Synthesis of polysubstituted 5-aminopyrimidine-2(1H)-thiones from vinyl azides and thiourea

Article abstract of DOI:10.1016/j.tet.2012.05.057

A simple, straightforward, and efficient method for the synthesis of polysubstituted 5-aminopyrimidine-2(1H)-thiones from vinyl azides and thiourea was developed. This reaction proceeded under relatively mild conditions and need no additional additives. Additionally, a possible mechanism for the entire sequence is proposed.

Full text of DOI:10.1016/j.tet.2012.05.057

Tetrahedron 68 (2012) 6565e6568
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Synthesis of polysubstituted 5-aminopyrimidine-2(1H)-thiones from vinyl azides
and thiourea
*
*
Zhanying Shao, Qinhai Pan, Jun Chen, Yongping Yu , Guolin Zhang
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple, straightforward, and efficient method for the synthesis of polysubstituted 5-aminopyrimidine-
2(1H)-thiones from vinyl azides and thiourea was developed. This reaction proceeded under relatively
mild conditions and need no additional additives. Additionally, a possible mechanism for the entire
sequence is proposed.
Received 20 March 2012
Received in revised form 7 May 2012
Accepted 15 May 2012
Available online 29 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
5-Aminopyrimidine
Azides
Thiourea
Cyclization
Mechanism
1. Introduction
from a
-azidovinyl ketones and amidines.15 In this paper, we pres-
ent a simple and straightforward reaction to provide the poly-
Pyrimidines, as a class of important and widespread heterocy-
cles, are widely distributed in active compounds.1 The pyrimidine
nucleotides have been recognized as important signaling mole-
cules.2 Some of these compounds have been proved to possess
antitumor,3 anti-inflammatory,4 anti-viral,5 anti-proliferative ac-
tivities,6 as well as the potential to inactivate human DNA repair.7 5-
Aminopyrimidine and pyrimidine thioethers derivatives show im-
portant pharmacological activities in many ways, such as anti-
anoxic, anti-lipid peroxidation activities to ameliorate brain is-
chemic damage and anti-HIV.8,9
Notably, the direct syntheses of 5-aminopyrimidinethiones are
rare in literature. The most common method for the preparation of
5-aminopyrimidines needs multiple steps.10,11 In this regard, de-
velopment of a facile access to synthesis polysubstituted 5-
aminopyrimidinethiones is desirable.
substituted 5-aminopyrimidine-2(1H)-thiones from vinyl azides.
2. Results and discussion
Initially, the experiment was carried out using 2-azido-3-(4-
bromophenyl)-1-(4-chlorophenyl)prop-2-en-1-one and thiourea
(Table 1). The reaction between vinyl azides and thiourea without
any heating gave the corresponding product in only 24% yield
(Table 1, entry 1). Temperature screening showed that the in-
creasing of the temperature was beneficial to the reaction (Table 1,
entries 1e6), and the best yield was up to 91%. However in the
reaction at 80 ꢀC, the yield of the product was decreased to 88%
(Table 1, entry 7). The above studies showed that temperature 60 ꢀC
is satisfactory to obtain the maximum yield of the product (Table 1,
entry 6).
Vinyl azide is an important three-atom synthon to form nitro-
gen-containing heterocycles. By exploiting the literature, novel
synthetic strategies exploiting vinyl azide have been emerged.12e14
Vinyl azides as a three-atom unit including one nitrogen to syn-
thesize heterocycles. Our previous work has developed an efficient
methodology to prepare structurally diverse 5-aminopyrimidines
Further, we have screened different solvents and DMF proved to
be the best solvent (Table 1, entries 5, 8e13). Various times in this
reaction were studied, and the results are shown in Table 1, entries
5, 14e17. It indicated that more than 12 h of time was meaningless.
Different equivalents of thiourea were added to the reaction (Table
1, entries 5, 18e20). Evidently, 2 equiv were suitable. On the basis of
above studies, the optimal reactivity was obtained in DMF at 60 ꢀC
when 2 equiv of thiourea was added.
Based on the optimal reaction condition, the scope of the re-
action was studied using a series of vinyl azides 1 and thiourea 2.
