Synthesis of dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5]triazines by 1,3-dipolar cycloaddition

Article abstract of DOI:10.1002/jhet.647

Figure represented. The 1,3-dipolar cycloaddition of an azomethine ylide generated by a decarboxylative route from sarcosine and isatin to 7-arylmethylidene-3-aryl-3,4-dihydro-2H-thiazolo[3,2-a][1,3,5]triazin-6(7H) -ones afforded novel dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5] triazines in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, and elemental analysis. The results of experiment indicated that this 1,3-dipolar cycloaddition proceeded with high stereoselectivity and regioselectivity.

Full text of DOI:10.1002/jhet.647

836
Synthesis of Dispiro[oxindole-pyrrolidine]-thiazolo
[3,2-a][1,3,5]triazines by 1,3-Dipolar Cycloaddition
Vol 48
Xiaofang Li, Zhikui Li, Aiting Zheng, 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 9, 2010
DOI 10.1002/jhet.647
Published online 12 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
The 1,3-dipolar cycloaddition of an azomethine ylide generated by a decarboxylative route from
sarcosine and isatin to 7-arylmethylidene-3-aryl-3,4-dihydro-2H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones
afforded novel dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5]triazines in moderate yields. The
structures of the products were determined and characterized thoroughly by NMR, MS, IR, and elemen-
tal analysis. The results of experiment indicated that this 1,3-dipolar cycloaddition proceeded with high
stereoselectivity and regioselectivity.
J. Heterocyclic Chem., 48, 836 (2011).
INTRODUCTION
6(7H)-ones (1a–1i) to azomethine ylide generated
in situ from isatin and sarcosine afforded novel dispiro-
heterocycles (2a–2i) in moderate yields (Table 1). This
cycloaddition reaction proceeded with high stereo-and
regio-selectivity to afford only one product, which was
Spirooxindoles are motifs in many pharmacologically
important alkaloids, as typified by rhyncophylline, cory-
noxeine, mitraphylline, horsifiline, and spirotryprostatins
[1]. The derivatives of spirooxindole find very wide
biological applications as antimicrobial, antitumoral, anti-
biotic agents, and inhibitors of human NK-1 receptor [2,3].
The 1,3-dipolar cycloaddition reaction of azomethine
ylides generated by a decarboxylative route from amino
acids and isatin with exocyclic olefins represents an
efficient method for the construction of the spirooxin-
dole structural unit [4,5].
1
evidenced from TLC and H-NMR of the crude reaction
mixture. The structures of all compounds 2a–2i were
established by different spectroscopic techniques
(IR, NMR, and MS) and elemental analysis. The IR
spectrum of 2c displayed mC¼O at 1721.8 and 1700.7
1
cmꢀ1. The H-NMR spectrum of 2c revealed a singlet
at d 2.03 resulting from NACH3 (H-10), two doublets
(J ¼ 15.5 Hz) at d 4.64 and 4.70 resulting from the
protons of methylene (H-2), two doublets (J ¼ 13.0 Hz)
at d 4.91 and 5.22 resulting from the protons of methyl-
ene (H-1). One doublet of doublets (J ¼ 9.5, 8.5 Hz) at
d 4.35 assignable to the proton H-6, two triplets at d
3.45 and 3.80 assignable to the protons of methylene
(H-7) in pyrrolidine ring, several doublets and multiplets
in the range of d 6.69–7.34 for aromatic protons. The
existence of a singlet at d 10.74 corresponds to the ANH.
The 13C-NMR spectrum of the product 2c exhibits the
presence of three methylenes carbons at d 57.80 (C-7),
60.01 (C-1), and 65.51 (C-2), N-CH3 carbon (C10) at d
34.72, carbonyl carbons at d 172.37 (C-5) and 176.57
(C-9). The signal at d 51.45 is assignable for carbon of
CH (C-6), which exists in pyrrolidine ring (based on
Triazine compounds are found to be associated with
various biological activities [6]. The incorporation of tria-
zine and spirooxindole into a dispiro heterocyclic system,
which we believe could be a useful framework with
potential biological activities, has not been investigated
yet. In the present work, we report the synthesis of novel
dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5]triazines
through the 1,3-dipolar cycloaddition of azomethine ylide
and 7-arylmethylidene-3-aryl-3,4-dihydro-2H-thiazolo[3,2-
a][1,3,5]triazin-6(7H)-ones (Scheme 1).
