Synthesis of novel disubstituted pyrazolo[1,5-a]pyrimidines, imidazo[1,2-a]pyrimidines, and pyrimido[1,2-a]benzimidazolescontaining thioether and aryl moieties

Article abstract of DOI:10.1002/hlca.201100495

A series of novel 6-[(1,3,4-thiadiazol-2-yl)sulfanyl]-7-phenylpyrazolo[1,5- a]pyrimidines, 5-phenyl-6-[(1,3,4-thiadiazol-2-yl)sulfanyl]imidazo[1,2-a] pyrimidines, and 2-phenyl-3-[(1,3,4-thiadiazol-2-yl)sulfanyl] pyrimido[1,2-a]benzimidazoles have been synthesized in four steps starting with 2-hydroxyacetophenone. The intermediate 3-[(1,3,4-thiadiazol-2-yl)sulfanyl]-4H- 1-benzopyran-4-ones reacted with pyrazol-3-amines, 5-methylpyrazol-3-amine, and 1H-imidazol-2-amine, 1H-benzimidazol-2-amine via a cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The approach affords the target compounds in acceptable-to-good yields. The new compounds were characterized by their IR, NMR, and HR mass spectra.

Full text of DOI:10.1002/hlca.201100495

Helvetica Chimica Acta – Vol. 95 (2012)
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Synthesis of Novel Disubstituted Pyrazolo[1,5-a]pyrimidines, Imidazo[1,2-
a]pyrimidines, and Pyrimido[1,2-a]benzimidazoles Containing Thioether and
Aryl Moieties
by Gang Li, Zun-Ting Zhang*, Li-Yan Dai, Yin-Li Du, and Dong Xue
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical
Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in
Northwest of China, and School of Chemistry and Materials Science, Shaanxi Normal University, Xiꢀan
710062, P. R. China (phone: þ 86-29-85303940; fax: þ 86-29-85307774; e-mail: zhangzt@snnu.edu.cn)
A series of novel 6-[(1,3,4-thiadiazol-2-yl)sulfanyl]-7-phenylpyrazolo[1,5-a]pyrimidines, 5-phenyl-6-
[(1,3,4-thiadiazol-2-yl)sulfanyl]imidazo[1,2-a]pyrimidines, and 2-phenyl-3-[(1,3,4-thiadiazol-2-yl)sulfa-
nyl]pyrimido[1,2-a]benzimidazoles have been synthesized in four steps starting with 2-hydroxyaceto-
phenone. The intermediate 3-[(1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-ones reacted with
pyrazol-3-amines, 5-methylpyrazol-3-amine, and 1H-imidazol-2-amine, 1H-benzimidazol-2-amine via a
cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The
approach affords the target compounds in acceptable-to-good yields. The new compounds were
characterized by their IR, NMR, and HR mass spectra.
Introduction. – Fused heterocyclic compounds commonly exhibit various biological
activities, and they mainly include [5,6], [6,6], and [7,6] ring systems [1]. In particular,
the fused [5,6] structural scaffold occurs in many pharmaceutical agents with diverse
physiological and pharmacological activities. For this reason, organic chemists paid
high attention to pyrimidine derivatives due to their chemotherapeutic relevance
[2][3]. There are a great number of compounds involving pyrimidines, such as
pyrazolo[1,5-a]pyrimidines (a), imidazo[1,2-a]pyramidines (b), and pyrimido[1,2-
a]benzimidazoles (c; Fig.).