The vinyl azides were prepared from the corresponding olefins by
* Corresponding authors. Tel./fax: þ86 571 88208450 (Y.Y.); tel./fax: þ86 571
88208452 (G.Z.); e-mail addresses: yyu@zju.edu.cn (Y. Yu), guolinzhang@zju.edu.cn
(G. Zhang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.057

6566
Z. Shao et al. / Tetrahedron 68 (2012) 6565e6568
Table 2 (continued)
Table 1
Optimization of reaction conditionsa
Entry
R1
R2
R3
Product Yieldb (%)
9
H
H
H
H
H
3i
70
82
49
55
57
10
11
12
13
3j
Entry
Solvent
Temp (ꢀC)
Time (h)
Thiourea (equiv)
Yieldb (%)
3k
3l
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
CH3CN
CH3OH
THF
CHCl3
1,4-Dioxane
DMF
DMF
DMF
DMF
DMF
20
30
40
50
60
70
80
50
60
60
60
60
60
60
60
60
60
60
60
60
12
12
12
12
12
12
12
12
12
12
12
12
12
24
5
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1.5
4
24
32
61
83
91
91
88
63
75
71
86
48
52
91
35
20
13
77
84
91
3m
14
15
16
17
18
H
H
H
H
3n
37
9
10
11
12
13
14
15
16
17
18
19
20
Trace
Trace
Trace
0
2
1
12
12
12
DMF
DMF
a
Reaction conditions: vinyl azide (0.2 mmol, 1.0 equiv), thiourea, solvent (3 mL).
The yield of the isolated product.
b
19
0
successive reaction with bromine then with sodium azide,16
respectively.
As Table 2 shows, various substituted vinyl azides with thiourea
worked well to provide polysubstituted 5-aminopyrimidine-2(1H)-
thiones. It showed that aromatic substituted vinyl azides with
various steric and electronic properties were applicable to this
reaction.
a
Reaction conditions: vinyl azide (0.2 mmol, 1.0 equiv), thiourea (0.4 mmol,
2.0 equiv), solvent (3 mL), 12 h, 60 ꢀC.
b
The yield of the isolated product.
First, the experiment carried out with R1 as 4-chlorophenyl. It
indicated that electron-withdrawing groups were more helpful to
the reaction than electron-donating groups. When the stronger
electron-withdrawing group substituted at the aryl ring, the yield
was raised as well (Table 2, entries 1e7). This law was also suitable
when R1 was other substituted aryl ring (Table 2, entries 11e13).
Notably, similar tendency was found when R2 was fixed (Table 2,
entries 8e10). The retarding effect of sterics on the reaction is il-
lustrated in entry 6 where ortho substituents on the aryl ring gave
slightly reduced yield (88%), compared to entry 7 (90%).
Furthermore, this procedure was then evaluated for its general
applicability. The use of vinyl azide bearing a thienyl at the R2-
position (Table 2, entry 14) gave low yield of the desired products
(37%). Treatment of vinyl azide with an isopropyl, gave the product
in trace yield (Table 2, entry 15). When R1 was substituted with
methyl or ethyl group, the corresponding product was obtained
with trace yield (Table 2, entries 16 and 17). However, no desired
product was detected when the reaction was performed with 1-(p-
tolyl)thiourea or 1-(4-chlorophenyl)thiourea (Table 2, entries 18
and 19).
Nevertheless, this new reaction constitutes an efficient and
simple way to carry out the formation of polysubstituted 5-
aminopyrimidine-2(1H)-thiones. This synthetic method is novel
and requires few steps.
On the basis of the results presented above, we proposed the
possible mechanism for this reaction, as shown in Scheme 1. The
reaction expected to rely on Michael addition of the thiourea 2 to
the vinyl azides 1 affording an active intermediate I. N2 was elim-
inated in the active intermediate I to afford II, followed by sub-
sequent intramolecular nucleophilic attack to the carbonyl group.
Dehydration of cyclized intermediate III and further rearrangement
of IV provided the desired product 3.
