Clean synthesis of furo[3,4-e]pyrazolo[3,4-b]pyridine-5-one derivatives in aqueous media

Article abstract of DOI:10.1002/jhet.224

(Chemical Equation Presented) A series of 4-aryl-3-methyl-1-phenyl-7H- furo[3,4-e]pyrazolo[3,4-b]pyridine-5-ones were synthesized via the three-component reaction of an aldehyde, 5-amino-3-methyl-1-phenyl-1H-pyrazole and tetronic acid in aqueous media in

Full text of DOI:10.1002/jhet.224

November 2009
Clean Synthesis of Furo[3,4-e]pyrazolo[3,4-b]pyridine-5-one
Derivatives in Aqueous Media
1335
Da-Qing Shia* and Hao Yaob
aCollege of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Organic
Synthesis of Jiangsu Province, Soochow University, Suzhou 215123, People’s Republic of China
bCollege of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou 221116,
People’s Republic of China
*E-mail: dqshi@suda.edu.cn
Received October 17, 2008
DOI 10.1002/jhet.224
Published online 11 November 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of 4-aryl-3-methyl-1-phenyl-7H-furo[3,4-e]pyrazolo[3,4-b]pyridine-5-ones were synthesized
via the three-component reaction of an aldehyde, 5-amino-3-methyl-1-phenyl-1H-pyrazole and tetronic
acid in aqueous media in the presence of triethylbenzylammonium chloride (TEBAC). This method has
the advantages of easier work-up, mild reaction conditions, high yields, and an environmentally benign
procedure.
J. Heterocyclic Chem., 46, 1335 (2009).
INTRODUCTION
this motif show a wide range of pharmacological activ-
ities [10] and used as calcium influx promoters, HIV-1
non-nucleoside reverse transcriptase inhibitors and ace-
tylcholinesterase inhibitors [11]. As part of our current
studies on the development of new routes to heterocy-
clic systems in aqueous media [12], we now report an
efficient and clean synthetic route to furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one derivatives (4) via the three-
component reaction of arylaldehyde 1, 5-amino-3-
methyl-1-phenyl-1H-pyrazole 2 and tetronic acid 3 in
aqueous media (Scheme 1).
The need to reduce the amount of toxic waste and by-
products arising from chemical processes requires
increasing emphasis on the use of less toxic and envi-
ronmentally compatible materials in the design of new
synthetic methods [1]. One of the most promising
approaches uses water as the reaction medium [2]. Bre-
slow [3], who showed that hydrophobic effects could
strongly enhance the rate of several organic reactions,
rediscovered the use of water as a solvent in organic
reactions in 1980s. In recent years, there has been
increasing recognition that water is an attractive medium
for many organic reactions [4]. The aqueous medium
with respect to organic solvent is less expensive, less
dangerous, and environment-friendly. Many important
types of heterocyclic compounds, such as triazines, acri-
dines, quinolines, pyridines, indoles, pyrazines, furans,
and pyrimidines [5], have been synthesized in aqueous
media. The synthesis of new and important type of het-
erocyclic compounds in water continues to attract wide
attention among synthetic chemists.
RESULTS AND DISCUSSION
Choosing an appropriate solvent is of crucial impor-
tance for the successful organic synthesis. To search for
the optimal solvent, the three-component reaction of
3,4-dimethoxybenzaldehyde 1a, 5-amino-3-methyl-1-
phenyl-1H-pyrazole 2 and tetronic acid 3 was examined
using water, acetonitrile, acetone, ethanol, DMF and
1,2-dichloroethane as solvent, respectively, at different
temperature for the synthesis of 4a. The results are sum-
marized in Table 1.
Pyrazole derivatives have been reported in the litera-
ture to be versatile building blocks for the synthesis of a
wide range of the heterocyclic motifs, such as pyrazolo-
pyridines [6], pyrazolequinolines [7], and pyrazolopyra-
zoles [8]. The pyrazolo[3,4-b]pyridine system has inter-
esting biological and pharmacological properties [9].