Figure. Structures of pyrazolo[1,5-a]pyrimidines, imidazo[1,2-a]pyrimidines, and pyrimido[1,2-a]benzi-
midazoles, a – c, respectively
Pyrazolo[1,5-a]pyrimidines have shown biological activities, e.g., as inhibitors of
protein kinases [4] and in the treatment of Alzheimerꢀs disease [5]. Meanwhile, the
importance of the imidazo[1,2-a]pyrimidines has been well established in pharmaceut-
ical chemistry due to their activities as HIV inhibitors [6]. Similarly, some pyrimido[1,2-
a]benzimidazoles are known as compounds with antiparasitic [7] and substance P
receptor-binding activity [8], as antibacterial drugs [9], anti-arrhythmics [10], and
central nervous system-depressing agents [11], as well as substances with marked
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Helvetica Chimica Acta – Vol. 95 (2012)
herbicidal activity [12]. The synthesis of pyrazolo[1,5-a]pyrimidines involved the
reaction between aminopyrazoles and 1,3-biselectrophilic compounds [13][14]. The
formation of imidazo[1,2-a]pyrimidines relied on the condensation of substituted
pyridin-2-amine or pyrimidin-2-amine with the appropriate a-halogenocarbonyl
compounds [15]. Construction of the pyrimido[1,2-a]benzimidazole scaffold involved
the condensation of 1H-benzimidazol-2-amine with acetylene esters [16], enamino
ester [17], 1,3-diketone [10], and a,b-unsaturated ketones [18], respectively.
Recently, we reported the synthesis of new 6,7-diarylpyrazolo[1,5-a]pyrimidines,
2,3-diarylpyrimido[1,2-a]benzimidazoles, and 1,2,4-triazole[4,3-a]pyrimidines based on
reactions with isoflavones [19]. Continuing our studies on the intriguing fused [5,6] ring
system, here, we describe a simple and concise method to synthesize a range of 6,7-
disubstitued pyrazolo[1,5-a]pyrimidines, 5,6-disubstitued imidazo[1,2-a]pyrimidines,
and 2,3-disubstituted pyrimido[1,2-a]benzimidazole derivatives, which contain thio-
ether and aryl moieties via the intermediate 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfan-
yl]-4H-1-benzopyran-4-ones 4 and its reaction with azol-amines 5 (Scheme 1).
Scheme 1. Synthesis of Pyrimidine Derivatives
i) N,N-Dimethylformamide dimethyl acetal, oil bath, 70 – 758, 30 min. ii) I2 in CHCl3, room temperature,
30 min. iii) 5-Methyl-1,3,4-thiadiazole-2-thiol, tBuOK, DMF, 858, MW 240 W. iv) Azol-amines, MeONa,
MeOH, 20 – 30 min.
Results and Discussion. – To the best of our knowledge, the first synthetic route of
3-iodochromones 3 was reported by Gammill [20a], and substituted compounds 3 were
also synthesized [20b][20c]. The condensation of 2-hydroxyacetophenones 1 with N,N-
dimethylformamide dimethyl acetal (3.5 equiv.) gave enamines 2 in desired yield.
Cyclization of 2 without further purification using I2 (3 equiv.) in CHCl3 afforded 3-
iodochromones in good yield (Scheme 1). The reaction of 3 with 5-methyl-1,3,4-
thiadiazole-2-thiol in the presence of tBuOK (1.1 equiv.) at 858 afforded compounds 4
in moderate-to-good yields [21]. A plausible mechanism for the reaction of 3 with
azolethiols was proposed by Sugita et al. [22]. Under basic reaction conditions (3 equiv.
MeONa, MeOH, reflux, 30 min), 4 reacted with 5 (1H-pyrazol-3-amine (5a), 5-methyl-

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1H-pyrazol-3-amine (5b), 1H-imidazol-2-amine (5c)) to give cyclocondensation
products 6 in fair yields.
The synthesis of compound 6a was chosen as model to optimize the reaction
(Table 1). A mixture of 4a (1 mmol) and 5a (3 mmol) was heated to reflux in MeOH.
In the course of optimizing the reaction, it was noted that 3 equiv. of MeONa gave 6a in
the highest yield (Table 1, Entry 3; 75%). NaOH, K2CO3, and Et3N were also
investigated, and their yields were inferior to those with MeONa as base (Table 1,
Entries 6 – 8).
Table 1. Base Effects on the Cyclocondensations of 4a and 5aa)
Entry
Base
Molar ratios (4a/5a/base)
Yieldb) [%]
1
2
3
4
5
6
7
8
MeONa
MeONa
MeONa
MeONa
MeONa
NaOH
K2CO3
Et3N
1 : 3 : 1
1 : 3 : 2
1 : 3 : 3
1 : 3 : 4
1 : 3 : 5
1 : 3 : 3
1 : 3 : 3
1 : 3 : 3
46
52
75
60
51
28
19
13
a) All reactions were carried out in boiling MeOH (8 ml) for 20 – 30 min. b) Yields of isolated products
after chromatography.
To evaluate the scope of the cyclocondensation, F-, Br-, and MeO-substituted 4
were examined, and the expected compounds 6a – 6i were obtained (Table 2). Whereas
the yields of 6c – 6g were ca. 80%, the results of the cyclocondensation to give
imidazo[1,2-a]pyrimidines 6h and 6i under the optimized conditions were unsatis-
factory (Table 2, Entries 8 and 9), but in DMSO as solvent, 6h and 6i were formed in
good yields (Table 2, Entries 8 and 9).
Focusing on the synthesis of disubstituted pyrimido[1,2-a]benzimidazole 6j – 6l, we
reacted 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-ones 4 with
1H-benzimidazol-2-amine (5d) in boiling MeOH. The products were obtained in good
yields (Table 3).
A proposed mechanism for the formation of compounds 6 by cyclocondensation of
4a with azol-amines 5a – 5d in the presence of MeONa is depicted in Scheme 2 in
analogy to reactions with isoflavone [19b][23]. Compounds 4 undergo ring opening in
the presence of a base to form a,b-unsaturated ketone intermediates 7, followed by the
attack of the NH2 group of 5a on the b-C-atom of 7. Subsequently, a condensation
between the ring N-atom and the C¼O group affords the target compounds 6.
Additionally, the concentration of base is very important for the cyclocondensations.

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Table 2. Synthesis of Pyrazolo[1,5-a]pyrimidines and Imidazo[1,2-a]pyrimidines
Entry
R1
R2
R3
X
Y
Substrate 5
Product
Yielda) [%]
1
2
3
4
5
6
7
8
9
H
H
MeO
H
H
H
MeO
H
H
F
H
H
F
Br
H
H
F
H
H
H
Me
Me
Me
Me
H
CH
CH
CH
CH
CH
CH
CH
N
N
N
N
N
N
N
N
CH
CH
5a
5a
5a
5b
5b
5b
5b
5c
5c
6a
6b
6c
6d
6e
6f
6g
6h
6i
75b)
79b)
83b)
85b)
80b)
82b)
88b)
36b), 78c)
47b), 84c)
H
H
N
a) Yields of isolated products after chromatography. b) Reaction in boiling MeOH as solvent. c) Re-
action in DMSO as solvent at 1008.
Table 3. Synthesis of Pyrimido[1,2-a]benzimidazoles from 4 and 1H-Benzimidazol-2-amine (5d)
Entry
R1
R2
Product
Yielda) [%]
1
2
3
H
H
MeO
H
F
H
6j
6k
6l
83
75
82
a) Yields of isolated products after chromatography.
Intermediate 7 would be converted to the ketone 8 at high concentration of base by
elimination of HC(OMe)3. However, it would be too difficult for 4 to produce the
intermediate 7 in low base concentration.

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Scheme 2. Proposed Mechanism of Cyclocondensation 4a with 5a
Conclusions. – In summary, we have developed a simple and efficient method for
the synthesis of 6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-7-phenylpyrazolo[1,5-
a]pyrimidines, 5-phenyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]imidazol[1,2-a]pyr-
imidines, and 2-phenyl-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrimido[1,2-a]benz-
imidazoles in the presence of base by reaction of 3-[(5-methyl-1,3,4-thiadiazol-2-
yl)sulfanyl]-4H-1-benzopyran-4-ones 4 with azol-amines 5. The target compounds
present an imported core with respect to biological activity. In further studies, we will
investigate the biological activities.
Experimental Part
General. TLC: silica gel 60 GF254 plates (SiO2); visualization under UV light (254 nm). M.p.: X-5
Macro melting-point instrument; uncorrected. IR Spectra: Nicolet 170SX FT-IR spectrophotometer; in

994
KBr pellets; ˜n in cmꢀ1
Helvetica Chimica Acta – Vol. 95 (2012)
.
1H- and 13C-NMR spectra: Bruker Avance 300 at 300 and 75 MHz, resp.; in
(D6)DMSO, unless otherwise indicated; d in ppm rel. to Me4Si as internal standard, J in Hz. LC/MS:
Mson Brukermicro TOF-Q II ESI-Q-ToF; in m/z. Elemental Analyses: elementar Analysensysteme
GmbH Vario EL III.
General Procedure for the Preparation of 3-Iodochromone (3) [20c]. A mixture of a substituted 2-
hydroxyacetophenone 1 (5 mmol) and N,N-dimethylformamide dimethyl acetal (17.5 mmol, 3.5 equiv.)
was heated to 70 – 758 in DMF (25 ml) for 30 min in an oil bath. The mixture was washed with sat. aq.
NaCl (100 ml), a yellow precipitation of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-enone (2; 99%)
was obtained. Then, to a soln. of 2 (10 mmol) in CHCl3 (15 ml) was added I2 (30 mmol, 3 equiv.), and the
mixture was stirred at r.t. for 30 min. The reaction was quenched with 5% aq. NaHSO3 (30 ml), and the
aq. layer was extracted with CHCl3 (3 ꢁ 10 ml). The org. phase was washed neutrally with 5% aq.
NaHCO3, dried (Na2SO4), and concentrated in vacuo, and recrystallized from abs. EtOH to give 3 as
colorless crystals.
General Procedure for the Preparation of Substituted 3-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-
4H-1-benzopyran-4-ones 4 [21]. Compound 3 (1 mmol) was added to a soln. of 5-methyl-1,3,4-
t
thiadiazole-2-thiol (132 mg, 1 mmol) and BuOK (134 mg, 1.2 mmol) in 8 ml of DMF. The mixture was
irradiated by 240 W microwave (MW) at 858 for 20 – 30 min. The reaction was monitored by TLC. The
resulting mixture was cooled and diluted with 40 ml of ice H2O. The obtained solid product was filtered
and purified by CC (SiO2; petroleum ether/AcOEt 5: 1) to afford the product 4.
3-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-one (4a) [21]. Yield: 215.5 mg
1
(78%). Yellow powder. M.p. 75 – 768. H-NMR (300 MHz, (D6)DMSO): 9.10 (s, 1 H); 8.11 (d, J ¼ 7.5,
1 H); 7.90 (d, J ¼ 7.5, 1 H); 7.77 (d, 1 H); 7.61 (m, 1 H); 2.63 (s, 3 H). Anal. calc. for C12H8N2O2S2 (276.33):
C 52.16, H 2.92, N 10.14; found: C 52.00, H 2.99, N 10.06.
6-Fluoro-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-one (4b). Yield: 247.3 mg
(84%). Yellow powder. M.p. 179 – 1808. 1H-NMR (300 MHz, CDCl3): 8.51 (s, 1 H); 7.80 (d, J ¼ 7.5, 1 H);
7.42 (m, 2 H); 2.63 (s, 3 H). Anal.calc. for C12H7FN2O2S2 (294.32): C 48.97, H 2.40, N 9.52; found: C 48.99,
H 2.38, N 9.51.
6-Bromo-3-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-one (4c). Yield: 284.2 mg
(80%). Yellow powder. M.p. 145 – 1468. 1H-NMR (300 MHz, CDCl3): 8.44 (s, 1 H); 8.29 (s, 17.75 (d, J ¼
7.4, 17.3 (d, J ¼ 8.9, 12.68 (s, 3 H). Anal. calc. for C12H7BrN2O2S2 (355.23): C 40.57, H 1.99, N 7.89; found:
C 40.60, H 1.98, N 7.88.
7-Methoxy-3-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-4H-1-benzopyran-4-one (4d). Yield:
1
229.8 mg (75%). Yellow powder. M.p. 190 – 1918. H-NMR (300 MHz, CDCl3): 8.44 (s, 1 H); 8.15 (d,
J ¼ 8.9, 1 H); 7.03 (d, J ¼ 8.8, 1 H); 6.88 (s, 1 H); 3.92 (s, 3 H); 2.69 (s, 3 H). Anal. calc. for C13H10N2O3S2
(306.36): C 50.97, H 3.29, N 9.14; found: C 50.94, H 3.30, N 9.16.
General Procedure for the Preparation of the Compounds 6a – 6l (Table 2, Entry 1 – 9; and Table 3,
Entry 1 – 3). A mixture of 4 (1mmol), 5 (3.0 mmol), and MeONa (3 mmol) in boiling MeOH (DMSO, at
1008, 5c) was heated for 20 – 30 min. The reaction was monitored by TLC, until the disappearances of the
starting materials. After addition of H2O (25 ml), the soln. was washed neutrally with aq. 5% HCl. A
yellow precipitate was formed and filtered. The crude product was obtained and purified by CC (SiO2;
CHCl3/MeOH 30 :1) to give the corresponding pure product 6.
2-{6-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}phenol (6a). Yield:
256.1 mg (75%). Yellow solid. M.p. 207 – 2088. IR (KBr): 3289, 3186, 3131, 1585, 1517, 1448, 1371, 755.
1H-NMR (300 MHz, (D6)DMSO): 10.08 (s, 1 H); 8.78 (s, 1 H); 8.26 (s, 1 H); 7.34 (m, 2 H); 7.04 (m, 2 H);
6.91 (s, 1 H); 2.62 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.7; 98.2; 112.1; 116.4; 117.1; 119.2; 130.7;
132.5; 146.7; 148.6; 149.5; 153.9; 155.6; 166.6; 166.9. ESI-HR-MS: 364.0304 ([M þ K]þ, C15H11KN5S2þ ;
calc. 364.0303).
4-Fluoro-2-{6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}phenol (6b).
Yield: 283.9 mg (79%). Yellow solid. M.p. 219 – 2208. IR (KBr): 3243, 3186, 3068, 1588, 1427, 1380,
1182, 819, 780. 1H-NMR (300 MHz, (D6)DMSO): 10.16 (s, 1 H); 8.80 (s, 1 H); 8.29 (s, 1 H); 7.28 (d, J ¼
8.1, 2 H); 7.01 (s, 1 H); 6.94 (s, 1 H); 2.62 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.2; 97.8; 111.8;
116.3; 116.7; 117.0; 117.1; 118.8; 146.3; 148.1; 151.6; 153.3; 156.2; 165.5; 166.7. ESI-HR-MS: 382.0200
([M þ Na]þ, C15H10FN5NaOSþ2 ; calc. 382.0208).

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5-Methoxy-2-{6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}phenol
(6c). Yield: 308.3 mg (83%). Yellow solid. M.p. 119 – 1208. IR (KBr): 3378, 3079, 1615, 1589, 1494, 1197,
1
839, 781. H-NMR (300 MHz, (D6)DMSO): 10.24 (s, 1 H); 8.75 (s, 1 H); 8.26 (s, 1 H); 7.30 (d, J ¼ 8.8,
2 H); 6.90 (s, 1 H); 6.56 (s, 1 H); 3.79 (s, 3 H); 2.50 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.7; 55.7;
98.1; 101.6; 105.6; 109.7; 112.3; 131.8; 146.5;148.7; 149.4; 153.8; 156.9; 157.2; 162.8; 166.8. ESI-HR-MS:
394.0411 ([M þ Na]þ, C16H13N5NaO2Sþ2 ; calc. 394.0408).
2-{2-Methyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}phenol (6d).
Yield: 302.1 mg (85%).Yellow solid. M.p. 232 – 2338. IR (KBr): 3400, 3033, 1594, 1492, 1380, 1148,
760. 1H-NMR (300 MHz, (D6)DMSO): 10.10 (s, 1 H); 8.71 (s, 1 H); 7.36 (m, 2 H); 7.00 (m, 2 H); 6.72 (s,
1 H); 2.62 (s, 3 H); 2.38 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 14.9; 15.7; 97.6; 111.1; 116.5; 117.4;
119.3; 130.5; 132.4; 149.1; 149.3; 153.7; 155.5; 156.5; 166.8; 170.0. ESI-HR-MS: 378.0460 ([M þ Na]þ,
C16H13N5NaOSþ2 ; calc.378.0459).
4-Fluoro-2-{2-methyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}phe-
nol (6e). Yield: 298.7 mg (80%). Yellow solid. M.p. 107 – 1088. IR (KBr): 3371, 3066, 1592, 1500, 1268,
1183, 819, 784. 1H-NMR (300 MHz, (D6)DMSO): 10.13 (s, 1 H); 8.73 (s, 1 H); 7.25 (d, J ¼ 8.2, 2 H); 7.00
(s, 1 H); 6.74 (s, 1 H); 2.62 (s, 3 H); 2.35 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 14.4; 15.2; 97.2; 110.7;
115.8; 116.4; 117.3; 118.3; 118.7; 147.0; 148.8; 151.5; 153.1; 155.5; 166.0; 166.5. ESI-HR-MS: 396.0369
([M þ Na]þ; C16H12FN5NaOSþ2 ; calc. 396.0365).
4-Bromo-2-{2-methyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}-
phenol (6f). Yield: 356.2 mg (82%). Yellow solid. M.p. 219 – 2208. IR (KBr): 3404, 3125, 1591, 1485, 1285,
1
813, 784. H-NMR (300 MHz, (D6)DMSO): 10.43 (s, 1 H); 8.72 (s, 1 H); 7.53 (t, 2 H); 6.98 (d, J ¼ 8.6,
1 H); 6.73 (s, 1 H); 2.62 (s, 3 H); 2.39 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 14.9; 15.7; 97.7; 110.0;
111.3; 118.7; 119.5; 132.7; 134.9; 147.3; 149.2; 153.5; 155.0; 156.7; 166.3; 167.0. ESI-HR-MS: 455.9574
([M þ Na]þ, C16H12BrN5NaOSþ2 ; calc.455.9564).
5-Methoxy-2-{2-methyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrazolo[1,5-a]pyrimidin-7-yl}-
phenol (6g). Yield: 339.2 mg (88%). Yellow solid. M.p. 135 – 1368. IR (KBr): 3401, 1615, 1591, 1494, 1204,
1033, 837, 788. 1H-NMR (300 MHz, (D6)DMSO): 10.19 (s, 1 H); 8.68 (s, 1 H); 7.25 (d, J ¼ 8.9, 2 H); 6.70
(s, 1 H); 6.62 (s, 1 H); 3.76 (s, 3 H); 2.60 (s, 3 H); 2.38 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 14.9;
15.7; 55.5; 97.3; 101.7; 105.0; 109.9; 111.4; 131.5; 148.9; 149.4; 153.4; 156.8; 157.0; 162.5; 166.7; 167.4. ESI-
HR-MS: 408.0568 ([M þ Na]þ, C17H15N5NaO2S2þ ; calc. 408.0565).
2-{6-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]imidazo[1,2-a]pyrimidin-5-yl}phenol (6h). Yield:
266.3 mg (78%). Yellow solid. M.p. 194 – 1958. IR (KBr): 3440, 1576, 1488, 1296, 1142, 1053, 755.
1H-NMR (300 MHz, (D6)DMSO): 10.41 (s, 1 H); 8.82 (s, 1 H); 7.81 (s, 1 H); 7.50 – 7.37 (m, 3 H); 7.10 –
6.98 (m, 3 H); 2.61 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.7; 112.4; 112.6; 116.9; 117.2; 119.9;
130.4; 133.3; 136.2; 147.9; 148.7; 154.4; 155.5; 166.5; 167.0. ESI-HR-MS: 364.0304 ([M þ Na]þ,
C15H11N5NaOSþ2 ; calc. 364.0303).
4-Fluoro-2-{6-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]imidazo[1,2-a]pyrimidin-5-yl}phenol (6i).
Yield: 301.9 mg (84%). Yellow solid. M.p. 149 – 1508. IR (KBr): 3430, 1582, 1496, 1426, 1250, 1194,
817, 733. 1H-NMR (300 MHz, (D6)DMSO): 10.33 (s, 1 H); 8.81 (s, 1 H); 7.81 (s, 1 H); 7.44 (s, 1 H); 7.36
(m, 2 H); 7.06 (m, 1 H); 2.50 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.2; 112.1; 116.1; 116.5; 117.7;
119.3; 119.6; 135.8; 146.6; 147.4; 151.4; 153.5; 156.5; 165.4; 166.7. ESI-HR-MS: 382.0218 ([M þ Na]þ,
C15H10FN5NaOSþ2 ; calc. 382.0208).
2-{3-[(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrimido[1,2-a]benzimidazol-4-yl}phenol (6j). Yield:
324.9 mg (83%). Yellow solid. M.p. 263 – 2648. IR (KBr): 3408, 1604, 1572, 1481, 1447, 1368, 1196, 756.
1H-NMR (300 MHz, (D6)DMSO): 10.48 (s,1 H); 9.30 (s,1 H); 8.12 (d, J ¼ 6.8, 1 H); 7.76 (t, 2 H), 7.62 (d,
J ¼ 6.6, 1 H); 7.34 (t, 3 H); 6.65 (d, J ¼ 8.0, 1 H); 2.83 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.7;
110.8; 114.7; 116.9; 117.7; 120.3; 120.4; 122.9; 127.0; 128.1; 129.9; 133.6; 144.9; 150.5; 152.4; 155.4; 160.3;
166.5; 167.0. ESI-HR-MS: 414.0474 ([M þ Na]þ, C19H13N5NaOS2þ ; calc. 414.0459).
4-Fluoro-2-{3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrimido[1,2-a]benzimidazol-4-yl}phenol
(6k). Yield: 307.1 mg (75%). Yellow solid. M.p. 278 – 2798. IR (KBr): 3425, 1574, 1486, 1443, 1269, 1199,
767. 1H-NMR (300 MHz, (D6)DMSO): 10.28 (s, 1 H); 9.11 (s, 1 H); 7.94 (d, J ¼ 8.2, 1 H); 7.55 (m, 3 H);
7.43 (m, 2 H); 6.54 (d, J ¼ 8.5, 1 H); 2.50 (s, 3 H). 13C-NMR (75 MHz, (D6)DMSO): 15.3; 110.5; 114.0;

996
Helvetica Chimica Acta – Vol. 95 (2012)
115.9; 116.2; 117.7; 119.6; 119.9; 122.6; 126.5; 127.5; 144.4; 150.5; 151.4; 153.7; 156.8; 159.6; 165.4; 166.8.
ESI-HR-MS: 432.0377 ([M þ Na]þ, C19H12FN5NaOS2þ ; calc. 432.0365).
5-Methoxy-2-{3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pyrimido[1,2-a]benzimidazol-4-yl}phenol
(6l). Yield: 345.6 mg (82%). Yellow solid. M.p. 278 – 2798. IR (KBr): 3438, 2359, 1613, 1485, 1442, 1296,
1
1200, 742. H-NMR (300 MHz, (D6)DMSO): 10.31 (s, 1 H); 9.05 (s,1 H); 7.90 (s,1 H); 7.51 (d, J ¼ 6.4,
1 H); 7.34 (d, J ¼ 7.34, 1 H); 7.20 (d, J ¼ 6.2, 1 H ); 6.66 (s, 3 H); 3.84 (s, 3 H); 2.50 (s, 3 H). 13C-NMR
(75 MHz, (D6)DMSO): 15.7; 55.8; 102.2; 106.5; 110.4; 111.4; 120.2; 122.8;126.9; 128.3; 130.9; 144.9;
150.6; 152.4; 156.9; 160.1; 163.4; 166.7; 166.8; 166.9. ESI-HR-MS: 444.0576 ([M þ Na]þ,
C20H15N5NaO2Sþ2 , calc. 444.0565).
We thank the National Natural Science Foundation of China (No. 20772076) and the Fundamental
Funds Research for the Central Universities (No. Gk200901010) for financial support of this research.
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Received December 9, 2011