Fused Heterocycles: Synthesis and Antitubercular Activity of Novel 6-Substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine

Article abstract of DOI:10.1002/jhet.2409

(Chemical Equation Presented) A series of 6-substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine derivatives 4a-4l is described. The antitubercular activity of the synthesized compounds was determined against Mycobacterium smegmatis MC² 155 strain. From the activity result, it was found that the phenyl or 4-fluorophenyl group at 2 position of thiazole nucleus and bromo substituent at 6 position of imidazo[1,2-a]pyridine showed good antitubercular activity.

Full text of DOI:10.1002/jhet.2409

Month 2015
Fused Heterocycles: Synthesis and Antitubercular Activity of Novel
6-Substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-
imidazo[1,2-a]pyridine
a
a
b
b
b
*
*
Yogita K. Abhale, Keshav K. Deshmukh, Amit V. Sasane, Abhijit P. Chavan, and Pravin C. Mhaske
aPost-Graduate and Research, Department of Chemistry, S. N. Arts, D. J. M. Commerce and B. N. S. Science College,
Sangamner 422 005, District Ahmednagar, India (Affiliated to University of Pune)
bPost Graduate Department of Chemistry, S. P. Mandali’s, Sir Parashurambhau College, Tilak Road, Pune 411 030,
India (Affiliated to University of Pune)
*
E-mail: mhaskepc18@gmail.com; keshav_deshmukh13@yahoo.in
Additional Supporting Information may be found in the online version of this article.
Received October 11, 2014
DOI 10.1002/jhet.2409
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
A series of 6-substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine deriva-
tives 4a–4l is described. The antitubercular activity of the synthesized compounds was determined against
Mycobacterium smegmatis MC2 155 strain. From the activity result, it was found that the phenyl or
4-fluorophenyl group at 2 position of thiazole nucleus and bromo substituent at 6 position of imidazo
[1,2-a]pyridine showed good antitubercular activity.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
new scaffold for antimycobacterial agents, it was thought to
synthesize novel clubbed 6-substituted-2-(4-methyl-2-substituted
phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine derivatives and
screen for their antitubercular activity.
Mycobacterium tuberculosis infects about 32% of the
world’s population, and it is a contagious disease with com-
paratively high mortality worldwide [1–3]. The last major
clinical advance in TB chemotherapy was the introduction
of rifampin in 1968 [4,5]. The current situation clearly
shows that TB is far from under control and requires the
new effective drug to treating TB. With the worldwide
emergence of multidrug-resistant TB and extensively
drug-resistant TB, the World Health Organization has
declared TB a global emergency [6–8].
Literature revealed that thiazole ring-containing and
pyridine ring-containing compounds showed antitubercular
and antimicrobial activities. Thiazole and their derivatives
are an important pharmacophore, and its coupling with
other rings could furnish new biologically active
compounds [9–11]. Thiazole compounds have exhibited a
broad range of biological activities such as antitumor [12],
anticancer [13], antibiotic [14], anti-inflammatory [15–18],
antibacterial and antifungal [19–23], antitubercular
[24–26], and antiviral [27] activities.
Isoniazid derivatives and pyridine-containing heterocyclic
compounds are known for the antimycobacterial activity
[28–31]. 2-Anilino-4-(thiazol-5-yl)pyrimidine derivatives
show potent inhibitors of cyclin-dependent kinase-2 activity
[32], oxadiazinylimidazopyridines, pyrimidines, and thiazoles
[33]; 6-methylimidazo[2,1-b]thiazole-5-carbohydrazide de-
rivatives show antimicrobial activities [34]; and oxazolines,
oxazoles, thiazolines, and thiazoles to imidazo[1,2-a]pyri-
dines show antitubercular activity [35]. For searching the
The synthesis of 6-substituted-2-(4-methyl-2-substituted
phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine 4a–l is illus-
trated in Scheme 1. The starting material 1-(4-methyl-2-
phenylthiazol-5-yl)ethanone 1a–d was synthesized by
cyclocondensation of aryl thioamide with 3-bromopentane-
2,4-dione. 1-(4-Methyl-2-phenylthiazol-5-yl)ethanone [36,37]
1a–d on bromination with bromine in dichloromethane
(DCM) gave 2-bromo-1-(4-methyl-2-substituted phenylthiazol-
5-yl)ethanone 2a–d, which on cyclocondensation with
substituted 2-aminopyridine 3a–c furnished target
compounds 4a–l. The physical properties of synthesized
compounds are given in Table 1.