RESULTS AND DISCUSSION
The 1,3-dipolar cycloaddition of the 7-arylmethyli-
dene-3-aryl-3,4-dihydro-2H-thiazolo[3,2-a][1,3,5]triazin-
C
V
2011 HeteroCorporation

July 2011
Synthesis of Dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5]triazines by 1,3-Dipolar
Cycloaddition
837
Scheme 1
1H), 3.85 (t, J ¼ 9.5 Hz, 1H), 4.34 (dd, J ¼ 10.0, 8.0 Hz,
1H), 4.64 (d, J ¼ 15.5 Hz, 1H), 4.69 (d, J ¼ 15.5 Hz, 1H),
4.89 (d, J ¼ 13.0 Hz, 1H), 5.22 (d, J ¼ 13.0 Hz, 1H), 6.69 (d,
J ¼ 8.0 Hz, 2H), 6.76 (d, J ¼ 8.0 Hz, 1H), 6.91–6.96 (m, 2H),
7.14–7.18 (m, 2H), 7.23–7.25 (m, 7H), 10.70 (br, 1H); 13C-
NMR (DMSO-d6, 125 MHz) d: 35.25, 52.72, 58.01, 60.43,
66.01, 68.39, 79.76, 110.26, 118.71, 122.24, 122.65, 124.09,
126.97, 127.91, 128.87, 129.69, 130.49, 131.01, 138.54,
144.12, 147.59, 149.05, 172.98, 177.01; IR (KBr) v: 1718.5,
1701.1 cmꢀ1; ESI MS m/z: 496 [MþH]þ.Anal. calcd. for
C28H25N5O2S: C 67.86, H 5.08, N 14.13; found C 67.74, H
5.15, N 14.10.
HMQC). The signals at d 67.80 and 79.21 are assignable
for the spiro carbon of C-4 and C-8, respectively. In the
1H-13C HMBC map of 2c (Fig. 1) ANH correlate with
C-9 (176.57 ppm), protons of -NH, H-7, and H-10 corre-
late with a spiro carbon C8 (79.21 ppm), protons of CH
(H-6) and CH2 (H-7) exist in pyrrolidine ring correlate
with the spiro carbon C4 (67.80 ppm). The correlation
of H-1 and H-6 with C-5 indicates the carbon atom of
carbonyl carbon (C-5) at d 172.37 ppm.
40-(4-Chlorophenyl)-10-methyl-300-phenyl-300,400-dihydro-
200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo[3,2-a][1,3,5]
triazine]-2,600(1H)-dione(2b). White solid, yield 75%; mp : 236–
237ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d 2.05 (s, 3H), 3.45
(t, J ¼ 8.5 Hz, 1H), 3.81 (t, J ¼ 9.5 Hz, 1H), 4.34 (t, J ¼ 8.5
Hz, 1H), 4.65 (d, J ¼ 15.5 Hz, 1H), 4.71 (d, J ¼ 15.5 Hz,
1H), 4.91 (d, J ¼ 13.0 Hz, 1H), 5.22 (d, J ¼ 13.0 Hz, 1H),
6.70 (d, J ¼ 8.0 Hz, 2H), 6.76 (d, J ¼ 8.0 Hz, 1H), 6.93 (t, J
¼ 7.5 Hz, 2H), 7.16 (t, J ¼ 8.0 Hz, 2H), 7.23–7.29 (m, 2H),
7.31–7.35 (m, 4H), 10.70 (br, 1H); 13C-NMR (DMSO-d6, 125
MHz) d: 34.72, 51.54, 57.53, 60.04, 65.51, 67.68, 79.22,
109.82, 118.22, 121.79, 122.20, 123.46, 126.47, 128.28,
129.20, 130.54, 131.88, 132.11, 137.11, 143.62, 147.06,
EXPERIMENTAL
1 [7] was prepared according to the reported procedures. All
NMR spectra were recorded on a Bruker AV-II 500 MHz
NMR spectrometer, operating at 500 MHz for 1H, and 125
MHz for 13C. TMS was used as an internal reference for 1H
and 13C chemical shifts. CDCl3 and DMSO-d6 were as solvent.
Elemental analysis was measured by an Elementar analyzer
(varioELII). MS was measured by a Finnigan LCQ Advantage
MAX mass spectrometer; IR spectra were recorded on Perkin-
Elmer spectrometer. Melting points were measure by a Yanaco
MP500 melting points apparatus and uncorrected.
General procedure for the synthesis of spirooxindoles
(2a–g).. A solution of isatin (1 mmol), sarcosine (1 mmol)
and 7-arylmethylidene-3-aryl-3,4-dihydro-2H-thiazolo[3,2-a]-
[1,3,5]triazin-6(7H)-ones 1 (1mmol) in dioxane (30 mL) was
refluxed overnight. Completion of the reaction was evidenced
by TLC analysis. The solvent was removed in vacuo. The
crude product was subjected to column chromatography using
petroleum ether-ethyl acetate (v/v 5:1) as eluent to afford the
corresponding 2.
148.33, 172.26, 176.52; IR (KBr) v: 1738.5, 1718.2 cmꢀ1
;
MS(ESI) m/z: 530 [MþH]þ. Anal. calcd. for C28H24ClN5O2S:
C 63.45, H 4.56, N 13.21; found C 63.37, H 4.70, N 13.16.
40-(4-Fluorophenyl)-10-methyl-300-phenyl-300,400-dihydro-
200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo[3,2-a]
[1,3,5]triazine]-2,600(1H)-dione(2c).. White solid, yield 72%;
mp: 229–230ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d 2.05 (s,
3H), 3.45 (t, J ¼ 8.5 Hz, 1H), 3.80 (t, J ¼ 9.5 Hz, 1H), 4.35
(dd, J ¼ 9.5 Hz, 8.5 Hz, 1H), 4.64 (d, J ¼ 15.5 Hz, 1H), 4.70
(d, J ¼ 15.5 Hz, 1H), 4.91 (d, J ¼ 13.0 Hz, 1H), 5.22 (d, J ¼
13.0 Hz, 1H), 6.69 (d, J ¼ 8.0 Hz, 2H), 6.76 (d, J ¼ 7.5 Hz,
1H), 6.91–6.96 (m, 2H), 6.69 (d, J ¼ 8.0 Hz, 1H), 6.77 (d, J
10-Methyl-300,40-diphenyl-300,400-dihydro-200H-dispiro[indole-
3,20-pyrrolidine-30,700-[1,3]thiazolo[3,2-a][1,3,5]triazine]-2,600(1H)-
dione (2a). White solid, yield 65%; mp : 206–207ꢁC; H-NMR
(DMSO-d6, 500 MHz): d 3.36 (s, 3H), 3.44 (t, J ¼ 8.0 Hz,
1
Table 1
The results of synthesis of 2a–2i.
Entry
R1
R2
Product
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
C6H5
C6H5
C6H5
C6H5
C6H4
C6H5
4-ClC6H4
4-FC6H4
2,4-Cl2C6H3
4-CH3C6H4
2,4-Cl2C6H3
C6H5
2a
2b
2c
2d
2e
2f
2g
2h
2i
20
18
18
20
24
24
24
24
24
65
75
72
75
68
76
65
70
75
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-ClC6H4
4-FC6H4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

838
X. Li, Z. Li, A. Zheng, G. Li, X. Yu, and P. Yi
Vol 48
(t, J ¼ 8.5 Hz, 1H), 3.83 (s, 3H), 4.13 (t, J ¼ 9.5 Hz, 1H),
4.61 (d, J ¼ 15.5 Hz, 1H), 4.67 (d, J ¼ 15.5 Hz, 1H), 4.87 (d,
J ¼ 13.0 Hz, 1H), 4.96 (t, J ¼ 9.0 Hz, 1H), 4.99 (d, J ¼ 13.0
Hz, 1H), 6.64–6.67 (m, 3H), 6.72–6.73 (m, 2H), 6.77 (t, J ¼
7.5 Hz, 1H), 7.14 (t, J ¼ 7.5 Hz, 1H), 7.22 (d, J ¼ 7.5 Hz,
1H), 7.35 (dd, J ¼ 8.5 Hz, 2.0 Hz, 1H), 7.38 (d, J ¼ 2.0 Hz,
1H), 7.84 (d, J ¼ 8.5 Hz, 1H), 8.52 (br, 1H); 13C-NMR
(CDCl3, 125 MHz) d: 35.61, 46.31, 55.48, 56.14, 63.05, 66.28,
67.06, 79.94, 109.88, 114.60, 121.31, 122.91, 122.98, 126.48,
127.42, 129.08, 130.46, 131.44, 133.80, 134.71, 136.91,
140.92, 142.38, 150.99, 155.56, 172.81, 176.90; IR (KBr) v:
1721.1, 1707.6 cmꢀ1; MS(ESI) m/z: 594 [MþH]þ. Anal. calcd.
for C29H25Cl2N5O3S: C 58.59, H 4.24, N 11.78; found C
58.73, H 4.16, N 11.59.
Figure 1. Part HMBC diagram of 2c.
300-(4-Methoxyphenyl)-10-methyl-40-phenyl-300,400-dihydro-
200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo[3,2-a]
[1,3,5]triazine]-2,600(1H)-dione (2g). White solid, yield 65%;
mp : 219–220ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d 2.04 (s,
3H), 3.43 (t, J ¼ 8.0 Hz, 1H), 3.72 (s, 3H), 3.85 (t, J ¼ 9.5
Hz, 1H), 4.34 (dd, J ¼ 9.5, 8.0 Hz, 1H), 4.52 (d, J ¼ 15.5 Hz,
1H), 4.60 (d, J ¼ 15.5 Hz, 1H), 4.82 (d, J ¼ 13.0 Hz, 1H),
5.12 (d, J ¼ 13.0 Hz, 1H), 6.58 (d, J ¼ 9.0 Hz, 2H), 6.69 (d,
J ¼ 9.0 Hz, 2H), 6.77 (d, J ¼ 8.0 Hz, 1H), 6.89 (t, J ¼ 7.5
Hz, 1H), 7.21–7.31 (m, 7H), 10.71 (br, 1H); 13C
NMR(DMSO-d6, 125 MHz) d: 35.23, 52.68, 55.65, 58.12,
61.52, 66.47, 68.22, 79.78, 110.28, 114.83, 120.35, 122.64,
124.10, 126.88, 127.93, 128.86, 130.58, 130.82, 138.63,
141.12, 144.11, 148.98, 154.93, 173.08, 177.03; IR (KBr)
v: 1719.1, 1708.4 cmꢀ1; MS(ESI) m/z: 526 [MþH]þ. Anal.
calcd. for C29H27N5O3S: C 66.27, H 5.18, N 13.32; found
C 66.35, H 5.26, N 13.20.
40-(4-Chlorophenyl)-300-(4-methoxyphenyl)-10-methyl-300,400-
dihydro-200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo
[3,2-a][1,3,5]triazine]-2,600(1H)-dione (2h). White solid, yield
70%; m.p.: 236–237ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d
2.03 (s, 3H), 3.45 (t, J ¼ 8.0 Hz, 1H), 3.73 (s, 3H), 3.80 (t, J
¼ 9.5 Hz, 1H), 4.35 (dd, J ¼ 9.5, 8.0 Hz, 1H), 4.54 (d, J ¼
15.5 Hz, 1H), 4.62 (d, J ¼ 15.5 Hz, 1H), 4.85 (d, J ¼ 13.0
Hz, 1H), 5.13 (d, J ¼ 13.0 Hz, 1H), 6.61 (d, J ¼ 9.0 Hz, 2H),
6.70 (d, J ¼ 9.0 Hz, 2H), 6.78 (d, J ¼ 8.0 Hz, 1H), 6.89 (t, J
¼ 7.5 Hz, 1H), 7.22–7.24 (m, 2H), 7.34–7.38 (m, 4H), 10.75
(br, 1H); 13C-NMR(DMSO-d6, 125 MHz) d: 35.19, 52.01,
55.62, 58.14, 61.63, 66.45, 67.96, 79.72, 110.34, 114.82,
120.34, 122.69, 123.95, 126.88, 128.78, 130.85, 132.46,
132.62, 137.69, 141.07, 144.10, 148.76, 154.94, 172.87,
177.04; IR (KBr) v: 1718.2, 1706.6 cmꢀ1; MS(ESI) m/z: 560
[MþH]þ. Anal. calcd. for C29H26ClN5O3S: C 62.19, H 4.68,
N 12.50; found C 62.30, H 4.57, N 12.40.
¼ 7.5 Hz, 2H), 6.91–6.95 (m, 2H), 7.11 (t, J ¼ 8.5 Hz, 2H),
7.15–7.18 (m, 2H), 7.23–7.25 (m, 2H), 7.32 (dd, J ¼ 8.5 Hz,
5.5 Hz, 2H), 10.74 (br, 1H); 13C-NMR (DMSO-d6, 125 MHz)
d: 34.72, 51.45, 57.80, 60.01, 65.51, 67.80, 79.21, 109.81,
115.01, 115.18, 118.22, 121.78, 122.21, 123.50, 126.46, 129.21,
130.54, 131.97, 132.04, 134.32, 134.35, 143.60, 147.07, 148.42,
172.37, 176.57; IR (KBr) v: 1721.8, 1700.7 cmꢀ1; MS(ESI)
m/z: 514 [MþH]þ. Anal. calcd. for C28H24FN5O2S: C 65.48, H
4.71, N 13.64; found C 65.62, H 4.78, N 13.50.
40-(2,4-Dichlorophenyl)-10-methyl-300-phenyl-300,400-dihydro-
200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo[3,2-a][1,3,5]
triazine]-2,600(1H)-dione(2d). White solid, yield 75%; mp : 247–
248ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d 2.05 (s, 3H), 3.47
(t, J ¼ 8.5 Hz, 1H), 3.95 (t, J ¼ 9.5 Hz, 1H), 4.65 (d, J ¼
15.5 Hz, 1H), 4.70–4.74 (m, 2H), 4.89 (d, J ¼ 13.0 Hz, 1H),
5.18 (d, J ¼ 13.0 Hz, 1H), 6.73 (d, J ¼ 8.0 Hz, 2H), 6.77
(d, J ¼ 8.0 Hz, 1H), 6.90 (t, J ¼ 7.5 Hz, 1H), 6.95 (t, J ¼ 7.5
Hz, 1H), 7.11–7.14 (m, 2H), 7.22 (d, J ¼ 7.5 Hz, 1H), 7.26 (t,
J ¼ 7.5 Hz, 1H), 7.51 (dd, J ¼ 8.5 Hz, 2.0 Hz, 1H), 7.54 (d, J
¼ 2.0 Hz, 1H), 7.80 (d, J ¼ 8.5 Hz, 1H), 10.73 (br, 1H); 13C-
NMR (DMSO-d6, 125 MHz) d: 34.92, 46.06, 55.30, 60.10,
65.50, 66.32, 66.36, 79.21, 110.01, 118.23, 121.80, 122.30,
122.82, 126.04, 127.42, 128.47, 129.12, 130.67, 131.79,
132.72, 135.07, 136.39, 143.68, 147.07, 148.52, 171.95,
176.30; IR (KBr) v: 1718.2, 1709.5 cmꢀ1; MS(ESI) m/z: 564
[MþH]þ. Anal. calcd. for C28H23Cl2N5O2S: C 59.58, H 4.11,
N 12.41; found C 59.40, H 4.18, N 12.32.
10-Methyl-40-(4-methylphenyl)-300-phenyl-300,400-dihydro-
200H-dispiro[indole-3,20-Pyrrolidine-30,700-[1,3]thiazolo[3,2-a]
[1,3,5]triazine]-2,600(1H)-dione (2e). White solid, yield 68%;
mp : 237–238ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d 2.05 (s,
3H), 2.28 (s, 3H), 3.41 (t, J ¼ 8.0 Hz, 1H), 3.84 (t, J ¼ 9.5 Hz,
1H), 4.31 (dd, J ¼ 9.5, 8.0 Hz, 1H), 4.63 (d, J ¼ 15.5 Hz, 1H),
4.70 (d, J ¼ 15.5 Hz, 1H), 4.88 (d, J ¼ 13.0 Hz, 1H), 5.21 (d, J
¼ 13.0 Hz, 1H), 6.69 (d, J ¼ 8.0 Hz, 2H), 6.76 (d, J ¼ 8.0 Hz,
1H), 6.91–6.96 (m, 2H), 7.08 (d, J ¼ 7.5 Hz, 2H),7.15–7.18 (m,
4H), 7.23–7.28 (m, 2H), 10.70 (br, 1H); 13C-NMR (DMSO-d6,
125 MHz) d: 21.18, 35.25, 52.43, 58.03, 60.36, 66.09, 68.57,
79.73, 110.25, 118.73, 122.26, 122.62, 124.15, 126.99, 129.46,
129.69, 130.35, 130.98, 135.51, 137.02, 144.14, 147.61, 149.13,
173.04, 177.02; IR (KBr) v: 1719.9, 1700.8 cmꢀ1; MS(ESI) m/
z: 510 [MþH]þ. Anal. calcd. for C29H27N5O2S: C 68.35, H
5.34, N 13.74; found C 68.21, H 5.26, N 13.89.
40-(4-Fluorophenyl)-300-(4-methoxyphenyl)-10-methyl-300,400-
dihydro-200H-dispiro[indole-3,20-pyrrolidine-30,700-[1,3]thiazolo
[3,2-a][1,3,5]triazine]-2,600(1H)-dione (2i). White solid, yield
75%; m.p.: 243–244ꢁC; 1H-NMR (DMSO-d6, 500 MHz): d
2.05 (s, 3H), 3.45 (t, J ¼ 8.0 Hz, 1H), 3.72 (s, 3H), 3.78 (t, J
¼ 9.5 Hz, 1H), 4.35 (dd, J ¼ 9.5, 8.0 Hz, 1H), 4.54 (d, J ¼
15.5 Hz, 1H), 4.60 (d, J ¼ 15.5 Hz, 1H), 4.84 (d, J ¼ 13.0
Hz, 1H), 5.11 (d, J ¼ 13.0 Hz, 1H), 6.58–6.60 (m, 2H), 6.67–
6.70 (m, 2H), 6.77 (d, J ¼ 7.5 Hz, 1H), 6.88 (t, J ¼ 7.0 Hz,
1H), 7.13 (t, J ¼ 8.5 Hz, 2H), 7.20 (d, J ¼ 8.0 Hz, 2H), 7.36
(dd, J ¼ 8.5 Hz, 5.5 Hz, 2H), 10.73 (br, 1H); 13C-NMR
(DMSO-d6, 125 MHz) d: 35.20, 51.88, 55.64, 58.40, 61.61,
66.44, 68.11, 79.73, 110.31, 114.83, 115.50, 115.67, 120.35,
40-(2,4-Dichlorophenyl)-300-(4-methoxyphenyl)-10-methyl-300,400-
0
dihydro-200 H-dispiro[indole-3,20-pyrrolidine-3 ,700 -[1,3]thiazolo[3,2-a]
00
[1,3,5]triazine]-2,6 (1H)-dione (2f). White solid, yield 76%; m.p.:
254–255ꢁC; H-NMR (CDCl3, 500 MHz): d 2.23 (s, 3H), 3.56
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2011
Synthesis of Dispiro[oxindole-pyrrolidine]-thiazolo[3,2-a][1,3,5]triazines by 1,3-Dipolar
Cycloaddition
839
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 Commun 2006, 36, 21; (e)
Jayashankaran, J.; Manian, R. D. R. S.; Venkatesan, R.; Raghunathan, R.
Tetrahedron 2005, 61, 5595.
122.69, 124.00, 126.85, 130.83, 132.55, 132.61, 134.92,
134.94, 141.10, 144.08, 148.83, 154.94, 172.94, 177.07; IR
(KBr) v: 1721.4, 1709.9 cmꢀ1; MS(ESI) m/z: 544 [MþH]þ.
Anal. calcd. for C29H26FN5O3S: C 64.07, H 4.82, N 12.88;
found C 64.14, H 4.90, N 12.76.
[5] (a) Kumar, R. S.; Rajesh, S. M.; Perumal, S.; Banerjee, D.;
Yogeeswari, P.; Sriram, D. Eur J Med Chem 2010, 45, 411; (b)
Karthikeyan, 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.; Loganayaki, 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.;
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2008, 64, 2962; (f) Kumar, R. R.; Perumal, S. Tetrahedron 2007, 63,
12220; (g) Kumar, R. R.; Perumal, S.; Senthilkumar, P.; Yogeeswari,
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Acknowledgments. This research was supported by National
Natural Science Foundation of China (Nos. 20772027, 20803020,
20971041), supported by the Key Project of Chinese Ministry of
Education (No. 210146), and supported by Scientific Research
Fund of Hunan Provincial Education Department (09B032,
09K081, 09C385)
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