DMSO-POCl3: A reagent for methylthiolation of imidazo[1,2-a]pyridines and other imidazo-fused heterocycles

Article abstract of DOI:10.1016/j.tet.2013.07.017

A practical and metal free method for methylthiolation of imidazo[1,2-a]pyridines and other imidazo-fused heterocycles using DMSO-POCl₃ complex is reported. The reactions are carried out at room temperature that give the corresponding methylthiolated products in good to excellent yield. Further, its application to indole has been demonstrated.

Full text of DOI:10.1016/j.tet.2013.07.017

Tetrahedron 69 (2013) 8255e8262
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Tetrahedron
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DMSOePOCl3: a reagent for methylthiolation of imidazo[1,2-a]
pyridines and other imidazo-fused heterocycles
Shashikant M. Patil a, Sarang Kulkarni a, Malcolm Mascarenhas a, Rajiv Sharma a,
,
S. Mohana Roopan b, Abhijit Roychowdhury a
*
a Department of Medicinal Chemistry, Piramal Enterprises Ltd, 1-Nirlon Complex, Goregaon (East), Mumbai 400063, Maharashtra, India
b Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical and metal free method for methylthiolation of imidazo[1,2-a]pyridines and other imidazo-
fused heterocycles using DMSOePOCl3 complex is reported. The reactions are carried out at room
temperature that give the corresponding methylthiolated products in good to excellent yield. Further, its
application to indole has been demonstrated.
Received 21 March 2013
Received in revised form 5 July 2013
Accepted 7 July 2013
Available online 12 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
methylthioimidazo[1,2-a]pyridines and other imidazo-fused het-
erocycles using DMSO activated by phosphorus oxychloride.
Functionalized imidazo[1,2-a]pyridines and other imidazo-
fused heterocycles are prevalent structural motifs in biologically
active and pharmaceutically important compounds.1e4 Function-
alization at 2 and 3 position of imidazo[1,2-a]pyridines is a topic of
importance, as substituents at these positions have great impact on
the biological activity.5 Further, these compounds found applica-
tion as fluorescent dyes.6,7 We have recently reported a synthesis of
3-bromoimidazo[1,2-a]pyridines and other imidazo-fused hetero-
cycles by electrophilic aromatic bromination using bromodimethyl
sulfonium ion generated in situ via activation of DMSO by HBr salt
of imidazo[1,2-a]pyridines.8 During the course of these reactions,
we had obtained 3-methylthioimidazo[1,2-a]pyridines as minor
products in 5e15% yield. The methyl thioether functionality has
found wide application in biologically active molecules.9e17 Further
methylthio substituted heterocycles have also found application in
metal-catalyzed cross-coupling reactions.18e21 There exist a limited
number of methods for introduction of methyl thioether in het-
erocyclic systems. Recently copper-mediated methylthiolation of
aryl and heteroaryl system using DMSO as the source of SMe (thi-
omethyl group) has been reported by various groups.22e24 These
reactions, although high yielding, employ metal catalysts and re-
quire high temperatures. Methylthiolation of imidazopyridines and
related heterocycles has not been fully explored. This prompted us
to explore the use of activated DMSO to develop a convenient ap-
proach for methylthiolation of these heterocycles. Herein, we re-
port a practical and metal free method for synthesis of 3-
DMSO activated by various electrophiles like acetic anhydride,
trifluoroacetic anhydride, oxalyl chloride, thionyl chloride, sulfuryl
chloride, sulfur trioxideepyridine complex, phosphorus oxy-
chloride, and phosphorus pentachloride has been widely used for
oxidation of alcohols to corresponding carbonyl compounds.25
These conditions, although mild, do give rise to side products. For
example, Liu and Nyangulu have reported
a-chlorination of car-
bonyl compounds using DMSOeoxalyl chloride.26 Further, they
have also shown DMSO activated by phenyl dichlorophosphate or
phosphorus oxychloride converted alkenes to chloroalkylsulfides.
Electrophilic chlorination of indoles and a-chlorination of ketones
have also been reported under Swern oxidation conditions.27,28 Our
group has observed corresponding methylthio derivatives as a side
product in microwave assisted one-pot synthesis of 3-
bromoimdazo[1,2-a]pyridines and imidazoheterocycles.8 Similar
observation was reported by Kawano and Kato in their synthesis of
3-bromoimidazo[1,2-a]pyridines.29
2. Results and discussion
As reported in our earlier communication,8 exposure of imidazo
[1,2-a]pyridine$HBr salts to DMSO at 80 ꢀC afforded 3-
bromoimidazo[1,2-a]pyridines in good to excellent yields along
with minor amount (5e15%) of the corresponding 3-SMe de-
rivatives. In order to optimize the reaction to selectively obtain 3-
SMe derivatives, we opted to subject 8-methyl-2-phenylimidazo
[1,2-a]pyridine30(1a) to DMSO activated by various electrophilic
reagents (Table 1).
As observed from Table 1, use of HBr as an activator for DMSO at
elevated temperature resulted in 12% isolation of methylthio
* Corresponding author. E-mail address: abhijit.roychowdhury@piramal.com
(A. Roychowdhury).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.017

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S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
Table 1
Results of methylthiolation.
Entry
Conditionsa
Product ratiob (%)
1a
2a
12
3a
1
2
3
HBr salt of 1a, 80 ꢀC, 2 h, method A
d
94
d
88 (Br)
6 (Br)
3 (Br)
5 (Cl)
d
HBr salt of 1a, 25 ꢀC, 24 h, method A
d
HBr salt of 1a and POCl3 (1.5 equiv), 5 ꢀC, 30 min, method A
92
4
5
6
7
8
9
10
11
12
1a, Ac2O (30 equiv), 25 ꢀC, 24 h, method B
1a, SO3$Py (1.5 equiv), 25 ꢀC, 24 h, method B
1a, P2O5 (1.5 equiv), 25 ꢀC, 24 h, method B
1a, POCl3 (1.5 equiv), 5e25 ꢀC, 20 min, method A
1a, POCl3 (1.5 equiv), 5 ꢀC, 20 min, method B
1a, POCl3 (1.5 equiv), 25 ꢀC, 20 min, method B
1a, (COCl)2 (1.5 equiv), 25 ꢀC, 30 min, method B
1a, SOCl2 (1.5 equiv), 25 ꢀC, 30 min, method B
1a, SO2Cl2 (1.5 equiv), 25 ꢀC, 30 min, method B
100
100
31
d
d
d
d
69
d
96
98
4 (Cl)
2 (Cl)
1 (Cl)
1 (Cl)
1 (Cl)
1
d
d
99c
11
88
42
80
57
19
Method A: an electrophile was added to a solution of 1a in DMSO at 5 ꢀC (exothermic). Method B: 1a was added to a complex of DMSOeelectrophilic activator (prepared below
20 ꢀC).
