Synthesis of spiro thiazolo[3,2-a]pyrimidine compounds by one-pot sequential 1,3-dipolar cycloadditions

Article abstract of DOI:10.1002/jhet.578

Figure represented. A new class of spiro thiazolo[3,2-a]pyrimidine compounds were synthesized by the one-pot sequential 1,3-dipolar cycloaddition of azomethine ylide (generated from isatin and sarcosine)-nitrile oxide to 2-arylmethylidene-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-ones in moderate yields. The structures of all the products were characterized thoroughly by NMR, MS, IR, elemental analysis, and NMR together with X-ray crystallographic analysis.

Full text of DOI:10.1002/jhet.578

776
Synthesis of Spiro Thiazolo[3,2-a]pyrimidine Compounds by
One-Pot Sequential 1,3-Dipolar Cycloadditions
Vol 48
Xiaofang Li, Aiting Zheng, Bin Liu, Guobin Li,
Xianyong Yu, and Pinggui Yi*
Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education,
Hunan Province College Key Laboratory of QSAR/QSPR, School of Chemistry and Chemical
Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China
*E-mail: pgyi@hnust.edu.cn
Received April 23, 2010
DOI 10.1002/jhet.578
Published online 1 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
A new class of spiro thiazolo[3,2-a]pyrimidine compounds were synthesized by the one-pot sequen-
tial 1,3-dipolar cycloaddition of azomethine ylide (generated from isatin and sarcosine)–nitrile oxide to
2-arylmethylidene-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-ones in moderate yields. The structures of
all the products were characterized thoroughly by NMR, MS, IR, elemental analysis, and NMR together
with X-ray crystallographic analysis.
J. Heterocyclic Chem., 48, 776 (2011).
INTRODUCTION
azolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine] 2 by one-pot
sequential azomethine ylide (generated from isatin and
sarcosine)–nitrile oxide cycloaddition to 2-arylmethyli-
Nitrile oxides are important intermediates as 1,3-
dipoles in cycloaddition reaction [1]. The C, N double
bond of pyridine, quinoline, isoquinoline, and 1,5-benzo-
thiazepine as heterodipolarophile can also react with
nitrile oxides to obtain oxadiazoles [2,3]. Oxadiazoles,
the important bioisosteres for esters and amides in drug
discovery, have been reported to have muscarinic ago-
nist, benzodiazepine receptor agonist, 5-HT agonist, and
antirhinoviral activities [4].
dene-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-ones
(Scheme 1).
1
RESULTS AND DISCUSSION
The structures of products 2a–2h were confirmed by
different spectroscopic techniques (MS, IR, and NMR)
and elemental analysis together with X-ray. The IR
spectrum of 2c exhibited two carbonyl peaks locating at
1698.2 and 1710.5 cmꢀ1, which was assigned to the car-
bonyl group in thiazole ring and the carbonyl group of
indole ring, respectively. Further, the mass spectrum of
2c showed a molecular ion peak at m/z 674 ([MþH]þ),
Thiazolo[3,2-a]pyrimidin-3-one derivatives are found to
be associated with various biological activities such as
antibacterial, antimicrobial, and anticancer activities [5].
The 1,3-dipolar cycloaddition reaction of azomethine
ylides generated by a decarboxylative route from amino
acids and isatin with exocyclic olefins represents an effi-
cient method for the construction of the spirooxindole
derivatives, which often have very wide biological
applications as antimicrobial, antitumoral, antibiotic
agents, and inhibitors of human NK-1 receptor [6,7].
The incorporation of oxadiazole, spirooxindole, and
thiazolo[3,2-a]pyrimidin-3-one into a heterocyclic frame-
work, which we believe could be a useful framework
with potential biological activities, has not been investi-
gated yet. In this work, we wish to report the synthesis
1
which indicates the existence of 2c. The H NMR spec-
trum of 2c revealed a singlet at 2.03 resulting from
NACH3, several multiplets at d 1.87–1.91, 2.82–2.91,
and 4.09–4.14 and a triplet at d 3.59 (J ¼ 8.5 Hz)
resulting from pyrrolidine ring and pyrimidine ring for
the six protons of three methylenes. One doublet of dou-
blets at d 5.24 assignable to the CH in pyrrole ring, sev-
eral multiplets in the range of d 6.86–7.37 and a doublet
at d 7.96 (J ¼ 8.5 Hz) for aromatic protons. The
of
dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxadi-
C
V
2011 HeteroCorporation

July 2011
Synthesis of Spiro Thiazolo[3,2-a]pyrimidine Compounds
by One-Pot Sequential 1,3-Dipolar Cycloadditions
777
Scheme 1
33.78 (C-3), 35.82 (C-9), 35.97 (C-1), 50.94 (C-7), 59.01 (C-
8), 67.08 (C-5), 81.08 (C-10), 110.26 (C-4), 115.82, 122.60,
122.73, 122.82, 124.82, 125.73, 128.37, 128.45, 128.62,
130.34, 130.38, 130.52, 132.58, 135.82, 136.73, 139.11,
142.93, 151.46 (C-13), 171.75 (C-6), 177.69 (C-11); IR (KBr)
m: 1718.2, 1700.1 cmꢀ1; ESI MS m/z: 606 [MþH]þ. Anal.
calcd for C30H25Cl2N5O3S: C, 59.41; H, 4.15; N, 11.55; found
C, 59.70; H, 4.11; N, 11.60.
existence of a singlet downfield at d 7.69 corresponds to
NH in indole ring.
The 13C NMR spectrum of the product 2c exhibits the
presence of three methylenes carbon at d 22.86, 33.74,
and 36.02, NACH3 carbons at d 35.98, two carbonyl
carbons at d 170.63 and 177.53, and C¼¼N carbon at d
151.65 (based on HMQC). The existence of signal at d
70.08 and 80.80 is assignable for the two spiro carbons.
Further, the structure of the product was confirmed by
X-ray diffraction analysis of 2a [8] (Fig. 1).
300-(2,6-Dichlorophenyl)-10-methyl-40-(4-chlorophenyl)-600,700-
dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxa-
diazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2b). Yield 48%. m.p. 249–251ꢁC; 1H NMR (DMSO-d6, 500
MHz) d: 1.74–1.80 (m, 2H), 2.09 (s, 3H), 2.35–2.41 (m, 1H),
2.64–2.70 (m, 1H), 2.91–2.95 (m, 1H), 3.40–3.42 (m, 1H),
3.81 (t, J ¼ 9.0 Hz, 1H), 3.93 (dd, J ¼ 8.5, 13.5 Hz, 1H),
4.57 (t, J ¼ 8.5 Hz, 1H), 6.85 (d, J ¼ 7.5 Hz, 1H), 6.96 (t, J
¼ 7.5 Hz, 1H), 7.10 (d, J ¼ 7.5 Hz, 1H), 7.28 (t, J ¼ 7.5 Hz,
1H), 7.41–7.43 (m, 2H), 7.46–7.47 (m, 2H), 7.59–7.65 (m,
3H), 10.68 (s, 1H); 13C NMR (d6-DMSO, 125 MHz) d: 22.45
(C-2), 33.92 (C-3), 35.06 (C-9), 35.49 (C-1), 49.85 (C-7),
57.92 (C-8), 70.73 (C-5), 79.89 (C-10), 109.76 (C-4), 115.28,
121.71, 124.53, 125.26, 128.46, 128.99, 130.12, 131.85,
131.96, 133.94, 135.02, 135.16, 138.12, 143.97, 151.26 (C-13),
170.74 (C-6), 176.66 (C-11); IR (KBr) m: 1717.4, 1685.7
EXPERIMENTAL
1 [9] and 2,6-dichlorobenzonitrile oxide [10] were prepared
according to the reported procedures. All NMR spectra were
recorded on a Bruker AV-II 500 MHz NMR spectrometer,
1
operating at 500 MHz for H and 125 MHz for 13C. TMS was
used as an internal reference for 1H and 13C chemical shifts,
and CDCl3 was used as a solvent. Elemental analysis was
measured by an Elemental analyzer (varioEL II). MS was con-
ducted by a Finnigan LCQ Advantage MAX mass spectrome-
ter. IR spectra were recorded on a Perkin-Elmer spectrometer
(Spectrum One). Melting points were measured by a Yanaco
MP500 melting point apparatus and uncorrected.
cmꢀ1
;
ESI MS m/z: 640 [MþH]þ. Anal. calcd for
C30H24Cl3N5O3S: C, 56.22; H, 3.77; N, 10.93; found C, 56.33;
H, 3.69; N, 11.01.
