Biginelli-like three component reaction: Synthesis of some new ethyl 6-ethoxycarbonylmethyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives

Article abstract of DOI:10.1002/jhet.5570440228

(Chemical Equation Presented) In the context of our high-throughput organic synthesis program, we have studied the reactivity of special β-keto esters toward the Biginelli reaction. We have found that a diethyl-3-oxoglutarate reacts with one molecule of u

Full text of DOI:10.1002/jhet.5570440228

Mar-Apr 2007
455
Biginelli-like Three Component Reaction: Synthesis of some New
Ethyl 6-ethoxycarbonylmethyl-4-aryl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate Derivatives
Javad Azizian,* Ali A. Mohammadi, M. Kohshari, Ali R. Karimi,
Mohammad R. Mohammadizadeh
Department of Chemistry, Faculty of Science, Shahid Beheshti University, P. O. Box 19395-4716, Tehran,
Iran, E-mail: E-mail: j-azizian@cc.sbu.ac.ir
Received March 30, 2006
O
R
O
+
O
O
EtO
EtO
NH
OEt
H2N
EtO
O
p-TSOH
1a-i
N
H
O
80 °C
NH2
O
RCHO
3
4a-i
2a-i
In the context of our high-throughput organic synthesis program, we have studied the reactivity of
special β-keto esters toward the Biginelli reaction. We have found that a diethyl-3-oxoglutarate reacts with
one molecule of urea and one molecule of aldehyde under solvent-free conditions to give a new family of
3,4-dihydropyrimidin-2(1H)-ones in good yields.
J. Heterocyclic Chem., 44, 455 (2007).
3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) are an
important class of heterocyclic compounds having
important biological activities. During the last decade
such compounds have shown interesting pharmacological
properties like antiviral [l,2], antitumour [3], antibacterial,
anti-inflammatory [4], and antihypertensive [5] activities.
One of the most important methods for synthesis of this
class of compounds is the one pot condensation of an
aldehyde, β-ketoester and urea under acidic conditions,
first reported by Biginelli (Scheme 1).
Herein we describe a higher yielding protocol for the
Biginelli-like three-component reactions of aldehydes,
diethyl-3-oxoglutarate and urea for the synthesis of the
new 6-substituted DHPMs 4a-i using p-TSOH under mild
conditions.
From a mixture of diethyl-3-oxoglutarate 1(1 mmol),
benzaldehyde 2a (1 mmol), urea 3 (1.2 mmol), and p-
TSOH (2 mol %), DHPMs 4a was isolated in 98% yield
(Scheme 2). The reaction was carried out at 80 ºC for 3 h
(until the diethyl-3-oxoglutarate disappeared, as shown by
TLC analysis). Then the Biginelli-like reactions of other
various aldehydes 2b-i under a established protocol
Scheme 1
O
O
O
R2
Scheme 2
Me
OR1
O
R1
Me
NH
+
O
R
O
O
O
R2CHO
H2N
NH2
N
H
O
EtO
EtO
NH
OEt
EtO
O
p-TSOH
1a-i
+
N
H
O
80 °C
H2N
NH2
Because of intense interest in the biological activity of
these compounds, in recent years, several synthetic
procedures for preparing of DHPMs have been reported
including classical conditions with microwave irradiation
[6,9c] and by using Lewis acids as well as protic acids as
promoters such as concentrated HCl [7,20a,b], BF3.OEt2 [8],
montmorillonite [9], InCl3 [10], LaCl3 [11], La(OTf)3 [12],
Yb(OTf)3 [12], InBr3 [13], BiCl3 [14], Bi(OTf)3 [15], In(OTf)3
[16], p-TSOH [17], Cu(OTf)2 [18], CeCL3 [19], FeCl3 [20a,c],
ZnCl2 [20,21], MgBr2 [22], MgCl2 [23], CdCl2 [24], Zn(OTf)2
[25], KHSO4 [26],have been used for this reaction.
In view of this and also in continuation to our interest
on Multi-Component reactions (MCRs) [27], we report
herein, a simple, facile, rapid and efficient MCRs for the
preparation of some new 6-substituted DHPMs
derivatives with p-TSOH as a nontoxic, inexpensive, very
soluble in water, and easily available reagent.