Furopyridines is one of the ‘‘privileged medical scaf-
folds,’’ which are used for the development of pharma-
ceutical agents of various applications. Compounds with
It can be seen from the Table 1 that the reactions using
water as the solvent resulted in higher yields and shorter
reaction times than those using organic solvents. On the
basis of the obtained results, H2O/TEBAC was found to
be superior in terms of yield. Under these optimized reac-
tion conditions, a series of furo[3,4-e]pyrazolo[3,4-b]pyr-
idine-5-one derivatives 4 were synthesized. The products
C
V
2009 HeteroCorporation

1336
D.-Q. Shi and H. Yao
Vol 46
Scheme 1
Table 2
The synthesis of 4 in aqueous media in the presence of TEBAC.a
Time
(h)
Yield
(%)
Entry
Compound
Ar
1
2
3
4a
4b
4c
4d
4e
4f
4g
4h
4i
3,4-(CH3O)2C6H3
4-BrC6H4
4-FC6H4
9
20
24
30
23
20
10
25
22
15
35
30
30
98
97
95
80
97
83
97
98
95
87
89
85
93
were different from those in ethanol in the presences of
L-proline [13]. The results are summarized in Table 2.
Apart from the mild conditions of the process and its
excellent results, the simplicity of product isolation and
the possibility to recycle the reaction solution offer a
significant advantage. Because TEBAC is soluble in
water and the desired product is less soluble in water,
the products can be directly separated by cooling to
room temperature and filtering after the reaction is com-
pleted. The remaining reaction solution can be recycled.
Studies using 1a, 2, and 3 as model substrates showed
that the recovered reaction solution could be succes-
sively recycled in subsequent reaction without any
decrease of yield (Table 3).
4
4-NO2C6H4
4-CH3OC6H4
2,4-Cl2C6H3
3,4-(CH3)2C6H3
4-ClC6H4
5
6
7
8
9
Pyridin-2-yl
Thiophen-2-yl
3-ClC6H4
10
11
12
13
4j
4k
4l
2-ClC6H4
3,4-Cl2C6H3
4m
a In all entries 90ꢁC temperature was used.
ient procedure and environmentally friendly reaction
conditions.
All the products 4 were characterized by mp, IR, and
1H NMR spectra as well as HRMS.
EXPERIMENTAL
Although the detailed mechanism of the aforemen-
tioned reaction remains to be fully clarified the formation
of furo[3,4-4]pyrazolo[3,4-b]pyridine-5-ones 4 could be
explained by a reaction sequence presented in Scheme 2.
We proposed that the reaction proceeded via a reaction
sequence of condensation, addition, cyclization, dehydra-
tion, and aromatization. First, the condensation of alde-
hyde 1 and tetronic acid 3 gave the intermediate product
5. The addition of 2 to 5 then furnished the intermediate
product 7, which upon intramolecular cyclization and
dehydration gave rise to 9. In the last step, the intermedi-
ate product 9 aromatized to product 4.
In conclusion, we have developed a simple and clean
three-component reaction of an aldehyde, 5-amino-3-
methyl-1-phenyl-1H-pyrazole and tetronic acid for the
synthesis of furo[3,4-e]pyrazolo[3,4-b]pyridine-5-one
derivatives in the presence of TEBAC in aqueous media.
This method has the advantages of good yields, conven-
Melting points are uncorrected. Infrared spectra were
recorded on a Tensor 27 spectrometer in KBr with absorption
in cmꢀ1 1H NMR spectra were recorded on a Bruker DPX
.
400-MHz spectrometer as DMSO-d6 solution, J values are in
Hz. Chemical shifts are expressed in d downfield from internal
tetramethylsilane. HRMS were obtained using TOF-MS or
Bruker-micro TOF-Q-MS instrument.
General procedure for the synthesis of furo[3,4-e]pyra-
4 in aqueous
zolo[3,4-b]pyridine-5-one derivatives
media. Aldehyde 1 (2 mmol), 5-amino-3-methyl-1-phenyl-
1H-pyrazole 2 (2 mmol), tetronic acid 3 (2 mmol) and TEBAC
(0.1 g) were added to a 50-mL round-bottom flask containing
10 mL water. The mixture was then stirred at 90ꢁC for given
times. After completion of the reaction, the reaction mixture
was cooled to room temperature. The precipitate was collected
by suction and purified by recrystallization from EtOH to give
products 4.
3-Methyl-1-phenyl-4-(3,4-dimethoxyphenyl)-7H-furo[3,4-e]
pyrazolo[3,4-b]pyridine-5-one (4a). This compound was
obtained as solid with mp 200–202ꢁC (lit. [14] 203–205ꢁC);
IR (potassium bromide): 3059, 3018, 1768, 1590, 1570, 1512,
1460, 1438, 1412, 1355, 1325, 1309, 1259, 1234, 1203, 1174,
1130, 1070, 1045, 1027, 843, 795, 761, 701 cmꢀ1 1H NMR
;
Table 1
(DMSO-d6): d 2.18 (s, 3H, CH3), 3.79 (s, 3H, CH3O), 3.88 (s,
3H, CH3O), 5.46 (s, 2H, CH2), 7.13 (d, J ¼ 7.6 Hz, 2H, ArH),
7.19 (s, 1H, ArH), 7.40 (t, J ¼ 7.6 Hz, 1H, ArH), 7.60 (t, J ¼
7.6 Hz, 2H, ArH), 8.19 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS
Solvent optimization for the synthesis of 4a.
Temperature
(ꢁC)
Time
(h)
Yield
(%)
Entry
Solvent
1
2
3
4
5
6
7
H2O/SDS
H2O/TEBAC
CH3CN
CH3COCH3
EtOH
DMF
90
90
15
9
90
98
41
0
Table 3
Reflux
Reflux
Reflux
100
20
20
20
22
15
Studies on the reuse of reaction solution in the preparation of 4a.
56
46
0
Round
1
2
3
4
5
6
ClCH2CH2Cl
Reflux
Yield (%)
98
97
92
94
95
92
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Clean Synthesis of Furo[3,4-e]pyrazolo[3,4-b]pyridine-5-one Derivatives
in Aqueous Media
1337
Naþ); calcd for C22H17N3O2Na:
Scheme 2
m/z 394.1164 (M
394.1168].
þ
3-Methyl-1-phenyl-4-(2,4-dichlorophenyl)-7H-furo[3,4-e]pyr-
azolo[3,4-b]pyridine-5-one (4f). This compound was obtained
as solid with mp 206–208ꢁC (lit. [14] 206–208ꢁC); IR (potas-
sium bromide): 3065, 1763, 1585, 1507, 1475, 1442, 1420,
1389, 1376, 1361, 1316, 1211, 1150, 1127, 1101, 1078, 1050,
1
1025, 853, 821, 801, 787, 758 cmꢀ1; H NMR (DMSO-d6): d
2.10 (s, 3H, CH3), 5.54 (d, J ¼ 16.0 Hz, 1H, CH), 5.61 (d, J
¼ 16.0 Hz, 1H, CH), 7.43 (t, J ¼ 7.2 Hz, 1H, ArH), 7.60-7.65
(m, 3H, ArH), 7.68 (d, J ¼ 8.4 Hz, 1H, ArH), 7.95 (s, 1H,
ArH), 8.19 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS [Found: m/z
409.0385 (Mþ); Calcd for C21H1335Cl2N3O2: M 409.0385].
3-Methyl-1-phenyl-4-(3,4-dimethylphenyl)-7H-furo[3,4-e]
pyrazolo[3,4-b]pyridine-5-one (4g). This compound was
obtained as solid with mp 232–233ꢁC (lit. [14] 231–233ꢁC);
IR (potassium bromide): 1768, 1513, 1500, 1459, 1433, 1385,
1355, 1310, 1268, 1227, 1210, 1182, 1070, 1041, 1026, 852,
[Found: m/z 402.1450 (M þ Hþ); calcd for C23H20N3O4:
402.1452].
1
818, 798, 758, 719 cmꢀ1; H NMR (DMSO-d6): d 2.11 (s, 3H,
CH3), 2.33 (s, 3H, CH3), 2.36 (s, 3H, CH3), 5.47 (s, 2H, CH2),
7.28 (d, J ¼ 8.0 Hz, 1H, ArH), 7.32-7.35 (m, 2H, ArH), 7.41
(t, J ¼ 7.6 Hz, 1H, ArH), 7.61 (t, J ¼ 8.0 Hz, 2H, ArH),, 8.19
(d, J ¼ 8.0 Hz, 2H, ArH). HRMS [Found: m/z 392.1355 (M þ
Naþ); calcd for C23H19N3O2Na: 392.1375].
3-Methyl-1-phenyl-4-(4-bromophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4b). This compound was obtained
as solid with mp 226–228ꢁC (lit. [14] 226–227ꢁC); IR (potas-
sium bromide): 3058, 1765, 1579, 1558, 1507, 1489, 1440,
1387, 1356, 1314, 1210, 1140, 1070, 1047, 1029, 1012, 847,
3-Methyl-1-phenyl-4-(4-chlorophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4h). This compound was obtained
as solid with mp 220–222ꢁC (lit. [14] 223–225ꢁC); IR (potas-
sium bromide): 3063, 1764, 1598, 1581, 1562, 1506, 1489,
1459, 1442, 1421, 1386, 1358, 1314, 1211, 1141, 1125, 1089,
1
821, 798, 758, 720 cmꢀ1; H NMR (DMSO-d6): d 2.11 (s, 3H,
CH3), 5.48 (s, 2H, CH2), 7.40 (t, J ¼ 7.2 Hz, 1H, ArH), 7.54
(d, J ¼ 8.0 Hz, 2H, ArH), 7.60 (t, J ¼ 7.6 Hz, 2H, ArH), 7.79
(d, J ¼ 8.0 Hz, 2H, ArH), 8.18 (d, J ¼ 8.0 Hz, 2H, ArH).
HRMS [Found: m/z 442.0161 (M
þ
Naþ); calcd for
1072, 1048, 1028, 1015, 915, 848, 799, 760, 723 cmꢀ1 1H
;
C21H1479BrN3O2Na: 442.0167].
NMR (DMSO-d6): d 2.12 (s, 3H, CH3), 5.49 (s, 2H, CH2),
7.39–7.43 (m, 1H, ArH), 7.59–7.67 (m, 6H, ArH), 8.19 (d,
J ¼ 8.0 Hz, 2H, ArH). HRMS [Found: m/z 398.0670 (M þ
Naþ); calcd for C21H14N3O2Na: 398.0672].
3-Methyl-1-phenyl-4-(4-fluorophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4c). This compound was obtained
as solid with mp 235–237ꢁC (lit. [14] 235–237ꢁC); IR (potas-
sium bromide): 3070, 1756, 1597, 1578, 1512, 1490, 1449,
1437, 1423, 1319, 1360, 1315, 1222, 1210, 1167, 1137, 1069,
3-Methyl-1-phenyl-4-(pyridine-2-yl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4i). This compound was obtained
as solid with mp 245–246ꢁC; IR (potassium bromide): 3032,
1760, 1578, 1515, 1490, 1437, 1383, 1359, 1340, 1311, 1266,
1225, 1201, 1130, 1115, 1076, 1050, 1027, 851, 817, 794, 762
1
1043, 1029, 830, 798, 757 cmꢀ1; H NMR (DMSO-d6): d 2.12
(s, 3H, CH3), 5.49 (s, 2H, CH2), 7.39–7.45 (m, 3H, ArH),
7.59–7.67 (m, 4H, ArH), 8.19 (d, J ¼ 8.0 Hz, 2H, ArH).
HRMS [Found: m/z 382.0945 (M
C21H14FN3O2Na: 382.0968].
þ
Naþ); calcd for
1
cmꢀ1; H NMR (DMSO-d6): d 2.11 (s, 3H, CH3), 5.53 (s, 2H,
CH2), 7.42 (t, J ¼ 7.6 Hz, 1H, ArH), 7.60–7.65 (m, 4H, ArH),
8.18 (d, J ¼ 8.0 Hz, 2H, ArH), 8.80 (d, J ¼ 5.2 Hz, 2H,
ArH). HRMS [Found: m/z 342.1119 (Mþ); Calcd for
C20H14N4O2: M 342.1117].
3-Methyl-1-phenyl-4-(4-nitrophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4d). This compound was obtained
as solid with mp 283–285ꢁC (lit. [14] 288–289ꢁC); IR (potas-
sium bromide): 3067, 1763, 1580, 1517, 1438, 1388, 1349,
1314, 1294, 1213, 1142, 1109, 1073, 1050, 1021, 838, 802,
3-Methyl-1-phenyl-4-(thiophen-2-yl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4j). This compound was obtained
as solid with mp 246–248ꢁC (lit. [14] 248–250ꢁC); IR (potas-
sium bromide): 3098, 1767, 1583, 1544, 1509, 1491, 1440,
1421, 1388, 1363, 1313, 1244, 1149, 1073, 1051, 1022, 796,
754, 709 cmꢀ1 1H NMR (DMSO-d6): d 2.10 (s, 3H, CH3),
;
5.54 (s, 2H, CH2), 7.42 (t, J ¼ 7.6 Hz, 1H, ArH), 7.62 (d, J ¼
8.0 Hz, 2H, ArH), 7.90 (d, J ¼ 8.4 Hz, 2H, ArH), 8.19 (d,
J ¼ 8.0 Hz, 2H, ArH), 8.43 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS
[Found: m/z 409.0891 (M þ Naþ); calcd for C21H14N4O4Na:
409.0913].
1
756 cmꢀ1; H NMR (DMSO-d6): d 2.22 (s, 3H, CH3), 5.47 (s,
2H, CH2), 7.30–7.33 (m, 1H, ArH), 7.39–7.46 (m, 2H, ArH),
7.61 (t, J ¼ 8.0 Hz, 2H, ArH), 7.97 (d, J ¼ 5.2 Hz, 1H, ArH),
8.17 (d, J ¼ 7.6 Hz, 2H, ArH). HRMS [Found: m/z 370.0621
(M þ Naþ); calcd for C19H13N3O2SNa: 370.0626].
3-Methyl-1-phenyl-4-(4-methoxyphenyl)-7H-furo[3,4-e]pyr-
azolo[3,4-b]pyridine-5-one (4e). This compound was obtained
as solid with mp 192–194ꢁC (lit. [14] 190–192ꢁC); IR (potas-
sium bromide): 3047, 1765, 1608, 1580, 1516, 1509, 1458,
1445, 1420, 1384, 1358, 1309, 1294, 1259, 1208, 1176, 1140,
3-Methyl-1-phenyl-4-(3-chlorophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4k). This compound was obtained
as solid with mp 201–203ꢁC; IR (potassium bromide): 1776,
1583, 1562, 1515, 1437, 1387, 1357, 1313, 1210, 1146, 1073,
1072, 1048, 1036, 1019, 824, 798, 758 cmꢀ1 1H NMR
;
(DMSO-d6): d 2.15 (s, 3H, CH3), 3.88 (s, 3H, CH3O), 5.45 (s,
2H, CH2), 7.13 (d, J ¼ 8.4 Hz, 2H, ArH), 7.40 (t, J ¼ 7.2 Hz,
1H, ArH), 7.52 (d, J ¼ 8.4 Hz, 2H, ArH), 7.59 (d, J ¼ 7.6
Hz, 2H, ArH), 8.19 (d, J ¼ 7.6 Hz, 2H, ArH). HRMS [Found:
1
1047, 1031, 939, 784, 752, 725, 707 cmꢀ1; H NMR (DMSO-
d6): d 2.12 (s, 3H, CH3), 5.50 (s, 2H, CH2), 7.41 (t, J ¼ 7.2
Hz, 1H, ArH), 7.55 (d, J ¼ 7.2 Hz, 1H, ArH), 7.61 (t, J ¼
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1338
D.-Q. Shi and H. Yao
Vol 46
Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. Tetrahedron Lett 2005,
46, 7169; (c) Cho, C. S.; Kim, J. S.; Oh, B. H.; Kim, T. J.; Shim,
S. C.; Yoon, N. S. Tetrahedron 2000, 56, 7747; (d) Khadikar, B. M.;
Gaikar, V. G.; Chitnavis, A. A. Tetrahedron Lett 1995, 36, 8083;
(e) Cho, C. S.; Kim, J. H.; Shim, S. C. Ttrahedron Lett 2000, 41,
1811; (f) Totlani, V. M.; Peterson, D. G. J Agric Food Chem 2005,
53, 4130; (g) Wnorowski, A.; Yaylayan, V. A. J Agric Food Chem
2000, 48, 3549; (h) Bose, D. S.; Fatima, L.; Mereyala, H. B. J Org
Chem 2003, 68, 587.
7.6 Hz, 3H, ArH), 7.67 (d, J ¼ 8.4 Hz, 1H, ArH), 7.71 (s, 1H,
ArH), 8.19 (d, J ¼ 8.0 Hz, 2H, ArH). HRMS [Found: m/z
375.0754 (Mþ); Calcd for C21H1435ClN3O2: M 375.0775].
3-Methyl-1-phenyl-4-(2-chlorophenyl)-7H-furo[3,4-e]pyra-
zolo[3,4-b]pyridine-5-one (4l). This compound was obtained
as solid with mp 227–228ꢁC; IR (potassium bromide): 1774,
1600, 1585, 1510, 1492, 1474, 1438, 1387, 1359, 1313, 1210,
1148, 1127, 1074, 1058, 1046, 1027, 872, 846, 757, 726, 710
1
cmꢀ1; H NMR (DMSO-d6): d 2.05 (s, 3H, CH3), 5.53 (d, J ¼
[6] (a) Quiroga, J.; Alvarado, M.; Insuasty, B.; Moreno, R. J.
Heterocyclic Chem 1999, 36, 1311; (b) Quiroga, J.; Hormaza, A.;
Insuasty, B. J. Heterocyclic Chem 1998, 35, 409; (c) Quiroga, J.;
Cruz, S.; Insuasty, B.; Abonia, R. J Heterocyclic Chem 2001, 42,
5625.
16.0 Hz, 1H, CH), 5.60 (d, J ¼ 16.0 Hz, 1H, CH), 7.42 (t, J ¼
7.6 Hz, 1H, ArH), 7.55–7.64 (m, 5H, ArH), 772 (d, J ¼ 8.0 Hz,
1H, ArH), 8.20 (d, J ¼ 7.6 Hz, 2H, ArH). HRMS [Found: m/z
375.0783 (Mþ); Calcd for C21H1435ClN3O2: M 375.0775].
3-Methyl-1-phenyl-4-(3,4-dichlorophenyl)-7H-furo[3,4-e]pyr-
azolo[3,4-b]pyridine-5-one (4m). This compound was obtained
as solid with mp 218–220ꢁC; IR (potassium bromide): 3036,
1771, 1582, 1551, 1506, 1473, 1439, 1382, 1359, 1315, 1212,
[7] Quiroga, J.; Insuasty, B. J Heterocyclic Chem 1998, 35,
575.
[8] Paul, S.; Gupta, M.; Gupta, R.; Loupy, A. Tetrahedron Lett
2001, 42, 3827.
1141, 1072, 1050, 1032, 944, 911, 820, 800, 756, 714 cmꢀ1
;
[9] (a) Hardy, C. R. Adv Heterocyclic Chem 1984, 36, 343;
(b) Orth, R. E. J Pharm Sci 1968, 57, 537; (c) Elnagdi, M. H.;
Elmoghayar, M. R. H.; Elgemeie, G. E. H. Adv Heterocyclic Chem
1987, 41, 319.
1H NMR (DMSO-d6): d 2.16 (s, 3H, CH3), 5.51 (s, 2H, CH2),
7.41 (t, J ¼ 7.2 Hz, 1H, ArH), 7.58–7.64 (m, 3H, ArH), 7.87
(d, J ¼ 8.0 Hz, 1H, ArH), 7.95 (s, 1H, ArH), 8.18 (d, J ¼ 7.6
Hz, 2H, ArH). HRMS [Found: m/z 409.0377 (Mþ); Calcd for
C21H1335Cl2N3O2: M 409.0385].
[10] (a) New, J. S.; Christopher, W. L.; Yevich, J. P.;
Schlemmer, R.; Francis, J.; Vander Maelen, C. P.; Cipollina, J. A. J
Med Chem 1989, 32, 1147; (b) Bukoski, R. D.; Bo, J.; Xue, H.; Bian,
K. J Pharmacol Exp Ther 1993, 265, 30; (c) Paronikyan, E. G.;
Oganisyan, A. K.; Noravyan, A. S.; Paronikyan, R. G.; Dzhagatspan-
yan, I. A. Pharm Chem J 2002, 36, 413; (d) Wagner, G.; Prantz, J.
Pharmazine 1993, 48, 250; (e) Jeschke, P.; Harder, A.; Etzel, W.; Gau,
W.; Goehrt, A.; Benet-Buchholz, J.; Thielking, G. Bioorg Med Chem
Lett 2005, 15, 2375.
Acknowledgments. The authors are grateful to the Foundation
of Key Laboratory of Organic Synthesis of Jiangsu Province for
financial support.
REFERENCES AND NOTES
[11] (a) Gerster, P.; Riegger, C.; Fallert, M. Arzneim, -Forsch.
1987, 37, 309; (b) Wishka, D. G.; Graber, D. R.; Seest, E. P.; Dolak,
L. A.; Han, F.; Watt, W.; Morris, J. J Org Chem 1998, 63, 7851;
(c) Marco, J. L.; Carreiras, M. C. Mini-Rev Med Chem 2003, 3, 578.
[12] (a) Shi, D. Q.; Niu, L. H.; Shi, J. W.; Wang, X. S.; Ji, S. J.
J Heterocyclic Chem 2007, 44, 1083; (b) Shi, D. Q.; Yao, H.; Shi,
J. W. Synth Commun 2008, 38, 1662; (c) Shi, D. Q.; Mou, J.; Zhuang,
Q. Y.; Niu, L. H.; Wu, N.; Wang, X. S. Synth Commun 2004, 34,
4557.
[1] (a) Amato, J. Science 1993, 259, 1538; (b) Illman, D. L.
Chem Eng News 1993, 71, 5; (c) Illman, D. L. Chem Eng News 1994,
72, 22.
[2] (a) Li, C. J.; Chang, T. H. Organic Reactions in Aqueous
Media; Wiley: New York, 1997; (b) Fringuell, F.; Piematti, O.; Pizzo,
F.; Vaccaro, L. Eur J Org Chem. 2001, 439; (c) Stinson, S. C. Chem
Eng News 1996, 74, 39.
[3] (a) Breslow, R.; Rideout, D. C. J Am Chem Soc 1980, 102,
7816; (b) Breslow, R. Acc Chem Res 1991, 24, 59.
[4] (a) Li, C. J Chem Rev 1993, 93, 2023; (b) Li, C. J Chem
Rev 2005, 105, 1273.
[13] Shi, C. L.; Shi, D. Q.; Kim, S. H.; Huang, Z. B.; Ji, S. J.;
Ji, M. Tetrahedron 2008, 64, 2425.
[5] (a) Dandia, A.; Arya, K.; Sati, M.; Sarangi, P. J Fluorine
Chem 2004, 125, 1273; (b) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.;
[14] Shi, D. Q.; Yang, F.; Ni, S. N. J Heterocyclic Chem 2009,
46, 469.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet