Efficient synthesis of 5H-thiazolo[3,2-a]pyrimidines from reactions of 3,4-dihydropyrimidine-thiones with α-bromoacetone in aqueous media

Article abstract of DOI:10.1002/hc.20386

An efficient and convenient method for thiazolo[3,2-a]pyrimidines from cyclization reaction of dihydropyrimidine-thiones with α-bromoacetone in aqueous media is described.

Full text of DOI:10.1002/hc.20386

Heteroatom Chemistry
Volume 19, Number 2, 2008
Efficient Synthesis of
5H-Thiazolo[3,2-a]pyrimidines from
Reactions of 3,4-Dihydropyrimidine-thiones
with α-Bromoacetone in Aqueous Media
Zheng-Jun Quan,1 Zhang Zhang,1 Jun-Ke Wang,1,2 Xi-Cun Wang,1
Ya-Juan Liu,1 and Peng-Yan Ji1
1Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu 730070, People’s Republic of China
2Key Laboratory of Resources and Environment, Chemistry of West China, Department of
Chemistry, Hexi University, Zhangye 734000, People’s Republic of China
Received 3 May 2007; revised 29 June 2007
were largely ignored in the early part of the 20th cen-
ABSTRACT: An efficient and convenient method for
tury [2]. In the past decades, the scope of the original
cyclocondensation reaction was gradually extended
by variation of all three building blocks, allowing
thiazolo[3,2-a]pyrimidines from cyclization reaction
of dihydropyrimidine-thiones with α-bromoacetone in
ꢀ
C
aqueous media is described. 2008 Wiley Periodicals,
access to a large number of structurelly diversified
Inc. Heteroatom Chem 19:149–153, 2008; Published online
multifunctionalized DHPMs [3]. These nonplanar
in Wiley InterScience (www.interscience.wiley.com). DOI
heterocyclic compounds have received considerable
10.1002/hc.20386
attention from the pharmaceutical industry because
of their interesting multifaceted pharmacological
profiles. Synthesis of DHPMs resulted in the discov-
INTRODUCTION
ery of calcium channel modulators, α1a-adrenergic
receptor antagonists, mitotic kinesin inhibitors, and
hepatitis B virus replication inhibitors [4]. Fur-
thermore, apart from synthetic DHPM derivatives,
several marine natural products with interesting
biological activities containing the DHPM core have
recently been isolated [5]. Among these compounds,
the batzelladine alkaloids A and B inhibit the bind-
ing of HIV gp120 human CD4 and, therefore, are
potential new leads for AIDS therapy [6].
Among the synthetic and natural products
containing DHPMs core, thiazolo[3,2-a]pyrimidine
derivatives (1) are of interesting compounds be-
cause of their calcium channel blocking activity [3b].
Few methods have been contributed for the prepa-
ration of thiazolo[3,2-a]pyrimidine derivatives, and
Although the acid-catalyzed one-pot condensation
of aldehyde, ketoester, and urea (or thiourea) to af-
ford 3,4-dihydropyrimidinone (DHPM), named as
the Biginelli reaction after the name of its inventor,
has been known for more than a century [1], the
Biginelli-type 3,4-dihydropyrimidinones (DHPMs)
Correspondence to: Xi-Cun Wang; e-mail; wangxicun@nwnu.
edu.cn.
Contract grant sponsor: Natural Science Foundation of Gansu
Province.
Contract grant number: 3ZS061-A25-019.
Contract grant sponsor: Scientific Research Fund of Gansu
Provincial Education Department.
Contract grant number: 0601-25.
2008 Wiley Periodicals, Inc.
c
ꢀ
149

150 Quan et al.
TABLE 1 Crystal and Experimental Data for Compound 1h
Compound
Formula
1h
C
17H17ClN2O2S
Formula weight
Crystal system
Space group
348
Monoclinic
C 2/c
˚
Unit-cell dimensions (A)
a= 25.457(2), b= 11.697(2),
FIGURE 1 Thiazolo[3,2-a]pyrimidine derivatives.
c= 14.231(3)
α = 90.00◦, β = 106.808(16)◦,
γ = 90.00◦
the existed methodologies required prolonged reac-
tion times and strict reaction conditions in organic
solvents [7,8]. Mishina et al. have completed the
preparation of thiazolo[3,2-a]pyrimidines 1 (Fig. 1)
by the reaction of enones with 2-aminothiazole
in ethanol under refluxing for 2 days [7]. Re-
cently, Balkan et al. have completed the synthesis
of these compounds by refluxing 2-thioxo-1,2,3,4-
tetrahydropyrimidine derivatives with phenacyl bro-
mide in glacial acetic acid [8]. More recently, the
reaction of dihydropyrimidine-2-thiones with α-
bromophenylacetaldehyde in acetonitrile to afford
thiazolo[3,2-a]pyrimidines has also been reported
[9]. However, in spite of their potential utility in
the preparation of this type of compounds, many of
these methods involve organic solvent, long-reaction
times, and unsatisfactory yields. Furthermore, to the
best of our knowledge, there has been no report on
the synthesis of thiazolo[3,2-a]pyrimidine analogs
by the reaction of DHPMs with α-bromoacetone in
aqueous media.
The use of water as a medium in organic re-
action has received considerable attention because
of its several advantages, such as it is the cheapest
solvent available on the earth, nonhazardous to the
environment, and nontoxic, and isolation of the or-
ganic products can be performed by simple phase
separation. Also, there are beneficial effects of aque-
ous solvents on the rates and selectivity of impor-
tant organic transformations, for example, the Diels–
Alder reaction, aldol reaction, and Michael addition
[10,11].
3
˚
Unit-cell volume, V (A )
4056.54 (1964)
4
Formula per unit cell, Z
Calc. density Dcalcd (g/cm3) 1.296
RESULTS AND DISCUSSION
To study the reaction for thiazolo[3,2-a]pyrimidines
1, we tested the reaction of 1a with α-bromoacetone
as simple model substrate and the results are shown
in Table 1. First, α-bromoacetone was used in a mo-
lar excess (2:1) to test the reaction in the presence
1
of K2CO3 as a base in refluxing water for 4 h. H
NMR and mass spectrometry indicated that during
this reaction the desired product 1a was obtained
with good yield (90%). After experimentation with
a variety of molar material, bases, temperatures,
and reaction times, we quickly arrived at conditions
where complete and clean conversion of the model
substrate DHPM 1a with α-bromoacetone could be
achieved within 4 h under refluxing water. These op-
timized conditions were equal amount of starting
material 1 and α-bromoacetone in refluxing water
for 4 h.
Under the optimized conditions, 3,4-dihydro-
pyrimidine-2-thiones (2) were treated with α-bromo-
acetone in refluxing water for 4 h to give thiazolo[3,2-
a]pyrimidines (1a–j) in good yields (Scheme 1).
To compare this procedure with the conventional
method in organic solvent, we carried out the
reaction for 1 by previously mentioned materials
in acetone. This reaction can also be completed
smoothly to afford the desired products. These
results are listed in Table 1. It can be indicated that
water is the optical solvent in this reaction from the
environment friendly point of view.
We herein report a methodology to efficiently
prepare 5H-thiazolo[3,2-a]pyrimidines through a
cyclization reaction of 3,4-dihydropyrimidine-2-
thione and α-bromoacetone in aqueous media.
SCHEME 1 Synthesis of 5H-thiazolo[3,2-a]pyrimidines 1a–j in water.
Heteroatom Chemistry DOI 10.1002/hc

Efficient Synthesis of 5H-Thiazolo[3,2-a]pyrimidines from Reactions of 3,4-Dihydropyrimidine-thiones 151
Crystallographic Data Centre as supplementary pub-
lication (for 1h CCDC No. CCDC 651561).
In this reaction, the nucleophilic addition of sul-
fur of dihydropyrimidine-thione to the α-position
of α-bromoacetone gave 3, followed by addition–
elimination to give dihydropyrimidine-fused thi-
azole 1 (Table 3). The regioselectivity of the
addition-cyclization step maybe due to a difference
in the electron density at N3 and N1 position
of 3,4-dihydropyrimidine-thione. The higher ba-
sisity of the former resulted in exclusive addition–
cyclization at this position [12]. Our previous
study also confirmed that the N3 atom possess
FIGURE 2 The ORTEP representation of the 1h.
higher reactivity than the N1 atom [13]. Moreover,
it has been reported that 3,4-dihydropyrimidine-
thiones reacted with 1,2-dichloroethane, affording
thiazolo[3,2-a]pyrimidines [14].
All the compounds were characterized by IR,
1H NMR, 13C NMR, MS, and elemental analyses.
1
Comparing the H NMR spectra with the data of
In summary, 5H-thiazolo[3,2-a]pyrimidine
can be efficiently prepared by the reaction of
dihydropyrimidine-2-thione with α-bromoacetone
only in water medium. The easy and efficacy of this
method provides an attractive route to the synthesis
of 5H-thiazolo[3,2-a]pyrimidine derivatives. To
the best of our knowledge, there has not been
any report on the preparation of 5H-thiazolo[3,2-
a]pyrimidine derivatives through the reaction of
dihydropyrimidine-thione with α-bromoacetone,
using water as the only solvent.
DHPMs 2 and relative cyclization products 1 shows
that peaks corresponding to the proton of N1 around
δ 7.80 and N3 around δ 6.30 disappeared at the same
time as the presence of the peaks corresponded to
the proton of C CH around δ 7.08. Meanwhile, the
C4 H comes as a singlet around δ 6.30 in the prod-
ucts, which is around δ 5.30 in DHPMs. The most
distinct signal between IR absorption of DHPMs 2
and products thiazolo[3,2-a]pyrimidines 1 is the dis-
appearance of two absorption around 3320 and 3118
cm−1, with the disappearance of absorption bands
around 1680 cm−1 corresponding to C O. The single
crystal X-ray crystallography of product 1h also con-
firmed the structures of obtained products (Fig. 2;
Tables 1 and 2). Crystallographic data for the struc-
ture analysis have been deposited at the Cambridge
EXPERIMENTAL
All reagents were obtained commercially and used
without further purification. Melting points were de-
termined on an XT-4 electrothermal micromelting
◦
˚
TABLE 2 Bond Lengths (A) and Angles ( ) for Compound 1h
C1–C2
C1–C6
C1–C7
C2–C3
C3–C4
C4–C5
C4–Cl1
C5–C6
1.397(6)
1.381(5)
1.587(5)
1.374(6)
1.398(6)
1.395(6)
1.781(4)
1.388(5)
1.538(5)
1.521(5)
1.414(5)
119.4(4)
120.3(4)
120.2(4)
119.4(4)
118.4(3)
122.2(4)
120.1(4)
120.2(4)
119.9(4)
120.7(3)
C8–C15
C9–N1
1.488(5)
1.450(5)
1.484(6)
1.332(5)
1.359(5)
1.799(4)
1.407(6)
1.801(4)
1.438(5)
1.504(5)
C13–H13A
C13–H13B
C13–H13C
C14–H14A
C14–H14B
C14–H14C
C15–O1
C15–O2
C16–C17
C16–O2
0.9600
0.9600
0.9600
0.9600
0.9600
0.9600
1.241(4)
1.355(5)
1.503(5)
1.514(4)
C9–C14
C10–N1
C10–N2
C10–S1
C11–C12
C11–S1
C12–N2
C12–C13
C7–C8
C7–N2
C8–C9
C2–C1–C7
C3–C2–C1
C2–C3–C4
C5–C4–C3
C5–C4–Cl1
C3–C4–Cl1
C6–C5–C4
C1–C6–C5
C6–C1–C2
C6–C1–C7
C8–C9–N1
116.6(3)
131.3(4)
124.2(4)
126.1(3)
109.7(3)
109.4(3)
112.9(4)
126.4(4)
120.7(3)
109.1(3)
N2–C7–C1
C8–C7–C1
C9–C8–C15
C9–C8–C7
C15–C8–C7
O1–C15–O2
O1–C15–C8
O2–C15–C8
C17–C16–O2
C10–S1–C11
108.1(3)
111.4(3)
124.8(3)
123.2(3)
111.9(3)
123.2(4)
121.1(4)
115.6(3)
109.6(3)
91.78(19)
C8–C9–C14
N1–C10–N2
N1–C10–S1
N2–C10–S1
C12–C11–S1
C11–C12–N2
C11–C12–C13
N2–C12–C13
N2–C7–C8
Heteroatom Chemistry DOI 10.1002/hc

152 Quan et al.
TABLE 3 Synthesis of 5H-Thiazolo[3,2-a]pyrimidines 1a–j
in Water and Acetone
(M + 1); Anal. Calcd for C17H18N2O2S: C, 64.94; H,
5.77; N, 8.91. Found: C, 65.07; H, 5.71; N, 8.78.
Yield (%)a
6-Ethoxycarbonyl-7-methyl-5-(4-hydroxyphenyl)-
5H-thiazolo[3,2-a]pyrimidine (1b)
Product
Ar
In Waterb
In Acetonec
mp 229–230◦C. IR (KBr) ν: 3382, 3112, 2986, 1689,
1605, 1530, 1260; 1H NMR (400 MHz, DMSO):
δ = 1.17 (t, J = 7.2 Hz, 3H), 2.19 (s, 3H), 2.39 (s, 3H),
4.02–4.13 (m, 2H), 6.27 (s, 1H), 6.74 (dd, J = 8.4 Hz,
J = 2.4 Hz, 2H), 7.08 (s, 1H), 7.12 (bs, 1H), 7.15
(d, J = 9.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
δ = 13.49, 14.15, 18.34, 59.09, 61.25, 102.93, 110.34,
126.67, 129.39, 129.63, 136.22, 139.08, 143.11,
160.57, 164.41; MS (FAB): m/z = 331 (M + 1); Anal.
Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48.
Found: C, 61.98; H, 5.58; N, 8.37.
1a
1b
1c
1d
1e
1f
C6H5
89
85
85
94
81
83
84
86
90
92
91
86
88
93
82
86
86
88
90
92
4-HOC6H4
2-CH3OC6H4
4-CH3OC6H4
4-NO2C6H4
3-NO2C6H4
4-ClC6H4
2-ClC6H4
4-CH3C6H4
2-CH3C6H4
1g
1h
1i
1j
aDetermined based on DHPMs and on weight of isolated sample.
bObtained by the reaction of DHPM with α-bromoacetone in water.
cObtained by the reaction of DHPM with α-bromoacetone in acetone
at 50◦C for 4 h.
6-Ethoxycarbonyl-7-methyl-5-(2-methoxyphen-
yl)-5H-thiazolo[3,2-a]pyrimidine (1c)
point apparatus and uncorrected. IR spectra were
recorded using KBr pellets on a Digilab Merlin FT-
IR spectrophotometer. NMR spectra were recorded
at 400 (1H) and 100 (13C) MHz, respectively, on a
Varian Mercury plus-400 instrument using CDCl3
or DMSO-d6 as solvent and TMS as an internal
standard. Elemental analyses were performed on
a Carlo-Erba 1106 elemental analysis instrument.
Mass-spectra were recorded on a ZAB-HS instru-
ment. Compounds 2a–j were prepared by following
the reported method [15].
mp 221–223◦C. IR (KBr) ν: 3086, 2976, 1692, 1605,
1530, 1461, 1236; 1H NMR (400 MHz, CDCl3): δ
= 1.17 (t, J = 7.2 Hz, 3H), 2.18 (s, 3H), 2.42 (s, 3H),
3.85 (s, 3H), 4.09 (q, J= 7.0 Hz, 2H, CH2O), 6.28
(s, 1H), 6.84 (dd, 1 H, J = 8 Hz, 0.8 Hz), 6.91 (t,
1 H, J = 0.8 Hz), 7.03 (s, 1H), 7.22 (t, 1H, J = 0.8
Hz), 7.35–7.32 (dd, 1H, J = 8 Hz, 1.6 Hz); 13C NMR
(100 MHz, CDCl3): δ = 13.5, 14.2, 19.3, 59.0, 58.7,
61.6, 102.9, 110. 2, 121.3, 129.1, 129.7, 129.7, 136.1,
146.0, 155.8, 160.2, 165.4; MS (FAB): m/z = 345 (M
+ 1); C18H20N2O3S: C, 62.77; H, 5.85; N, 8.13. Found:
C, 63.01; H, 5.75; N, 8.33.
Experimental Procedure
Bromoacetone (1.5 mmol) was added to a suspen-
sion of 3,4-dihydropyrimidine-thione 2a–j (1 mmol)
in water (5 mL). After the reaction mixture was
stirred under refluxing for 4 h, the resulting mix-
ture was cooled to room temperature. Then, the pre-
cipitate was filtered and washed with aqueous solu-
tion of NaOH (1%) and subsequently with water. The
solid was recrystallization from ethanol–acetone to
give a pure product in high yield.
