 1
A glycoluril molecule (e.g., 1 and 2) can be modified in
a similar way by creating a partial or integer positive charge
on the amino group of a substituent as in piracetam
and GABA.
The synthesis of Nꢀ(2ꢀdimethylaminoethyl)glycoluril
hydrochlorides 1 from 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones
and Nꢀ(2ꢀdimethylaminoethyl)urea hydrochloride has
been described previously.1 The present study is devoted to
αꢀureidoalkylation of Nꢀ(2ꢀacetylaminoethyl)ureas 3a—c
with 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones (DHI) 4a—d as a
route to Nꢀ(2ꢀacetylaminoethyl)glycolurils 2a—h.
R = Me (b), Ph (c)
* For Part 3, see Ref. 1.
i. H2O, HCl (pH 1), reflux, 15 min; ii. H2O, 30 min
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 628—632, March, 2010.
1066ꢀ5285/10/5903ꢀ0642 © 2010 Springer Science+Business Media, Inc.

αꢀUreidoalkylation of (2ꢀacetylaminoethyl)ureas
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
643
Scheme 2
Comꢀ
pound
2a
2b
2c
R1
R2
R3
Comꢀ
pound
2f
2g
2h
R1
R2
R3
Comꢀ
pound
4a
4b
4c
R1
R2
Comꢀ
pound
5a
5b
5c
R1
R2
H
H
H
H
H
H
H
H
Me
Me
H
Me
Ph
H
H
H
Ph
H
Me
Et
Me
H
Ph
H
H
H
H
H
H
Me
Et
H
H
H
H
Me
Et
2d
2e
6a
Me
4d
Ph
Me
Me
The target glycolurils 2a—h were obtained by cycloꢀ
condensation of ureas 3a—c with DHI 4a—d (Scheme 2)
in hot water, methanol, aqueous propanꢀ2ꢀol, or aqueous
methanol, depending on the solubilities of the reagents
and the products at pH 1. The reaction time was varied
from 1 to 2.5 h.
phenylꢀDHI 4d with urea 3a gave the corresponding glyꢀ
coluril 2h in 65—67% yield. Apparently, the phenyl subꢀ
stituents stabilize the carbocations in situ generated from
the starting DHI upon its dehydration,13 which makes the
reaction with urea more probable than the rearrangement14
into the corresponding hydantoin.
The dependence of the yields of glycolurils 2 on the
reaction time τ was studied with DHI 4a and urea 3b as
the starting reagents. We found that the yield of comꢀ
pound 2b is 44% (1 h), 43% (1.5 h), and 27% (2 h). With
an increase in the time of the reaction of DHI 4a with urea
3c, the yield of glycoluril 2c decreases from 42% (1.5 h) to
Compounds 2a—h are white hygroscopic powders.
When dried over CaCl2, all of them allow satisfactory eleꢀ
mental analysis. Glycolurils 2b and 2f contain water of
1
crystallization. Structures 2a—h were proved by H and
1
13C NMR spectroscopy (Table 2). The H NMR spectra
of the compounds obtained show singlets for the acetyl
protons at δ 1.7—1.8, signals for the ethylene fragment at
δ 2.7—3.5, two doublets (AB system) of the bridgehead
CH—CH protons at δ 5.0—6.0, and signals for the NH
protons in the acetamide fragments at δ 7.8—8.5. The
13C NMR spectra exhibit signals for the methyl groups at
δ 22.3—23.0 (COMe), the CH2 groups at δ 35.5—37.9 and
40.0—42.7, the bridgehead CH atoms at δ 62.3—70.1 and
66.2—71.9 (or the bridgehead CPh atoms at δ 82.5 and
87.6), and the CO groups at δ 155.2—159.4, 158.9—161.6,
and 169.3—170.5. The 1H NMR spectrum of glycoluril 6a
does not contain the signals for the NH and COMe proꢀ
tons of the acetamide fragment.
1
26% (2 h) and 19% (2.5 h). According to the H NMR
spectra of the dryꢀevaporated reaction mixtures, the reacꢀ
tion gives not only the target products 2a—g but also
known11,12 hydantoins 5a—c via dehydration of DHI
4a—c. At τ > 1.5 h, the reaction mixtures contain an
increased fraction of hydantoins and some amount of
Nꢀdeacylated aminoethylglycolurils; one of them (6a) was
isolated and characterized. That is why the reaction time
should not exceed 1—1.5 h and DHI 4a—c should be used
in small excess.
The yields of the target glycolurils also decrease at
a reaction temperature above 80 °C (because of the formaꢀ
tion of the corresponding hydantoin) and with an increase
in the amount of hydrochloric acid, which favors the forꢀ
mation of deacylated aminoethylglycolurils.
While comparing the yield of glycoluril 2a (49—52%,
Table 1) with the yields of compounds 2d (39—41%) and
2g (18—20%) or 2b (43—45%) and 2c (40—42%), one can
conclude that the yields of the glycolurils decrease in the
presence of Nꢀalkyl substituents in DHI 4a—c (cf. 2a,d,g)
and, to a lesser degree, in the presence of a bulky substituꢀ
ent at the second N atom of the starting Nꢀ(2ꢀacetylꢀ
aminoethyl)ureas 3b,c (cf. 2a,b,c). A reaction of 4,5ꢀdiꢀ
The nootropic effect of 2ꢀ(2ꢀacetylaminoethyl)ꢀ4ꢀ
methylglycoluril 2b was examined with mice at the Instiꢀ
tute of Technical Chemistry (Ural Division of the Russian
Academy of Sciences). Compound 2b proved to be superiꢀ
or to piracetam in nootropic activity*.
Thus, when studying αꢀureidoalkylation of 4,5ꢀdihydrꢀ
oxyimidazolidinꢀ2ꢀones with Nꢀ(2ꢀacetylaminoethyl)ꢀ
* Comparative quantitative data on the nootropic activities of
2ꢀ(2ꢀacetylaminoethyl)ꢀ4ꢀmethylglycoluril and piracetam will
be published elsewhere.

644
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Gazieva et al.
Table 1. Yields, melting points, and elemental analysis data for compounds 2a—h, 3a—c, and 6a
Comꢀ
pound
Yield
(%)
Tm/°C
(solvent)
Found
Molecular
formula
(%)
Calculated
C
H
N
2a
49—52
43—45
40—42
39—41
237—239
(H2O—MeOH, 1 : 1)
126—128
(dioxane)
215—217
(H2O—PriOH, 1 : 2)
142—144
42.25
42.29
41.71
41.69
55.49
55.44
47.08
47.05
48.97
49.06
5.74
5.77
6.68
6.61
5.67
5.65
6.69
6.71
7.25
7.16
30.87
30.82
26.93
27.01
23.06
23.09
27.41
27.44
26.08
26.01
C8H13N5O3
2b•H2O
C9H15N5O3•H2O
C14H17N5O3
2c
2d
2e
C10H17N5O3
(dioxane)
127—130
(acetone)
34—36
(Ref.20: 34)
C11H19N5O3
(Ref.20: 127—130)
189—191
2f•0.5H2O
14—16
18—20
65—67
50—52
56.41
56.46
50.83
50.87
64.91
64.85
41.40
41.37
45.28
45.27
6.43
6.51
7.49
7.46
6.22
6.18
7.67
7.64
8.27
8.23
20.63
20.57
24.70
24.72
17.24
17.19
28.91
28.95
26.36
26.40
C16H21N5O3•0.5H2O
C12H21N5O3
(dioxane)
151—153
(ethyl acetate)
265—267
(acetone)
133—135
(methanol)
155—157
(acetone)
(Ref.20: 155—157)
189—191
(ethanol)
(Ref.10: 191)
>300 (methanol)
2g
2h
3a
3b
C22H25N5O3
C5H11N3O2
74—76
(Ref.20: 76)
C6H13N3O2
3c
6a
81—83
8
60.52
60.54
5.51
5.54
19.29
19.25
C11H12N3O2
35.62
35.67
6.04
5.99
29.66
29.72
C7H14ClN5O2
30 min without heating. On cooling, the mixture was acidified
with conc. HCl to pH 1, the solvent was removed on a rotary
evaporator, and the product was extracted from the residue with
methanol. The precipitate of KCl was filtered off and the filtrate
was concentrated on a rotary evaporator to 1/4 of its initial volꢀ
ume and cooled. The precipitate of urea 3a that formed overꢀ
night was filtered off and recrystallized from methanol.
ureas, we found out how the yields of earlier unknown
Nꢀ(2ꢀacetylaminoethyl)glycolurils depend on the reaction
time, the presence of substituents at the N and C atoms
of 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones, and the size of the
substituent at the second N atom of Nꢀ(2ꢀacetylaminoꢀ
ethyl)ureas.
Synthesis of Nꢀ(2ꢀacetylaminoethyl)ꢀN´ꢀmethylurea (3b) and
Nꢀ(2ꢀacetylaminoethyl)ꢀN´ꢀphenylurea (3c) (general procedure).
Methyl or phenyl isocyanate (0.1 mol) was added dropwise in
0.2ꢀmL portions to an iceꢀcooled solution of Nꢀacetylethyleneꢀ
diamine (10.2 g, 0.1 mol) in water (5 mL). After the addition was
completed, the reaction mixture was stirred at room temperaꢀ
ture for 30 min. The precipitate of urea 3b that formed was
filtered off, washed with a small portion of acetone, and recrysꢀ
tallized from boiling acetone. The precipitate of urea 3c was
filtered off, washed repeatedly with water, and recrystallized
from ethanol.
Synthesis of glycolurils 2a—h (general procedure). An approꢀ
priate DHI 4a—d (10.1 mmol) and an appropriate urea (10 mmol)
were dissolved in water (10 mL) (for 2a,d,e,g), water—propanꢀ
2ꢀol (2 : 3, 10 mL) (2b,f), water—methanol (3 : 2, 15 mL) (2c),
or methanol (20 mL) (2h) with stirring and heating to 50 °C. The
resulting solution was acidified with conc. HCl to pH 1 and
stirred at 80 °C (or in boiling methanol) for 1 (for 2a,b,g) or 1.5 h
Experimental
NMR spectra were recorded on Bruker AMꢀ250 (250.13 MHz
(1H)) and Bruker AMꢀ300 spectrometers (300.13 (1H) and
1
75.5 MHz (13C)) in DMSOꢀd6. H and 13C chemical shifts are
given on the δ scale with respect to Me4Si as the internal stanꢀ
dard. Melting points were determined on a GALLENKAMP
instrument (Sanyo). Acetylethylenediamine and DHI were preꢀ
pared according to known procedures from ethylenediamine and
ethyl acetate16 and from glyoxal (diphenylglyoxal) and ureas,17—20
respectively.
Nꢀ(2ꢀAcetylaminoethyl)urea (3a). Concentrated HCl was
gradually added to an iceꢀcooled solution of freshly prepared
Nꢀacetylethylenediamine (10.2 g, 0.1 mol) in water (5 mL) to
pH 1. Then KOCN (8.1 g, 0.1 mol) was added in small portions
with stirring. After the addition was completed, the reaction
mixture was refluxed for 15 min and stirred for an additional

αꢀUreidoalkylation of (2ꢀacetylaminoethyl)ureas
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
645
Table 2. 1H and 13C NMR spectra of compounds 2a—d,f—h*, 3a—c, and 6a
Comꢀ
pound
1H (DMSOꢀd6), δ (J/Hz)
13C (DMSOꢀd6), δ
2a
1.78 (s, 3 Н, СОМе); 2.93—3.31 (m, 4 Н, 2 СН2); 5.18, 5.31
(both d, 1 Н, СН, J = 8.1); 7.25, 7.30, 7.39, 7.84 (all br.s,
1 Н, NH)
22.65 (COМе), 36.65 (СН2), 40.01 (СН2), 62.33
(СН), 67.74 (СН), 159.36 (СО), 161.15 (СО),
169.44 (СО)
2b
1.77 (s, 3 Н, СОМе); 2.63 (s, 3 Н, NМе); 2.93—3.11 (m, 2 Н,
2 СН2); 3.12—3.32 (m, 2 Н, СН2); 5.10, 5.27 (both d, 1 Н, СН,
J = 8.1); 7.49, 7.56 (both br.s, 1 Н, NH); 7.86 (t, 1 Н, NH,
J = 5.1)
22.86 (COМе), 28.05 (NMe), 37.08 (СН2), 41.00
(СН2), 66.16 (СН), 67.93 (СН), 158.36 (СО),
161.61 (СО), 170.52 (СО)
2c
1.78 (s, 3 Н, СОМе); 3.05—3.30 (m, 4 Н, 2 СН2); 5.41, 5.82
(both d, 1 Н, СН, J = 8.3); 7.05 (t, 1 Н, pꢀPh, J = 7.3); 7.31
(t, 2 Н, mꢀPh, J = 7.9); 7.55 (d, 2 Н, oꢀPh, J = 7.9); 7.71,
7.87, 7.92 (all br.s, 1 Н, NH)
22.61 (COМе), 36.21 (СН2), 40.70 (СН2), 65.11
(СН), 66.24 (СН), 118.48 (oꢀPh), 122.73 (mꢀPh),
128.73 (pꢀPh), 138.66 (Ph), 155.17 (СО), 161.11
(СО), 169.53 (СО)
2d
2f
1.78 (s, 3 Н, СОМе); 2.64 (s, 3 Н, NМе); 2.82 (s, 3 Н, NМе);
2.98—3.39 (m, 4 Н, 2 СН2); 5.06, 5.22 (both d, 1 Н, СН, J = 8.3); (СН2), 41.38 (СН2), 65.65 (СН), 71.31 (СН),
7.65 (br.s, 1 Н, NH); 7.97 (t, 1 Н, NH, J = 5.1)
22.59 (COМе), 27.81 (NMe), 30.14 (NMe), 36.79
158.25 (СО), 159.51 (СО), 169.52 (СО)
1.78 (s, 3 Н, СОМе); 2.46 (s, 3 Н, NМе); 2.89 (s, 3 Н, NМе);
22.97 (COМе), 30.54 (NMe), 30.64 (NMe), 37.00
3.18—3.34 (m, 4 Н, 2 СН2); 5.39, 6.00 (both d, 1 Н, СН, J = 8.5); (СН2), 42.67 (СН2), 69.74 (СН), 70.04 (СН),
7.17 (t, 1 Н, pꢀPh, J = 7.3); 7.38 (t, 2 Н, Phꢀm, J = 7.7); 7.49
(d, 2 Н, Phꢀo, J = 7.7); 8.04 (t, 1 Н, NH, J = 4.8)
123.21 (oꢀPh), 125.25 (mꢀPh), 129.27 (pꢀPh), 138.71
(Ph), 156.49 (СО), 158.87 (СО), 170.06 (СО)
2g
2h
1.04 (m, 6 H, 2 Me); 1.79 (s, 3 Н, СОМе); 2.95—3.25 (m, 6 Н,
3 NСН2); 3.29—3.50 (m, 8 Н, 4 NСН2); 5.18 (dd, 1 Н, СН,
J = 8.3, J = 1.9); 5.37 (d, 1 Н, СН, J = 8.3); 7.67 (s, 1 Н, NH);
7.97 (t, 1 Н, NH, J = 5.4)
12.91 (Me), 13.02 (Me), 22.53 (COМе), 35.53
(СН2), 36.74 (СН2), 37.10 (СН2), 41.28 (СН2),
63.79 (СН), 68.68 (СН), 157.42 (СО), 159.50
(СО), 169.44 (СО)
1.74 (s, 3 Н, COMe); 2.61 (s, 3 H, NMe); 2.86 (s, 3 H, NMe);
2.77—2.91 (m, 1 Н, СН2); 3.21—3.38 (m, 3 Н, СН2); 6.79 (m,
2 Н, Ph); 6.89 (m, 2 Н, Ph); 7.09 (m, 6 Н, Ph); 7.95 (br.s, 1 Н,
NH); 8.52 (s, 1 H, NH)
22.33 (COМе), 26.13 (NMe), 27.75 (NMe), 37.91
(СН2), 42.05 (СН2), 82.48 (СPh), 87.64 (СPh),
127.22, 127.90, 128.04, 128.14, 128.20, 128.39,
132.84, 134.64 (all Ph), 158.42 (СО), 159.52 (СО),
169.32 (СО)
3a
3b
1.78 (s, 3 Н, СОМе); 2.98—3.05 (m, 4 Н, 2 СН2); 5.49 (s, 2 Н,
NH2); 5.99 (br.s, 1 Н, NH); 7.89 (br.s, 1 Н, NH)
—
1.79 (s, 3 Н, СОМе); 2.55 (s, 3 Н, NМе); 2.97—3.07 (m, 4 Н,
2 СН2); 5.81 (m, 1 Н, NH); 5.95 (br.s, 1 Н, NH); 7.87 (t, 1 Н,
NH, J = 4.8)
—
3c
6a
1.81 (s, 3 Н, СОМе); 3.12 (br.s, 4 Н, 2 СН2); 6.17 (br.s, 1 Н,
NH); 6.88 (t, 1 Н, pꢀPh, J = 7.0); 7.21 (t, 2 Н, mꢀPh, J = 7.8);
7.39 (d, 2 Н, oꢀPh, J = 7.8); 7.94 (br.s, 1 Н, NH); 8.54 (s, 1 H,
NH)
—
—
2.62 (s, 3 Н, NМе); 2.99—3.14 (m, 2 Н, 2 СН2); 3.21—3.34
(m, 2 Н, СН2); 5.12, 5.27 (both d, 1 Н, СН, J = 7.9); 7.43, 7.57
(both br.s, 1 Н, NH)
* The 1H and 13C NMR spectra of glycoluril 2e were cited earlier.15
(2c—f,h). The solvent was removed on a rotary evaporator. Comꢀ
pounds 2d—g were extracted from the oily residue with boiling
ether (4×5 mL) and triturated with ethyl acetate—methanol
(1 : 1) (for 2a), propanꢀ2ꢀol (2b,c,f), ethyl acetate—ether (1 : 1)
(2d,e,g), or water (2h). The precipitate that formed was filtered
off and recrystallized from an appropriate solvent (see Table 1).
This procedure was used to obtain 2ꢀ(2ꢀacetylaminoethyl)ꢀ
2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ3,7ꢀdione (2a), 2ꢀ(2ꢀacetylꢀ
aminoethyl)ꢀ4ꢀmethylꢀ2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ
3,7ꢀdione (2b), 2ꢀ(2ꢀacetylaminoethyl)ꢀ4ꢀphenylꢀ2,4,6,8ꢀtetraꢀ
azabicyclo[3.3.0]octaneꢀ3,7ꢀdione (2c), 6ꢀ(2ꢀacetylaminoethyl)ꢀ
2,4ꢀdimethylꢀ2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ3,7ꢀdione
(2d), 2ꢀ(2ꢀacetylaminoethyl)ꢀ4,6,8ꢀtrimethylꢀ2,4,6,8ꢀtetraazaꢀ
bicyclo[3.3.0]octaneꢀ3,7ꢀdione (2e), 2ꢀ(2ꢀacetylaminoethyl)ꢀ
6,8ꢀdimethylꢀ4ꢀphenylꢀ2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ
3,7ꢀdione (2f), 6ꢀ(2ꢀacetylaminoethyl)ꢀ2,4ꢀdiethylꢀ2,4,6,8ꢀ
tetraazabicyclo[3.3.0]octaneꢀ3,7ꢀdione (2g), and 6ꢀ(2ꢀacetylꢀ
aminoethyl)ꢀ2,4ꢀdimethylꢀ1,5ꢀdiphenylꢀ2,4,6,8ꢀtetraazabicycloꢀ
[3.3.0]octaneꢀ3,7ꢀdione (2h).
2ꢀ(2ꢀAminoethyl)ꢀ4ꢀmethylglycoluril hydrochloride (6a). Conꢀ
centrated HCl (0.2 mL) was added to a solution of DHI 4a (1.18 g,
10 mmol) and urea 3b (1.59 g, 10 mmol) in water (10 mL). The

646
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Gazieva et al.
reaction mixture was stirred at 80 °C for 2 h. The solvent was
removed on a rotary evaporator and the oily residue was trituratꢀ
ed with acetone—methanol (1 : 1). The precipitate of compound
6a that formed was filtered off and recrystallized. The filtrate
was concentrated in vacuo and the product was extracted from
the residue with boiling ether (4×5 mL) and triturated with proꢀ
panꢀ2ꢀol. The resulting precipitate of hydrate 2b•H2O (0.51 g,
20%) was filtered off and recrystallized.
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Received October 7, 2009;
in revised form December 1, 2009