ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 9, pp. 1426–1427. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © F.A. Khaliullin, E.E. Klen, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 9, pp. 1438–1439.
SHORT
COMMUNICATIONS
New Synthesis of 6,7-Dihydro[1,3]thiazolo[2,3-f]purine-
2,4(1H,3H)-diones
F. A. Khaliullin and E. E. Klen
Bashkir State Medical University, ul. Lenina 3, Ufa, 450000 Bashkortostan, Russia
e-mail: khaliullin_ufa@yahoo.com
Received March 13, 2009
DOI: 10.1134/S1070428009090231
Several methods of synthesis of 6,7-dihydro[1,3]-
thiazolo[2,3-f]purine-2,4(1H,3H)-diones have been re-
ported, e.g., from 8-brom-7-(2-haloethyl)-3,7-dihydro-
1H-purine-2,6-diones and sodium sulfide [1], by reac-
tion of 8-halo-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-
purin-2,6-diones with nucleophilic reagents [2], etc.
We now propose a new one-step procedure for the
preparation of 6,7-dihydro[1,3]thiazolo[2,3-f]purin-
2,4(1H,3H)-dione derivatives via reaction of 8-halo-
3,7-dihydro-1H-purine-2,6-diones with thiiranes. The
reactions were carried out in DMF with 8-halo-3,7-di-
hydro-1H-purine-2,6-diones Ia–Ic as free bases (in the
presence of a base) or potassium salts and an equi-
molar amount of thiirane IIa–IIc. 6,7-Dihydro[1,3]-
thiazolo[2,3-f]purine-2,4(1H,3H)-diones IIIa–IIIc
were thus obtained in 59–68% yield.
no depression of the melting point on mixing, and their
1H NMR spectra were fully identical. Our results
indicated that opening of the thiirane ring follows the
Krasuskii rule [3].
1,3-Dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]-
purine-2,4(1H,3H)-dione (IIIa). A solution of 2.59 g
(10 mmol) of purine Ia, 0.56 g (10 mmol) of potas-
sium hydroxide, and 0.60 g (10 mol) of thiirane IIa in
40 ml of DMF was heated for 3 h at 45–50°C. The
mixture was cooled, and the precipitate was filtered off
and washed with water. Yield 1.40 g (59%), mp 259–
260°C (from i-BuOH) [1]. 1H NMR spectrum, δ, ppm:
3.38 s (3H, 3-CH3), 3.54 s (3H, 1-CH3), 3.88–4.00 m
(2H, SCH2), 4.42–4.53 m (2H, NCH2). Found, %:
C 45.56; H 4.33; N 23.18. C14H21N5O2S. Calculated,
%: C 45.37; H 4.23; N 23.51.
The structure of compounds IIIa–IIIc was con-
7-(Diethylaminomethyl)-1,3-dimethyl-6,7-dihy-
dro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-dione
(IIIb). A solution of 1.49 g (5 mmol) of purine Ib
potassium salt and 0.73 g (5 mmol) of thiirane IIb in
30 ml of DMF was heated for 1 h under reflux. The
mixture was cooled and diluted with water until a solid
separated. The precipitate was filtered off and washed
with water. Yield 1.10 g (68%), mp 177–178°C (from
1
firmed by elemental analyses and H and 13C NMR
spectra. The properties of compound IIIa were consist-
ent with published data [1]. Substituted thiiranes IIb
and IIc gave rise to 7-substituted dihydrothiazolo-
purines IIIb and IIIc whose structure was additionally
proved by independent synthesis of compound IIIb
from 8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-
3,7-dihydro-1H-purine-2,6-dione and diethylamine [2].
Samples of IIIb prepared by the two methods showed
1
EtOH). H NMR spectrum, δ, ppm: 0.99 t (6H,
3
3
CH2CH3, J = 7.1 Hz), 2.55 q (4H, NCH2CH3, J =
O
O
R'
X
N
R
R
N
N
N
S
Hlg
+
R'
S
N
N
O
N
O
N
Me
Me
Ia–Ic
IIa–IIc
IIIa–IIIc
I, R = Me, Hlg = Br, X = H (a), K (b); R = H, Hlg = Cl, X = K (c); II, R′ = H (a), Et2NCH2 (b), MeOCH2 (c);
III, R = Me, R′ = H (a), Et2NCH2 (b); R = H, R′ = MeOCH2 (c).
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