A microwave assisted synthesis of highly substituted 7-methyl-5H- thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives via one-pot reaction of aminothiazole, aldehyde and ethyl acetoacetate

Article abstract of DOI:10.3987/COM-13-12797

The synthesis of highly substituted 7-methyl-5H-thiazolo[3,2-a]pyrimidine- 6-carboxylate derivatives by one-pot reaction of aminothiazole, aldehyde and ethyl acetoacetate under microwave irradiation have been accomplished without any catalyst. This approa

Full text of DOI:10.3987/COM-13-12797

HETEROCYCLES, Vol. 87, No. 10, 2013
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HETEROCYCLES, Vol. 87, No. 10, 2013, pp. 2093 - 2102. © The Japan Institute of Heterocyclic Chemistry
Received, 1st August, 2013, Accepted, 26th August, 2013, Published online, 28th August, 2013
DOI: 10.3987/COM-13-12797
A MICROWAVE ASSISTED SYNTHESIS OF HIGHLY SUBSTITUTED
7-METHYL-5H-THIAZOLO[3,2-a]PYRIMIDINE-6-CARBOXYLATE
DERIVATIVES VIA ONE-POT REACTION OF AMINOTHIAZOLE,
ALDEHYDE AND ETHYL ACETOACETATE
Bing Zhao,1 Li-Li Jiang,1 Zhuo Liu,1 Qi-Gang Deng,1* Li-Yan Wang,1 Bo
Song,1 and Yan Gao2*
1Chemistry and Chemical Engineering Institute, Qiqihar University, Qiqihar
161006, China. e-mail:zhao_submit@aliyun.com 2School of Chemical
Engineering, University of Science and Technology LiaoNing, Anshan 114051,
China
Abstract
–
The synthesis of highly substituted 7-methyl-5H-
thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives by one-pot reaction of
aminothiazole, aldehyde and ethyl acetoacetate under microwave irradiation have
been accomplished without any catalyst. This approach provides a simple, rapid,
and green method for the synthesis of 7-methyl-5H-thiazolo[3,2-a]pyrimidine-
6-carboxylate derivatives.
Since Strecker in 1850 reported the first multicomponent reactions for the synthesis of amino acids,1
multicomponent reactions (MCRs) as a powerful tool have been widely utilized in organic synthesis,
combinatorial and medicinal chemistry due to their simplicity and flexibility, good yield, high variability
and selectivity, superior atom economy, energy savings, and reduced waste. In the past decades, these
types of reactions were used to produce a number of interesting heterocyclic scaffolds, and are useful in
the construction of diverse chemical libraries of ‘drug-like’ molecules.2,3
Thiazolopyrimidine derivatives are an important kind of heterocyclic compound and have been paid
particular attention and widely recognized as biologically useful systems because of their being important
structural components of purine bases. Accordingly, thiazolopyrimidine derivatives exhibited a wide
range of biological activities, acting as calcium channel antagonists and CXCR2 receptor antagonist,4,5
anti-tumor, anti-metastatic and anti-inflammatory agents.6,7 As a consequence, some methods have been

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HETEROCYCLES, Vol. 87, No. 10, 2013
contributed for the synthesis of thiazolo[3,2-a]pyrimidine derivatives.8,9 Among the existed
methodologies, the preparation of most thiazolo[3,2-a]pyrimidine derivatives was completed by the
dihydropyrimidinones (DHPMs)10 as precursors. Recently, the reactions of DHPMs with
α-bromophenylacetaldehyde,8e enolizable ketones,9a α-bromoketones,8c,9b methyl chloroacetate8a etc. have
been reported. However, in spite of their potential utility in the synthesis of this type of compounds, the
precursors DHPMs have to be prepared in advance, during the synthetic procedure of which usually
involves harsh reaction conditions, such as expensive or highly metal catalyst, organic solvent, long
reaction time and unsatisfactory yield. Herein, the development of a direct, efficient and green alternative
approach to functionalized thiazolo[3,2-a]pyrimidine derivatives is current interest to organic chemistry.