RESULTS AND DISCUSSION
The structure of the title compounds 4a–4l was
confirmed by IR, NMR, and HRMS. The IR (KBr) spectra
of compound 4d showed C¼C/C¼N absorption bands at
1
1608–1493cmꢀ1. The H NMR spectra of compound 4d
showed two singlets at δ 2.65 for methyl group and δ 8.19
because of imidazo[1,2-a]pyridine CH. The signals, a
double of triplet at δ 6.86, multiplet at δ 7.21–7.26, doublet
at δ 7.51, and doublet of doublet at δ 8.46 are accountable
for the protons of pyridine ring, whereas doublets at δ 7.45
and δ 7.90 correspond to orthoprotons and metaprotons of
4-chlorobenzene ring. The 13C NMR spectrum of
© 2015 HeteroCorporation

Y. K. Abhale, K. K. Deshmukh, A. V. Sasane, A. P. Chavan, and P. C. Mhaske
Vol 000
Scheme 1
Table 1
Antitubercular activity of synthesized compounds 4a–4l.
Compound
R
R1
Yield (%)
Mp (°C)
M. smegmatisa
MIC (μg/mL)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
H
H
H
Cl
Cl
Cl
F
F
F
H
60
62
62
64
65
60
60
64
60
66
62
60
172–174
100–112
178–180
180–182
190–192
187–188
172–174
206–208
178–179
242
2.5
55.6
9.8
NA
4.4
>50
25
>50
—
>50
>50
27.9
20.8
—
>50
>50
>50
5.07
6-Br
6-Cl
H
6-Br
6-Cl
H
6-Br
6Cl
H
6-Br
6-Cl
1.8
29.5
50.5
NA
12.3
4.7
CH3
CH3
CH3
256
188–190
4.4
96
Isoniazid
a% inhibition.
compound 4d showed signal at δ 16.9 for methyl group,
whereas the aromatic and heterocyclic carbon showed
signals at δ 109.7 to δ 162.2. Compound 4d was further
confirmed by HRMS and molecular ion peaks at m/z
326.0371 (M + H)+. The mass spectra for the respective
compounds with chlorine and/or bromine substitution
showed M + 2 peaks.
closer look into structure activity relationships (SARs) of
these compounds reveals the following points.
The compound 2-(4-methyl-2-phenylthiazol-5-yl)H-imidazo
[1,2-a]pyridine (4a) is inactive. When the phenyl ring was
substituted by 4-fluorophenyl and 4-methylphenyl in
compounds 4g and 4j, increase in activity is reported.
The compound 4b reported moderate activity
with MIC 25 μg/mL. If the phenyl ring was substituted
by 4-chlorophenyl (4e) or 4-methyl phenyl (4k), the ac-
tivity decreases. Whereas when the phenyl ring was
substituted by 4-fluorophenyl (4h), the activity retains.
The substitution at imidazo[1,2-a]pyridine also affects
the activity. The compound 4a is inactive, whereas the
substitution of hydrogen of 6 position of imidazo
[1,2-a]pyridine by bromine (4b) and chlorine (4c)
increases the activity by 22-fold and fivefold, respec-
tively. The compound 4d is found to be inactive. Further,
the substitution of hydrogen of 6 position of imidazo[1,2-
a]pyridine by bromine (4e) and chlorine (4f) did not
affect the activity. The compound 4g showed moderate
activity. The substitution of hydrogen of 6 position of
imidazo[1,2-a]pyridine by bromine in compound 4h
reported moderate activity, while the substitution of
hydrogen by chlorine in compound 4i was inactive. With
the substitution of hydrogen of 6 position of compound
Antitubercular activity.
As an initial screening,
the synthesized compounds (4a–4l) were screened for
their antitubercular activity against Mycobacterium
smegmatis as a surrogate organism, at 30-μM compound
concentration [38]. The percentage inhibition was
determined against DMSO, and those compounds that
showed inhibition at 30% or more were further analyzed to
determine their minimum inhibitory concentration (MIC)
values. Isoniazid was used as reference drug. The result of
antitubercular activity is reported in Table 1.
From in vitro antitubercular activity data, the structure–
activity relationship of compounds was studied. Various
substituents, viz. Br, Cl, F, and CH3 on the phenyl ring of
2 position of thiazole, were introduced, and substituent at
6 position of imidazo[1,2-a]pyridine nucleus was ex-
changed with Br and Cl. It was found that these substituents
affect the activity. From the activity data, compounds 4b
and 4h recorded good activity at 30-μM concentration. A
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
6-Substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo
[1,2-a]pyridine
Representative procedure for synthesis of compounds
4a–4l. mixture of 2-bromo-1-(2-(4-substituted-phenyl)-4-
4j by bromine and chlorine in compounds 4k and 4l, the
activity decreases.
A
methyl thiazol-5yl)ethanone (1 mmol) and 2-aminopyridine
(1.1 mmol) was refluxed in dry ethanol (15 mL). The reaction
was monitored on TLC. After the completion of reaction,
solvent was evaporated under vacuum, and residue was
dissolved in ethyl acetate. The organic layer was washed with
sodium bicarbonate and water. The solvent was dried over
sodium sulfate and distilled under vacuum. The product was
purified by crystallization in ethanol. The structure of all the
synthesized compounds was confirmed by spectral analysis.
2-(4-Methyl-2-phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4a). IR (KBr): 3060, 3028, 1602, 1498, 1432, 1394, 1340,
CONCLUSION
To summarize, we have synthesized a series of novel
6-substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)
H-imidazo[1,2-a]pyridine 4a–l. The in vitro antitubercular
activity results revealed that compounds 4b and 4h reported
moderate activity. From SARs, it is noted that the phenyl or
4-fluorophenyl group at 2 position of thiazole nucleus and
bromo substituent at 6 position of imidazo[1,2-a]pyridine
contributed to the activity. The antitubercular activity
results make them interesting lead molecules for further
synthetic and biological evaluation.
1
1232, 1089, 1060, 1001, 930, 824 cmꢀ1; H NMR (400 MHz,
DMSO-d6): δ 2.69 (s, 3H CH3), 6.79 (dt, J = 6.84 and 1.00 Hz,
1H, Ar-H), 7.17–7.21 (m, 1H, Ar-H), 7.37–7.45 (m, 3H, Ar-H),
7.63 (d, J = 8.72 Hz, 1H, Ar-H), 7.72 (s, 1H, imidazol-H),
7.94–7.97 (m, 2H, Ar-H), 8.10 (dd, J = 6.84 and 1.00 Hz, 1H);
13C NMR (100 MHz, DMSO-d6): δ 16.9, 109.8, 112.2, 116.4,
125.3, 126.3, 127.4, 127.5, 128.5, 129.6, 132.4, 134.1, 144.2,
149.0, 163.2; HRMS calculated (m/z): 292.0908, found (m/z):
292. 0777 (M + H)+.
EXPERIMENTAL
All the reactions were monitored, and purity of the products
was checked by thin-layer chromatography (TLC). TLC was
performed on Merck 60 F-254 silica gel plates with visualization
by UV light. Melting points were determined in capillary tubes
in silicon oil bath using a Veego melting point apparatus and are
uncorrected. 1H (300 MHz) NMR and 13C (75 MHz) NMR
spectra were recorded on Varian mercury XL-300 and BRUKER
AVANCE II 400 NMR spectrometer (Bruker Instruments Inc.,
Billerica, MA, USA) at either 400-MHz (1H NMR) and
100-MHz (13C NMR) spectrometer instruments. Chemical shifts
are reported from internal tetramethylsilane standard and are given
in δ units. Infrared spectra were taken on Shimadzu FTIR (KBr)
(Shimadzu Corporation, Kyoto, Japan) – 408 in KBr. Electron-
impact HR mass spectra were obtained using MAT model 8400
mass spectrometer using an ionizing voltage of 70 eV. Column
chromatography was performed on silica gel (100–200 mesh) sup-
plied by Acme Chemical Co. (Mumbai, Maharashtra, India). The
chemicals and solvents used were laboratory grade and were puri-
fied as per literature methods.
6-Bromo-2-(4-methyl-2-phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4b). IR (KBr): 3060, 3032, 1605, 1490, 1429, 1395, 1330,
1
1228, 1196, 1089, 1060, 1001, 932, 820, 756 cmꢀ1; H NMR
(400 MHz, DMSO-d6): δ 2.70 (s, 3H, CH3), 7.26 (dd, J = 9.56
and 1.84 Hz, 1H, Ar-H), 7.40–7.46 (m, 3H, Ar-H), 7.52 (d,
J = 9.52 Hz, 1H, Ar-H), 7.71 (s, 1H, imidazol-H), 7.96 (dd,
J = 8.08 and 1.88 Hz, 2H, Ar-H), 8.27–8.28 (m, 1H, Ar-H); 13C
NMR (100 MHz, DMSO-d6): δ 17.3, 107.6, 109.2, 118.1,
125.4, 126.9, 128.2, 128.9, 129.5, 132.1, 135.7, 138.1, 143.5,
149.4, 164.9; HRMS calculated (m/z): 370.0014, found (m/z):
369.9898 (M + H)+.
6-Chloro-2-(4-methyl-2-phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4c). IR (KBr): 3058, 3022, 1599, 1488, 1413, 1387, 1329,
1
1218, 1148, 1078, 1058, 1001, 928, 820, 803 cmꢀ1; H NMR
(400 MHz, CDCl3): δ 2.61 (s, 3H, CH3), 7.34–7.55 (m, 5H,
Ar-H), 7.67 (s, 1H, imidazol-H), 7.85–7.89 (m, 2H, Ar-H),
8.20 (d, J = 1.2 Hz, 1H, Ar-H); 13C NMR (100 MHz, CDCl3): δ
17.1, 109.3, 116.1, 116.7, 117.8, 123.4, 126.5, 127.0, 128.8,
129.5, 131.8, 133.6, 143.5, 149.1, 164.7; HRMS calculated
(m/z): 326.0519, found (m/z): 326.0379 (M + H)+.
Synthesis of 1-(4-methyl-2-phenylthiazol-5-yl)ethanone
(1a).
A mixture of thiobenzamide (6.62 mmol) and of
2-(2-(4-Chlorophenyl)-4-methylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4d). IR (KBr): 3062, 3036, 1608, 1493, 1432, 1397, 1336,
3-bromopentane-2,4-dione (6.62 mmol) was refluxed in ethanol.
After completion of reaction (TLC), the solvent was removed
under reduced pressure, and the residue was dissolved in ethyl
acetate. Organic layer was extracted with sodium bicarbonate
and then water, dried over sodium sulfate, and distilled under
vacuum. The product obtained was purified by column
chromatography using hexane: ethyl acetate (9:1) as eluate.
1
1236, 1199, 1087, 1062, 1003, 933, 826, 804 cmꢀ1; H NMR
(400 MHz, DMSO-d6): δ 2.65 (s, 3H, CH3), 6.86 (dt, J = 6.72
and 1.04 Hz, 1H, Ar-H), 7.21–7.26 (m, 1H, Ar-H), 7.45 (d,
J = 8.6 Hz, 2H, Ar-H), 7.51 (d, J = 8.8 Hz, 1H, Ar-H), 7.90 (d,
J = 8.6 Hz, 2H, Ar-H), 8.19 (s, 1H, imidazol-H), 8.46 (dd,
J = 8.8 and 1.04 Hz, 1H, Ar-H); 13C NMR (100 MHz,
DMSO-d6): δ 16.9, 109.7, 112.3, 116.2, 125.3, 126.7, 127.2,
127.6, 128.9, 131.9, 134.6, 136.9, 144.4, 148.6, 162.2; HRMS
calculated (m/z): 326.0519, found (m/z): 326.0371 (M + H)+.
6-Bromo-2-(2-(4-chlorophenyl)-4-methylthiazol-5-yl)H-
imidazo[1,2-a]pyridine (4e). IR (KBr): 3055, 3027, 1602, 1486,
1426, 1392, 1330, 1232, 1188, 1085, 1060, 1001, 930, 822,
Synthesis of 2-bromo-1-(4-methyl-2-(4-substituted phenyl)thiazol-
5yl)ethanone (2a). A mixture of 1-(4-methyl-2-phenylthiazol-5-
yl)ethanone (10 mmol) and p-toluenesulfonic acid (5 mmol) in
DCM (50 mL) was stirred at 0 °C for 10 min; then, Br2
(10 mmol) in DCM (20 mL) was added dropwise in the reaction
mixture. The reaction mixture was stirred for 12 h at room
temperature (TLC). After completion of the reaction, sodium
bicarbonate solution was added in the reaction mixture and
stirred for 10 min. The aqueous layer was extracted with DCM,
and combined organic layer was washed with water, dried with
sodium sulfate, and distilled under vacuum. The product was
used without further purification.
802, 760 cmꢀ1 1H NMR (300 MHz, CDCl3): δ 2.69 (s, 3H,
;
CH3), 7.27 (dd, J= 7.2 and 2.1 Hz, 1H, Ar-H), 7.41
(d, J= 8.1 Hz, 2H, Ar-H), 7.52 (d, J= 9.6 Hz, 1H, Ar-H), 7.71
(s, 1H, imidazol-H), 7.89 (d, J= 8.1 Hz, 2H, Ar-H), 8.28 (s, 1H,
Ar-H); 13C NMR (75MHz, CDCl3): δ 17.3, 107.4, 109.0, 117.9,
125.5, 126.6, 127.4, 128.8, 129.1, 132.1, 135.8, 139.2, 143.6,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Y. K. Abhale, K. K. Deshmukh, A. V. Sasane, A. P. Chavan, and P. C. Mhaske
Vol 000
149.8, 164.2; HRMS calculated (m/z): 403.9624, found (m/z):
403.9622 (M + H)+.
(d, J = 8.1 Hz, 2H, Ar-H), 7.29 (dd, J = 7.2 and 1.6 Hz, 1H, Ar-H),
7.52 (d, J = 7.2 Hz, 1H, Ar-H), 7.71 (s, 1H, imidazol-H), 7.88
(d, J = 8.1 Hz, 2H, Ar-H), 8.28 (d, J = 1.6 Hz, 1H, Ar-H);
13C NMR (75 MHz, CDCl3): δ 17.1, 29.2, 107.8, 110.1, 114.7,
117.6, 125.3, 127.7, 129.5, 130.6, 132.0, 135.9, 139.0, 143.7,
149.6, 164.1; HRMS calculated (m/z): 384.0170, found (m/z):
384.0155 (M + H)+.
6-Chloro-2-(2-(4-chlorophenyl)-4-methylthiazol-5-yl)H-
imidazo[1,2-a]pyridine (4f). IR (KBr): 3060, 3032, 1601, 1489,
1430, 1394, 1335, 1232, 1193, 1084, 1058, 1003, 933, 820, 807
1
cmꢀ1; H NMR (400 MHz, CDCl3): δ 2.62 (s, 3H, CH3), 7.13 (d,
J= 8.64Hz, 2H, Ar-H), 7.27 (dd, J= 9.56 and 1.92 Hz, 1H, Ar-H),
7.49 (d, J= 9.56 Hz, 1H, Ar-H), 7.65 (s, 1H, imidazol-H),
7.85–7.89 (d, J= 8.64 Hz, 2H, Ar-H), 8.11 (d, J= 1.4 Hz, 1H,
Ar-H); 13C NMR (100 MHz, CDCl3): δ 17.3, 109.2, 115.9,
116.1, 117.6, 123.3, 126.4, 126.7, 128.2, 130.2, 139.4, 143.6,
149.6, 162.5, 164.5; HRMS calculated (m/z): 360.0129, found
(m/z): 360.0122 (M + H)+.
