Synthesis of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives

Article abstract of DOI:10.1134/S1070428013040143

The reaction of 2-aminothiazoles with ethyl acetoacetate in acetic or polyphosphoric acid gave a series of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives which were nitrated with a mixture of nitric and sulfuric acid to 6-nitro-5H-[1,3]thiazolo[3,2-a]

Full text of DOI:10.1134/S1070428013040143

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 4, pp. 575–579. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.A. Veretennikov, A.V. Pavlov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 4, pp. 591–595.
Synthesis of 5H-[1,3]Thiazolo[3,2-a]pyrimidin-5-one Derivatives
E. A. Veretennikova and A. V. Pavlovb
a Chemical and Pharmaceutical Technologies Ltd., Zheleznodorozhnyi pr. 40/D, St. Petersburg, 192148 Russia
e-mail: vea@iihr.ru
b “Applied Chemistry” Russian Scientific Center, ul. Krylenko 26A, St. Petersburg, 193232 Russia
Received November 11, 2011
Abstract—The reaction of 2-aminothiazoles with ethyl acetoacetate in acetic or polyphosphoric acid gave
a series of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives which were nitrated with a mixture of nitric and
sulfuric acid to 6-nitro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-ones, and the latter were reduced to the corre-
sponding amines.
DOI: 10.1134/S1070428013040143
Thiazolopyrimidine derivatives exhibit a broad
spectrum of physiological activity [1–3]; however, com-
pounds of this series remain poorly studied. Among
known thiazolopyrimidine derivatives, Ritanserin [1]
acts as antidepressant, anxiolytic, and 5-HT2A-recep-
tor antagonist. Thiazolopyrimidine derivatives were re-
ported as metabotropic glutamate receptor antagonists
and were found to possess antiallergic, anti-inflam-
matory, antiulcer, immune stimulating, and psycho-
tropic properties [2, 3].
Fused heterocyclic systems containing a pyrimidine
and another nitrogen heterocycle can be synthesized by
reaction of β-ketoesters with amino-substituted nitro-
gen heterocycles. For example, triazolopyrimidinone
derivatives were obtained by reaction of 5-amino-
1,2,4-triazoles with β-ketoesters [4–6]. Depending on
the conditions, either [1,2,4]triazolo[1,5-a]pyrimidin-
5-ones (in acid medium) or [1,2,4]triazolo[1,5-a]-
pyrimidin-7-ones (in basic medium) were formed. The
reaction under solvent-free conditions in the absence
of other reagents afforded [1,2,4]triazolo[1,5-a]pyrimi-
din-7-ones or their mixtures with isomeric 5-oxo
derivatives [4–6]. 2-Aminothiazoles reacted with ethyl
acetoacetate or other β-ketoesters in polyphosphoric
acid (PPA) to produce the corresponding thiazolo-
[3,2-a]pyrimidin-5-ones [2, 7, 8].
With a view to synthesize potentially biologically
active compounds on the basis of amino derivatives of
thiazolopyrimidine, aminothiazoles Ia–If were brought
into reaction with ethyl acetoacetate in acid medium,
the resulting thiazolopyrimidines IIa–IIf were subjec-
ted to nitration, and nitro derivatives IIIa–IIIe were
reduced to amines IVa–IVe (Scheme 1).
1,3-Thiazol-2-amine (Ia) reacted with ethyl aceto-
acetate in acetic acid to give 7-methyl-5H-[1,3]thia-
zolo[3,2-a]pyrimidin-5-one (IIa) as the only product in
37% yield. Introduction of alkyl (Ib–Ie) or aryl (If)
substituents into aminothiazole molecule reduced its
Scheme 1.
R1
O
R1
O
O
N
PPA
N
+
R2
R2
NH2
Me
OEt
S
S
N
Me
O
Ia–If
IIa–IIf
O
N
R1
R1
NO2
NH2
Me
97% HNO3–96% H2SO4
Fe, HCl
N
N
R2
R2
S
S
Me
N
IIIa–IIIe
IVa–IVe
R1 = R2 = H (a); R1 = H, R2 = Me (b); R1 = Me, R2 = H (c); R1 = Et, R2 = H (d); R1 = R2 = Me (e); R1 = Ph, R2 = H (f).
575

VERETENNIKOV, PAVLOV
576
Scheme 2.
O
O2N
65% HNO3
96% H2SO4
Me
N
N
O
S
Me
V
N
N
NO2
N
NH2
N
O
O
O2N
H2N
S
IIf
97% HNO3
96% H2SO4
Me
Me
Fe, HCl
N
N
S
S
IIIf
IVf
reactivity, and we failed to obtain the corresponding
condensation products with ethyl acetoacetate under
the same conditions. Thiazolopyrimidin-5-ones IIb–IIf
were synthesized using PPA as condensing agent; in
this case, the yield of IIa was also improved.
It is known that the 6-position in fused azolopy-
rimidines is active in electrophilic substitution reac-
tions [6, 9]. In fact, the nitration of IIa–IIe with 97%
nitric acid in 96% sulfuric acid led to the formation of
the corresponding 6-nitro-5H-[1,3]thiazolo[3,2-a]py-
rimidin-5-ones IIIa–IIIe. The yield depended on the
number and position of alkyl substituents in the thia-
zole ring. Presumably, alkyl substituents, especially
those in the 3-position, destabilize thiazolopyrimidines
under the nitration conditions and favor their decom-
position. The contribution of side reactions can be
reduced by using a lesser excess of nitric acid.
The nitration of the heteroring in compound IIf
with 97% nitric acid in 96% sulfuric acid was accom-
panied by nitration of the phenyl substituent, and the
product was 7-methyl-6-nitro-3-(4-nitrophenyl)-5H-
[1,3]thiazolo[3,2-a]pyrimidin-5-one (IIIf). Under
milder conditions (equimolar amount of 65% nitric
acid) we obtained 7-methyl-3-(4-nitrophenyl)-5H-
[1,3]thiazolo[3,2-a]pyrimidin-5-one (V) as the only
product (Scheme 2).
Nitro derivatives IIIa–IIIe were reduced to the cor-
responding amines IVa–IVe with iron in hydrochloric
acid; the yield of IVa–IVe ranged from 50 to 80%. The
reduction of IIIf under analogous conditions afforded
no more than 5% of 6-amino-3-(4-aminophenyl)-7-
methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (IVf).
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
WM-400 spectrometer using tetramethylsilane as in-
ternal reference. Analytical thin-layer chromatography
was performed on PTSKh-AF-V plates using chloro-
form–ethyl acetate (5:1) or chloroform–ethyl acetate–
ethanol (5:1:1) as eluent; spots were detected under
UV light (λ 254 nm). The elemental compositions were
determined on a Hewlett Packard 185B analyzer.
Initial 4-phenyl-1,3-thiazol-2-amine (If) [10],
4-ethyl-1,3-thiazol-2-amine (Id) [11], and 4,5-dimeth-
yl-1,3-thiazol-2-amine (Ie) [12] were synthesized ac-
cording to known procedures. The other aminothia-
zoles were commercial products.
4-Ethyl-1,3-thiazol-2-amine (Ie) was synthesized
from 1-chlorobutan-2-one. Yield 73%, mp 71–72°C.
1H NMR spectrum (CDCl3), δ, ppm: 1.13 t (3H, CH3,
3
3J = 7.3 Hz), 2.48 q (2H, CH2, J = 7.3 Hz), 5.58 br.s
(2H, NH2), 5.96 s (1H, 4-H). Found, %: C 46.95;
H 6.35; N 21.66. C5H8N2S. Calculated, %: C 46.85;
H 6.29; N 21.85.
4,5-Dimethyl-1,3-thiazol-2-amine (Ie). Thiourea,
30.4 g (0.4 mol), was added to a solution of 42.6 g
(0.4 mol) of 3-chlorobutan-2-one in 250 ml of propan-
2-ol, and the mixture was heated for 5 min under
reflux with stirring. The precipitate (aminothiazole hy-
drochloride) was filtered off, washed with propan-2-ol,
and dissolved in water, the solution was adjusted to
pH 11 by adding sodium carbonate and extracted with
methylene chloride (2×30 ml), the extract was dried
over sodium sulfate and evaporated under reduced
pressure, and the residue was used without additional
purification. Yield 32.2 g (63%), mp 80–81°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.96 s (3H,
CH3), 2.09 s (3H, CH3), 6.38 br.s (2H, NH2). Found,
The purity of the isolated compounds was checked
by TLC, and their structure was confirmed by elemen-
tal analyses and 1H NMR spectra.
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SYNTHESIS OF 5H-[1,3]THIAZOLO[3,2-a]PYRIMIDIN-5-ONE DERIVATIVES
577
%: C 46.92; H 6.37; N 21.76. C5H8N2S. Calculated, %:
C 46.85; H 6.29; N 21.85.
7-Methyl-3-phenyl-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IIf). Phosphoric anhydride, 20.0 g
(0.141 mol), was added under stirring to 21.0 g
(0.182 mol) of 85% phosphoric acid, and the mixture
was heated for 2 h at 120°C. Polyphosphoric acid thus
obtained was cooled to 35°C, 9.0 g (0.069 mol) of
ethyl acetoacetate was slowly added dropwise, the
mixture was stirred for 10 min, and 10.0 g (0.057 mol)
of 4-phenyl-1,3-thiazol-2-amine (If) was added. The
mixture was slowly heated to 120–130°C and was
stirred for 4 h at that temperature. After cooling, the
mixture was diluted with 300 ml of water and
neutralized to pH 5–6 with sodium carbonate. The
precipitate was filtered off, washed with water, and
recrystallized from propan-2-ol. The product was treat-
ed with dilute hydrochloric acid to remove unreacted
aminothiazole, washed with water, and recrystallized.
Yield 3.85 g (28%), mp 202–204°C (from i-PrOH).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.27 s (3H,
CH3), 5.99 s (1H, 6-H), 7.24 s (1H, 2-H), 7.36 s
(5H, Harom). Found, %: C 64.53; H 4.21; N 11.47.
C13H10N2OS. Calculated, %: C 64.44; H 4.16; N 11.56.
2,7-Dimethyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-
5-one (IIb). A mixture of 21.0 g (0.182 mol) of 85%
phosphoric acid and 24.0 g (0.169 mol) of phosphoric
anhydride was stirred for 2 h at 120°C. Polyphosphoric
acid thus obtained was cooled to 35°C, 13.5 g
(0.104 mol) of ethyl acetoacetate was slowly added
dropwise, the mixture was stirred for 10 min, and 10 g
(0.088 mol) of 5-methyl-1,3-thiazol-2-amine (Ib) was
added. The mixture was slowly heated to 120–130°C
and was stirred for 4 h at that temperature. After
cooling, the mixture was treated with 200 ml of water
and neutralized to pH 5–6 with sodium carbonate. The
precipitate was filtered off, washed with water, and
recrystallized. Yield 8.9 g (56%), mp 162–164°C (from
1
H2O–i-PrOH, 1:2). H NMR spectrum (DMSO-d6),
δ, ppm: 2.25 s (3H, CH3), 2.41 s (3H, CH3), 6.04 s
(1H, 6-H), 7.76 s (1H, 3-H). Found, %: C 53.34;
H 4.41; N 15.45. C8H8N2OS. Calculated, %: C 53.31;
H 4.47; N 15.54.
Compounds IIa and IIc–IIe were synthesized in
a similar way.
7-Methyl-6-nitro-5H-[1,3]thiazolo[3,2-a]pyrimi-
din-5-one (IIIa). Compound IIa, 18.7 g (0.113 mol),
was dissolved at 10–15°C in 60 ml of 96% sulfuric
acid, and 14.2 g (0.219 mol) of 97% nitric acid was
added dropwise under stirring, maintaining the tem-
perature at 10–15°C. The mixture was then allowed to
slowly warm up to 23–25°C, kept for 1 h at that tem-
perature, and poured onto ice. The precipitate was
filtered off, washed with water, and recrystallized.
Yield 22.0 g (92%), mp 166–168°C (from i-PrOH–
7-Methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIa). Yield 57%, mp 130–132°C (from H2O).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.28 s (3H,
CH3), 6.08 s (1H, 6-H), 7.47 d (1H, 2-H, 3J = 4.9 Hz),
3
7.94 d (1H, 3-H, J = 4.9 Hz). Found, %: C 50.51;
H 3.67; N 16.89. C7H6N2OS. Calculated, %: C 50.59;
H 3.64; N 16.85.
3,7-Dimethyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-
5-one (IIc). Yield 62%, mp 138–140°C (from H2O–
1
EtOAc, 4:1). H NMR spectrum (DMSO-d6), δ, ppm:
2.45 s (3H, CH3), 7.72 d (1H, 2-H, 3J = 4.9 Hz), 8.16 d
1
i-PrOH, 1:2). H NMR spectrum (DMSO-d6), δ, ppm:
3
(1H, 3-H, J = 4.9 Hz). Found, %: C 39.87; H 2.46;
2.21 s (3H, CH3), 2.66 s (3H, CH3), 5.93 s (1H, 6-H),
6.92 s (1H, 2-H). Found, %: C 53.25; H 4.41; N 15.57.
C8H8N2OS. Calculated, %: C 53.31; H 4.47; N 15.54.
N 19.81. C7H5N3O3S. Calculated, %: C 39.81; H 2.39;
N 19.90.
Compounds IIIb and IIIf were synthesized in
3-Ethyl-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimi-
din-5-one (IId). Yield 51%, mp 131–132°C (from
a similar way.
1
H2O–i-PrOH, 1:2). H NMR spectrum (DMSO-d6), δ,
2,7-Dimethyl-6-nitro-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IIIb). Yield 72%, mp 178–180°C
3
ppm: 1.21 t (3H, CH3, J = 6.9 Hz), 2.21 s (3H,
7-CH3), 3.14 q (2H, CH2, 3J = 6.9 Hz), 5.95 s (1H, 6-H),
6.92 s (1H, 2-H). Found, %: C 55.59; H 5.26; N 14.47.
C9H10N2OS. Calculated, %: C 55.65; H 5.19; N 14.42.
1
(from i-PrOH–EtOAc, 4 : 1). H NMR spectrum
(DMSO-d6), δ, ppm: 2.43 s (3H, CH3), 2.48 s (3H,
CH3), 8.04 s (1H, 3-H). Found, %: C 42.59; H 3.18;
N 18.78. C8H7N3O3S. Calculated, %: C 42.66; H 3.13;
N 18.66.
2,3,7-Trimethyl-5H-[1,3]thiazolo[3,2-a]pyrimi-
din-5-one (IIe). Yield 63%, mp 111–113°C (from
1
H2O). H NMR spectrum (DMSO-d6), δ, ppm: 2.20 s
7-Methyl-6-nitro-3-(4-nitrophenyl)-5H-[1,3]thia-
zolo[3,2-a]pyrimidin-5-one (IIIf). Yield 42%,
(3H, CH3), 2.26 s (3H, CH3), 2.60 s (3H, CH3), 5.91 s
(1H, 6-H). Found, %: C 55.62; H 5.15; N 14.49.
C9H10N2OS. Calculated, %: C 55.65; H 5.19; N 14.42.
