An efficient one-pot four-component synthesis of functionalized imidazo[1,2-a]pyridines

Article abstract of DOI:10.1002/hlca.201200231

An efficient one-pot four-component protocol for the synthesis of imidazo[1,2-a]pyridines was developed by condensing ethane-1,2-diamine (2), 1,1-bis(methylthio)-2-nitroethene (1), aldehydes 3, and activated methylene compounds in EtOH under reflux conditions (Tables 1-3). The features of this procedure are operational simplicity, good yields of products, in situ preparation of heterocyclic ketene aminals (HKA), and catalyst-free conditions. Copyright

Full text of DOI:10.1002/hlca.201200231

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An Efficient One-Pot Four-Component Synthesis of Functionalized
Imidazo[1,2-a]pyridines
by Siyavash Kazemi Movahed, Minoo Dabiri*, and Ayoob Bazgir
Department of Chemistry, Shahid Beheshti University, P.O. Box 1983963113, Tehran, Iran
(e-mail: m-dabiri@sbu.ac.ir)
An efficient one-pot four-component protocol for the synthesis of imidazo[1,2-a]pyridines was
developed by condensing ethane-1,2-diamine (2), 1,1-bis(methylthio)-2-nitroethene (1), aldehydes 3,
and activated methylene compounds in EtOH under reflux conditions (Tables 1 – 3). The features of this
procedure are operational simplicity, good yields of products, in situ preparation of heterocyclic ketene
aminals (HKA), and catalyst-free conditions.
Introduction. – Multicomponent reactions (MCRs) are of increasing importance in
organic and medicinal chemistry [1]. They have distinct advantages over a linear
stepwise process, including the removal of the need to purify after each chemical
transformation, the ability to produce a large number of derivatives around a common
scaffold by varying each of the components involved in the reaction, and high atom
economy [2].
Heterocyclic ketene aminals (HKAs) are powerful and versatile intermediates in
heterocyclic synthesis [3]. Reactions of HKAs with a variety of bis-electrophilic
reagents have so far been applied to make five- and six-membered and fused
heterocycles during the past years [4]. HKAs have been frequently found as
pharmacophores and could play important roles in drug discovery. Recently, Alizadeh
and co-workers, have reported new MCRs via in situ formation of nitroketene aminal
for the synthesis of various heterocycles [5]. In this context, imidazo[1,2-a]pyridine
derivatives show interesting features that make them attractive for use in HKA-based
MCRs. HKAs are one of the main intermediates used to synthesize of imidazo[1,2-
a]pyridines [6].
Imidazo[1,2-a]pyridines are becoming more and more important in medicinal and
organic chemistry. They have displayed a broad spectrum of pharmacological and
biological activities, such as antitumoral [7], antiviral [8], anti-inflammatory [9],
antibacterial [10], antifungal [11], anti-ulcer [12], antiprotozoal [13], and antiretroviral
activities [14]. They are contained in marketed drugs such as the clinical anti-ulcer
compound soraprazan, alpidem (a nonsedative anxiolytic), the PDE 3 inhibitor
olprinone, and the sedative zolpidem (Fig.) [15]. Bicyclic pyridin motifs I are of general
interest within medicinal chemistry with therapeutic properties, and a series of
substituted variants of I (n ¼ 1 or 2) have been reported as a basis for analgesics and
anti-inflammatory agents (Fig.) [16].
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Figure. Representatives of medicinally important imidazopyridines
As a part of our current studies on the MCRs to synthesize novel heterocycles [17],
we describe herein an efficient four-component synthesis of imidazo[1,2-a]pyridines via
in situ preparation of a nitroketene aminal.
Results and Discussion. – In the initial stage, the reaction of ethane-1,2-diamine (1),
1,1-bis(methylthio)-2-nitroethene (2), aldehyde 3, and 3-oxo-3-phenylpropanenitrile
(4) in EtOH under reflux conditions in the absence of any catalysts led to the formation
of imidazo[1,2-a]pyridine-6-carbonitriles 5a – 5d in good yields after 8 h (Table 1). It
was interesting that the desired products 6 or 7 were not detected at all. The structures
1
of the products 5a – 5d were fully characterized by IR and H- and 13C-NMR spectra,
and elemental analysis. The 1H-NMR spectrum of 5a exhibited two d at d(H) 4.27 and
Table 1. Synthesis of [1,2-a]Pyridine-6-carbonitriles 5
Product 5
RCHO (3)
Yield [%]
5a
5b
5c
5d
Benzaldehyde
61
55
85
91
1H-Indole-3-carboxaldehyde
4-Fluorobenzaldehyde
3-Nitrobenzaldehyde

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3.52 with 3J ¼ 11.5 Hz for the CH groups that confirmed non-dehydration of product 5
and indicated trans-configuration of the two vicinal H-atoms.
The formation of products 5 can be rationalized by the initial formation of
intermediate 8 via Knoevenagel condensation of 3 and 4. Subsequent addition of HKA
II (formed in situ by reaction of 1 with 2) to the intermediate 8 followed by cyclization
afforded products 5 (Scheme).
Scheme. Proposed Mechanism of the Formation of Product 5
To further explore the potential of this protocol for the imidazo[1,2-a]pyridine
synthesis, the 3-oxo-3-(piperidin-1-yl)propanenitrile (9) was selected as an activated-
methylene compound in the four-component reaction (Table 2). It was interesting that
the 5-aminoimidazo[1,2-a]pyridin 11 was not detected at all, while imidazo[1,2-
a]pyridines 10 were obtained in good yields. All the products were characterized by IR,
mass, and NMR spectra and elemental analysis.
Table 2. Synthesis of Imidazo[1,2-a]pyridines 10
Product 10
RCHO (3)
Yield [%]
10a
10b
10c
10d
Benzaldehyde
65
83
79
75
3-Nitrobenzaldehyde
Pyridine-2-carboxaldeyde
2-Nitrobenzaldehyde

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When Meldrum’s acid (12) and dimedone (14) were selected as active b-dicarbonyl
compounds in the four-component reaction, the desired imidazo[1,2-a]pyridines 13 and
15 were obtained in good yields (Table 3).
Table 3. Synthesis of Compounds 13 and 15
Product
RCHO (3)
Yield [%]
13a
13b
13c
13d
13e
15a
15b
15c
15d
15e
Benzaldehyde
57
71
74
67
70
51
68
45
83
54
2,4-Dichlorobenzaldehyde
3-Nitrobenzaldehyde
4-Methoxybenzaldehyde
Pyridine-2-carboxaldeyde
Benzaldehyde
Pyridine-2-carboxaldeyde
1H-Indole-3-carboxaldehyde
3-Nitrobenzaldehyde
4-Methoxybenzaldehyde
In conclusion, we achieved the new one-pot, four-component, and catalyst-free
synthesis of highly functionalized imidazo[1,2-a]pyridines. The catalyst-free reactions
carried out in EtOH are considerably safer, nontoxic, environmentally friendly, and
inexpensive. The absence of a catalyst for the reaction avoids the use of moisture
sensitive and heavy metal such as Lewis acids. This method is applicable to the synthesis
of different types of imidazo[1,2-a]pyridines.
We gratefully acknowledge financial support from the Research Council of Shahid Beheshti
University.
Experimental Part
General. The chemicals used in this work were obtained from Fluka and Merck and were applied
without further purification. M.p.: Electrothermal-9100 apparatus; uncorrected. IR Spectra: BOMEM-
1
MB-series FT-IR apparatus; ˜n in cmꢀ1. H-and 13C- Spectra: Bruker-DRX-300-Avance spectrometer; at
300.13 and 75.47 MHz, resp.; in (D6)DMSO; d in ppm rel. to Me4Si as internal standard, J in Hz. EI-MS

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(70 eV): Shimadzu-GCMS-QP1100EX mass spectrometer; in m/z. VarioEL-CHNS apparatus Elemental
analyses: (Elementar Analysensysteme GmbH).
Compounds 5a – 5d. General Procedure. A soln. of ethane-1,2-diamine (1; 1 mmol) and 1,1-
bis(methylthio)-2-nitroethene (2; 1 mmol) in EtOH (5 ml) was magnetically stirred for 3 h under reflux.
Then a soln. of aldehyde 3 (1 mmol) and 3-oxo-3-phenylpropanenitrile (4; 1 mmol) in EtOH (3 ml) was
added to the mixture and refluxed for 5 h. The mixture was cooled to r.t. and the precipitated product
collected by filtration and washed with AcOEt (2 ꢁ 3 ml): 5.
1,2,3,5,6,7-Hexahydro-5-hydroxy-8-nitro-5,7-diphenylimidazo[1,2-a]pyridine-6-carbonitrile (5a):
Yield 61%. White solid. M.p. 205 – 2088. IR (KBr): 3362, 2903, 2251, 1601. 1H-NMR: 3.29 – 3.39 (m,
CH2); 3.52 (d, J ¼ 11.5, CH); 3.62 – 3.64 (m, CH2), 4.26 (d, J ¼ 11.5, CH); 7.20 – 7.67 (m, 10 arom. H); 9.35
(br. s, NH). 13C-NMR: 42.8; 43.1; 45.1; 50.5; 83.7; 105.8; 118.2; 126.9; 127.1; 127.9; 128.6; 129.4; 139.3;
141.7; 157.4. MS: 362 (Mþ). Anal. calc. for C20H18N4O3 (362.38): C 66.29, H 5.01, N 15.46; found: C 66.32,
H 5.06, N 15.43.
1,2,3,5,6,7-Hexahydro-5-hydroxy-7-(1H-indol-3-yl)-8-nitro-5-phenylimidazo[1,2-a]pyridine-6-car-
bonitrile (5b): Yield 55%. White solid. M.p. 198 – 2008. IR (KBr): 3333, 2923, 2251, 1620. 1H-NMR: 3.40 –
3.47 (m, CH2); 3.52 – 3.62 (m, CH2); 4.46 (d, J ¼ 6.9, CH); 4.83 (d, J ¼ 6.9, CH); 7.41 – 7.95 (m, 9 arom. H);
8.57 (s, 1 arom. H); 9.38 (br. s, NH); 10.11 (br. s, NH). 13C-NMR: 19.0; 42.5; 44.3; 56.5; 82.9; 105.0; 117.1;
123.8; 127.1; 127.2; 127.4; 129.0; 129.4; 138.5; 139.9; 147.9; 155.7; 157.5. MS: 401 (Mþ). Anal. calc. for
C22H19N5O3 (401.42): C 66.83, H 4.77, N 17.45; found: C 66.80, H 4.71, N 17.45.
7-(4-Fluorophenyl)-1,2,3,5,6,7-hexahydro-5-hydroxy-8-nitro-5-phenylimidazo[1,2-a]pyridine-6-car-
bonitrile (5c): Yield 85%. White solid. M.p. 209 – 2128. IR (KBr): 3283, 2879, 2257, 1617. 1H-NMR: 3.32 –
3.35 (m, CH2); 3.54 – 3.63 (m, CH, CH2); 4.26 (d, J ¼ 11.4, CH); 7.05 – 7.65 (m, 9 arom. H); 9.34 (br. s,
NH). 13C-NMR: 42.0; 43.1; 45.5; 50.1; 83.6; 105.6; 115.0; 118.1; 127.3; 128.9; 129.4; 129.8; 129.9; 139.2;
139.9; 157.3. MS: 380 (Mþ). Anal. calc. for C20H17FN4O3 (380.37): C 63.15, H 4.50, N 14.73; found: C
63.20, H 4.52, N 14.71.
1,2,3,5,6,7-Hexahydro-5-hydroxy-8-nitro-7-(3-nitrophenyl)-5-phenylimidazo[1,2-a]pyridine-6-car-
bonitrile (5d): Yield 91%. White solid. M.p. 224 – 2568. IR (KBr): 3300, 3097, 2965, 2905, 2247, 1613.
1H-NMR: 3.12 – 3.20 (m, CH2); 3.66 – 3.88 (m, CH, CH2); 4.24 – 4.47 (d, J ¼ 11.3, CH); 6.79 – 7.04 (m, 9
arom. H); 9.37 (br. s, NH). 13C-NMR: 43.0; 43.8; 55.4; 83.6; 104.8; 117.9; 122.2; 127.2; 127.3; 128.9; 129.5;
129.9; 135.6; 139.1; 139.8; 143.8; 157.3. MS: 407 (Mþ). Anal. calc. for C20H17N5O5 (407.38): C 58.97, H 4.21,
N 17.19; found: C 59.02, H 4.25, N 17.15.
Compounds 10a – 10d. General Procedure. As described for 5a – 5d, with ethane-1,2-diamine (1;
1 mmol), l,l-bis(methylthio)-2-nitroethene (2; 1 mmol), EtOH (5 ml), aldehyde 3 (1 mmol), and 3-oxo-
3-(piperidin-1-yl)propanenitrile (9; 1 mmol) in EtOH (3 ml): 10.
1,2,3,7-Tetrahydro-5-hydroxy-8-nitro-7-phenylimidazo[1,2-a]pyridine-6-carbonitrile (10a): Yield
1
65%. Yellow solid. M.p. 260 – 2658 (dec.). IR (KBr): 3395, 3288, 2887, 1641, 1614. H-NMR: 3.68 – 3.74
(m, CH2); 3.88 – 3.94 (m, CH2); 4.97 (s, CH); 7.08 – 7.17 (m, 3 arom. H); 7.28 – 7.30 (m, 2 arom. H); 8.30
(br. s, OH); 9.21 (br. s, NH). 13C-NMR: 43.2; 43.5; 43.8; 74.7; 108.3; 126.2; 127.7; 128.1; 146.4; 153.8;
162.6. MS: 284 (Mþ). Anal. calc. for C14H12N4O3 (284.27): C 59.15, H 4.25, N 19.71; found: C 59.19, H
4.20, N 19.75.
1,2,3,7-Tetrahydro-5-hydroxy-8-nitro-7-(3-nitrophenyl)imidazo[1,2-a]pyridine-6-carbonitrile (10b).
Yield 83%. Yellow solid. M.p. 256 – 2588 (dec.). IR (KBr): 3340, 3321, 2879, 1640, 1638. 1H-NMR:
3.73 – 3.81 (m, CH2); 3.90 – 3.97 (m, CH2); 5.15 (s, CH); 7.30 (s, 1 arom. H); 7.47 – 7.52 (m, 1 arom. H);
7.71 – 7.64 (m, 1 arom. H); 7.97 – 7.99 (m, 1 arom. H); 8.36 (br. s, OH); 9.16 (br. s, NH). 13C-NMR: 43.2;
43.5; 43.8; 73.8; 107.4; 121.5; 122.5; 129.7; 134.5; 147.5; 148.5; 153.6; 152.4; 162.8. MS: 329 (Mþ). Anal.
calc. for C14H11N5O5 (329.27): C 51.07, H 3.37, N 21.27; found: C 51.19, H 3.20, N 21.21.
1,2,3,7-Tetrahydro-5-hydroxy-8-nitro-7-(pyridin-2-yl)imidazo[1,2-a]pyridine-6-carbonitrile (10c).
Yield 79%. Yellow solid. M.p. 264 – 2688 (dec.). IR (KBr): 3385, 3288, 2885, 1643, 1630. 1H-NMR:
3.73 – 3.92 (m, 2 CH2); 5.03 (s, CH); 7.13 (s, 1 arom. H); 7.26 – 7.28 (m, 1 arom. H); 7.45 (s, 1 arom. H);
7.60 – 7.63 (m, 1 arom. H); 8.36 (br. s, OH), 9.28 (br. s, NH). 13C-NMR: 43.2; 43.5; 43.9; 73.8; 106.3; 121.3;
121.8; 136.9; 148.9; 154.1; 162.1; 163.3; 164.4. MS: 285 (Mþ). Anal. calc. for C13H11N5O3 (285.26): C 54.74,
H 3.89, N 24.55; found: C 34.75, H 3.89, N 24.56.

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1,2,3,7-Tetrahydro-5-hydroxy-8-nitro-7-(2-nitrophenyl)imidazo[1,2-a]pyridine-6-carbonitrile (10d).
Yield 75%. Yellow solid. M.p. 236 – 2388. IR (KBr): 3517, 3391, 2941, 2864, 1644, 1530. 1H-NMR:
3.61 – 3.66 (m, CH2); 4.11 – 4.14 (m, CH2); 4.74 (s, CH); 7.21 – 7.23 (m, 1 arom. H); 7.50 – 7.53 (m, 1 arom.
H); 7.61 – 7.64 (m, 1 arom. H); 7.93 – 7.95 (m, 1 arom. H); 8.75 (br. s, OH), 9.59 (br. s, NH). 13C-NMR:
43.3; 43.6; 45.1; 74.6; 106.3; 124.8; 128.8; 128.9; 134.3; 136.8; 149.3; 166.4. MS: 329 (Mþ). Anal. calc. for
C14H11N5O5 (329.27): C 51.07, H 3.37, N 21.27; found: C 51.10, H 3.39, N 21.25.
Compounds 13a – 13e. General Procedure. As described for 5a – 5d, with ethane-1,2-diamine (1;
1 mmol) 1,1-bis(methylthio)-2-nitroethene (2; 1 mmol), EtOH (5 ml), aldehyde 3 (1 mmol), and
Meldrumꢂs acid (¼2,2-dimethyl-1,3-dioxane-4,6-dione; 12; 1 mmol) in EtOH (3 ml): 13.
2,3,6,7-Tetrahydro-8-nitro-7-phenylimidazo[1,2-a]pyridin-5(1H)-one (13a). Yield 57%. White solid.
1
M.p. 252 – 2568. IR (KBr): 3224, 3007, 2917, 1699. H-NMR: 2.55 – 2.60 (m, CH); 3.16 – 3.24 (m, CH);
3.75 – 3.97 (m, 2 CH2); 4.52 – 4.55 (m, CH); 7.13 – 7.18 (m, 2 arom. H); 7.20 – 7.32 (m, 3 arom. H); 9.71 (br.
s, NH). 13C-NMR: 37.6; 40.6; 43.05; 43.9; 106.7; 126.8; 127.3; 129.1; 142.9; 153.1; 167.8. MS: 259 (Mþ).
Anal. calc. for C13H13N3O3 (259.26): C 60.22, H 5.05, N 16.21; found: C 60.25, H 5.08, N 16.13.
7-(2,4-Dichlorophenyl)-2,3,6,7-tetrahydro-8-nitroimidazo[1,2-a]pyridin-5(1H)-one (13b): Yield
71%. White solid. M.p. 246 – 2478. IR (KBr): 3294, 3073, 2923, 1709. 1H-NMR: 2.46 – 2.50 (m, CH);
3.25 – 3.31 (m, CH); 3.81 – 3.91 (m, 2 CH2); 4.83 – 4.86 (m, CH); 7.10 (d, J ¼ 8.18, 1 arom. H); 7.30 (d, J ¼
8.18, 1 arom. H); 7.64 (s, 1 arom. H); 9.82 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 35.5; 37.7; 43.2;
44.1; 104.9; 128.2; 128.7; 129.8; 132.8; 133.8; 138.8; 153.4; 166.9. MS: 328 (Mþ). Anal. calc. for
C13H11Cl2N3O3 (328.15): C 47.58, H 3.38, N 12.81; found: C 47.60, H 3.31, N 12.85.
2,3,6,7-Tetrahydro-8-Nitro-7-(3-nitrophenyl)imidazo[1,2-a]pyridin-5(1H)-one (13c). Yield 74%.
1
White solid. M.p. 236 – 2408. IR (KBr): 3378, 3058, 2917, 1713. H-NMR: 2.64 – 2.69 (m, CH); 3.22 –
3.30 (m, CH); 3.79 – 3.93 (m, 2 CH2); 4.70 – 4.73 (m, CH); 7.58 – 7.60 (m, 2 arom. H); 8.01 – 8.04 (m, 1
arom. H); 8.06 (s, 1 arom. H); 9.75 (br. s, NH). 13C-NMR: 37.3; 37.7, 39.9; 44.0; 105.9; 121.9; 122.4; 130.7;
133.4; 145.2; 148.4; 153.1; 167.4. MS: 304 (Mþ). Anal. calc. for C13H12N4O5 (304.26): C 51.32, H 3.98, N
18.41; found: C 51.36, H 4.02, N 18.40.
2,3,6,7-Tetrahydro-7-(4-methoxyphenyl)-8-nitroimidazo[1,2-a]pyridin-5(1H)-one (13d): Yield 67%.
White solid. M.p. 237 – 2418 (dec.). IR (KBr): 3224, 3000, 2911, 1699. 1H-NMR (300 MHz, (D6)DMSO):
2.55 – 2.57 (m, CH); 3.11 – 3.17 (m, CH); 3.68 (s, Me); 3.77 – 3.92 (m, 2 CH2); 4.45 – 4.47 (m, CH); 6.82 (d,
J ¼ 6.4, 2 arom. H); 7.04 (d, J ¼ 6.4, 2 arom. H); 9.75 (br. s, NH). 13C-NMR: 36.7; 43.0; 43.9; 55.5; 107.0;
114.4; 127.8; 134.7; 153.0; 158.2; 167.9. MS: 289 (Mþ). Anal. calc. for C14H15N3O4 (289.29): C 58.13, H
5.23, N 14.53; found: C 58.15, H 5.25, N 14.55.
2,3,6,7-Tetrahydro-8-nitro-7-(pyridin-2-yl)imidazo[1,2-a]pyridin-5(1H)-one (13e). Yield 70%.
White solid. M.p. 242 – 2448. IR (KBr): 3204, 3013, 2930, 1699, 1636, 1588. 1H-NMR: 2.63 – 2.69 (m,
CH); 3.08 – 3.13 (m, CH); 3.77 – 3.94 (m, 2 CH2); 4.44 – 4.46 (m, CH); 7.21 – 7.29 (m, 2 arom. H); 7.68 –
7.70 (m, 1 arom. H); 8.39 – 8.41 (m, 1 arom. H); 9.64 (br. s, NH). 13C-NMR: 37.2; 42.9; 43.7; 106.5; 122.4;
122.8; 137.2; 149.7; 153.3; 161.5; 167.9. MS: 260 (Mþ). Anal. calc. for C12H12N4O3 (260.25): C 55.38, H
4.65, N 21.53; found: C 55.40, H 4.68, N 21.50.
Compounds 15a – 15e. General Procedure. As described for 5a – 5d, with ethane-1,2-diamine (1;
1 mmol), and 1,1-bis(methylthio)-2-nitroethene (2; 1 mmol), EtOH (5 ml), aldehyde 3 (1 mmol), and
dimedone (¼ 5,5-dimethylcyclohexane-1,3-dione; 14, 1 mmol) in EtOH (3 ml): 15.
2,3,5,7,8,9-Hexahydro-8,8-dimethyl-4-nitro-5-phenylimidazo[1,2-a]quinolin-6(1H)-one (15a): Yield
51%. Yellow solid. M.p. 264 – 2678. IR (KBr): 3338, 2960, 2929, 2863, 1722, 1637. 1H-NMR: 0.83 (s, Me);
1.03 (s, Me); 2.08 (ABq, J ¼ 15.5, CH2); 2.49 – 2.57 (m, CH2); 3.56 – 3.82 (m, CH2); 4.06 (m, CH2); 5.07 (s,
CH); 7.09 – 7.20 (m, 5 arom. H); 9.41 (br. s, NH). 13C-NMR: 26.5; 29.8; 32.2; 38.7; 43.8; 45.2; 49.9; 107.8;
114.1; 126.5; 128.1; 128.3; 144.7; 149.5; 152.1; 193.7. MS: 339 (Mþ). Anal. calc. for C19H21N3O3 (339.39): C
67.24, H 6.26, N 12.38; found: C 67.20, H 6.29, N 12.35.
2,3,5,7,8,9-Hexahydro-8,8-dimethyl-4-nitro-5-(pyridin-2-yl)imidazo[1,2-a]quinolin-6(1H)-one (15b):
Yield 68%. Yellow solid. M.p. 280 – 2858 (dec.). IR (KBr): 3340, 2949, 2901, 1667. 1H-NMR: 0.78 (s, Me);
1.01 (s, Me); 2.06 (ABq, J ¼ 15.9, CH2); 2.42 – 2.59 (m, CH2); 3.80 – 3.86 (m, CH2); 3.98 – 4.15 (m, CH2);
5.07 (s, CH); 7.06 – 7.09 (m, 1 arom. H); 7.37 – 7.39 (m, 1 arom. H); 7.57 – 7.61 (m, 1 arom. H); 8.30 – 8.33
(m, 1 arom. H); 9.44 (br. s, NH). 13C-NMR: 26.2; 29.9; 32.2; 38.7; 40.3; 43.7; 45.1; 49.8; 107.3; 113.1; 121.9;

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124.5; 135.7; 149.2; 150.1; 152.5; 162.15; 193.8. MS: 340 (Mþ). Anal. calc. for C18H20N4O3 (340.38): C
63.52, H 5.92, N 16.46; found: C 63.56, H 5.95, N 16.47.
2,3,5,7,8,9-Hexahydro-5-(1H-indol-3-yl)-8,8-dimethyl-4-nitro-imidazo[1,2-a]quinolin-6(1H)-one
(15c): Yield 45%. Yellow solid. M.p. 275 – 2778 (dec.). IR (KBr): 3359, 3321, 2955, 2879, 1655. 1H-NMR:
0.77 (s, Me); 1.01 (s, Me); 2.05 (ABq, J ¼ 15.8, CH2); 2.51 – 2.59 (m, CH2); 3.80 – 3.87 (m, CH2); 4.02 – 4.21
(m, CH2); 5.04 (s, CH); 6.90 – 7.96 (m, 5 arom. H); 9.32 (br. s, NH); 10.76 (br. s, NH). 13C-NMR: 26.6;
29.1; 29.9; 32.1; 38.6; 43.8; 45.3; 49.9; 107.9; 111.6; 114.3; 117.8; 118.7; 119.7; 120.7; 124.0; 126.2; 136.4;
148.5; 152.1; 193.8. MS: 378 (Mþ). Anal. calc. for C21H22N4O3 (378.42): C 66.65, H 5.86, N 14.81; found: C
66.60, H 5.85, N 14.80.
2,3,5,7,8,9-Hexahydro-8,8-dimethyl-4-nitro-5-(3-nitrophenyl)-imidazo[1,2-a]quinolin-6(1H)-one
(15d). Yield 83%. Yellow solid. M.p. 285 – 2878 (dec.). IR (KBr): 3359, 3071, 2943, 2935, 1661. 1H-NMR:
0.83 (s, Me); 1.04 (s, Me); 2.08 (ABq, J ¼ 16.0, CH2); 2.56 – 2.65 (m, CH2); 3.82 – 3.88 (m, CH2); 3.98 – 4.23
(m, CH2); 5.14 (s, CH); 7.48 – 7.54 (m, 1 arom. H); 7.68 – 7.70 (m, 1 arom. H); 7.98 – 8.04 (m, 2 arom. H);
9.5 (br. s, NH). 13C-NMR: 26.4; 29.8; 32.3; 38.2; 38.7; 43.9; 45.3; 49.6; 107.0; 112.8; 121.7; 123.0; 129.7;
135.0; 146.9; 147.6; 150.3; 151.8; 193.8. MS: 384 (Mþ). Anal. calc. for C19H20N4O5 (384.39): C 59.37, H
5.24, N 14.58; found: C 59.30, H 5.29, N 14.52.
2,3,5,7,8,9-Hexahydro-5-(4-methoxyphenyl)-8,8-dimethyl-4-nitro-imidazo[1,2-a]quinolin-6(1H)-one
(15e): Yield 54%. Yellow solid. M.p. 286 – 2898 (dec.). IR (KBr): 3346, 3007, 2962, 2898, 1656. 1H-NMR:
0.85 (s, Me); 1.04 (s, Me); 2.08 (ABq, J ¼ 16.0, CH2); 2.45 – 2.61 (m, CH2); 3.67 (s, Me); 3.82 – 3.86 (m,
CH2); 3.98 – 4.18 (m, CH2); 5.03 (s, CH); 6.73 (d, J ¼ 7.8, 2 arom. H); 7.11 (d, J ¼ 7.4, 2 arom. H); 9.33 (br.
s, NH). 13C-NMR: 26.5; 29.9; 32.2; 38.7; 38.6; 43.8; 45.2; 49.9; 55.3; 108.0; 113.4; 114.4; 129.2; 136.9;
149.1; 152.0; 157.9; 193.7. MS: 369 (Mþ). Anal. calc. for C20H23N3O4 (369.41): C 65.03, H 6.28, N 11.37;
found: C 65.08, H 6.30, N 11.35.
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Received May 5, 2012