a
DMSO was used as a solvent.
b
The ratio was determined by HPLC analysis of the crude reaction mixture. Method: Asentis express C18, (100ꢁ4.6 mm, 2.7
mm) column; mobile phase: A: 0.1% HCOOH in
water, B: acetonitrile. Flow rate 1.0 mL/min. 1a: tR¼3.42 min, 2a: tR¼6.23 min, 3a (Br): tR¼11.36 min, and 3a (Cl): tR¼12.31 min.
c
Optimized condition: substrate (1 equiv) was added to a complex of DMSO (solvent)ePOCl3 (1.5 equiv) at 25 ꢀC.
product (entry 1); however at 25 ꢀC, majority of unreacted starting
material (1a) was recovered along with minor halogenated prod-
uct. Use of acetic anhydride, sulfur trioxideepyridine complex
(entries 4 and 5) resulted in complete recovery of starting material.
Activating DMSO by phosphorus pentoxide, oxalyl chloride, thionyl
chloride, and sulfuryl chloride at 25 ꢀC resulted in a varied ratio of
3-SMe derivative, starting material, and traces of halogenated
product (entries 6, 10e12). When HBr salt of 1a in DMSO was
treated with POCl3 at 5 ꢀC (entry 3) a 9:1 ratio of 3-SMe (2a) to
halogenated product (3a) was obtained. Encouraged by this result,
we then treated 1a with POCl3 under various conditions (entries
7e9). These conditions furnished 3-SMe (2a) as the major product
in ratio of >20:1. Table 1, entry 9 shows the optimized conditions
for the reaction wherein, a complex of DMSO and POCl3 (prepared
below 20 ꢀC) was treated with 8-methyl-2-phenylimidazo[1,2-a]
pyridine (1a) and allowed to stir at 25 ꢀC for 20 min. Under these
conditions we achieved complete conversion and isolated 8-
methyl-3(methylthio)-2-phenylimidazo[1,2-a]pyridine (2a) in 91%
yield, as the sole product. To further demonstrate the scope of this
transformation, substituted imidazo[1,2-a]pyridines were sub-
jected to optimized reaction condition to yield corresponding 3-
SMe products (Table 2).
As observed from Table 2, 2-aryl substituted imidazo[1,2-a]
pyridines (entries 1ael) gave the corresponding 3-SMe derivatives
in good to excellent yields (entries 2ael). Replacement of aryl
group at 2-position with a carboxylate group or t-Bu group resulted
in corresponding 3-SMe derivatives in moderate to good yields
(entries 2mep). In these cases, the reaction was sluggish and took
up to 24 h to reach an acceptable conversion. Small amount of
starting material was isolated and the yields in parentheses are
based on recovered starting material. When imidazo[1,2-a]pyri-
dines devoid of a substituent at 2-position were subjected to the
optimized reaction conditions, we did not observe any formation of
the expected product even after 24 h.
tyrosine kinase-3 (FLT3) inhibitor (Quizartinib, phase II).35 Due to
the importance of imidazoheterocyclic scaffold, it would be useful
to extend the scope of this reaction to its analogs possessing im-
idazole ring fused with another aromatic unit (Table 3). When
imidazo[1,2-a]pyrimidines (entries 4aec) were exposed to the
optimized reaction condition, we obtained the corresponding 3-
SMe derivatives (entries 5aec) in good to excellent yields. Simi-
larly imidazo[2,1-b]thiazoles (entries 4def), imidazo[2,1-b][1,3,4]
thiadiazole (entry 4g), and benzo[d]imidazo[2,1-b]thiazoles (en-
tries 4hej) resulted in the corresponding SMe derivatives (entries
5def, 5g, 5hej) in moderate to good yields.
In line with imidazoheterocycles, sulfinated indoles have also
exhibited biological activity in disease areas like obesity, cancer,
heart disease, and bacterial infection.36 Earlier reports showed that
3-SMe indoles were isolated as minor products during Swern oxi-
dation.37 Consequently we applied our optimized reaction condi-
tion for indoles. Upon treatment indoles 6a, 6b, and 6c under
optimized reaction condition, corresponding 3-SMe indoles were
obtained in good yields (Table 4, 7a: 86%, 7b: 73%, 7c: 58%). Parent
indole underwent extensive polymerization and N-protected ben-
zenesulfonyl indole 6d did not afford any product (Scheme 1).
We propose that the reaction of DMSO with phosphorus oxy-
chloride produces an electrophilic chlorodimethylsulfonium salt.
Attack by imidazo[1,2]pyridine on sulfur [path I] of chlor-
odimethylsulfonium ion leads to formation of methylthio product
via subsequent demethylation. On other hand, attack on the chloro
[path II] leads to the formation of chloro product along with
dimethylsulfide.
3. Conclusions
In conclusion, we have developed a practical and metal free
method for methylthiolation of imidazo[1,2-a]pyridines and other
imidazo-fused heterocycles using DMSOePOCl3 as a reagent. The
reactions are carried out at 25 ꢀC and are typicallyover in 30 minwith
moderate to excellent yields. A variety of methylthioimidazo[1,2-a]
pyridines and other imidazo-fused heterocycles were synthesized
Imidazoheterocycles have exhibited a broad range of biological
activity in various therapeutic areas like antitubercular,31 antitu-
mor,32 antiviral,33 p38 MAP kinase inhibitors34 and FMS-like

S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
8257
Table 2
Synthesis of 3-methylthioimidazo[1,2-a]pyridines
and methodology has also been extended to the synthesis of
3-methylthioindoles from the corresponding indoles. This method of
methylthiolation can be further explored on other heterocycles.
advances CombiFlashÒ Rf automated flash chromatography system
(Lincoln, USA) equipped with a UV variable dual-wavelength,
software selectable, 200e360 nm using prefabricated ‘RediSepÒ
Flash Column silica’ columns (size according to requirements).
Analytical high-pressure liquid chromatography (HPLC) was per-
formed on Shimadzu 2010 HPLC with SPD-M20A PDA.
4. Experimental section
4.1. General information
4.2. General procedure for synthesis of compounds 1g, 1j, 4b,
All the reagents and starting materials (except 1g, 1j, 4b, 4f, and
4iek) were obtained commercially and used without purification.