6-Ethoxycarbonyl-7-methyl-5-(4-methoxyphen-
yl)-5H-thiazolo[3,2-a]pyrimidine (1d)
mp 227–228◦C. IR (KBr) ν: 3106, 2974, 1689, 1605,
1530, 1461, 1248; 1H NMR (400 MHz, CDCl3):
δ = 1.18 (t, J = 7.2 Hz, 3H), 2.18 (s, 3H), 2.35 (s, 3H),
3.78 (s, 3H), 4.06–4.15 (m, 2H), 6.30 (s, 1H), 6.80 (d,
J = 8.8 Hz, 2H), 7.05 (s, 1H), 7.23 (d, J = 8.8 Hz, 2H);
13C NMR (100 MHz, CDCl3): δ = 13.6, 14.7, 18.3, 59.0,
59.9, 61.1, 102.9, 108.6, 113.9, 127.8, 129.6, 136.1,
146.1, 163.6, 159.2, 164.7; MS (FAB): m/z = 345 (M
+ 1); C18H20N2O3S: C, 62.77; H, 5.85; N, 8.13. Found:
C, 62.58; H, 5.99; N, 7.98.
6-Ethoxycarbonyl-7-methyl-5-phenyl-5H-
thiazolo[3,2-a]pyrimidine (1a)
mp 242–243◦C. IR (KBr) ν: 3106, 2986, 1668, 1572,
1602, 1491, 1242; 1H NMR (400 MHz, CDCl3):
δ = 1.30 (t, J = 7.2 Hz, 3H), 2.26 (s, 3H), 2.63
(s, 3H), 4.16–4.28 (m, 2H), 6.33 (s, 1H), 7.05
(s, 1H), 7.27 (dd, J = 6.0 Hz, J= 3.6 Hz, 2H),
7.33 (dd, J = 6.4 Hz, J = 3.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ = 13.49, 14.15, 18.34, 59.09,
61.25, 102.93, 110.34, 126.67, 129.39, 129.63, 136.22,
139.08, 143.11, 160.57, 164.41; MS (FAB): m/z = 315
6-Ethoxycarbonyl-7-methyl-5-(4-nitrophenyl)-
5H-thiazolo[3,2-a]pyrimidine (2e)
mp 243–244◦C. IR (KBr) ν: 3088, 1722, 1648, 1608,
1527, 1473, 1239; 1H NMR (400 MHz, CDCl3):
δ = 1.29 (t, J = 8.4 Hz, 3H), 2.01 (s, 3H), 2.60 (s, 3H),
4.19–4.24 (m, 2H), 6.46 (s, 1H), 7.09 (s, 1H), 7.45 (d,
J = 8.4, 2H), 7.33 (d, J = 9.2 Hz, 2H); 13C NMR (100
Heteroatom Chemistry DOI 10.1002/hc

Efficient Synthesis of 5H-Thiazolo[3,2-a]pyrimidines from Reactions of 3,4-Dihydropyrimidine-thiones 153
MHz, CDCl3): δ = 13.5, 14.2, 18.6, 59.1, 61.8, 102.0,
δ = 1.17 (t, J = 7.2 Hz, 3H), 2.24 (s, 3H), 2.36 (s,
3H), 2.48 (s, 3H), 4.17–4.20 (m, 2H), 6.31 (s, 1H),
6.80 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 7.05 (s,
1H), 7.24 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ = 14.2, 14.3, 18.6, 19.1, 59.5, 61.8, 103.7,
110.2, 127.1, 129.5, 134.7, 136.5, 138.2, 141.3, 160.1,
164.5; MS (FAB): m/z = 329 (M + 1); Anal. Calcd for
C18H20N2O2S: C, 65.83; H, 6.14; N, 8.53. Found: C,
65.98; H, 5.99; N, 8.38.
111.3, 124.7, 127.9, 135.8, 144.4, 145.1, 148.4, 160.9,
164.3; MS (FAB): m/z = 360 (M + 1); Anal. Calcd for
C17H17N3O4S: C, 56.81; H, 4.77; N, 11.69. Found C,
56.96; H, 4.71; N, 11.55.
6-Ethoxycarbonyl-7-methyl-5-(3-nitrophenyl)-
5H-thiazolo[3,2-a]pyrimidine (2f)
mp 241–243◦C. IR (KBr) ν: 3088, 1692, 1606, 1527,
1
1473, 1223; H NMR (400 MHz, CDCl3): δ = 1.14 (t,
3H, J= 7.2 Hz, CH3CH2O), 2.35 (s, 3H, CH3), 2.60
(s, 3H), 4.01 (q, 2H, J= 7.2 Hz, CH3CH2O), 6.42 (s,
1H), 7.09 (s, 1H), 7.75–7.64 (m, 2H), 8.14–8.05 (m,
2H); 13C NMR (100 MHz, CDCl3): δ = 13.5, 14.2, 18.6,
58.5, 61.7, 103.0, 111.3, 120.7, 125.8, 130.7, 135.6,
138.8, 145.2, 148.5, 155.5, 160.7, 164.3; MS (FAB):
m/z = 360 (M + 1); Anal. Calcd for C17H17N3O4S: C,
56.81; H, 4.77; N, 11.69. Found C, 56.98; H, 4.65; N,
11.80.
6-Ethoxycarbonyl-7-methyl-5-(2-methylphenyl)-
5H-thiazolo[3,2-a]pyrimidine (1j)
mp 252–253◦C. IR (KBr) ν: 3110, 2977, 1688, 1649,
1603, 1534, 1254, 1105; 1H NMR (400 MHz, CDCl3):
δ = 1.27 (t, J = 7.2 Hz, 3H), 2.21 (s, 3H), 2.55 (s,
3H), 2.62 (s, 3H), 4.17–4.20 (m, 2H), 6.51 (s, 1H),
6.85 (s, 1H), 7.18–7.29 (m, 4H); 13C NMR (100 MHz,
CDCl3): δ = 13.8, 14.2, 18.5, 19.2, 56.6, 61.3, 103.4,
109.2, 127.7, 128.5, 129.6, 131.4, 134.7, 136.7, 138.2,
142.2, 160.6, 164.7; MS (FAB): m/z = 329 (M + 1);
Anal. Calcd for C18H20N2O2S: C, 65.83; H, 6.14; N,
8.53. Found: C, 65.67; H, 5.98; N, 8.70.
6-Ethoxycarbonyl-7-methyl-5-(4-chlorophenyl)-
5H-thiazolo[3,2-a]pyrimidine (1g)
mp 241–242◦C. IR (KBr) ν: 3112, 2986, 1683, 1638,
1608, 1524, 1494, 1269; 1H NMR (400 MHz, CDCl3):
δ = 1.22 (t, J = 7.2 Hz, 3H), 2.00 (s, 3H), 2.55 (s,
3H), 4.10–4.21 (m, 2H), 6.27 (s, 1H), 7.10 (s, 1H),
7.14–7.24 (m, 2H), 7.26–7.29 (m, 2H); 13C NMR (100
MHz, CDCl3): δ = 13.4, 14.1, 18.3, 58.4, 61.3, 102.6,
111.1, 128.1, 129.5, 135.6, 135.9, 137.5, 143.2, 160.4,
164.2; MS (FAB): m/z = 349 (M + 1); Anal. Calcd for
C17H17ClN2O2S: C, 58.53; H, 4.91; N, 8.03; Found: C,
58.74; H, 5.12; N, 7.88.
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6-Ethoxycarbonyl-7-methyl-5-(2-chlorophenyl)-
5H-thiazolo[3,2-a]pyrimidine (1h)
mp 243–245◦C. IR (KBr) ν: 3088, 2991, 1692, 1649,
1606, 1527, 1473, 1223; 1H NMR (400 MHz, CDCl3):
δ = 1.13 (t, 3H, J= 7.2 Hz, CH3CH2O), 2.43 (s, 3H,
CH3), 2.60 (s, 3H), 4.05–3.99 (m, 2H, CH2O), 6.46
(s, 1H), 7.08 (s, 1H), 7.31–7.18 (m, 3H), 7.51 (dd,
1H, J = 8 Hz, 1.6 Hz); 13C NMR (100 MHz, CDCl3):
δ = 14.2, 19.6, 22.9, 59.5, 61.7, 103.0, 110.1, 126.3,
128.5, 129.6, 133.6, 134.8, 140.1, 143.4, 154.5, 161.0,
165.1; MS (FAB): m/z = 349 (M + 1); Anal. Calcd for
C17H17ClN2O2S: C, 58.53; H, 4.91; N, 8.03. Found C,
58.72; H, 4.99; N, 8.23.
6-Ethoxycarbonyl-7-methyl-5-(4-methylphenyl)-
5H-thiazolo[3,2-a]pyrimidine (1i)
[15] Fu, N. Y.; Yuan, Y. F.; Cao, Z.; Wang, S. W.;
Wang, J. T.; Peppe, C. Tetrahedron 2002, 58,
4801.
mp 251–253◦C. IR (KBr) ν: 3088, 2976, 1694, 1645,
1604, 1532, 1254, 1103; 1H NMR (400 MHz, CDCl3):
Heteroatom Chemistry DOI 10.1002/hc