O
RCHO
3
4a-i
2a-i
Table
The Reaction of Aldehydes, Diethyl-3-oxoglutarate and Urea
Mp (°C)
Yield (%)
Time (h)
R
Productsa 4
178-180
156-158
138-140
136-138
215-217
229-231
136-138
148-150
184-186
98
95
95
97
90
91
92
94
97
3
Ph
a
b
c
d
e
f
3
2-BrC6H4
3-ClC6H4
4-ClC6H4
2-HOC6H4
4-HOC6H4
4-CH3C6H4
3-NO2C6H4
4-NO2C6H4
2.5
2.5
3
3
3.5
2.5
3.5
g
h
i
aAll products were characterized by 1H, 13C NMR, IR, MS and elemental
analyses.

456
J. Azizian, A. A. Mohammadi, M. Kohshari, A. R. Karimi, M. R. Mohammadizadeh
Vol 44
54.45 (CH), 60.34 (CH2), 61.48 (CH2), 101.27 (C=C), 122.77,
128.55, 129.71, 132.94 (arom), 140.80 (C=C), 144.44 (arom),
152.84, 164.77, 168.79 (CO). MS (m/z, %): 411 (M+, 10), 367
(20), 365 (20), 339 (45), 337 (50), 293 (25), 291 (25), 286 (40),
255 (100), 239 (15), 209 (70), 181 (80), 155 (25), 137 (25), 102
(25), 75 (15). Anal. Calcd. for C17H19N2BrO5: C, 49.64; H, 4.62;
N, 6.81. Found: C, 49.61; H, 4.59; N, 6.79.
wherein we used a 0.02:1:1:1.2 ratio of p-TSOH, diethyl-
3-oxoglutarate, aldehyde, and urea, respectively,
furnished the respective DHPMs 4b-i in good yields. The
optimized results are summarized in Table 1.
In summary, we have described a mild, convenient
method for the preparation of some new 6-substituted
DHPMs by
the Biginelli-like
three-component
Ethyl 6-ethoxycarbonylmethyl-4-(3-chlorophenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4c).
White
cyclocondensation reaction of diethyl-3-oxoglutarate,
aldehydes, and urea using cheap, non-toxic, very soluble
in water, and easily available p-TsOH catalyst.
Additionally, this new reaction might be a useful tool for
high-throughput organic synthesis.
powder, yield 95%, mp 138-140 °C, IR (KBr), (vmax/cm-1): 3303,
3115, 2980, 1738, 1701, 1674, 1651. 1H NMR (CDCl3) δH: 1.04
(t, 3H, J=7.1 Hz, CH3), 1.18 (t, 3H, J=7.1 Hz, CH3), 3.58 (d, 1H,
J=16.9 Hz, CH2), 3.86 (d, 1H, J=16.9 Hz, CH2), 3.95 (q, 2H,
J=7.0 Hz, CH2), 4.10 (q, J=7.0 Hz, CH2), 5.17 (d, 1H, J=3.2 Hz,
CH), 7.28-7.40 (m, 4H), 7.87 (s, 1H, NH), 9.36 (s, 1H, NH). 13
C
NMR (CDCl3) δC: 14.32 (CH3), 14.53 (CH3), 37.54 (CH2), 54.10
(CH), 60.10 (CH2), 61.01 (CH2), 100.64 (C=C), 125.71, 126.92,
127.90, 130.92, 133.46 (arom), 145.67 (C=C), 147.12 (arom),
152.90, 165.20, 169.19 (CO). MS (m/z, %): 366 (M+, 20), 321
(30), 320 (25), 295 (30), 294 (25), 293 (100), 279 (20), 265 (30),
255 (100), 249 (25), 247 (50), 220 (30), 209 (65), 183 (45), 181
(75), 140 (20), 111 (15). Anal. Calcd. for C17H19N2ClO5: C,
55.66; H, 5.18; N, 7.64. Found: C, 55.66; H, 5.18; N, 7.64.