General procedure for the synthesis of 300-(2,6-dichloro-
phenyl)-10-methyl-40-aryl-600,700-dihydro-500H-dispiro[indole-
3,20-pyrrolidine-30,1000-[1,2,4]oxadiazolo[4,5-a][1,3]thiazolo[2,3-
b]pyrimidine]-2,900(1H)-dione. A solution of isatin (1 mmol),
sarcosine (1 mmol), and 2-arylmethylidene-6,7-dihydro-5H-
thiazolo[3,2-a]pyrimidin-3-ones 1 (1 mmol) in dioxane (30
mL) was refluxed for 24 h, after that 2,6-dichlorobenzonitrile
oxide (1.5 mmol) was added, and the resulting solution was
further refluxed for 24 h; the solvent was removed in vacuo.
The residue was subjected to column chromatography using
petroleum ether–ethyl acetate (v/v 5:1) as eluent to afford the
corresponding 2.
300-(2,6-Dichlorophenyl)-10-methyl-40-phenyl-600,700-dihydro-
500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxadiazolo[4,5-
a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2a). Yield
55%. m.p. 202–204ꢁC; 1H NMR (CDCl3, 500 MHz) d: 1.83–
1.87 (m, 2H), 2.29 (s, 3H, ANCH3), 2.51–2.58 (m, 1H), 2.74–
2.85 (m, 2H), 3.60 (t, J ¼ 8.5 Hz, 1H), 4.04–4.14 (m, 2H),
4.77 (t, J ¼ 8.5 Hz, 1H), 6.91 (d, J ¼ 7.5 Hz, 1H), 7.00 (t, J
¼ 7.5 Hz, 1H), 7.27–7.38 (m, 8H), 7.52 (d, J ¼ 8.0 Hz, 2H),
8.61 (br, 1H); 13C NMR (CDCl3, 125 MHz) d: 22.67 (C-2),
Figure 1. ORTEP diagram of 2a (H atoms have been omitted for
clarity).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

778
X. Li, A. Zheng, B. Liu, G. Li, X. Yu, and P. Yi
Vol 48
300-(2,6-Dichlorophenyl)-10-methyl-40-(2,4-dichlorophenyl)-
4H), 7.71 (t, J ¼ 8.5 Hz, 2H), 7.78 (br, 1H), 8.20 (d, J ¼ 8.5
Hz, 2H); 13C NMR (CDCl3, 125 MHz) d: 22.91 (C-2), 33.84
(C-3), 35.81 (C-9), 36.05, 50.48, 58.99, 70.56, 80.93 (C-10),
110.18 (C-4), 115.79, 122.64, 122.89, 123.87, 124.26, 125.76,
128.39, 128.68, 130.68, 131.31, 132.70, 135.81, 136.78,
142.48, 146.79, 147.33, 151.57 (C-13), 171.16 (C-6), 176.98
(C-11); IR (KBr) m: 1711.6, 1699.9 cmꢀ1; ESI MS m/z: 651
[MþH]þ. Anal. calcd for C30H24Cl2N6O5S: C, 55.30; H, 3.71;
N, 12.90; found C, 55.39; H, 3.94; N, 12.80.
300-(2,6-Dichlorophenyl)-10-methyl-40-(4-methylphenyl)-600,700-
dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxa-
diazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2g). Yield 50%. m.p. 200–202ꢁC; 1H NMR (CDCl3, 500
MHz) d: 1.82–1.88 (m, 2H), 2.29 (s, 3H), 2.35 (s, 3H, ACH3),
2.55–2.61 (m, 1H), 2.77–2.84 (m, 2H), 3.57 (t, J ¼ 8.5 Hz,
1H), 4.02–4.06 (m, 2H), 4.71 (t, J ¼ 9.0 Hz, 1H), 6.87 (d, J ¼
7.5 Hz, 1H), 7.01 (t, J ¼ 7.5 Hz, 1H), 7.15 (t, J ¼ 7.5 Hz, 2H),
7.27–7.28 (m, 2H), 7.32–7.35 (m, 3H), 7.38 (d, J ¼ 7.5 Hz,
2H), 7.59 (s, 1H); 13C NMR (CDCl3, 125 MHz) d: 21.20,
23.04, 33.68, 35.85, 36.03, 50.46, 59.12, 71.47, 80.97, 109.89,
115.79, 122.96, 124.86, 125.84, 128.36, 128.58, 129.34, 130.12,
130.32, 132.51, 135.87, 135.94, 136.80, 136.99, 142.53, 151.49,
171.70, 176.96; IR (KBr) m: 1719.9, 1697.9 cmꢀ1; ESI MS m/z:
620 [MþH]þ. Anal. calcd for C31H27Cl2N5O3S: C, 60.00; H,
4.39; N, 11.29; found C, 59.85; H, 4.58; N, 11.24.
300-(2,6-Dichlorophenyl)-10-methyl-40-(4-methylthiophenyl)-
600,700-dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-
[1,2,4]oxadiazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-
dione (2h). Yield 51%. m.p. 200–203ꢁC; 1H NMR (CDCl3,
500 MHz) d: 1.80–1.91 (m, 2H), 2.28 (s, 3H), 2.49 (s, 3H),
2.55–2.59 (m, 1H), 2.78–2.84 (m, 2H), 3.58 (dd, J ¼ 8.0, 9.0
Hz, 1H), 4.00–4.07 (m, 2H), 4.70 (dd, J ¼ 8.0, 10.0 Hz, 1H),
6.88 (d, J ¼ 7.5 Hz, 1H), 7.00 (t, J ¼ 7.5 Hz, 1H), 7.22 (d, J
¼ 8.5 Hz, 2H), 7.27–7.29 (m, 2H), 7.31–7.35 (m, 3H), 7.44
(d, J ¼ 8.0 Hz, 2H), 7.97 (s, 1H); 13C NMR (CDCl3, 125
MHz) d: 15.66 (ASCH3), 23.04, 33.73, 35.91, 36.04, 50.38,
59.08, 71.34, 81.03, 110.21, 115.81, 122.64, 122.82, 124.74,
125.70, 126.48, 128.35, 128.63, 130.41, 130.78, 132.58,
135.82, 135.92, 136.80, 137.34, 142.79, 151.50, 171.69,
177.51; IR (KBr) m: 1705.8, 1689.3 cmꢀ1; ESI MS m/z: 652
[MþH]þ. Anal. calcd for C31H27Cl2N5O3S2: C, 57.05; H,
4.17; N, 10.73; found C, 57.27; H, 4.26; N, 10.59.
600,700-dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]
oxadiazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2c). Yield 50%. m.p. 245–246ꢁC; 1H NMR (CDCl3, 500
MHz) d: 1.87–1.91 (m, 2H, H-2), 2.30 (s, 3H, ANCH3), 2.82–
2.91 (m, 3H, H-1, H-3), 3.59 (t, J ¼ 8.5 Hz, 1H, H-8), 4.09–
4.14 (m, 2H, H-3, H-8), 5.24 (dd, J ¼ 8.5, 9.5 Hz, 1H, H-7),
6.86–6.87 (m, 1H), 7.01–7.04 (m, 1H), 7.28–7.31 (m, 2H),
7.32–7.37 (m, 5H), 7.69 (s, 1H, H-11), 7.96 (d, J ¼ 8.5 Hz,
1H); 13C NMR (CDCl3, 125 MHz) d: 22.86 (C-2), 33.74 (C-
3), 35.98 (C-9), 36.02 (C-1), 45.04 (C-7), 57.14 (C-8), 70.08
(C-5), 80.80 (C-10), 110.34 (C-4), 116.03, 122.92, 124.08,
126.04, 127.70, 128.34, 128.62, 128.95, 130.56, 131.96,
132.60, 133.54, 135.54, 135.89, 136.76, 136.85, 142.44,
151.65 (C-13), 170.63 (C-6), 177.53 (C-11); IR (KBr) m:
1710.5, 1698.2 cmꢀ1; ESI MS m/z: 674 [MþH]þ. Anal. calcd
for C30H23Cl4N5O3S: C, 53.35; H, 3.43; N, 10.37; found C,
53.05; H, 3.39; N, 10.26.
300-(2,6-Dichlorophenyl)-10-methyl-40-(4-fluorophenyl)-600,700-
dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxa-
diazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2d). Yield 55%. m.p. 190–192ꢁC; 1H NMR (CDCl3, 500
MHz) d: 1.82–1.91 (m, 2H), 2.29 (s, 3H, H-9), 2.51–2.58 (m,
1H), 2.77–2.84 (m, 2H), 3.60 (dd, J ¼ 8.0, 9.0 Hz, 1H), 4.00–
4.07 (m, 2H), 4.73 (dd, J ¼ 8.0, 10.0 Hz, 1H, H-7), 6.88 (d, J
¼ 7.5 Hz, 1H), 7.00–7.05 (m, 3H), 7.28–7.35 (m, 5H), 7.46–
7.49 (m, 2H), 7.78 (s, 1H, H-12); 13C NMR (CDCl3, 125
MHz) d: 22.93, 33.68, 35.93, 35.99, 50.17, 59.15, 71.29,
80.97, 110.11, 115.51, 122.68, 124.60, 125.68, 128.31, 128.59,
130.41, 131.77, 131.84, 132.57, 134.80, 135.77, 136.72,
142.57, 151.46, 171.53, 177.40; IR (KBr) m: 1720.5, 1689.8
cmꢀ1
;
ESI MS m/z: 624 [MþH]þ. Anal. calcd for
C30H24Cl2FN5O3S: C, 57.70; H, 3.87; N, 11.21; found C,
57.45; H, 3.91; N, 11.07.
300-(2,6-Dichlorophenyl)-10-methyl-40-(2-nitrophenyl)-600,700-
dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxa-
diazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2e). Yield 52%. m.p. 220–222ꢁC; 1H NMR (CDCl3, 500
MHz) d: 1.85–1.93 (m, 1H), 2.05–2.10 (m, 1H), 2.29 (s, 3H),
2.75–2.89 (m, 3H), 3.59 (t, J ¼ 8.5 Hz, 1H), 4.11 (t, J ¼ 9.0
Hz, 1H), 4.17 (dd, J ¼ 8.5, 13.5 Hz, 1H), 4.92 (t, J ¼ 9.0 Hz,
1H), 6.88 (d, J ¼ 7.5 Hz, 1H), 7.04 (t, J ¼ 7.5 Hz, 1H), 7.29–
7.37 (m, 5H), 7.42 (t, J ¼ 7.5 Hz, 1H), 7.59 (s, 1H), 7.68 (t, J
¼ 7.5 Hz, 1H), 7.73 (d, J ¼ 7.5 Hz, 1H), 8.41 (d, J ¼ 8.0 Hz,
1H); 13C NMR (CDCl3, 125 MHz) d: 22.86 (C-2), 33.82 (C-
3), 35.83 (C-9), 36.07 (C-1), 44.52 (C-7), 58.89 (C-8), 70.58
(C-5), 80.75 (C-10), 109.98 (C-4), 116.44, 122.93, 122.98,
123.68, 124.16, 126.37, 128.21, 128.38, 128.50, 130.54,
132.32, 132.52, 133.10, 133.54, 135.95, 136.67, 142.33,
151.67 (C-13) 170.05 (C-6), 177.30 (C-11); IR (KBr) m:
1709.7, 1693.6 cmꢀ1; ESI MS m/z: 651 [MþH]þ. Anal. calcd
for C30H24Cl2N6O5S: C, 55.30; H, 3.71; N, 12.90; found C,
55.00; H, 3.83; N, 12.78.
300-(2,6-Dichlorophenyl)-10-methyl-40-(4-nitrophenyl)-600,700-
dihydro-500H-dispiro[indole-3,20-pyrrolidine-30,1000-[1,2,4]oxa-
diazolo[4,5-a][1,3]thiazolo[2,3-b]pyrimidine]-2,900(1H)-dione
(2f). Yield 55%. m.p. 226–228ꢁC; 1H NMR (CDCl3, 500
MHz) d: 1.79–1.96 (m, 2H), 2.30 (s, 3H), 2.49–2.55 (m, 1H),
2.79–2.85 (m, 2H), 3.64 (t, J ¼ 8.0 Hz, 1H), 4.05–4.09 (m,
2H), 4.85 (dd, J ¼ 8.0, 9.5 Hz, 1H), 6.91 (d, J ¼ 7.5 Hz, 1H),
7.03 (t, J ¼ 7.5 Hz, 1H), 7.29–7.31 (m, 1H), 7.32–7.36 (m,
Acknowledgments. This research was supported by National
Natural Science Foundation of China (Nos. 20971041, 20803020,
20772027), a project supported by Scientific Research Fund of
Hunan Provincial Education Department (09B032, 09K081,
09C385), and the Key Project of the Chinese Ministry of Science
(No. 210146).
REFERENCES AND NOTES
[1] Caramella, P.; Grunanger, P. In 1,3-Dipolar Cycloaddition
Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; Vol. 1, p 291.
[2] Caramella, P.; Bandiera, T.; Albini, F. M.; Gamba, A.; Cor-
saro, A.; Perrini, G. Tetrahedron 1988, 44, 4917.
[3] Baouid, A.; Elhazazi, S.; Hasnaoui, A.; Compain, P.; Lav-
ergne, J.-P.; Huet, F. New J Chem 2001, 25, 1479.
[4] (a) Sako, M.; Oda, S.; Ohara, S.; Hirota, K.; Maki, Y. J Org
Chem 1988, 63, 6947; (b) Macor, J. E.; Ordway, T.; Smith, R. L.;
Verhoest, P. R.; Mack, R. A. J Org Chem 1996, 61, 3228; (c)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2011
Synthesis of Spiro Thiazolo[3,2-a]pyrimidine Compounds
by One-Pot Sequential 1,3-Dipolar Cycloadditions
779
Romano, M. R.; Lograno, M. D. Eur J Pharmacol 2009, 608, 48;
(d) Quan, C.; Kurth, M. J Org Chem 2004, 69, 1470.
[7] (a) Kumar, R. S.; Rajesh, S. M.; Perumal, S.; Banerjee, D.;
Yogeeswari, P.; Sriram, D. Eur J Med Chem 2010, 45, 411; (b) Karthi-
keyan, S. V.; Bala, B. D.; Raja, V. P. A.; Perumal, S.; Yogeeswari, P.;
Sriram, D. Bioorg Med Chem Lett 2010, 20, 350; (c) Kumar, R. R.; Loga-
nayaki, B.; Perumal, S. Synth Commun 2009, 39, 3197; (d) Kumar, R. R.;
Perumal, S.; Senthilkumar, P.; Yogeeswari, P.; Sriram, D. Eur J Med Chem
2009, 44, 3821; (e) Kumar, R. R.; Perumal, S.; Senthilkumar, P.; Yogees-
wari, P.; Sriram, D. Tetrahedron 2008, 64, 2962; (f) Kumar, R. R.; Perumal,
S. Tetrahedron 2007, 63, 12220; (g) Kumar, R. R.; Perumal, S.; Senthilku-
mar, P.; Yogeeswari, P.; Sriram, D. J Med Chem 2008, 51, 5731.
[5] (a) Ashok, M.; Holla, B. S.; Kumari, N. S. Eur J Med
Chem 2007, 42, 380; (b) Holla, B. S.; Rao, B. S.; Sarojini, B. K.;
Akberali, P. M. Eur J Med Chem 2004, 39, 777; (c) Mohan, J.;
Kumar, A. Indian J Heterocycl Chem 2002, 11, 325.
[6] (a) Sridhar, G.; Gunasundari, T.; Raghunathan, R. Tetrahe-
dron Lett 2007, 48, 319; (b) Periyasami, G.; Raghunathan, R.; Sure-
ndiran, G.; Mathivanan, N. Eur J Med Chem 2009, 44, 959; (c) Babu,
A. R. S.; Raghunathan, R.; Gayatri, G.; Sastry, G. N. J Heterocycl
Chem 2006, 43, 1467; (d) Sridhar, G.; Raghunathan, R. Synth Com-
mun 2006, 36, 21; (e) Jayashankaran, J.; Manian, R. D. R. S.; Venka-
tesan, R.; Raghunathan, R. Tetrahedron 2005, 61, 5595.
[8] Wang, Z. X.; Zheng, A. T. Acta Cryst E, submitted.
[9] Mohan, J.; Kumar, A. Indian J Heterocycl Chem 2002, 11, 325.
[10] Grundamann, C.; Dean, J. M. J Org Chem 1965, 30, 2810.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet