Synthesis of thiazolo[3,2-a]pyrimidines from 3,4-dihydropyrimidine-2(1H)- thiones

Full text of DOI:10.1134/S1070428006120232

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 12, pp. 1871–1872. © Pleiades Publishing, Inc., 2006.
Original Russian Text © M.M. Kurbanova, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 12, pp. 1878–1879.
SHORT
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Synthesis of Thiazolo[3,2-a]pyrimidines
from 3,4-Dihydropyrimidine-2(1H)-thiones
M. M. Kurbanova
Baku State University, ul. Z. Khalilova 23, Baku, AZ-1073, Azerbaijan
e-mail: kurbanova1972@rambler.ru
Received April 26, 2006
DOI: 10.1134/S1070428006120232
Some functional derivatives of dihydropyrimidi-
nones are known to exhibit a broad spectrum of bio-
logical activity, such as antiviral, antitumor, and anti-
bacterial [1–3]. 4-Aryldihydropyrimidinones were
recently reported as a new class of calcium channel
blocking agents [4, 5]. The potential of dihydropyri-
midinones and dihydropyrimidinethiones and their
derivatives as new pharmacologically active sub-
stances attracts interest of many researchers.
firmed by the IR and NMR spectra. In the IR spectra of
IIIa, IIIb, Va, and Vb we observed no absorption
bands in the region 3200–3400 cm–1, which are typical
of stretching vibrations of the N–H bonds in the initial
pyrimidines Ia and Ib.
Scheme 2.
R
O
ClCH2CH2Cl (II)
N
OEt
Ia, Ib
The most convenient procedure for the synthesis
of 3,4-dihydropyrimidine-2(1H)-thiones (known as the
Biginelli reaction) is based on one-pot three-com-
ponent condensation of aldehydes with β-keto esters
and thiourea. Following the procedure reported in [6]
we synthesized 3,4-dihydropyrimidine-2(1H)-thiones
Ia and Ib (Scheme 1) and converted them into fused
thiazolo[3,2-a]pyrimidines IIIa, IIIb, Va, and Vb by
treatment with halogen derivatives II and IV in di-
methylformamide (Scheme 2).
S
N
Me
O
IIIa, IIIb
R
O
ClCH2COOH (IV)
N
OEt
Ia, Ib
S
N
Me
Va, Vb
R = Me (a), Ph (b).
Ethyl 5,7-dimethyl-2,3-dihydro-5H-[1,3]thiazolo-
[3,2-a]pyrimidine-6-carboxylate (IIIa). A mixture of
0.9 ml (0.011 mol) of 1,2-dichloroethane, 2.14 g
(0.01 mol) of dihydropyrimidinethione Ia, and 10 ml
of DMF was heated for 4 h under reflux. The mixture
was left overnight at room temperature and cooled to
0°C, and the precipitate was filtered off, washed with
cold ethanol, and recrystallized from ethanol. Yield
65%, mp 219–220°C. IR spectrum, ν, cm–1: 1670,
Scheme 1.
O
O
S
RCHO
+
+
Me
OEt
R
H2N
NH2
O
HN
OEt
S
N
Me
H
1
1533, 1280, 750. H NMR spectrum, δ, ppm: 1.04 t
Ia, Ib
(3H, CH3), 1.35 d (3H, CH3 ), 2.37 s (3H, CH3), 3.2–
3.54 m (4H, CH2CH2), 3.95 q (2H, OCH2), 4.19 q (1H,
5-H). Found, %: C 55.07; H 6.59; N 11.70; S 13.41.
C11H16O2N2S. Calculated, %: C 55.00; H 6.66;
N 11.66; S 13.33.
R = Me (a), Ph (b).
The progress of reactions was monitored by TLC,
following the disappearance of the initial thiones.
Compounds IIIa, IIIb, Va, and Vb are colorless high-
melting crystalline substances; their structure was con-
Compound IIIb was synthesized in a similar way.
1871

KURBANOVA
1872
1
trum, ν, cm–1: 1710, 1680, 1533, 1280, 755. H NMR
spectrum, δ, ppm: 1.05 t (3H, CH3), 2.41 s (3H, CH3),
3.75 s (2H, CH2), 4.02 q (2H, OCH2), 5.79 s (1H, 5-H),
7.35 m (5H, Harom). Found, %: C 60.79; H 5.11; N 8.81;
S 10.19. C16H16O3N2S. Calculated, %: C 60.75; H 5.06;
N 8.86; S 10.12.
Ethyl 7-methyl-5-phenyl-2,3-dihydro-5H-[1,3]-
thiazolo[3,2-a]pyrimidine-6-carboxylate (IIIb).
Yield 65%, mp 197–199°C. IR spectrum, ν, cm–1:
1
1675, 1535, 1280, 755. H NMR spectrum, δ, ppm:
1.02 t (3H, CH3), 2.35 s (3H, CH3), 3.1–3.51 m (4H,
CH2CH2), 4.01 q (2H, OCH2), 5.74 s (1H, 5-H),
7.45 m (5H, Harom). Found, %: C 63.61; H 6.01; N 9.31;
S 10.54. C16H18O2N2S. Calculated, %: C 63.57; H 5.96;
N 9.27; S 10.59.
1
The H NMR spectra were recorded from solutions
in DMSO-d6 on a Bruker-300 spectrometer (300 MHz)
at 25°C. The IR spectra were measured on a Specord
75IR instrument from samples dispersed in mineral oil.
The purity of the products was checked by TLC on
Silufol UV-254 plates.
Ethyl 5,7-dimethyl-3-oxo-2,3-dihydro-5H-[1,3]-
thiazolo[3,2-a]pyrimidine-6-carboxylate (Va). A mix-
ture of 1.04 g (0.011 mol) of chloroacetic acid, 2.14 g
(0.01 mol) of 3,4-dihydropyrimidinethione Ia, and
10 ml of DMF was heated for 4 h under reflux. The
mixture was left to stand at room temperature and
cooled to 0°C, and the precipitate was filtered off and
washed with cold ethanol. Yield 60%, mp 200–202°C.
IR spectrum, ν, cm–1: 1715, 1670, 1530, 1275, 750.
1H NMR spectrum, δ, ppm: 1.06 t (3H, CH3), 1.41 d
(3H, CH3), 2.45 s (3H, CH3), 3.8 s (2H, CH2), 4.05 q
(2H, OCH2), 4.70 q (1H, 5-H). Found, %: C 51.89;
H 5.57; N 11.09; S 12.63. C11H14O3N2S. Calculated,
%: C 51.96; H 5.51; N 11.02; S 12.59.
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