Nuclear magnetic resonance (1H and 13C NMR) spectra were
recorded on Bruker FT-NMR (Avance DPX300) spectrometer (Fae-
llandon, Switzerland) in CDCl3 using TMS as internal standard.
4f, 4iek
Compounds were prepared according to literature procedure.38
To a solution of 2-aminoheteroarene (10 mmol) in ethanol (50 mL),
phenacyl bromide (10 mmol) and NaHCO3 (30 mmol) were added
at rt and the reaction mixture was refluxed for 8 h. On removal of
solvent, the residue was dissolved with ethyl acetate (100 mL) and
washed with water (50 mL), brine (50 mL), and dried over sodium
sulfate. The solvent was evaporated to give crude product, which
was purified by combiflash chromatography (1e20% EtOAc/PE) to
give the desired product.
Chemical shifts are reported in parts per million (d), coupling
constants (J values) are reported in Hertz (Hz). ESI-MS and ESI-
HRMS were recorded on Bruker Daltonics Micro TOF-Q spectrom-
eter (Bremen, Germany). Melting points were determined on
a capillary melting point apparatus (Mumbai, India) and are un-
corrected. Flash chromatography was conducted on a Teledyne Isco

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S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
Table 3
Synthesis of methylthioimidazoheterocycles
4.2.1. 8-Methyl-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine
(1g). Isolated yield 71%; Rf (1:1 EtOAc/PE) 0.48; brown solid: mp
61e64 ꢀC; 1H NMR (300 MHz, CDCl3)
(ppm): 2.51 (s, 3H), 6.84 (t,
d
J¼6.6 Hz, 1H), 7.10 (d, J¼6.6 Hz, 1H), 7.80 (d, J¼8.1 Hz, 2H), 8.20 (d,
J¼8.1 Hz, 2H), 8.41 (d, J¼6.6 Hz, 1H), 8.54 (s, 1H); 13C NMR (75 MHz,
Table 4
Methylthiolation of indoles using DMSOePOCl3 complex
CDCl3)
d
(ppm): 17.1, 109.5,112.1, 123.5,123.8,125.6 (q), 126.2 (ꢁ2C),
127.8, 129.7, 137.5, 143.6, 146.4; HRMS (ESI): m/z [MþH]þ calcd for
C15H12F3N2: 277.0947, found 277.0959; HPLC: 95.3%.
4.2.2. 2-(3-(Benzyloxy)phenyl)-8-methylimidazo[1,2-a]pyridine
(1j). Isolated yield 86%; Rf (1:1 EtOAc/PE) 0.75; light brown solid:
mp 96e98 ꢀC; 1H NMR (300 MHz, CDCl3)
d (ppm): 2.69 (s, 3H),
5.19 (s, 2H), 6.71 (t, J¼6.0 Hz, 1H), 6.97 (m, 2H), 7.33e7.45 (m, 4H),
7.52 (d, J¼6.0 Hz, 2H), 7.57 (d, J¼9.0 Hz, 1H), 7.69 (br s, 1H), 7.84 (s,
1H), 8.00 (d, J¼6.9 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d (ppm):
17.1, 70.1, 108.8, 112.4, 114.5, 119.0, 123.3, 123.4, 127.7 (ꢁ3C), 128.0,
128.6, 129.7, 135.6, 137.1, 145.0, 146.2, 159.2; HRMS (ESI): m/z
[MþH]þ calcd for C21H18N2O: 315.1492, found 315.1505; HPLC:
98.2%.
4.2.3. 2-(4-(Trifluoromethyl)phenyl)imidazo[1,2-a]pyrimidine
(4b). Isolated yield 66%; Rf (1:9 MeOH/chloroform) 0.53; off white
solid: mp 233e235 ꢀC; 1H NMR (300 MHz, CDCl3)
d (ppm): 7.46 (dd,
J¼4.2, 6.6 Hz, 1H), 7.94 (d, J¼8.1 Hz, 2H), 8.24 (d, J¼8.1 Hz, 2H), 8.78
(s, 1H), 8.88 (dd, J¼1.6, 4.2 Hz, 1H), 9.22 (dd, J¼1.8 Hz, 4.2 Hz, 1H);
13C NMR (75 MHz, CDCl3)
d (ppm): 111.1, 113.4, 126.7 (q), 127.3
(ꢁ2C), 132.7, 137.1, 137.9 (ꢁ2C), 145.9, 156.6; HRMS (ESI): m/z

S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
8259
Scheme 1. Plausible reaction mechanism for the methylthiolation.
[MþH]þ calcd for C13H9F3N3: 264.0743, found 264.0746; HPLC:
temperature below 20 ꢀC), 1a (0.42 g, 2 mmol) was added at 25 ꢀC.
The reaction mixture was stirred for 20 min at same temperature
and then poured into ice-water (20 mL) and the pH of solution was
adjusted to 9 with aqueous 10% sodium hydroxide solution. The
aqueous layer was extracted with ethyl acetate (2ꢁ25 mL). The
combined organic layer was washed with water and brine, and then
dried over anhydrous Na2SO4. After removal of the solvent, the
residue was purified by combiflash silica column chromatography
(eluent: 1e20% ethyl acetate/petroleum ether) to give 2a as white
solid (0.46 g, 91%); Rf (1:5 EtOAc/PE) 0.50; mp: 120 ꢀC; 1H NMR
96.3%.
4.2.4. 3-(4-Bromophenyl)-6-(4-(trifluoromethyl)phenyl)imidazo[2,1-
b]thiazole (4f). Isolated yield 41%; Rf (1:4 EtOAc/PE) 0.71; off white
solid: mp 192e194 ꢀC; 1H NMR (300 MHz, CDCl3)
d (ppm): 6.86 (s,
1H), 7.57 (d, J¼8.4 Hz, 2H), 7.67 (d, J¼8.4 Hz, 2H), 7.72 (d, J¼8.4 Hz,
2H), 7.94 (s, 1H), 7.96 (d, J¼8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d
(ppm): 108.1,109.4,122.5,124.0,125.3 (ꢁ2C),125.8 (q),128.4,128.6,
129.0,129.5,131.5,132.7,137.4,146.5,150.5; HRMS (ESI): m/z [MþH]þ
calcd for C18H11BrF3N2S: 422.9773, found 422.9768; HPLC: 99.2%.
(300 MHz, CDCl3) d (ppm): 2.27 (s, 3H), 2.69 (s, 3H), 6.87 (t,
J¼6.9 Hz, 1H), 7.11 (d, J¼6.9 Hz, 1H), 7.40 (t, J¼7.2 Hz, 1H), 7.50 (dd,
4.2.5. 6-Ethoxy-2-(3-methoxyphenyl)benzo[d]imidazo[2,1-b]thiazole
J¼7.2, 8.4 Hz, 2H), 8.28 (d, J¼8.4 Hz, 2H), 8.38 (d, J¼6.9 Hz, 1H); 13
C
(4i). Isolated yield 63%; Rf (1:1 EtOAc/PE) 0.72; pale yellow solid:
NMR (75 MHz, CDCl3) d (ppm): 16.8, 18.3, 111.6, 112.7, 122.1, 124.7,
mp 147e148 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 1.48 (t,
127.7, 128.1, 128.4 (ꢁ2C), 134.2, 146.7, 148.6; HRMS (ESI): m/z
[MþH]þ calcd for C15H15N2S: 255.0950, found 255.0941; HPLC:
99.5%.
J¼7.2 Hz, 3H), 3.91 (s, 3H), 4.11 (q, J¼7.2 Hz, 2H), 6.87 (dd, J¼1.8,
8.4 Hz,1H), 7.02 (dd, J¼2.4, 8.7 Hz,1H), 7.22 (d, J¼2.4 Hz,1H), 7.34 (t,
J¼7.8 Hz, 1H), 7.43e7.48 (m, 2H), 7.51 (d, J¼8.7 Hz, 1H), 7.92 (s, 1H);
13C NMR (75 MHz, CDCl3)
d
(ppm): 14.8, 55.4, 64.3, 107.1, 109.3,
4.2.9. 3-(Methylthio)-2-phenylimidazo[1,2-a]pyridine (2b). Rf (1:3
110.0, 113.1, 113.6, 113.9, 117.5, 126.2, 129.7, 131.4, 135.4, 147.0, 147.4,
156.6, 160.0; HRMS (ESI): m/z [MþH]þ calcd for C18H17N2O2S:
325.1005, found 325.1017; HPLC: 98.5%.
EtOAc/PE) 0.44; off white solid: mp 66 ꢀC; 1H NMR (300 MHz,
CDCl3)
d
(ppm): 2.29 (s, 3H), 6.97 (t, J¼6.9 Hz, 1H), 7.32 (t, J¼9.0 Hz,
1H), 7.42 (d, J¼7.2 Hz, 1H), 7.51 (dd, J¼6.9, 7.8 Hz, 2H), 7.69 (d,
J¼9.0 Hz, 1H), 8.31 (d, J¼8.4 Hz, 2H), 8.51 (d, J¼6.9 Hz, 1H); 13C NMR
4.2.6. 6-Ethoxy-2-(4-(trifluoromethyl)phenyl)benzo[d]imidazo[2,1-b]
thiazole (4j). Isolated yield 41%; Rf (1:1 EtOAc/PE) 0.52; white solid:
(75 MHz, CDCl3) d (ppm): 18.2, 111.4, 112.7, 117.7, 124.3, 125.9, 128.3
(ꢁ2C), 128.4, 133.8, 146.4, 148.9; HRMS: (ESI) m/z [MþH]þ calcd for
mp<250 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 1.36 (t, J¼6.9 Hz,
C14H13N2S: 241.0641, found 241.0657; HPLC: 98.7%.
3H), 4.10 (q, J¼6.9 Hz, 2H), 7.16 (dd, J¼2.4, 9.0 Hz, 1H), 7.68 (d,
J¼2.4 Hz, 1H), 7.80 (d, J¼8.4 Hz, 2H), 7.91 (d, J¼9.0 Hz, 1H), 8.04 (d,
4.2.10. 8-Methyl-3-(methylthio)-2-(p-tolyl)imidazo[1,2-a]pyridine
J¼8.4 Hz, 2H), 8.91 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
(ppm): 15.0,
(2c). Rf (1:4 EtOAc/PE) 0.48; off white solid: mp 71 ꢀC, 1H NMR
64.3, 110.4, 111.3, 114.4, 114.7, 114.9, 125.4, 126.0, 126.2 (q), 127.2,
(300 MHz, CDCl3) d (ppm): 2.26 (s, 3H), 2.44 (s, 3H), 2.69 (s, 3H),
131.1, 137.8, 143.9, 147.4, 156.9; HRMS (ESI): m/z [MþH]þ calcd for
6.86 (t, J¼6.0 Hz, 1H), 7.09 (d, J¼6.0 Hz, 1H), 7.29 (t, J¼9.0 Hz, 2H),
C
18H14F3N2OS: 363.0951, found 363.0772; HPLC: 99.8%.
8.18 (d, J¼9.0 Hz, 2H), 8.36 (d, J¼6.0 Hz, 1H); 13C NMR (75 MHz,
CDCl3)
d (ppm): 16.8, 18.2, 21.4, 111.3, 112.6, 122.0, 124.6, 127.6,
4.2.7. 2-(4-(Trifluoromethyl)phenyl)imidazo[1,2-a]quinoline
(4k). Isolated yield 34%; Rf (1:5 EtOAc/PE) 0.55; pale yellow solid:
128.3, 129.1, 131.3, 137.9, 146.9, 148.7; HRMS (ESI): m/z [MþH]þ
calcd for C16H17N2S: 269.1107, found 269.1119; HPLC: 99.8%.
mp 180e182 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 7.53 (dd, J¼6.6,
7.2 Hz, 1H), 7.61 (d, J¼4.5 Hz, 2H), 7.68 (br s, 1H), 7.73 (d, J¼8.1 Hz,
2H), 7.86 (d, J¼8.4 Hz, 1H), 8.00 (d, J¼8.4 Hz, 1H), 8.14 (d, J¼8.1 Hz,
4.2.11. 2-(4-Methoxyphenyl)-8-methyl-3-(methylthio)imidazo[1,2-a]
pyridine (2d). Rf (1:3 EtOAc/PE) 0.57; colorless oil; 1H NMR
2H), 8.42 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
(ppm): 107.7, 115.1,
(300 MHz, CDCl3) d (ppm): 2.26 (s, 3H), 2.73 (s, 3H), 3.89 (s, 3H),
117.0, 123.4, 125.0, 125.7, 125.8 (q), 126.0, 126.9, 129.0, 129.3, 129.7,
6.85 (t, J¼6.0 Hz, 1H), 7.04 (d, J¼9.0 Hz, 2H), 7.09 (d, J¼6.0 Hz, 1H),
132.5, 137.2, 143.3, 144.4; HRMS (ESI): m/z [MþH]þ calcd for
8.25 (d, J¼9.0 Hz, 2H), 8.35 (d, J¼6.0 Hz, 1H); 13C NMR (75 MHz,
C
18H12F3N2: 313.0947, found 313.0943; HPLC: 99.8%.