Generally, to our knowledge, all of the studies have been proved that the reaction of aldehyde, primary
amines (either aryl or alkyl amine) and acetoacetate could give the products of N-substituted
1,4-dihydropyridines (1,4-DHP).11 Surprisingly, when the 2-aminothiazole takes the place of other
N-alkyl or N-aryl primary amine to engage in the Hantzsch reaction with the aldehyde and acetoacetate,
the target product was not N-thiazolo-1,4-dihydropyridines, but thiazolo[3,2-a]pyrimidine derivative.
Further experiments have shown that a new synthetic protocol for the thiazolo[3,2-a]pyrimidine
derivatives has been formed through the reaction of 2-aminothiazole, aldehyde and ethyl acetoacetate.
Herein, we describe the efficient protocol avoiding the use of DHPMs and microwave combination for a
environment-friendly, rapid, and convenient synthesis of thiazolo[3,2-a]pyrimidine derivatives in
excellent yield through a one-pot three component condensation reaction of 2-aminothiazole, aldehyde
and ethyl acetoacetate. To the best of our knowledge, there is few studies related to the multicomponent
reactions (MCRs) in one - pot for the synthesis of thiazolo[3,2-a]pyrimidine derivatives.
The studies were initiated to carry out the reaction of a one-pot three component condensation reaction of
2-aminothiazole, benzaldehyde, and ethyl acetoacetate in acetic acid, in which the aim product of
N-thiazolo-1,4-dihydropyridine dicarboxylate should be afforded according to the literature. After work
up, a yellow solid was isolated in about 30% yield and characterized. Amazingly, the result showed that
the solid was not N-thiazolo-1,4-dihydropyridine dicarboxylate, but ethyl 7-methyl-5-phenyl-5H-
thiazolo[3,2-a]pyrimidine-6-carboxylate and there is no unit of 1,4-dihydropyridine in the molecule. This
interesting result encouraged us to further optimize the reaction conditions and to achieve a highly
efficient protocol for the synthesis of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives.
The initial three components of 2-aminothiazole, benzaldehyde, and ethyl acetoacetate were stirred in the
refluxing acetic acid for the 48 h to obtain the ethyl 7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-
6-carboxylate in about 30% yield. In order to elevate the efficiency and reduce the reaction time, we
carried out the same reaction under the microwave heating. The result came out as we had hoped and the
microwave reaction provided a faster reaction time and a higher yield compared with the conventional

HETEROCYCLES, Vol. 87, No. 10, 2013
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methods. Furthermore, the pure product was easily obtained through the simple recrystallization with
ethyl acetate along with the improvement in yield. Under microwave assistant, the optimization of
reaction conditions for the three components of 2-aminothiazole, benzaldehyde, and ethyl acetoacetate as
model reaction were studied and the results are shown summarized in Table 1. Varying microwave
powers (100–450 W) and the reaction temperatures were investigated during the experiments. The results
were found that, if the microwave power exceeded 400 W and the temperature achieve 100 C (Table 1,
entry 6), the color of reaction system became dark quickly and there was a decrease in the yield (60%),
which could be attributed that the higher temperature led to decomposition of the component. To our
delight, when the microwave power was 350 W and the temperature was decreased to 80 C, the desired
product was got in 89% (entry 3). Finally, it was found that at 80 C irradiation with microwave for 30
min gave the quantitative amounts of ethyl 7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-
carboxylate as a light yellow solid in acetic acid.
Given that chemists have paid much attention to the solvent-free reaction, we tried to carry out the model
reaction in solvent-free condition. But the results were very disappointing. When there are no solvents in
the reaction system, the reaction mixture became highly viscous, then churned and formed a hard lump
even if the intensity of microwave radiation decreased (Table 1, entries 7–9). Although the model
reaction could be in progress and afford the aim product in the presence of ethanol, [Bmin]Br,
[Bmin]HSO4, and H2O, the yields were fallen to below 50% (Table 1, entries 10–13). So acetic acid is an
effective solvent in this one-pot reaction.
Table 1. The effect of different conditions on the model reaction
CHO
O
N
O
O
acetic acid
MWI
+
+
N
OEt
NH2
S
1
OEt
S
N
Me
2
3
4
Ethyl
acetoacetate
(equiv)
Yielda
(%)
Temp
(C)
Time Power Aminothiazole Aldehyde
Entry
Solvent
(min) (Watt)
(equiv)
(equiv)
1
2
3
4
AcOH
AcOH
AcOH
AcOH
80
80
80
80
10
20
30
30
350
350
350
350
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
1.5
1.5
1.0
65
80
89
45

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5
6
7
AcOH
AcOH
–
80
100
40
30
30
30
350
450
200
1.0
1.0
1.0
1.0
1.0
1.0
2.0
1.5
1.5
90
60
nrb
–
8
9
70
30
350
1.0
1.0
1.5
trace
–
100
reflux
80
30
30
30
30
30
350
350
350
350
350
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
1.5
1.5
1.5
1.5
trace
30
10
11
EtOH
[Bmin]Br
37
12 [Bmin]HSO4 80
13 H2O 80
48
nr
a
b
Isolated yields.
No reaction.
Under the optimized set of microwave reaction conditions the role of aromatic aldehydes with various
substituent groups on the benzene ring was examined in this one-pot reaction (Table 2). The results have
shown that, all aromatic aldehydes with electron-donating or electron-withdrawing at different positions
gave the corresponding products 4 in reasonable good to excellent yields within 30 min. Moreover,
4-nitrobenzaldehyde expressed more efficiently in comparison to those bearing electron-donating groups
and gave better yield and shorter reaction time (Table 2, entries 4 and 10). Next, we replaced the
2-aminothiazole with 2-aminobenzo[d]thiazole. The similar results were observed and the corresponding
5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives were obtained in excellent yield (85–
93%).
Table 2. Synthesized 5H-thiazolo[3,2-a]pyrimidine-6-carboxylate derivative by
three-component condensation reaction a
a
one-pot
Ar
O
N
O
O
acetic acid
N
OEt
+
ArCHO
2
+
R
R
NH2
S
OEt MWI, 300 ~ 400 W
15 ~ 30 min
S
N
4
Me
1
3
Entry
R
Ar
Product
4a
Time (min)
Yieldb (%)
1
2
3
4
H
H
H
H
C6H5
30
20
30
10
89
85
83
95
4-ClC6H5
4-MeOC6H5
4-O2NC6H5
4b
4c
4d

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2097
5
6
H
3-MeO-4-HOC6H4
2-C4H3O
4e
4f
4g
4h
4i
30
20
30
20
30
10
30
20
85
88
88
85
86
93
87
90
H
7
benzo[d]
benzo[d]
benzo[d]
benzo[d]
benzo[d]
benzo[d]
C6H5
8
4-ClC6H5
9
4-MeOC6H5
4-O2NC6H5
3-MeO-4-HOC6H4
2-C4H3O
10
11
12
4j
4k
4l
a The reaction were performed useing aminothiazole (1.0 mmol), aldehyde (1.0 mmol) and ethyl
acetoacetate (1.5 mmol) in acetic acid (5 mL) under microwave irradiation.
b Isolated yield based on aldehyde.
Each compound was isolated by easy recrystallization method by the solvent of ethyl acetate. The
products were characterized by the IR, 1H NMR, 13C NMR and elementary analysis, further confirmed by
single-crystal X-ray diffraction determination of compound 4g (Figure 1). The crystal structure of
compound 4g had been deposited at the Cambridge Crystallographic Data Center (CCDC). Any request
to the CCDC for this material should quote the full literature citation and the reference number 956188.
In conclusion, we have described an efficient, clean, and direct procedure to generate the
5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate
derivative
via
a
microwave
assisted
multicomponent reaction of 2-aminothiazole or 2-aminobenzo[d]thiazole, aromatic aldehydes, and ethyl
acetoacectate in acetic acid without any catalyst. The advantages of this protocol are catalyst-free reaction
conditions, easy work-up, easy of product isolation and high yield. We believe that this method is a useful
condensation reaction for synthesis of 5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate derivative.
