A novel one-pot isocyanide-based four-component reaction: Synthesis of highly functionalized 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates

Article abstract of DOI:10.1016/j.tet.2012.05.078

A new protocol has been developed for the efficient synthesis of structurally diverse 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates via a four-component reaction of hydrazine hydrate, dialkyl acetylenedicarboxylates, isocyanides and various cyclic anhydrides such as succinic anhydride, maleic anhydride and phthalic anhydride in ethanol/acetone (1:1) at room temperature in good to moderate yields.

Full text of DOI:10.1016/j.tet.2012.05.078

Tetrahedron 68 (2012) 6141e6145
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A novel one-pot isocyanide-based four-component reaction: synthesis of highly
functionalized 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates
and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates
*
Sajjad Keshipour, Salman Shojaei, Ahmad Shaabani
Department of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A new protocol has been developed for the efficient synthesis of structurally diverse 1H-pyrazolo[1,2-b]
Received 10 March 2012
Received in revised form 6 May 2012
Accepted 21 May 2012
phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates via
a
four-
component reaction of hydrazine hydrate, dialkyl acetylenedicarboxylates, isocyanides and various cy-
clic anhydrides such as succinic anhydride, maleic anhydride and phthalic anhydride in ethanol/acetone
(1:1) at room temperature in good to moderate yields.
Available online 27 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Pyrazolo-phthalazine
Multi-component
Bridgehead nitrogen-containing
heterocyclic
Isocyanide
1. Introduction
for the preparation of these triheterocyclic structures.7 The most
common and convenient approach toward diverse pyrazoles is
Bridgehead nitrogen-containing heterocycles are an important
class of compounds due to their presence in natural and non-
natural products, which exhibit useful biological activities.1
Among such compounds, heterocycles containing bridgehead hy-
drazine are interesting because of their pharmacological properties
and clinical applications.2 Naturally occurring compounds with two
ring junction nitrogen atoms are rare, nigellicine (A), and its de-
rivatives (B) are compounds from this category and are isolated
from the seeds of nigella sativa.3 Cinnopentazone (C), another ex-
ample, exhibits anti-inflammatory, analgesic, antihypoxic, antipy-
retic and antibacterial activities.4 A series of pyrazolone-based
compounds D have been reported as potent inhibitors of cyto-
kines, namely tumor necrosis factor-R (TNF-R).2j Bridgehead
nitrogen-containing heterocycles with phthalazine scaffold such as
1-arylamino-2,3-dihydro-1H-pyrazolo[1,2-b]phthalazine-5,10-
dione derivatives E have anti-inflammatory, analgesic, antihypoxic
and antipyretic properties (Fig. 1).5
a three-component reaction of isocyanides, dialkyl acetylenedi-
carboxylates, and phthalhydrazide.8
Multi-component reactions (MCRs) are useful synthetic strategy
for the achievement of high levels of diversity and brevity, as they
allow three or more, simple building blocks to be combined in
In 1937, Drew and Hatt reported the first route for the synthesis
of compounds with the 1H-pyrazolo[1,2-b]phthalazine-5,10-dione
skeleton via the reaction between phthalhydrazide and cinna-
maldehyde.6 After that, only a few procedures have been reported
Fig. 1. Examples of biologically active compounds with two ring junction nitrogen
* Corresponding author. E-mail address: a-shaabani@sbu.ac.ir (A. Shaabani).
atoms.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.078

6142
S. Keshipour et al. / Tetrahedron 68 (2012) 6141e6145
practical one-pot operations.9 Because of the unique reactivity of
the isocyanide functional group, isocyanide-based multi-compo-
nent reactions (IMCRs) are among the most versatile, in terms of
number and variety of compounds that can be generated. Such
considerations are of particular importance in connection with the
design and discovery of novel IMCRs.10
acid (12) and dimethyl 3-(cyclohexylamino)-7-((1,3-dioxo-1,3-
dihydroisobenzofuran-5-yl)(hydrazono)methyl)-5,10-dioxo-5,10-
dihydro-1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylate (13) in rel-
atively good yields (Fig. 3).