CDCl3) d (ppm): 16.8, 18.2, 55.3, 110.7, 112.5, 113.8, 122.0, 124.6,
126.8, 127.4, 129.7, 146.6, 148.4, 159.6; HRMS (ESI): m/z [MþH]þ
4.2.8. Typical reaction condition and representative spectroscopic
data of 8-methyl-3(methylthio)-2-phenylimidazo[1,2-a]pyridine
(2a). To a solution of 1.5 equiv of phosphorus oxychloride (0.27 mL,
3 mmol) in DMSO (5 mL) (a complex prepared maintaining
calcd for C16H17N2OS: 285.1056, found 285.1066; HPLC: 99.5%.
4.2.12. 2-(4-Chlorophenyl)-8-methyl-3-(methylthio)imidazo[1,2-a]
pyridine (2e). Rf (1:4 EtOAc/PE) 0.50; off white solid: mp

8260
S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
101e102 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 2.26 (s, 3H), 2.68
8.33 (d, J¼8.4 Hz, 2H), 8.77 (s, 1H); 13C NMR (75 MHz, CDCl3)
(s, 3H), 6.88 (t, J¼6.0 Hz,1H), 7.11 (d, J¼6.0 Hz, 1H), 7.46 (d, J¼9.0 Hz,
d
(ppm): 18.3, 55.3, 113.9, 114.2, 117.0, 120.6, 121.9 (q), 124.2, 124.9,
2H), 8.28 (d, J¼9.0 Hz, 2H), 8.36 (d, J¼6.0 Hz,1H); 13C NMR (75 MHz,
125.2, 129.8, 143.3, 150.9, 160.3; HRMS (ESI): m/z [MþH]þ calcd for
CDCl3)
d
(ppm): 16.8, 18.2, 111.8, 112.9, 122.1, 124.9, 127.7, 128.5,
C16H13ClF3N2OS: 373.0384, found 373.0363; HPLC: 99.9%.
129.6, 132.7, 134.0, 146.7, 147.3; HRMS (ESI): m/z [MþH]þ calcd for
C
15H14ClN2S: 289.0561, found 289.0534; HPLC: 99.3%.
4.2.20. Ethyl 8-methyl-3-(methylthio)imidazo[1,2-a]pyridine-2-carb
oxylate (2m). Rf (1:1 EtOAc/PE) 0.54; white solid: mp 118e119 ꢀC;
4.2.13. 2-(4-Bromophenyl)-8-methyl-3-(methylthio)imidazo[1,2-a]
1H NMR (500 MHz, CDCl3)
d
(ppm): 1.50 (t, J¼7.0 Hz, 3H), 2.44 (s,
pyridine (2f). Rf (1:4 EtOAc/PE) 0.51; brown solid: mp 96e97 ꢀC; 1H
3H), 2.69 (s, 3H), 4.54 (q, J¼7.0 Hz, 2H), 6.93 (t, J¼6.5 Hz,1H), 7.14 (d,
NMR (300 MHz, CDCl3)
d (ppm): 2.26 (s, 3H), 2.68 (s, 3H), 6.88 (t,
J¼6.5 Hz, 1H), 8.41 (d, J¼6.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
J¼6.0 Hz, 1H), 7.12 (d, J¼6.0 Hz, 1H), 7.62 (d, J¼9.0 Hz, 2H), 8.23 (d,
d (ppm): 14.4, 16.9, 18.8, 61.4, 114.1, 121.1, 122.6, 125.6, 129.1, 139.1,
J¼9.0 Hz, 2H), 8.36 (d, J¼6.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
146.1, 163.1; HRMS (ESI): m/z [MþH]þ calcd for C12H15N2O2S:
d
(ppm): 16.8, 18.2,111.9, 113.0, 122.1, 122.4,125.2,127.7, 130.0,131.5,
251.0849, found 251.0863; HPLC: 97.8%.
132.9, 146.5, 147.1; HRMS (ESI): m/z [MþH]þ calcd for C15H14BrN2S:
333.0056, found 333.0050; HPLC: 99.8%.
4.2.21. Ethyl 8-(benzyloxy)-3-(methylthio)imidazo[1,2-a]pyridine-2-
carboxylate (2n). Rf (1:1 EtOAc/PE) 0.61; light brown solid: mp
4.2.14. 8-Methyl-3-(methylthio)-2-(4-(trifluoromethyl)phenyl)imi-
dazo[1,2-a]pyridine (2g). Rf (1:4 EtOAc/PE) 0.50; off white solid: mp
95e97 ꢀC; 1H NMR (500 MHz, CDCl3)
d
(ppm): 1.48 (t, J¼7.0 Hz, 3H),
2.45 (s, 3H), 4.52 (q, J¼7.0 Hz, 2H), 5.38 (s, 2H), 6.59 (d, J¼7.0 Hz,
102e104 ꢀC; 1H NMR (300 MHz, CDCl3)
d (ppm): 2.28 (s, 3H), 2.70
1H), 6.83 (t, J¼7.0 Hz, 1H), 7.34e7.41 (m, 3H), 7.50 (d, J¼7.5 Hz, 2H),
(s, 3H), 6.90 (t, J¼6.9 Hz,1H), 7.14 (d, J¼6.9 Hz,1H), 7.75 (d, J¼8.4 Hz,
8.16 (d, J¼7.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d (ppm): 14.4, 18.8,
2H), 8.38 (d, J¼6.9 Hz,1H), 8.45 (d, J¼8.7 Hz, 2H); 13C NMR (75 MHz,
61.2, 70.9, 104.6, 113.9, 117.5, 121.9, 127.3, 128.2, 128.7, 135.8, 138.9,
140.2, 148.7, 162.9; HRMS (ESI): m/z [MþH]þ calcd for C18H19N2O3S:
343.1111, found 343.1130; HPLC: 96.5%.
CDCl3)
d (ppm): 16.8, 18.2, 112.6, 113.1, 122.1, 125.1, 125.2 (q), 126.2,
127.9, 128.5 (ꢁ2C), 129.7, 137.7, 146.8; HRMS (ESI): m/z [MþH]þ
calcd for C16H14F3N2S: 323.0824, found 323.0817; HPLC: 98.8%.
4.2.22. Ethyl 3-(methylthio)-8-(trifluoromethyl)imidazo[1,2-a]pyri-
dine-2-carboxylate (2o). Rf (1:1 EtOAc/PE) 0.63; white solid: mp
4.2.15. 8-Methyl-3-(methylthio)-2-(4-nitrophenyl)imidazo[1,2-a]
pyridine (2h). Rf (1:4 EtOAc/PE) 0.41; yellow solid: mp 160e162 ꢀC;
104e106 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 1.49 (t, J¼7.2 Hz,
1H NMR (300 MHz, CDCl3)
d
(ppm) 2.32 (s, 3H), 2.80 (s, 3H), 7.05 (t,
3H), 2.47 (s, 3H), 4.53 (q, J¼7.2 Hz, 2H), 7.10 (t, J¼6.9 Hz, 1H), 7.20 (d,
J¼6.6 Hz, 1H), 7.29 (d, J¼6.6 Hz, 1H), 8.37 (d, J¼8.4 Hz, 2H), 8.45 (d,
J¼6.9 Hz, 1H), 8.73 (d, J¼6.9 Hz, 1H); 13C NMR (75 MHz, CDCl3)
J¼6.6 Hz, 1H), 8.58 (d, J¼8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d
(ppm): 14.3, 18.9, 61.6, 112.3, 120.6, 120.9, 122.3, 125.7 (q), 128.3,
d
(ppm): 17.2,18.2,114.6,116.0,122.4,123.7,127.6,127.7,129.4,138.3,
140.6, 141.1, 162.6; HRMS (ESI): m/z [MþH]þ calcd for
144.1, 145.5, 147.6; HRMS (ESI): m/z [MþH]þ calcd for C15H14N3O2S:
C12H12F3N2O2S: 305.0566, found 305.0550; HPLC: 99.5%.
300.0801, found 300.0798; HPLC: 97.6%.
4.2.23. 2-(tert-Butyl)-3-(methylthio)imidazo[1,2-a]pyridine (2p). Rf
(1:1 EtOAc/PE) 0.70; oil; 1H NMR (300 MHz, CDCl3)
(ppm): 1.58 (s,
4.2.16. 2-([1,10-Biphenyl]-4-yl)-8-methyl-3-(methylthio)imidazo[1,2-
d
a]pyridine (2i). Rf (1:4 EtOAc/PE) 0.48; white solid: mp 135e137 ꢀC;
9H), 2.23 (s, 3H), 6.91 (t, J¼6.6 Hz, 1H), 7.25 (t, J¼9.0 Hz, 1H), 7.64 (d,
1H NMR (300 MHz, CDCl3)
d (ppm): 2.30 (s, 3H), 2.71 (s, 3H), 6.88 (t,
J¼9.0 Hz, 1H), 8.43 (d, J¼6.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
J¼6.9 Hz, 1H), 7.12 (d, J¼6.9 Hz, 1H), 7.40 (d, J¼7.2 Hz, 1H), 7.49 (dd,
d (ppm): 18.4, 30.5, 33.8,110.0,112.4,117.4,123.4,125.0,145.0,160.1;
J¼7.2, 7.8 Hz, 2H), 7.66e7.69 (m, 4H), 8.41 (m, 3H); 13C NMR (75 MHz,
HRMS (ESI): m/z [MþH]þ calcd for C12H17N2S: 221.1107, found.
CDCl3)
d
(ppm): 16.9,18.3,111.7,112.8,122.1,124.8,127.1 (ꢁ2C),127.3,
221.1107; HPLC: 96.3%.
127.7, 128.8 (ꢁ2C), 133.1, 140.7, 140.9, 146.7, 148.1; HRMS (ESI): m/z
[MþH]þ calcd for C21H19N2S: 331.1263, found 331.1254; HPLC: 99.8%.
4.2.24. 3-(Methylthio)-2-phenylimidazo[1,2-a]pyrimidine
(1:9 MeOH/chloroform) 0.55; pale yellow solid: mp 130e131 ꢀC; 1H
NMR (300 MHz, CDCl3)
(ppm): 2.30 (s, 3H), 7.02 (dd, J¼2.4, 7.2 Hz,
1H), 7.44 (q, J¼7.2 Hz, 1H), 7.52 (m, 2H), 8.44 (d, J¼7.2 Hz, 2H), 8.64
(m, 1H), 8.77 (m, 1H); 13C NMR (75 MHz, CDCl3)
(ppm): 18.3, 109.1,
(5a). Rf
4.2.17. 2-(3-(Benzyloxy)phenyl)-8-methyl-3-(methylthio)imidazo
d
[1,2-a]pyridine (2j). Rf (1:4 EtOAc/PE) 0.49; semisolid; 1H NMR
(300 MHz, CDCl3)
d
(ppm): 2.24 (s, 3H), 2.69 (s, 3H), 5.21 (s, 2H),
d
6.87 (t, J¼6.0 Hz, 1H), 7.03 (dd, J¼3.0, 9.0 Hz, 1H), 7.10 (d, J¼6.0 Hz,
1H), 7.35e7.44 (m, 4H), 7.52 (d, J¼6.0 Hz, 2H), 7.92 (d, J¼9.0 Hz, 1H),
8.00 (br s, 1H), 8.37 (d, J¼6.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
110.2, 128.5, 128.8, 130.1, 131.9, 133.2, 149.4, 150.2, 150.9; HRMS
(ESI): m/z [MþH]þ calcd for C13H12N3S: 242.0746, found 242.0742;
HPLC: 99.0%.
d
(ppm): 16.8, 18.2, 70.0, 111.8, 112.7, 114.4, 115.1, 121.2, 122.1, 124.7,
127.6, 127.7, 127.9, 128.6, 129.4, 135.5, 137.2, 146.6, 148.2, 158.8;
HRMS (ESI): m/z [MþH]þ calcd for C22H21N2OS: 361.1369, found
361.1356; HPLC: 99.1%.
4.2.25. 3-(Methylthio)-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]
pyrimidine (5b). Rf (1:9 MeOH/chloroform) 0.62; brown solid: mp
118e119 ꢀC; 1H NMR (300 MHz, CDCl3)
d (ppm): 2.31 (s, 3H), 7.07
(q, J¼6.9 Hz, 1H), 7.77 (d, J¼8.1 Hz, 2H), 8.59 (d, J¼8.1 Hz, 2H), 8.68
4.2.18. 6-Chloro-3-(methylthio)-2-phenylimidazo[1,2-a]pyridine
(dd, J¼2.1, 6.9 Hz, 1H), 8.79 (dd, J¼2.1, 6.9 Hz, 1H); 13C NMR
(2k). Rf (3:7 EtOAc/PE) 0.65; white solid: mp 173 ꢀC; 1H NMR
(75 MHz, CDCl3) d (ppm): 18.3, 109.4, 111.3, 122.4, 125.4, 128.6,
(300 MHz, CDCl3)
d
(ppm): 2.30 (s, 3H), 7.28 (br s,1H), 7.40e7.53 (m,
130.7 (q), 132.0, 136.7, 148.5, 149.4, 151.5; HRMS (ESI): m/z
[MþH]þ calcd for C14H11F3N3S: 310.0620, found 310.0620; HPLC:
99.7%.
3H), 7.63 (d, J¼9.3 Hz, 1H), 8.29 (d, J¼7.2 Hz, 2H), 8.54 (s, 1H); 13C
NMR (75 MHz, CDCl3) d (ppm): 18.2, 112.2, 118.0, 121.2, 122.3, 127.3,
128.2, 128.5 (ꢁ2C), 133.4, 144.6, 149.7; HRMS (ESI): m/z [MþH]þ
calcd for C14H12ClN2S: 275.0404, found 275.0420; HPLC: 93.0%.
4.2.26. 5,7-Dimethyl-3-(methylthio)-2-phenylimidazo[1,2-a]pyrimi-
dine (5c). Rf (1:9 MeOH/chloroform) 0.54; light brown solid: mp
4.2.19. 8-Chloro-2-(4-methoxyphenyl)-3-(methylthio)-6-(tri-
fluoromethyl)imidazo[1,2-a]pyridine (2l). Rf (1:4 EtOAc/PE) 0.62;
pale yellow solid: mp 158e159 ꢀC; 1H NMR (300 MHz, CDCl3)
158e159 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 2.30 (s, 3H), 2.60
(s, 3H), 3.17 (s, 3H), 6.55 (s, 1H), 7.41e7.51 (m, 3H), 8.33 (d, J¼7.5 Hz,
2H); 13C NMR (75 MHz, CDCl3)
(ppm): 20.4, 23.0, 24.4, 111.2, 111.8,
128.2, 128.4, 128.9, 133.7, 146.7, 150.4, 151.7, 161.0; HRMS (ESI): m/z
d
d
(ppm): 2.31 (s, 3H), 3.90 (s, 3H), 7.04 (d, J¼8.4 Hz, 2H), 7.52 (s, 1H),

S.M. Patil et al. / Tetrahedron 69 (2013) 8255e8262
8261
[MþH]þ calcd for C15H16N3S: 270.1059, found 270.1041; HPLC:
[MþH]þ calcd for C19H16F3N2OS2: 409.0651, found 409.0643; HPLC:
99.0%.
98.4%.
4.2.27. 5-(Methylthio)-6-phenylimidazo[2,1-b]thiazole (5d). Rf (1:1
EtOAc/PE) 0.70; off white solid: mp 96e97 ꢀC; 1H NMR (300 MHz,
4.2.34. 1-(Methylthio)-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]
quinoline (5k). Rf (1:3 EtOAc/PE) 0.62; white solid: mp 166 ꢀC; 1H
CDCl3)
d
(ppm): 2.33 (s, 3H), 6.91 (d, J¼4.5 Hz, 1H), 7.37 (d, J¼7.5 Hz,
NMR (300 MHz, CDCl3)
d
(ppm): 2.39 (s, 3H), 7.55 (t, J¼7.8 Hz, 1H),
1H), 7.46 (dd, J¼7.2, 7.8 Hz, 2H), 7.61 (d, J¼4.5 Hz, 1H), 8.20 (d,
7.63 (br s, 2H), 7.71e7.78 (m, 3H), 7.86 (d, J¼7.8 Hz, 1H), 8.29 (d,
J¼7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3)
(ppm): 19.4, 112.7 (ꢁ2C),
d
J¼8.1 Hz, 2H), 10.0 (d, J¼8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3)
117.9, 127.3, 127.8, 128.4, 134.0, 150.0, 150.1; HRMS (ESI): m/z
[MþH]þ calcd for C12H11N2S2: 247.0358, found 247.0364; HPLC:
99.9%.
d (ppm): 20.6, 116.5, 116.8, 117.4, 122.5, 124.8, 125.1 (q), 126.1, 128.6,
128.9, 129.3 (ꢁ2C), 130.0, 135.6, 137.5, 146.1, 148.8; MS (ESI): m/z
[MþH]þ calcd for C19H14F3N2S: 359.1, found 359.0. Elemental
analysis: C19H13F3N2S (358.38): C 63.68, H 3.66, N 7.82, F 15.9, S
8.95; found C 63.18, H 3.34, N 7.96; HPLC: 98.2%.
4.2.28. 2-Methyl-5-(methylthio)-6-phenylimidazo[2,1-b]thiazole
(5e). Rf (1:1 EtOAc/PE) 0.75; light brown solid: mp 93e94 ꢀC; 1H
NMR (300 MHz, CDCl3)
1H), 7.36 (t, J¼7.2 Hz, 1H), 7.46 (t, J¼7.2 Hz, 2H), 8.15 (d, J¼7.2 Hz,
2H); 13C NMR (75 MHz, CDCl3)
(ppm): 14.7, 22.3, 107.5, 114.1,
127.8 (ꢁ2C), 128.2, 131.0, 134.1, 151.1, 151.8; HRMS (ESI): m/z
[MþH]þ calcd for C13H13N2S2: 261.0515, found 261.0521; HPLC:
99.8%.
d
(ppm): 2.34 (s, 3H), 2.80 (s, 3H), 6.42 (s,
4.2.35. Ethyl 5-chloro-3-(methylthio)-1H-indole-2-carboxylate
(7a). Rf (3:7 EtOAc/PE) 0.65; yellow solid: mp 145 ꢀC; 1H NMR
d
(300 MHz, CDCl3)
d
(ppm): 1.48 (t, J¼7.2 Hz, 3H), 2.49 (s, 3H), 4.49
(q, J¼7.2 Hz, 2H), 7.28e7.38 (m, 2H), 7.88 (s, 1H), 9.12 (br s, 1H); 13
C
NMR (75 MHz, CDCl3)
d (ppm): 14.4, 19.7, 61.6, 113.2, 115.3, 120.9,
126.6, 127.0, 128.9, 131.1, 133.6, 160.9; HRMS (ESI): m/z (MþNa)þ
calcd for C12H12ClNNaO2S: 292.0169, found 292.0189; HPLC: 96.5%.
4.2.29. 3-(4-Bromophenyl)-5-(methylthio)-6-(4-(trifluoromethyl)
phenyl)imidazo[2,1-b]thiazole (5f). Rf (1:4 EtOAc/PE) 0.44; white
4.2.36. 2-Chloro-1-methyl-3-(methylthio)-1H-indole-6-carbonitrile
solid: mp 226e227 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 1.79 (s,
(7b). Rf (1:1 EtOAc/PE) 0.50; white solid: mp 152e154 ꢀC; 1H NMR
3H), 6.74 (s,1H), 7.54 (d, J¼7.8 Hz, 2H), 7.64 (d, J¼8.1 Hz, 2H), 7.69 (d,
(300 MHz, CDCl3) d (ppm): 2.32 (s, 3H), 3.85 (s, 3H), 7.46 (d,
J¼8.1 Hz, 2H), 8.24 (d, J¼7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3)
J¼8.4 Hz, 1H), 7.65 (s, 1H), 7.79 (d, J¼8.1 Hz, 1H); 13C NMR (75 MHz,
d
(ppm): 20.5, 111.3, 115.6, 124.3, 125.1 (q), 126.1, 127.9, 128.1, 129.7,
CDCl3) d (ppm): 19.2, 30.9, 105.1, 105.4, 114.1, 119.8, 120.2, 123.9,
131.0,131.8, 133.6,137.4,149.7, 151.8; HRMS (ESI): m/z [MþH]þ calcd
131.8, 134.7, 135.2; MS (ESI): m/z [MþH]þ calcd for C11H9ClN2S:
237.0, found 237.1. Elemental analysis: C11H9ClN2S (236.02): C
55.83, H 3.83, N 11.83, Cl 14.98, S 13.55; found C 55.65, H 3.28, N
12.11; HPLC: 99.4%.
for C18H13BrF3N2S2: 468.9650, found 468.9661; HPLC: 98.3%.
4.2.30. 2-Methyl-5-(methylthio)-6-phenylimidazo[2,1-b][1,3,4]thia-
diazole (5g). Rf (1:1 EtOAc/PE) 0.41; off white solid: mp 110e111 ꢀC;
1H NMR (300 MHz, CDCl3)
d
(ppm): 2.45 (s, 3H), 2.80 (s, 3H), 7.37 (d,
4.2.37. Methyl
carboxylate (7c). Rf (1:4 EtOAc/PE) 0.62; colorless oil; 1H NMR
(300 MHz, CDCl3)
2-chloro-1-isopropyl-3-(methylthio)-1H-indole-4-
J¼6.6 Hz,1H), 7.49 (m, 2H), 8.16 (d, J¼6.6 Hz, 2H); 13C NMR (75 MHz,
CDCl3)
d
(ppm): 18.0, 19.0, 114.6, 127.3, 127.8, 128.4, 133.9, 145.9,
d
(ppm): 1.67 (d, J¼6.9 Hz, 6H), 2.29 (s, 3H), 4.00
147.8, 159.8; HRMS (ESI): m/z [MþH]þ calcd for C12H12N3S2:
(s, 3H), 5.05 (septet, J¼6.9 Hz, 1H), 7.25 (dd, J¼7.2, 8.4 Hz, 1H), 7.34
262.0467, found 262.0468; HPLC: 97.8%.
(d, J¼7.2 Hz, 1H), 7.60 (d, J¼8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
(ppm): 19.6, 21.3, 49.1, 52.1, 103.7, 113.3, 120.5, 121.2, 125.5, 125.8,
4.2.31. 3-(Methylthio)-2-phenylbenzo[d]imidazo[2,1-b]thiazole
133.1, 134.5, 170.0; MS (ESI): m/z [MþNa]þ calcd for C14H16ClNO2S:
(5h). Rf (1:4 EtOAc/PE) 0.55; white solid: mp 172e174 ꢀC; 1H NMR
320.1; found 320.5; HPLC: 96.8%.
(300 MHz, CDCl3)
d
(ppm): 2.51 (s, 3H), 7.39 (d, J¼7.2 Hz,1H), 7.49 (t,
J¼7.5 Hz, 3H), 7.63 (t, J¼7.2 Hz, 1H), 8.11 (dd, J¼8.1, 9.0 Hz, 3H), 8.61
Acknowledgements
(d, J¼8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d (ppm): 20.4, 114.1,
115.3,124.1,124.8,126.3,127.7,127.9,128.3,130.3,133.7,133.8,149.4,
150.9; HRMS (ESI): m/z [MþH]þ calcd for C16H13N2S2: 297.0515,
found 297.0506; HPLC: 99.2%.
The authors want to thank the analytical facility at Piramal En-
terprises Ltd, Mumbai, India, for their support.
Supplementary data
4.2.32. 6-Ethoxy-2-(3-methoxyphenyl)-3-(methylthio)benzo[d]imi-
The characterization copies of 1H NMR, 13C NMR, and HRMS
spectra for the thiomethylated products and 1g, 1j, 4b, 4f, 4iek.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2013.07.017.
dazo[2,1-b]thiazole (5i). Rf (3:7 EtOAc/PE) 0.60; pale yellow solid:
mp 116 ꢀC; 1H NMR (300 MHz, CDCl3)
d
(ppm): 1.48 (t, J¼6.9 Hz,
3H), 2.40 (s, 3H), 3.91 (s, 3H), 4.10 (q, J¼6.9 Hz, 2H), 6.93 (d,
J¼6.6 Hz, 1H), 7.05 (d, J¼7.2 Hz, 1H), 7.22 (s, 1H), 7.38 (t, J¼7.8 Hz,
1H), 7.80 (d, J¼9.0 Hz, 2H), 8.54 (d, J¼9.0 Hz, 1H); 13C NMR (75 MHz,
CDCl3)
d
(ppm): 14.8, 20.3, 55.3, 64.2,109.0,112.5,114.0 (ꢁ2C),114.7,
References and notes
115.2, 120.0, 127.8, 129.3, 131.6, 135.2, 148.7, 149.9, 156.4, 159.6;
HRMS (ESI): m/z [MþH]þ calcd for C19H19N2O2S2: 371.0882, found
371.0884; HPLC: 98.6%.
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J¼6.9 Hz, 3H), 2.41 (s, 3H), 4.12 (q, J¼6.9 Hz, 2H), 7.07 (dd, J¼2.4,
9.0 Hz, 1H), 7.23 (d, J¼2.4 Hz, 1H), 7.71 (d, J¼8.4 Hz, 2H), 8.34 (d,
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127.5, 129.2, 129.6, 131.6, 137.2, 148.4, 149.1, 156.6; HRMS (ESI): m/z

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~
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