Synthesis of pyrimido[6,1-a]isoquinolines via a one-pot, four-component reaction

Article abstract of DOI:10.1016/j.tet.2010.06.033

An efficient one-pot synthesis of pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives is described. This involves the four-component reaction between primary amines, alkyl acetoacetates, isoquinoline and trichloromethylchloroformate (diphosgene) under mild conditions at ambient temperature. A facile and direct synthetic entry to pyrimido[6,1-a]isoquinolines via a one-pot, four-component reaction of primary amines and alkyl acetoacetates, isoquinoline and trichloromethylchloroformate (diphosgene) under mild conditions at ambient temperature is reported.

Full text of DOI:10.1016/j.tet.2010.06.033

Tetrahedron 66 (2010) 6924e6927
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Tetrahedron
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Synthesis of pyrimido[6,1-a]isoquinolines via a one-pot, four-component reaction
,
a
b
Abdolali Alizadeh a , Atieh Rezvanian , Log-Guan Zhu
*
a Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran 14115, Iran
b Department of Chemistry, 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 8 April 2010
Received in revised form 24 May 2010
Accepted 14 June 2010
Available online 18 June 2010
An efficient one-pot synthesis of pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives is described. This
involves the four-component reaction between primary amines, alkyl acetoacetates, isoquinoline and
trichloromethylchloroformate (diphosgene) under mild conditions at ambient temperature.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Trichloromethylchloroformate
Alkyl acetoacetates
Enaminone
Pyrimido-isoquinoline
Four-component reaction
1. Introduction
agent Trequinsin 2 (Scheme 1), for instance,7 is one of the most
potent in vitro inhibitors of platelet phosphodiesterase and platelet
Bridgehead nitrogen heterocycles are of interest because they
constitute an important class of natural and unnatural products,
many of which exhibit useful biological activity and are used in
pharmaceutical preparations.1-4 A broad range of biological activi-
ties has been reported for compounds containing the pyrimido-[6,1-
a]isoquinoline ring system and a number of these compounds
(pyrimidoisoquinoline derivatives 1) are patented as potential
therapeutic agents (Scheme 1).5,6 Amongst the reported ones are
antihypertensive, bronchodilator, blood pressure lowering, anti
inflammatory and anti-allergic activities. The antihypertensive
aggregation known to date.2 This makes the pyrimido[6,1-a]iso-
quinoline skeleton an important synthetic target and a lot of re-
search has been directed towards it.
Compounds of this type are usually synthesized by ring closure
of suitable tetrahydroisoquinolines,5,7e14 BischlereNapieralsky cy-
clization of 1-(3,4-dimethoxyphenylethyl) barbituric acid5 or other
appropriate N-phenethyl amides.15,16 An interesting and versatile
pyrimido-[6,1-a]isoquinoline synthesis involves enaminones.17
Enaminones and related compounds possessing this structural
unit are versatile synthetic intermediates in organic chemistry that
combine the ambient nucleophilicity of an enamine and the elec-
trophilicity of enones.18 They are frequently applied in the prepa-
ration of heterocycles.19
R1
MeO
N
N
O
N
N
O
As part of our continuing effort into the design of new routes for
the preparation of biologically active heterocyclic compounds using
the synthesis and reactions of enamines and enaminones,20e23
herein we describe a simple, one-pot, four-component synthesis
of pyrimido-[6,1-a]isoquinoline-4-one derivatives.
R2
MeO
N
N
R4
R3
.HCl
2. Results and discussion
Pyrimidoisoquinoline derivatives 1
Trequinsin 2
Our new synthetic method leading to the formation of the title
compounds is given in Scheme 2. Reaction between an enaminone,
derived from the addition of various primary amines 3 to alkyl
acetoacetates 4, with trichloromethylchloroformate in the presence
of isoquinoline in dry CH2Cl2 at ambient temperature to produce
the methyl or ethyl 3-alkyl-2-methyl-4-oxo-3,11b-dihydro-4H-
Scheme 1.
* Corresponding author. Tel.: þ98 21 8800663; fax: þ98 21 88006544; e-mail
address: aalizadeh@modares.ac.ir (A. Alizadeh).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.033

A. Alizadeh et al. / Tetrahedron 66 (2010) 6924e6927
6925
pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives in 80e90%
yields (Scheme 2).
spectrum of 5a displayed the molecular ion peak at m/z 360, which is
in agreement with the proposed structure. The IR spectrum of this
compound showed absorption bands due to the two carbonyl groups
at 1710,1673 and a NC]C group at 1633 cmꢀ1. The 1H NMR spectrum
of 5a showed three sharp singlets for CH3, OCH3 and CH groups
R-NH2
3
(
d
¼2.50, 3.66 and 5.47 ppm),
¼4.99e5.02 ppm), two doublets for the NeCH]CH (
¼6.95 ppm, J¼9.0 Hz), and the aromatic
a
multiplet for CH2Ph
+
(d
d¼6.45 ppm,
J¼9.0 Hz) and NeCH]CH (
d
O
moieties gave rise to multiplets in the aromatic region of the spec-
CO2R'
trum (
d
¼7.12e7.34 ppm). The 1H decoupled 13C NMR spectrum of 5a
Me
showed 20 distinct resonances in agreement with the suggested
structure. Finally, the structure of 5, for example, 5d was further
confirmed by a single crystal X-ray diffraction analysis (Fig. 1).
4
CH2Cl2
r.t 3 h
N
O
R
+
N
R'O2C
N
Me
+
5
O
Cl
OCCl3
Scheme 2. The reaction of primary amine 3, alkyl acetoacetates 4, isoquinoline and
trichloromethylchloroformate (diphosgene).
The diversity of the MCR with respect to the amine component
was investigated and indicated in Table 1.
The structures of compounds 5aef were deduced from their el-
emental analysis, IR and high-field 1H and 13C NMR spectra. The mass
Figure 1. The molecular structure of compound 5d.
Table 1
Methyl or ethyl 3-alkyl-2-methyl-4-oxo-3,11b-dihydro-4H-pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives prepared by the mentioned reaction
Entry
Primary amine 3
Alkyl acetoacetates 4
Product 5
Yield %
85
O
N
O
NH2
a
CO2Me
Me
N
MeO2C
Me
O
N
O
OMe
Me
NH2
b
c
87
85
CO2Me
Me
N
MeO2C
MeO
Me
Me
N
O
O
NH2
CO2Me
Me
N
MeO2C
Me
O
N
O
NH2
d
90
CO2Et
Me
N
EtO2C
Me
N
O
O
NH2
e
80
85
CO2Me
Me
N
N
MeO2C
EtO2C
Me
N
O
O
f
CO2Et
Me
NH2
Me

6926
A. Alizadeh et al. / Tetrahedron 66 (2010) 6924e6927
Although we have not established the mechanism of reaction
CH2Cl2 (5 mL) after 1 h was added isoquinoline (0.13 g, 1 mmol),
and finally a solution of trichloromethylchloroformate (0.20 g,
1 mmol) in anhydrous CH2Cl2 (3 mL) was added dropwise at rt over
15 min. The reaction mixture was stirred for 3 h, then the solvent
was removed under reduced pressure and the residue was purified
by column chromatography (n-hexaneeEtOAc, 8:1).
experimentally, a possible explanation is proposed in Scheme 3. On
the basis of the well-established chemistry of enaminone nucleo-
philes,24e26 it is reasonable to assume that enaminone 6, produced
by the addition of primary amine 3 to alkyl acetoacetates 4, can add
to the electrophilic C]N bond of N-acyliminium compound 7
(which is derived from the addition of isoquinoline to tri-
chloromethylchloroformate) resulting in the formation of 8. Finally,
cyclization of the intermediate 8 and subsequent elimination of
OCCl2 and HCl leads to pyrimido[6,1-a]isoquinoline-1-carboxylate
derivatives 5.
4.2.1. Methyl 3-benzyl-2-methyl-4-oxo-3,11b-dihydro-4H-pyrimido
[6,1-a]isoquinoline-1-carboxylate (5a). Yellow oil, 0.30 g, yield 85%.
IR (KBr) (nmax, cmꢀ1): 1710 (CO2Me), 1673 (NCON), 1633 (NC]C),
1267 and 1215 (C-O of ester). Anal. Calcd for C22H20N2O3 (360.41):
C, 73.32; H, 5.59; N, 7.77%. Found: C, 73.14; H, 5.43; N, 7.82%. MS (EI,
70 eV): m/z (%)¼360 (Mþ, 7), 345 (4), 328 (6), 289 (15), 223 (14),158
(30), 128 (95), 106 (41), 91 (100). 1H NMR (500.13 MHz, CDCl3):
dH¼2.50 (3H, s, CH3), 3.66 (3H, s, OCH3), 5.00 (2H, AB quartet,
3JHH¼15.3 Hz, CH2), 5.47 (1H, s, CH), 6.45 (1H, d, 3JHH¼7.2 Hz, NCH]
R
O
O
HN
CO2R'
R-NH2
Me
N
R'O
Me
6
4
3
3
CH), 6.95 (1H, d, JHH¼7.6, NCH]CH), 7.12e7.34 (9H, m, 9ꢁCH of
isoquinoline and Ph). 13C NMR (125.75 MHz, CDCl3): dC¼16.80
(CH3), 46.79 (CH2), 51.55 (OCH3), 55.20 (CH), 99.79 (NCH]CH),
116.10 (C]CeCH3), 122.67 (CH of isoquinoline), 124.24 (CH of iso-
quinoline), 125.86 (2ꢁCH of Ph), 127.13 (CH of isoquinoline), 127.20
(NCH]CH), 127.55 (CH of isoquinoline), 128.57 (CHpara of Ph),
128.83 (2ꢁCH of Ph), 131.86 (C11a), 131.94 (C7a), 137.76 (Cipso of Ph),
149.23 (CH3C]C), 149.54 (NCON), 167.22 (CO2Me).
O
Cl
OCCl3
N
O
Cl
OCCl3
7
N
O
-HCl
-OCCl2
4.2.2. Methyl 3-(4-methoxybenzyl)-2-methyl-4-oxo-3,11b-dihydro-
4H-pyrimido[6,1-a]isoquinoline-1-carboxylate (5b). Yellow oil, 0.33 g,
yield 87%. IR (KBr) (nmax, cmꢀ1): 1709 (CO2Me), 1671 (NCON), 1631
(NC]C), 1247 and 1219 (CeO of ester). Anal. Calcd for C23H22N2O4
(390.43): C, 70.75; H, 5.68; N, 7.17%. Found: C, 70.78; H, 5.59; N, 7.11%.
MS (EI, 70 eV): m/z (%)¼390 (Mþ, 21), 374 (15), 359 (14), 269 (16),
255 (12), 237 (16), 167 (30), 149 (60), 121 (100). 1H NMR
(500.13 MHz, CDCl3): dH¼2.52 (3H, s, CH3), 3.65 (3H, s, OCH3), 3.77
6
5
HCl
OCCl3
R'O2C
NH
Me
R
8
Scheme 3. Possible mechanism for the formation of pyrimido[6,1-a]isoquinoline-1-
carboxylate derivatives.
3
(3H, s, OCH3), 4.90 (2H, AB quartet, JHH¼15.0 Hz, CH2), 5.45 (1H, s,
3. Conclusion
3
3
CH), 6.44 (1H, d, JHH¼7.2 Hz, NCH]CH), 6.94 (1H, d, JHH¼7.1 Hz,
NCH]CH), 6.80e7.26 (8H, m, 8ꢁCH of isoquinoline and Ar).13C NMR
(125.7 MHz, CDCl3): dC¼16.78 (CH3), 46.31 (CH2), 51.52 (OCH3), 55.19
(OCH3), 55.30 (CH), 99.73 (NCH]CH), 114.27 (2ꢁCH of Ar), 116.02
(C]CeCH3),122.67 (CH of isoquinoline),124.21 (CH of isoquinoline),
127.10 (CH of isoquinoline), 127.29 (2ꢁCH of Ar), 127.52 (CH of iso-
quinoline), 128.60 (NCH]CH), 129.81 (CipsoeCH2), 131.87 (C11a),
131.95 (C7a), 149.30 (CH3C]C), 149.57 (NCON), 158.83 (CipsoeOCH3),
167.24 (CO2Me).
In summary, we have demonstrated that the one-pot
four-component reaction between primary amines, alkyl
acetoacetates, isoquinoline and trichloromethylchloroformate
(diphosgene) provides a simple method for the preparation of
pyrimido-isoquinolines of potential synthetic and pharmacologi-
cal interest. Fairly high yields of the products without any
activation, the ready availability of the starting materials, the
reaction’s simplicity and its mild conditions are the main
advantages of this method.
4.2.3. Methyl 2-methyl-3-(4-methylbenzyl)-4-oxo-3,11b-dihydro-4H-
pyrimido[6,1-a]isoquinoline-1-carboxylate (5c). Yellow oil, 0.31 g,
yield 85%. IR (KBr) (nmax, cmꢀ1): 1722 (CO2Me), 1675 (NCON), 1622
(NC]C), 1267 and 1214 (CeO of ester). Anal. Calcd for C23H22N2O3
(374.43): C, 73.78; H, 5.92; N, 7.48%. Found: C, 73.90; H, 6.00; N,
7.12%. MS (EI, 70 eV): m/z (%)¼374 (Mþ, 38), 359 (27), 314 (9), 269
(22), 255 (22), 167 (47), 149 (85), 105 (100), 71 (54), 57 (85), 43 (84).
1H NMR (500.13 MHz, CDCl3): dH¼2.30 (3H, s, CH3), 2.50 (3H, s,
4. Experimental
4.1. General
Primary amines, alkyl acetoacetates, and trichloromethyl-
chloroformate were obtained from Merck (Germany) and Fluka
(Switzerland). Elemental analyses for C, H and N were performed
using a Heraeus CHNeOeRapid analyzer. 1H and 13C NMR
spectra were measured (CDCl3 solution) with a Bruker DRX-500
AVANCE spectrometer at 500.13 and 125.75 MHz, respectively. IR
spectra were recorded on a Shimadzu IR-460 spectrometer.
Chromatography columns were prepared from Merck silica gel
230e240 mesh. Mass spectra were obtained using a FINNIGAN-
MAT 8430 spectrometer operating at an ionization potential of
70 eV.
3
CH3), 3.65 (3H, s, OCH3), 4.97 (2H, AB quartet, JHH¼15.2 Hz, CH2),
3
5.45 (1H, s, CH), 6.44 (1H, d, JHH¼7.25 Hz, NCH]CH), 6.94 (1H, d,
3JHH¼7.10 Hz, NCH]CH), 7.14e7.28 (8H, m, 8ꢁCH of isoquinoline
and Ar). 13C NMR (125.75 MHz, CDCl3): dC¼16.80 (CH3), 21.02 (CH3),
46.60 (CH2), 51.51 (OCH3), 55.19 (CH), 99.70 (NCH]CH), 116.02 (C]
CeCH3), 122.67 (CH of isoquinoline), 124.21 (CH of isoquinoline),
125.88 (2ꢁCH of Ar), 127.10 (CH of isoquinoline), 127.52 (CH of
isoquinoline), 128.62 (NCH]CH), 129.47 (2ꢁCH of Ar), 131.88 (C11a),
131.96 (C7a), 134.73 (CipsoeCH2), 136.83 (CipsoeCH3), 149.34 (CH3C]
C), 149.55 (NCON), 167.24 (CO2Me).
4.2. General synthesis procedure: (for example, 5a)
4.2.4. Ethyl
3-benzyl-2-methyl-4-oxo-3,11b-dihydro-4H-pyrimido
To a magnetically stirred solution of benzylamine (0.11 g,
1 mmol) and methyl acetoacetate (0.12 g, 1 mmol) in anhydrous
[6,1-a]isoquinoline-1-carboxylate (5d). Yellow oil, 0.33 g, yield 90%.
IR (KBr) (nmax, cmꢀ1): 1702 (CO2Me), 1669 (NCON), 1629 (NC]C),

A. Alizadeh et al. / Tetrahedron 66 (2010) 6924e6927
6927
1264 and 1216 (CeO of ester). Anal. Calcd for C23H22N2O3 (374.44):
C, 73.78; H, 5.92; N, 7.48%. Found: C, 73.69; H, 5.87; N, 7.56%. MS (EI,
70 eV): m/z (%)¼374 (Mþ, 45), 359 (14), 345 (84), 300 (16), 237 (16),
195 (5), 167 (18), 129 (12), 91 (100). 1H NMR (500.13 MHz, CDCl3):
dH¼1.13 (3H, t, 3JHH¼7.1 Hz, OCH2CH3), 2.51 (3H, s, CH3), 4.12e4.22
1.82e1.90 (1H, m, CH), 2.58 (3H, s, CH3), 3.37 (1H, dd, 2JHH¼13.7 Hz,
3JHH¼7.0 Hz, CH2N), 3.82 (1H, dd, 2JHH¼13.8 Hz, 3JHH¼7.1 Hz, CH2N),
4.16e4.20 (2H, m, OCH2CH3), 5.39 (1H, s, CH), 6.40 (1H, d,
3
3JHH¼7.25 Hz, NCH]CH), 6.95 (1H, d, JHH¼7.25 Hz, NCH]CH),
7.09e7.22 (4H, m, 4ꢁCH of isoquinoline). 13C NMR (125.7 MHz,
CDCl3): dC¼14.07 (OCH2CH3), 16.88 (CH3), 19.67 (CH3), 19.82 (CH3),
28.77 (CH), 49.73(CH2N), 55.07 (CH), 60.35 (OCH2CH3), 100.27
(NCH]CH), 115.82 (C]CeCH3), 122.69 (CH of isoquinoline), 124.07
(CH of isoquinoline), 126.87 (CH of isoquinoline), 127.37 (NCH]
CH), 128.68 (CH of isoquinoline), 131.82 (C11a), 131.86 (C7a), 148.86
(CH3C]C), 149.60 (NCON), 166.89 (CO2Me).
3
(2H, m, OCH2CH3), 4.96 (2H, AB quartet, JHH¼15.0 Hz, CH2), 5.49
3
(1H, s, CH), 6.45 (1H, d, JHH¼7.3 Hz, NCH]CH), 6.99 (1H, d,
3JHH¼6.9 Hz, NCH]CH), 7.13e7.30 (9H, m, 9ꢁCH of isoquinoline
and Ph). 13C NMR (125.7 MHz, CDCl3): dC¼14.08 (OCH2CH3), 16.75
(CH3), 46.76 (CH2), 55.21 (CH), 60.43 (OCH2CH3), 100.12 (NCH]CH),
116.04 (C]CeCH3), 122.86 (CH of isoquinoline), 124.15 (CH of iso-
quinoline), 125.86 (2ꢁCH of Ph), 126.96 (CH of isoquinoline), 127.17
(NCH]CH), 127.51 (CH of isoquinoline), 128.52 (CHpara of Ph),
128.80 (2ꢁCH of Ph), 131.76 (C11a), 131.89 (C7a), 137.81 (Cipso of Ph),
148.83 (CH3C]C), 149.56 (NCON), 166.72 (CO2Me). Crystal data for
5d C23H22N2O3 (CCDC 771562): MW¼374.4, monoclinic, space
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.06.033. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
group Cc, a¼21.0287(7) Å, b¼9.6284(4) Å, c¼19.1859(8) Å,
a
¼90
b
¼92.730(3),
g
¼90ꢂ, V¼3880.21(6) Å3, Z¼8, Dc¼1.282 mg/m3,
F (000)¼1584, crystal dimension 0.46ꢁ0.20ꢁ0.16 mm, radiation,
Mo K
295(2) K with a Bruker APEX area-detector diffractometer, and
employing /2
a
(l¼0.71073 Å), 3.6ꢃ2qꢃ25.2, intensity data were collected at
References and notes
u
q
scanning technique, in the range of ꢀ25ꢃhꢃ21,
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1996; Chapter 8.23, p 563.
ꢀ11ꢃkꢃ11, ꢀ19ꢃlꢃ22; the structure was solved by a direct method,
all non-hydrogen atoms were positioned and anisotropic thermal
parameters refined from 2372 observed reflections with R (into)¼
0.0643 by a full-matrix least-squares technique converged to
R¼0.042 and Raw¼0.105 [I>2sigma(I)].
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4.2.5. Methyl 2-methyl-4-oxo-3-propyl-3,11b-dihydro-4H-pyrimido
[6,1-a]isoquinoline-1-carboxylate (5e). Yellow oil, 0.25 g, yield 80%.
IR (KBr) (nmax, cmꢀ1): 1704 (CO2Me), 1671 (NCON), 1627 (NC]C),
1264 and 1224 (CeO of ester). Anal. Calcd for C18H20N2O3 (312.37):
C, 69.21; H, 6.45; N, 8.97%. Found: C, 69.25; H, 6.32; N, 8.84%. MS (EI,
70 eV): m/z (%)¼312 (Mþ, 89), 297 (100), 269 (28), 255 (49), 237
(18), 211 (20), 167 (31), 129 (27), 43 (39). 1H NMR (500.13 MHz,
CDCl3): dH¼0.94 (3H, t, 3JHH¼7.30 Hz, CH3), 1.61e1.66 (2H, m, CH2),
2.60 (3H, s, CH3), 3.67 (3H, s, OCH3), 3.61e3.68 (2H, m, NCH2), 5.38
3
(1H, s, CH), 6.40 (1H, d, JHH¼7.30 Hz, NCH]CH), 6.90 (1H, d,
3JHH¼7.10 Hz, NCH]CH) 7.10e7.26 (4H, m, 4ꢁCH of isoquinoline).
13C NMR (125.75 MHz, CDCl3): dC¼10.94 (CH3), 16.45 (CH3), 22.94
(CH2), 45.22 (NCH2), 51.44 (OCH3), 55.06 (CH), 99.09 (NCH]CH),
115.61 (C]CeCH3), 122.59 (CH of isoquinoline), 124.06 (CH of iso-
quinoline), 126.95 (CH of isoquinoline), 127.39 (CH of isoquinoline),
128.47 (NCH]CH), 131.84 (C11a), 131.90 (C7a), 148.90 (CH3C]C),
148.97 (NCON), 167.41 (CO2Me).
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18. Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277.
4.2.6. Ethyl 3-isobutyl-2-methyl-4-oxo-3,11b-dihydro-4H-pyrimido
[6,1-a]isoquinoline-1-carboxylate (5f). Yellow oil, 0.29 g, yield 85%.
IR (KBr) (nmax, cmꢀ1): 1704 (CO2Me), 1672 (NCON), 1630 (NC]C),
1273 and 1228 (CeO of ester). Anal. Calcd for C20H24N2O3 (340.42):
C, 70.57; H, 7.11; N, 8.23%. Found: C, 70.66; H, 7.03; N, 7.33%. MS (EI,
70 eV): m/z (%)¼340 (Mþ, 93), 325 (17), 311 (100), 283 (16), 266
(20), 255 (90), 211 (21), 167 (21), 129 (15), 57 (18), 41 (36). 1H NMR
(500.13 MHz, CDCl3): dH¼0.75 (3H, d, 3JHH¼6.75 Hz, CH3), 0.85 (3H,
19. (a) Tu, S. J.; Zhang, Y.; Jiang, B.; Jia, H. R.; Zhang, J. Y.; Zhang, J. P.; Ji, S. J. Synthesis
2006, 3874; (b) Valla, A.; Valla, B.; Cartier, D.; Guillou, R. L.; Labia, R.; Potier, P.
Tetrahedron Lett. 2005, 46, 6671; (c) Tu, S. J.; Jiang, B.; Jia, R. H.; Zhang, J. Y.;
Zhang, Y.; Yao, C. S.; Shi, F. Org. Biomol. Chem. 2006, 4, 3664.
20. Alizadeh, A.; Rezvanian, A.; Zhu, L. G. Tetrahedron 2008, 64, 351.
21. Alizadeh, A.; Rezvanian, A. Synthesis 2008, 11, 1747.
22. Alizadeh, A.; Rezvanian, A.; Bijanzadeh, H. R. Synthesis 2008, 5, 725.
23. Alizadeh, A.; Rezvanian, A.; Zhu, L. G. Helv. Chem. Acta 2007, 90, 2414.
24. Lue, P.; Greenhill, J. V. Adv. Heterocycl. Chem. 1996, 67, 207.
25. Elassar, A.-Z. A.; El-Khair, A. A. Tetrahedron 2003, 59, 8463.
26. Negri, G.; Kascheres, C.; Kascheres, A. J. J. Heterocycl. Chem. 2004, 41, 461.
3
3
d, JHH¼6.75 Hz, CH3), 1.12 (3H, t, JHH¼7.10 Hz, OCH2CH3),