Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1740—1743, August, 2008
1740
Threeꢀcomponent condensation of 2,4ꢀdiaminothiazoles
with aldehydes and Meldrum´s acid. The synthesis of 7ꢀarylꢀ
and 7ꢀalkylꢀ6,7ꢀdihydroꢀ4Hꢀthiazolo[4,5ꢀb]pyridinꢀ5ꢀones
A. A. Dudinov, B. V. Lichitsky, I. A. Antonov, A. N. Komogortsev, P. A. Belyakov, and M. M. Krayushkin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: mkray@ioc.ac.ru
7ꢀArylꢀ and 7ꢀalkylꢀ6,7ꢀdihydroꢀ4Hꢀthiazolo[4,5ꢀb]pyridinꢀ5ꢀones were obtained by threeꢀ
component condensation of 5ꢀunsubstituted 2ꢀaminoꢀ4ꢀiminothiazolidine hydrochlorides with
aromatic or aliphatic aldehydes and Meldrum´s acid.
Key words: 2ꢀaminoꢀ4ꢀiminothiazolidinium chlorides, threeꢀcomponent condensation,
Meldrum´s acid, 7ꢀarylꢀ and 7ꢀalkylꢀ6,7ꢀdihydroꢀ4Hꢀthiazolo[4,5ꢀb]pyridinꢀ5ꢀones.
We have proposed a convenient route to 4,7ꢀdihydroꢀ
5Hꢀthieno[2,3ꢀb]pyridinꢀ6ꢀones through unstable 2ꢀaminoꢀ
thiophenes.1 Here we applied this approach to the syntheꢀ
sis of earlier unknown 7ꢀarylꢀ and 7ꢀalkylꢀ6,7ꢀdihydroꢀ
4Hꢀthiazolo[4,5ꢀb]pyridinꢀ5ꢀones 1 (Scheme 1). Threeꢀ
component condensation involves reactions of labile
2,4ꢀdiaminothiazoles generated from stable 2ꢀaminoꢀ
4ꢀiminothiazolidinium chlorides 2 with aromatic (or
aliphatic) aldehydes 3 and Meldrum´s acid (4). 2,4ꢀDiaminoꢀ
thiazoles are known to be ambident nucleophiles: they
react with appropriate substrates at both the amino N
atom in position 4 and the C(5) atom of the thiazole ring
to form a new ring annulated with the thiazole fragment.
The resulting novel heterocyclic system can be
regarded as modified 2,4ꢀdiaminothiazole, whose known
derivatives exhibit a high specific biological activity in
inhibition of cyclineꢀdependent kinases.2—5 The sole
relevant example described in the literature includes the
annulation of 2ꢀaminoꢀ4ꢀiminothiazolidinium chloride
with ethyl acetoacetate or pentaneꢀ2,5ꢀdione, giving the
corresponding 2ꢀaminoꢀ5,7ꢀdimethylthiazolo[4,5ꢀb]pyriꢀ
dines and 2ꢀaminoꢀ7ꢀmethylꢀ4Hꢀthiazolo[4,5ꢀb]pyridinꢀ
5ꢀones.6
We used stable 5ꢀunsubstituted 2ꢀaminoꢀ4ꢀiminothiaꢀ
zolidinium chlorides 2. The synthesis of such salts is
described for either a primary or tertiary amino group
(amino, 1ꢀpiperidyl, 4ꢀmorpholino, etc.) as a substituent
in position 2.6 In this case, 5ꢀunsubstituted 2,4ꢀdiaminoꢀ
thiazoles are difficult to use as the starting reagents
because of their instability.7 Moreover, when dissolved,
they are in equilibrium with their tautomer 2ꢀaminoꢀ
4ꢀiminothiazolidine; the imino form is dominant,8,9 which
makes them prone to hydrolysis.
Scheme 1
O
O
+
–
Cl H2N
O
O
N
+
+
R″CHO
R´
S
3
2a—c
4
H
N
N
O
N
O
R´
S
AcONa
EtOH
R″
1a—n
Comꢀ
pound
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
R´
R″
NH
NH
NH
NH
NH
NH
NH
NH
Me CHCH
2
3ꢀPyridyl
3,4ꢀ(MeO) C H
2,5ꢀ(MeO) C H
2ꢀThienyl
4ꢀPhCH2OꢀC H
CH(CH )
2 5
4ꢀClꢀC H
4ꢀClꢀC H
4ꢀClꢀC H
6
2ꢀMeOꢀC H
2,4ꢀ(MeO) C H
2 6
2,4ꢀ(MeO) C H
2,5ꢀClꢀC H
2
2
2
2
2
2
2
2
2
2
6
3
3
2 6
6
4
6
4
4
4
N(CH )
2 5
6
N(CH ) O
2 4
N(CH )
2 5
6 4
N(CH ) O
2 4
3
3
N(CH )
2 5
2
6
N(CH ) O
2 4
6
3
The condensation was carried out in boiling ethanol
in the presence of a small excess of AcONa and a catalytic
amount of Nꢀmethylmorpholine (see Scheme 1, Table 1).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1707—1710, August, 2008.
1066ꢀ5285/08/5708ꢀ1740 © 2008 Springer Science+Business Media, Inc.