Figure 1. ORTEP view of compound 4g. Displacement ellipsoids are drawn at the 55% probability
level.

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EXPERIMENTAL
All melting points were estimated using a X4 melting apparatus apparatus in open capillaries and are
uncorrected. IR spectra were determined as KBr disks with a Perkin-Elmer Spectrum one FT-IR. The 1H
NMR spectra were recorded using a Bruker AV400MHz spectrometer using CDCl3 as solvent and TMS
as an internal standard. The 13C NMR spectra were determined using TMS as an internal reference with a
Bruker AV400MHz spectrometer operating at 100 MHz. Elemental analyses were performed on a
Perkin-Elmer 240 microanalyser. Purity of compounds was checked by TLC. TLC was carried out on a
Merck Kieselgel GF254. Column chromatography was performed using Merck Kieselgel 60 (0.075-0.15
mm). All of the organic solvents used in this study were dried over appropriate drying agents and distilled
prior to use.
Starting Materials. All other chemicals used in this study were commercially available.
Typical Procedure for the Preparation of Products 4a-4l. A mixture of thiazol-2-amine or
benzo[d]thiazol-2-amine (1 mmol), appropriate aldehyde (1 mmol), ethyl acetoacetate (1.5 mmol) and 5
mL acetic acid was placed in a pressurized microwave vial with snap on cap. The reaction mixture was
subjected to microwave irradiation for appropriate time at 350 W at 80 C. After the completion of the
reaction (as indicated by TLC), the reaction mixture was cooled to room temperature and added to the ice
water. The result precipitate was collected and recrystallized with EtOAc to give pure product for
analysis.
Ethyl 7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4a): light yellow solid, 89%,
1
mp 240.4–240.8 C. IR (KBr): υ 3098, 2983, 1691, 1540, 1290 cm–1. H NMR (400 MHz, CDCl3,) δ:
7.40 (m, 3H, ArH), 7.32 (m, 2H, ArH), 7.17 (d, J = 4.0 Hz, 1H, ArH), 7.01 (d, J = 4.0 Hz, 1H, ArH), 6.38
13
(s, 1H, CH), 4.08–4.19 (m, 2H, CH2), 2,67 (s, 3H, CH3), 1,19 (t, J = 7.2 Hz, 3H, CH3); C NMR (100
MHz, CDCl3,) δ: 166.9, 158.3, 135.3, 129.1, 127.5, 110.2, 100.5, 61.5, 58.7, 23.3, 14.7. Anal. Calcd for
C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33%. Found: C, 63.87; H, 5.31; N, 9.56%.
Ethyl 5-(4-chlorophenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4b): light yellow
1
solid, 85%, mp 138.6–139.6 C. IR (KBr): υ 3068, 2982, 1693, 1575, 1320 cm–1. H NMR (400 MHz,
CDCl3,) δ: 7.28 (d, J = 8.0 Hz, 2H, ArH), 7.26 (d, J = 8.0 Hz, 2H, ArH), 6.52 (d, J = 4.8 Hz, 1H, ArH),
6.29 (d, J = 4.8 Hz, 1H, ArH), 6.16 (s, 1H, CH), 4.04–4.10 (m, 2H, CH2), 2,44 (s, 3H, CH3), 1,18 (t, J =
13
7.2 Hz, 3H, CH3); C NMR (100 MHz, CDCl3,) δ: 167.2, 165,7, 134.8, 129.1, 128.3, 126.4, 99.5, 60.1,
59.8, 23.4, 14.3. Anal. Calcd. for C16H15ClN2O2S: C, 57.40; H, 4.52; N, 8.37%. Found: C, 57.58; H, 4.40;

HETEROCYCLES, Vol. 87, No. 10, 2013
2099
N,8.26%.
Ethyl 5-(4-methoxyphenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4c): light yellow
1
solid, 83%, mp 135.0–135.6 C. IR (KBr): υ 3114, 2981, 1683, 1573, 1317 cm–1. H NMR (400 MHz,
CDCl3,) δ: 7.27 (d, J = 8.4 Hz, 2H, ArH), 6.83 (d, J = 8.4 Hz, 2H, ArH), 6.55 (d, J = 4.8 Hz, 1H, ArH),
6.25 (d, J = 4.8 Hz, 1H, ArH), 6.13 (s, 1H, CH), 4.04–4.09 (m, 2H, CH2), 3.77 (s, 3H, OCH3), 2,44 (s, 3H,
13
CH3), 1,17 (t, J = 7.2 Hz, 3H, CH3); C NMR (100 MHz, CDCl3,) δ: 166.5, 159,7, 135.6, 128.2, 126.7,
114.1, 99.9, 60.1, 59.7, 55.2, 23.0, 14.3. Anal. Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48%.
Found: C, 61.95; H, 5.37; N, 8.47%.
Ethyl 7-methyl-5-(4-nitrophenyl)-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4d): light yellow
1
solid, 95%, mp 137.2–138.3 C. IR (KBr): υ 3073, 2971, 2927, 1653, 1522, 1451, 1202 cm–1. H NMR
(400 MHz, CDCl3,) δ: 8.18 (d, J = 8.8 Hz, 2H, ArH), 7.54 (d, J = 8.8 Hz, 2H, ArH), 6.57 (d, J = 4.8 Hz,
1H, ArH), 6.38 (d, J = 4.8 Hz, 1H, ArH), 6.32 (s, 1H, CH), 4.05–4.13 (m, 2H, CH2), 2,44 (s, 3H, CH3),
13
1,19 (t, J = 7.2 Hz, 3H, CH3); C NMR (100 MHz, CDCl3,) δ: 165.2, 149.1, 147.8, 127.7, 126.1, 124.1,
123.7, 122.7, 111.7, 102.5, 60.7, 57.3, 24.8, 14.3. Anal. Calcd for C16H15N3O4S: C, 55.64; H, 4.38; N,
12.17%. Found: C, 55.52; H, 4.41; N, 12.32%.
Ethyl 5-(4-hydroxy-3-methoxyphenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4e):
light yellow solid, 85%, mp 142.3–143.9 C. IR (KBr): υ 3434, 2971, 1694, 1490, 1277, 1200, 1080 cm–1.
1H NMR (400 MHz, CDCl3,) δ: 6.83–6.88 (m, 3H, ArH), 6.57 (d, J = 4.8 Hz, 1H, ArH), 6.26 (d, J = 4.8
Hz, 1H, ArH), 6.10 (s, 1H, CH), 5.95 (b, 1H, OH), 4.03–4.13 (m, 2H, CH2), 3.84 (s, 3H, OCH3), 2,45 (s,
13
3H, CH3), 1,18 (t, J = 7.2 Hz, 3H, CH3); C NMR (100 MHz, CDCl3,) δ: 166.3, 164.2, 136.4, 128.6,
126.3, 120.9, 101.7, 60.3, 58.9, 56.8, 23.3, 14.3. Anal. Calcd for C17H18N2O4S: C, 58.94; H, 5.24; N,
8.09%. Found: C, 60.04; H, 5.11; N, 7.95%.
Ethyl 5-(furan-2-yl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate (4f): light yellow solid,
1
88%, mp 148.4–149.1 C. IR (KBr): υ 3045, 2974, 2920, 1637, 1480, 1202, 1079 cm–1. H NMR (400
MHz, CDCl3,) δ: 7.33 (b, 1H, ArH), 6.82 (d, J = 4.4 Hz, 1H, ArH), 6.35 (d, J = 4.8 Hz, 1H, ArH), 6.28 (b,
2H, ArH + CH), 6.22 (d, J = 4.8 Hz, 1H, ArH), 4.10–4.14 (m, 2H, CH2), 2,45 (s, 3H, CH3), 1,19 (t, J =
7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3,) δ: 167.5, 163.5, 154.2, 152.7, 143.1, 133.6, 123.0, 110.6,
106.5, 97.8, 61.5, 60.9, 20.7,14.2; Anal. Calcd for C14H14N2O3S: C, 57.92; H, 4.86; N, 9.65%. Found: C,
57.88; H, 4.77; N, 9.89%.

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Ethyl 7-methyl-5-phenyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate (4g): light yellow
1
solid, 88%, mp 184.2–185.1 C. IR (KBr): υ 3069, 2957, 1572, 1519, 1247, 1100 cm–1. H NMR (400
MHz, CDCl3,) δ: 7.47 (t, 3H, J = 8.0 Hz, ArH), 7.18–7.27 (m, 4H, ArH), 7.12 (t, J = 8.0 Hz, 3H, ArH),
13
6.41 (s, 1H, CH), 4.12–4.21 (m, 2H, CH2), 2,46 (s, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH3); C NMR
(100 MHz, CDCl3,) δ: 166.4, 162.8, 158.7, 136.2, 132.9, 127.7, 126.4, 124.0, 123.9, 122.2, 113.9, 111.9,
103.4, 60.09, 57.32, 55.2, 23.3, 14.3. Anal. Calcd for C20H18N2O2S: C, 68.55; H, 5.18; N, 7.99%. Found:
C, 68.69; H, 5.07; N, 7.71%.
Ethyl 5-(4-chlorophenyl)-7-methyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate (4h): light
1
yellow solid, 85%, mp 181.1–182.3 C. IR (KBr): υ 3112, 2971, 1696, 1504, 1240, 1090 cm–1. H NMR
(400 MHz, CDCl3,) δ: 7.42 (d, J = 8.0 Hz, 1H, ArH), 7.33 (d, J = 8.0 Hz, 2H, ArH), 7.18 (t, J = 8.0 Hz,
3H, ArH), 7.11 (t, J = 8.0 Hz, 1H, ArH), 7.02 (t, J = 8.0 Hz, 1H, ArH), 6.35 (s, 1H, CH), 4.08–4.18 (m,
2H, CH2), 2,41 (s, 3H, CH3), 1.25 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3,) δ: 166.3, 163.2,
139.6, 137.7, 134.3, 128.9, 128.5, 126.8, 124.3, 123.9, 122.4, 111.7, 102.8, 60.3, 57.2, 23.4, 14.4. Anal.
Calcd for C20H17ClN2O2S: C, 62.41; H, 4.45; N, 7.28%. Found: C, 62.20; H, 4.62; N, 7.15%.
Ethyl 5-(4-methoxyphenyl)-7-methyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate (4i): light
1
yellow solid, 86%, mp 184.2–185.0 C. IR (KBr): υ 2956, 1695, 1511, 1243, 1175cm–1. H NMR (400
MHz, CDCl3,) δ: 7.44 (d, J = 8.0 Hz, 1H, ArH), 7.35 (d, J = 8.0 Hz, 2H, ArH), 7.23 (d, J = 8.0 Hz, 1H,
ArH), 7.13 (t, J = 8.0 Hz, 2H, ArH), 6.77 (d, J = 8.0 Hz, 2H, ArH), 6.35 (s, 1H, CH), 4.11–4.21 (m, 2H,
CH2), 3.77 (s, 3H, OCH3), 2,45 (s, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3,)
δ: 167.2, 163.4, 159.7, 147.9, 145.2, 137.9, 129.2, 128.0, 127.6, 127.2, 126.6, 124.1, 123.6, 122.7, 102.4,
60.7 57.3, 23.2, 14.3. Anal. Calcd for C21H20N2O3S: C, 66.29; H, 5.30; N, 7.36%. Found: C, 66.11; H,
5.46; N, 7.19%.
Ethyl 5-(4-nitrophenyl)-7-methyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate (4j): light
1
yellow solid, 93%, mp 181.5–182.1 C. IR (KBr): υ 3024, 2951, 1702, 1520, 1242, 1078 cm–1. H NMR
(400 MHz, CDCl3,) δ: 8.13 (d, J = 8.0 Hz, 2H, ArH), 7.61 (d, J = 8.0 Hz, 2H, ArH), 7.49 (d, J = 8.0 Hz,
1H, ArH), 7.26 (t, J = 8.0 Hz, 1H, ArH), 7.18 (t, J = 8.0 Hz, 1H, ArH), 7.03 (d, J = 8.0 Hz, 1H, ArH),
13
6.53 (s, 1H, CH), 4.17–4.21 (m, 2H, CH2), 2,45 (s, 3H, CH3), 1.30 (t, J = 7.2 Hz, 3H, CH3); C NMR
(100 MHz, CDCl3,) δ: 167.2, 163.4, 158.1, 147.8, 145.2, 138.3, 129.7, 126.5, 125.7, 123.1, 122.0, 119.6,
118.5, 115.2, 63.6, 61.7, 2.0, 14.6. Anal. Calcd for C20H17N3O4S: C, 60.75; H, 4.33; N, 10.63%. Found: C,
60.82; H, 4.18; N, 10.46%.

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Ethyl
5-(4-hydroxy-3-methoxyphenyl)-7-methyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carbox-
ylate (4k): light yellow solid, 87%, mp 189.0–191.2 C. IR (KBr): υ 3434, 2920, 1701, 1497, 1274, 1125,
1068 cm–1. 1H NMR (400 MHz, CDCl3,) δ: 7.46 (d, J = 8.0 Hz, 1H, ArH), 7.27 (s, 1H, ArH), 7.15 (t, J =
8.0 Hz, 2H, ArH), 6.92 (d, J = 8.0 Hz, 1H, ArH), 6.91 (d, J = 8.0 Hz, 1H, ArH), 6.77 (d, J = 8.0 Hz, 1H,
ArH), 6.35 (s, 1H, CH), 4.13–4.22 (m, 2H, CH2), 3.81 (s, 3H, OCH3), 2,46 (s, 3H, CH3), 1.29 (t, J = 7.2
13
Hz, 3H, CH3); C NMR (100 MHz, CDCl3,) δ: 166.6, 163.1, 146.9, 145.9, 138.0, 133.3, 126.4, 124.0,
123.9, 122.1, 120.4, 114.1, 109.4, 103.4, 60.1, 57.6, 55.9, 23.4, 14.4. Anal. Calcd for C21H20N2O4S: C,
63.62; H, 5.08; N, 7.07%. Found: C, 63.80; H, 5.24; N, 7.25%.
Ethyl 5-(furan-2-yl)-7-methyl-5H-benzo[d]thiazolo[3,2-a]pyrimidine-6-carboxylate (4l): light yellow
1
solid, 90%, mp 182.2–183.0 C. IR (KBr): υ 3052, 2971, 2918, 1646, 1509, 1455, 1239, 1011 cm–1. H
NMR (400 MHz, CDCl3,) δ: 7.48 (d, J = 8.0 Hz, 1H, ArH), 7.37 (d, J = 15.0 Hz, 1H, ArH), 7.35 (t, J =
15.0 Hz, 1H, ArH), 7.25 (d, J = 8.0 Hz, 1H, ArH), 7.20 (t, J = 8.0 Hz, 1H, ArH), 6.52 (s, 1H, CH), 6.29(d,
J = 3.0 Hz, 1H, ArH), 6.24(d, J = 3.0 Hz, 1H, ArH), 4.13–4.24 (m, 2H, CH2), 2,50 (s, 3H, CH3), 1.26 (t, J
= 7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3,) δ:167.5, 163.1, 154.0, 152.6, 142.1, 139.4, 130.2,
126.4, 122.3 ,122.0, 117.5, 113.8, 110.6, 106.7, 61.2, 60.5, 23.0, 14.4. Anal. Calcd for C18H16N2O3S: C,
63.51; H, 4.74; N, 8.23%. Found: C, 63.36; H, 4.81; N, 8.40%.
ACKNOWLEDGEMENTS
This work was supported by the Science Fund for Young Scholars of Heilongjiang Province of China (no.
QC2009C61), the Program for Young Teachers’ Scientific Research at Qiqihar University (no.
2012K–Z09).
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