Table 2
Reactions of various vinyl azides with thioureaa
Entry
R1
R2
R3
Product Yieldb (%)
1
2
H
H
3a
3b
77
78
3
4
5
6
H
H
H
H
3c
3d
3e
3f
52
95
93
88
7
8
H
H
3g
3h
91
66

Z. Shao et al. / Tetrahedron 68 (2012) 6565e6568
6567
S
NMR (500 MHz, DMSO-d6)
d
8.23 (d, J¼8.6 Hz, 2H), 7.99 (s, 1H), 7.80
S
H2N
O
R2
O
(d, J¼8.6 Hz, 2H), 7.52e7.44 (m, 6H), 7.41 (t, J¼7.4 Hz, 2H), 7.35 (t,
OH HN
NH2
S
N3
R1
NH
-N2
+
J¼7.2 Hz,1H), 7.12 (d, J¼8.6 Hz, 2H), 5.19 (s, 2H); 13C NMR (125 MHz,
R1
N
R2
H2N
NH2
R1
R2
DMSO-d6)
d 163.01, 160.79, 152.61, 143.76, 137.18, 134.82, 134.13,
N
N
NH
II
132.24, 130.97, 130.19, 129.89, 128.95, 128.53, 128.43, 128.27, 115.77,
69.90. HRMS (ESI) m/z calcd for C23H18ClN3OS [MþH]þ: 420.0932.
Found: 420.0931.
2
1
I
S
S
4.2.3. 5-Amino-4-(4-chlorophenyl)-6-(4-methoxyphenyl)pyrimi-
S
dine-2(1H)-thione (3c). Pale yellow solid; mp: 177.4e178.9 ꢀC; 1H
N
NH
R2
N
NH
R2
H
-H2
O
HN
NH
R2
HO
R1
NMR (500 MHz, DMSO-d6)
d
8.23 (d, J¼8.7 Hz, 2H), 8.00 (s, 1H), 7.81
R1
R1
(d, J¼8.7 Hz, 2H), 7.49 (d, J¼8.7 Hz, 2H), 7.46 (s, 2H), 7.05 (d,
NH2
NH
IV
NH
III
J¼8.7 Hz, 2H), 3.83 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
d 163.01,
3
160.79, 152.61, 143.76, 137.18, 134.82, 134.13, 132.24, 130.97, 130.19,
129.89, 128.95, 128.53, 128.43, 128.27, 115.77, 69.90. HRMS (ESI) m/z
calcd for C17H14ClN3OS [MþH]þ: 344.0619. Found: 344.0613.
Scheme 1. Proposed mechanism for the synthesis of 5-aminopyrimidine-2(1H)-
thione.
3. Conclusion
4.2.4. 5-Amino-4-(4-chlorophenyl)-6-(4-fluorophenyl)pyrimidine-
2(1H)-thione (3d). Pale yellow solid; mp: 213.1e214.4 ꢀC; 1H NMR
In conclusion, we have developed a simple, straightforward, and
efficient method for the synthesis of polysubstituted 5-
aminopyrimidine-2(1H)-thione. The reaction is realized by 1,4-
Michael addition and subsequent rearrangement and moreover it
is economical in atom count as only a molecule of nitrogen and
water is lost in the entire process.
(500 MHz, DMSO-d6)
d
8.21 (d, J¼8.7 Hz, 2H), 8.06 (s, 1H), 7.90 (t,
J¼8.7, 5.7 Hz, 2H), 7.57 (s, 2H), 7.50 (d, J¼8.7 Hz, 2H), 7.32 (t,
J¼8.8 Hz, 2H); 13C NMR (125 MHz, DMSO-d6)
d 164.76, 163.62,
162.78, 151.50, 145.07, 134.14, 133.93, 133.57, 132.53, 131.12, 130.58,
128.58, 116.57, 116.40. HRMS (ESI) m/z calcd for C16H11ClFN3S
[MþH]þ: 332.0419. Found: 332.0414.
4. Experimental section
4.1. General method
4.2.5. 5-Amino-4,6-bis(4-chlorophenyl)pyrimidine-2(1H)-thione
(3e). Pale yellow solid; mp: 206.2e208.4 ꢀC; 1H NMR (500 MHz,
DMSO-d6)
d
8.20 (d, J¼8.7 Hz, 2H), 8.04 (s, 1H), 7.85 (d, J¼8.5 Hz,
2H), 7.63 (s, 2H), 7.54 (d, J¼8.5 Hz, 2H), 7.51 (d, J¼8.7 Hz, 2H); 13C
All solvents were purified according to standard methods prior
to use. Reactions were run under an atmosphere in air. Purifications
of reaction products were carried out by chromatography using
silica gel (200e300mesh). Melting points were recorded on
NMR (125 MHz, DMSO-d6)
d 163.93, 151.21, 145.66, 135.82, 135.20,
134.04,133.86,132.65,131.17,129.92,129.47,128.60. HRMS (ESI) m/z
calcd for C16H11Cl2N3S [MþH]þ: 348.0123. Found: 348.0120.
€
a BUCHI B-540 melting point apparatus. NMR spectra were recor-
4.2.6. 5-Amino-6-(2-bromophenyl)-4-(4-chlorophenyl)pyrimidine-
ded for 1H NMR at 500 MHz and for 13C NMR at 125 MHz. For 1H
2(1H)-thione (3f). Pale yellow solid; mp: 234.7e236.9 ꢀC; 1H NMR
NMR, tetramethylsilane (TMS) served as internal standard (
and data are reported as follows: chemical shift, integration, mul-
d
¼0)
(500 MHz, DMSO-d6)
J¼7.8, 1.2 Hz, 1H), 7.75 (s, 2H), 7.71 (d, J¼7.8 Hz, 1H), 7.51 (m, 3H),
7.40e7.32 (m, 1H); 13C NMR (125 MHz, DMSO-d6)
164.17, 149.64,
d
8.20 (d, J¼8.6 Hz, 2H), 8.16 (s, 1H), 8.03 (dd,
tiplicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet),
d
and coupling constant(s) in hertz. For 13C NMR, TMS (
d
¼0) or DMSO
146.86, 134.71, 133.89, 133.84, 133.64, 132.96, 132.34, 131.29, 128.80,
128.67, 128.59, 124.63. HRMS (ESI) m/z calcd for C16H11BrClN3S
[MþH]þ: 391.9618. Found: 391.9673.
(
d
¼40.45) was used as internal standard and spectra were obtained
with complete proton decoupling. HRMS data were obtained using
ESI ionization. The starting material 1a, 1b, 1c, 1d, 1e, 1f, 1h, 1i, 1j,
1k, 1l, 1m, 1n were prepared according to literature methods.16,17
4.2.7. 5-Amino-6-(4-bromophenyl)-4-(4-chlorophenyl)pyrimidine-
2(1H)-thione (3g). Pale yellow solid; mp: 203.4e204.6 ꢀC; 1H NMR
4.2. General procedure for the synthesis of 3
(500 MHz, DMSO-d6)
J¼7.9 Hz, 2H), 7.67 (d, J¼7.2 Hz, 2H), 7.64 (s, 2H), 7.51 (d, J¼8.4 Hz,
2H); 13C NMR (125 MHz, DMSO-d6)
163.96, 151.30, 145.73, 136.17,
134.07, 133.89, 132.66, 132.38, 131.18, 130.13, 128.59, 124.08. HRMS
(ESI) m/z calcd for C16H11BrClN3S [MþH]þ: 391.9618. Found:
391.9658.
d
8.20 (d, J¼8.7 Hz, 2H), 8.03 (s, 1H), 7.78 (d,
A mixture of vinyl azide 1 (0.2 mmol) and thiourea 2 (0.4 mmol)
was stirred in anhydrous DMF (3 mL) at 60 ꢀC for 12 h. The reaction
mixture was poured into water (10 mL), and then extracted three
times withEtOAc. The combined organiclayer waswashed with water
for three times (20 mLꢁ3), and then dried over Na2SO4. The organic
layer was concentrated to get crude product. The crude product was
purified by chromatography (silica gel, eluent PE/EA) to afford 3.
d
4.2.8. 5-Amino-6-(4-bromophenyl)-4-(p-tolyl)pyrimidine-2(1H)-thi-
one (3 h). Deep yellow solid; mp: 197.1e199.5 ꢀC; 1H NMR
(500 MHz, DMSO-d6)
J¼8.5 Hz, 2H), 7.67 (d, J¼8.5 Hz, 2H), 7.57 (s, 2H), 7.25 (d, J¼8.1 Hz,
2H), 2.35 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
163.83, 150.16,
d
8.07 (d, J¼8.2 Hz, 2H), 7.98 (s, 1H), 7.75 (d,
4.2.1. 5-Amino-4-(4-chlorophenyl)-6-phenylpyrimidine-2(1H)-thi-
one (3a). Pale yellow solid; mp: 218.2e220.3 ꢀC; 1H NMR
d
(500 MHz, DMSO-d6)
d
8.23 (d, J¼8.7 Hz, 2H), 8.05 (s, 1H), 7.85 (d,
147.42, 137.59, 136.40, 132.97, 132.45, 132.36, 129.89, 129.56, 129.12,
123.75, 21.35. HRMS (ESI) m/z calcd for C17H14BrN3S [MþH]þ:
372.0165. Found: 372.0160.
J¼6.8 Hz, 2H), 7.58 (s, 2H), 7.52 (d, J¼8.7 Hz, 2H), 7.48 (d, J¼7.4 Hz,
2H), 7.46 (d, J¼6.9 Hz, 1H); 13C NMR (125 MHz, DMSO-d6)
d 163.65,
152.69, 145.08, 136.90, 134.27, 133.96, 132.54, 131.12, 130.86, 129.39,
128.59, 128.42. HRMS (ESI) m/z calcd for C16H12ClN3S [MþH]þ:
314.0513. Found: 314.0501.
4.2.9. 5-Amino-6-(4-bromophenyl)-4-phenylpyrimidine-2(1H)-thi-
one (3i). Pale yellow solid; mp: 202.3e203.7 ꢀC; 1H NMR
(500 MHz, DMSO-d6)
J¼6.8 Hz, 2H), 7.66 (d, J¼8.6 Hz, 2H), 7.59 (s, 2H), 7.47 (m, 7.0 Hz,
3H); 13C NMR (125 MHz, DMSO-d6)
163.67, 152.72, 145.14, 136.89,
d
8.17 (d, J¼8.6 Hz, 2H), 8.06 (s, 1H), 7.85 (d,
4.2.2. 5-Amino-6-(4-(benzyloxy)phenyl)-4-(4-chlorophenyl)pyrimi-
dine-2(1H)-thione (3b). Pale yellow solid; mp: 203.2e205.5 ꢀC; 1H
d

6568
Z. Shao et al. / Tetrahedron 68 (2012) 6565e6568
134.34, 134.30, 131.51, 131.43, 130.86, 129.39, 128.44, 121.29. HRMS
(ESI) m/z calcd for C16H12BrN3S [MþH]þ: 358.0008. Found:
358.0013.
DMSO-d6) d 164.25, 149.88, 143.05, 137.57, 136.06, 135.03, 131.25,
129.90, 129.51, 128.45, 127.69, 127.53. HRMS (ESI) m/z calcd for
C14H10ClN3S2 [MþH]þ: 320.0077. Found: 320.0079.
4.2.10. 5-Amino-4,6-bis(4-bromophenyl)pyrimidine-2(1H)-thione
Acknowledgements
(3j). Pale yellow solid; mp: 218.0e220.1 ꢀC; 1H NMR (500 MHz,
DMSO-d6)
d
8.13 (d, J¼8.6 Hz, 2H), 8.03 (s, 1H), 7.78 (d, J¼8.5 Hz,
This research was supported by the National Natural Science
Foundation of China (81072516) and Natural Science Foundation of
Zhejiang Province (No. Z2110655).
2H), 7.68 (d, J¼8.5 Hz, 2H), 7.63e7.65(m, 4H); 13C NMR (125 MHz,
DMSO-d6)
d 163.39, 150.78, 145.19, 135.58, 133.63, 133.52, 131.82,
130.96, 130.90, 129.58, 123.52, 120.83. HRMS (ESI) m/z calcd for
C16H11Br2N3S [MþH]þ: 435.9113. Found: 435.9117.
Supplementary data
4.2.11. 5-Amino-6-(4-bromophenyl)-4-(4-methoxyphenyl)pyr-
amidine-2(1H)-thione (3k). Pale yellow solid; mp: 206.5e207.8 ꢀC;
Experimental procedures, characterization data, and copies of
1H and 13C NMR spectra for all products. Supplementary data as-
sociated with this article can be found in the online version, at
doi:10.1016/j.tet.2012.05.057.
1H NMR (500 MHz, DMSO-d6)
d
8.18 (d, J¼8.6 Hz, 2H), 8.00 (s, 1H),
7.81 (d, J¼8.8 Hz, 2H), 7.63 (d, J¼8.7 Hz, 2H), 7.48 (s, 2H), 7.05 (d,
J¼8.8 Hz, 2H), 3.83 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
d 163.00,
161.71, 152.68, 143.75, 134.90, 134.48, 131.44, 131.28, 130.22, 129.70,
120.95, 114.94, 55.84. HRMS (ESI) m/z calcd for C17H14BrN3OS
[MþH]þ: 388.0114. Found: 388.0119.
References and notes
1. Lagoja, I. M. Chem. Biodivers. 2005, 2, 1.
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10. (a) Zapol’kii, V. A.; Namyslo, J. C.; Altug, C.; Gjikaj, M.; Kaufmann, D. E. Synthesis
2008, 304; (b) Kaname, T.; Masaaki, T.; Yukitoshi, M.; Kuniyoshi, O.; Katsuyuki,
I.; Hikari, M.; Tomoji, A. J. Heterocycl. Chem. 1987, 24, 1003; (c) Masaaki, T.;
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11. (a) Khanzhin, N. U.S. Patent 7,066,612, 2007; Chem. Abstr. 2007, 146, 337905; (b)
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12. (a) Wang, Y.-F.; Toh, K. K.; Chiba, S.; Narasaka, K. Org. Lett. 2008, 10, 5019; (b)
Chiba, S.; Wang, Y.-F.; Lapointe, G.; Narasaka, K. Org. Lett. 2008, 10, 313; (c)
(3l). Pale yellow solid; mp: 200.3e201.6 ꢀC; 1H NMR (500 MHz,
DMSO-d6)
d
8.10 (d, J¼8.2 Hz, 2H), 8.01 (s,1H), 7.82 (d, J¼7.1 Hz, 2H),
7.53 (s, 2H), 7.48 (t, J¼7.3 Hz, 2H), 7.43 (t, J¼7.2 Hz, 1H), 7.26 (d,
J¼8.1 Hz, 2H), 2.35 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
d 163.53,
151.52, 146.77, 137.47, 137.13, 133.13, 132.52, 130.56, 129.52, 129.35,
129.11, 128.19, 21.35. HRMS (ESI) m/z calcd for C17H15N3S [MþH]þ:
294.1059. Found: 294.1061.
4.2.13. 5-Amino-6-(4-(benzyloxy)phenyl)-4-(p-tolyl)pyrimidine-
2(1H)-thione (3m). Pale yellow solid; mp: 207.6.0e209.5 ꢀC; 1H
NMR (500 MHz, DMSO-d6)
d
8.09 (d, J¼8.2 Hz, 2H), 7.95 (s, 1H), 7.77
(d, J¼8.8 Hz, 2H), 7.47 (d, J¼7.2 Hz, 2H), 7.41 (m, 4H), 7.35 (t,
J¼7.3 Hz, 1H), 7.24 (d, J¼8.1 Hz, 2H), 7.12 (d, J¼8.8 Hz, 2H), 5.18 (s,
2H), 2.34 (s, 3H); 13C NMR (125 MHz, DMSO-d6)
d 162.88, 160.58,
151.48, 145.42, 137.20, 137.16, 133.59, 132.67, 130.13, 129.90, 129.36,
129.07, 128.95, 128.44, 128.30, 115.75, 69.89, 21.35. HRMS (ESI) m/z
calcd for C24H21N3OS [MþH]þ: 400.1478. Found: 400.1474.
€
Wang, Y.-F.; Chiba, S. J. Am. Chem. Soc. 2009, 131, 12570; (d) Brase, S.; Gil, C.;
4.2.14. 5-Amino-4-(4-chlorophenyl)-6-(thiophen-2-yl)pyrimidine-
Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44, 5188.
13. Yang, Y. Y.; Shou, W. G.; Chen, Z. B.; Wang, Y. G. J. Org. Chem. 2008, 73, 3928.
14. Chen, Z.-B.; Hong, D.; Wang, Y.-G. J. Org. Chem. 2009, 74, 903.
15. Hu, M.; Wu, J.; Zhang, Y.; Qiu, F.; Yu, Y. g Tetrahedron 2011, 67, 2676.
16. Gilchrist, T. L.; Mendonca, R. ARKIVOC 2000, 769.
2(1H)-thione (3n). Pale yellow solid; mp: 189.5e191.3 ꢀC; 1H NMR
(500 MHz, DMSO-d6)
d
7.98 (s, 1H), 7.92 (d, J¼8.5 Hz, 2H), 7.78 (dd,
J¼3.6, 1.1 Hz, 1H), 7.68 (s, 2H), 7.61 (dd, J¼5.1, 1.1 Hz, 1H), 7.56 (d,
J¼8.5 Hz, 2H), 7.13 (dd, J¼5.1, 3.7 Hz, 1H); 13C NMR (125 MHz,
17. Patonay, T.; Jekȍ, J.; Riman, E. Synth. Commun. 2002, 32, 2403.