1
mp 222–224°C (from i-PrOH–EtOAc, 4:1). H NMR
spectrum (DMSO-d6), δ, ppm: 2.45 s (3H, CH3), 7.69 s
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VERETENNIKOV, PAVLOV
578
(1H, 2-H), 7.73 d (2H, Harom, 3J = 8.9 Hz), 8.25 d (2H,
at 75–80°C. The mixture was filtered while hot, and
the precipitate was washed on a filter with hot propan-
2-ol (150 ml) and treated with chloroform (50 ml). The
filtrate was combined with the washings, evaporated to
a volume of 10–15 ml, and extracted with chloroform
(3×50 ml). The combined extracts were dried over
sodium sulfate and evaporated, and the residue was
recrystallized from propan-2-ol. Yield 17.7 g (57%),
3
Harom, J = 8.9 Hz). Found, %: C 46.87; H 2.36;
N 16.98. C13H8N4O5S. Calculated, %: C 46.99; H 2.43;
N 16.86.
3,7-Dimethyl-6-nitro-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IIIc). Compound IIc, 20.3 g
(0.113 mol), was dissolved at 10–15°C in 70 ml of
96% sulfuric acid, and 10.8 g (0.167 mol) of 97% ni-
tric acid was added dropwise under stirring, maintain-
ing the temperature at 10–15°C. The mixture was
allowed to slowly warm up to 23–25°C, kept for 1 h at
that temperature, and poured onto ice. The precipitate
was quickly filtered off, washed with water, and
recrystallized. Yield 14.2 g (56%), mp 152–154°C
1
mp 162–164°C (from i-PrOH). H NMR spectrum
(DMSO-d6), δ, ppm: 2.22 s (3H, CH3), 4.45 br.s (2H,
3
NH2), 7.35 d (1H, 2-H, J = 4.9 Hz), 7.82 d (1H, 3-H,
3J = 4.9 Hz). Found, %: C 46.84; H 3.96; N 23.08.
C7H7N3OS. Calculated, %: C 46.40; H 3.89; N 23.19.
Compounds IVb–IVe were synthesized in a sim-
ilar way.
1
(from i-PrOH–EtOAc, 4:1). H NMR spectrum
(DMSO-d6), δ, ppm: 2.37 s (3H, CH3), 2.72 s (3H,
CH3), 7.21 s (1H, 2-H). Found, %: C 42.57; H 3.21;
N 18.80. C8H7N3O3S. Calculated, %: C 42.66; H 3.13;
N 18.66.
6-Amino-2,7-dimethyl-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IVb). Yield 70%, mp 139–141°C
1
(from i-PrOH). H NMR spectrum (DMSO-d6), δ,
ppm: 2.19 s (3H, CH3), 2.37 s (3H, CH3), 4.40 br.s
(2H, NH2), 7.62 s (1H, 3-H). Found, %: C 49.28;
H 4.73; N 21.44. C8H9N3OS. Calculated, %: C 49.21;
H 4.65; N 21.52.
Compounds IIId and IIIe were synthesized in
a similar way.
2-Ethyl-7-methyl-6-nitro-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IIId). Yield 68%, mp 154–154°C
6-Amino-3,7-dimethyl-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IVc). Yield 52%, mp 201–204°C
(from i-PrOH). 1H NMR spectrum, δ, ppm: 2.17 s (3H,
CH3), 2.68 s (3H, CH3), 4.35 br.s (2H, NH2), 6.79 s
(1H, 2-H). Found, %: C 49.15; H 4.54; N 21.61.
C8H9N3OS. Calculated, %: C 49.21; H 4.65; N 21.52.
1
(from H2O–i-PrOH, 1 : 2). H NMR spectrum
3
(DMSO-d6), δ, ppm: 1.25 t (3H, CH3, J = 6.9 Hz),
3
2.38 s (3H, 7-CH3), 3.19 q (2H, CH2, J = 6.9 Hz),
7.21 s (1H, 2-H). Found, %: C 45.11; H 3.73; N 17.67.
C9H9N3O3S. Calculated, %: C 45.18; H 3.79; N 17.56.
2,3,7-Trimethyl-6-nitro-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IIIe). Yield 27%, mp 149–151°C
6-Amino-3-ethyl-7-methyl-5H-[1,3]thiazolo-
[3,2-a]pyrimidin-5-one (IVd). Yield 81%, mp 150–
1
(without recrystallization). H NMR spectrum
1
151°C (from i-PrOH). H NMR spectrum (DMSO-d6),
(DMSO-d6), δ, ppm: 2.34 s (3H, CH3), 2.36 s (3H,
CH3), 2.65 s (3H, CH3). Found, %: C 45.09; H 3.68;
N 17.71. C9H9N3O3S. Calculated, %: C 45.18; H 3.79;
N 17.56.
3
δ, ppm: 1.22 t (3H, CH3, J = 6.9 Hz), 2.17 s (3H,
3
7-CH3), 3.16 q (2H, CH2, J = 6.9 Hz), 4.36 br.s
(2H, NH2), 6.79 s (1H, 2-H). Found, %: C 51.57;
H 5.37; N 20.17. C9H11N3OS. Calculated, %: C 51.66;
H 5.30; N 20.08.
6-Amino-7-methyl-5H-1,3-thiazolo[3,2-a]pyrimi-
din-5-one (IVa). A three-necked flask equipped with
a mechanical stirrer and reflux condenser was charged
with a mixture of 500 ml of propan-2-ol and 120 ml of
water, 39.0 g (0.696 mol) of reduced iron powder was
added under vigorous stirring, and 11.7 g (0.112 mol)
of 35% aqueous HCl was then added dropwise from
a dropping funnel. The mixture was heated to 75°C,
kept for 5 min at that temperature, and cooled to room
temperature, 36.3 g (0.172 mol) of nitro compound
IIIa was added, and 24.6 g (0.236 mol) of 35% aque-
ous HCl was slowly added dropwise from a dropping
funnel. The mixture was heated for 4 h at 75–80°C,
a saturated solution of 18.5 g (0.174 mol) of sodium
carbonate was added, and the mixture was kept for 1 h
6-Amino-2,3,7-trimethyl-5H-[1,3]thiazolo[3,2-a]-
pyrimidin-5-one (IVe). Yield 71%, mp 164–167°C
1
(from i-PrOH). H NMR spectrum (DMSO-d6), δ,
ppm: 2.15 s (3H, CH3), 2.21 s (3H, CH3), 2.62 s (3H,
CH3), 4.31 br.s (2H, NH2). Found, %: C 51.51; H 5.26;
N 20.15. C9H11N3OS. Calculated, %: C 51.66; H 5.30;
N 20.08.
6-Amino-3-(4-aminophenyl)-7-methyl-5H-[1,3]-
thiazolo[3,2-a]pyrimidin-5-one (IVf). A three-necked
flask equipped with a mechanical stirrer and reflux
condenser was charged with a mixture of 45 ml of
propan-2-ol and 11 ml of water, 2.8 g (0.05 mol) of
iron powder was added under vigorous stirring, and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013

SYNTHESIS OF 5H-[1,3]THIAZOLO[3,2-a]PYRIMIDIN-5-ONE DERIVATIVES
579
1.17 g (0.0112 mol) of 35% aqueous HCl was then
added from a dropping funnel. The mixture was heated
to 75°C, kept for 5 min at that temperature, and cooled
to room temperature, 1.8 g (0.0054 mol) of compound
IIIf was added, and 1.5 g (0.0144 mol) of 35% aque-
ous HCl was slowly added from a dropping funnel.
The mixture was heated for 4 h at 75–80°C, a saturated
solution of 1.4 g (0.0132 mol) of sodium carbonate
was added, and the mixture was kept for 1 h at 75–
80°C and filtered while hot. The precipitate was
washed on a filter with hot propan-2-ol and treated
with chloroform. The filtrate was combined with the
washings, evaporated to a small volume, and extracted
with chloroform (3×50 ml). The combined extracts
were dried over sodium sulfate and evaporated under
reduced pressure, and the residue was recrystallized
from propan-2-ol. Yield 0.08 g (5%), mp 233–235°C
(DMSO-d6), δ, ppm: 2.30 s (3H, CH3), 6.03 s (1H,
6-H), 7.49 s (1H, 2-H), 7.64 d (2H, Harom, 3J = 8.9 Hz),
3
8.21 d (2H, Harom, J = 8.9 Hz). Found, %: C 54.47;
H 3.25; N 14.55. C13H9N3O3S. Calculated, %: C 54.35;
H 3.16; N 14.63.
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DE Patent no. 3743935, 1988; Chem. Abstr., 1989,
vol. 110, no. 75547g; Adam, G., EP Patent no. 891978,
1999; Chem. Abstr., 1999, vol. 130, no. 125087t.
1
(from i-PrOH–EtOAc, 4 : 1). H NMR spectrum
(DMSO-d6), δ, ppm: 2.20 s (3H, CH3), 4.52 br.s
4. Beckett, A.H., Spickett, R.G.W., and Wright, S.H.B.,
(2H, NH2), 4.91 br.s (2H, NH2), 6.51 d (2H, Harom, 3J =
Tetrahedron, 1968, vol. 24, p. 2839.
3
7.9 Hz), 6.83 s (1H, 2-H), 7.01 d (2H, Harom, J =
5. Reiter, J., Pongó, L., and Dyortsák, P., Tetrahedron,
7.9 Hz). Found, %: C 57.41; H 4.57; N 20.43.
C13H12N4OS. Calculated, %: C 57.34; H 4.44; N 20.57.
1987, vol. 43, p. 2497.
6. Fischer, G., Z. Chem., 1990, vol. 30, no. 9, p. 305.
7-Methyl-3-(4-nitrophenyl)-5H-[1,3]thiazolo-
[3,2-a]pyrimidin-5-one (V). Thiazolopyrimidinone
IIf, 3.80 g (0.0157 mol), was dissolved in a mixture of
10 ml of 96% sulfuric acid and 0.70 g (0.0071 mol)
of 65% nitric acid on cooling to 0–5°C, 0.83 g
(0.0086 mol) of 65% nitric acid was added dropwise
under stirring at 0–5°C, and the mixture was stirred for
3 h, allowing it to slowly warm up to 15°C. The mix-
ture was poured onto ice, and the precipitate was
filtered off, washed with water, and recrystallized from
propan-2-ol. The product was dissolved in ethyl
acetate, the solution was filtered, and the solvent was
removed under reduced pressure. Yield 1.90 g (42%),
7. Okabe, T., Maekawa, K., and Taniguchi, E., Agric. Biol.
Chem., 1973, vol. 37, p. 1197.
8. Khan, R.H. and Rastogi, R.C., J. Agric. Food Chem.,
1991, vol. 39, p. 2300.
9. Shukurov, S.Sh., Kukaniev, M.A., Nasyrov, I.M.,
Zakharov, K.S., and Karakhanov, R.A., Russ. J. Gen.
Chem., 1993, vol. 63, p. 1610.
10. Dodson, R.M. and King, L.C., J. Am. Chem. Soc., 1945,
vol. 67, p. 2242.
11. Byers, J.R. and Dickey, J.B., Organic Syntheses,
Blatt, A.H., Ed., New York: Wiley, 1943, collect.
vol. 2, p. 31.
12. Morton, A. and Penner, H., J. Am. Chem. Soc., 1951,
1
vol. 73, p. 3300.
mp 210–213°C (from i-PrOH). H NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 4 2013