Convenient synthesis of alkenyl-, alkynyl-, and allenyl-substituted imidazo[1,2-a]pyridines via palladium-catalyzed cross-coupling reactions

Article abstract of DOI:10.1002/hlca.200790241

A systematic study on the Stille and Sonogashira cross-coupling of iodinated imidazo[1,2-a]pyridines was performed, permitting the preparation of various vinyl-, ethynyl-, and allenyl-substituted derivatives. These methods are particularly valuable, given their experimental simplicity and high degree of flexibility with regard to functional groups that can be introduced in positions 3, 6, or 8 of the imidazo[1,2-a]-pyridine core. Effects concerning different substitution positions and the nature of the 2-substituent under various reaction conditions are reported in detail for the above types of unsaturated groups introduced.

Full text of DOI:10.1002/hlca.200790241

Helvetica Chimica Acta – Vol. 90 (2007)
2349
Convenient Synthesis of Alkenyl-, Alkynyl-, and Allenyl-Substituted
Imidazo[1,2-a]pyridines via Palladium-Catalyzed Cross-CouplingReactions
by Ce´cile Enguehard-Gueiffiera), Ce´cile Croixa), Maud Herveta), Jean-Yves Kazocka),
Alain Gueiffier*a), and Mohamed Abarbrib)
a
´
´
) Universite FranÅois Rabelais, SPOT EA 3857, Faculte de Pharmacie, 31 avenue Monge, F-37200 Tours
(phone: þ 33-247-367-138; fax: þ 33-247-367-288; e-mail: alain.gueiffier@univ-tours.fr)
b
´
´
) Universite FranÅois Rabelais, SPOT EA 3857, Faculte des Sciences, Parc de Grandmont,
F-37200 Tours
A systematic study on the Stille and Sonogashira cross-coupling of iodinated imidazo[1,2-a]pyridines
was performed, permitting the preparation of various vinyl-, ethynyl-, and allenyl-substituted derivatives.
These methods are particularly valuable, given their experimental simplicity and high degree of flexibility
with regard to functional groups that can be introduced in positions 3, 6, or 8 of the imidazo[1,2-a]-
pyridine core. Effects concerning different substitution positions and the nature of the 2-substituent
under various reaction conditions are reported in detail for the above types of unsaturated groups
introduced.
Introduction. – The significant and potential biological activities of compounds
sharing the imidazo[1,2-a]pyridine moiety have been widely exploited in various
pharmacological areas in medicinal chemistry, for example in virology, including
treatment of hepatitis C [1], herpes [2] and HIV [3]; in cancerology, as antagonists of
the gonadotropin-releasing hormone receptor [4], PI3 kinase p110a inhibitors [5] and
histone deacetylase inhibitors [6]; as well as in neurology, as C3a-receptor antagonists
[7] and D4 partial agonist [8]. In the course of our studies evaluating the chemical and
pharmacological properties of this heterocyclic system, we have extensively inves-
tigated metallo-catalyzed methods of functionalization that allow the rapid preparation
of a number of structural variants [9]. The aim of these systematic studies is to
determine the best cross-coupling reaction conditions, depending on the nature of the
imidazo[1,2-a]pyridine starting material and the coupling partner. These novel
synthetic methodologies are being applied to broaden the available tools in
pharmacology [2][8][9c][10].
While performing further investigations into the functionalization of the imida-
zo[1,2-a]pyridine core, we have focused on the transfer of unsaturated groupings
mainly through Stille and Sonogashira cross-coupling reactions. Vinyl and ethynyl
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 90 (2007)
functions are present in many biologically active compounds [11], and are very useful in
synthetic organic chemistry. Considerable effort has, therefore, been expended to
develop efficient methods for introducing ethynyl groups [12].
Here, we report our results on the preparation of alkenyl, alkynyl, and allenyl
imidazo[1,2-a]pyridines, emphasizing the versatility of the Sonogashira reaction in
these series according to the nature of the halogenated starting material and the alkyne.
We also present the first methodology for the preparation of allenyl-substituted
imidazo[1,2-a]pyridines.
Results and Discussion. – 1. Synthesis of Alkenyl-Substituted Imidazo[1,2-a]pyr-
idines. One of our initial studies comprised the synthesis of 3-, 6-, and 8-vinylated
imidazo[1,2-a]pyridines using the iodoimidazo[1,2-a]pyridines 1a – e as starting materi-
als (see Tables 1 and 2 below). The introduction of vinyl groups through organozinc
reagents (generated in situ from organolithium or organomagnesium compounds) in
THF or HMPA solution was tested, but resulted in low yields of the desired products,
and did not provide a high degree of flexibility with regard to functional groups (data
not shown). To achieve high diversity in the vinyl substituents, we, therefore, decided to
introduce them by Stille cross-coupling [13]. Few examples of Stille reaction have been
reported in such series. To our knowledge, an example of vinyl or allyl substitution has
been reported in position 6 [14] and in position 3 [15], and the coupling of aryl or
heteroaryl groups from 1a in position 6 was reported by our laboratory [16].
We began with the 6- and 8-iodinated 2-(4-fluorophenyl)imidazo[1,2-a]pyridines
1a – c as starting materials to carry out the coupling reaction (Table 1). As reported in
our previous studies in these series, the phenyl-substituted compounds 1a – c are
convenient starting materials, as they are air-stable and easily obtained in good yields.
Moreover, NMR interpretation is facilitated by extra fluorine coupling. Thus, Stille
cross-coupling of 1a – c with different vinyl stannanes in the presence of a catalytic
amount (3 mol-%) of dichlorobis(acetonitrile)palladium(II) ([PdCl2(MeCN)2]) at 408
stereoselectively provided good yields of the 6- or 8-alkenylated compounds 2a – h
(Table 1). At ambient temperature, the coupling rate was slow, affording poor yields of
the products (<20%), leaving a significant amount of starting material.
The results presented in Table 1 indicated that this synthetic strategy is a general
entry to these compounds, compatible with various alkenyl groups, the position of the I-
atoms in the starting materials being irrelevant for the course of the coupling reaction.
Further, cross-coupling occurred with retention of the configuration of the C¼C bond
of the vinyl moiety, and no degradation products were observed.
Attention was next focused on the reactivity of the 3-iodinated imidazo[1,2-
a]pyridines 1d and 1e, bearing either a fluorophenyl or an ester group in 2-position
(Table 2). The aim here was to determine the potential influence of the nature of the 2-
substituent on the reactivity at position 3 toward metallo-catalyzed coupling. We found
that, under the previously described conditions, temperature was again a crucial
parameter, as the coupling of vinyltributyltin did not proceed at 408, but required
heating at 808, thus demonstrating a difference in reactivity between compounds 1a – c
and 1d or 1e.
As shown in Table 2, better yields were obtained when the substituent at position 2
was an ester group (Entries 4 – 6) compared to an aryl group (Entries 1 – 3). The

Helvetica Chimica Acta – Vol. 90 (2007)
2351
Table 1. Stille Cross-Coupling of 1a – c with Vinyltributyltin Compounds. Conditions: iodoimidazo[1,2-
a]pyridine (3 mmol), vinyltributyltin (3.1 mmol), [PdCl2(MeCN)2] (3 mol-%), DMF (10 ml), 408, 4 h.
Entry
R1
R2
R3
R4
Product
Yield [%]a)
1
2
3
4
5
6
7
8
H
H
H
Me
Me
I
I
I
I
I
Me
H
H
H
H
H
H
H
H
Ph
H
Me3Si
Ph
H
Me3Si
Ph
2a
2b
2c
2d
2e
2f
2g
2h
82
81
79
83
84
81
86
83
I
Me
Me
Me
I
I
a) After purification.
Table 2. Stille Cross-Coupling of 1d or 1e with Vinyltributyltin Compounds. Conditions: iodoimidazo[1,2-
a]pyridine (3 mmol), vinyltributyltin (3.1 mmol), [PdCl2(MeCN)2] (3 mol-%), DMF (10 ml), 808, 4 h.
Entry
R
R1
Product
Yield [%]a)
1
2
3
4
5
6
4-F-C6H4
4-F-C6H4
4-F-C6H4
EtOOC
EtOOC
EtOOC
H
Ph
Me3Si
H
Ph
2i
2j
2k
2l
2m
2n
66
68
63
72
70
74
Me3Si
a) After purification.

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Helvetica Chimica Acta – Vol. 90 (2007)
beneficial influence of the ester group on cross-coupling has already been reported in
Suzuki reactions [17]. In our case, cross-coupling provided ready access to different 3-
alkenylimidazo[1,2-a]pyridines of defined configuration.
In all of the above cases, the use of vinylstannane reagents, permit the transfer of a
vinyl group to generate a variety of structurally diverse products, 2a – n, bearing alkenyl
groups in positions 3, 6, or 8. The Stille reaction showed great versatility in the
construction of C(sp2)ꢀC(sp2) bonds, and required only a very simple procedure.
2. Synthesis of Alkynyl-Substituted Imidazo[1,2-a]pyridines. In the second part of
this project, we decided to introduce an alkynyl group in positions 3, 6, or 8 of our target
structure. Pd-Catalyzed cross-coupling reactions of aryl halides or aryl triflates with
terminal alkynes, commonly referred to as Sonogashira reactions, are a powerful,
versatile, and popular tool. However, to our knowledge, few Sonogashira couplings
have been reported at the 3- and 6-positions of imidazo[1,2-a]pyridines. Initially, the
yields reported in the literature were very low for Sonogashira-type cross-coupling in
position 3 (< 35%) [18]. However, El Kazzouli et al. [19] recently described a
Sonogashira-coupling procedure starting from 6-bromo- or 3-iodo-2-phenylimida-
zo[1,2-a]pyridines that provided good yields of the alkynylated compounds. However,
as we will demonstrate herein, this particular procedure applied for couplings at C(3) is
largely influenced by the nature of the 2-substituent.
We began our study by applying the Sonogashira protocol to the coupling of various
terminal alkynes to compounds 1a, 1f, and 1g (Table 3). We used catalytic amounts
(6 mol-%) of tetrakis(triphenylphosphine)palladium(0) ([Pd(PPh3)4]) in the presence
of CuI (10 mol-%) and 12 equiv. of diisopropylamine in THF. After 1 h of stirring at
room temperature (24 h at 508 in the alternative procedure reported in [19]), good
yields of coupling products 3 were obtained (74 – 92%), whatever the nature of the 2-
substituent. Only the coupling with ethyl propiolate (¼ethyl prop-2-ynoate; Table 3,
Entry 7) was unsuccessful, affording an inseparable mixture of the desired product and
starting material. In some cases, heating at 608 for 5 h accelerated the rate of the
reaction and improved the yield of the products (Entries 3 and 11).
The same reaction conditions as above were then applied to compounds 1c, 1h, and
1i, providing similar results, with good yields of coupling products, whatever the
substituent in position 2, again with the exception of ethyl propiolate derivatives
(Table 4).
As shown in Scheme 1, the previously synthesized (trimethylsilyl)ethynyl deriva-
tives 3d,h,l and 4d,h,l, also obtained via Sonogashira coupling, could be efficiently
desilylated to the corresponding 6-ethynylimidazo[1,2-a]pyridines 5a – c and 6a – c,
respectively. Good yields of alkyne deprotection (80 – 90%) were obtained in THF in
the presence of tetrabutylammonium fluoride (TBAF) at room temperature. This
methodology, thus, provides a convenient two-step procedure to introduce a terminal
ethynyl group into the heterocycle. Indeed, acetylene coupling under Sonogashira
conditions often gives rise to side products due to double substitution (for
representative reviews on the Pd-catalyzed homo-coupling reactions of alkynes, see
[20]).
Our Sonogashira-type coupling conditions were unsuccessful in position 3 of
compound 1d (Table 5, Entry 1). We, therefore, decided to test the conditions described
by El Kazzouli et al. [19], using phenylacetylene in the presence of catalytic amounts

Helvetica Chimica Acta – Vol. 90 (2007)
2353
Table 3. Sonogashira Cross-Coupling of Alkynes with 6-Iodoimidazo[1,2-a]pyridines. Conditions: 6-
iodoimidazo[1,2-a]pyridine (1 mmol), alkyne (1.5 mmol), [Pd(PPh3)4] (6 mol-%), CuI (10 mol-%),
(i-Pr)2NH (12 mmol), THF (2 ml), r.t., 1 h.
Entry
R
R’
Product
Yield [%]a)
1
2
Me
Me
Me
Me
4-F-C6H4
4-F-C6H4
4-F-C6H4
4-F-C6H4
EtOOC
EtOOC
EtOOC
EtOOC
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
83
79
74
92
92
HOCH2
EtOOC
Me3Si
3b)
4
5
6
7
8
C6H5
HOCH2
EtOOC
Me3Si
c
)
83
87
92
37
83
9
C6H5
10
11b)
12
HOCH2
EtOOC
Me3Si
3j
3k
3l
a) After purification. b) At 608 for 5 h. c) Inseparable mixture.
(10 mol-%) of bis(triphenylphosphine)palladium(II) chloride ([PdCl2(PPh3)2]) and
CuI (10 mol-%) in a mixture of Et3N and DMF. Starting from 2-(4-fluorophenyl)-3-
iodoimidazo[1,2-a]pyridine (1d), the coupling product 8a was obtained in 75% yield
(Table 5, Entry 2). Unfortunately, when position 2 was substituted with an ester group,
only 16% of the alkynylated compound 8b was formed after 24 h at room temperature
(Entry 3). When using tris(dibenzylideneacetone)dipalladium(0) ([Pd2(dba)3]), a
much better yield (64%) of 8b was obtained (Entry 4). From these experiments, we
conclude that the reactivity at position 3 of imidazo[1,2-a]pyridines toward Sonogashira
coupling is largely influenced by the nature of the substituent in position 2.
We next decided to determine the influence of pyridine substitution on the coupling
efficacy. Interestingly, our methodology (6 mol-% [Pd(PPh3)4], 10 mol-% CuI, 12
equiv. of i-Pr2NH in THF), completely unsuccessful in the synthesis of 1d, was
modestly efficient in the case of 1j (Entry 5, 30% yield, not optimized), which possesses
a Me group and a Br-atom in positions 6 and 8, respectively. Thus, the reactivity at
position 3 toward Sonogashira coupling seems also to be largely influenced by the
nature of the substituents on the six-membered ring.
Introduction of an ethynyl or propynyl group is often difficult via Sonogashira
coupling due to the gaseous nature of these alkynes and the formation of double-
substitution products in the case of ethyne. We previously proposed the use of silylated
acetylene for the introduction of the acetylene group, which then requires a

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Helvetica Chimica Acta – Vol. 90 (2007)
Table 4. Sonogashira Cross-Couplings of Alkynes with 8-Iodoimidazo[1,2-a]pyridines. Conditions: as in
Table 3.
Entry
R
R’
Product
Yield [%]a)
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
4-F-C6H4
4-F-C6H4
4-F-C6H4
4-F-C6H4
EtOOC
EtOOC
EtOOC
EtOOC
C6H5
4a
4b
4c
4d
4e
4f
4g
4h
4i
83
81
HOCH2
EtOOC
Me3Si
n.i.b)
54
C6H5
94
87
49
81
85
74
n.i.
79
HOCH2
EtOOC
Me3Si
C6H5
10
11
12
HOCH2
EtOOC
Me3Si
4j
4k
4l
a) After purification. b) Not isolated.
Table 5. Sonogashira Cross-Couplings of Phenylacetylene with 3-Iodoimidazo[1,2-a]pyridines
Entry
R
R’
Catalyst
Base
Product
Yield [%]a)
1
2
3
4
5
4-F-C6H4
4-F-C6H4
EtOOC
EtOOC
4-F-C6H4
H
H
H
H
[Pd(PPh3)4]
[PdCl2(PPh3)2]
[PdCl2(PPh3)2]
[Pd2(dba)3]
(i-Pr2)NH
Et3N
Et3N
Et3N
(i-Pr2)NH
8a
8a
8b
8b
8c
0b)
75c)
16c)
64c)
30b)
6-Me, 8-Br
[Pd(PPh3)4]
a) After purification. b) Conditions: 1 (1 mmol), phenylacetylene (1.5 mmol), Pd(0) (6 mol-%), CuI
(10 mol-%), base (12 mmol), THF (2 ml), r.t., 1 h. c) Conditions: 1 (1.5 mmol), phenylacetylene
(1.8 mmol), Pd(0) (10 mol-%), CuI (10 mol-%), base (1.5 ml), DMF (1.5 ml), r.t., 24 h.

Helvetica Chimica Acta – Vol. 90 (2007)
2355
Scheme 1
deprotection step. Stille coupling may be an alternative for the introduction of ethynyl
or propynyl groups. We therefore chose ethynyl- and allenyl(tributyl)stannanes as
reagents [21a]. Thereby allenyltin compounds were prepared from 3-bromoprop-1-yne,
Mg, and Bu3SnCl under Pb(II) catalysis [21b]. The reactions proceeded smoothly in
DMF in the presence of [Pd(PPh3)4] (6 mol-%) at 808, affording good yields of
compounds 5a and 5c as well as 9a – d (Table 6). The coupling of 1a or 1e with
allenyl(tributyl)tin afforded the new 6- or 3-(prop-1-ynyl)imidazo[1,2-a]pyridines 9c
and 9d, respectively, as the only products, without any trace of the corresponding
allenyl-coupled analogues.
In conclusion, we now have various methods at our disposal for the synthesis of
alkynyl-substituted imidazo[1,2-a]pyridine compounds, depending on the nature of the
alkyne and the substitution position in the heterocycle. As previously noted with Stille
couplings, C(3) appears to be less reactive to Sonogashira reactions than C(6) or C(8),
especially when there is an ester at position 2. This could be rationalized by
coordination of the Cusalts and the polar ester group. Nevertheless, adapting the
Sonogashira conditions, particularly in terms of the catalyst and solvent, allows alkyne
introduction in the three positions studied; and ethynyl and propynyl groups can be
efficiently transferred to positions 3 and 6 under Stille conditions.
3. Synthesis of Allenyl-Substituted Imidazo[1,2-a]pyridines. At this point in our
study, we observed that the coupling reactions of allenyl(tributyl)stannane to 3- or 6-
iodoimidazo[1,2-a]pyridines under Stille conditions led to the complete rearrangement
of the allenyl to a propynyl group. We then applied the Nakamura method, consisting of
allene transformation of propargylic amines [22]. The heterocyclic allene precursor was
synthesized using the previously described Sonogashira coupling of N,N-diisopropyl-
(prop-2-ynyl)amine (¼ N,N-bis(1-methylethyl)prop-2-yn-1-amine) with 3-, 6-, or 8-
iodoimidazo[1,2-a]pyridines (Scheme 2). The propargylic diisopropylamines were
obtained from the corresponding bromides. Allene transformation took 24 h in the
presence of [Pd2(dba)3(CHCl3/ligand)] as catalyst at 1008 in CHCl3.

2356
Helvetica Chimica Acta – Vol. 90 (2007)
Table 6. Palladium-Catalyzed Synthesis of Alkynyl-Substituted Imidazo[1,2-a]pyridines. Conditions:
iodoimidazo[1,2-a]pyridine (1 mmol), allene or alkyne (1.8 mmol), Pd(0) (6 mol-%), DMF (5 ml),
4 h, 808.
R
X
H
Y
I
Product
Product
Yield [%]a)
78
4-F-C6H4
5a
EtOOC
EtOOC
H
I
I
5c
9a
75
70
H
4-F-C6H4
I
H
9b
64
4-F-C6H4
EtOOC
H
I
I
9c
66
55
H
9d
a) After purification.
The Sonogashira coupling of N,N-diisopropyl(prop-2-ynyl)amine to the 6-iodo-
imidazo[1,2-a]pyridines 1a and 1g proceeded efficiently, when using our previously
described procedure, giving rise to 81 and 75% yield, respectively (Scheme 2). Two
ligands were then evaluated for the allene transformation of 10. Moderate yields (ca.
40%) were obtained with tris(pentafluorophenyl)phosphine (P(C6F5)3) as ligand,

Helvetica Chimica Acta – Vol. 90 (2007)
2357
Scheme 2
while the efficiency of the reaction was considerably improved (70% yield) when using
ꢁ1,2-bis[bis(pentafluorophenyl)phosphino]ethaneꢂ1).
There were difficulties with the Sonogashira coupling of N,N-diisopropyl(prop-2-
ynyl)amine in 3-position. In this case, the coupling efficiently yielded 12 (53% yield) in
the presence of an ester group in position 2, but failed in the presence of a 4-
fluorophenyl group, leading to inseparable mixtures. The allene transformation of 12,
performed in the presence of (C6F5)2PCH2CH2P(C6F5)2 as ligand provided 32% of the
expected compound 13 (Scheme 3).
Scheme 3
The Nakamura methodology, thus, gave us the opportunity to introduce an allenyl
group in positions 3 and 6 of the imidazo[1,2-a]pyridine nucleus. Further studies are in
1
)
Systematic name: 1,2-ethanediylbis[bis(pentafluorophenyl)phosphine].

2358
Helvetica Chimica Acta – Vol. 90 (2007)
progress to improve this original method and to expand it to the 8-position of this
important heterocycle.
Conclusions. – We have demonstrated that the Stille reaction is a suitable method to
introduce alkenyl substituents into positions 3, 6, and 8 of imidazo[1,2-a]pyridines. The
use of allenyl- or ethynyl(tributyl)stannanes permits the transfer of a propynyl or
ethynyl group, respectively. It should be noted that better yields of 6- and 8-alkenylated
(or alkynylated) imidazo[1,2-a]pyridines were obtained than for the corresponding 3-
substituted congeners, thus showing better reactivity of 1a – c compared to 1d or 1e.
Sonogashira coupling generally provided a more versatile approach for the introduc-
tion of alkynyl substituents into the 3-, 6-, and 8-positions of imidazo[1,2-a]pyridines,
the reaction conditions requiring modification according to the nature of the alkyne
used and the substitution position. Finally, we achieved the synthesis of 3- or 6-allenyl-
substituted imidazo[1,2-a]pyridines by means of Sonogashira coupling and the Pd-
catalyzed allene transformation. Further studies are in progress to ascertain the scope
and limitations of this procedure, as well as its applicability to the preparation of new
imidazo[1,2-a]pyridine derivatives.
Experimental Part
General. The following compounds were prepared according to published procedures: 2-(4-
fluorophenyl)-6-iodoimidazo[1,2-a]pyridine (1a) [9a], 2-(4-fluorophenyl)-8-iodo-6-methylimidazo[1,2-
a]pyridine (1c) [23], 2-(4-fluorophenyl)-3-iodoimidazo[1,2-a]pyridine (1d) [17], ethyl 3-iodoimidazo[1,2-
a]pyridine-2-carboxylate (1e) [17], ethyl 6-iodoimidazo[1,2-a]pyridine-2-carboxylate (1g) [24], 8-iodo-
2,6-dimethylimidazo[1,2-a]pyridine (1h) [23], ethyl 8-iodo-6-methylimidazo[1,2-a]pyridine-2-carboxylate
(1i) [23]. The reagent (E)-1-(tributylstannyl)-2-(trimethylsilyl)ethene was prepared by hydrostannation
of (trimethylsilyl)acetylene [25]. (E)-Tributyl(b-styryl)stannane was prepared by hydrostannation of
phenylacetylene [26]. (Tributylstannyl)acetylene was prepared from ethynyllithium – ethylene-1,2-
diamine complex and Bu3SnCl [21a]. All reactions were carried out under inert atmosphere (Ar or
N2). THF and Et2O were dried and freshly distilled from Na/benzophenone. DMF was distilled from
CaH2. Flash chromatography (FC) was carried out on Merck silica gel (230 – 400 mesh) or Al2O3.
Melting points (m.p.) are uncorrected. IR Spectra: Perkin-Elmer 781 FT-IR spectrophotometer; in cmꢀ1
.
1H-NMR Spectra: Bruker DPX-200; at 200 MHz in CDCl3 (unless noted otherwise); d in ppm rel. to
residual solvent signals (d(H) ¼ 7.25 ppm), J in Hz. 13C-NMR Spectra: at 50.32 MHz in CDCl3 (unless
noted otherwise); solvent peak at d(C) 77.0 ppm. Mass spectra: recorded on a Hewlett-Packard 5989A
GC/EI-MS apparatus, at 70 eV; in m/z.
2-(4-Fluorophenyl)-6-iodo-8-methylimidazo[1,2-a]pyridine (1b). A mixture of 2-amino-5-iodo-3-
methylpyridine (1.5 g, 6.4 mmol) and a-bromo-4-fluoroacetophenone (1.53 g, 7.0 mmol) in EtOH (20 ml)
was refluxed for 5 h. After cooling, the precipitate was filtered off and suspended in H2O. The suspension
was rendered alkaline with Na2CO3, and the solid was filtered off. After dissolution of the solid in
CH2Cl2, the org. phase was washed with H2O, dried (CaCl2), and concentrated to afford 1.46 g (64%) of
1b. M.p. 1878. 1H-NMR: 8.26 (s, HꢀC(5)); 7.95 (dd, J ¼ 8.6, 5.4, HꢀC(2,6) of C6H4F); 7.73 (s, HꢀC(3));
7.20 (s, HꢀC(7)); 7.15 (t, J ¼ 8.6, HꢀC(3,5) of C6H4F); 2.65 (s, Me). 13C-NMR: 163.2 (J ¼ 245.5); 145.2;
145.1; 131.6; 130.1; 129.3; 128.7; 128.3 (J ¼ 8); 116.1 (J ¼ 21.5); 108.2; 75.7; 17.2.
Ethyl 3-Iodoimidazo[1,2-a]pyridine-2-carboxylate (1e). N-Iodosuccinimide (5.3 g, 23.6 mmol) was
added to a soln. of ethyl imidazo[1,2-a]pyridine-2-carboxylate (3 g, 15.8 mmol) in anh. MeCN (50 ml).
The mixture was stirred at r.t. for 1 h. The filtrate was concentrated, and the residue was purified by FC
(Al2O3; CH2Cl2) to afford 3.3 g (66%) of 1e. M.p. 1448. 1H-NMR: 8.31 (dt, J ¼ 7, 1.1, H ꢀC(5)); 7.72 (dt,
J ¼ 9.2, 1.1, HꢀC(8)); 7.38 (ddd, J ¼ 9.2, 7, 1.1, HꢀC(7)); 7.05 (td, J ¼ 7, 1.1, H ꢀC(6)); 4.54 (q, J ¼ 7.1,
CH2); 1.51 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.1; 148.2; 138.5; 127.5 (2C); 119.6; 115.1; 68.5; 61.9; 14.8.

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6-Iodo-2-methylimidazo[1,2-a]pyridine (1f). A mixture of 2-amino-5-iodopyridine (4 g, 18.2 mmol)
and chloroacetone (2.5 g, 27.2 mmol) in EtOH (25 ml) was refluxed for 24 h. After cooling, the solvent
was evaporated, and the residue was suspended in H2O. The suspension was rendered alkaline with
Na2CO3, and extracted with CH2Cl2. After drying (CaCl2), the org. layers were concentrated, and the
residue was purified by FC (SiO2; AcOEt) to afford 4.0 g (85%) of 1f. M.p. 152 – 1538. 1H-NMR: 8.30 (m,
HꢀC(5)); 7.29 – 7.34 (m, HꢀC(7), HꢀC(8), HꢀC(3)); 2.45 (s, Me). 13C-NMR: 144.6; 144.0; 132.1;
130.4; 118.2; 107.9; 74.7; 14.7.
8-Bromo-2-(4-fluorophenyl)-3-iodo-6-methylimidazo[1,2-a]pyridine (1j). To a soln. of 8-bromo-2-
(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridine (2 g, 6.6 mmol) [23] in anh. MeCN (20 ml) was added
N-iodosuccinimide (1.63 g, 7.2 mmol). The mixture was stirred at r.t. overnight. The mixture was filtered
off to afford 2.7 g (95%) of 1j. M.p. 2258. 1H-NMR: 7.98 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.96 (d,
J ¼ 1.4, HꢀC(5)); 7.39 (d, J ¼ 1.4, HꢀC(7)); 7.13 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 2.38 (s, Me).
General Procedure for the Preparation of 2a – n. A dry three-necked flask equipped with a magnetic
stirring bar and a septum was charged with 1 (3 mmol) in DMF (10 ml) and vinyl(tributyl)tin
(3.1 mmol). Then, [PdCl2(MeCN)2] (63 mg, 0.09 mmol, 3 mol-%) was added, and the resulting soln. was
stirred under Ar gas for 4 h at 40 or 808. The mixture was diluted with Et2O (30 ml), washed with a sat.
NH4Cl soln. (2 ꢁ 20 ml), and dried (MgSO4). After evaporation of the solvents, the crude product 2
was purified either by FC (SiO2; petroleum ether (PE)/Et2O/Et3N 25 :73 :2) or by crystallization from
Et2O.
2-(4-Fluorophenyl)-6-(1-methylethenyl)imidazo[1,2-a]pyridine (2a). Colorless solid. M.p. 1148.
1H-NMR: 8.16 (br. s, HꢀC(5)); 7.94 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.82 (s, HꢀC(3)); 7.62 (d,
J ¼ 10, HꢀC(8)); 7.46 (dd, J ¼ 10, 2, HꢀC(7)); 7.15 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 5.48 (s, HC¼); 5.21
(s, H2C¼)); 2.20 (s, Me). 13C-NMR: 163.3 (J ¼ 244); 145.0; 144.6; 138.9; 129.4; 127.7 (J ¼ 8); 127.0; 124.3;
122.1; 116.4; 115.7 (J ¼ 21); 113.7; 108.3; 53.5. EI-MS: 252 (100, Mþ), 251 (17), 237 (11), 212 (11). HR-
EI-MS: 252.1067 (Mþ, C16H13FN2þ ; calc. 252.1063).
2-(4-Fluorophenyl)-6-(1-phenylethenyl)imidazo[1,2-a]pyridine (2b). Colorless solid. M.p. 2088.
1H-NMR: 8.12 (br. s, HꢀC(5)); 7.92 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.77 (s, HꢀC(3)); 7.63 (d,
J ¼ 10, HꢀC(8)); 7.54 – 7.50 (m, HꢀC(2,6) of C6H5, Hꢀ(C7)); 7.43 – 7.26 (m, HꢀC(3,5) and HꢀC(4) of
C6H5); 7.13 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 7.10, 6.98 (2d, J ¼ 16.5 each, H2C¼). 13C-NMR: 163.6 (J ¼
250); 145.6; 145.5; 137.1; 130.3 (J ¼ 3); 129.8; 129.2; 128.5; 128.0 (J ¼ 8); 127.0; 124.4; 124.3; 124.0; 123.2;
117.7; 116.0 (J ¼ 21.6); 108.6. EI-MS: 314 (100, Mþ), 178 (6), 165 (8). HR-EI-MS: 314.1225 (Mþ,
C21H15FNþ2 ; calc. 314.1219).
6-Ethenyl-2-(4-fluorophenyl)imidazo[1,2-a]pyridine (2c). Colorless solid. M.p. 1868. 1H-NMR: 8.02
(br. s, HꢀC(5)); 7.93 (dd, J ¼ 8.6, 5, HꢀC(2,6) of C6H4F); 7.76 (s, HꢀC(3)); 7.59 (d, J ¼ 9.5, HꢀC(8));
7.41 (dd, J ¼ 9.5, 1.6, HꢀC(7)); 7.14 (t, J ¼ 8.6, HꢀC(3,5) of C6H4F); 6.65 (dd, J ¼ 16.2, 11, HC¼); 5.76 (d,
J ¼ 16.2, H2C¼); 5.35 (d, J ¼ 11, H2C¼). 13C-NMR: 163.1 (J ¼ 245); 145.6; 145.5; 132.8; 130.2 (J ¼ 3);
128.0 (J ¼ 8); 124.1; 124.0; 123.0; 117.5, 116.0 (J ¼ 21.5); 114.8; 108.5. EI-MS: 238 (100, Mþ), 237 (14), 104
(10). HR-EI-MS: 238.0911 (Mþ, C15H11FNþ2 ; calc. 238.0906).
2-(4-Fluorophenyl)-8-methyl-6-[(E)-2-(trimethylsilyl)ethenyl]imidazo[1,2-a]pyridine (2d). Color-
1
less solid. M.p. 1188. H-NMR: 7.96 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.95 (br. s, HꢀC(5)); 7.76
(s, HꢀC(3)); 7.28 (br. s, HꢀC(7)); 7.15 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 6.79 (d, J ¼ 19, HC¼)); 6.47 (d,
J ¼ 19, HC¼); 2.69 (s, Me); 0.22 (s, 3 Me). 13C-NMR: 163.0 (J ¼ 245); 146.2; 144.8; 139.4; 130.7; 130.2;
128.2 (J ¼ 8); 127.4; 125.0; 123.0; 122.0; 115.5 (J ¼ 21.6); 109.0; 17.7; ꢀ 0.86. EI-MS: 324 (97, Mþ), 323
(20), 310 (24), 309 (100). HR-EI-MS: 324.1462 (Mþ, C19H21FN2Siþ; calc. 324.1458).
2-(4-Fluorophenyl)-8-methyl-6-[(E)-2-phenylethenyl]imidazo[1,2-a]pyridine (2e). Colorless solid.
M.p. 2008. 1H-NMR: 8.01 (br. s, HꢀC(5)); 7.97 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.75 (s, HꢀC(3));
7.55 (d, J ¼ 8, HꢀC(2,6) of C6H5); 7.46 – 7.32 (m, HꢀC(3,5) and HꢀC(4) of C6H5); 7.33 (d, J ¼ 2,
HꢀC(7)); 7.16 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 7.12 (d, J ¼ 16, HC¼); 7.00 (d, J ¼ 16, HC¼); 2.72 (s, Me).
13C-NMR: 163.1 (J ¼ 245); 145.7; 144.6; 137.0; 130.1; 129.1; 129.0; 128.0; 127.7; 127.2; 126.5; 124.4; 123.5;
122.0; 121.4; 115.5 (J ¼ 21.6); 108.6; 17.3. EI-MS: 328 (100, Mþ), 327 (37), 313 (10), 165 (7). HR-EI-MS:
328.1381 (Mþ, C22H17FNþ2 ; calc. 328.1376).
8-Ethenyl-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridine (2f). Colorless solid. M.p. 928.
1H-NMR: 7.96 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.82 (br. s, HꢀC(5)); 7.72 (s, HꢀC(3)); 7.17 (t,

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Helvetica Chimica Acta – Vol. 90 (2007)
J ¼ 8.8, HꢀC(3,5) of C6H4F); 7.12 (dd, J ¼ 17.5, 11, HC¼); 7.04 (br. s, HꢀC(7)); 6.75 (dd, J ¼ 17.5, 1.7,
H2C¼); 5.64 (dd, J ¼ 11, 1.7, H2C¼); 2.32 (s, Me). 13C-NMR: 163 (J ¼ 246); 144.7; 143.6; 132.4; 130.6;
128.0 (J ¼ 8); 126.3; 126.0; 122.7; 122.2; 120.0; 116.5 (J ¼ 21.6); 108.0; 18.5. EI-MS: 252 (100, Mþ), 251
(97), 226 (10). HR-EI-MS: 252.1071 (Mþ, C16H13FN2þ ; calc. 252.1063).
2-(4-Fluorophenyl)-6-methyl-8-[(E)-2-(trimethylsilyl)ethenyl]imidazo[1,2-a]pyridine (2g). Color-
1
less solid. M.p. 1528. H-NMR: 7.92 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.77 (br. s, HꢀC(5)); 7.67
(s, HꢀC(3)); 7.34 (s, HꢀC(7)); 7.28 (d, J ¼ 20, HC¼); 7.08 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 7.06 (d, J ¼
20, HC¼); 2.28 (s, Me); 0.19 (s, 3 Me). 13C-NMR: 163 (J ¼ 246); 144.7; 143.8; 138.6; 135.8; 130.8; 128.1
(J ¼ 7.5); 126.8; 125.3; 122.8; 122.3; 116 (J ¼ 22); 108.0; 18.5; ꢀ 0.7. EI-MS: 324 (29, Mþ), 309 (35), 279
(12), 252 (18), 251 (100). HR-EI-MS: 324.1462 (Mþ, C19H21FN2Siþ; calc. 324.1458).
2-(4-Fluorophenyl)-6-methyl-8-[(E)-2-phenylethenyl]imidazo[1,2-a]pyridine (2h). Colorless solid.
1
M.p 137.58. H-NMR: 8.17 (d, J ¼ 18, HC¼)); 7.97 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.76 (br. s,
HꢀC(5)); 7.69 (s, HꢀC(3)); 7.63 (d, J ¼ 8, HꢀC(2,6) of C6H5); 7.47 (d, J ¼ 18, HC¼); 7.41 – 7.20 (m,
HꢀC(3,5) and H-C(4) of C6H5); 7.10 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 7.08 (br. s, HꢀC(7)); 2.25 (s, Me).
13C-NMR: 162.2 (J ¼ 246); 143.8; 142.7; 137.2; 133.3; 129.9; 128.2 (2 arom. C); 127.4 (J ¼ 8.1); 127.3;
126.6 (2 arom. C); 126.0; 125.6; 125.1; 123.4; 121.6; 115.0 (J ¼ 21.6); 107.3; 17.7. EI-MS: 328 (59, Mþ), 327
(100), 251 (6). HR-EI-MS: 328.1380 (Mþ, C22H17FN2þ ; calc. 328.1376).
1
3-Ethenyl-2-(4-fluorophenyl)imidazo[1,2-a]pyridine (2i). Colorless solid. M.p. 998. H-NMR: 8.40
(d, J ¼ 7, H ꢀC(5)); 7.82 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.67 (d, J ¼ 9, HꢀC(8)); 7.30 – 7.12 (m,
HꢀC(3,5) of C6H4F, HꢀC(7)); 6.95 (dd, J ¼ 18, 12, HC¼)); 6.89 (t, J ¼ 7, H ꢀC(6)); 5.73 (dd, J ¼ 18, 0.7,
H2C¼)); 5.58 (dd, J ¼ 12, 0.7, H2C¼). 13C-NMR: 162.0 (J ¼ 247); 145.4; 143.8; 131.0; 130.7; 130.5; 125.0;
124.2; 118.7; 117.7; 116.1; 115.5 (J ¼ 21.6); 112.8. EI-MS: 238 (60, Mþ), 237 (100), 236 (25), 118 (12). HR-
EI-MS: 238.0911 (Mþ, C15H11FN2þ ; calc. 238.0906).
2-(4-Fluorophenyl)-3-[(E)-2-phenylethenyl]imidazo[1,2-a]pyridine (2j). Colorless solid. M.p. 1148.
1H-NMR: 8.42 (dd, J ¼ 7, 1, H ꢀC(5)); 7.88 (dd, J ¼ 8.8, 5.3, HꢀC(2,6) of C6H4F); 7.70 (dd, J ¼ 9, 1,
HꢀC(8)); 7.53 – 7.15 (m, HꢀC(7), 5 H of C6H5, HꢀC(3,5) of C6H4F); 7.14 (d, J ¼ 17, HC¼); 7.10 (d, J ¼
17, HC¼); 6.89 (td, J ¼ 7, 1, H ꢀC(6)). 13C-NMR: 163.0 (J ¼ 246); 146.0; 144.7; 137.0; 133.2; 129.3; 129.0;
128.4; 128 (J ¼ 7); 126.8; 126.6; 125.3; 124.7; 119.2; 118.2; 116.0 (J ¼ 20); 113.0. EI-MS: 314 (100, Mþ),
313 (69), 237 (16), 78 (12). HR-EI-MS: 314.1225 (Mþ, C21H15FN2þ ; calc. 314.1219).
2-(4-Fluorophenyl)-3-[(E)-2-(trimethylsilyl)ethenyl]imidazo[1,2-a]pyridine (2k). Colorless solid.
M.p. 107 – 1098. 1H-NMR: 8.46 (dd, J ¼ 7, 1.1, H ꢀC(5)); 7.79 (dd, J ¼ 8.8, 5.5, HꢀC(2,6) of C6H4F);
7.65 (dd, J ¼ 9, 1.2, HꢀC(8)); 7.23 (ddd, J ¼ 9, 7, 1.1, HꢀC(7)); 7.15 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 7.10
(d, J ¼ 20, HC¼); 6.88 (td, J ¼ 7, 1.2, HꢀC(6)); 6.40 (d, J ¼ 20, HC¼); 0.20 (s, 3 Me). 13C-NMR: 163.2
(J ¼ 245); 147.6; 144.8; 134.2; 131.2; 128.7 (J ¼ 5); 127.1; 126.0; 125.7; 118.3; 117.0 (J ¼ 21.3); 114.2; 107.2;
0.1 (3C). EI-MS: 310 (88, Mþ), 309 (100), 295 (73), 237 (43), 217 (57). HR-EI-MS: 310.1306 (Mþ,
C18H19FN2Siþ; calc. 310.1302).
1
Ethyl 3-Ethenylimidazo[1,2-a]pyridine-2-carboxylate (2l). Colorless solid. M.p. 47 – 498. H-NMR:
8.41 (dt, J ¼ 8, 1.1, HꢀC(5)); 7.70 (dd, J ¼ 10, 1.1, HꢀC(8)); 7.41 (dd, J ¼ 18, 12, HC¼); 7.26 (ddd, J ¼ 10,
8, 1.1, HꢀC(7)); 6.91 (td, J ¼ 8, 1.1, HꢀC(6)); 5.91 (d, J ¼ 18, H2C¼); 5.73 (d, J ¼ 12, H2C¼); 4.47 (q, J ¼
6, CH2); 1.46 (t, J ¼ 6, Me). 13C-NMR: 168.0; 145.0; 134.0; 129.0; 126.4; 125.2; 124.1; 119.6; 118.0; 114.0;
61.4; 14.8. EI-MS: 216 (75, Mþ), 171 (26), 144 (81), 143 (100). HR-EI-MS: 216.0902 (Mþ, C12H12N2O2þ
;
calc. 216.0899).
Ethyl 3-[(E)-2-Phenylethenyl]imidazo[1,2-a]pyridine-2-carboxylate (2m). Colorless solid. M.p. 1988.
1H-NMR: 8.50 (d, J ¼ 7, H ꢀC(5)); 7.84 (d, J ¼ 16, HC¼); 7.74 (d, J ¼ 9.2, HꢀC(8)); 7.61 (d, J ¼ 7,
HꢀC(2,6) of C6H4F); 7.49 – 7.21 (m, HꢀC(3,5) and HꢀC(4) of C6H4F, HꢀC(7)); 7.34 (d, J ¼ 16, HC¼);
6.97 (t, J ¼ 7, H ꢀC(6)); 4.91 (q, J ¼ 7.2, CH2); 1.49 (t, J ¼ 7.2, Me). 13C-NMR: 163.6; 144.7; 136.4; 131.3;
135.0; 129.7; 128.6; 128.2; 126.7; 126.4; 124.8; 119.2; 113.6; 112.7; 61.0; 14.2. EI-MS: 292 (65, Mþ), 219
(100), 206 (24), 118 (61), 78 (46). HR-EI-MS: 292.1217 (Mþ, C18H16N2O2þ ; calc. 292.1212).
Ethyl 3-[(E)-2-(Trimethylsilyl)ethenyl]imidazo[1,2-a]pyridine-2-carboxylate (2n). Colorless solid.
M.p. 58 – 608. 1H-NMR: 8.45 (dd, J ¼ 7, 1, H ꢀC(5)); 7.64 (dd, J ¼ 9, 1, HꢀC(8)); 7.60 (d, J ¼ 20, HC¼);
7.21 (ddd, J ¼ 9, 7, 1, HꢀC(7)); 6.87 (td, J ¼ 7, 1, H ꢀC(6)); 6.53 (d, J ¼ 20, HC¼); 4.43 (q, J ¼ 7, CH2); 1.4
(t, J ¼ 7, Me); 0.29 (s, 3 Me). 13C-NMR: 162.8; 144.8; 137.7; 134.1; 128.2; 127.6; 125.2; 119.4; 114.0; 111.7;

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61.2; 14.2; 0.2 (3 C). EI-MS: 288 (19, Mþ), 273 (39), 245 (100), 187 (15), 73 (13). HR-EI-MS: 288.1298
(Mþ, C15H20N2O2Siþ; calc. 288.1294).
General Procedure for Sonogashira Cross-Coupling. Method A. Into a three-necked round-bottom
flask were introduced 1 (1 mmol), [Pd(PPh3)4] (69 mg, 6 mol-%), CuI (19 mg, 10 mol-%), N2-sat. (i-
Pr)2NH (1.7 ml, 12 mmol), THF (2 ml) and the appropriate alkyne (1.5 mmol), and the mixture was
stirred at r.t. for 1 h.
Method B. Into a three-necked round-bottom flask were introduced 1 (1.5 mmol), [PdCl2(PPh3)2]
(100 mg, 10 mol-%), CuI (28 mg, 10 mol-%), and the appropriate alkyne (1.8 mmol) in Et3N/DMF 1:1
(3 ml). The mixture was stirred at r.t. for 24 h.
Method C. Into a three-necked round-bottom flask were introduced 1 (1.5 mmol), [Pd2(dba)3]
(140 mg, 10 mol-%), CuI (28 mg, 10 mol-%), and the appropriate alkyne (1.8 mmol) in Et3N/DMF 1:1
(3 ml). The mixture was stirred at r.t. for 24 h.
2-Methyl-6-(phenylethynyl)imidazo[1,2-a]pyridine (3a). Prepared according to Method A; purified
by FC (Al2O3; CH2Cl2). Yield: 80%. M.p. 102 – 1038. 1H-NMR: 8.31 (m, HꢀC(5)); 7.57 (m, HꢀC(2,6) of
C6H5); 7.52 (d, J ¼ 9.4, HꢀC(8)); 7.40 (m, HꢀC(3,5) and HꢀC(4) of C6H5); 7.38 (s, HꢀC(3)); 7.26 (dd,
J ¼ 9.4, 1.6, HꢀC(7)); 2.50 (s, Me). 13C-NMR: 144.9; 144.4; 131.9; 129.0; 128.9; 128.8; 127.3; 123.1; 116.9;
110.2; 109.0; 90.7; 86.0; 14.9. Anal. calc. for C16H12N2: C 82.73, H 5.21, N 12.06; found: C 83.07, H 5.19, N
12.14.
6-(3-Hydroxyprop-1-ynyl)-2-methylimidazo[1,2-a]pyridine (¼ 3-(2-Methylimidazo[1,2-a]pyridin-6-
yl)prop-2-yn-1-ol; 3b)2). Prepared according to Method A; purified by FC (Al2O3; AcOEt). Yield:
83%. M.p. 150 – 1518. 1H-NMR: 8.18 (m, HꢀC(5)); 7.48 (d, J ¼ 9.3, HꢀC(8)); 7.34 (s, HꢀC(3)); 7.11 (dd,
J ¼ 9.3, 1.3, HꢀC(7)); 4.53 (s, CH2); 2.49 (s, Me). 13C-NMR: 144.8; 144.3; 128.7; 127.4; 116.9; 110.2; 108.5;
89.1; 82.1; 51.7; 14.7. Anal. calc. for C11H10N2O: C 70.95, H 5.41, N 15.04; found: C 71.13, H 5.29, N 15.14.
Ethyl 3-(2-Methylimidazo[1,2-a]pyridin-6-yl)prop-2-ynoate (3c). Method A, but for 5 h at 608;
purified by FC (Al2O3; CH2Cl2). Yield: 79%. M.p. 106 – 1078. 1H-NMR: 8.42 (m, HꢀC(5)); 7.53 (d, J ¼
9.3, HꢀC(8)); 7.40 (s, HꢀC(3)); 7.24 (dd, J ¼ 9.3, 1.6, HꢀC(7)); 4.34 (q, J ¼ 7.1, CH2); 2.50 (s, Me); 1.39
(t, J ¼ 7.1, Me ) . 13C-NMR: 154.1; 145.8; 144.6; 131.4; 126.8; 117.4; 110.6; 105.4; 83.4; 82.3; 62.7; 14.8; 14.5.
Anal. calc. for C13H12N2O2: C 68.41, H 5.30, N 12.27; found: C 68.53, H 5.29, N 12.14.
2-Methyl-6-[(trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine (3d). Prepared according to Method A;
purified by FC (SiO2; PE). Yield: 74%. M.p. 85 – 868. 1H-NMR: 8.24 (m, HꢀC(5)); 7.45 (d, J ¼ 9.3,
HꢀC(8)); 7.32 (s, HꢀC(3)); 7.16 (dd, J ¼ 9.3, 1.5, HꢀC(7)); 2.48 (s, Me); 0.28 (s, 3 Me). 13C-NMR: 144.9;
144.4; 129.9; 127.3; 117.0; 110.2; 108.9; 101.5; 96.0; 14.8; 0.30. Anal. calc. for C13H16N2Si: C 68.37, H 7.06, N
12.27; found: C 68.53, H 7.12, N 12.14.
2-(4-Fluorophenyl)-6-(phenylethynyl)imidazo[1,2-a]pyridine (3e). Prepared according to Method
A; purified by FC (Al2O3; CH2Cl2). Yield: 92%. M.p. 211 – 2128. 1H-NMR: 8.36 (m, HꢀC(5)); 7.95 (dd,
J ¼ 8.8, 5.5, HꢀC(2,6) of C6H4F); 7.81 (s, HꢀC(3)); 7.62 (d, J ¼ 9.4, HꢀC(8)); 7.57 (m, HꢀC(2,6) of
C6H5); 7.42 (m, HꢀC(3,5) and HꢀC(4) of C6H5); 7.31 (dd, J ¼ 9.4, 1.6, HꢀC(7)); 7.15 (t, J ¼ 8.8,
HꢀC(3,5) of C6H4F). 13C-NMR: 163.3 (J ¼ 246); 146.2; 145.0; 132.0; 130.0; 129.1; 128.9; 128.7; 128.3;
128.2 (J ¼ 8); 123.0; 117.5; 116.2 (J ¼ 21.5); 109.8; 108.4; 91.2; 85.8. Anal. calc. for C21H13FN2: C 80.75, H
4.20, N 8.97; found: C 80.98, H 4.19, N 9.03.
2-(4-Fluorophenyl)-6-(3-hydroxyprop-1-ynyl)imidazo[1,2-a]pyridine (¼ 3-[2-(4-Fluorophenyl)imi-
dazo[1,2-a]pyridin-6-yl]prop-2-yn-1-ol; 3f)2). Prepared according to Method A; purified by FC
(Al2O3; CH2Cl2). Yield: 92%. M.p. 185 – 1868. 1H-NMR: 8.77 (s, HꢀC(5)); 8.37 (s, HꢀC(3)); 8.02
(dd, J ¼ 8.8, 5.7, C(2,6) of C6H4F); 7.59 (d, J ¼ 9.2, HꢀC(8)); 7.29 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 7.23 (d,
J ¼ 9.2, HꢀC(7)); 5.44 (t, J ¼ 5.9, OH); 4.36 (d, J ¼ 5.9, CH2). 13C-NMR: 162.8 (J ¼ 243); 145.2; 144.5;
130.8; 130.6; 128.5 (J ¼ 8); 128.3; 117.5; 116.5 (J ¼ 21); 110.2; 108.6; 91.6; 81.1; 50.3. Anal. calc. for
C16H11FN2O: C 72.17, H 4.16, N 10.52; found: C 72.45, H 4.19, N 10.68.
2-(4-Fluorophenyl)-6-[(trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine (3h). Prepared according to
Method A; purified by FC (Al2O3; CH2Cl2). Yield: 83%. M.p. 198 – 1998. 1H-NMR: 8.33 (m, HꢀC(5));
7.95 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.80 (s, HꢀC(3)); 7.57 (d, J ¼ 9.3, HꢀC(8)); 7.24 (dd, J ¼ 9.3,
2
)
Systematic name in parenthesis. The atom numbering of the imidazo[1,2-a]pyridine core is used for
the anal. data.

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1.6, HꢀC(7)); 7.17 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 0.31 (s, 3 Me). 13C-NMR: 161.9 (J ¼ 245.5); 144.9;
143.6; 128.6; 128.0; 127.0; 126.8 (J ¼ 8.5); 116.0; 114.8 (J ¼ 21); 108.3; 106.9; 99.9; 95.3; 0.20. Anal. calc.
for C18H17FN2Si: C 70.10, H 5.56, N 9.08; found: C 70.35, H 5.44, N 9.13.
Ethyl 6-(Phenylethynyl)imidazo[1,2-a]pyridine-2-carboxylate (3i). Prepared according to Method
1
A; purified by FC (Al2O3; CH2Cl2). Yield: 87%. M.p. 157 – 1588. H-NMR: 8.37 (m, HꢀC(5)); 8.20 (s,
HꢀC(3)); 7.68 (d, J ¼ 9.4, HꢀC(8)); 7.56 (m, HꢀC(2,6) of C6H5); 7.41 (m, HꢀC(3,5) and HꢀC(4) of
C6H5); 7.36 (dd, J ¼ 9.4, 1.7, HꢀC(7)); 4.50 (q, J ¼ 7.1, CH2); 1.47 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.5; 144.5;
138.0; 132.1; 129.5; 129.4; 129.1; 128.9; 122.6; 119.1; 117.5; 111.5; 92.1; 85.1; 61.7; 14.9. Anal. calc. for
C18H14N2O2: C 74.47, H 4.86, N 9.65; found: C 74.45, H 4.89, N 9.68.
Ethyl 6-(3-Hydroxyprop-1-yn-1-yl)imidazo[1,2-a]pyridine-2-carboxylate (3j). Prepared according
to Method A; purified by FC (Al2O3; CH2Cl2/MeOH 95 :5). Yield: 92%. M.p. 172 – 1738. 1H-NMR: 8.79
(m, HꢀC(5)); 8.53 (s, HꢀC(3)); 7.65 (d, J ¼ 9.4, HꢀC(8)); 7.32 (dd, J ¼ 9.4, 1.4, HꢀC(7)); 5.45 (t, J ¼ 5.9,
OH); 4.33 (m, 2 CH2); 1.34 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.3; 144.2; 137.0; 131.3; 129.6; 119.2; 118.8;
109.8; 92.4; 80.5; 61.2; 50.3; 15.1. Anal. calc. for C13H12N2O3: C 63.93, H 4.95, N 11.47; found: C 94.07, H
5.19, N 11.38.
Ethyl 6-(3-Ethoxy-3-oxoprop-1-yn-1-yl)imidazo[1,2-a]pyridine-2-carboxylate (3k). Prepared ac-
cording to Method A, but for 5 h at 608; purified by FC (Al2O3; CH2Cl2). Yield: 37%. M.p. 128 – 1298.
1H-NMR: 8.51 (m, HꢀC(5)); 8.23 (s, HꢀC(3)); 7.72 (d, J ¼ 9.5, HꢀC(8)); 7.35 (dd, J ¼ 9.5, 1.6,
HꢀC(7)); 4.50 (q, J ¼ 7.1, CH2); 4.35 (q, J ¼ 7.1, CH2); 1.48 (t, J ¼ 7.1, Me); 1.41 (t, J ¼ 7.1, Me ) . 13C-NMR:
163.3; 153.8; 144.6; 138.7; 132.2; 128.7; 119.6; 117.8; 107.9; 83.1; 81.8; 62.9; 61.9; 14.8; 14.5. Anal. calc. for
C15H14N2O4: C 62.93, H 4.93, N 9.79; found: C 62.99, H 4.86, N 9.71.
Ethyl 6-[(Trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine-2-carboxylate (3l). Prepared according to
Method A; purified by FC (SiO2; Et2O).Yield: 83%. M.p. 156 – 1578. 1H-NMR: 8.32 (s, HꢀC(5)); 8.16 (s,
HꢀC(3)); 7.63 (d, J ¼ 9.3, HꢀC(8)); 7.27 (d, J ¼ 9.3, HꢀC(7)); 4.49 (q, J ¼ 7.1, CH2); 1.46 (t, J ¼ 7.1, Me ) ;
0.30 (s, 3 Me). 13C-NMR: 163.4; 144.5; 138.1; 129.8; 129.6; 119.0; 117.4; 111.3; 100.4; 97.9; 61.7; 14.8; 0.20.
Anal. calc. for C15H18N2O2Si: C 62.90, H 6.33, N 9.78; found: C 62.95, H 6.36, N 9.74.
2,6-Dimethyl-8-(phenylethynyl)imidazo[1,2-a]pyridine (4a). Prepared according to Method A;
purified by FC (SiO2; Et2O). Yield: 83%. M.p. 101 – 1028. 1H-NMR: 7.83 (m, HꢀC(5)); 7.67 (m,
HꢀC(2,6) of C6H5); 7.59 (m, HꢀC(3,5) and HꢀC(4) of C6H5); 7.31 (s, HꢀC(3)); 7.26 (d, J ¼ 1,
HꢀC(7)); 2.52 (s, Me); 2.31 (s, Me). 13C-NMR: 144.0; 143.9; 132.4; 131.6; 128.9; 128.7; 123.7; 123.4;
121.4; 112.1; 110.5; 95.2; 85.1; 18.2; 14.9. Anal. calc. for C17H14N2: C 82.90, H 5.73, N 11.37; found: C 83.24,
H 6.06, N 11.02.
2,6-Dimethyl-8-(3-hydroxyprop-1-yn-1-yl)imidazo[1,2-a]pyridine (¼ 3-(2,6-Dimethylimidazo[1,2-
a]pyridin-8-yl)prop-2-yn-1-ol; 4b)2). Prepared according to Method A; purified by FC (Al2O3;
1
CH2Cl2/MeOH 95 :5). Yield: 81%. M.p. 166 – 1678. H-NMR: 7.91 (s, HꢀC(5)); 7.23 (s, HꢀC(3)); 7.14
(d, J ¼ 1.4, HꢀC(7)); 5.33 (t, J ¼ 5.2, OH); 4.66 (d, J ¼ 5.2, CH2); 2.49 (s, Me); 2.29 (s, Me). 13C-NMR:
144.1; 143.6; 131.0; 123.5; 121.6; 111.6; 110.4; 94.9; 80.4; 51.6; 18.3; 14.7. Anal. calc. for C12H12N2O: C
71.98, H 6.04, N 13.99; found: C 72.35, H 6.07, N 14.05.
2,6-Dimethyl-8-[(trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine (4d). Prepared according to Method
A; purified by FC (SiO2; Et2O). Yield: 54%. M.p. 84 – 858. 1H-NMR: 7.84 (m, HꢀC(5)); 7.30 (s,
HꢀC(3)); 7.25 (d, J ¼ 1.2, HꢀC(7)); 2.50 (s, Me); 2.29 (s, Me); 0.24 (s, 3 Me). 13C-NMR: 144.1; 143.9;
132.6; 123.8; 121.2; 111.9; 110.5; 100.9; 100.1; 18.2; 14.9; 0.4. Anal. calc. for C14H18N2Si: C 69.37, H 7.48, N
11.56; found: C 69.54, H 7.49, N 11.47.
2-(4-Fluorophenyl)-6-methyl-8-(phenylethynyl)imidazo[1,2-a]pyridine (4e). Prepared according to
Method A; purified by FC (Al2O3; Et2O/PE 75 :25). Yield: 94%. M.p. 156 – 1578. 1H-NMR: 8.01 (dd, J ¼
8.8, 5.4, HꢀC(2,6) of C6H4F); 7.89 (m, HꢀC(5)); 7.77 (s, HꢀC(3)); 7.73 (m, HꢀC(2,6) of C6H5); 7.42 (m,
HꢀC(3,5) and HꢀC(4) of C6H5); 7.32 (d, J ¼ 1.5, HꢀC(7)); 7.15 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 2.34 (s,
Me). 13C-NMR: 163.1 (J ¼ 245.5); 145.3; 144.5; 132.4; 132.1; 130.3 (J ¼ 3.5); 129.1; 128.7; 128.3 (J ¼ 8);
124.0; 123.4; 122.2; 115.9 (J ¼ 21.5); 112.8; 108.8; 95.8; 84.9; 18.4. Anal. calc. for C22H15FN2: C 80.96; H
4.63, N 8.58; found: C 81.22, H 4.71, N 8.56.
2-(4-Fluorophenyl)-8-(3-hydroxyprop-1-yn-1-yl)-6-methylimidazo[1,2-a]pyridine (¼ 3-[2-(4-Fluoro-
phenyl)-6-methylimidazo[1,2-a]pyridin-8-yl]prop-2-yn-1-ol; 4f)2). Prepared according to Method A;
purified by FC (SiO2; CH2Cl2/Et2O 1:1). Yield: 87%. M.p. 181 – 1828. 1H-NMR: 8.35 (s, HꢀC(3),

Helvetica Chimica Acta – Vol. 90 (2007)
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HꢀC(5)); 8.02 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.29 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 7.28 (s,
HꢀC(7)); 5.51 (t, J ¼ 5.9, OH); 4.45 (d, J ¼ 5.9, CH2); 2.28 (s, Me). 13C-NMR: 162.7 (J ¼ 243); 144.3
(2C); 132.7; 131.2; 128.4 (J ¼ 8); 125.7; 122.2; 116.4 (J ¼ 21.5); 111.7; 110.5; 95.7; 80.3; 50.6; 18.1. Anal.
calc. for C17H13FN2O: C 72.84, H 4.67, N 9.99; found: C 72.88, H 4.68, N 9.97.
Ethyl 3-[2-(4-Fluorophenyl)-6-methylimidazo[1,2-a]pyridin-8-yl]prop-2-ynoate (4g). Prepared ac-
cording to Method A; purified by FC (Al2O3; Et2O/PE 1:1). Yield: 49%. M.p. 107 – 1088. 1H-NMR: 8.00
(m, HꢀC(5)); 7.98 (dd, J ¼ 8.9, 5.4, HꢀC(2,6) of C6H4F); 7.78 (s, HꢀC(3)); 7.40 (d, J ¼ 1.5, HꢀC(7));
7.15 (t, J ¼ 8.9, HꢀC(3,5) of C6H4F); 4.38 (q, J ¼ 7.1, CH2); 2.35 (s, Me); 1.42 (t, J ¼ 7.1, Me ) . 13C-NMR:
163.2 (J ¼ 245.5); 154.3; 145.9; 144.1; 134.8; 129.8; 128.4; 126.1; 122.1; 116.0 (J ¼ 21.5); 109.1; 108.9; 85.9;
81.5; 62.8; 18.2; 14.5. Anal. calc. for C19H15FN2O2: C 70.80, H 4.69, N 8.69; found: C 70.85, H 4.73, N 8.54.
2-(4-Fluorophenyl)-6-methyl-8-[(trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine (4h). Prepared ac-
1
cording to Method A; purified by FC (SiO2; CH2Cl2). Yield: 81%. M.p. 165 – 1668. H-NMR: 7.99 (dd,
J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.89 (m, HꢀC(5)); 7.75 (s, HꢀC(3)); 7.27 (d, J ¼ 1.6, HꢀC(7)); 7.13 (t,
J ¼ 8.8, HꢀC(3,5) of C6H4F); 2.33 (s, Me); 0.33 (s, 3 Me). 13C-NMR: 163.1 (J ¼ 245); 145.5; 144.7; 132.9;
130.4; 128.3 (J ¼ 8); 124.1; 122.0; 115.9 (J ¼ 21.5); 112.7; 108.5; 101.6; 99.9; 18.2; 0.38. Anal. calc. for
C19H19FN2Si: C 70.77, H 5.94, N 8.69; found: C 70.89, H 6.01, N 8.84.
Ethyl 6-Methyl-8-(phenylethynyl)imidazo[1,2-a]pyridine-2-carboxylate (4i). Prepared according to
Method A; purified by FC (SiO2; Et2O). Yield: 85%. M.p. 102 – 1038. 1H-NMR: 8.16 (s, HꢀC(3)); 7.94 (s,
HꢀC(5)); 7.68 (m, HꢀC(2,6) of C6H5); 7.40 (m, HꢀC(3,5) and HꢀC(4) of C6H5, HꢀC(7)); 4.52 (q, J ¼
7.1, CH2); 2.37 (s, Me); 1.47 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.6; 144.3; 137.3; 135.6; 133.5; 129.2; 128.7;
124.0; 123.8; 123.1; 117.9; 114.7; 92.1; 85.1; 61.7; 14.9. Anal. calc. for C19H16N2O2: C 74.98, H 5.30, N 9.20;
found: C 75.03, H 5.29, N 9.17.
Ethyl 8-(3-Hydroxyprop-1-yn-1-yl)-6-methylimidazo[1,2-a]pyridine-2-carboxylate (4j). Prepared
according to Method A; purified by FC (Al2O3; CH2Cl2/MeOH 95 :5). Yield: 74%. M.p. 186 – 1878.
1H-NMR: 8.51 (s, HꢀC(3)); 8.39 (s, HꢀC(5)); 7.40 (d, J ¼ 1.1, HꢀC(7)); 5.52 (br. s, OH); 4.43 (br. s,
CH2); 4.34 (q, J ¼ 7.2, CH2); 2.28 (s, Me); 1.34 (t, J ¼ 7.2, Me). 13C-NMR: 163.4; 143.9; 136.2; 134.2; 126.1;
123.5; 119.4; 112.9; 96.4; 79.6; 61.1; 50.5; 18.1; 15.2. Anal. calc. for C14H14N2O3: C 65.11, H 5.46, N 10.85;
found: C 65.47, H 5.79, N 11.12.
Ethyl 6-Methyl-8-[(Trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine-2-carboxylate (4l). Prepared ac-
cording to Method A; purified by FC (SiO2; Et2O). Yield: 79%. M.p. 126 – 1278. 1H-NMR: 8.14 (s,
HꢀC(3)); 7.93 (m, HꢀC(5)); 7.36 (d, J ¼ 1.4, HꢀC(7)); 4.46 (q, J ¼ 7.1, CH2); 2.34 (s, Me); 1.46 (t, J ¼ 7.1,
Me); 0.29 (s, 3 Me). 13C-NMR: 163.7; 144.2; 137.3; 134.7; 124.3; 123.7; 117.9; 114.4; 102.8; 99.0; 61.6; 18.3;
14.7; 0.58. Anal. calc. for C16H20N2O2Si: C 63.97, H 6.71, N 9.32; found: C 64.28, H 6.82, N 9.24.
2-(4-Fluorophenyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine (8a). Prepared according to Method
B; purified by FC (Al2O3; CH2Cl2). Yield: 75%. M.p. 119 – 1208. 1H-NMR: 8.41 (m, HꢀC(2,6) of C6H4F,
HꢀC(5)); 7.71 (dt, J ¼ 9, 1, HꢀC(8)); 7.64 (m, HꢀC(2,6) of C6H5); 7.47 (m, HꢀC(3,5) and HꢀC(4) of
C6H5); 7.34 (ddd, J ¼ 9, 6.8, 1, HꢀC(7)); 7.22 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F); 6.99 (td, J ¼ 6.8, 1,
HꢀC(6)). 13C-NMR: 163.5 (J ¼ 248); 147.6; 145.7; 131.7 (2 arom. C); 130.2 (J ¼ 3); 129.5 (J ¼ 8); 129.3;
129.1 (2 arom. C); 126.9; 125.6; 123.1; 117.9; 116,0 (J ¼ 21.5); 113.5; 104.9; 101.8; 78.5. Anal. calc. for
C21H13FN2: C 80.75, H 4.20, N 8.97; found: C 80.88, H 4.14, N 8.92.
Ethyl 3-(Phenylethynyl)imidazo[1,2-a]pyridine-2-carboxylate (8b). Prepared according to Method
1
C; purified by FC (Al2O3; CH2Cl2). Yield: 64%. M.p. 108 – 1098. H-NMR: 8.42 (d, J ¼ 6.9, HꢀC(5));
7.77 (d, J ¼ 9.1, HꢀC(8)); 7.67 (m, HꢀC(2,6) of C6H5); 7.42 (m, HꢀC(3,5) and HꢀC(4) of C6H5); 7.33
(m, HꢀC(7)); 7.05 (t, J ¼ 6.8, HꢀC(6)); 4.55 (q, J ¼ 7.1, CH2); 1.51 (t, J ¼ 7.1, Me ) . 13C-NMR: 162.9;
145.1; 138.8; 132.0 (2 arom. C); 129.6; 129.0 (2 arom. C); 127.9; 125.9; 122.6; 119.6; 114.8; 112.7; 102.4;
76.8; 61.8; 14.9. Anal. calc. for C18H14N2O2: C 74.47, H 4.86, N 9.65; found: C 74.53, H 4.91, N 9.66.
8-Bromo-2-(4-fluorophenyl)-6-methyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (8c). Prepared ac-
cording to Method A; purified by FC (SiO2; CH2Cl2). Yield: 30%. M.p. 1508. 1H-NMR: 8.39 (dd, J ¼ 8.6,
5.6, HꢀC(2,6) of C6H4F); 8.04 (br. s, HꢀC(5)); 7.62 (m, HꢀC(2,6) of C6H5); 7.44 (m, HꢀC(3,5) and
HꢀC(4) of C6H5); 7.39 (s, HꢀC(7)); 7.18 (t, J ¼ 8.6, HꢀC(3,5) of C6H4F); 2.38 (s, Me). 13C-NMR: 163.3
(J ¼ 244.6); 147.6; 142.4; 131.9; 131.7 (2 arom. C); 129.8; 129.6 (J ¼ 8); 129.3, 129.0 (2 arom. C); 123.5;
122.8; 122.7; 115.8 (J ¼ 21); 111.2; 106.6; 101.8; 78.4; 18.5.

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General Procedure for Desilylation. To a stirred soln. of 3d,h,l or 4d,h,l (0.35 mmol) in THF (1 ml)
was added TBAF (104 ml, 0.35 mmol) at r.t., and the resulting soln. was stirred for a further 10 min. After
quenching the reaction by adding sat. aq. NH4Cl soln., the org. solvent was removed by evaporation, and
the residue was extracted with AcOEt, dried (Na2SO4), and concentrated.
6-Ethynyl-2-(4-fluorophenyl)imidazo[1,2-a]pyridine (5a). Purified by FC (Al2O3; CH2Cl2). Yield:
1
88%. M.p. 216 – 2178. H-NMR: 8.35 (m, HꢀC(5)); 7.95 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.81 (s,
HꢀC(3)); 7.59 (d, J ¼ 9.3, HꢀC(8)); 7.25 (dd, J ¼ 9.3, 1.4, HꢀC(7)); 7.17 (t, J ¼ 8.7, HꢀC(3,5) of C6H4F);
3.16 (s, HCꢂ). 13C-NMR: 163.3 (J ¼ 245.5); 144.8; 143.6; 129.7 (2C); 128.3; 128.2 (J ¼ 8); 117.6; 116.2
(J ¼ 21.5); 108.7; 106.4; 80.1; 79.3. Anal. calc. for C15H9FN2: C 76.26, H 3.84, N 11.86; found: C 76.32, H
3.92, N 11.89.
6-Ethynyl-2-methylimidazo[1,2-a]pyridine (5b). Purified by FC (Al2O3; CH2Cl2). Yield: 94%. M.p.
116 – 1178. 1H-NMR: 8.25 (m, HꢀC(5)); 7.47 (d, J ¼ 9.3, HꢀC(8)); 7.33 (s, HꢀC(3)); 7.17 (d, J ¼ 9.3, 1.5,
HꢀC(7)); 3.12 (s, HCꢂ); 2.48 (s, Me). 13C-NMR: 145.0; 144.2; 129.4; 127.3; 117.0; 110.2; 107.8; 80.5;
78.8; 14.8. Anal. calc. for C10H8N2: C 76.90, H 5.16, N 17.94; found: C 76.94, H 5.21, N 17.88.
Ethyl 6-Ethynylimidazo[1,2-a]pyridine-2-carboxylate (5c). Purified by FC (SiO2; Et2O). Yield: 67%.
M.p. 130 – 1318. 1H-NMR: 8.36 (m, HꢀC(5)); 8.19 (s, HꢀC(3)); 7.67 (d, J ¼ 9.4, HꢀC(8)); 7.31 (dd, J ¼
9.4, 1.6, HꢀC(7)); 4.50 (q, J ¼ 7.1, CH2); 3.20 (s, HCꢂ); 1.47 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.4; 144.5;
138.2; 130.3; 129.4; 119.2; 117.5; 110.2; 80.3; 79.5; 61.7; 14.8. Anal. calc. for C12H10N2O2: C 67.28, H 4.71, N
13.08; found: C 67.33, H 4.69, N 13.07.
8-Ethynyl-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridine (6a). Purified by FC (Al2O3; CH2Cl2).
Yield: 82%. M.p. 211 – 2128. 1H-NMR: 7.99 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.94 (m, HꢀC(5)); 7.78
(s, HꢀC(3)); 7.29 (d, J ¼ 1.2, HꢀC(7)); 7.14 (t, J ¼ 8.8, HꢀC(3,5) of C6H4F); 3.60 (s, HCꢂ); 2.35 (s, Me).
13C-NMR: 163.2 (J ¼ 245); 145.6; 144.9; 132.9; 130.2; 128.4 (J ¼ 8); 124.4; 122.0; 155.9 (J ¼ 21.5); 111.6;
108.7; 83.8; 79.0; 18.3. Anal. calc. for C16H11FN2: C 76.79, H 4.43, N 11.19; found: C 76.88, H 4.72, N 11.14.
8-Ethynyl-2,6-Dimethylimidazo[1,2-a]pyridine (6b). Purified by FC (SiO2; Et2O). Yield: 89%. M.p.
72 – 738. 1H-NMR: 7.86 (m, HꢀC(5)); 7.31 (s, HꢀC(3)); 7.24 (s, HꢀC(7)); 3.50 (s, HC ꢂ ); 2.50 (s, Me);
2.31 (s, Me). 13C-NMR: 144.2; 132.4; 132.0; 124.1; 121.2; 110.8; 110.5; 83.4; 79.0; 18.2; 14.9. Anal. calc. for
C11H10N2: C 77.62, H 5.92, N 16.46; found: C 77.78, H 5.97, N 16.40.
Ethyl 8-Ethynyl-6-methylimidazo[1,2-a]pyridine-2-carboxylate (6c). Purified by FC (Al2O3; Et2O).
Yield: 86%. M.p. 140 – 1418. 1H-NMR: 8.16 (s, HꢀC(3)); 7.96 (m, HꢀC(5)); 7.37 (d, J ¼ 1.4, HꢀC(7));
4.48 (q, J ¼ 7.1, CH2); 3.55 (s, HCꢂ); 2.36 (s, Me); 1.46 (t, J ¼ 7.1, Me ) . 13C-NMR: 163.6; 144.5; 137.5;
134.4; 124.6; 123.7; 117.9; 113.5; 85.0 (2 C); 61.6; 18.4; 14.8. Anal. calc. for C13H12N2O2: C 68.41, H 5.30, N
12.27; found: C 68.54, H 5.24, N 12.33.
Typical Procedure for the Preparation of Compounds 5a,c and 9a,d. [Pd(PPh3)4] (69 mg, 6 mol-%)
and tributyl(ethynyl)stannane (0.57 g, 1.8 mmol) or allenyl(tributyl)stannane (0.59 g, 1.8 mmol) in DMF
(5 ml) were added dropwise to a soln. of the appropriate starting material (1a, 1d, 1e, or 1g; 1 mmol) in
DMF (35 ml). The mixture was stirred at 808 for 4 h, and then diluted with Et2O (50 ml). The org. layer
was washed with sat. aq. NH4Cl soln. (3 ꢁ 25 ml), dried (MgSO4), and concentrated in vacuo. The crude
product (5a,c or 9a,d) was purified by FC (SiO2; PE/Et2O/Et3N 25 :73 :2).
Ethyl 3-Ethynylimidazo[1,2-a]pyridine-2-carboxylate (9a). Colorless solid. M.p. 102 – 1048. 1H-NMR
(CDCl3, 400 MHz): 8.40 (d, J ¼ 6.9, HꢀC(5)); 7.78 (d, J ¼ 9.2, HꢀC(8)); 7.30 (dd, J ¼ 9.1, 6.9, HꢀC(7));
7.0 (t, J ¼ 6.9, HꢀC(6)); 4.55 (q, J ¼ 7.2, CH2); 2.10 (s, HC ꢂ ); 1.50 (t, J ¼ 7.2, Me). 13C-NMR (CDCl3,
100 MHz): 163.0; 144.2; 139.1; 128.3; 126.1; 119.7; 115.2; 113.1; 90.1; 79.0; 61.2; 14.3. EI-MS: 214 (58,
Mþ); 169 (27); 143 (100). HR-EI-MS: 214.0748 (Mþ, C12H10N2Oþ2 ; calc. 214.0742).
3-Ethynyl-2-(4-Fluorophenyl)imidazo[1,2-a]pyridine (9b). Colorless solid. M.p. 196 – 1988. 1H-NMR
(CDCl3, 400 MHz): 8.34 (d, J ¼ 6.8, HꢀC(5)); 7.70 (dd, J ¼ 8.8, 5.4, HꢀC(2,6) of C6H4F); 7.62 (d, J ¼ 9.2,
HꢀC(8)); 7.36 (dd, J ¼ 9.2, 6.8, HꢀC(7)); 7.20 – 7.06 (m, HꢀC(3,5) of C6H4F); 6.99 (t, J ¼ 6.8, HꢀC(6));
1.91 (s, HC ꢂ ). 13C-NMR (CDCl3, 100 MHz): 162.5 (J ¼ 246); 147.5; 145.5; 129.0; 126.8; 124.8; 124.5;
117.5; 115.4 (J ¼ 21); 113.3; 107.5, 89.2; 78.0. EI-MS: 236 (Mþ, 100); 141 (43); 117 (72). HR-EI-MS:
236.0756 (Mþ, C15H9FNþ2 ; calc. 236.0750).
2-(4-Fluorophenyl)-6-prop-1-yn-1-ylimidazo[1,2-a]pyridine (9c). Colorless solid. M.p. 164 – 1668.
1H-NMR (CDCl3, 400 MHz): 8.14 (br. s, HꢀC(5)); 7.89 (dd, J ¼ 8.7, 5.4, HꢀC(2,6) of C6H4F); 7.70 (s,
HꢀC(3)); 7.51 (d, J ¼ 9.2, HꢀC(8)); 7.15 – 7.09 (m, HꢀC(3,5) of C6H4F, H ꢀC(7)); 2.06 (s, MeꢀCꢂ).

Helvetica Chimica Acta – Vol. 90 (2007)
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13C-NMR (CDCl3, 100 MHz): 162.5 (J ¼ 246); 145.2; 144.2; 129.4; 128.0; 127.6; 127.4 (J ¼ 8); 116.6; 115.4
(J ¼ 21.6); 109.8; 107.5; 87.2; 75.4; 29.4. EI-MS: 250 (100, Mþ), 211 (61), 155 (66). HR-EI-MS: 250.0910
(Mþ, C16H11FNþ2 ; calc. 250.0906).
Ethyl 3-Prop-1-yn-1-ylimidazo[1,2-a]pyridine-2-carboxylate (9d). Colorless solid. M.p. 58 – 608.
1H-NMR: 8.31 (dd, J ¼ 8, 2, HꢀC(5)); 7.70 (dd, J ¼ 10, 2, HꢀC(8)); 7.32 (m, HꢀC(7)); 6.97 (td, J ¼ 8, 2,
HꢀC(6)); 4.51 (q, J ¼ 7.2, CH2); 2.31 (s, MeꢀCꢂ); 1.47 (t, J ¼ 7.2, Me). 13C-NMR: 163.1; 145.3; 139.1;
128.3; 126.2; 119.8; 115.2; 113.3; 89.3; 77.3; 61.6; 29.4; 15.1. EI-MS: 228 (37, Mþ), 183 (45), 143 (100).
HR-EI-MS: 228.0904 (Mþ, C13H12N2O2þ ; calc. 228.0899).
3-[2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-6-yl]-N,N-bis(1-methylethyl)prop-2-yn-1-amine (10a).
Into a three-necked round-bottom flask were introduced 1a (800 mg, 2.4 mmol), [Pd(PPh3)4] (160 mg,
6 mol-%), CuI (45 mg, 10 mol-%), N2-sat. (i-Pr)2NH (4 ml, 28.8 mmol), N,N-bis(1-methylethyl)prop-2-
yn-1-amine (422 mg, 3.1 mmol) and THF (5 ml). The mixture was stirred at r.t. for 1 h. The product was
purified by FC (Al2O3; CH2Cl2). Yield: 81%. M.p. 150 – 1528. 1H-NMR (CDCl3, 500 MHz): 8.20 (s,
HꢀC(5)); 7.91 (dd, J ¼ 8, 5.5, HꢀC(2,6) of C6H4F); 7.76 (s, HꢀC(3)); 7.53 (d, J ¼ 9.5, HꢀC(8)); 7.14 (m,
HꢀC(3,5) of C6H4F, HꢀC(7)); 3.66 (s, NCH2); 3.28 (t, J ¼ 6.5, 2 CH); 1.17 (d, J ¼ 6.5, 4 Me). 13C-NMR
(CDCl3, 100.6 MHz): 162.5 (J ¼ 247); 145.4; 144.3; 129.4; 127.7 (2 C); 127.5 (J ¼ 8); 116.7; 115.4 (J ¼
21.6); 109.4; 107.5; 90.4; 79.2; 48.4; 34.6; 20.4.
Ethyl 6-{3-[Bis(1-methylethyl)amino]prop-1-yn-1-yl}imidazo[1,2-a]pyridine-2-carboxylate (10b).
Into a three-necked round-bottom flask were introduced 1g (1 g, 3.2 mmol), [Pd(PPh3)4] (220 mg,
6 mol-%), CuI (60 mg, 10 mol-%), N2-sat. (i-Pr)2NH (5.4 ml, 38.9 mmol), N,N-bis(1-methylethyl)prop-
2-yn-1-amine (650 mg, 4.8 mmol), and THF (6 ml). The mixture was stirred at r.t. for 1 h, and the product
was purified by FC (SiO2; AcOEt). Yield: 75%. M.p. 678. 1H-NMR (CDCl3, 500 MHz): 8.20 (s,
HꢀC(5)); 8.13 (s, HꢀC(3)); 7.59 (d, J ¼ 9.5, HꢀC(8)); 7.21 (d, J ¼ 9.5, HꢀC(7)); 4.46 (q, J ¼ 7.5, CH2);
3.65 (s, CH2); 3.26 (m, 2 CH); 1.44 (t, J ¼ 7.5, Me); 1.16 (d, J ¼ 6.5, 4 Me). 13C-NMR: 163.4; 144.5; 138.0;
129.7; 128.8; 118.9; 117.3; 111.7; 92.3; 79.3; 61.6; 49.1; 35.3; 21; 14.8.
Ethyl 3-{3-[Bis(1-methylethyl)amino]prop-1-yn-1-yl}imidazo[1,2-a]pyridine-2-carboxylate (12). In-
to a three-necked round-bottom flask were introduced 1e (1 g, 3.2 mmol), [Pd2(dba)3(CHCl3)] (280 mg,
10 mol-%), CuI (60 mg, 10 mol-%), and N,N-bis(1-methylethyl)prop-2-yn-1-amine (563 mg, 4.1 mmol)
in Et3N/DMF 1:1 (6 ml). The mixture was stirred at r.t. for 24 h, and the product was purified by FC
(SiO2; AcOEt). Yield: 53%. Oil. 1H-NMR: 8.17 (d, J ¼ 6.8, HꢀC(5)); 7.57 (d, J ¼ 8.5, HꢀC(8)); 7.20 (dd,
J ¼ 8.5, 6.8, HꢀC(7)); 6.87 (t, J ¼ 6.8, HꢀC(6)); 4.38 (q, J ¼ 7, CH2); 3.76 (s, CH2); 3.20 (t, J ¼ 6.5, 2 CH);
1.34 (t, J ¼ 7, Me); 1.08 (d, J ¼ 6.5, 4 Me). 13C-NMR: 162.8; 144.6; 138.2; 127.5; 125.6; 119.3; 114.5; 112.8;
102.9; 70.8; 61.5; 49.1; 35.7; 21.0; 14.8.
General Procedure for the Preparation of 11 and 13. A mixtu re of10 or 12 (200 mg),
[Pd2(dba)3(CHCl3)] (2.5 mol-%), and ꢁ1,2-bis[bis(pentafluorophenyl)phosphino]ethaneꢂ1) (10 mol-%)
was dissolved in anh. CHCl3 (3 ml) under Ar gas. The mixture was stirred at 1008 for 24 h in a sealed tube.
The solvent was removed under reduced pressure, and the residue was purified by FC (SiO2; AcOEt) to
afford 11 or 13, resp.
2-(4-Fluorophenyl)-6-propadienylimidazo[1,2-a]pyridine (11a). Yield: 66%. M.p. 1468 (dec.).
1H-NMR (CDCl3, 400 MHz): 7.94 (m, HꢀC(5)); 7.90 (dd, J ¼ 8.8, 5.6, C(2,6) of C6H4F); 7.72 (s,
HꢀC(3)); 7.56 (d, J ¼ 9.3, HꢀC(8)); 7.23 (dd, J ¼ 9.3, 1.5, HꢀC(7)); 7.11 (t, J ¼ 8.8, C(3,5) of C6H4F);
6.12 (t, J ¼ 6.8, CH); 5.25 (d, J ¼ 6.8, CH2). 13C-NMR (CDCl3, 100.6 MHz): 209.9; 162.4 (J ¼ 247.5); 144.6
(2 C); 129.5; 127.3 (J ¼ 7); 124.2; 121.8; 119.8; 116.9; 115.4 (J ¼ 21.1); 107.7; 90.2; 79.9. Anal. calc. for
C16H11FN2: C 76.79, H 4.43, N 11.19; found: C 76.72, H 4.48, N 11.22.
Ethyl 6-Propadienylimidazo[1,2-a]pyridine-2-carboxylate (11b). Yield: 71%. M.p. 1398. 1H-NMR
(CDCl3, 500 MHz): 8.10 (s, HꢀC(5)); 7.95 (s, HꢀC(3)); 7.58 (d, J ¼ 9.3, HꢀC(8)); 7.28 (d, J ¼ 9.3,
HꢀC(7)); 6.11 (t, J ¼ 7, CH); 5.24 (d, J ¼ 7, CH2); 4.43 (q, J ¼ 7.5, CH2); 1.41 (t, J ¼ 7.5, Me). 13C-NMR
(CDCl3, 100.6 MHz): 209.8; 162.9; 144.3; 136.7; 125.5; 122.0; 121.3; 118.4; 116.8; 90.0; 80.1; 60.8; 14.1.
Anal. calc. for C13H12N2O2: C 68.41, H 5.30, N 12.27; found: C 68.53, H 5.24, N 12.58.
Ethyl 3-Propadienylimidazo[1,2-a]pyridine-2-carboxylate (13). Yield: 32%. M.p. 1268. 1H-NMR
(CDCl3, 500 MHz): 8.76 (d, J ¼ 7, H ꢀC(5)); 7.71 (d, J ¼ 9.5, HꢀC(8)); 7.61 (t, J ¼ 7, CH); 7.30 (m,
HꢀC(7)); 6.90 (t, J ¼ 7, H ꢀC(6)); 5.42 (d, J ¼ 7.5, CH2); 4.49 (q, J ¼ 7, CH2); 1.46 (t, J ¼ 7.5, Me).

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Helvetica Chimica Acta – Vol. 90 (2007)
13C-NMR (CDCl3, 125.8 MHz): 209.4; 163.9; 144.9; 133.1; 126.2; 125.3; 120.3; 119.2; 113.7; 82.8; 80.4;
61.2; 14.5. Anal. calc. for C15H16N2O2: C 70.29, H 6.29, N 10.93; found: C 70.51, H 6.32, N 10.88.
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Received July 17, 2007