Ethyl 6-ethoxycarbonylmethyl-4-(4-chlorophenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4d). White
powder, yield 97%, mp 136-138 °C, IR (KBr), (vmax/cm-1): 3315,
3145, 2980, 1739, 1704, 1673, 1650. 1H NMR (CDCl3) δH: 1.05
(t, 3H, J=7.0 Hz, CH3), 1.18 (t, 3H, J=7.0 Hz, CH3), 3.62 (d, 1H,
J=16.9 Hz, CH2), 3.81 (d, 1H, J=16.9 Hz, CH2), 3.94 (q, 2H,
J=7.0 Hz, CH2), 4.10 (q, 2H, J=7.0 Hz, CH2), 5.17 (s, 1H, CH),
7.34 (d, 2H, J=8.4 Hz, CH), 7.41 (d, 2H, J=8.4 Hz, CH) 7.84 (s,
1H, NH), 9.33 (s, 1H, NH). 13C NMR (CDCl3) δC: 14.33 (CH3),
14.51 (CH3), 37.49 (CH2), 53.92 (CH), 60.03 (CH2), 60.98
(CH2), 100.93 (C=C), 128.84, 128.89, 132.46 (arom), 143.76
(C=C), 145.44 (arom), 152.16, 165.24, 169.07(CO). MS (m/z,
%): 367 (M+, 25), 321 (30), 320 (25), 293 (100), 279 (25), 255
(90), 247 (55), 220 (40), 209 (75), 181 (70), 166 (50), 140 (45),
110 (20). Anal. Calcd. for C17H19N2ClO5: C, 55.66; H, 5.18; N,
7.64. Found: C, 55.63; H, 5.14; N, 7.60.
Ethyl 6-ethoxycarbonylmethyl-4-(2-hydroxyphenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4e): White
powder, yield 90%, mp 215-217 °C, IR (KBr), (vmax/cm-1): 3370,
3225, 3090, 2940, 1728, 1698, 1654, 1608, 1590. 1H NMR
(DMSO-d6) δH: 1.01 (t, 3H, J=7.0 Hz, CH3), 1.18 (t, 3H, J=7.0
Hz, CH3), 3.62 (d, 1H, J=16.9 Hz, CH2), 3.84 (d, 1H, J=16.9 Hz,
CH2), 3.90 (q, 2H, J=7.0 Hz, CH2), 4.11 (q, 2H, J=7.0 Hz,
CH2), 5.52 (s, 1H, CH), 6.71 (t, 1H, J=7.3 Hz, CH), 6.80 (d, 1H,
J=7.9 Hz, CH), 7.06 (t, 1H, J=6.9 Hz, CH), 7.17 (s, 1H, OH),
7.22 (d,1H, J=7.41 Hz, CH) 9.18 (s, 1H, NH), 9.68 (s, 1H, NH).
13C NMR (DMSO-d6) δC: 13.81 (CH3), 14.02 (CH3), 37.02
(CH2), 48.29 (CH), 59.33 (CH2), 60.47 (CH2), 99.87 (C=C),
115.16, 118.73, 127.19, 128.38, 129.40 (arom), 144.87 (C=C),
152.15 (arom), 154.42, 164.96, 168.74 (CO). MS (m/z, %): 348
(M+, 30), 302 (45), 301 (50), 275(50), 274 (45), 261 (50), 255
(100), 229 (80), 228 (50), 215 (50), 209 (55), 201 (50), 181 (70),
148 (25), 122 (25), 91 (20). Anal. Calcd. for C17H20N2O6: C,
58.62; H, 5.75; N, 8.05. Found: C, 58.58; H, 5.71; N, 8.01.
Ethyl 6-ethoxycarbonylmethyl-4-(4-hydroxyphenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4f). White
powder, yield 91%, mp 229-231°C, IR (KBr), (vmax/cm-1): 3300,
3100, 2965, 1728, 1692, 1659, 1608, 1508. 1H NMR (DMSO-d6)
δH: 0.90 (t, 3H, J=6.9 Hz, CH3), 1.03 (t, 3H, J=7.0 Hz, CH3),
EXPERIMENTAL
Melting points were measured on the Electro thermal 9100
apparatus and are uncorrected. IR spectra were measured on a
1
Shimadzu IR-470 Spectrophotometer. H NMR and 13C NMR
spectra were determined on Bruker 500 DRX AVANCE
instrument at 500 and 125 MHz, respectively. Elemental
analyses were performed using
analyzer.
a Heracus CHN-O-Rapid
General Procedure for the Preparation of Ethyl 6-ethoxy-
carbonylmethyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 4a-i. A mixture of the appropriate aldehyde (1
mmol), diethyl-3-oxoglutarate (1 mmol), urea (1.2 mmol), and
p-TsOH (0.02 mmol) was heated with stirring at 80 °C for the
time period as indicated in Table 1. After completion of the
reaction (TLC analysis), water was added to the mixture, and the
crude products were directly filtrated through a sintered funnel.
The crude products were further purified by recrystalization
(EtOH) to afford products 4a-i (Table 1). All products were
characterized by 1H, 13C NMR, IR, MS spectral data and by
elemental analyses.
Ethyl 6-ethoxycarbonylmethyl-4-phenyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (4a). White powder,
yield 98%, mp 178-180 °C, IR(KBr), (vmax/cm-1): 3315, 3100,
2975, 1739, 1701, 1678, 1651.1H NMR (CDCl3) δH: 1.14 (t, 3H,
J=7.2 Hz, CH3), 1.26 (t, 3H, J=7.0 Hz, CH3), 3.67 (d, 1H,
J=16.8 Hz, CH2), 3.94 (d, 1H, J=16.8 Hz, CH2), 4.06 (q, 2H,
J=7.2 Hz, CH2), 4.18 (q, 2H, J=7.0 Hz, CH2), 5.43 (s, 1H, CH),
6.02 (s, 1H, NH), 7.28-7.41 (m, 5H, arom), 8.88 (s, 1H, NH). 13
C
NMR (CDCl3) δC: 14.01 (CH3), 14.0 (CH3), 37.34 (CH2), 55.74
(CH), 60.32 (CH2), 61.37 (CH2), 103.06 (C=C), 126.81, 128.07,
128.77 (arom), 142.56 (C=C), 143.28 (arom), 153.32, 165.07,
168.79 (CO). MS (m/z, %): 332 (M+, 20), 286 (35), 275 (20),
255 (100), 245 (30), 229 (25), 213 (65), 209 (75), 186 (45), 181
(85), 153 (25), 132 (25), 106 (15), 77 (15). Anal. Calcd. for
C17H20N2O5: C, 61.44; H, 6.02; N, 8.43. Found: C, 61.42; H,
6.00; N, 8.40.
Ethyl 6-ethoxycarbonylmethyl-4-(2-bromophenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4b). White
powder, yield 95%, mp 156-158 °C, IR (KBr), (vmax/cm-1): 3325,
3225, 3100, 2970, 1727, 1693, 1646. 1H NMR (CDCl3) δH: 1.06
(t, 3H, J=7.1 Hz, CH3), 1.31 (t, 3H, J=7.1 Hz, CH3), 3.56 (d, 1H,
J=16.8 Hz, CH2), 4.21 (d, 1H, J=16.8 Hz, CH2), 4.01 (q, 2H,
J=7.1 Hz, CH2), 4.23 (q, 2H, J=7.1 Hz, CH2), 5.77 (s, 1H, CH),
5.90 (s, 1H, NH), 7.14-7.58 (m, 4H, arom), 8.82 (s, 1H, NH).
13C NMR (CDCl3) δC: 13.93 (CH3), 14.19 (CH3), 37.39 (CH2),

Mar-Apr 2007
Biginelli-like Three Component Reaction
457
3.45 (d, 1H, J=16.9 Hz, CH2), 3.64 (d, 1H, J=16.9 Hz, CH2),
3.78 (q, 2H, J=7.0 Hz, CH2), 3.94 (q, 2H, J=6.9 Hz, CH2), 4.92
(s, 1H, CH), 6.54 (d, 2H, J=8.1 Hz, CH), 6.98 (d, 2H, J=8.1 Hz,
CH), 7.52 (s, 1H, OH), 9.04 (s, 1H, NH), 9.24 (s, 1H, NH). 13C
NMR (DMSO-d6) δC: 13.86 (CH3), 14.00 (CH3), 36.98 (CH2),
53.45 (CH), 59.41 (CH2), 60.44 (CH2), 101.35 (C=C), 114.92,
127.68, 134.92 (arom), 143.99 (C=C), 151.90 (arom), 156.60,
164.97, 168.67 (CO). MS (m/z, %): 348(M+, 20), 319 (15), 303
(50), 302(50), 275 (100), 274 (50), 273 (50), 261 (75), 255 (75),
229 (100), 209 (70), 202 (70), 201 (50), 181 (75), 148 (50), 122
(45). Anal. Calcd. for C17H20N2O6: C, 58.62; H, 5.75; N, 8.05.
Found: C, 58.60; H, 5.72; N, 8.02.
Acknowledgments. We gratefully acknowledge the financial
support from the Research Council of Shahid Beheshti
University.
REFERENCES
[1a] C. O. Kappe, Eur. J. Med. Chem., 35, 1043-1052 (2000); [b]
K. S. Atwal, B. N. Swanson, S. E. Unger, D. M. Floyd, S. Moreland, A.
Hedberg and B. C. O'Rielly, J. Med. Chem., 34, 806 (1991).
[2] A. D. Patil, N. V. Kumar, W. C. Kokke, M. F. Bean, A. J.
Freyer, C. De Brosse, S. Mai, A. Truneh, D. J. Faulkner et al. J. Org.
Chem., 60, 1182 (1995).
Ethyl 6-ethoxycarbonylmethyl-4-(4-methylphenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4g). White
powder, yield 92%, mp 136-138 °C, IR (KBr), (vmax/cm-1): 3310,
3105, 2980, 1737, 1701, 1675, 1650. 1H NMR (CDCl3) δH: 1.15
(t, 3H, J=7.1 Hz, CH3), 1.27 (t, 3H, J=7.1 Hz, CH3), 2.34 (d, 3H,
J=6.9, CH3), 3.68 (d, 1H, J=16.8 Hz, CH2), 3.94 (d, 1H, J=16.8
Hz, CH2), 4.06 (q, 2H, J=7.1 Hz, CH2), 4.19 (q, 2H, J=7.1 Hz,
CH2), 5.39 (s, 1H, CH), 5.69 (s, 1H, NH), 7.14 (d, 2H, J=7.6
Hz), 7.27 (d, 2H, J=7.9 Hz), 8.49 (s, 1H, NH).13C NMR
(CDCl3) δC: 14.05 (CH3), 14.12(CH3), 21.14(CH3), 37.36(CH2),
55.46(CH), 60.29(CH2), 61.35(CH2), 103.14 (C=C), 126.71,
129.41, 137.74 (arom), 140.51 (C=C), 142.43 (arom), 153.35,
165.15, 168.81(CO). MS (m/z, %): 346 (M+, 5), 301 (10), 300
(10), 273 (45), 255 (45), 227 (25), 209 (30), 181 (45), 146 (25),
110 (15), 91 (25), 81 (20), 65 (50), 56 (25), 45 (50), 43 (50), 32
(100), 31 (25), 30 (20). Anal. Calcd. for C18H22N2O5: C, 62.46;
H, 6.36; N, 8.09. Found: C, 62.42; H, 6.31; N, 8.05.
[3] C. O. Kappe, Tetrahedron, 49, 6937 (1993).
[4] C. O. Kappe, D. Kumar and R. S. Varma, Synthesis, 1799
(1999).
[5] G. J. Grover, S. Dzwonczyk, D. M. Mc Multen, D. E.
Normandin, C. S. Parham, P. G. Sleph and S. Moreland, J. Cardiovase,
Pharmacol, 26, 289 (1995).
[6] J. S. Yadav, B. V. S. Reddy, E. J. Reddy and T. Ramalingam,
J. Chem. Res. (S)., 354 (2000).
[7] K. S. Atwal, G. C. Rovnyak, B. C. O,reilly and J. Schwartz,
J. Org. Chem., 54, 5898 (1989).
[8] E. H. Hu, D. R. Sidler and U. H. Dolling, J. Org. Chem., 63,
3454 (1998).
[9a] F. Bigi, S. Carloni, B. Frullanti, R. Maggi and G. Sartori,
Tetrahedron Lett., 40, 3465 (1999); [b] A. K. Mitra and K. Banerjee,
Synlett., 1509 (2003); [c] H. Lin, J. Ding, X. Chen and Z. Zhang,
Molecules, 5, 1240 (2000); [d] R. S. Varma, and D. Kumar, Tetrahedron
Lett., 40, 7665 (1999).
[10] B. C. Ranu, A. Hajra and U. Jana, J. Org. Chem., 65, 6270
(2000).
Ethyl 6-ethoxycarbonylmethyl-4-(3-nitrophenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4h). White
powder, yield 94%, mp 148-150 °C, IR (KBr), (vmax/cm-1): 3235,
3105, 2975, 1736, 1714, 1692, 1645, 1517. 1H NMR (DMSO-
d6) δH: 1.04 (t, 3H, J=6.2 Hz, CH3), 1.16 (t, 3H, J=6.26 Hz,
CH3), 3.61 (d, 1H, J=16.9 Hz, CH2), 3.85 (d, 1H, J=16.9 Hz,
CH2), 3.94 (q, 2H, J=7.0 Hz, CH2), 4.10 (q, 2H, J=6.4 Hz, CH2),
5.33 (s, 1H, CH), 7.66-7.69 (m, 1H, arom), 7.77-7.80 (m, 1H,
arom), 7.97 (S, 1H, NH), 8.13-8.18 (m, 2H, arom), 9.45 (S, 1H,
NH), 13C NMR (DMSO-d6) δC: 13.76, 13.97, 37.04, 53.53,
59.66, 60.53, 99.90, 121.31, 122.48, 130.14, 133.14, 145.57,
146.45, 147.77, 151.49, 164.60, 168.49, MS (m/z, %): 377 (M+,
20), 360 (45), 332 (30), 304 (70), 274 (25), 258 (45), 255 (100),
231 (20), 209 (75), 181 (100), 163 (20), 137 (20), 110 (15).
Anal. Calcd. for C17H19N3O7: C, 54.11; H, 5.04; N, 11.14.
Found: C, 54.09; H, 5.01; N, 11.10.
[11] J. Lu, Y. Bai, Z. Wang, B. Yang and H. Ma, Tetrahedron
Lett., 41, 9075 (2000).
[12a] Y. Ma, C. Qian, L. Wang and M. Yang, J. Org. Chem., 65,
3864 (2000); [b] R. F. Chen and C. T. Qian, Chinese J. Chem., 20, 427
(2002); [c] L. M. Wang, C. T. Qian, H. Tian and Y. Ma, Synth.
Commun., 33, 1459 (2003).
[13a] N. Y. Fu, Y. F. Yuan, Z. Cao, S. W. Wang, J. W. Wang and
C. Peppe, Tetrahedron, 58, 4801 (2002); [b] N. Y. Fu, Y. F. Yuan, M. L.
Pang and J. T. Wang, Chem. J. Chinese Univ., 24, 79 (2003).
[14] K. Ramalinga, P. Vijayalakshmi and T. N. B. Kaimal,
Synlett., 863 (2001).
[15] R. Varala, M. M. Alam and S. R. Adapa, Synlett., 67 (2003).
[16] R. Ghosh, S. Maiti and A. Chakraborty, J. Molecular
Catalysis A, 217, 47 (2004).
[17a] A. Bose, S. Pednekar, S. N. Ganguly, G. Chakraborty and M.
S. Manhas, Tetrahedron Lett., 45, 8351 (2004); [b] T. Jin, S. Zhang and
T. Li, Synth. Commun., 32, 1847 (2002).
Ethyl 6-ethoxycarbonylmethyl-4-(4-nitrophenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4i). White
powder, yield 97%, mp 184-186 °C, IR (KBr), (vmax/cm-1): 3305,
3095, 2970, 1727, 1702, 1692, 1654, 1527. 1H NMR (DMSO-d6)
δH: 1.04 (t, 3H, J=6.9 Hz, CH3), 1.17 (t, 3H, J=7.0 Hz, CH3),
3.64 (d, 1H, J=16.9 Hz, CH2), 3.82 (d, 1H, J=16.9 Hz, CH2),
3.94 (q, 2H, J=6.9 Hz, CH2), 4.10 (q, 2H, J=7.0 Hz, CH2), 5.30
(d, 1H, CH), 7.59 (d, 2H, CH), 7.98 (s, 1H, NH), 8.21 (d, 2H,
J=8.2 Hz, CH), 9.44 (s, 1H, NH). 13C NMR (DMSO-d6) δC:
13.80(CH3), 14.02(CH3), 37.00(CH2), 53.60(CH), 59.69(CH2),
60.55(CH2), 99.82 (C=C), 123.78, 127.82 (arom), 145.53 (C=C),
146.79, 151.41(arom), 151.48, 164.60, 168.53(CO). MS (m/z,
%): 377 (M+, 25), 332 (45), 331 (30), 305 (20), 304 (98), 303
(45), 290 (25), 276 (25), 274 (25), 258 (55), 255 (95), 231 (30),
209 (90), 181 (100), 163 (30), 137 (25), 110 (15). Anal. Calcd.
for C17H19N3O7: C, 54.11; H, 5.04; N, 11.14. Found: C, 54.08; H,
5.00; N, 11.11.
[18] A. S. Paraskar, G. K. Dewkar and A. Sudalai, Tetrahedron
Lett., 44, 3305 (2003).
[19] D. S. Bose, L. Fatima and H. B. Mereyala, J. Org. Chem., 68,
587 (2003).
[20a] S. Xue, Y. C. Shen, Y. L. Li, X. M. Shen and Q. X. Guo,
Chinese J. Chem., 20, 385 (2002); [b] M. Kidwai, S. Saxena, R. Mohan
and R.Venkataramanan, J. Chem. Soc. Perkin Trans. 1, 1845 (2002); [c]
J. Lu and H. Ma, Synlett., 63 (2000).
[21] Q. Sun, Y. Q. Wang, Z. M. Ge, T. M. Cheng and R. T. Li,
Synthesis, 1047 (2004).
[22] H. Salehi and Q. Guo, Synth. Commun., 34, 171 (2004).
[23] G. L. Zhang and X. H. Cai, Synth. Commun., 35, 829 (2005).
[24] A. V. Narsaiah, A. K. Basak and K.Nagaiah, Synthesis, 1253
(2004).
[25a] H. Xu and Y. G. Wang, Indian J. Chem. B., 42, 2604 (2003);
[b] H. Xu and Y. G. Wang, Chinese J. Chem., 21, 327 2003).
[26] S. Tu, F. Fang, S. Zhu, T. Li, X. Zhang and Q. Zhuang,
Synlett., 537 (2004).

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J. Azizian, A. A. Mohammadi, M. Kohshari, A. R. Karimi, M. R. Mohammadizadeh
Vol 44
[27a] J. Azizian, A. A. Mohammadi, E. Soleimani, A. R. Karimi
2263 (2004; [d] J. Azizian, A. A. Mohammadi and A. R. Karimi, Synth.
Commun., 33, 415 (2003); [e] J. Azizian, A. R. Karimi and A. A.
Mohammadi, Synth. Commun., 33, 387 (2003); [f] J. Azizian, A. R.
Karimi, H. Arefrad, A. A. Mohammadi and M. R. Mohammadizadeh,
Molecular Diversity, 6, 223 (2003).
and M. R. Mohammadizadeh, J. Heterocyclic Chem., 43, 187 (2006); [b]
J. Azizian, A. A. Mohammadi, A. R. Karimi and M. R.
Mohammadizadeh, J. Org. Chem., 70, 350 (2005); [c] J. Azizian, A. R.
Karimi, A. A. Mohammadi and M. R. Mohammadizadeh, Synthesis, 14,