6-Chloro-2-(4-methyl-2-p-tolylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4l). IR (KBr): 3388, 3022, 1604, 1510, 1492, 1378, 1335, 1199,
1
1058, 891, 830, 756 cmꢀ1; H NMR (400 MHz, CDCl3): δ 2.46
(s, 3H, CH3), 2.65 (s, 3H, CH3), 7.13 (d, J = 8.4 Hz, 2H,
Ar-H), 7.26 (dt, J = 8.8 and 1.4 Hz, 1H, Ar-H), 7.49 (d,
J = 8.8 Hz, 1H, Ar-H), 7.65 (s, 1H, imidazol-H), 7.89 (d,
J = 8.4 Hz, 2H, Ar-H), 8.11 (d, J = 1.4 Hz, 1H, Ar-H); 13C
NMR (100 MHz, CDCl3): δ 17.3, 29.2, 109.0, 115.1, 116.4,
123.3, 125.2, 127.1, 128.0, 129.7, 130.4, 132.5, 139.0, 143.5,
149.6; 164.0; HRMS calculated (m/z): 340.0675, found (m/z):
340.0658 (M + H)+.
2-(2-(4-Fluorophenyl)-4-methylthiazol-5-yl)H-imidazo[1,2-a]
pyridine (4g). IR (KBr): 3085, 3025, 1608, 1497, 1430, 1399,
1
1340, 1237, 1196, 1088, 1059, 1006, 931, 835, 799 cmꢀ1; H
NMR (400 MHz, DMSO-d6): δ 2.65 (s, 3H, CH3), 6.86
(dt, J = 6.72 and 1.04 Hz, 1H, Ar-H), 7.02 (t, J = 8.6 Hz, 2H,
Ar-H), 7.21–7.26 (m, 1H, Ar–H), 7.52 (d, J = 8.8 Hz, 1H,
Ar-H), 7.88–7.91 (m, 2H, Ar-H), 8.19 (s, 1H, imidazol-H),
8.46 (dd, J = 8.8 and 1.04 Hz, 1H, Ar-H); 13C NMR
(100 MHz, DMSO-d6): δ 17.0, 109.6, 112.5, 116.0, 116.8,
125.2, 126.6, 128.9, 129.2, 130.5, 133.5, 144.3, 148.6, 162.2,
165.8; HRMS calculated (m/z): 310.0814, found (m/z):
310.0809 (M + H)+.
Antitubercular activity: The compounds were tested for their
antimycobacterial ability on M. smegmatis MC2 155 strain. The
series of compounds was obtained in 10-mM stock concentra-
tions. Further, each compound was diluted with the required
100% (v/v) DMSO to achieve a working concentration of
1.5 mM. The inoculum for the assay was prepared by reviving a
glycerol stock in Middlebrook 7H9 Broth supplemented with
0.1% Tween 80 (Sigma Aldrich, USA) and 0.5% glycerol. At
the time of inoculation, 10% Albumin-Dextrose-Saline (ADS)
was added to the media, and the culture was incubated in a shaker
incubator at 37 °C and 200 rpm. When the optical density (O.D.)
of the inoculum reached 0.8–1 approximately, a secondary inocu-
lum was inoculated and subsequently incubated. This was incu-
bated overnight till the O.D. of the inoculum reached 0.4
approximately; following which, the inoculum was diluted
1:1000 times. In a 96-well microtiter plate, a 2-μL aliquot of the
1.5-mM dilution of compound was added to each well in triplicate,
to which 98 μL of inoculum dilution was added, making the final
concentration of compound 30 μM. To each plate, a set of controls
was added to better ascertain the activity of the compounds. These
included DMSO, which was taken as a growth control, and media
control (blank) and rifampin and isoniazid, which were taken as
positive controls of inhibition of M. smegmatis. After the comple-
tion of the period of 32 h, the absorbance of the inoculum in wells
was measured at 600 nm using a multimode reader. Absorbance
is considered directly proportional to the increase in growth of
bacteria; thus, it gives a measure of the growth of bacteria in
each well. The percentage inhibition was determined against
DMSO, and those compounds that showed inhibition at 30%
or more were further analyzed to determine their MIC values.
In order to attain this objective, the inhibition was tested at in-
creasing concentrations of compound from 6.25 to 100 μM. Af-
ter the period of 30-h incubation, the absorbance of the
inoculum was observed at 600 nm using a multimode reader,
and the MIC values were calculated for the respective
compounds.
6-Bromo-2-(2-(4-fluorophenyl)-4-methylthiazol-5-yl)H-
imidazo[1,2-a]pyridine (4h). IR (KBr): 3101, 3030, 1609, 1487,
1434, 1389, 1333, 1240, 1187, 1080, 1055, 1007, 930, 828, 810,
760, 738 cmꢀ1 1H NMR (300 MHz, CDCl3): δ 2.70 (s, 3H,
;
CH3), 7.01 (t, J= 8.6 Hz, 2H, Ar-H), 7.26 (dd, J=7.6 and
1.0 Hz, 1H, Ar-H), 7.52 (d, J= 7.6 Hz, 1H, Ar-H), 7.71 (s, 1H,
imidazol-H), 7.89–7.91 (m, 2H, Ar-H), 8.28 (d, J= 1.0 Hz, 1H,
Ar-H); 13C NMR (75 MHz, CDCl3): δ 17.0, 109.0, 113.5, 115.1,
116.5, 117.9, 125.4, 128.9, 129.3, 132.1, 136.2, 143.8, 149.6,
162.5, 164.2; HRMS calculated (m/z): 387.9919, found (m/z):
387.9912 (M + H)+.
6-Chloro-2-(2-(4-fluorophenyl)-4-methylthiazol-5-yl)H-
imidazo[1,2-a]pyridine (4i). IR (KBr): 3122, 3043, 1601,
1527, 1483, 1447, 1394, 1288, 1246, 1183, 1069, 1009, 974,
916, 826, 815, 761, 738 cmꢀ1 1H NMR (400MHz, CDCl3):
;
δ 2.71(s, 3H, CH3), 7.02 (t, J = 8.6 Hz, 2H, Ar-H), 7.49
(dd, J = 8.8 and 1.4 Hz, 1H, Ar-H), 7.58 (d, J = 8.8 Hz, 1H,
Ar-H), 7.73 (s, 1H, imidazol-H), 7.88–7.91 (m, 2H, Ar-H),
8.18 (d, J = 1.4 Hz, 1H, Ar-H); 13C NMR (100 MHz, CDCl3):
δ 17.1, 109.5, 113.8, 116.4, 117.7, 123.3, 125.0, 127.8, 129.2,
130.0, 132.2, 143.8, 149.5, 162.2, 164.7; HRMS calculated
(m/z): 344.0424, found (m/z): 344.0419 (M + H)+.
2-(4-Methyl-2-p-tolylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4j). IR (KBr): 3084, 3037, 1600, 1557, 1530, 1443, 1404,
1
1377, 1305, 1212, 1185, 1003, 903, 820, 759 cmꢀ1; H NMR
(400 MHz, DMSO-d6): δ 2.45, (s, 3H, CH3), 2.66 (s, 3H,
CH3), 6.86–6.88 (m, 1H, Ar-H), 7.05–7.08 (m, 2H, Ar-H),
7.20 (d, J = 8.6 Hz, 2H, Ar-H), 7.88 (d, J = 8.6 Hz, 2H, Ar-H),
8.19 (s, 1H, imidazol-H), 8.46 (dd, J = 8.0 and 1.04 Hz, 1H,
Ar-H); 13C NMR (100 MHz, DMSO-d6): δ 16.9, 29.1, 109.5,
112.7, 116.1, 125.2, 126.4, 127.3, 129.2, 130.0, 130.8, 133.7,
136.8, 144.3, 148.8, 163.6; HRMS calculated (m/z):
306.1065, found (m/z): 306.0834 (M + H)+.
Acknowledgments. PCM would like to thank the University Grant
Commission (UGC No. 42-355(SR)/2013), New Delhi, India, for
the financial assistance and CSIR-OSDD for supporting anti-TB
activity. SAIF, Panjab University, Chandigarh, is also
acknowledged for the spectral analysis. Y. K. A. expresses her
gratefulness to CSIR for the financial support.
6-Bromo-2-(4-methyl-2-p-tolylthiazol-5-yl)H-imidazo[1,2-a]pyridine
(4k). IR (KBr): 3107, 3030, 1610, 1518, 1496, 1383, 1333,
1197, 1060, 890, 802, 761, 716 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): δ 2.46 (s, 3H, CH3), 2.70 (s, 3H, CH3), 7.26
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
6-Substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo
[1,2-a]pyridine
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet