A novel approach for the synthesis of 5-pyridylindolizine derivatives via 2-(2-pyridyl)pyridinium ylides

Article abstract of DOI:10.1002/jhet.997

New indolizine derivatives were synthesized by an efficient one-pot three-component procedure starting from commercially available materials such as 2,2′-dipyridyl, substituted bromoacetophenones, and electron-poor alkynes in 1,2-epoxybutane as reaction solvent and acid scavenger.

Full text of DOI:10.1002/jhet.997

78
A Novel Approach for the Synthesis of 5-Pyridylindolizine Derivatives
Vol 50
via 2-(2-Pyridyl)pyridinium Ylides
a
b
a
b
*
Emilian Georgescu, Florea Dumitrascu, Florentina Georgescu, Constantin Draghici,
and Loredana Barbub
aResearch Center Oltchim, 1 Uzinei Street, 240050 Ramnicu Valcea, Romania
bCentre of Organic Chemistry “C. D. Nenitzescu”, Romanian Academy, 202B Spl. Independentei,
Bucharest 060023, Romania
*
E-mail: fdumitra@yahoo.com
Received March 22, 2011
DOI 10.1002/jhet.997
View this article online at wileyonlinelibrary.com.
New indolizine derivatives were synthesized by an efficient one-pot three-component procedure starting
from commercially available materials such as 2,20-dipyridyl, substituted bromoacetophenones, and
electron-poor alkynes in 1,2-epoxybutane as reaction solvent and acid scavenger.
J. Heterocyclic Chem., 50, 78 (2013).
INTRODUCTION
two steps. In the first step, 2-(2-pyridyl)pyridinium salts
are prepared starting from 2,20-dipyridyl 1 and substi-
tuted bromoacetophenones 2. Subsequently, 2-(2-pyridyl)
pyridinium salts are converted into 2-(2-pyridyl)pyridinium-
N-ylides by the treatment with an organic or inorganic base
in the presence of the acetylenic dipolarophile.
The new 5-(2-pyridyl)indolizine derivatives were synthe-
sized by a one-pot three-component procedure. The key
components of the one-pot, three-component pathway
are 2,20-dipyridyl 1, substituted bromoacetophenones 2,
and electron-deficient alkynes 3 in 1,2-epoxybutane that
acts both as solvent and proton scavenger. The reaction
conditions are mild, involving only mixing of the components
at reflux temperature, followed by solvent evaporation
and subsequent purification by column chromatography
(Scheme 1).
Indolizine is a simple heteroaromatic isomeric with
1H-indole molecule. The variety of biological activities
[1–9] and the well-known fluorescence properties of
indolizine derivatives [10–12] and of pyridyl indolizines
in particular [13–17] make them important synthetic
targets.
Two general ways of indolizine synthesis are known
[18–20]. The first way is based on intramolecular conden-
sation of suitable substituted pyridine precursors [18–20].
The second route is based on 1,3-dipolar cycloaddition
reactions of pyridinium-ylides with activated carbon—
carbon multiple bonds [14–22]. Monosubstituted pyridinium
N-ylides dipols are generally unstable compounds, and they
are generated in situ by treatment of pyridinium salts with
an organic or inorganic base.
In the one-pot, three-component pathway, the reaction
mechanism implies the intermediate formation of the 2-
(2-pyridyl)pyridinium salt 17 from the corresponding
2,20-dipyridyl 1 and 2-bromoacetophenone 2. In the next
step, the bromide ion from the 2-(2-pyridyl)pyridinium
salt attacks the oxirane ring of epoxide resulting in the
generation of an alkoxide. The alkoxide substracts one
of the methylene protons in the bromide salt with the
in situ generation of the N-ylide 18. The N-ylide reacts
with the activated alkyne 3 to give the corresponding
dihydroindolizine that is dehydrogenated to the 5-(2-pyridyl)
indolizines 4–16 (Scheme 2).
Sequential transformations, multicomponent processes,
and one-pot procedures have become increasingly interesting
because they offer simple and efficient synthetic ways to
pyrroloazines [23–30].
Herein, we present an efficient one-pot three-component
synthesis of 5-(2-pyridyl)indolizines on the basis of consec-
utive quaternization, N-ylide generation, and 1,3-dipolar
cycloaddition sequence.
RESULTS AND DISCUSSIONS
The synthesis of several 5-(2-pyridyl)indolizines by
1,3-dipolar cycloaddition reactions of pyridinium-N-ylides
with activated carbon—carbon multiple bonds was
already described [16,21,22]. The synthesis of 5-(20-pyridyl)
indolizines via 2-(2-pyridyl)-pyridinium-N-ylides implies
The new compounds are presented in the table as follows:
Table 1
The structure of the compounds 4–16 was determined by
IR and NMR spectroscopy.
© 2013 HeteroCorporation

January 2013
A Novel Approach for the Synthesis of 5-Pyridylindolizine Derivatives
79
via 2-(2-Pyridyl)pyridinium Ylides
Scheme 1. One-pot three-component synthesis of 5-(2-pyridyl)indolizines 4–16.
6'
5'
6
7
5
8
4'
CCOR
BrCH COAr
HC
+
+
2
1'
Et
8a
N
N
4
N
N
3'
2'
COR
O
1
ArCO
3
2
3
2
1
4-16
4: Ar = C6H5, R = Me; 5: Ar = 4-C6H5C6H4, R = Me; 6: Ar = 3-NO2C6H4, R = Me; 7: Ar =
4-ClC6H4, R = Me; 8: Ar = C6H5, R = OMe; 9: Ar = 4-C6H5C6H4, R = OMe; 10: Ar = 4-
BrC6H4, R = OMe; 11: Ar = 4-MeC6H4, R = OEt; 12: Ar = 1-naphthyl, R = OEt; 13: Ar = 2-
naphthyl, R = OEt; 14: Ar = 2-NO2C6H4, R = OEt; 15: Ar = 3-NO2C6H4, R = OEt; 16: Ar =
4-FC6H4, R = OEt.
Scheme 2. The reaction mechanism (R = Me, OMe, OEt).
Et
O
1
2
+
+
N
N
N
N
+
-
Br
CH2COAr
CHCOAr
18A
17
COR
- 2H
N
N
+
N
N
ArCOCH
-
COR
ArCO
4-16
18B
Table 1
New 5-(2-pyridyl)indolizines.
The IR spectra of the compounds show the characteristic
bands for the carbonyl groups. For all the compounds, the
carbonyl group in the aroyl moiety appears in the range
1620–1647 cmꢀ1. The band for the carbonyl groups in the
acetyl moiety for compounds 4–7 appears superimposed
in the same range because of electronic effects that
decrease the double C=O bond character. The carbonyl
groups in the ester for compounds 8–16 appear in the
range 1679–1703 cmꢀ1. Also, for the compounds 6, 14,
and 15, the vibration bands of the NO2 group are present
Compd.
Ar
R
mp (ꢁC)
Yield (%)
4
5
6
7
8
9
10
11
12
13
14
15
16
C6H5
Me
Me
Me
Me
OMe
OMe
OMe
OEt
OEt
OEt
OEt
OEt
OEt
183–185
212–214
212–214
238–240
181–182
190–192
184–186
202–204
199–201
166–168
234–236
173–175
186–188
54
61
44
42
52
47
59
43
46
43
51
49
48
4-C6H5C6H4
3-NO2C6H4
4-ClC6H4
C6H5
4-C6H5C6H4
4-BrC6H4
4-MeC6H4
1-naphthyl
2-naphthyl
2-NO2C6H4
3-NO2C6H4
4-FC6H4
in the ranges 1514–1534 cmꢀ1 and 1346–1356 cmꢀ1
,
1
respectively. The H-NMR spectra show as main charac-
teristics the signals of the hydrogen atoms H-6, H-7, and
H-8 attached on the pyridine moiety of the indolizine
skeleton, which appear as doublets of doublets (J7,8 =9.0Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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E. Georgescu, F. Dumitrascu, F. Georgescu, C. Draghici, and L. Barbu
Vol 50
1-Acetyl-3-(4-phenylbenzoyl)-5-(2-pyridyl)indolizine (5). This
compound was obtained as yellow crystals; IR (ATR): 3065,
1642, 1625, 1570, 1507, 1236 cmꢀ1; 1H-NMR: d 2.53 (s, 3H, Me);
7.13–7.16 (m, 2H, 6-H, H-40); 7.39–7.57 (m, 5H, 2-H, 7-H,
biphenylyl); 7.66–7.74 (m, 5H, 60-H, biphenylyl); 7.87 (td, 1H, 50-H,
J= 7.7, 1.7, 1.2 Hz); 7.97 (d, 2H, biphenylyl, J=8.5Hz); 8.25
(ddd, 1H, 30-H, J= 4.8, 1.7, 0.9 Hz); 8.73 (dd, 8-H, J=9.0,
1.3 Hz);13C-NMR: d 28.1 (Me); 114.2 (1-C); 118.6, 120.9, 122.1,
123.8, 127.2, 127.4, 127.9, 128.3, 128.6, 129.1, 130.3, 138.2, 148.7
(2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C, biphenylyl); 126.5,
136.6, 139.1, 140.0, 140.9, 145.2, 148.7, 155.3 (3-C, 5-C, 8a-C,
20-C, biphenylyl); 183.7 (COAr); 193.2 (COMe). Anal. Calcd for
C28H20N2O2: C 80.75; H 4.84; N 6.73; Found: C 80.51; H 5.12; N 7.04.
1-Acetyl-3-(3-nitrobenzoyl)-5-(2-pyridyl)indolizine (6). This
compound was obtained as yellow crystals; IR (ATR): 1653,
J6,7 =7.0Hz, and J6,8 = 1.3 Hz). The hydrogen atom H-2
appears as a sharp singlet at ~7.20 ppm. All the signals for
the aroyl and pyridine moieties attached to positions 3
and 5 respectively are in good accordance with the
proposed structures and were confirmed by COSY and
HETCOR experiments. The 13C-NMR spectra of the com-
pounds 4–16 present the signals of the carbon atom C-1
strongly shielded. The signal of C-1 appears in the
range 114–116 ppm for compounds 4–7 because of the
influence of the acetyl moiety. By replacing acetyl
with a carbomethoxy group, the shielding effect is greater
C-1 signal being observed at 105–106 ppm. The carbon
atoms C-5, C-6, C-8, and C-8a are deshielded because
of their a and g positions in respect with the nitrogen
atom. The carbon atoms in the carbonyl groups appear in
expected ranges.
1
1631, 1526, 1510, 1352, 1234 cmꢀ1; H-NMR: d 2.52 (s, 3H,
Me); 7.15–7.20 (m, 2H, 6-H, 40-H); 7.48 (s, 1H, 2-H); 7.60 (dd,
1H, 7-H, J = 9.0, 7.0Hz); 7.69 (t, 1H, 500-H, J = 7.9 Hz); 7.74 (dt,
1H, 60-H, J = 7.7, 1.2Hz); 7.89 (td, 1H, H-50, J = 7.7, 1.7, 1.2 Hz);
8.19–8.24 (m, 2H, 30-H, 600-H); 8.42–8.35 (m, 1H, 400-H); 8.70
(t, 1H, 200-H, J =1.9 Hz); 8.75 (dd, 8-H, J = 9.0, 1.3 Hz);
13C-NMR: d 28.1 (Me); 114.6 (1-C); 119.1, 121.0, 122.2, 124.1,
124.3, 126.8, 127.2, 128.6, 129.7, 135.2, 138.3, 148.6 (2-C, 6-C,
7-C, 8-C, 30-C, 40-C, 50-C, 60-C, 200-C, 400-C, 500-C, 600-C); 125.6,
139.1, 139.7, 141.4, 148.4, 155.0 (3-C, 5-C, 8a-C, 20-C, 100-C, 300-C);
181.3 (COAr); 193.0 (COMe); Anal. Calcd for C22H15N3O4:
C 68.57; H 3.92; N 10.90; Found: C 68.89; H 4.17; N 11.21.
1-Acetyl-3-(4-chlorobenzoyl)-5-(2-pyridyl)indolizine (7). This
compound was obtained as yellow crystals; IR (ATR): 1640,
1620, 1584, 1510, 1423, 1233 cmꢀ1; 1H-NMR: d 2.50 (s, 3H, Me);
7.13–7.18 (m, 2H, 6-H, 40-H); 7.46 (d, 2H, 300-H, 500-H, J=8.5Hz);
7.48 (s, 1H, 2-H); 7.54 (dd, 1H, 7-H, J= 9.0, 7.0 Hz); 7.71 (dt, 1H,
60-H, J= 7.7, 1.2 Hz); 7.83 (d, 2H, 200-H, 600-H, J= 8.5 Hz); 7.87 (td,
1H, 50-H, J= 7.7, 1.7, 1.2 Hz); 8.21 (ddd, 1H, 30-H, J= 4.8, 1.7,
0.9 Hz); 8.73 (dd, 8-H, J= 9.0, 1.3 Hz); 13C-NMR: d 28.1 (Me);
114.6 (1-C); 119.1, 120.9, 122.1, 124.0, 126.9, 128.1, 138.3, 148.6
(2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C); 126.0, 136.3, 138.7,
139.0, 141.0, 155.1 (3-C, 5-C, 8a-C, 10-C, 100-C, 400-C); 128.8,
131.0 (200-C, 300-C, 500-C, 600-C); 182.9 (COAr); 193.1 (COMe);
Anal. Calcd for C22H15ClN2O2: C 70.50; H 4.03; Cl 9.46; N 7.47;
Found: C 70.71; H 4.39; Cl 9.81; N 7.69.
CONCLUSION
In conclusion, the one-pot three-component reaction of
2,20-dipyridyl with 2-bromoacetophenones and nonsymmetrical
electron-deficient alkynes in 1,2-epoxybutane is an efficient
procedure for the preparation of 5-(2-pyrydil)indolizines by
sequential quaternization, ylide generation, and 1,3-dipolar
cycloaddition.
EXPERIMENTAL
Melting points were determined on a Boëtius hot plate micro-
scope. The elemental analysis was carried out on a COSTECH
Instruments EAS32 apparatus. The IR spectra were recorded on a
Nicolet Impact 410 spectrometer in KBr pellets. The NMR spectra
were recorded on a Varian Gemini 300 BB instrument, operating
at 300MHz for 1H-NMR and 75 MHz for 13C-NMR, using CDCl3
as solvent and TMS as internal standard. Supplementary evidence
was given by COSY and HETCOR experiments.
2,20-Dipyridyl, 2-bromoacetophenones, methyl propiolate, ethyl
propiolate, 3-butin-2-one, 1,2-epoxybutane, and neutral alumina
were purchased from Aldrich and used without further purification.
Methyl 3-benzoyl-5-(2-pyridyl)indolizine-1-carboxylate (8). This
compound was obtained as yellow crystals; IR (ATR): 3047,
General procedure for the synthesis of 5-(2-pyridyl)
indolizines (4–16). A suspension of 2,20-dipyridyl 1 ( 0.4g,
2.5 mmol), phenacyl bromide 2 (2.5 mmol), and a nonsymmetrical
acetylene 3 (3.5mmol) in 20mL 1,2-epoxybutane was heated at
reflux temperature for 40 h. The solvent was evaporated under
reduced pressure, and the residue was purified by column
chromatography on neutral alumina [benzene : ethyl acetate (4:1)].
The recovered solid was crystallized from CHCl3/MeOH.
1685, 1626, 1594, 1517 1245 cmꢀ1 1H-NMR: d 3.89 (s, 3H,
;
Me); 7.09 (dd, 1H, 6-H, J = 7.0, 1.3 Hz); 7.14 (ddd, 40-H, J = 7.7,
4.8, 1.2 Hz); 7.43–7.51 (m, 3H, 7-H, 300-H, 500-H); 7.54–7.59 (m,
1H, 400-H); 7.60 (s, 1H, 2-H); 7.71 (dt, 1H, 60-H, J = 7.7, 1.2 Hz);
7.83–7.89 (m, 3H, 50-H, 200-H, 600-H); 8.23 (ddd, 1H, 30-H,
J = 4.8, 1.7, 0.9 Hz); 8.47 (dd, 8-H, J = 9.0, 1.3 Hz); 13C-NMR: d
51.3 (Me); 105.2 (1-C); 118.0, 119.9, 122.0, 123.8, 126.7,
127.5, 138.2, 148.7 (2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C);
126.2, 138.0, 139.3, 141.5, 155.4 (3-C, 5-C, 8a-C, 10-C, 100-C);
128.4, 129.7 (200-C, 300-C, 500-C, 600-C); 132.4 (400-C); 164.7
(COO); 184.1 (COAr); Anal. Calcd for C22H16N2O3: C 74.15; H
4.53; N 7.86; Found 74.42; H 4.81; N 7.69.
1-Acetyl-3-benzoyl-5-(2-pyridyl)indolizine (4). This compound
was obtained as yellow crystals; IR (ATR): 3058, 1636, 1586,
1
1503, 1233 cmꢀ1; H-NMR: d 2.53 (s, 3H, Me); 7.12–7.17 (m,
2H, 6-H, 40-H); 7.45–7.63 (m, 5H, 2-H, 7-H, phenyl); 7.71 (dt,
1H, 60-H, J = 7.7, 1.2 Hz); 7.83–7.90 (m, 3H, 5-H, phenyl); 8.22
(ddd, 1H, 30-H, J = 4.8, 1.7, 0.9 Hz); 8.73 (dd, 8-H, J = 9.0,
1.3 Hz,); 13C-NMR: d 28.1 (Me); 114.2 (1-C); 118.7, 120.9,
122.0, 123.9, 127.2, 127.9, 138.2, 148.7 (2-C, 6-C, 7-C, 8-C, 30-
C, 40-C, 50-C, 60-C); 126.4, 138.0, 139.1, 140.9, 155.1 (3-C, 5-C,
8a-C, 10-C, 100-C); 128.5, 129.7 (200-C, 300-C, 500-C, 600-C); 184.2
(COAr); 193.2 (COMe). Anal. Calcd for C22H16N2O2: C 77.63; H
4.74; N 8.23; Found: C 77.92; H 4.51; N 8.58.
Methyl 3-(4-phenylbenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(9). This compound was obtained as yellow crystals; IR (ATR):
3055, 1697, 1624, 1596, 1522, 1220cmꢀ1 1H-NMR: d 3.89
;
(s, 3H, Me); 7.09 (dd, 1H, 6-H, J = 7.0, 1.3 Hz); 7.13 (ddd,
40-H, J = 7.7, 4.8, 1.2 Hz); 7.37–7.51 (m, 4H, 7-H, biphenylyl);
7.62–7.73 (m, 6H, 2-H, 60-H, biphenylyl); 7.87 (td, 1H, 50-H,
J = 7.7, 1.7, 1.2 Hz); 7.96 (d, 2H, biphenylyl, J = 8.5 Hz); 8.25
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A Novel Approach for the Synthesis of 5-Pyridylindolizine Derivatives
81
via 2-(2-Pyridyl)pyridinium Ylides
(ddd, 1H, 30-H, J = 4.8, 1.7, 0.9 Hz); 8.67 (dd, 8-H, J = 9.0,
1.3 Hz); 13C-NMR: d 51.3 (Me); 105.2 (1-C); 117.9, 119.9,
122.0, 123.8, 126.6, 127.1, 127.3, 127.4, 128.2, 129.0, 130.3,
138.2, 148.7 (2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C,
biphenylyl); 126.8, 136.6, 139.3, 140.1, 141.5, 145.1, 148.7,
155.4 (3-C, 5-C, 8a-C, 20-C, biphenylyl); 164.7 (COOMe);
183.7 (COAr); Anal. Calcd for C28H20N2O3: C 77.76; H 4.66;
N 6.48; Found: C 77.49; H 4.92; N 6.78.
naphthyl); 8.18 (ddd, 1H, 30-H, J=4.8, 1.7, 0.9Hz); 8.48–8.52
(m, 2H, 8-H, naphthyl); 13C-NMR: d 14.5 (Me); 60.0 (CH2); 105.5
(1-C); 117.7, 119.8, 121.8, 123.6, 126.6, 127.2, 138.0, 148.5 (2-C,
6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C); 125.4, 126.4, 128.0, 128.1,
129.4, 131.0, 131.1 (100-C, 300-C, 400-C, 500-C, 600-C, 700-C, 800-C);
126.5, 139.1, 141.3, 155.2 (3-C, 5-C, 8a-C, 10-C); 132.4, 135.1,
135.3 (200-C, 4a00-C, 8a00-C); 164.2 (COO); 184.0 (COAr); Anal.
Calcd for C27H20N2O3: C 77.13, H 4.79, N 7.29; Found C 76.88, H
4.91, N 7.61.
Methyl 3-(4-bromobenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(10). This compound was obtained as yellow crystals; IR (ATR):
Ethyl 3-(2-nitrobenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(14). This compound was obtained as yellow crystals; IR (ATR):
1
3053, 1678, 1645, 1578, 1522, 1220 cmꢀ1; H-NMR: d 3.89 (s,
1
3H, Me); 7.08 (dd, 1H, 6-H, J = 7.0, 1.3 Hz); 7.14 (ddd, 1H, 40-H,
J = 7.7, 4.8, 1.2 Hz); 7.47 (dd, 1H, 7-H, J = 9.0, 7.0 Hz); 7.58
(s, 1H, 2-H); 7.70 (dt, 1H, 60-H, J = 7.7, 1.2 Hz); 7.60, 7.79
(2d, 4H, 200-H, 300-H, 500-H, 600-H, J = 8.5Hz); 7.87 (td, 1H, 50-H,
J = 7.7, 1.7, 1.2 Hz); 8.21 (ddd, 1H, 30-H, J = 4.8, 1.7, 0.9 Hz);
8.47 (dd, 8-H, J = 9.0, 1.3 Hz); 13C-NMR: d 51.3 (Me); 105.3
(1-C); 118.0, 119.9, 122.0, 123.9, 126.8, 127.1, 138.2, 148.6
(2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C); 126.2, 127.4,
136.7, 139.2, 141.5, 155.2 (3-C, 5-C, 8a-C, 10-C, 100-C, 400-C);
131.3, 131.7 (200-C, 300-C, 500-C, 600-C); 164.5 (COO); 182.9
(COAr); Anal. Calcd for C22H15BrN2O3: C 60.71; H 3.47; Br
18.66; N 6.44. Found: C 61.06; H 3.81; Br 18.79; N 6.79;
Ethyl 3-(4-methylbenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(11). This compound was obtained as yellow crystals; IR (ATR):
2976, 1692, 1644, 1534, 1356, 1235cmꢀ1; H-NMR: d 1.37 (t,
3H, Me, J = 7.1 Hz); 4.37 (q, 2H, CH2O, J = 7.1Hz); 7.17 (dd, 1H,
6-H, J = 7.0, 1.3Hz); 7.23 (ddd, 1H, 40-H, J = 7.7, 4.8, 1.2 Hz);
7.51–7.75 (m, 5H, 7-H, 60-H, 300-H, 400-H, 600-H); 7.54 (s, 1H, 2-
H); 7.87 (td, 1H, 50-H, J = 7.7, 1.7, 1.2 Hz); 8.23 (ddd, 1H, 30-H,
J= 4.8, 1.7, 0.9 Hz); 8.46–8.50 (m, 2H, 8-H, 500-H); 13C-NMR: d
14.6 (Me); 60.3 (CH2); 106.8 (1-C); 119.1, 119.8, 122.1, 123.8,
124.6, 127.8, 129.4, 130.0, 133.1, 135.9, 137.7, 148.5 (2-C, 6-C, 7-
C, 8-C, 30-C, 40-C, 50-C, 60-C, 300-C, 400-C, 500-C, 600-C); 125.9,
135.8, 140.3, 142.4, 147.8, 155.3 (3-C, 5-C, 8a-C, 10-C, 100-C,
200-C); 163.9 (COO); 179.0 (COAr); Anal. Calcd for C23H17N3O5:
C 66.50, H 4.12, N 10.12; Found: C 66.26, H 4.37, N 9.87.
Ethyl 3-(3-nitrobenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(15). This compound was obtained as yellow crystals; IR (ATR):
1
1
3071, 1686, 1630, 1518 1350, 1242 cmꢀ1; H-NMR: d 1.38 (t,
3097, 1703, 1629, 1526, 1348, 1240cmꢀ1; H-NMR: d 1.37 (t,
3H, J = 7.1 Hz, Me-ester, J = 7.1 Hz); 2.45 (s, 3H, Me); 4.37 (q,
2H, CH2O, J = 7.1 Hz); 7.06 (dd, 1H, 6-H, J = 7.0, 1.3 Hz); 7.11
(ddd, 40-H, J = 7.7, 4.8, 1.2 Hz); 7.26 (d, 2H, 300-H, 500-H,
J = 8.2 Hz); 7.45 (dd, 1H, 7-H, J = 9.0, 7.0 Hz); 7.60 (s, 1H, 2-
H); 7.69 (dt, 1H, 60-H, J = 7.7, 1.2 Hz); 7.79 (d, 2H, 200-H, 600-
H, J = 8.2 Hz); 7.83 (td, 1H, 50-H, J = 7.7, 1.7, 1.2 Hz); 8.23
(ddd, 1H, 30-H, J = 4.8, 1.7, 0.9 Hz); 8.46 (dd, 8-H, J = 9.0,
1.3 Hz); 13C-NMR: d 14.4, 21.7 (2Me); 60.1 (CH2); 105.4
(1-C); 117.7, 119.9, 121.8, 123.7, 126.3, 127.0, 138.0, 148.6
(2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C); 126.6, 135.2,
139.2, 141.2, 143.1,155.4 (3-C, 5-C, 8a-C, 10-C, 100-C, 400-C);
129.1, 129.8 (200-C, 300-C, 500-C, 600-C); 164.3 (COO); 184.0
(COAr); Anal. Calcd for C24H20N2O3: C 74.98; H 5.24; N
7.29; Found: C 75.12; H 5.41; N 7.60.
3H, Me, J = 7.1 Hz); 4.37 (q, 2H, CH2O, J = 7.1Hz); 7.11 (dd, 1H,
6-H, J = 7.0, 1.3Hz); 7.15 (ddd, 1H, 40-H, J = 7.7, 4.8, 1.2 Hz);
7.51 (dd, 1H, 7-H, J = 9.0, 7.0 Hz); 7.55 (s, 1H, 2-H); 7.65 (t, 1H,
500-H, J = 7.9 Hz); 7.71 (dt, 1H, 60-H, J = 7.7, 1.2 Hz); 7.87 (td, 1H,
50-H, J = 7.7, 1.7, 1.2 Hz); 8.16–8.22 (m, 2H, 30-H, 600-H); 8.38–
8.42 (m, 1H, 400-H); 8.47 (dd, 8-H, J = 9.0, 1.3 Hz); 8.66 (t, 1H,
200-H, J = 1.9 Hz); 13C-NMR: d 14.4 (Me); 60.1 (CH2); 106.1 (1-
C); 118.1, 119.9, 121.9, 123.8, 124.2, 126.4, 127.0, 127.3, 129.4,
135.0, 138.0, 148.3 (2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C, 60-C,
200-C, 400-C, 500-C, 600-C); 125.5, 138.0, 139.2, 141.7, 148.2, 155.0
(3-C, 5-C, 8a-C, 10-C, 100-C, 300-C); 163.8 (COO); 181.0 (COAr);
Anal. Calcd for C23H17N3O5: C 66.50, H 4.12, N 10.12; Found: C
66.82, H 4.49, N 10.40.
Ethyl 3-(4-fluorobenzoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(16). This compound was obtained as yellow crystals; IR
(ATR): 3075, 1684, 1640, 1592, 1518, 1237 cmꢀ1; 1H-NMR: d
1.40 (t, 3H, Me, J = 7.1 Hz); 4.38 (q, 2H, CH2O, J = 7.1 Hz);
7.08 (dd, 1H, 6-H, J = 7.0, 1.3 Hz); 7.11–7.17 (m, 3H, 40-H,
300-H, 500-H); 7.47 (dd, 1H, 7-H, J = 9.0, 7.0 Hz); 7.57 (s, 1H, 2-H);
7.70 (dt, 1H, 60-H, J = 7.7, 1.2 Hz); 7.84–7.93 (m, 3H, 50-H,
200-H, 600-H); 8.17 (ddd, 1H, 30-H, J = 4.8, 1.7, 0.9 Hz); 8.47
(dd, 1H, 8-H, J = 9.0, 1.3 Hz); 13C-NMR: d 14.7 (Me); 60.1
(CH2); 105.7 (1-C); 115.5 (d, 300-C, 500-C, J = 21.8 Hz); 117.9,
120.0, 122.0, 123.9, 126.6, 127.0, 138.3, 148.6 (2-C, 6-C,
7-C, 8-C, 30-C, 40-C, 50-C, 60-C); 126.3, 139.2, 141.4, 155.4 (3-C,
5-C, 8a-C); 132.2 (d, 200-C, 600-C, J = 9.2 Hz,); 134.2 (d, 100-C,
J = 2.8 Hz); 163.8 (COO); 165.7 (d, 400-C, J = 252.2Hz); 182.8
(COAr); Anal. Calcd for C23H17FN2O3: C 71.13, H 4.41, N 7.21;
Found: C 71.02, H 4.78, N 7.53.
Ethyl 3-(1-naphthoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(12). This compound was obtained as yellow crystals; IR
1
(ATR): 3047, 1686, 1628, 1519, 1349, 1238 cmꢀ1; H-NMR: d
1.32 (t, 3H, Me, J = 7.1 Hz); 4.37 (q, 2H, CH2O, J = 7.1 Hz);
7.10–7.16 (m, 2H, 6-H, 40-H); 7.42 (s, 1H, 2-H); 7.43–7.76 (m,
6H, 7-H, 60-H, naphthyl); 7.83–7.91 (m, 2H, 50-H, naphthyl);
7.96–7.99 (m, 1H, naphthyl); 8.31–8.38 (m, 2H, 30-H,
naphthyl); 8.46 (dd, 8-H, J = 9.0, 1.3 Hz); 13C-NMR: d 14.5
(Me); 60.0 (CH2); 105.9 (1-C); 118.2, 119.8, 121.7, 123.7,
1026.8, 127.1, 138.0, 148.5 (2-C, 6-C, 7-C, 8-C, 30-C, 40-C, 50-C,
6 -C); 124.5, 125.8, 126.2, 128.1, 128.4, 128.5, 131.5 (200-C,
300-C, 400-C, 500-C, 600-C, 700-C, 800-C); 128.6, 139.7, 141.8, 155.4
(3-C, 5-C, 8a-C, 10-C); 131.1, 133.6, 136.3 (100-C, 5a00-C, 8a00-
C); 164.1 (COO); 184.4 (COAr); Anal. Calcd for C27H20N2O3:
C 77.13, H 4.79, N 7.29; Found: C 77.42, H 5.04, N 7.58.
Ethyl 3-(2-naphthoyl)-5-(2-pyridyl)indolizine-1-carboxylate
(13). This compound was obtained as yellow crystals; IR (ATR):
3055, 1679, 1623, 1523, 1357, 1231 cmꢀ1; 1H-NMR: d 1.37 (t, 3H,
Me, J= 7.1 Hz); 4.36 (q, 2H, CH2O, J= 7.1 Hz); 7.06–7.10 (m, 2H,
6-H, 40-H); 7.48 (dd, 1H, 7-H, J= 9.0, 7.0 Hz); 7.53–7.63 (m, 3H,
naphthyl); 7.66 (s, 1H, 2-H); 7.72 (dt, 1H, 60-H, J= 7.7, 1.2 Hz); 7.83
(td, 1H, 50-H, J=7.7, 1.7, 1.2Hz); 7.87–7.92, 7.96–7.99 (m, 3H,
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