Although no detailed mechanistic studies have been carried out
at this point, it is conceivable that, the initial event is the formation
of 2,3-dihydrophthalazine-1,4-dione 14 from condensation be-
tween phthalic anhydride 1 and hydrazine (2).6 It is reasonable to
assume that protonation of the 1:1 zwitterionic intermediate 15 by
the NH acid of 2,3-dihydrophthalazine-1,4-dione 14 followed by
quenching of the cationic center by the conjugate base of the NH
acid can generate the intermediate 16. Then, products 5aeo
obtained by an intramolecular nucleophilic reaction of in-
termediates 16 (Scheme 2).
In summary, we have developed an interesting 4-IMCR of hy-
drazine hydrate, dialkyl acetylenedicarboxylates, isocyanides and
various cyclic anhydrides providing of the 1H-pyrazolo[1,2-b]
phthalazine-1,2-dicarboxylate and 1H-pyrazolo[1,2-a]pyridazine-
1,2-dicarboxylate derivatives in ethanol/acetone (1:1) as the sol-
vent at room temperature in good to moderate yields. Broader
substrate scope and mild reaction conditions of this reaction make
it a useful and attractive process for the synthesis of a great library
In view of our current studies on IMCRs,11 we wish to highlight
our findings about synthesis of highly functionalized 1H-pyrazolo
[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyr-
idazine-1,2-dicarboxylates via a one-pot 4-IMCR of various cyclic
anhydrides 1, hydrazine hydrate (2), isocyanides 3 and dialkyl
acetylenedicarboxylates 4 in EtOH/acetone (1:1) at room temper-
ature (Scheme 1). Notably, one of the drawbacks of the previously
described methods for the synthesis of pyrazoles was the necessity
of phthalhydrazide; it limits the above mentioned procedure to the
commercially available derivatives of phthalhydrazide.8 Using hy-
drazine and cyclic anhydrides, improved diversity of the available
starting materials and obtained fairly good combinatorial libraries
of products. Replacement of the two-step procedure of phthalhy-
drazide preparation and its use in the 3-IMCR8 with 4-IMCR is
economically beneficial, and also, has advantages such as ease of
handling, simple work-up and improvement of general yields.
Scheme 1. Synthesis of 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylate and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylate derivatives 5aeo.
In a pilot experiment, phthalic anhydride 1 (1 mmol) and hy-
drazine hydrate (2) (1 mmol) were stirred in ethanol (10 mL) at
room temperature. After 6 h, 1,1,3,3-tetramethylbuthyl isocyanide
(3a) (1 mmol) and solution of dimethyl acetylenedicarboxylate (4a)
(1 mmol) in acetone (10 mL) was added to the reaction mixture
over 15 min, respectively, and stirring continued for 42 h. After
completion of the reaction, the product 5a was obtained in 60%
yield. To evaluate the use of this interesting approach, a variety of
cyclic anhydrides 1, various aliphatic and benzylic isocyanides 3
and dialkyl acetylenedicarboxylates 4 were examined. The reaction
is straightforward and proceeds very cleanly under mild reaction
conditions at room temperature to produce the corresponding
products 5aeo in relatively good yields, and no undesirable side
reactions were observed under the reaction conditions. Represen-
tative structures of products are shown in Fig. 2.
of these important compounds. The potential uses of this route in
synthetic and medicinal chemistry may be significant, since the
products share structural and functional group properties of the
biologically active molecules.
2. Experimental procedures
2.1. General
Melting points were measured on an Electrothermal 9100 ap-
paratus and are uncorrected. Mass spectra were recorded on Agi-
lent 5973 mass spectrometers operating at an ionization potential
of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spec-
trometer. 1H NMR Spectra were recorded on a Bruker DRX-300
Avance spectrometer 300.13 MHz and a Bruker WP 200 SY spec-
trometer 250.13 MHz in CDCl3 or DMSO-d6 solutions with TMS as
internal standards. The 13C NMR spectra were recorded at 75.47 and
The structures of the new products (5ieo) were deduced from
their IR, 1H NMR, and 13C NMR spectra. The 1H NMR spectrum of
5i consisted of a multiplet for the cyclohexyl ring (
two singlets for the two OMe (
¼3.41 and 3.44), a broad singlet
for the NHeCH cyclohexyl proton (
¼3.64), a singlet for CHCO
d
¼1.01e1.85),
62.47 MHz; for all NMR spectra data chemical shifts (d scale) are
d
reported in parts per million (parts per million). The elemental
analyses were performed with an Elementar Analysensysteme
GmbH VarioEL. The chemicals used in this work were purchased
from Merck and Fluka Chemical Companies.
d
3
(
d
¼4.29) and a doublet for NHeCH ( ¼8.60, JHH¼7.5 Hz). The
d
1H decoupled 13C NMR spectrum of 5i showed 19 distinct
resonances.
It is important to note that our attempts to replace the phthalic
anhydride 1 with phthalimide (6), N-aminophthalimide (7), 2-
benzofuran-1(3H)-one (8) and isochroman-1,3-dione (9) failed.
The versatility of this IMCR with respect to the compounds 10 and
11 containing two anhydride functional groups with two molar
equivalents of reagents under the same reaction conditions was also
studied (Fig. 3). Using this approach, gave a new class of products: 3-
(cyclohexylamino)-7-(hydrazinecarbonyl)-1,2-bis(methoxycarbonyl)-
5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-8-carboxylic
2.2. Product 5a; typical procedure
Phthalic anhydride 1 (1 mmol) and hydrazine hydrate (2)
(1 mmol) were stirred in ethanol (10 mL) at room temperature. The
progress of the reaction was monitored by TLC with CH2Cl2/n-
hexane (1:3). After 6 h, 1,1,3,3-tetramethylbuthyl isocyanide (3a)
(1 mmol) and solution of dimethyl acetylenedicarboxylate (4a)
(1 mmol) in acetone (10 mL) was added to the reaction mixture

S. Keshipour et al. / Tetrahedron 68 (2012) 6141e6145
6143
Fig. 2. The structures of products 5aeo.
over 15 min, respectively, and stirring continued for 42 h. After
(5j). Green powder (0.41 g, 73%); mp 150e153 ꢀC. IR (KBr) cmꢁ1
3378, 3192, 3032, 2975, 2917, 2834, 1790, 1733, 1655, 1534, 1375,
1299,1200.1HNMR(250.13 MHz, DMSO-d6)
:3.18 (3H, s, OMe), 3.39
(3H, s, OMe), 4.32 (2H, m, CH2), 6.09 (1H, br s, CHCO), 7.24e7.36 (5H,
m, CHeAr), 8.60 (1H, br s, NH). 13C NMR (62.47 MHz, DMSO-d6)
:
completion of the reaction, the solvent was removed under vacuum
and the residue crystallized from CH2Cl2/n-hexane (1:3) and the
product 5a was obtained as a yellow solid in 60% yield.
d
d
:
2.2.1. Dimethyl 6,7,8,9-tetrachloro-3-(cyclohexylamino)-5,10-dioxo-
5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylate
(5i). White powder (0.35 g, 64%); mp >300 ꢀC. IR (KBr) cmꢁ1: 3272,
3123, 2911, 2850, 1637, 1571, 1337, 1299, 1200. H NMR (300.13 MHz,
DMSO-d6) d: 1.01e1.85 (10H, m, 5CH2 of cyclohexyl), 3.41 (3H, s, OMe),
42.6, 48.7, 52.3, 62.1, 64.8, 124.9, 126.7, 126.8, 127.1, 128.3, 128.4,
130.9,131.6,133.4,138.5,139.3,163.5,164.5,173.9,174.4. MS, m/z (%):
559 (Mþ, 5), 497 (5), 450 (10), 393 (25), 311 (25), 289 (40), 267 (45),
215 (60), 191 (80), 108 (60), 56 (100). Anal. Calcd for C22H15Cl4N3O6:
C, 47.25; H, 2.70; N, 7.51; found C, 47.23; H, 2.67; N, 7.55.
1
3.44 (3H, s, OMe), 3.64 (1H, br s, NHCH), 4.29 (1H, s, CHCO), 8.60 (1H, d,
3J¼7.5 Hz, NH). 13C NMR (75.47 MHz, DMSO-d6)
d
: 24.2, 25.6, 32.2, 48.5,
2.2.3. Diethyl 6,7,8,9-tetrachloro-5,10-dioxo-3-(2,4,4-
trimethylpentan-2-ylamino)-5,10-dihydro-1H-pyrazolo[1,2-b]phtha-
lazine-1,2-dicarboxylate (5k). White powder (0.36 g, 59%); mp
175e178 ꢀC. IR (KBr) cmꢁ1: 3444, 2963, 1747, 1683, 1627, 1538, 1335,
49.8, 56.5, 62.7, 62.8, 127.3, 128.3, 132.1, 132.4, 135.8, 136.0, 138.5, 162.1,
162.9, 164.1, 165.5. MS, m/z (%): 551 (Mþ, 10), 489 (5), 450 (10), 411 (20),
371 (15), 329 (30), 267 (45), 171 (60), 121 (60), 56 (100). Anal. Calcd for
C21H19Cl4N3O6: C, 45.76; H, 3.47; N, 7.62; found: C, 45.73; H, 3.45; N, 7.61.
1297. 1H NMR (250.13 MHz, DMSO-d6)
d
: 0.98 (15H, br, 5CH3), 1.32
(6H, br, 2CH3), 1.56 (2H, br, CH2), 4.01 (5H, br, 2OCH2 and CHCO),
7.92 (1H, br, NH). 13C NMR (62.47 MHz, DMSO-d6)
: 14.1, 14.4, 27.0,
31.4, 31.6, 52.4, 55.3, 58.0, 58.2, 62.5, 85.3, 122.1, 124.3, 128.3, 131.4,
2.2.2. Dimethyl
3-(benzylamino)-6,7,8,9-tetrachloro-5,10-dioxo-
d
5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylate

6144
S. Keshipour et al. / Tetrahedron 68 (2012) 6141e6145
Fig. 3. Investigation of the MCR.
Scheme 2. Proposed mechanism for the formation of compounds 5aeo.
137.1, 139.4, 149.7, 155.2, 159.1, 167.1, 170.3. MS, m/z (%): 609 (Mþ,
10), 592 (15), 562 (15), 550 (5), 478 (10), 422 (20), 397 (15), 321 (15),
295 (50), 267 (40), 99 (100). Anal. Calcd for C25H29Cl4N3O6: C,
49.28; H, 4.80; N, 6.90; found C, 49.25; H, 4.77; N, 6.91.
150.1, 159.8, 161.2, 165.9, 169.9. MS, m/z (%): 365 (Mþ, 10), 334 (25), 299
(30), 267 (80), 223 (65), 186 (45), 112 (60), 99 (100). Anal. Calcd for
C17H23N3O6: C, 55.88; H, 6.34; N, 11.50; found C, 55.87; H, 6.43; N, 11.51.
2.2.6. Dimethyl 3-(cyclohexylamino)-5,8-dioxo-5,8-dihydro-1H-pyr-
2.2.4. Dimethyl
5,6,7,8-tetrahydro-1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylate
(5l). White powder (0.28 g, 72%); mp 179e182 ꢀC. IR (KBr) cmꢁ1
3308, 3205, 2960, 1716,1615,1506, 1453,1208. 1H NMR (250.13 MHz,
DMSO-d6) : 0.99 (9H, s, 3CH3), 1.33 (6H, s, 2CH3), 1.57 (2H, br, CH2),
2.37e2.56(4H, m,2CH2),3.75(3H,s,OMe),3.79(3H, s,OMe), 5.94(1H,
s, CHCO), 9.82 (1H, br, NH). 13C NMR (62.47 MHz, DMSO-d6)
: 26.7,
27.2, 28.4, 29.0, 29.3, 31.4, 34.9, 52.2, 52.5, 55.6, 91.9,153.2,160.9,170.5,
174.2,174.7. MS, m/z (%): 395 (Mþ,15), 380 (10), 351 (20), 336 (25), 311
(15), 291 (35), 267 (65), 207 (60), 99 (70), 56 (100). Anal. Calcd for
C19H29N3O6:C, 57.71;H, 7.39;N,10.63;foundC, 57.72;H, 7.43;N,10.61.
5,8-dioxo-3-(2,4,4-trimethylpentan-2-ylamino)-
azolo[1,2-a]pyridazine-1,2-dicarboxylate
(0.21 g, 59%); mp 204e207 ꢀC. IR (KBr) cmꢁ1: 3452, 2933, 2853,1709,
1656, 1592, 1536, 1453, 1194. 1H NMR (250.13 MHz, DMSO-d6)
d:
(5n). White
powder
:
1.24e1.64 (10H, m, 5CH2 ofcyclohexyl), 3.18 (1H, br, NHCH), 3.38 (6H,
d
br, 2OMe), 3.98 (1H, s, CHCO), 6.95 (2H, br, 2CH), 7.72 (1H, br s, NH).
13C NMR (62.47 MHz, DMSO-d6)
d: 24.1, 25.5, 32.9, 47.1, 55.3, 58.6,
d
62.5, 84.4, 129.0, 129.8, 151.7, 157.9, 160.4, 165.1, 167.8. MS, m/z (%):
363 (Mþ,15), 332 (10), 304 (20), 280 (15), 265 (40), 219 (35),199 (45),
161 (60), 110 (70), 99 (90), 56 (100). Anal. Calcd for C17H21N3O6: C,
56.19; H, 5.83; N, 11.56; found C, 56.13; H, 5.81; N, 11.52.
2.2.7. Diethyl 3-(cyclohexylamino)-5,8-dioxo-5,8-dihydro-1H-pyr-
2.2.5. Dimethyl 3-(cyclohexylamino)-5,8-dioxo-5,6,7,8-tetrahydro-
azolo[1,2-a]pyridazine-1,2-dicarboxylate
(0.24 g, 61%); mp 145e148 ꢀC. IR (KBr) cmꢁ1: 3388, 2934, 2857,1739,
1651,1539,1202. 1H NMR (250.13 MHz, DMSO-d6)
: 1.21e1.65 (16H,
(5o). Yellow
powder
1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylate (5m). Yellow pow-
der (0.24 g, 67%); mp 290 ꢀC. IR (KBr) cmꢁ1: 3375, 2932, 2856,1739,1650,
d
1
1537, 1445, 1202. H NMR (300.13 MHz, CDCl3)
d: 1.23e1.77 (10H, m,
m, 5CH2 of cyclohexyl and 2CH3), 2.98 (1H, br, NHCH), 3.57e4.10 (5H,
3
5CH2 of cyclohexyl), 2.61 (4H, br, 2CH2), 2.80 (1H, br, NHCH), 3.70 (3H, s,
br, 2OCH2 and CHCO), 6.34 (1H, d, JHH¼6.8 Hz, CH), 6.95 (1H, d,
OMe), 3.83 (3H, s, OMe), 3.88 (1H, s, CHCO), 7.75 (1H, br s, NH). 13C NMR
3JHH¼6.8 Hz, CH), 7.15 (1H, br s, NH).13C NMR (62.47 MHz, DMSO-d6)
(75.47 MHz, CDCl3)
d: 24.4, 25.5, 32.7, 48.7, 49.3, 50.6, 51.7, 59.2, 67.2, 83.4,
d: 14.4, 14.9, 24.1, 25.5, 32.8, 48.9, 56.3, 58.3, 62.3, 81.2, 128.1, 129.9,

S. Keshipour et al. / Tetrahedron 68 (2012) 6141e6145
6145
151.2, 157.7, 160.6, 164.3, 165.9. MS, m/z (%): 391 (Mþ, 15), 386 (15),
References and notes
373 (10), 365 (25), 346 (25), 293 (30), 287 (45), 211 (60),187 (50),110
(80), 99 (100). Anal. Calcd for C19H25N3O6: C, 58.30; H, 6.44; N,10.74;
found C, 58.23; H, 6.51; N, 10.79.
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R. J. Org. Chem. 1974, 39, 3187e3191; (d) Heine, H. W.; Baclawski, L. M.;
Bonser, S. M.; Wachob, G. D. J. Org. Chem. 1976, 41, 3229e3232; (e) Sher-
adsky, T.; Moshenberg, R. J. Org. Chem. 1986, 51, 3123e3125; (f) Jungheim, L.
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2.2.8. 3-(Cyclohexylamino)-7-(hydrazinecarbonyl)-1,2-
bis(methoxycarbonyl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]
phthalazine-8-carboxylic acid (12). Yellow powder (0.39 g, 76%);
mp >300 ꢀC. IR (KBr) cmꢁ1: 3526, 3173, 2929, 2857, 1742, 1655,
1559, 1363. 1H NMR (300.13 MHz, DMSO-d6)
d: 1.00e1.96 (10H, m,
5CH2 of cyclohexyl), 2.92 (1H, br, NHCH), 3.40 (3H, s, OCH3), 3.43
(3H, s, OCH3), 5.13 (1H, s, CHCO), 8.27 (1H, s, CHeAr), 8.45 (2H, br,
NHCO and NHCH), 8.65 (1H, s, CHeAr), 11.93 (3H, br, NH2 and OH).
MS, m/z (%): 514 (Mþꢁ1, 5), 431 (5), 380 (30), 337 (20), 299 (65), 246
(90), 188 (65), 160 (95), 56 (100). Anal. Calcd for C23H25N5O9: C,
53.59; H, 4.89; N, 13.59; found C, 53.51; H, 4.91; N, 13.58.
3. Marsden, S. P. Nat. Chem. 2009, 1, 685e687.
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6. Drew, H. D. K.; Hatt, H. H. J. Chem. Soc. 1937, 16e26.
2.2.9. Dimethyl 3-(cyclohexylamino)-7-((1,3-dioxo-1,3-
dihydroisobenzofuran-5-yl)(hydrazono)methyl)-5,10-dioxo-5,10-
dihydro-1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylate
7. (a) Sinkkonen, J.; Ovcharenko, V.; Zelenin, K. N.; Bezhan, I. P.; Chakchir, B. A.; Al-
Assar, F.; Pihlaja, K. Eur. J. Org. Chem. 2002, 2046e2053; (b) Sinkkonen, J.; Ov-
charenko, V.; Zelenin, K. N.; Bezhan, I. P.; Chakchir, B. A.; Al-Assar, F.; Pihlaja, K.
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(13). Yellow powder (0.42 g, 70%); mp 149e152 ꢀC. IR (KBr) cmꢁ1
:
3381, 2933, 2853,1826,1734,1664,1533,1244.1H NMR (300.13 MHz,
DMSO-d6) : 1.18e1.75 (10H, m, 5CH2 of cyclohexyl), 3.41e3.76 (7H,
d
br, NHCH, 2OMe), 4.34 (1H, s, CHCO), 7.24 (2H, br, NH2), 7.90e8.39
(6H, m, CHeAr). MS, m/z (%): 529 (Mþꢁ72, 5), 504 (5), 484 (5), 458
(15), 431 (15), 403 (10), 376 (25), 322 (20), 303 (15), 277(15),174 (25),
103 (30), 86 (45), 56 (100). Anal. Calcd for C30H27N5O9: C, 59.90; H,
4.52; N, 11.64; found C, 59.81; H, 4.49; N, 11.71.
8. Teimouri, M. B. Tetrahedron 2006, 62, 10849e10853.
9. Multi-Component Reactions; Zhu, J., Bienayme, H., Eds.; Wiley-VCH: Weinheim,
Germany, 2005.
ꢀ
10. (a) Shaabani, A.; Maleki, A.; Rezayan, A. H.; Sarvary, A. Mol. Diversity 2011, 15,
€
41e68; (b) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168e3210; (c)
€
Domling, A. Chem. Rev. 2006, 106, 17e89.
11. (a) Shaabani, A.; Soleimani, E.; Rezayan, A. H.; Sarvary, A.; Khavasi, H. R. Org.
Lett. 2008, 10, 2581e2584; (b) Shaabani, A.; Rezayan, A. H.; Keshipour, S.; Sar-
vary, A.; Ng, S. W. Org. Lett. 2009, 11, 3342e3345; (c) Shaabani, A.; Sarvary, A.;
Keshipour, S.; Rezayan, A. H.; Ghadari, R. Tetrahedron 2010, 66, 1911e1914; (d)
Shaabani, A.; Sarvary, A.; Rezayan, A. H.; Keshipour, S. Tetrahedron 2009, 65,
3492e3495; (e) Shaabani, A.; Keshipour, S.; Shaabani, S.; Mahyari, M. Tetrahe-
dron Lett. 2012, 53, 1641e1644.
Acknowledgements
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University.