A new, one-pot, multi-component synthesis of imines of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines

Article abstract of DOI:10.1016/j.tet.2008.09.002

An efficient, one-pot, multi-component synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines is described. Heating?a mixture of a 2-aminopyridine, 2-aminopyrazine or 2-aminopyrimidine, a benzaldehyde, and imidazoline-2,4,5-trione under solvent-free conditions afforded imine derivatives of the title compounds in excellent yields. Single-crystal X-ray analysis conclusively confirms the structure of these bridgehead bicyclic 5-6 heterocycles.

Full text of DOI:10.1016/j.tet.2008.09.002

Tetrahedron 64 (2008) 10681–10686
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A new, one-pot, multi-component synthesis of imines of 3-amino-
2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines,
and 3-amino-2-arylimidazo[1,2-a]pyrimidines
,
a
b
c
Mehdi Adib a , Esmail Sheibani , Hamid Reza Bijanzadeh , Long-Guan Zhu
*
a School of Chemistry, University College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
b Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
c Chemistry Department, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2008
Received in revised form 20 August 2008
Accepted 4 September 2008
Available online 11 September 2008
An efficient, one-pot, multi-component synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-
2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines is described. Heating a
mixture of a 2-aminopyridine, 2-aminopyrazine or 2-aminopyrimidine, a benzaldehyde, and imidazoline-
2,4,5-trione under solvent-free conditions afforded imine derivatives of the title compounds in excellent
yields. Single-crystal X-ray analysis conclusively confirms the structure of these bridgehead bicyclic 5–6
heterocycles.
Keywords:
2-Aminopyridines
Ó 2008 Published by Elsevier Ltd.
2-Aminopyrazine
2-Aminopyrimidine
Benzaldehydes
Imidazoline-2,4,5-trione
3-Amino-2-arylimidazo[1,2-a]pyridines
3-Amino-2-arylimidazo[1,2-a]pyrazines
3-Amino-2-arylimidazo[1,2-a]pyrimidines
Multi-component reactions
1. Introduction
Compounds containing imidazo[1,2-a]pyridine ring system
have been shown to possess antibacterial, anthelmintic, antiin-
Multi-component reactions (MCRs) have emerged as an efficient
and powerful tool in modern synthetic organic chemistry due to
their valued features such as atom economy, straightforward re-
action design, and the opportunity to construct target compounds
by the introduction of several diversity elements in a single
chemical event. Typically, purification of products resulting from
MCRs is also simple since all the organic reagents employed are
consumed and are incorporated into the target compound.1 MCRs,
leading to interesting heterocyclic scaffolds, are particularly useful
for the construction of diverse chemical libraries of ‘drug-like’
molecules.
flammatory, anticonvulsant, hypnotic (e.g., zolpidem; Fig. 1), gas-
trointestinal, and immunomodulatory activities.2
Some imidazo[1,2-a]pyrazines have exhibited chemi- and bio-
luminescence reactivities.4 Compound 1 (Fig.1) is a selective GABAA
a2/a
3 agonist for the treatment of anxiety.5 Some examples have
also been used in the treatment of kinase-implicated disorders.6
Derivatives containing the imidazo[1,2-a]pyrimidine ring sys-
tem have been shown to possess antiinflammatory, analgesic,
O
N
Et
Me
MeO
Et
N
O
N
N
N
Imidazo[1,2-a]pyridines, -pyrazines, and -pyrimidines, nitro-
gen-bridgehead fused heterocycles containing an imidazole ring,
are a common structural motif in pharmacologically important
molecules, with activities spanning a diverse range of targets.2,3
N
N
N
Ph
Me
NC
Me
CH2CONMe2
F
F
1, a selective GABAA agonist
Divaplon
Zolpidem
* Corresponding author. Tel./fax: þ98 21 66495291.
E-mail address: madib@khayam.ut.ac.ir (M. Adib).
Figure 1. Examples of imidazo[1,2-a]pyridines, -pyrazines, and -pyrimidines with
pharmaceutical and/or pharmacological activity.
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.09.002

10682
M. Adib et al. / Tetrahedron 64 (2008) 10681–10686
Table 1
antipyretic, bronchodilator, anxiolytic (e.g., divaplon; Fig. 1), and
antifungal activities.7
Multi-component synthesis of imidazo[1,2-a]pyridines
R
There are several methods reported in the literature for the
preparation of 2- or 3-substituted imidazo[1,2-a]pyridines with the
majority relying on the condensation of 2-aminopyridine with
R
O
O
solvent-free
200 °C, 5 min
+ ArCHO +
N
HN
NH
N
N
NH2
a
-bromoketones to form the five-membered cyclic system.2
O
6
ArCH
N
Ar
Particularly interesting are those structures that contain an amino
group at C-2 or C-3. There are well established methods for the
preparation of 3-aminoimidazo[1,2-a]pyridines; these include ni-
tration at C-3 of the already formed heterocycle and subsequent
7
4
5
7
a
R
Ar
% Yielda
95
reduction,8
a multi-component reaction between 2-amino-
H
pyridines, aldehydes, and isonitriles9–11 or preparation from
pyridinium fluorides,12 Strecker-type reaction between 2-amino-
pyridines, cyanide ions, and a limited number of aldehydes,13a ionic
liquid promoted reaction between an 2-aminoazine, an aldehyde,
and trimethylsilylcyanide,13b or by use of benzotriazole as an
auxiliary group.14 Most of these methods involve three or more
sequential synthetic steps, the use of harsh reaction conditions that
give low yields, and in some cases, use of hazardous or expensive
starting materials.
b
c
H
H
H
92
92
94
CH3
H3C
d
CH3O
CH3O
F
To date, the most common synthetic methods reported for the
preparation of imidazo[l,2-a]pyrazine and imidazo[1,2-a]pyrimi-
dine ring systems involve closure of the imidazole ring by the
condensation of 2-aminopyrazine or 2-aminopyrimidine and clo-
sure of the pyrazine or pyrimidine ring by the condensation of
2-aminoimidazole with appropriate electrophilic compounds.3
e
f
6-CH3
6-CH3
97
97
g
7-CH3
6-CH3
94
92
CH3O
CH3
2. Results and discussion
h
As part of our continuing efforts on the development of new
routes for the preparation of biologically active heterocyclic com-
pounds,15 we recently described two new syntheses of fused im-
idazoles: imidazo[1,2-a]pyridin-3-ones 2 via condensation reaction
of 2-aminopyridines with diaroylacetylenes16 and imidazo[1,2-
i
8-CH3
93
CH3O
a
Isolated yields.
a]pyridines
3 via a catalyst-free reaction between 2-amino-
pyridines, aldehydes, and isocyanides in water.17
structure. The 1H NMR spectrum of 7d exhibited three sharp sin-
glets, arising from the two CH3O ( 3.81 and 3.82 ppm) and aldi-
mine ( 8.67 ppm) groups along with characteristic multiplets with
appropriate chemical shifts and coupling constants for the four H
atoms of the electron-rich diene moiety of the six-membered ring
and the eight H atoms of the two aryl substituents. The 1H-
decoupled 13C NMR spectrum of 7d showed 18 distinct resonances,
in agreement with the proposed structure.
The isolated imidazo[l,2-a]azines 9a–h were characterized on
the basis of their elemental analyses and IR, 1H NMR, and 13C NMR
spectra. The nature of these products was apparent from their mass
spectra, which displayed molecular ion peaks at the appropriate m/z
values. The 1H NMR spectrum of 9f exhibited three sharp singlets,
O
N
d
N
N
N
d
Ar
R
O
N
Ar
Ar
H
2
3
Considering the important biological properties of imidazo[1,2-
a]pyridines, imidazo[1,2-a]pyrazines, and imidazo[1,2-a]pyrimi-
dines we report herein18 an efficient simple synthesis of these
nuclei using simple starting materials bearing in mind previously
reported syntheses. Thus, a mixture of 2-aminopyridines 4 or 2-
aminoazines 8, benzaldehydes 5, and imidazoline-2,4,5-trione 6
were found to undergo a new one-pot multi-component reaction
at 200 ꢀC within 5 min under solvent-free conditions to produce
3-amino-2-arylimidazo[1,2-a]pyridines 7a–i (Table 1), 3-amino-2-
arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]-
pyrimidines 9a–j in 92–97% yields (Table 2).
arising from the two methyl (d 2.37 and 2.41 ppm) and aldimine
(d
8.80 ppm) groups along with four doublets with appropriate
chemical shifts and coupling constants for the eight H atoms of the
two aryl substituents. Three characteristic doublet of doublets
When the reaction was performed using equivalent ratios of
2-aminopyridine (4, R¼H), benzaldehyde (5, Ar¼C6H5), and imi-
dazoline-2,4,5-trione 6, 1H NMR analysis of the reaction mixture
indicated the formation of imidazo[1,2-a]pyridine 7a in nearly 45%
(
d
6.87, 8.50, and 8.63 ppm; J¼6.8, 4.1, and 2.0 Hz) were seen for the
three mutually coupling CHs in positions 5, 6, and 7 of the bicyclic
ring. The 1H-decoupled 13C NMR spectrum of 9f showed 17 distinct
resonances, in agreement with the suggested structure. Partial
assignments of these resonances are given in Section 4.
Single-crystal X-ray analysis of 7d confirmed conclusively the
structure of the isolated products. An ORTEP diagram of 7d is
shown in Figure 2.19
yield. Almost half of the 2-aminopyridine
4 was recovered
unreacted at the end of the reaction. The best results were obtained
when the reactions were carried out using the three components in
a ratio of 1:2.5:1.5 (see Section 4).
The structures of imidazo[1,2-a]pyridines 7a–i were confirmed
by IR, 1H and 13C NMR spectroscopy, mass spectrometry, and ele-
mental analysis. The mass spectrum of 7d displayed the molecular
ion (Mþ) peak at m/z 357, which was consistent with the product
Although we have not yet established the mechanism of the
reaction between 2-aminopyridines or 2-aminoazines, benzalde-
hydes, and imidazoline-2,4,5-trione in an experimental manner,
a mechanistic rationalization for this reaction is provided in

M. Adib et al. / Tetrahedron 64 (2008) 10681–10686
10683
Table 2
Multi-component synthesis of imidazo[1,2-a]pyrazines and imidazo[1,2-a]-
pyrimidines
Ar
+ ArCHO
+ArCHO
N
Ar
N
10
+
..
AcO_
AcO_
N
NH2
O
O_N
N
X
H
N
+
O
O
Y
X
N
O
Ar
Ar
+
N
Y
AcOH
solvent-free
200 °C, 5 min
N
O
+
NH2
ArCHO +
N
O
HN
NH
O
N
N
H
N
O
O
O
N
H
H
11
O
6
ArCH
N
Ar
12
9
8
5
Ar
+
+
9
a
X, Y
Ar
% Yielda
95
AcO_
AcO_
N
AcO_
+
N
N
N
N
N
O_
_CO2
_
+
O
+
7
Ar
Ar
Ar
N
_HNCO
N
N
X¼N, Y¼CH
X¼N, Y¼CH
Ar
Ar
O
O
H
_AcOH
N
O
O
O
N
N
H
O
O
b
c
92
92
H
H
CH3O
13
14
15
Scheme 1.
X¼N, Y¼CH
X¼N, Y¼CH
CH3
d
94
adjacent carbonyl group would yield epoxide intermediate 13,
which may undergo ring opening to form ylide 14. This ylide may
undergo intramolecular cyclization to dihydroimidazo[1,2-a]pyri-
dine intermediate 15 from which a carbon dioxide, an isocyanic
acid, and an acetic acid molecule may be removed to afford the
imidazo[1,2-a]pyridine 7.
H3C
e
f
X¼CH, Y¼N
X¼CH, Y¼N
96
94
CH3
3. Conclusion
g
X¼CH, Y¼N
97
97
H3C
In conclusion, we have developed a new, efficient, one-pot
multi-component synthesis of 3-amino-2-arylimidazo[1,2-a]pyr-
idine, 3-amino-2-arylimidazo[1,2-a]pyrazine, and 3-amino-2-
arylimidazo[1,2-a]pyrimidine imine derivatives of potential
synthetic and pharmacological interest. Solvent-free conditions,
excellent yields of the products, and use of simple starting
materials are the main advantages of this method. The simplicity
of this method makes it an interesting alternative to other
approaches.
h
X¼CH, Y¼N
CH3O
a
Isolated yields.
Scheme 1 (exemplified by 4, R¼H). The first step may involve
condensation of the aldehyde with 2-aminopyridine and imidazo-
line-2,4,5-trione with formation of aldimine 10 and imidazolium
ion 11, respectively. Then the imidazolium ion 11 is probably
attacked by the pyridine-N atom of the aldimine 10 leading to ad-
duct 12. Intramolecular nucleophilic addition of alkoxide to the
4. Experimental
4.1. General
2-Aminopyridines, 2-aminopyrazine, 2-aminopyrimidine, and
aromatic aldehydes were obtained from Merck (Germany) and
were used without further purification. Imidazoline-2,4,5-trione
was prepared according to the procedure.20 Melting points were
measured on an Electrothermal 9100 apparatus. Elemental
analyses for C, H, and N were performed using a Heraeus CHN-
O-Rapid analyzer. Mass spectra were recorded on an Agilent
Technologies (HP) 5973 mass spectrometer operating at an
ionization potential of 20 eV. 1H and 13C NMR spectra were
measured with Bruker DRX-500 AVANCE (at 500.1 and
125.8 MHz) spectrometer using CDCl3 solvent with TMS as an
internal standard. IR spectra were recorded on a Shimadzu IR-
460 spectrometer. Chromatography columns were prepared from
Merck silica gel 60 mesh.
4.2. General procedure
A mixture of the appropriate 2-aminopyridine or 2-aminoazine,
4 or 8 (2 mmol), the appropriate aldehyde (5 mmol), and imida-
zoline-2,4,5-trione (0.342 g, 3 mmol) was stirred at 200 ꢀC for
5 min. Then the reaction mixture was cooled to room temperature
and the residue was purified by column chromatography using
n-hexane–ethyl acetate (1:3) as eluent. The solvent was removed
and the product was recrystallized from 1:2 n-hexane–EtOAc.
Figure 2. ORTEP diagram of the structure of 7d.

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M. Adib et al. / Tetrahedron 64 (2008) 10681–10686
4.2.1. 2-Phenyl-N3-[(E)-1-phenylmethylidene]imidazo[1,2-
a]pyridin-3-amine (7a)
4.2.5. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
methylidene]-6-methylimidazo[1,2-a]pyridin-3-amine (7e)
Yellow crystals, mp 189–190 ꢀC, yield: 0.72 g, 97%. IR (KBr) (nmax
Yellow crystals, mp 161–163 ꢀC, yield: 0.56 g, 95% (relative to 2-
aminopyridine). IR (KBr) (nmax/cmꢁ1): 1604, 1575, 1497, 1435, 1416,
1362, 1301, 1275, 1239, 1214, 1100, 1043, 804, 765, 690. MS m/z (%):
297 (Mþ, 100), 208 (19), 194 (15), 181 (63), 105 (21), 91 (16), 78 (39),
68 (21), 52 (43). Anal. Calcd for C20H15N3 (297.36): C, 80.78; H, 5.08;
N, 14.13. Found: C, 80.9; H, 5.2; N, 14.0%. 1H NMR (500.1 MHz,
/
cmꢁ1): 1610, 1580, 1537, 1514, 1348, 1302, 1252, 1163, 1109, 1080,
1028, 852, 802, 731. MS m/z (%): 371 (Mþ, 25), 364 (6), 325 (13), 225
(20), 195 (11), 149 (10), 135 (16), 114 (21), 92 (11), 84 (100). Anal.
Calcd for C23H21N3O2 (371.44): C, 74.37; H, 5.70; N, 11.31. Found: C,
74.4; H, 5.8; N, 11.2%. 1H NMR (500.1 MHz, CDCl3):
d 2.37 (3H, s,
CDCl3):
d
6.89 (1H, t, J¼6.7 Hz, CH), 7.24 (1H, dd, J¼7.5 and 7.6 Hz,
CH3), 3.85 and 3.87 (6H, 2s, 2CH3), 6.94 (2H, d, J¼8.8 Hz, 2CH), 6.97
(2H, d, J¼8.8 Hz, 2CH), 7.06 (1H, dd, J¼1.6 and 9.1 Hz, CH), 7.50 (1H,
d, J¼9.1 Hz, CH), 7.73 (2H, d, J¼8.8 Hz, 2CH), 7.79 (2H, d, J¼8.8 Hz,
2CH), 8.16 (1H, d, J¼1.6 Hz, CH), 8.70 (1H, s, CH). 13C NMR
1CH), 7.36 (1H, t, J¼7.4 Hz, CH), 7.40–7.48 (5H, m, 5CH), 7.60 (1H, d,
J¼9.0 Hz, 1CH), 7.83 (2H, d, J¼7.5 Hz, 2CH), 7.84 (2H, d, J¼7.5 Hz,
2CH), 8.46 (1H, d, J¼6.8 Hz, CH), 8.79 (1H, s, CH). 13C NMR
(125.8 MHz, CDCl3):
d
113.0, 118.0, 123.9, 125.7, 128.5, 128.9, 129.0,
(125.8 MHz, CDCl3): d 18.4 (CH3), 55.3 and 55.5 (2CH3), 114.2, 114.3,
129.3, 129.4 and 131.9 (10CH), 135.5, 137.1 and 143.6 (3C), 157.9
(CH).
116.4 and 120.8 (4CH), 121.9 and 127.3 (2C), 127.9 (CH), 128.7 (C),
129.6 and 130.0 (2CH), 132.8 and 141.7 (2C), 157.0 (CH), 159.3 and
162.4 (2C–O).
4.2.2. 2-(4-Methylphenyl)-N3-[(E)-1-(4-methylphenyl)-
methylidene]imidazo[1,2-a]pyridin-3-amine (7b)
4.2.6. 2-(4-Fluorophenyl)-N3-[(E)-1-(4-fluorophenyl)methylidene]-
Yellow crystals, mp 154–155 ꢀC, yield: 0.60 g, 92%. IR (KBr) (nmax
/
6-methylimidazo[1,2-a]pyridin-3-amine (7f)
cmꢁ1): 1601, 1574, 1502, 1435, 1414, 1366, 1340, 1304, 1271, 1236,
1188, 1175, 1109, 1067, 1043, 1020, 926, 825, 779, 752, 745. MS m/z
(%): 325 (Mþ, 45), 310 (7), 220 (10), 198 (47), 183 (10), 145 (25), 135
(24), 121 (100), 105 (31), 91 (82), 84 (60), 78 (88), 67 (32), 56 (55).
Anal. Calcd for C22H19N3 (325.41): C, 81.20; H, 5.89; N, 12.91. Found:
Yellow crystals, mp 154–156 ꢀC, yield: 0.67 g, 97%. IR (KBr) (nmax
/
cmꢁ1): 1608, 1597, 1539, 1504, 1474, 1414, 1393, 1340, 1223, 1215,
1157, 1145, 1096, 842, 816. MS m/z (%): 347 (Mþ, 100), 279 (13), 213
(80), 167 (31), 149 (83), 137 (13), 123 (14), 113 (13), 92 (90), 81 (41),
69 (81), 57 (50). Anal. Calcd for C21H15F2N3 (347.37): C, 72.61; H,
4.35; N, 12.10. Found: C, 72.4; H, 4.5; N, 11.9%. 1H NMR (500.1 MHz,
C, 81.3; H, 5.9; N,12.8%. 1H NMR (500.1 MHz, CDCl3):
d 2.37 and 2.38
(6H, 2s, 2CH3), 6.79 (1H, t, J¼6.7 Hz, CH), 7.15 (1H, dt, J¼1.2 and
6.7 Hz, CH), 7.20 (2H, d, J¼8.1 Hz, 2CH), 7.22 (2H, d, J¼8.0 Hz, 2CH),
7.53 (1H, d, J¼9.0 Hz, CH), 7.69 (2H, d, J¼8.0 Hz, 2CH), 7.72 (2H, d,
J¼8.1 Hz, 2CH), 8.35 (1H, d, J¼6.7 Hz, CH), 8.73 (1H, s, CH). 13C NMR
CDCl3):
d
2.39 (3H, s, CH3), 7.08 (1H, d, J¼9.1 Hz, CH), 7.11 (2H, dd,
3 3
3JFH¼8.6 Hz, JHH¼8.7 Hz, 2CH), 7.16 (2H, dd, JFH¼8.6 Hz,
3JHH¼8.7 Hz, 2CH), 7.48 (1H, d, J¼9.1 Hz, CH), 7.77 (2H, dd,
4JFH¼5.4 Hz, JHH¼8.7 Hz, 2CH), 7.82 (2H, dd, JFH¼5.5 Hz,
3
4
(125.8 MHz, CDCl3):
d
21.3 and 21.6 (2CH3), 112.1, 117.3, 123.2, 124.7,
3JHH¼8.7 Hz, 2CH), 8.17 (1H, br s, CH), 8.67 (1H, s, CH). 13C NMR
2
128.2 and 128.3 (6CH),128.9 (C), 129.4 and 129.5 (2CH), 132.1,133.8,
134.0, 137.6, 141.8 and 142.8 (6C), 157.4 (CH).
(125.8 MHz, CDCl3):
d
18.4 (CH3), 115.8 (d, JFC¼21.6 Hz, CH), 116.0
2
(d, JFC¼22.1 Hz, CH), 116.7 and 120.9 (2CH), 122.3 and 128.4 (2C),
3
3
128.5 (CH), 130.1 (d, JFC¼8.5 Hz, CH), 130.2 (d, JFC¼8.8 Hz, CH),
4.2.3. 2-(3-Methylphenyl)-N3-[(E)-1-(3-methylphenyl)-
131.0 (d, JFC¼4.0 Hz, C), 132.7 (d, JFC¼3.1 Hz, C), 132.8 and 142.1
4
4
1
methylidene]imidazo[1,2-a]pyridin-3-amine (7c)
(2C), 155.5 (CH), 162.5 (d, JFC¼247.5 Hz, C–F), 164.7 (d,
Yellow crystals, mp 165 ꢀC, yield: 0.60 g, 92%. IR (KBr) (nmax
/
1JFC¼252.9 Hz, C–F).
cmꢁ1): 1606, 1580, 1499, 1435, 1364, 1303, 1273, 1240, 1215, 1151,
1094, 1043, 910, 885, 788, 752, 690. MS m/z (%): 325 (Mþ, 100), 310
(9), 221 (13), 195 (91), 135 (13), 121 (82), 105 (12), 94 (48), 86 (15),
84 (22), 78 (97), 67 (13). Anal. Calcd for C22H19N3 (325.41): C, 81.20;
H, 5.89; N, 12.91. Found: C, 81.2; H, 5.8; N, 12.7%. 1H NMR
4.2.7. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
methylidene]-7-methylimidazo[1,2-a]pyridin-3-amine (7g)
Yellow crystals, mp 176 ꢀC, yield: 0.70 g, 94%. IR (KBr) (nmax
/
cmꢁ1): 1603, 1572, 1514, 1366, 1306, 1254, 1167, 1134, 1107, 1018,
827, 804. MS m/z (%): 371 (Mþ, 100), 364 (5), 325 (6), 250 (9), 225
(61), 167 (8), 149 (20), 135 (12), 114 (42), 92 (36), 86 (28), 81 (11), 69
(18). Anal. Calcd for C23H21N3O2 (371.44): C, 74.37; H, 5.70; N, 11.31.
(500.1 MHz, CDCl3):
d 2.37 and 2.38 (6H, 2s, 2CH3), 6.79 (1H, dt,
J¼1.0 and 6.7 Hz, CH), 7.12–7.15 (2H, m, 2CH), 7.22 (1H, d, J¼7.8 Hz,
CH), 7.25–7.29 (2H, m, 2CH), 7.53–7.60 (3H, m, 3CH), 7.61 (1H, s,
CH), 7.70 (1H, s, CH), 8.36 (1H, d, J¼6.7 Hz, CH), 8.72 (1H, s, CH). 13C
Found: C, 74.5; H, 5.7; N, 11.1%. 1H NMR (500.1 MHz, CDCl3):
d 2.42
NMR (125.8 MHz, CDCl3):
d
21.3 and 21.5 (2CH3), 112.3, 117.3, 123.3,
(3H, s, CH3), 3.86 and 3.88 (6H, 2s, 2CH3), 6.68 (1H, dd, J¼1.2 and
7.0 Hz, CH), 6.94 (2H, d, J¼8.7 Hz, 2CH), 6.96 (2H, d, J¼8.7 Hz, 2CH),
7.32 (1H, d, J¼1.2 Hz, CH), 7.75 (2H, d, J¼8.7 Hz, 2CH), 7.78 (2H, d,
J¼8.7 Hz, 2CH), 8.28 (1H, d, J¼7.0 Hz, CH), 8.7 (1H, s, CH). 13C NMR
124.9, 125.2, 125.7, 128.6, 128.7, 128.8 and 128.9 (10CH), 129.0 (C),
129.4 and 132.1 (2CH), 134.0, 134.9, 136.5, 138.4, 138.5 and 142.9
(6C), 157.5 (CH).
(125.8 MHz, CDCl3): d 21.4 (CH3), 55.3 and 55.5 (2CH3), 114.2, 114.3,
4.2.4. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
methylidene]imidazo[1,2-a]pyridin-3-amine (7d)
114.8, 115.6 and 122.4 (5CH), 127.5 and 128.5 (2C), 129.6 (CH), 129.7
(C), 129.9 (CH), 133.5, 135.2 and 143.1 (3C), 156.2 (CH), 159.3 and
162.3 (2C–O).
Yellow crystals, mp 175 ꢀC, yield: 0.67 g, 94%. IR (KBr) (nmax
/
cmꢁ1): 1605, 1575, 1517, 1475, 1362, 1310, 1239, 1169, 1097, 1067,
1036, 825, 769, 751. MS m/z (%): 357 (Mþ, 100), 342 (8), 239 (9),
211 (88), 196 (9), 178 (5), 78 (72). Anal. Calcd for C22H19N3O2
(357.41): C, 73.93; H, 5.36; N, 11.76. Found: C, 73.8; H, 5.4; N,
4.2.8. 6-Methyl-2-(4-methylphenyl)-N3-[(E)-1-(4-methylphenyl)-
methylidene]imidazo[1,2-a]pyridin-3-amine (7h)
Yellow crystals, mp 139–140 ꢀC, yield: 0.62 g, 92%. IR (KBr) (nmax
/
11.6%. 1H NMR (300.1 MHz, CDCl3):
d
3.81 and 3.82 (6H, 2s,
cmꢁ1): 1626, 1574, 1510, 1500, 1407, 1400, 1344, 1278, 1248, 1200,
1175, 1162, 1105, 1054, 964, 825, 800, 766, 725. MS m/z (%): 339 (Mþ,
100), 325 (78), 312 (15), 297 (15), 234 (26), 209 (77), 195 (55), 92
(32), 78 (30), 65 (15). Anal. Calcd for C23H21N3 (339.44): C, 81.38; H,
6.24; N, 12.38. Found: C, 81.5; H, 6.4; N, 12.2%. 1H NMR (250.1 MHz,
2CH3), 6.79 (1H, dt, J¼1.0 and 6.8 Hz, CH), 6.91 (2H, d, J¼8.7 Hz,
2CH), 6.93 (2H, d, J¼8.8 Hz, 2CH), 7.14 (1H, ddd, J¼1.3, 6.6, and
6.7 Hz, CH), 7.54 (1H, d, J¼9.0 Hz, CH), 7.74 (2H, d, J¼8.7 Hz,
2CH), 7.76 (2H, d, J¼8.8 Hz, 2CH), 8.32 (1H, d, J¼6.8 Hz, CH), 8.67
(1H, s, CH). 13C NMR (75.5 MHz, CDCl3):
d
55.2 and 55.4 (2CH3),
CDCl3):
d
2.37, 2.38, and 2.42 (9H, 3s, 3CH3), 7.04 (1H, dd, J¼1.5 and
112.2, 114.1, 114.2, 116.9, 123.1 and 124.8 (6CH), 126.9, 128.8 and
129.3 (3C), 129.5 and 130.0 (2CH), 132.6 and 142.3 (2C), 157.3
(CH), 159.3 and 162.3 (2C).
9.0 Hz, CH), 7.21 (2H, d, J¼8.0 Hz, 2CH), 7.26 (2H, d, J¼8.3 Hz, 2CH),
7.46 (1H, d, J¼9.0 Hz, CH), 7.70 (2H, d, J¼8.0 Hz, 2CH), 7.72 (2H, d,
J¼8.3 Hz, 2CH), 8.18 (1H, d, J¼1.5 Hz, CH), 8.75 (1H, s, CH). 13C NMR

M. Adib et al. / Tetrahedron 64 (2008) 10681–10686
10685
(62.9 MHz, CDCl3):
d
18.4, 21.3, and 21.6 (3CH3), 116.6 and 120.9
130.9, 133.3, 136.1, and 137.8 (6C), 138.4 (CH), 142.9 (C), 143.4 and
160.8 (2CH).
(2CH), 121.8 (C), 127.9, 128.1, and 128.3 (3CH), 128.8 (C), 129.4 and
129.5 (2CH), 132.2, 133.8, 134.0, 137.4, 141.7, and 142.0 (6C), 157.2
(CH).
4.2.13. 2-(3-Methylphenyl)-N3-[(E)-1-(3-methylphenyl)-
methylidene]imidazo[1,2-a]pyrazin-3-amine (9d)
4.2.9. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
Yellow crystals, mp 149–150 ꢀC, yield: 0.61 g, 94%. IR (KBr)
methylidene]-8-methylimidazo[1,2-a]pyridin-3-amine (7i)
(
nmax/cmꢁ1): 1612, 1578, 1492, 1357, 1313, 1256, 1207, 1182, 1111,
Yellow crystals, mp 155–156 ꢀC, yield: 0.69 g, 93%. IR (KBr) (nmax
/
1022, 978, 881, 793, 756, 688. MS m/z (%): 326 (Mþ, 95), 235 (6),
196 (100), 122 (13), 114 (32), 86 (26), 79 (50). Anal. Calcd for
C21H18N4 (326.40): C, 77.28; H, 5.56; N, 17.17. Found: C, 77.4; H, 5.6;
cmꢁ1): 1601, 1572, 1539, 1514, 1481, 1423, 1367, 1344, 1308, 1246,
1184, 1167, 1123, 1101, 1067, 1032, 831, 750. MS m/z (%): 371 (Mþ,
55), 364 (12), 325 (100), 253 (13), 234 (12), 225 (32), 195 (84), 149
(14), 92 (23), 83 (15), 78 (39), 69 (23), 57 (21). Anal. Calcd for
C23H21N3O2 (371.44): C, 74.37; H, 5.70; N, 11.31. Found: 74.4; H, 5.7;
N, 17.0%. 1H NMR (500.1 MHz, CDCl3):
d 2.41 and 2.43 (6H, 2s,
2CH3), 7.20 (1H, d, J¼7.6 Hz, CH), 7.30–7.38 (3H, m, 3CH), 7.58 (1H,
d, J¼7.7 Hz, CH), 7.62 (1H, d, J¼7.7 Hz, CH), 7.68 (1H, s, CH), 7.70
(1H, s, CH), 7.94 (1H, d, J¼4.6 Hz, CH), 8.28 (1H, dd, J¼1.3 and
4.6 Hz, CH), 8.78 (1H, s, CH), 9.04 (1H, d, J¼1.3 Hz, CH). 13C NMR
N, 11.2%. 1H NMR (250.1 MHz, CDCl3):
d 2.63 (3H, s, CH3), 3.85 and
3.87 (6H, 2s, 2CH3), 6.77 (1H, t, J¼6.8 Hz, CH), 6.94 (2H, d, J¼8.5 Hz,
2CH), 6.96 (2H, d, J¼8.5 Hz, 2CH), 7.01 (1H, t, J¼6.8 Hz, CH), 7.74 (2H,
d, J¼8.5 Hz, 2CH), 7.76 (2H, d, J¼8.5 Hz, 2CH), 8.28 (1H, d, J¼6.8 Hz,
(125.8 MHz, CDCl3):
d 21.3 and 21.4 (2CH3), 115.9, 125.2, 126.2,
128.7, 128.8, 129.0, 129.2, 129.3, and 129.8 (9CH), 130.1 (C), 133.0
(CH), 133.7, 135.8, 136.2, 137.9, 138.7 and 138.8 (6C), 143.5 and
161.1 (2CH).
CH), 8.67 (1H, s, CH). 13C NMR (62.9 MHz, CDCl3):
d 16.7 (CH3), 55.3
and 55.5 (2CH3), 112.2, 114.2, 114.3, 121.0 and 123.8 (5CH), 126.9,
127.5, 129.2 and 129.6 (4C), 129.9 and 130.0 (2CH), 132.6 and 142.8
(2C), 156.7 (CH), 159.3 and 162.3 (2C–O).
4.2.14. 2-Phenyl-N3-[(E)-1-phenylmethylidene]imidazo[1,2-
a]pyrimidin-3-amine (9e)
4.2.10. 2-Phenyl-N3-[(E)-1-phenylmethylidene]imidazo[1,2-
Yellow crystals, mp 194 ꢀC, yield: 0.57 g, 96%. IR (KBr) (nmax
/
a]pyrazin-3-amine (9a)
cmꢁ1): 1610, 1579, 1549, 1515, 1479, 1449, 1356, 1222, 799, 760. MS
m/z (%): 298 (Mþ, 97), 193 (29), 182 (93), 166 (12), 122 (100), 114
(10), 104 (12), 95 (13), 89 (11), 79 (56), 68 (20), 52 (20). Anal. Calcd
for C19H14N4 (298.35): C, 76.49; H, 4.73; N, 18.78. Found: 76.3; H,
Yellow crystals, mp 219–220 ꢀC, yield: 0.57 g, 95%. IR (KBr) (nmax
/
cmꢁ1): 1604, 1580, 1545, 1479, 1450, 1356, 1220, 802, 766. MS m/z
(%): 298 (Mþ, 30), 196 (24), 182 (47), 149 (14), 129 (13), 95 (100), 89
(10), 79 (38), 68 (62). Anal. Calcd for C19H14N4 (298.35): C, 76.49; H,
4.73; N, 18.78. Found: 76.5; H, 4.7; N, 18.7%. 1H NMR (500.1 MHz,
4.9; N, 18.6%. 1H NMR (500.1 MHz, CDCl3):
d
6.89 (1H, dd, J¼4.0 and
6.7 Hz, CH), 7.34 (1H, t, J¼7.2 Hz, CH), 7.39–7.45 (5H, m, 5CH), 7.80
(2H, d, J¼7.2 Hz, 2CH), 7.88 (2H, d, J¼7.6 Hz, 2CH), 8.54 (1H, dd,
J¼2.0 and 4.0 Hz, CH), 8.65 (1H, dd, J¼2.0 and 6.7 Hz, CH), 8.81 (1H,
CDCl3):
d
7.41 (1H, t, J¼7.4 Hz, CH), 7.45–7.54 (4H, m, 4CH), 7.53 (1H,
t, J¼7.4 Hz, CH), 7.84 (2H, d, J¼7.5 Hz, 2CH), 7.86 (2H, d, J¼7.5 Hz,
2CH), 7.96 (1H, d, J¼4.6 Hz, CH), 8.30 (1H, dd, J¼1.3 and 4.6 Hz, CH),
8.80 (1H, s, CH), 9.06 (1H, d, J¼1.3 Hz, CH). 13C NMR (125.8 MHz,
s, CH). 13C NMR (125.8 MHz, CDCl3):
d 108.7 (CH), 127.3 (C), 128.4,
128.5, 128.6, 128.8, 128.9, 130.7, and 131.8 (7CH), 134.2, 135.3, 136.1,
and 146.1 (4C), 150.0 and 159.2 (2CH).
CDCl3):
d 115.9, 128.4, 128.6, 128.7, 128.9, 129.0, and 129.8 (7CH),
130.0 (C), 132.2 (CH), 133.8, 135.8, 136.2, and 137.9 (4C), 143.6 and
160.8 (2CH).
4.2.15. 2-(4-Methylphenyl)-N3-[(E)-1-(4-methylphenyl)-
methylidene]imidazo[1,2-a]pyrimidin-3-amine (9f)
4.2.11. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
Yellow crystals, mp 165–167 ꢀC, yield: 0.61 g, 94%. IR (KBr) (nmax
/
methylidene]imidazo[1,2-a]pyrazin-3-amine (9b)
cmꢁ1): 1610, 1578, 1565, 1479, 1358, 1229, 1185, 1130, 1039, 999,
802, 729. MS m/z (%): 326 (Mþ, 54), 235 (4), 224 (18), 208 (4), 196
(54), 135 (5), 119 (18), 95 (100), 84 (18), 68 (52). Anal. Calcd for
C21H18N4 (326.40): C, 77.28; H, 5.56; N, 17.17. Found: C, 77.4; H, 5.8;
Yellow crystals, mp 168–170 ꢀC, yield: 0.66 g, 92%. IR (KBr) (nmax
/
cmꢁ1): 1605, 1599, 1479, 1408, 1344, 1291, 1218, 1098, 960, 825, 815,
784, 750. MS m/z (%): 358 (Mþ, 45), 343 (9), 251 (12), 212 (78), 134
(20), 107 (18), 95 (36), 79 (41), 52 (21). Anal. Calcd for C21H18N4O2
(358.40): C, 70.38; H, 5.06; N, 15.63. Found: C, 70.5; H, 5.2; N, 15.3%.
N, 17.1%. 1H NMR (500.1 MHz, CDCl3):
d 2.37 and 2.41 (6H, 2s, 2CH3),
6.87 (1H, dd, J¼4.1 and 6.8 Hz, CH), 7.22 (2H, d, J¼7.9 Hz, 2CH), 7.25
(2H, d, J¼8.0 Hz, 2CH), 7.71 (2H, d, J¼7.9 Hz, 2CH), 7.76 (2H, d,
J¼8.0 Hz, 2CH), 8.50 (1H, dd, J¼2.0 and 4.1 Hz, CH), 8.63 (1H, dd,
J¼2.0 and 6.8 Hz, CH), 8.80 (1H, s, CH). 13C NMR (125.8 MHz, CDCl3):
1H NMR (500.1 MHz, CDCl3):
d 3.86 and 3.88 (6H, 2s, 2CH3), 6.97
(2H, d, J¼8.7 Hz, 2CH), 6.98 (2H, d, J¼8.6 Hz, 2CH), 7.77 (2H, d,
J¼8.7 Hz, 2CH), 7.80 (2H, d, J¼8.6 Hz, 2CH), 7.89 (1H, d, J¼4.6 Hz,
CH), 8.22 (1H, dd, J¼1.3 and 4.6 Hz, CH), 8.73 (1H, s, CH), 9.00 (1H, d,
d
21.3 and 21.6 (2CH3), 108.5 (CH), 127.3 (C), 128.3 and 128.5 (2CH),
J¼1.3 Hz, CH). 13C NMR (125.8 MHz, CDCl3):
d
55.3 and 55.5 (2CH3),
129.3 (C), 129.5, 129.6, and 130.6 (3CH), 131.2, 133.5, 138.1, 142.4,
and 145.8 (5C), 149.6 and 159.3 (2CH).
114.3, 114.4, and 115.7 (3CH), 126.3 and 128.8 (2C), 129.5 (CH), 129.6
and 130.0 (2C), 130.6 (CH), 135.7 (C), 137.6 and 143.2 (2CH), 159.8
(C–O), 160.3 (CH), 163.0 (C–O).
4.2.16. 2-(3-Methylphenyl)-N3-[(E)-1-(3-methylphenyl)-
methylidene]imidazo[1,2-a]pyrimidin-3-amine (9g)
4.2.12. 2-(4-Methylphenyl)-N3-[(E)-1-(4-methylphenyl)-
Yellow crystals, mp 155–157 ꢀC, yield: 0.63 g, 97%. IR (KBr) (nmax
/
methylidene]imidazo[1,2-a]pyrazin-3-amine (9c)
cmꢁ1): 1602, 1578, 1545, 1516, 1479, 1450, 1358, 1326, 1223, 1175,
1040, 802, 730. MS m/z (%): 326 (Mþ, 92), 221 (54), 196 (100), 169
(5), 146 (5), 129 (7), 119 (14), 103 (8), 95 (32), 79 (44), 68 (8). Anal.
Calcd for C21H18N4 (326.40): C, 77.28; H, 5.56; N, 17.17. Found: C,
Yellow crystals, mp 155–156 ꢀC, yield: 0.60 g, 92%. IR (KBr) (nmax
/
cmꢁ1): 1609, 1600, 1566, 1483, 1411, 1346, 1294, 1222, 1176, 1107,
1032, 960, 814, 786, 752. MS m/z (%): 326 (Mþ, 79), 235 (7), 196
(100), 118 (25), 103 (9), 91 (16), 79 (50). Anal. Calcd for C21H18N4
(326.40): C, 77.28; H, 5.56; N, 17.17. Found: C, 77.3; H, 5.7; N, 17.1%.
77.3; H, 5.7; N, 16.9%. 1H NMR (500.1 MHz, CDCl3):
d 2.37 and 2.40
(6H, 2s, 2CH3), 6.89 (1H, dd, J¼4.0 and 6.7 Hz, CH), 7.16 (1H, d,
J¼7.6 Hz, CH), 7.27 (1H, t, J¼7.6 Hz, CH), 7.29 (1H, d, J¼7.6 Hz, CH),
7.33 (1H, t, J¼7.5 Hz, CH), 7.58 (1H, d, J¼7.5 Hz, CH), 7.62 (1H, d,
J¼7.5 Hz, CH), 7.64 (1H, s, CH), 7.75 (1H, s, CH), 8.52 (1H, dd, J¼2.0
and 4.0 Hz, CH), 8.66 (1H, dd, J¼2.0 and 6.7 Hz, CH), 8.80 (1H, s, CH).
1H NMR (500.1 MHz, CDCl3):
d 2.39 and 2.42 (6H, 2 s, 2CH3), 7.23
(2H, d, J¼8.0 Hz, 2CH), 7.26 (2H, d, J¼7.9 Hz, 2CH), 7.71 (2H, d,
J¼8.0 Hz, 2CH), 7.73 (2H, d, J¼7.9 Hz, 2CH), 7.89 (1H, d, J¼4.6 Hz,
CH), 8.22 (1H, dd, J¼1.3 and 4.6 Hz, CH), 8.76 (1H, s, CH), 9.01 (1H,
d, J¼1.3 Hz, CH). 13C NMR (125.8 MHz, CDCl3):
d
21.4 and 21.7
13C NMR (125.8 MHz, CDCl3):
d 21.3 and 21.4 (2CH3), 108.6, 125.3
(2CH3), 115.8, 128.2, 128.8, 129.6 and 129.7 (5CH), 129.8, 130.0,
and 125.9 (3CH),127.3 (C),128.6,128.7,128.8,129.1,129.4,130.7, and

10686
M. Adib et al. / Tetrahedron 64 (2008) 10681–10686
5. Goodacre, S. C.; Hallett, D. J.; Carling, R. W.; Castro, J. L.; Reynolds, D. S.; Pike, A.;
Wafford, K. A.; Newman, R.; Atack, J. R.; Street, L. J. Bioorg. Med. Chem. Lett.
2006, 16, 1582–1585.
132.6 (7CH), 134.0, 135.2, 136.1, 138.5, 138.6, and 145.9 (6C), 149.8
and 159.4 (2CH).
6. Currie, K. S.; DeSimone, R. W.; Pippin, D. A.; Darrow, J. W.; Mitchell, S. A. U.S.
Patent 6,919,340B2, 2005; Chem. Abstr. 2006, 145, 230654h.
4.2.17. 2-(4-Methoxyphenyl)-N3-[(E)-1-(4-methoxyphenyl)-
7. Abignente, E.; Arena, F.; Luraschi, E.; Saturnino, C.; Berrino, L.; De Santis, D.;
Marmo, E. Farmaco Ed. Sci. 1987, 42, 657–669; Loiseau, P. R.; Payard, M.; Grassy,
G.; Pinto, Z. D.; Advenier, C.; Gnassounou, J. P.; Adams, Y. Eur. J. Med. Chem. 1987,
22, 457–462; Rival, Y.; Grassy, G.; Taudou, A.; Escalle, R. Eur. J. Med. Chem. 1991,
26, 13–18; Clements-Jewery, S.; Danswan, G.; Gardner, C. R.; Matharu, S. S.;
Murdoch, R.; Tully, W. R.; Westwood, W. J. Med. Chem. 1988, 31, 1220–1226.
8. Roubaud, C.; Vanelle, P.; Maldonado, J.; Crozet, M. P. Tetrahedron 1995, 51,
9643–9656.
methylidene]imidazo[1,2-a]pyrimidin-3-amine (9h)
Yellow crystals, mp 160–162 ꢀC, yield: 0.69 g, 97%. IR (KBr) (nmax
/
cmꢁ1): 1610, 1579, 1539, 1520, 1479, 1455, 1359, 1222, 798, 758. MS
m/z (%): 358 (Mþ, 64), 326 (17), 212 (78),196 (21),135 (44), 95 (100),
84 (93), 77 (13), 68 (45). Anal. Calcd for C21H18N4O2 (358.40): C,
70.38; H, 5.06; N, 15.63. Found: C, 70.5; H, 5.2; N, 15.4%. 1H NMR
9. Groebke, K.; Weber, L.; Mehlin, F. Synlett 1998, 661–663.
(500.1 MHz, CDCl3):
d 3.81 and 3.83 (6H, 2 s, 2CH3), 6.83 (1H, dd,
10. Bienayme´, H.; Bouzid, K. Angew. Chem., Int. Ed. 1998, 37, 2234–2237.
11. Blackburn, C.; Guan, B.; Fleming, P.; Shiosaki, K.; Tsai, S. Tetrahedron Lett. 1998,
39, 3635–3638.
J¼4.1 and 6.8 Hz, CH), 6.91 (2H, d, J¼8.7 Hz, 2CH), 6.93 (2H, d,
J¼8.8 Hz, 2CH), 7.74 (2H, d, J¼8.7 Hz, 2CH), 7.81 (2H, d, J¼8.8 Hz,
2CH), 8.46 (1H, dd, J¼2.0 and 4.1 Hz, CH), 8.56 (1H, dd, J¼2.0 and
12. Kiselyov, A. Tetrahedron Lett. 2005, 46, 4487–4490.
13. (a) Bristow, N. W.; Charlton, P. T.; Peak, D. A.; Short, W. F. J. Chem. Soc. 1954, 616–
629; (b) Shaabani, A.; Maleki, A. Monatsh. Chem. 2007, 138, 51–56.
14. Katritzky, A. R.; Xu, Y. J.; Tu, H. B. J. Org. Chem. 2003, 68, 4935–4937.
15. Adib, M.; Mohammadi, B.; Bijanzadeh, H. R. Synlett 2008, 177–180; Adib, M.;
Sayahi, M. H.; Ziyadi, H.; Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron 2007, 63,
11135–11140; Adib, M.; Mahdavi, M.; Alizadeh Noghani, M.; Bijanzadeh, H. R.
Tetrahedron Lett. 2007, 48, 8056–8059; Adib, M.; Sheibani, E.; Mostofi, M.;
Ghanbary, K.; Bijanzadeh, H. R. Tetrahedron 2006, 62, 3435–3438; Adib, M.;
Tahermansouri, H.; Aali Koloogani, S.; Mohammadi, B.; Bijanzadeh, H. R.
Tetrahedron Lett. 2006, 47, 5957–5960; Adib, M.; Mahdavi, M.; Mahmoodi, N.;
Pirelahi, H.; Bijanzadeh, H. R. Synlett 2006, 1765–1767; Adib, M.; Ghanbary,
K.; Mostofi, M.; Bijanzadeh, H. R. Tetrahedron 2005, 61, 2645–2648.
16. Adib, M.; Mahdavi, M.; Abbasi, A.; Haghighat Jahromi, A.; Bijanzadeh, H. R.
Tetrahedron Lett. 2007, 48, 3217–3220.
6.8 Hz, CH), 8.73 (1H, s, CH). 13C NMR (125.8 MHz, CDCl3):
d 55.3
and 55.5 (2CH3), 108.4, 114.2, and 114.3 (3CH), 126.6, 127.2, and
129.0 (3C), 129.7, 130.2, and 130.4 (3CH), 134.5 and 145.6 (2C), 149.3
and 159.5 (2CH), 159.6 and 162.7 (2C–O).
Acknowledgements
This research was supported by the Research Council of the
University of Tehran as research project (6102036/1/03).
17. Adib, M.; Mahdavi, M.; Alizadeh Noghani, M.; Mirzaei, P. Tetrahedron Lett. 2007,
48, 7263–7265.
18. The first part of this paper has been published as a preliminary form:
Adib, M.; Sheibani, E.; Zhu, L. G.; Mirzaei, P. Tetrahedron Lett. 2008, 49,
5108–5110.
References and notes
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575–579; (c) Ramo´n, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005, 44, 1602–1634;
(d) Do¨mling, A. Chem. Rev. 2006, 106, 17–89.
2. Howard, A. S. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees,
C. W., Scriven, E. V. F., Eds.; Pergamon: London, 1996; Vol. 8, Chapter 10, pp
262–274, and references therein.
3. Sliskovic, D. R. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees,
C. W., Scriven, E. V. F., Eds.; Pergamon: London, 1996; Vol. 8, Chapter 12, pp
345–365, and references therein.
19. Selected X-ray crystallographic data for compound 7d: C22H19N3O2, monoclinic,
space group¼P21/n, a¼10.4920(16) Å, b¼8.7631(13) Å, c¼20.768(3) Å,
b
¼91.
269(2)ꢀ, V¼1908.96(5) Å3, T¼295(2) K, Z¼4, Dcalcd¼1.24 g cmꢁ3
,
m
¼0.081 mmꢁ1
,
1986 observed reflections, final R1¼0.054, wR2¼0.124 and for all data R1¼0.107,
wR2¼0.124. CCDC 666888 contains the supplementary crystallographic data for
the structure reported in this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
20. Murray, J. I. Organic Synthesis Collective Volume IV; Wiley: New York, NY, 1963;
p 744.
4. Teranishi, K. Bioorg. Chem. 2007, 35, 82–111.