Transformation of 2-acylamino-3,3-dichloroacrylonitriles into substituted 4-amino[1,3]oxazolo[4,5-e]pyrazolo-[1,5-a]pyrimidines

Full text of DOI:10.1134/S1070363207080361

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 8, pp. 1480 1481.
Pleiades Publishing, Ltd., 2007.
Original Russian Text O.V. Shablykin, V.S. Brovarets, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 8, pp. 1403 1404.
LETTERS
TO THE EDITOR
Transformation of 2-Acylamino-3,3-dichloroacrylonitriles
into Substituted 4-Amino[1,3]oxazolo[4,5-e]pyrazolo-
[
1,5-a]pyrimidines
O. V. Shablykin and V. S. Brovarets
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev, 02660 Ukraine
e-mail: brovarets@bpci.kiev.ua
Received February 7, 2007
DOI: 10.1134/S1070363207080361
As shown previously, accessible 2-acylamino-3,3-
dichloroacrylonitriles I can be readily converted into
oxazole [1], imidazole [2], pyrazole [3], 1,3,4-oxa-
diazole [4], 1,3,4-thiadiazole [5], pyrazolo[1,5-a]-
pyrimidine [6], and oxazolo[4,5-d]pyrimidine deriva-
tives [7] via simple transformations. Here we report
on a facile route to representatives of a new fused
heterocyclic system, [1,3]oxazolo[4,5-e]pyrazolo[1,5-
a]pyrimidines, on the basis of compounds I. The
procedure involves initial treatment of acrylonitriles I
with hydrazine hydrate, followed by reactions with
benzoylacetonitrile and sodium hydride. The trans-
formation sequence I II III IV is shown in the
scheme given below.
H
C
N
R
N
C
N
H N NH H O (excess)
N
2
2
2
O
R
O
NH
Cl
Cl
Ia, Ib
NH2
O
IIa, IIb
CN
Ph
,
NH2
C
N
N
NH2
N3
2
4
5N
R
O
NaH
N
N
1
O
R
N8
N
6
7
Ph
Ph
IIIa, IIIb
IVa, IVb
R = Me (a), Ph (b).
480
1

TRANSFORMATION OF 2-ACYLAMINO-3,3-DICHLOROACRYLONITRILES
1481
The first step of the process was studied in [8], and
cyclocondensation II III is a particular case of
numerous cyclizations of N-substituted hydrazines
with acylacetonitriles [9]. The occurrence of intra-
molecular cycloaddition III IV catalyzed by sodium
trum, , ppm: 2.69 s (3H, CH ), 6.49 s (1H, 6-H),
3
7.25 br.s (2H, NH ), 7.43 7.95 m (5H, Harom). Found,
2
%: C 63.25; H 4.26; N 26.28. C H N O. Calculated,
1
4
11
5
%: C 63.39; H 4.18; N 26.40.
1
Yield of IVb 95%, mp >300 C. H NMR spectrum,
ppm: 6.66 s (1H, 6-H), 7.43 8.16 m (10H, Harom),
1
hydride was confirmed not only by IR and H NMR
,
spectroscopy but also by X-ray analysis of final
product IVa. The results of the X-ray diffraction
study, as well as further modifications of compounds
IVa and IVb and their analogs, will be reported
elsewhere.
7
2
.52 br.s (2H, NH ). Found, %: C 69.92; H 3.93; N
2
1.18. C H N O. Calculated, %: C 69.71; H 4.00;
1
9
13
5
N 21.39.
The IR spectra were recorded in KBr on a UR-20
1
spectrometer. The H NMR spectra were measured on
5
-(5-Amino-3-phenyl-1H-pyrazol-1-yl)-2-methyl-
a Varian VXR-300 instrument from solutions in
(
phenyl)-1,3-oxazole-4-carbonitriles IIIa and IIIb
DMSO-d using tetramethylsilane as internal reference.
6
(general procedure). Concentrated hydrochloric acid,
0
.85 ml, and benzoylacetonitrile, 0.01 mol, were
REFERENCES
added to a suspension of 0.01 mol of compound IIa
or IIb in 40 ml of ethanol, and the mixture was heated
for 4 h under reflux with stirring. It was then cooled
to 20 25 C, and the precipitate was filtered off,
washed with a 1% solution of sodium hydrogen
carbonate and with water, dried, and recrystallized.
Yield of IIIa 71%, mp 210 211 C (from ethanol). IR
1
2
. Drach, B.S., Sviridov, E.P., Kisilenko, A.A., and Kir-
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1
1
3. Brovarets, V.S., Pil’o, S.G., Chernega, A.N., Roma-
spectrum: 2245 cm (C N). H NMR spectrum, ,
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ppm: 2.52 s (3H, CH ), 5.83 s (1H, 4-H), 6.11 br.s
3
1
999, vol. 69, no. 10, p. 1577.
(
2H, NH ), 7.38 7.77 m (5H, Harom). Found, %: C
2
6
6
3.10; H 4.34; N.26. C H N O. Calculated, %: C
3.39; H 4.18; N 26.40.
4. Golovchenko, A.V., Pil’o, S.G., Brovarets, V.S.,
1
4
11
5
Chernega, A.N., and Drach, B.S., Russ. J. Gen. Chem.,
2
005, vol. 75, no. 3, p. 425.
Yield of IIIb 87%, mp 259 260 C (from ethanol
1
1
DMF, 3:1). IR spectrum:
2250 cm (C N). H
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NMR spectrum, , ppm: 5.93 s (1H, 4-H), 6.23 br.s
2H, NH ), 7.43 8.12 m (10H, Harom). Found, %: C
(
2
6
9.92; H 3.81; N 21.09. C H N O. Calculated, %:
19 13 5
6. Popil’nichenko, S.V., Pil’o, S.G., Brovarets, V.S.,
C 69.71; H 4.00; N 21.39.
Chernega, A.N., and Drach, B.S., Russ. J. Gen. Chem.,
2
005, vol. 75, no. 11, p. 1816.
4
-Amino-2-methyl(phenyl)-7-phenyl-7,8-dihy-
dro[1,3]oxazolo[4,5-e]pyrazolo[1,5-a]pyrimidines
IVa and IVb (general procedure). Sodium hydride,
7
8
. Sviripa, V.M., Gakh, A.A., Brovarets, V.S., Gu-
tov, A.V., and Drach, B.S., Synthesis, 2006, no. 20,
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0
.005 mol, was added under stirring to a suspension
of 0.01 mol of compound IIIa or IIIb in 40 ml of
. Pil’o, S.G., Brovarets, V.S., Vinogradova, T.K., Cher-
nega, A.N., and Drach, B.S., Russ. J. Gen. Chem.,
tetrahydrofuran, the mixture was stirred for 0.5 h at
2
4
0 25 C, a solution of 0.005 mol of acetic acid in
0 ml of water was added, and the precipitate was
2
001, vol. 71, no. 2, p. 280.
filtered off and recrystallized from dimethylform-
amide. Yield of IVa 78%, mp >300 C. H NMR spec-
9. Elnagdi, M.H., Abdel-Galil, F.M., and Riad, B.Y.,
1
Heterocycles, 1983, vol. 20, no. 12, p. 2437.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 8 2007