Metal-Free Approach to Zolpidem, Alpidem and their Analogues via Amination of Dibromoalkenes Derived from Imidazopyridine and Imidazothiazole

Article abstract of DOI:10.1002/ejoc.201900279

A novel efficient approach towards Zolpidem, Alpidem and their analogues was elaborated. The corresponding amides derived from imidazopyridine and imidazothiazole were prepared by the reaction of amines with previously unknown dibromoalkenes having these heterocyclic fragments. Amination of dibromoalkenes in the presence of water led directly to target drugs and their analogues in up to 95 % yield.

Full text of DOI:10.1002/ejoc.201900279

DOI: 10.1002/ejoc.201900279
Full Paper
Heterocyclic Amides
Metal-Free Approach to Zolpidem, Alpidem and their Analogues
via Amination of Dibromoalkenes Derived from Imidazopyridine
and Imidazothiazole
Vasiliy M. Muzalevskiy,[a] Zoia A. Sizova,[a] Alexey V. Shastin,[b] and
Valentine G. Nenajdenko*[a]
Abstract: A novel efficient approach towards Zolpidem, Alpi- dibromoalkenes having these heterocyclic fragments. Amin-
dem and their analogues was elaborated. The corresponding ation of dibromoalkenes in the presence of water led directly
amides derived from imidazopyridine and imidazothiazole were to target drugs and their analogues in up to 95 % yield.
prepared by the reaction of amines with previously unknown
Several imidazo[1,2-a]pyridine derivatives have been already
Introduction
marketed.[4] Alpidem, Saripidem and Necopidem are the anxio-
lytic drugs;[5] Zolpidem is one of the most popular medicines
Heterocyclic compounds are of great importance for modern
drug discovery and agrochemistry.[1] Majority of current drugs
contains a heterocyclic moiety in the structure. Nowadays,
about 59 % of small-molecule drugs, approved by US FDA, con-
tain a nitrogen heterocycle in their structure.[2] Among those
imidazo[1,2-a]pyridine derivatives are the one of the most at-
tractive compounds, which possess a broad range of pharmaco-
for treatment of insomnia having very low dose for patients and
low side effects[6] (Figure 1). Olprinone is a cardiotonic agent,[7]
Zolimidine is used as gastroprotective drug,[8] Miroprofen is an
analgesic and nonsteroidal anti-inflammatory drug,[9] Mino-
dronic acid is approved for treatment osteoporosis.[10]
Most strategies for the synthesis of Zolpidem started from
logical activities such as antiinflammatory, anticancer, antiviral, assembly of imidazopyridine core, followed by functionalization
antiosteoporotic, antiparasitic, antihypertensive and others (Fig- of the 3-position. As a rule the last steps of the majority of
ure 1).[3]
approaches include preparation of amide functionality from
Figure 1. Some pharmaceuticals of imidazopyridine family.
cyano, ester or carboxylic groups which usually demands 2–3
additional routine synthetic operations. For example, a Man-
nich-type alkylation of appropriate imidazopyridine followed by
quaternization with methyl iodide and nucleophilic substitution
with sodium cyanide led to the corresponding nitrile, which
was converted into Zolpidem in two steps (Scheme 1).[11]
[a] Department of Chemistry, Lomonosov Moscow State University,
119899 Moscow, Russia
E-mail: nenajdenko@org.chem.msu.ru
http://www.chem.msu.ru/rus/chair/org_w/os/welcome.html
[b] Institute of Problems of Chemical Physics, Russian Academy of Sciences,
142432 Chernogolovka, Russia
http://www.chem.msu.ru/rus/chair/org_w/os/welcome.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900279.
Alternatively this key nitrile can be prepared in one step via
a visible light-promoted reaction of imidazopyridine with
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Scheme 1. Most significant examples of Zolpidem synthesis.
bromoacetonitrile or iodoacetonitrile using fac-Ir(ppy)3 as a cat- Results and Discussions
alyst.[12] Another approach towards this Zolpidem precursor
Several years ago a novel catalytic olefination reaction (COR)
was discovered in our lab.[26] This novel reaction opened effi-
cient access to various dihaloalkenes.[27] We decided to prepare
novel type of heterocyclic dibromoalkenes derived from imidaz-
opyridine and imidazothiazole and use them for synthesis of
Zolpidem, Alpidem and their analogues. To start our investiga-
tion, a set of 3-imidazopyridine carbaldehydes 1a–g and 3-imid-
azothiazole carbaldehydes 1h–j was prepared by Vilsmeier–
Haack formylation of the corresponding heterocycles. Next, COR
with model aldehyde 1b was studied. It turned out that the
reaction proceeded with the formation of only trace amounts
of the corresponding alkene. As alternative method to prepare
desired alkenes, we decided to use the Wittig type olefination.
To our delight, standard protocol for the olefination with CBr4/
PPh3 permited to prepare previously unknown dibromoalkenes
containing the imidazopyridine 2a–g and imidazothiazole 2h–j
moieties in moderate to high yields (Scheme 2). It should be
noted, that this is the first synthesis of dibromoalkenes with
such heterocyclic fragment. To date no examples of their syn-
thesis were reported.
was based on iron-catalyzed dehydrogenative sp3–sp2 coupling
via direct oxidative C–H activation of acetonitrile.[13] Modifica-
tion of 3-position was also performed by alkylation with xantha-
tes,[14] 2-bromo-N,N-dimethylacetamide,[15] oxalyl chloride,[16]
ethyl (chlorocarbonyl)formate,[17] formyl-N,N-dimethylform-
amide,[18] formylformic acid,[19] methyl formylformate and
methyl 2-hydroxy-2-methoxyacetate[20] to form the correspond-
ing precursors of Zolpidem. Synthesis of Zolpidem has also
been achieved by one step reaction of Morita–Baylis–Hillman
acetates of nitroalkenes with 2-amino-5-methylpyridine.[21] Sim-
ilarly condensation of 3-bromo(iodo)-N,N-dimethyl-4-oxo-4-p-
tolylbutanamides with 2-amino-5-methylpyridine led directly to
Zolpidem.[22] However, preparation of these starting reagents
required several steps. Gevorgyan and co-workers elaborated
an efficient one pot copper-catalyzed three-component cou-
pling of 2-aminopyridines, benzaldehydes and acetylenes to
synthesize Zolpidem and their analogues.[23] Recently “on air”
(without isolation from the atmosphere) modifications of this
approach were elaborated.[24] In spite of this approach is
shorter than other methods, application of copper catalyst may
inflict difficulties aroused from toxicity of traces of copper in
the final product and application of such methods is restricted
by FDA for industrial processes. Therefore, shorter procedures
to prepare diverse imidazo[1,2-a]pyridine derivatives as well as
developing environmentally friendly reaction conditions are still
highly desirable.
Having in hand this promising dibromoalkenes, their reac-
tion with amines was investigated. This approach has demon-
strated effectiveness for the synthesis of amides when the reac-
tion proceeds in the presence of water.[25b] First, model reaction
with highly nucleophilic pyrrolidine was studied. It was found,
that the reaction of model alkene 2a with excess of pyrrolidine
1,1-Dihalo-1-alkenes are highly attractive multipurpose (20 equivalents) in the presence of water in THF gave the corre-
building blocks due to possibility of their functionalization by sponding amide 3a in 85 % isolated yield (Scheme 3). The reac-
substitution of halogens. The presence of active for substitution tion was performed overnight at room temperature. These con-
halogen atoms in the structure of 1,1-dihalo-1-alkenes makes ditions were found applicable also for other alkenes. Dibromod-
them highly attractive multipurpose building blocks.[25] This erivatives 2b–g were converted successfully to amides 3b–g in
study is devoted to a novel simple approach to various deriva- up to 85 % yield. To demonstrate generality of the method, the
tives of imidazopyridine and imidazothiazole including Zolpi- reaction with imidazothiazole derivatives 2h–j was examined.
dem and Alpidem.
To our delight, these alkenes also reacted with pyrrolidine
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Scheme 2. Synthesis of alkenes 2.
Scheme 3. Synthesis of amides 3.
highly efficiently to form desired amides 3h–j in up to 95 % mixture homogeneous. Alkene 2d was totally consumed during
yield (Scheme 3).
1 day, but the reaction led to expected amide in less than 10 %
yield accompanying with formation of several non identifying
products. The possible explanation of this fact could be influ-
ence of water (molar ratio of H2O/Me2NH is about 5:1 in 33 %
solution of dimethylamine). To eliminate excessive amount of
water to the mixture of 33 % Me2NH (1 mL) with THF (1 mL)
1 g of KOH was added and stirred for several minutes. After
formation of two layers (lower one is saturated water solution
of KOH) the upper layer was decanted and thus obtained solu-
tion of water and dimethylamine in THF was treated with alk-
ene 2d. This modification of the reaction gave smoothly amide
4d in 60 % yield. Using these optimal conditions a set of imidaz-
opyridine and imidazothiazoles 4 dimethylamides was synthe-
sized in up to 86 % yield (Scheme 5).
The mechanism of the transformation of alkenes 2 into
amides 3 was not investigated in detail in this study. We assu-
mied that the mechanism is similar to the previously reported
one for the transformation of dibromostyrenes to amides.[25d]
Most probably the reaction scheme includes following steps
(Scheme 4). Firstly, elimination of hydrogenbromide afforded
bromoalkyne A. Next, acetylene A reacts with amine to form
ynamine B, which is a key intermediate of the reaction. Addition
of water to the ynamine B leads to the final amide 3.
Next, the reaction with dimethylamine was investigated.
First, the reaction of model alkene 2d with 33 % solution of
dimethylamine in water (the cheapest commercial source) was
studied. Alkene 2d is not soluble in water, however, using of
1:1 mixture of aqueous solution of dimethylamine with THF al-
Next, various primary and secondary amines were studied as
lowed to dissolve alkene 2d in a few hours to make the reaction nucleophiles in the reaction. It was found that the efficiency
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Scheme 4. Synthesis of amides 3.
amine (Scheme 6). As a result the approach was found very
general in terms of scope of amines.
Rounding up our investigation, we decided to prepare Zolpi-
dem and Alpidem. Using optimal conditions found for the reac-
tion with dimethylamine, alkene 2a was successfully trans-
formed to Zolpidem in 81 % yield at room temperature
(Scheme 7). The reaction of alkene 2b with di(n-propyl)amine
afforded Alpidem in 79 % yield at heating (Scheme 7). The pro-
posed approach has some advantages comparing to known
methods for synthesis of these drugs. For example, Zolpidem
can be prepared only in two synthetic steps starting from com-
mercially available aldehyde. Moreover, the approach demands
no manipulations aroused from contamination of products with
copper and other metals.
Scheme 5. Synthesis of dimethylamides 4.
of the reaction depends significantly on the nucleophilicity of
amines. In contrast to the reaction with pyrrolidine and dimeth-
ylamine, complete conversion of 2a in the reaction with less
nucleophilic piperidine, hexamethyleneimine and di(n-
propyl)amine required to increase temperature up to 80–85 °C.
As a rule the reaction proceeded smoothly to give the corre-
sponding amides 5–7 in up to 70 % yield (Scheme 6). Primary
amines were also successfully involved into this transformation.
Thus, amides 8–10 were synthesized in good yields by the reac-
tion with methylamine, n-hexylamine and 3-methoxypropyl-
Scheme 7. Synthesis of Zolpidem and Alpidem.
Scheme 6. Scope of amines.
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2-PhenylH-imidazo[1,2-a]pyridine-3-carbaldehyde (1e). Pale
beige-yellow powder; m.p. 147–148 °C; 1H NMR (400 MHz, CDCl3):
δ [ppm] = 7.30 (td, J = 7.0, 1.1 Hz, 1H), 7.50–7.56 (m, 3H), 7.71 (ddd,
J = 8.9, 7.0, 1.2 Hz, 1H), 7.86–7.89 (m, 3H), 9.54 (d, J = 6.7 Hz, 1H),
9.98 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ [ppm] = 115.9, 117.2,
120.1, 128.2, 128.8, 129.7, 131.0, 132.1, 147.0, 156.7, 179.2. The NMR
data are in agreement with those in the literature.[31]
Conclusion
In summary, a novel two step procedure towards Zolpidem,
Alpidem and their analogues was elaborated. A set of previ-
ously unknown dibromoalkenes derived from imidazopyridine
and imidazothiazole was prepared using Wittig olefination of
the corresponding aldehydes. This key step can be performed
efficiently using CBr4/PPh3 system. Amination of dibromoalk-
enes with different primary and secondary amines in the pres-
ence of water led directly to target drugs and their analogues
in up to 95 % yield. The method was successfully used for the
synthesis of Zolpidem, Alpidem and their analogues.
6-Bromo-2-phenylH-imidazo[1,2-a]pyridine-3-carbaldehyde
(1f). Pale beige powder; m.p. 184.6–187 °C; 1H NMR (400 MHz,
CDCl3): δ [ppm] = 7.51–7.56 (m, 3H), 7.63–7.71 (m, 2H), 7.79–7.83
(m, 2H), 9.84 (s, 1H), 10.06 (s, 1H). The NMR data are in agreement
with those in the literature.[31]
2-(4-Methoxyphenyl)H-imidazo[1,2-a]pyridine-3-carbaldehyde
(1g). Pale beige-gray powder; m.p. 188.5–189.1 °C; 1H NMR
(400 MHz, CDCl3): δ [ppm] = 3.82 (s, 3H), 6.99 (d, J = 8.8 Hz, 2H),
7.04 (td, J = 6.9, 1.2 Hz, 1H), 7.50 (ddd, J = 8.9, 7.0, 1.3 Hz, 1H), 7.69–
7.72 (m, 1H), 7.73 (d, J = 8.8 Hz, 2H), 9.58 (d, J = 6.8 Hz, 1H), 9.99
(s, 1H); 13C NMR (CDCl3, 100 MHz): δ [ppm] = 55.3, 114.2, 114.9,
117.0, 120.3, 124.6, 128.6, 130.2, 131.0, 147.6, 158.0, 160.9, 179.3.
The NMR data are in agreement with those in the literature.[32]
Experimental Section
General Remarks: NMR spectra were recorded at 400.1 (1H) and
100.6 (13C) MHz respectively from solutions in CDCl3. Chemical
shifts (δ) in ppm are reported with the use of the residual chloro-
form signals (7.25 for 1H and 77.00 for 13C) as internal references.
The coupling constants (J) are given in Hertz (Hz). The multiplicity
of the signals is indicated as “s”, “d”, “t” or “m” for singlet, doublet,
triplet or multiplet, respectively. The abbreviation “br” is given for
broadened signals. The silica gel used for flash chromatography was
230–400 mesh. All reagents were of reagent grade and were either
used as such or distilled prior to use.
6-Phenylimidazo[2,1-b]thiazole-5-carbaldehyde (1h). Beige-yel-
low powder; m.p. 129–130 °C (lit. data,[33] 133–135 °C); 1H NMR
(400 MHz, CDCl3): δ [ppm] = 6.99 (d, J = 4.4 Hz, 1H), 7.39–7.46 (m,
3H), 7.71–7.76 (m, 2H), 8.31 (d, J = 4.4 Hz, 1H), 9.84 (s, 1H); 13C NMR
(CDCl3, 100 MHz): δ [ppm] = 114.5, 121.3, 123.8, 128.7, 128.9, 129.5,
132.3, 155.4, 157.9, 177.8. HRMS (ESI): m/z calcd. for C12H9N2OS+ [M
+ H+]: 229.043, found 229.0428.
Aldehydes 1 were prepared by Vilsmeier–Haack formylation of cor-
responding imidazo fused heterocycles using literature proce-
dures.[28]
2-Phenylimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde (1i).
White powder; m.p. 189.5–191.5 °C; 1H NMR (400 MHz, CDCl3): δ
[ppm] = 7.39 (td, J = 7.7, 1.2 Hz, 1H), 7.48–7.53 (m, 4H), 7.69 (dd,
J = 8.0, 0.9 Hz, 1H), 7.72–7.76 (m, 2H), 9.17 (d, J = 8.2 Hz, 1H), 9.83
(s, 1H); 13C NMR (CDCl3, 100 MHz): δ [ppm] = 118.5, 123.5, 125.7,
126.5, 126.7, 128.65, 128.74, 129.6, 129.7, 132.3, 133.7, 154.7, 161.2,
178.0. The NMR data are in agreement with those in the litera-
ture.[34] HRMS (ESI): m/z calcd. for C16H11N2OS+ [M + H+]: 279.0587,
found 279.0587.
6-Methyl-2-p-tolylH-imidazo[1,2-a]pyridine-3-carbaldehyde
(1a). Pale brown solid; m.p. 151.5–153.5 °C; 1H NMR (400 MHz,
CDCl3): δ [ppm] = 2.43 (s, 6H), 7.32 (d, J = 7.8 Hz, 2H), 7.41 (dd, J =
9.0, 1.3 Hz, 1H), 7.67–7.71 (m, 3H), 9.47 (s, 1H), 10.01 (s, 1H); 13C
NMR (CDCl3, 100 MHz): δ [ppm] = 18.3, 21.3, 116.5, 120.4, 125.2,
126.7, 129.5, 129.6, 133.1, 139.8, 146.6, 158.2, 179.4. The NMR data
are in agreement with those in the literature.[28c,29]
6-(3,4-Dichlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde
(1j). Beige-green powder; m.p. 217.5–219.5 °C; 1H NMR (400 MHz,
CDCl3): δ [ppm] = 7.34 (d, J = 4.4 Hz, 1H), 7.59 (dd, J = 8.3, 2.0 Hz,
1H), 7.66 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 8.50 (d, J =
4.4 Hz, 1H), 9.86 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ [ppm] = 117.8,
121.5, 123.2, 128.2, 128.9, 130.8, 131.5, 133.9, 135.7, 152.5, 154.2,
177.9. HRMS (ESI): m/z calcd. for C12H7Cl2N2OS+ [M + H+]: 296.9651,
found 296.9652.
6-Chloro-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridine-3-carb-
aldehyde (1b). Pale brown powder; m.p. 194.5–195.1 °C; 1H NMR
(400 MHz, CDCl3): δ [ppm] = 7.51 (d, J = 8.5 Hz, 2H), 7.55 (dd, J =
9.6, 2.1 Hz, 1H), 7.73 (d, J = 9.6 Hz, 1H), 7.75 (d, J = 8.5 Hz, 2H), 9.73
(d, J = 1.3 Hz, 1H), 10.04 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ
[ppm] = 117.6, 120.8, 123.7, 126.7, 129.3, 130.4, 130.9, 131.7, 136.5,
146.0, 156.9, 179.2. The NMR data are in agreement with those in
the literature.[30]
General procedure for the synthesis dibromoalkenes 2. A three
neck 100 mL round-bottom flask equipped with stirring bar, drop-
ping funnel, thermometer and calcium chloride drying tube was
charged with dry CH2Cl2 (25 mL), aldehyde 1 (10 mmol), PPh3
(24 mmol, 2.4 equiv.) and cooled to 0 °C on ice bath. Next, solution
of CBr4 (12 mmol, 1.2 equiv.) in CH2Cl2 (25 mL) was added dropwise
at stirring keeping temperature below 5–10 °C (about 10–15 min).
The bath was removed and the reaction mixture was left at room
temperature overnight. After that the reaction mixture was brought
into saturated NaHCO3 solution (100 mL) and extracted with CH2Cl2
(3 × 25 mL). Combined extract was washed with brine (30 mL),
dried with Na2SO4 and the solvents evaporated in vacuo. The resi-
due was purified by column chromatography on silica gel using
appropriate eluents (CH2Cl2, CH2Cl2/MeOH = 30:1, hexane/EtOAc =
1:1).
2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridine-3-carbaldehyde
(1c). Pale beige powder; m.p. 211.3–212.1 °C; 1H NMR (400 MHz,
CDCl3): δ [ppm] = 7.12 (td, J = 9.6, 1.0 Hz, 1H), 7.49 (d, J = 8.6 Hz,
2H), 7.57 (ddd, J = 8.9, 7.0, 1.3 Hz, 1H), 7.75 (d, J = 8.6 Hz, 2H), 7.78
(d, J = 8.6 Hz, 1H), 9.62 (d, J = 6.9 Hz, 1H), 10.02 (s, 1H); 13C NMR
(CDCl3, 100 MHz): δ [ppm] = 115.4, 117.4, 120.7, 128.8, 129.1, 130.6,
130.8, 130.9, 136.2, 147.7, 156.9, 179.0. The NMR data are in agree-
ment with those in the literature.[31]
2-(4-Bromophenyl)H-imidazo[1,2-a]pyridine-3-carbaldehyde
(1d). Pale beige powder; m.p. 211.9–212.7 °C; 1H NMR (400 MHz,
CDCl3): δ [ppm] = 7.12 (t, J = 6.9 Hz, 1H), 7.55–7.59 (m, 1H), 7.64 (d,
J = 8.5 Hz, 2H), 7.68 (d, J = 8.5 Hz, 2H), 7.77 (d, J = 8.9 Hz, 1H), 9.62
(d, J = 6.8 Hz, 1H), 10.01 (s, 1H); 13C NMR (CDCl3, 100 MHz): δ
[ppm] = 115.5, 117.4, 120.6, 124.5, 128.8, 130.6, 131.15, 131.22,
132.1, 147.7, 156.8, 179.0. The NMR data are in agreement with 3-(2,2-Dibromovinyl)-6-methyl-2-p-tolylH-imidazo[1,2-a]pyrid-
those in the literature.[31]
ine (2a). Pale brown solid (2.65 g, 65 % yield); m.p. 185–187.5 °C;
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1H NMR (400 MHz, CDCl3): δ [ppm] = 2.35 (s, 3H), 2.38 (s, 3H), 7.07
(dd, J = 9.2, 1.6 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 9.2 Hz,
for C15H1079Br3N2+ [M + H+]: 454.8394, found 454.8400 (34 %); calcd.
for C15H1079Br281BrN2 [M + H+]: 456.8374, found 456.8375 (99 %);
+
1H), 7.62 (s, 1H), 7.66 (s, 1H), 7.76 (d, J = 8.0, 2H); 13C NMR (CDCl3, calcd. for C15H1079Br81Br2N2 [M + H+]: 458.8353, found 458.8352
+
100 MHz): δ [ppm] = 18.3, 21.3, 97.9, 115.1, 116.9, 122.01, 122.04, (100 %), calcd. for C15H1081Br3N2 [M + H+]: 460.8333, found
+
126.9, 127.4, 128.2, 129.3, 131.3, 137.8, 143.9, 144.3. HRMS (ESI): m/z 460.8332 (32 %).
calcd. for C17H1579Br2N2+ [M + H+]: 404.9602, found 404.9607; calcd.
3-(2,2-Dibromovinyl)-2-(4-methoxyphenyl)H-imidazo[1,2-a]pyr-
idine (2g). Pale gray crystals; (1.44 g, 35 % yield); m.p. 154.4–
for C17H1579Br81BrN2+ [M + H+]: 406.9582, found 406.9580; calcd. for
+
C
17H1581Br2N2 [M + H+]: 408.9561, found 408.9554.
155.4 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 3.85 (s, 3H), 6.87 (td,
J = 6.8, 1.1 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H), 7.25 (ddd, J = 9.1, 6.8,
1.2 Hz, 1H), 7.65 (d, J = 9.1 Hz, 1H), 7.66 (s, 1H), 7.83 (d, J = 8.9 Hz,
2H), 7.92 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] =
55.2, 98.1, 112.2, 114.0, 114.9, 117.4, 124.3, 125.1, 126.6, 126.7, 128.9,
143.9, 145.3, 159.6. HRMS (ESI): m/z calcd. for C16H1379Br2N2O + [M
+ H+]: 406.9395, found 406.9395; calcd. for C16H1379Br81BrN2O + [M
+ H+]: 408.9374, found 408.9374; calcd. for C16H1381Br2N2O + [M +
H+]: 410.9354, found 410.9354.
3-(2,2-Dibromovinyl)-6-chloro-2-(4-chlorophenyl)H-imidazo-
[1,2-a]pyridine (2b). Pale brown solid (2.72 g, 61 % yield); m.p.
212–214 °C; 1H NMR (400.1 MHz, CDCl3): δ [ppm] = 7.24 (dd, J =
9.5 Hz, J =1.8 Hz, 1 H), 7.42 (d, J =8.5 Hz, 2 H), 7.59 (d, J =9.5 Hz, 1
H), 7.61 (s, 1H), 7.79 (d, J =8.5 Hz, 2 H), 7.94 (d, J =1.8 Hz, 1 H);
13C NMR (100.6 MHz, CDCl3): δ [ppm] = 100.1, 116.3, 118.1, 121.1,
122.2, 125.6, 126.9, 128.8, 129.0, 132.1, 134.4, 143.66, 143.68. HRMS
(ESI): m/z calcd. for C15H9Br2Cl2N2 [M + H+]: 444.8510, found
+
444.8512 (39 %); calcd. for C15H9Br2Cl2N2+ [M + H+]: 446.8489, found
5-(2,2-Dibromovinyl)-6-phenylimidazo[2,1-b]thiazole (2h).
Brown-yellow powder; (3.52 g, 92 % yield); m.p. 121–124 °C; 1H NMR
(400 MHz, CDCl3): δ [ppm] = 6.87 (d, J = 4.5 Hz, 1H), 7.31–7.35 (m,
1H), 7.42–7.45 (m, 3H), 7.60 (s, 1H), 7.73–7.78 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ [ppm] = 95.0, 112.2, 117.3, 119.1, 127.07, 127.13,
127.7, 128.6, 134.0, 145.6, 150.1. HRMS (ESI): m/z calcd. for
446.8486 (100 %); calcd. for C15H9Br2Cl2N2 [M + H+]: 448.8460,
+
found 448.8457 (89 %); calcd. for C15H9Br2Cl2N2+ [M + H+]: 450.8430,
found 450.8428 (31 %).
3-(2,2-Dibromovinyl)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyrid-
ine (2c). White powder (1.77 g, 42 % yield); m.p. 229–231 °C; 1H
NMR (400 MHz, [D6]DMSO): δ [ppm] = 7.42 (t, J = 6.6, 1H), 7.69 (d,
J = 8.5 Hz, 2H), 7.83 (d, J = 8.5 Hz, 2H), 7.88–7.96 (m, 2H), 8.13 (s,
1H), 8.63 (d, J = 6.6 Hz, 1H); 13C NMR (100 MHz, [D6]DMSO): δ
[ppm] = 103.5, 113.2, 117.0, 118.0, 123.5, 127.0, 127.2, 129.3, 129.6,
C
13H979Br2N2S+ [M + H+]: 382.8853, found 382.8850 (50 %); calcd.
for C13H979Br81BrN2S + [M + H+]: 384.8833, found 384.8827 (100 %);
calcd. for C13H981Br2N2S+ [M + H+]: 386.8812, found 386.8804 (52 %).
3-(2,2-Dibromovinyl)-2-phenylimidazo[2,1-b][1,3]benzothiazole
(2i). Beige-yellow crystals; (2.44 g, 56 % yield); m.p. 152–153.5 °C;
1H NMR (400 MHz, CDCl3): δ [ppm] = 7.31–7.36 (m, 2H), 7.42–7.47
(m, 3H), 7.68–7.73 (m, 2H), 7.79–7.83 (m, 3H); 13C NMR (100 MHz,
CDCl3): δ [ppm] = 101.0, 113.3, 118.7, 124.2, 124.8, 126.3, 126.6,
126.9, 127.7, 128.6, 130.2, 132.7, 134.0, 144.7, 148.3. HRMS (ESI): m/z
calcd. for C17H1179Br2N2S+ [M + H+]: 432.9010, found 432.9012
(52 %); calcd. for C17H1179Br81BrN2S + [M + H+]: 434.8989, found
434.8989 (100 %); calcd. for C17H1181Br2N2S+ [M + H+]: 436.8969,
found 436.8966 (51 %).
133. 1, 133. 4, 135. 0, 140. 3. HRMS (ESI): m/ z c al cd. for
C
15H1079Br2ClN2 [M + H+]: 410.8899, found 410.8900 (44 %); calcd.
+
for C15H1079Br81BrClN2+ [M + H+]: 412.8879, found 412.8875 (100 %);
calcd. for C15H1081Br2ClN2 [M + H+]: 414.8858, found 414.8851
+
(72 %).
3-(2,2-Dibromovinyl)-2-(4-bromophenyl)H-imidazo[1,2-a]pyrid-
ine (2d). Pale beige powder; (3.11 g, 68 % yield); m.p. 226–228 °C;
1H NMR (400 MHz, [D6]DMSO): δ [ppm] = 7.50 (td, J = 6.7, 1.6 Hz,
1H), 7.76 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H), 7.91–7.98 (m,
2H), 8.13 (s, 1H), 8.70 (d, J = 6.9 Hz, 1H); 13C NMR (100 MHz,
[D6]DMSO): δ [ppm] = 103.6, 113.1, 117.1, 118.0, 123.4, 123.9,
127.17, 127.23, 129.5, 132.5, 133.27, 133.32, 140.2. HRMS (ESI): m/z
calcd. for C15H1079Br3N2+ [M + H+]: 454.8394, found 454.8399 (31 %);
5-(2,2-Bibromovinyl)-6-(3,4-dichlorophenyl)imidazo[2,1-b]thi-
azole (2j). White-beige powder; (1.85 g, 41 % yield); m.p. 152.3–
153 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 6.92 (d, J = 4.5 Hz,
1H), 7.43 (d, J = 4.5 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.55 (dd, J =
8.4, 2.0 Hz, 1H), 7.57 (s, 1H), 7.90 (d, J = 2.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ [ppm] = 96.8, 112.9, 117.8, 118.8, 125.9, 126.2,
128.7, 130.5, 131.5, 132.8, 134.1, 142.9, 150.2. HRMS (ESI): m/z calcd.
for C13H7Br2N2Cl2S+ [M + H+]: 450.8074, found 450.8077 (33 %);
calcd. for C13H7Br2N2Cl2S+ [M + H+]: 452.8053, found 452.8053
(100 %); calcd. for C13H7Br2N2Cl2S+ [M + H+]: 454.8024, found
454.8027 (89 %); calcd. for C13H7Br2N2Cl2S+ [M + H+]: 456.8003,
found 456.8000 (24 %).
calcd. for C15H1079Br281BrN2 [M + H+]: 456.8374, found 456.8376
+
+
(100 %); calcd. for C15H1079Br81Br2N2 [M + H+]: 458.8353, found
458.8355 (97 %), calcd. for C15H1081Br3N2+ [M + H+]: 460.8333, found
460.8335 (31 %).
3-(2,2-Dibromovinyl)-2-phenylH-imidazo[1,2-a]pyridine (2e).
Slightly brown-green crystals; (1.68 g, 45 % yield); m.p. 129.2–
130.3 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 6.89 (td, J = 6.9,
1.1 Hz, 1H), 7.27 (ddd, J = 9.0, 6.9, 1.3 Hz, 1H), 7.35–7.39 (m, 1H),
7.45–7.48 (m, 2H), 7.66–7.69 (m, 2H), 7.87–7.91 (m, 2H), 7.94 (d, J =
6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 98.4, 112.4, 115.7,
117.7, 124.4, 125.2, 126.6, 127.6, 128.2, 128.6, 134.0, 144.0, 145.3.
HRMS (ESI): m/z calcd. for C15H1179Br2N2+ [M + H+]: 376.9289, found
General procedure for the reaction of dibromoalkenes 2 with
amines. A screw cap vial equipped with magnetic stirring bar was
charged with corresponding dibromoalkene (0.25 mmol), THF
(0.5 mL), amine (5 mmol) and water (1 mmol, 18 mg, 4 equiv.)*.
The reaction mixture was stirred at room temperature for 1–2 day
(pyrrolidine, dimethylamine, methylamine) or heated at 85 °C for 6–
10 h (other amines). Volatiles were evaporated in vacuo, the residue
was purified by column chromatography on silica gel using appro-
priate eluents (CH2Cl2/MeOH = 100:1–30:1).
376.9287 (52 %); calcd. for C15H1179Br81BrN2 [M + H+]: 378.9269,
+
found 378.9263 (100 %); calcd. for C15H1081Br2N2 [M + H+]:
+
380.9248, found 380.9243 (49 %).
6-Bromo-3-(2,2-dibromovinyl)-2-phenylH-imidazo[1,2-a]pyrid-
ine (2f). Slightly beige-yellow crystals; (2.73 g, 60 % yield); m.p.
1
144–148 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 7.32 (dd, J = 9.5, * In the case of methylamine and dimethylamine the following pro-
1.9 Hz, 1H), 7.36–7.40 (m, 1H), 7.44–7.48 (m, 2H), 7.55 (d, J = 9.5 Hz,
1H), 7.65 (s, 1H), 7.84–7.89 (m, 2H), 8.05 (d, J = 1.1 Hz, 1H). 13C NMR ture of 33 % Me2NH (1 mL) or 40 % MeNH2 (1 mL) with THF (1 mL)
(100 MHz, CDCl3): δ [ppm] = 99.4, 107.2, 116.0, 118.3, 124.4, 126.0, in screw cap vial was cooled in ice bath and 1 g of KOH was added
127.6, 128.4, 128.6, 128.7, 133.5, 143.7, 144.7. HRMS (ESI): m/z calcd. in 3 portions during 5 min. After stirring for several minutes two
cedure was used to introduce the amine into the reaction. The mix-
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layers were formed (lower one is saturated water solution of KOH).
The upper layer was decanted and thus obtained solution of water
(100 MHz, CDCl3): δ [ppm] = 24.2, 26.1, 30.9, 46.0, 46.7, 106.7, 114.8,
117.8, 124.7, 127.7, 127.9, 128.5, 128.6, 134.1, 143.4, 144.8, 166.2.
and amine in THF (20–25 equivalents of amine) was engaged with HRMS (ESI): m/z calcd. for C19H1979BrN3O+ [M + H+]: 384.0711, found
dibromoalkene.
384.0703; C19H1981BrN3O+ [M + H+]: 386.0691, found 386.0684.
2-(6-Methyl-2-p-tolylH-imidazo[1,2-a]pyridin-3-yl)-1-(pyrrol-
idin-1-yl)ethanone (3a). Pale brown solid (0.071 g, 85 % yield);
m.p. 162–164.5 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.74–1.85
2-[2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]-1-(pyrrol-
idin-1-yl)ethanone (3g). Light yellow powder; (0.071 g, 85 % yield);
m.p. 61–63 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.70–1.80 (m,
1
1
(m, 4H), 2.29 (s, 3H), 2.35 (s, 3H), 3.19 (t, J = 6.5 Hz, 2H), 3.42 (t, J =
6.5 Hz, 2H), 3.97 (s, 2H), 6.99 (d, J = 9.1, 1H), 7.21 (d, J = 7.9 Hz, 2H),
7.48 (d, J = 9.2 Hz, 1H), 7.51 (d, J = 7.9 Hz, 2H), 7.99 (s, 1H); 13C NMR
(CDCl3, 100 MHz): δ [ppm] = 18.4, 21.2, 24.1, 26.1, 31.3, 46.0, 46.6,
113.4, 116.4, 121.5, 122.2, 127.3, 128.3, 129.2, 131.8, 137.2, 143.9,
144.0, 166.8. HRMS (ESI): m/z calcd. for C21H24N3O+ [M + H+]:
334.1914, found 334.1921.
4H), 3.16 (t, J = 6.5 Hz, 2H), 3.38 (t, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.96
(s, 2H), 6.72 (t, J = 6.5 Hz, 1H), 6.93 (d, J = 8.7 Hz, 2H), 7.10 (t, J =
7.6 Hz, 1H), 7.51–7.57 (m, 3H), 8.17 (d, J = 6.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ [ppm] = 24.0, 26.0, 31.2, 45.9, 46.5, 55.1, 111.8,
113.4, 113.9, 116.9, 124.1, 124.5, 127.0, 129.6, 143.7, 144.8, 159.1,
166.5. HRMS (ESI): m/z calcd. for C20H22N3O2 [M + H+]: 336.1707,
+
found 336.1707.
2-[6-Chloro-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl]-1-
(pyrrolidin-1-yl)ethanone (3b). Pale brown powder; (0.067 g, 72 %
yield); m.p. 199–199.6 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.82–
1.97 (m, 4H), 3.33 (t, J = 6.6 Hz, 2H), 3.48 (t, J = 6.8 Hz, 2H), 3.97 (s,
2H), 7.15 (dd, J = 9.5 Hz, J = 1.6 Hz, 1 H), 7.41 (d, J = 8.5 Hz, 2 H),
7.54 (d, J = 9.5 Hz, 1 H), 7.58 (d, J = 8.5 Hz, 2H), 8.24 (d, J = 1.6 Hz,
1 H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 24.2, 26.2, 31.0, 46.1,
46.9, 115.1, 117.7, 120.5, 122.5, 126.0, 128.9, 129.8, 132.7, 134.0,
143.5, 144.0, 166.0. HRMS (ESI): m/z calcd. for C19H1835Cl2N3O+ [M +
H+]: 374.0827, found 374.0826; calcd. for C19H1835Cl37ClN3O+ [M +
H+]: 376.0797, found 376.0796.
2-(6-Phenylimidazo[2,1-b]thiazol-5-yl)-1-(pyrrolidin-1-yl)ethan-
one (3h). Pale brown-green solid; (0.065 g, 84 % yield); m.p. 142–
144 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.72–1.79 (m, 4H), 3.12
(t, J = 6.5 Hz, 2H), 3.37 (t, J = 6.5 Hz, 2H), 3.91 (s, 2H), 6.72 (d, J =
4.5 Hz, 1H), 7.25–7.28 (m, 1H), 7.35–7.39 (m, 2H), 7.53–7.57 (m, 2H),
7.63 (d, J = 4.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 24.0,
25.9, 31.8, 45.8, 46.5, 111.5, 115.4, 119.1, 127.2, 127.8, 128.4, 134.6,
144.6, 149.1, 166.6. HRMS (ESI): m/z calcd. for C17H18N3OS+ [M +
H+]: 312.1165, found 312.1164.
2-(2-Phenylbenzo[d]imidazo[2,1-b]thiazol-3-yl)-1-(pyrrolidin-1-
yl)ethanone (3i). Light beige crystals; (0.086 g, 95 % yield); m.p.
205–206 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.78–1.95 (m, 4H),
3.35 (t, J = 6.2 Hz, 2H), 3.46 (t, J = 6.2 Hz, 2H), 4.03 (s, 2H), 7.16–
7.22 (m, 1H), 7.25–7.30 (m, 2H), 7.35–7.39 (m, 2H), 7.53–7.59 (m, 4H);
13C NMR (100 MHz, CDCl3): δ [ppm] = 24.1, 26.0, 31.7, 46.0, 46.6,
113.1, 118.0, 123.8, 124.1, 125.8, 127.2, 127.8, 128.4, 130.0, 133.0,
134.2, 145.4, 147.1, 166.9. HRMS (ESI): m/z calcd. for C21H20N3OS+
[M + H+]: 362.1322, found 362.1320.
2-[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-1-(pyrrolidin-
1-yl)ethanone (3c). White powder; (0.051 g, 60 % yield); m.p.
1
181.5–183.8 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.75–1.89 (m,
4H), 3.24 (t, J = 6.7 Hz, 2H), 3.42 (t, J = 6.8 Hz, 2H), 3.98 (s, 2H), 6.78
(td, J = 6.9, 1.0 Hz, 1H), 7.16 (ddd, J = 9.0, 6.8, 1.1 Hz, 1H), 7.39 (d,
J = 8.5 Hz, 2H), 7.58 (t, J = 9.0 Hz, 1H), 7.59 (d, J = 8.5 Hz, 2H), 8.18
(d, J = 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 24.1, 26.1,
31.1, 46.0, 46.7, 112.2, 114.2, 117.2, 124.6, 128.7, 129.7, 133.1, 133.6,
142.9, 145.0, 166.3. HRMS (ESI): m/z calcd. for C19H19ClN3O+ [M +
H+]: 340.1211, found 340.1213.
2-[6-(3,4-Dichlorophenyl)imidazo[2,1-b]thiazol-5-yl]-1-(pyrrol-
idin-1-yl)ethanone (3j). Light yellow powder; (0.055 g, 58 % yield);
m.p. 189–190 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.79–1.93
(m, 4H), 3.27 (t, J = 6.6 Hz, 2H), 3.43 (t, J = 6.7 Hz, 2H), 3.91 (s, 2H),
6.79 (d, J = 4.5 Hz, 1H), 7.41–7.47 (m, 2H), 7.63 (d, J = 4.5 Hz, 1H),
7.67 (d, J = 1.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 24.2,
26.1, 31.7, 46.1, 46.8, 112.2, 116.2, 119.0, 126.8, 129.4, 130.5, 131.1,
132.6, 134.8, 142.3, 149.5, 166.3. HRMS (ESI): m/z calcd. for
2-[2-(4-Bromophenyl)imidazo[1,2-a]pyridin-3-yl]-1-(pyrrolidin-
1-yl)ethanone (3d). Pale beige powder; (0.063 g, 66 % yield); m.p.
1
183.6–184.1 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.75–1.88 (m,
4H), 3.23 (t, J = 6.6 Hz, 2H), 3.41 (t, J = 6.8 Hz, 2H), 3.96 (s, 2H), 6.77
(td, J = 6.8, 0.6 Hz, 1H), 7.15 (ddd, J = 8.9, 6.8, 0.8 Hz, 1H), 7.50–7.57
(m, 5H), 8.15 (d, J = 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
[ppm] = 24.1, 26.1, 31.1, 46.0, 46.7, 112.2, 114.2, 117.2, 121.8, 124.50,
124.54, 130.0, 131.6, 133.5, 142.8, 145.0, 166.3. HRMS (ESI): m/z
calcd. for C19H1879BrN3ONa+ [M + Na+]: 406.0531, found 406.0521;
C19H1881BrN3ONa+ [M + Na+]: 408.0510, found 408.0505.
C
1 7 H1 6 3 5 Cl2 N3 OS+ [M + H+ ]: 380.0391, found 380.0391;
C17H1635Cl37ClN3OS+ [M + H+]: 382.0362, found 382.0362.
2-[6-Chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-
dimethylacetamide (4b). Light brown powder; (0.071 g, 82 %
1
yield); m.p. 219–221 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 2.94
2-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-1-(pyrrolidin-1-yl)ethan-
one (3e). Pale brown powder; (0.054 g, 70 % yield); m.p. 156–
157 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.74–1.85 (m, 4H), 3.18
(t, J = 6.5 Hz, 2H), 3.40 (t, J = 6.6 Hz, 2H), 4.02 (s, 2H), 6.77 (td, J =
6.8, 1.1 Hz, 1H), 7.15 (ddd, J = 9.1, 6.7, 1.2 Hz, 1H), 7.32 (tt, J = 7.4,
2.0 Hz, 1H), 7.39–7.44 (m, 2H), 7.58 (d, J = 9.1 Hz, 1H), 7.62–7.66 (m,
2H), 8.23 (d, J = 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] =
24.1, 26.0, 31.2, 45.9, 46.6, 112.0, 114.0, 117.1, 124.3, 124.7, 127.6,
128.5, 134.6, 144.0, 145.0, 166.5. HRMS (ESI): m/z calcd. for
C19H20N3O+ [M + H+]: 306.1601, found 306.1605.
(s, 6H, Me), 3.98 (s, 2H), 7.11 (dd, J = 9.5 Hz, J = 2.0 Hz, 1H), 7.38 (d,
J = 8.5 Hz, 2H), 7.50 (d, J = 9.5 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 8.13
(d, J = 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 29.6,
35.8, 37.4, 115.2, 117.6, 120.4, 122.3, 125.9, 128.8, 129.6, 132.6, 133.9,
143.4, 143.8, 167.4. The NMR data are in agreement with those in
the literature.[35]
2-[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dimethyl-
acetamide (4c). Pale beige powder; (0.043 g, 54 % yield); m.p. 170–
1
172 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 2.90 (s, 3H, Me), 2.93
2-(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)-1-(pyrrolidin-
1-yl)ethanone (3f). Pale beige powder; (0.066 g, 69 % yield); m.p.
176–177 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.78–1.90 (m, 4H),
3.26 (t, J = 6.6 Hz, 2H), 3.45 (t, J = 6.7 Hz, 2H), 3.98 (s, 2H), 7.21 (dd,
J = 9.5, 1.8 Hz, 1H), 7.32–7.36 (m, 1H), 7.39–7.45 (m, 2H), 7.47 (d, J =
(s, 3H, Me), 4.06 (s, 2H), 6.80 (td, J = 6.9, 1.1 Hz, 1H), 7.19 (ddd, J =
9.1, 6.8, 1.1 Hz, 1H), 7.41 (d, J = 8.5 Hz, 2H), 7.59 (t, J = 9.0 Hz, 1H),
7.60 (d, J = 8.5 Hz, 2H), 8.16 (d, J = 6.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ [ppm] = 30.0, 35.8, 37.5, 112.3, 114.3, 117.3, 124.5, 124.6,
128.8, 129.8, 133.1, 133.7, 142.8, 145.1, 167.9. HRMS (ESI): m/z calcd.
9.5 Hz, 1H), 7.59–7.62 (m, 2H), 8.37 (d, J = 1.0 Hz, 1H). 13C NMR for C17H1735ClN3O+ [M + H+]: 314.1055, found 314.1045.
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2-[2-(4-Bromophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dimethyl-
acetamide (4d). Pale beige powder; (0.054 g, 60 % yield); m.p.
(s, 3H), 2.89 (d, J = 4.7 Hz, 3H), 3.86 (s, 2H), 6.84 (dd, J = 9.0 Hz,
1.0 Hz, 1H), 7.04 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 9.0 Hz, 1H), 7.12 (br
182.5–183.3 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 2.89 (s, 3H, s, 1H), 7.33 (d, J = 7.9 Hz, 2H), 7.60 (s, 1H); 13C NMR (100 MHz,
Me), 2.91 (s, 3H, Me), 4.03 (s, 2H), 6.78 (t, J = 6.7 Hz, 1H), 7.16 (t, J =
CDCl3): δ [ppm] = 18.3, 21.2, 26.5, 32.5, 112.6, 116.0, 120.5, 122.3,
7.8 Hz, 1H), 7.50–7.58 (m, 5H), 8.12 (d, J = 6.9 Hz, 1H); 13C NMR 127.4, 129.2, 130.5, 137.3, 143.7, 144.3, 169.2. The NMR data are in
(100 MHz, CDCl3): δ [ppm] = 29.9, 35.7, 37.4, 112.3, 114.3, 117.3,
121.9, 124.5, 124.6, 130.0, 131.7, 133.5, 142.8, 145.1, 167.8. HRMS
(ESI): m/z calcd. for C17H1779BrN3O+ [M + H+]: 358.0555, found
358.0551; C17H1781BrN3O+ [M + H+]: 360.0535, found 360.0538.
agreement with those in the literature.[38]
N-(3-Methoxypropyl)-2-(6-methyl-2-p-tolylH-imidazo[1,2-a]pyr-
idin-3-yl)acetamide (9). Brown powder; (0.043 g, 49 % yield); m.p.
1
139.7–141.5 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.57–1.63 (m,
N,N-Dimethyl-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetamide
(4h). Green-yellow powder; (0.061 g, 86 % yield); m.p. 100–112 °C;
1H NMR (400 MHz, CDCl3): δ [ppm] = 2.76 (s, 3H, Me), 2.87 (s, 3H,
Me), 4.00 (s, 2H), 6.75 (d, J = 4.5 Hz, 1H), 7.27–7.31 (m, 1H), 7.38–
7.41 (m, 2H), 7.54–7.57 (m, 2H), 7.62 (d, J = 4.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ [ppm] = 30.7, 35.6, 37.4, 111.7, 115.5, 119.0,
127.3, 127.8, 128.5, 134.5, 144.5, 149.2, 168.3. The NMR data are in
agreement with those in the literature.[36]
2H), 2.32 (s, 3H), 2.36 (s, 3H), 2.92 (s, 3H), 3.23 (t, J = 5.6 Hz, 2 H),
3.30 (t, J = 5.9 Hz, 2H), 3.92 (s, 2H), 6.49 (br s, 1H), 7.03 (dd, J =
9.2 Hz, 1.2 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 9.2 Hz, 1H),
7.59 (d, J = 8.0 Hz, 2H), 7.71 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
[ppm] = 18.3, 21.2, 28.5, 32.7, 38.8, 58.4, 71.8, 112.8, 116.7, 120.9,
122.3, 127.8, 127.9, 129.3, 131.0, 137.6, 144.2, 144.5, 168.2. HRMS
+
(ESI): m/z calcd. for C21H26N3O2 [M + H+]: 352.2020, found
352.2024.
N,N-Dimethyl-2-(2-phenylbenzo[d]imidazo[2,1-b]thiazol-3-yl)-
acetamide (4i). Pale beige powder; (0.060 g, 72 % yield); m.p. 203–
204 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 3.00 (s, 3H, Me), 3.05
(s, 3H, Me), 4.12 (s, 2H), 7.21–7.25 (m, 1H), 7.28–7.34 (m, 2H), 7.38–
7.42 (m, 2H), 7.51 (d, J = 8.1 Hz, 1H), 7.55–7.61 (m, 3H); 13C NMR
(100 MHz, CDCl3): δ [ppm] = 30.7, 35.9, 37.3, 113.0, 118.1, 124.0,
124.2, 125.8, 127.3, 127.9, 128.5, 130.1, 133.1, 134.2, 145.5, 147.2,
168.5. The NMR data are in agreement with those in the litera-
ture.[37]
N-Hexyl-2-[6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl]acet-
amide (10). Brown-greenish powder; (0.063 g, 69 % yield); m.p.
159–161 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 0.81 (t, J = 6.8 Hz,
3H), 1.07–1.23 (m, 6H), 1.32–1.39 (m, 2H), 2.32 (s, 3H), 2.37 (s, 3H),
3.19 (q, J = 6.7 Hz, 2H), 3.94 (s, 2H), 5.90 (br s, 1H), 7.03 (dd, J =
9.2 Hz, 1.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 9.2 Hz, 1H),
7.56 (d, J = 8.0 Hz, 2H), 7.70 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
[ppm] = 13.9, 18.3, 21.2, 22.4, 26.3, 29.3, 31.3, 32.7, 39.7, 112.8, 116.6,
120.8, 122.4, 127.75, 127.81, 129.3, 130.8, 137.7, 144.2, 144.5, 168.3.
HRMS (ESI): m/z calcd. for C23H30N3O+ [M + H+]: 364.2383, found
364.2381.
1
2-(6-Methyl-2-p-tolylH-imidazo[1,2-a]pyridin-3-yl)-1-(piperidin-
1-yl)ethanone (5). Pale green-brown powder; (0.028 g, 32 % yield);
1
m.p. 79–81 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 1.16–1.21 (m,
N,N-Dimethyl-2-[6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-
yl]acetamide (Zolpidem). Slightly brown solid; (0.062 g, 81 %
yield); m.p. 191–193 °C; (lit. data,[12] 193–195 °C); 1H NMR (400 MHz,
CDCl3): δ [ppm] = 2.30 (s, 3H), 2.36 (s, 3H), 2.84 (s, 3H), 2.91 (s, 3H),
4.03 (s, 2H), 7.00 (dd, J = 9.6, 1.5 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H),
7.49 (d, J = 9.6 Hz, 1H), 7.51 (d, J = 8.1, 2H), 7.95 (s, 1H); 13C NMR
(CDCl3, 100 MHz): δ [ppm] = 18.4, 21.2, 30.2, 35.8, 37.4, 113.6, 116.5,
121.6, 122.1, 127.4, 128.3, 129.3, 131.8, 137.3, 143.8, 144.1, 168.3.
The NMR data are in agreement with those in the literature.[12,23,24]
2H), 1.41–1.46 (m, 2H), 1.48–1.55 (m, 2H), 2.34 (s, 3H), 2.39 (s, 3H),
3.19 (t, J = 5.5 Hz, 2H), 3.50 (t, J = 5.5 Hz, 2H), 4.09 (s, 2H), 7.03 (dd,
J = 9.0, J = 1.5, 1H), 7.25 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 9.0 Hz, 1H),
7.54 (d, J = 7.8 Hz, 2H), 8.06 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
[ppm] = 18.5, 21.3, 24.3, 25.7, 26.3, 30.4, 43.3, 47.1, 113.8, 116.6,
121.7, 122.3, 127.5, 128.4, 129.3, 131.7, 137.5, 143.6, 144.1, 166.5.
HRMS (ESI): m/z calcd. for C22H26N3O+ [M + H+]: 348.2070, found
348.2061.
1-(Azepan-1-yl)-2-(6-methyl-2-p-tolylH-imidazo[1,2-a]pyridin-3-
yl)ethanone (6). Pale brown powder; (0.023 g, 25 % yield); m.p. 99–
102 °C; 1H NMR (400 MHz, CDCl3): δ [ppm] = 1.36–1.50 (m, 6H),
1.63–1.69 (m, 2H), 2.33 (s, 3H, Me), 2.39 (s, 3H, Me), 3.24 (t, J =
5.6 Hz, 2H), 3.48 (t, J = 6.0 Hz, 2H), 4.09 (s, 2H), 7.03 (dd, J = 9.2, J =
1.4, 1H), 7.24 (d, J = 8.1 Hz, 2H), 7.52 (d, J = 9.2 Hz, 1H), 7.54 (d, J =
8.1 Hz, 2H), 8.06 (s, 1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 18.5,
21.3, 26.4, 27.0, 27.2, 29.0, 30.7, 46.5, 48.1, 113.9, 116.5, 121.7, 122.3,
127.4, 128.4, 129.3, 131.7, 137.4, 143.6, 144.1, 167.8. HRMS (ESI): m/z
calcd. for C23H28N3O+ [M + H+]: 362.2231, found 362.2231.
2-[6-Chloro-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl]-
N,N-dipropylacetamide (Alpidem). Slightly brownish powder;
(0.080 g, 79 % yield); m.p. 236.5–237.5 °C; 1H NMR (400.1 MHz,
CDCl3): δ [ppm] = 0.75 (t, J = 7.4 Hz, 3H), 0.84 (t, J = 7.4 Hz, 3H),
1.43–1.57 (m, 4 H), 3.11 (q, J = 7.6 Hz, 2 H), 3.28 (q, J = 7.8 Hz, 2 H),
4.02 (s, 2 H), 7.14 (dd, J = 9.5 Hz, J = 1.8 Hz, 1 H), 7.41 (d, J = 8.5 Hz,
2 H), 7.52 (d, J = 9.5 Hz, 1 H), 7.56 (d, J = 8.5 Hz, 2 H), 8.22 (d, J =
1.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 10.9, 11.2, 20.9,
22.2, 29.9, 48.0, 49.9, 115.6, 117.6, 120.5, 122.5, 125.9, 128.9, 129.8,
132.6, 134.1, 143.5, 143.7, 167.2. The NMR data are in agreement
with those in the literature.[23,24a,35]
2-(6-Methyl-2-p-tolylH-imidazo[1,2-a]pyridin-3-yl)-N,N-diprop-
ylacetamide (7). Light brown-yellow powder; (0.053 g, 59 % yield);
Supporting Information: For copy of all 1H and 13C NMR data see
Supporting Information.
1
m.p. 102–104 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 0.62 (t, J =
7.4 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H), 1.33–1.42 (m, 2H), 1.45–1.54 (m,
2H), 2.31 (s, 3H), 2.38 (s, 3H), 3.03 (t, J = 7.6 Hz, 2 H), 3.25 (t, J =
7.8 Hz, 2H), 4.07 (s, 2H), 7.01 (dd, J = 9.2 Hz, 1.4 Hz, 1H), 7.24 (d, J =
8.0 Hz, 2H), 7.50 (d, J = 9.2 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 8.04 (s,
1H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 10.7, 11.2, 18.4, 20.8,
21.2, 22.0, 30.5, 47.8, 49.7, 113.9, 116.5, 121.5, 122.3, 127.3, 128.4,
129.2, 131.7, 137.4, 143.5, 144.1, 167.9. The NMR data are in agree-
ment with those in the literature.[35]
Acknowledgments
This work was supported by RFBR project 16-03-00936-a. The
authors acknowledge partial support in measuring of NMR from
M.V. Lomonosov Moscow State University Program of Develop-
ment. The authors acknowledge Thermo Fisher Scientific Inc.,
MS Analytica (Moscow, Russia), and personally Prof. A. Makarov
N-Methyl-2-[6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl]acet-
amide (8). Light brown-yellow powder; (0.051 g, 70 % yield); m.p.
1
173–175 °C; H NMR (400 MHz, CDCl3): δ [ppm] = 2.30 (s, 3H), 2.33 for providing mass spectrometry equipment for this work.
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Full Paper
Stivanello, O. De Lucchi, E. Grendele, D. Sperandio, IT Patent 2002MI0574,
Sep 19, 2003; h) Boehringer Ingelheim Pharma K.-G. Germany DE Patent
10121638, Nov 14, 2002; i) A. A. Salcedo, MX Patent 2000004847, Mar
14, 2002.
Keywords: Aldehydes · Alkenes · Amines · Amides ·
Heterocycles
[23] N. Chernyak, V. Gevorgyan, Angew. Chem. Int. Ed. 2010, 49, 2743; Angew.
Chem. 2010, 122, 2803.
[24] a) I. V. Rassokhina, V. Z. Shirinian, I. V. Zavarzin, V. Gevorgyan, Y. A. Volk-
ova, J. Org. Chem. 2015, 80, 11212; b) B. Zhang, G. Shan, Q. Ma, Q. Xu,
X. Lei, Heterocycl. Commun. 2017, 23, 445; c) X. Lei, G. Lin, Q. Xu, P. Liu,
Ping, CN Patent 103360387, Oct 23, 2013.
[25] a) G. Chelucci, Chem. Rev. 2012, 112, 1344; b) For amides, see: W. Shen,
A. Kunzer, Org. Lett. 2002, 4, 1315; c) For amidines, see: D. H. Huh, H.
Ryu, Y. G. Kim, Tetrahedron 2004, 60, 9857; d) D. H. Huh, J. S. Jeong, H. B.
Lee, H. Ryu, Y. G. Kim, Tetrahedron 2002, 58, 9925.
[26] a) A. V. Shastin, V. N. Korotchenko, V. G. Nenaidenko, E. S. Balenkova,
Russ. Chem. Bull. 1999, 48, 2184; b) A. V. Shastin, V. N. Korotchenko, V. G.
Nenaidenko, E. S. Balenkova, Tetrahedron 2000, 56, 6557.
[27] a) A. V. Shastin, V. N. Korotchenko, V. G. Nenajdenko, E. S. Balenkova,
Synthesis 2001, 2081; b) V. N. Korotchenko, A. V. Shastin, V. G. Nenaj-
denko, E. S. Balenkova, J. Chem. Soc., Perkin Trans. 1 2002, 883; c) V. N.
Korotchenko, A. V. Shastin, V. G. Nenajdenko, E. S. Balenkova, Org. Biomol.
Chem. 2003, 1, 1906; d) V. G. Nenajdenko, A. V. Shastin, V. N. Korotch-
enko, G. N. Varseev, E. S. Balenkova, Eur. J. Org. Chem. 2003, 302; e) V. G.
Nenajdenko, G. N. Varseev, V. N. Korotchenko, A. V. Shastin, E. S. Balen-
kova, J. Fluorine Chem. 2003, 124, 115; f) V. M. Muzalevskiy, A. V. Shastin,
A. D. Demidovich, N. G. Shikhaliev, A. M. Magerramov, V. N. Khrustalev,
R. D. Rakhimov, S. Z. Vatsadze, V. G. Nenajdenko, Beilstein J. Org. Chem.
2015, 11, 2072; g) A. V. Shastin, V. M. Muzalevsky, E. S. Balenkova, V. G.
Nenajdenko, Mendeleev Commun. 2006, 16, 179; h) V. M. Muzalevskiy,
N. G. Shikhaliev, A. M. Magerramov, N. V. Gurbanova, S. D. Geydarova,
E. S. Balenkova, A. V. Shastin, V. G. Nenajdenko, Russ. Chem. Bull. 2013,
62, 678; i) V. M. Muzalevskiy, A. M. Magerramov, N. G. Shikhaliev, E. S.
Balenkova, A. V. Shastin, P. V. Dorovatoskii, Y. V. Zubavitchus, V. N. Khrus-
talev, V. G. Nenajdenko, Russ. Chem. Bull. Int. Ed. 2016, 65, 1541.
[28] a) Q. Li, M. Zhou, L. Han, Q. Cao, X. Wang, L. Zhao, J. Zhou, H. Zhang,
Chem. Biol. Drug Des. 2015, 86, 849; b) The Vilsmeier Reaction of Fully
Conjugated Carbocycles and Heterocycles. In Organic Reactions (Eds.: G.
Jones, S. P. Stanforth), 1997, John Wiley & Sons; c) Q. K. Fang, F. X. Wu,
P. T. Grover, S. C. Hopkins, U. Campbell, M. Chytil, K. L. Spear, WO Patent
2009143156, Nov 26, 2009.
[1] a) A. P. Taylor, R. P. Robinson, Y. M. Fobian, D. C. Blakemore, L. H. Jones,
O. Fadeyi, Org. Biomol. Chem. 2016, 14, 6611; b) M. Baumann, I. R. Baxen-
dale, S. V. Ley, N. Nikbin, Beilstein J. Org. Chem. 2011, 7, 442; c) M. Bau-
mann, I. R. Baxendale, Beilstein J. Org. Chem. 2013, 9, 2265; d) Progress
in Heterocyclic Chemistry V. 24: (Eds.: G. W. Gribble, J. A. Joule), Academic
Press, Elsevier, 2012; e) J. A. Joule, K. Mills, Heterocyclic Chemistry at a
Glance. Blackwell Publishing: Oxford, U. K. 2007; f) A. Yu. Rulev, A. R.
Romanov, RSC Adv. 2016, 6, 1984.
[2] E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257.
[3] a) L. Dymin′ska, Bioorg. Med. Chem. 2015, 23, 6087 and references cited
therein; b) A. K. Bagdi, S. Santra, K. Monir, A. Hajra, Chem. Commun. 2015,
51, 1555 and references cited therein.
[4] a) T. Swainston Harrison, G. M. Keating, CNS Drugs 2005, 19, 65; b) N.
Hsua, S. K. Jha, T. Coleman, M. G. Frank, Behav. Brain Res. 2009, 201, 233.
[5] a) T. Okubo, R. Yoshikawa, S. Chaki, S. Okuyamac, A. Nakazato, Bioorg.
Med. Chem. 2004, 12, 423; b) A. N. Jain, J. Med. Chem. 2004, 47, 947.
[6] S. Z. Langer, S. Arbilla, J. Benavides, B. Scatton, Adv. Biochem. Psychophar-
macol. 1990, 46, 61.
[7] K. Mizushige, T. Ueda, K. Yukiiri, H. Suzuki, Cardiovasc. Drug Rev. 2002,
20, 163.
[8] L. Almirante, L. Polo, A. Mugnaini, E. Provinciali, P. Rugarli, A. Biancotti,
A. Gamba, W. Murmann, J. Med. Chem. 1965, 8, 305.
[9] Y. Maruyama, K. Anami, M. Terasawa, K. Goto, T. Imayoshi, Y. Kadobe, Y.
Mizushima, Arzneim.-Forsch. 1981, 31, 1111.
[10] L. A. Sorbera, J. Castaner, P. A. Leeson, Drugs Future 2002, 27, 935.
[11] a) G. Rossey, D. Long, U. S. Patent 4,794,185, Dec 27, 1988; b) P. George,
G. Rossey, H. Depoortere, B. Mompon, J. Allen, A. Wick, Farmaco 1991,
46, 277; c) J. Allen, A. Tizot, J. Labelled Compd. Radiopharm. 1986, 23,
393; d) A. Katsifis, F. Mattner, Z. Zhang, B. Dikic, V. Papazian, J. Labelled
Compd. Radiopharm. 2000, 43, 385; e) Y. Sumalatha, T. R. Reddy, P. P.
Reddy, B. Satyanarayana, ARKIVOC 2009, 315.
[12] Q. Chang, Z. Liu, P. Liu, L. Yu, P. Sun, J. Org. Chem. 2017, 82, 5391.
[13] H. Su, L. Wang, H. Rao, H. Xu, Org. Lett. 2017, 19, 2226.
[14] a) S. Wang, X. Huang, Z. Ge, X. Wang, R. Li, RSC Adv. 2016, 6, 63532; b)
V. M. Pérez, D. Fregoso-López, L. D. Miranda, Tetrahedron Lett. 2017, 58,
1326.
[15] P. Sun, P. Liu, Q. Chang, Zh. Liu, CN Patent 106946876, Jul 14, 2017.
[16] a) B. Yang, G. Chen, X. Li, Ch. Sun, Ch. CN Patent 106749237, May 31,
2017; b) I. A. Modi, S. P. Bhujbal, S. M. Pishave, J. V. Raman, B. M. Khamar,
IN Patent 2003MU01081, Sep 09, 2005; c) M. Rey, A. Roessler, G. Derungs,
J.-K. Pak, WO Patent 2002014306, Feb 21, 2002.
[17] a) S. Ji, Zhongguo Yaoye 2014, 23, 16–17; b) G. Castaldi, EP Patent
1172364, Jan 16, 2002.
[18] a) T. G. Gant, S. Sarshar, US Patent 20070281965, Dec 06, 2007; b) G. C.
Schloemer, US Patent 20040010146, Jan 15, 2004.
[19] G. J. B. Ettema, J. M. Lemmens, T. H. A. Peters, F. Picha, EP Patent 1038875
Sep 27, 2000.
[20] R. Labriola, WO Patent 2000008021, Feb 17, 2000.
[29] H. Wang, Y. Wang, D. Liang, L. Liu, J. Zhang, Q. Zhu, Angew. Chem. Int.
Ed. 2011, 50, 5678; Angew. Chem. 2011, 123, 5796.
[30] K. Dinnell, J. Elliott, G. Hollingworth, D. Shaw, U. S. Patent 20020022624,
21 Feb 2002.
[31] L.-H. Zhai, L.-H. Guo, B.-W. Sun, RSC Adv. 2015, 5, 93631.
[32] J. B. Bharate, S. Abbat, P. V. Bharatam, R. A. Vishwakarma, S. B. Bharate,
Org. Biomol. Chem. 2015, 13, 7790.
[33] Andreani, Bonazzi, Rambaldi, Greci, Bollettino Chimico Farmaceutico
1979, 118, 694.
[34] A.-N. El-Shorbagi, S. Sakai, M. A. El-Gendy, Omar, H. H. Farag, Chem.
Pharm. Bull. 1989, 37, 2971.
[35] L. Guetzoyan, N. Nikbin, I. R. Baxendale, V. Steven, Chem. Sci. 2013, 4,
764–769.
[21] D. K. Nair, S. M. Mobin, I. N. N. Namboothiri, Org. Lett. 2012, 14, 4580.
[22] a) M. S. Karlsen, H. Liu, J. E. Johansen, WO Patent 2014013063, Jan 23,
2014; b) S. You, H. Wang, CN Patent 102234275, Nov 09, 2011; c) S. S.
Patil, S. V. Patil, V. D. Bobade, Org. Prep. Proced. Int. 2011, 43, 260; d) J. L.
Falco, G. Plasencia, I. Zamora, M. Pique, M. Gonzalez, A. Morato, J. I. Bor-
rell, J. Teixido, I. Buira, E. Mendez, J. Terencio, M. Princep, A. Palomer, A.
Guglietta, Afinidad 2007, 64, 324; e) A. Zaworska, J. Dzikowska, J. Cybul-
ski, K. Bankowski, W. Szelejewski, PL Patent 196300, Dec 31, 2007; f) Y.
Kumar, M. Prasad, A. Nath, WO Patent 2005010002, Feb 03, 2005; g) M.
[36] Q. Huang, S. Zard, Org. Lett. 2018, 20, 1413.
[37] I. V. Rassokhina, T. A. Tikhonova, S. G. Kobylskoy, I. Yu. Babkin, V. Z. Shirin-
ian, V. Gevorgyan, I. V. Zavarzin, Yu. A. Volkova, J. Org. Chem. 2017, 82,
9682.
[38] Y. Sumalatha, P. P. Reddy, R. Reddy, B. Satyanarayana, ARKIVOC 2009, 143.
Received: February 20, 2019
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Full Paper
Heterocyclic Amides
V. M. Muzalevskiy,
Z. A. Sizova, A. V. Shastin,
V. G. Nenajdenko* ........................... 1–10
Metal-Free Approach to Zolpidem,
Alpidem and their Analogues via
Amination of Dibromoalkenes De-
rived from Imidazopyridine and
Imidazothiazole
A novel two step procedure towards hydes by CBr4-PPh3 system. Amination
Zolpidem, Alpidem and their ana- of dibromoalkenes with different pri-
logues was elaborated. A set of previ- mary and secondary amines in the
ously unknown dibromoalkenes de- presence of water led directly to target
rived from imidazopyridine and imid- drugs and their analogues in up to
azothiazole was prepared using Wittig 95 % yield.
olefination of the corresponding alde-
DOI: 10.1002/ejoc.201900279
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim