Introduction

Nitrogen is considered to be a key element with a vital role in bioactive compounds providing a noticeable range of activities [1], especially in polycyclic frameworks classified as important synthetic targets in medicinal chemistry. Nitrogen-containing polycyclic compounds have a widespread distribution in plants with interesting pharmaceutical and medicinal properties [2]. For instance, quinoline-containing compounds like cryptolepine 1 and quindoline 2 display antiplasmodial activity [3] while luotonins 3 as well as camptothecin 4 are antitumor agents [4–6] (Fig. 1). Thus, assembly of such a complex structures via effective and fast synthetic routes like multi-component reactions remains as a hot topic in organic chemistry [7–13].

Fig. 1
figure 1

Examples of N-rich bioactive polycyclic heterocycles

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Scheme 1
scheme 1

Synthetic route for target compounds 11a–l

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Isocyanide-based multi-component reactions (IMCRs) have witnessed considerable upturn due to their ability in generating diverse and complex arrays of heterocyclic compounds under mild conditions [14–17]. Among the several named reactions based on isocyanides, every chemist has heard about the pioneering Ugi reaction at least once. In 1998, the Groebke–Blackburn–Bienaymé reaction (GBB–MCR) [18–20] which involves interaction of 2-amidine functionalities, aldehydes, and isocyanides, emerged as an outstanding analog of the Ugi reaction, resulting in a high number of publications later on [21–23]. The resultant multi-functional frameworks obtained from multi-component reactions offer opportunities for further transformations. Such post-transformations allow chemists to expand the chemical space by combining MCRs with a broad synthesis arsenal [24–26]. In this context, the role of transition-metals in bond activation has gained a lot of attention due to their access to heterocyclic scaffolds with greater levels of complexity.

Copper, an inexpensive metal with a broad range of applications, has received less attention compared to other metals (i.e., palladium). The activation of aryl halides with copper dates back to 1901, in a classical reaction called the Ullmann reaction [27]. Considering the valuable reports on the association of GBB-adducts with post-transformations affording a unique diversification strategy for the synthesis of novel compounds [28–33], herein we report a new coupled GBB–MCR–Ullmann-type N-arylation affording fused pentacyclic heterocycles.

Results and Discussions

Following our interests in the efficient creation of polycyclic heterocycles [34–38], our endeavor began with the preparation of an aldehyde precursor by the action of Vilsmeier’s reagent [39]. After acetylating aniline with acetyl chloride and potassium carbonate in acetone, the acetylated intermediate underwent cyclization when exposed to the Vilsmeier reagent at 80 \(^{\circ }\)C to afford aldehyde 7 in 77 % yield. Then, aldehyde 7 was reacted with 2-aminothiazole or 2-aminopyridine derivatives 9a–e and isocyanides 8a–c in refluxing toluene to afford biologically and synthetically attractive GBB-products 10a–l in 65–93 % yields (Scheme 1). The biological properties of these compounds have been investigated by our group.

Then, we focused our efforts in obtaining the best conditions for the subsequent Ullmann-type reaction. First, 10a was chosen as the model substrate, and the reaction was performed in the presence of \(\hbox {Pd}(\hbox {PPh}_{3})_{4}\) and \(\hbox {K}_{2}\hbox {CO}_{3}\) in toluene at reflux which was previously examined [40].

Since under these conditions the product was obtained in low yield (33 %), and because of the high cost of the palladium catalyst, a copper system was chosen as an inexpensive and efficient catalyst for the Ullmann-type coupling using three different ligands. By employing CuI and \(\hbox {K}_{2}\hbox {CO}_{3}\) in refluxing methanol, the desired product 11a was produced in good yield utilizing \({\textsc {l}}\)-proline. With this result in hand, other bases were investigated, and \(\hbox {Cs}_{2}\hbox {CO}_{3}\) was found to be the best choice affording the product in 65 % yield (Table 1, entries 4–7). Methanol proved to be the most optimal solvent for this reaction compared to DMF, \(\hbox {CH}_{3}\hbox {CN}\), and toluene (entries 8–10). It must be noted that no reaction was observed in the absence of ligand and copper salts, which completely ruled out \(\hbox {S}_{\mathrm{N}}\hbox {Ar}\) pathway (entries 11–12). In addition, the yield decreased when the reaction was performed at lower temperatures (entry 13).

Table 1 Optimization of intramolecular N-arylation
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Having established the optimized reaction conditions, all the GBB–MCR products were subjected to copper- mediated intramolecular C–N bond formation leading to the generation of 11a–l in good yields (Table 2). In all cases, the reactions proceeded smoothly, and the corresponding polycyclic compounds were obtained in moderate to good yields.

Table 2 Synthesis of pentacyclic compounds via sequential IMCR–Ullmann-type coupling
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Products 11a–l were characterized by IR, \(^{1}\)H NMR, \(^{13}\)C NMR, mass spectrometry and elemental analysis. The mass spectra of products displayed the molecular ion signal consistent with the loss of HCl upon the cyclization of 10a–l.

Conclusion

In summary, an efficient sequential synthesis of fused {6–5–5–6–6} and {5–5–5–6–6} ring systems is reported. The prominent aspects of this approach are utilizing inexpensive ligand, readily available starting materials and good yields. Copper-mediated intramolecular C–N bond formation of Groebke–Blackburn–Bienaymé adducts represents an efficient way to the formation of polycyclic compounds.

Experimental section

General remarks

All commercially available chemicals and reagents were purchased from Merck and Fluka Chemical Company and were used without further purification. 2-Chloroquinoline-3-carbaldehyde was prepared according to the literature [41, 42]. Melting points were measured with a Kofler hot stage apparatus and are uncorrected. \(^{1}\hbox {H}\) and \(^{13}\hbox {C}\) NMR spectra were recorded on a Bruker FT-400 in \(\hbox {CDCl}_{3}\), using tetramethylsilane (TMS) as an internal standard. The following abbreviations were used to designate multiplicities: s = singlet, d = doublet, t = triplet, dd = doublet of doublet, m = multiplet. IR spectra were recorded on a Shimadzu 470 spectrophotometer (KBr disks) in \(\hbox {cm}^{-1}\). Mass spectra were obtained using an Agilent Technology (HP) mass spectrometer operating at an ionization potential of 70 eV. Elemental analysis was performed using an Elemental Analyser system GmbH VarioELCHNS mode.

General procedure for synthesis of IMCR products 10a–l

A mixture of 2-chloro-3-formyl quinoline 7 (1 mmol), appropriate 2-aminoazines and -azoles 9a–e (1 mmol), isocyanide derivatives 8a–c (1.2 mmol), and ammonium chloride (1 mmol) in toluene (10 mL) was heated to reflux for 12–24 h. After the reaction was completed as indicated by TLC, the solvent was evaporated under reduced pressure, and the residue was recrystallized from petroleum ether–EtOAc (5:1) to afford desired products (10a–l) in 65–93 % yields.

General procedure for synthesis of 11a–l

To a solution of 1 mmol IMCR product in methanol (4 mL), 2 mmol \(\hbox {Cs}_{2}\hbox {CO}_{3}\), 10 mol% CuI and 10 mol% \(\textsc {l}\)-proline were added. The resulting mixture was stirred at reflux for 2 h under a nitrogen atmosphere. Then, the solvent was removed under vacuum, and the residue was purified by column chromatography petroleum ether/ EtOAc (10:1) to give the desired polycyclic products 11a–l in 50–86 % yields.

6-Cyclohexyl-6H-pyrido[1 \(''\),2 \(''\):1 \('\),2 \('\) ]imidazo[4 \('\),5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11a) Yellow solid; yield: 0.22 g (65 %); m.p.: 158–160 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2912, 2835, 1524, 1238. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3})\): \(\delta \) = 1.01–1.68 (m, 10H, 5CH\(_{2}\), cyclohexyl), 2.67 (m, 1H, NCH), 6.92 (dd, J = 6.4, 4.0 Hz, 1H, H–Ar), 7.60 (t, J = 7.6 Hz, 1H, H–Ar), 7.77 (t, J = 7.6 Hz, 1H, H–Ar), 7.91 (d, J = 8.8 Hz, 1H, H–Ar), 8.06 (d, J = 8.0 Hz, 1H, H–Ar), 8.24–8.27 (m, 1H, H–Ar), 8.59 (m, 1H, H–Ar), 8.64 (dd, J = 6.4, 1.2 Hz, 1H, H–Ar), 8.67 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 26.1, 27.2, 34.9, 56.5, 112.2, 115.3, 127.2, 130.1, 130.3, 131.1, 131.3, 132.5, 134.5, 135.4, 141.2, 145.6, 148.1, 150.7, 152.3, 154.1. MS: m/z (%) = 340 (35) [M]\(^{+}\), 257 (100), 230 (18), 130 (46), 127 (28), 83 (35), 52 (64). Anal. Calcd for \(\hbox {C}_{22}\hbox {H}_{20}\hbox {N}_{4}\): C, 77.62; H, 5.92; N, 16.46. Found: C, 77.51; H, 5.96; N, 16.40.

6-Cyclohexyl-10-methyl-6H-pyrido[1 \(''\),2 \(''\) :1 \('\),2 \('\) ]imidazo[4 \('\),5\('\) :4,5]pyrrolo[2,3-b]quinoline (11b) Pale yellow solid; yield: 0.24 g (70 %); m.p.: 146–148 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1})\): 2841, 2812, 1632, 1551. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 1.02–1.76 (m, 10H, 5 \(\hbox {CH}_{2}\), cyclohexyl), 2.24 (s, 3H, \(\hbox {CH}_{3}\)), 2.69 (m, 1H, NCH), 6.66 (dd, J = 6.4, 1.2 Hz, 1H, H–Ar), 7.31 (s, 1H, H–Ar), 7.58–7.62 (m, 1H, H–Ar), 7.73–7.77 (m, 1H, H–Ar), 7.91 (d, J = 7.6 Hz, 1H, H–Ar), 8.08 (d, J = 8.0 Hz, 1H, H–Ar), 8.23 (d, J = 6.4 Hz, 1H, H–Ar), 8.58 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 22.1, 25.7, 26.9, 34.5, 57.0, 115.9, 117.1, 124.0, 125.9, 128.1, 128.2, 129.1, 129.3, 131.3, 132.7, 136.9, 137.0, 142.8, 144.0, 148.9, 150.0. MS: m/z (%) = 354 (22) [M]\(^{+}\), 256 (100), 212 (72), 129 (35), 83 (41), 51 (24). Anal. Calcd for \(\hbox {C}_{23}\hbox {H}_{22}\hbox {N}_{4}\): C, 77.94; H, 6.26; N, 15.81. Found: C, 77.88; H, 6.22; N, 15.78.

6-Cyclohexyl-11-methyl-6H-pyrido[1 \(''\),2\(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\),5\('\) :4,5]pyrrolo[2,3-b]quinoline (11c) Yellow solid; yield: 0.29 g (82 %); m.p.: 140–142 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2925, 1685, 1423, 1315. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3})\): \(\delta \) = 1.02–1.79 (m, 10H, 5 \(\hbox {CH}_{2}\), cyclohexyl), 2.47 (s, 3H, \(\hbox {CH}_{3}\)), 2.73 (m, 1H, NCH), 6.93 (t, J = 6.4 Hz, 1H, H–Ar), 7.12 (d, J = 6.4 Hz, 1H, H–Ar), 7.77–7.81 (m, 1H, H–Ar), 7.97–8.01 (m, 1H, H–Ar), 8.46 (d, J = 8.4 Hz, 1H, H–Ar), 8.56 (d, J = 7.2 Hz, 2H, H–Ar), 8.72 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 18.5, 26.6, 27.4, 34.6, 56.8, 110.5, 122.0, 123.0, 126.0, 127.3, 127.5, 127.8, 128.0, 129.0, 129.8, 129.9, 136.2, 141.0, 143.5, 148.1, 149.2. Anal. Calcd for \(\hbox {C}_{23}\hbox {H}_{22}\hbox {N}_{4}\): C, 77.94; H, 6.26; N, 15.81. Found: C, 77.83; H, 6.31; N, 15.73.

5-Cyclohexyl-5H-thiazolo[3 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11d) Yellow solid; yield: 0.18 g (53 %); m.p.: 196–198 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2971, 2832, 1341. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 1.02–1.66 (m, 10H, 5 \(\hbox {CH}_{2}\), cyclohexyl), 2.78 (m, 1H, NCH), 6.82 (d, J = 4.4 Hz, 1H, H–Ar), 7.47 (d, J = 4.4 Hz, 1H, H–Ar), 7.58–7.62 (m, 1H, H–Ar), 7.74–7.78 (m, 1H, H–Ar), 7.89 (d, J = 8.0 Hz, 1H, H–Ar), 8.07 (d, J = 8.4 Hz, 1H, H–Ar), 8.50 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 25.9, 26.9, 33.9, 56.7, 108.3, 114.3, 118.8, 128.4, 128.5, 128.8, 129.5, 130.1, 131.8, 137.2, 142.1, 146.9, 148.2, 150.0. MS: m/z (%) = 346 (33) [M]\(^{+}\), 263 (100), 235 (15), 205 (61), 135 (42), 127 (17), 83 (41), 52 (24). Anal. Calcd for \(\hbox {C}_{20}\hbox {H}_{18}\hbox {N}_{4}\hbox {S}\): C, 69.34; H, 5.24; N, 16.17. Found: C, 69.28; H, 5.20; N, 16.21.

6-(Tert-butyl)-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11e) Pale yellow solid; yield: 0.19 g (62 %); m.p.: 238–240 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2921, 2365, 1624. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.95 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 6.94 (dd, J = 7.2, 4.0 Hz, 1H, H–Ar), 7.62 (t, J = 7.6 Hz, 1H, H–Ar), 7.79 (t, J = 7.6 Hz, 1H, H–Ar), 7.93 (d, J =8.4 Hz, 1H, H–Ar), 8.09 (d, J = 8.0 Hz, 1H, H–Ar), 8.50–8.53 (dd, J = 7.2, 2.0 Hz, 1H, H–Ar), 8.58–8.59 (m, 2H, H–Ar), 8.63 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 30.0, 56.3, 108.3, 113.0, 127.0, 128.4, 128.8, 128.9, 129.5, 129.8, 131.9, 132.0, 137.0, 142.6, 146.6, 148.3, 150.0, 151.9. MS: m/z (%) = 314 (46) [M]\(^{+}\), 262 (100), 187 (36), 130 (71), 76 (61), 57 (46). Anal. Calcd for \(\hbox {C}_{20}\hbox {H}_{18}\hbox {N}_{4}\): C, 76.41; H, 5.77; N, 17.82. Found: C, 76.35; H, 5.87; N, 17.90.

6-(Tert-butyl)-10-methyl-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11f) White solid; yield: 0.28 g (86 %); m.p.: 184–186 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2981, 1368, 1243. \(^{1}\hbox {H}\) NMR (400 MHz, CDCl\(_{3})\): \(\delta \) = 0.98 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 2.48 (s, 3H, \(\hbox {CH}_{3}\)), 6.69 (dd, J = 7.2, 2.0 Hz, 1H, H–Ar), 7.34 (s, 1H, H–Ar), 7.62 (t, J = 7.6 Hz, 1H, H–Ar), 7.79 (t, J = 7.6 Hz, 1H, H–Ar), 7.90 (d, J = 8.4 Hz, 1H, H–Ar), 8.09 (d, J = 8.8 Hz, 1H, H–Ar), 8.26 (d, J = 7.6 Hz, 1H, H–Ar), 8.58 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 21.2, 33.5, 56.3, 114.3, 115.8, 120.1, 123.9, 128.0, 128.5, 129.4, 129.6, 130.0, 131.6, 135.6, 136.4, 141.8, 144.3, 150.0, 150.1. Anal. Calcd for \(\hbox {C}_{21}\hbox {H}_{20}\hbox {N}_{4}\): C, 76.80; H, 6.14; N, 17.06. Found: C, 76.71; H, 6.22; N, 16.94.

6-(Tert-butyl)-11-methyl-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11g) Pale yellow solid; yield: 0.24 g (73 %); m.p.: 212–214 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2931, 1614, 1348. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.95 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 2.66 (s, 3H, \(\hbox {CH}_{3}\)), 6.77 (t, J = 7.2 Hz, 1H, H–Ar), 7.02 (d, J = 7.2 Hz, 1H, H–Ar), 7.61 (t, J = 7.0 Hz, 1H, H–Ar), 7.75–7.79 (m, 1H, H–Ar), 7.92 (d, J = 8.0 Hz, 1H, H–Ar), 8.08 (d, J = 8.4 Hz, 1H, H–Ar), 8.25 (d, J = 7.2 Hz, 1H, H–Ar), 8.59 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) =18.3, 29.9, 56.2, 112.5, 123.4, 123.9, 126.0, 127.9, 128.5, 128.7, 128.9, 129.2, 130.3, 131.6, 137.3, 142.3, 144.4, 148.5, 150.1. MS: m/z (%) = 328 (31) [M]\(^{+}\), 256 (100), 195 (23), 144 (64), 129 (20), 57 (52). Anal. Calcd for \(\hbox {C}_{21}\hbox {H}_{20}\hbox {N}_{4}\): C, 76.80; H, 6.14; N, 17.06. Found: C, 76.76; H, 6.20; N, 17.11.

5-(Tert-butyl)-5H-thiazolo[3 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11h) Yellow solid; yield: 0.16 g (50 %); m.p.: 119–121 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2932, 1412, 1304. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.93 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{2}\)), 6.82 (dd, J = 4.4 Hz, 1H, H–Ar), 7.50 (dd, J = 4.4 Hz, 1H, H–Ar), 7.57–7.62 (m, 1H, H–Ar), 7.75–7.79 (m, 1H, H–Ar), 7.89 (d, J = 8.4 Hz, 1H, H–Ar), 8.08 (d, J = 8.4 Hz, 1H, H–Ar), 8.47 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 30.8, 56.1, 113.2, 119.0, 127.7, 128.1, 128.9, 129.1, 129.5, 130.4, 130.9, 138.0, 142.8, 146.8, 148.7, 150.0. MS: m/z (%) = 320 (38) [M]\(^{+}\), 262 (100), 193 (31), 135 (29), 76 (18), 57 (49). Anal. Calcd for \(\hbox {C}_{18}\hbox {H}_{16}\hbox {N}_{4}\)S: C, 67.47; H, 5.03; N, 17.49. Found: C, 67.41; H, 5.10; N, 17.59.

6-(2,4,4-Trimethylpentan-2-yl)-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11i) Pale yellow solid; yield: 0.22 g (59 %); m.p.: 116–118 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2812, 1619, 1254. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.93 (s, 6H, C \((\hbox {CH}_{3})_{2}\)), 0.94 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3})\), 1.46 (s, 2H, \(\hbox {CH}_{2})\), 6.93 (dd, J = 6.8, 4.4 Hz, 1H, H–Ar), 7.60 (t, J = 7.6 Hz, 1H, H–Ar), 7.78 (t, J = 7.6 Hz, 1H, H–Ar), 7.91 (d, J =8.0 Hz, 1H, H–Ar), 8.06 (d, J = 8.4 Hz, 1H, H–Ar), 8.26–8.28 (m, 1H, H–Ar), 8.58–8.59 (m, 1H, H–Ar), 8.64 (dd, J = 6.8, 1.2 Hz, 1H, H–Ar), 8.67 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 29.0, 29.9, 30.3, 56.1, 59.3, 109.1, 112.2 125.9, 127.9, 128.4, 128.7, 128.9, 129.1, 130.9, 131.4, 136.0, 142.5, 146.6, 147.8, 149.6, 150.0. MS: m/z (%) = 370 (38) [M]\(^{+}\), 313 (54), 257 (100), 127 (14), 113 (43), 56 (53). Anal. Calcd for \(\hbox {C}_{24}\hbox {H}_{26}\hbox {N}_{4}\): C, 77.80; H, 7.07; N, 15.12. Found: C, 77.71; H, 7.10; N, 15.19.

10-Methyl-6-(2,4,4-trimethylpentan-2-yl)-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11j) Yellow solid; yield: 0.26 g (69 %); m.p.: 208–210 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2954, 2863, 1639, 1271. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.98 (s, 6H, C \((\hbox {CH}_{3})_{2})\), 1.00 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 1.46 (s, 2H, \(\hbox {CH}_{2}\)), 2.56 (s, 3H, \(\hbox {CH}_{3}\)), 6.68 (dd, J = 6.8, 1.6 Hz, 1H, H–Ar), 7.34 (s, 1H, H–Ar), 7.58–7.62 (m, 1H, H–Ar), 7.75–7.79 (m, 1H, H–Ar), 7.89 (d, J = 7.6 Hz, 1H, H–Ar), 8.08 (d, J = 8.0 Hz, 1H, H–Ar), 8.23 (d, J = 6.8 Hz, 1H, H–Ar), 8.58 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 21.1, 29.1, 31.7, 31.9, 56.9, 59.7, 115.3, 116.2, 123.0, 127.2, 128.2, 128.3, 128.7, 129.2, 129.6, 130.8, 134.6, 135.9, 141.2, 142.4, 148.2, 150.0. Anal. Calcd for \(\hbox {C}_{25}\hbox {H}_{28}\hbox {N}_{4}\): C, 78.09; H, 7.34; N, 14.57. Found: C, 78.15; H, 7.29; N, 14.64.

9-Chloro-6-(2,4,4-trimethylpentan-2-yl)-6H-pyrido[1 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11k) White solid; yield: 0.21 g (53 %); m.p.: 214–216 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2912, 1624, 1254. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 1.03 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 1.39 (s, 6H, C \((\hbox {CH}_{3})_{2}\)), 1.51 (s, 2H, \(\hbox {CH}_{2}\)), 7.18 (dd, J = 9.2, 1.6 Hz, 1H, H–Ar), 7.54 (dd, J = 9.2, 0.4 Hz, 1H, H–Ar), 7.60–7.64 (m, 1H, H–Ar), 7.77–7.82 (m, 1H, H–Ar), 7.92 (d, J = 8.4 Hz, 1H, H–Ar), 8.11 (d, J = 8.4 Hz, 1H, H–Ar), 8.24 (dd, J = 1.6, 0.4 Hz, 1H, H–Ar), 8.49 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 30.0, 31.5, 31.7, 56.5, 59.3, 120.0, 122.3, 122.8, 126.9, 129.0, 129.3, 129.5, 129.9, 130.0, 130.3, 131.9, 135.8, 141.9, 142.0, 150.1, 150.4. MS: m/z (%) = 406 (11) [M+2]\(^{+,}\) 404 (30) [M]\(^{+}\), 347 (37), 291 (100), 256 (36), 113 (67), 57 (46). Anal. Calcd for \(\hbox {C}_{24}\hbox {H}_{25}\hbox {ClN}_{4}\): C, 71.19; H, 6.22; N, 13.84. Found: C, 71.23; H, 6.12; N, 13.96.

5-(2,4,4-Trimethylpentan-2-yl)-5H-thiazolo[3 \(''\) ,2 \(''\) :1 \('\) ,2 \('\) ]imidazo[4 \('\) ,5 \('\) :4,5]pyrrolo[2,3-b]quinoline (11l) White solid; yield: 0.19 g (51 %); m.p.: 122–124 \(^{\circ }\hbox {C}\). IR (KBr) (\(\nu _{\mathrm{max}}\), \(\hbox {cm}^{-1}\)): 2938, 2821, 1664. \(^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 0.91 (s, 6H, \(\hbox {C}(\hbox {CH}_{3})_{2}\)), 0.97 (s, 9H, \(\hbox {C}(\hbox {CH}_{3})_{3}\)), 1.49 (s, 2H, \(\hbox {CH}_{2}\)), 6.82 (d, J= 4.4 Hz, 1H, H–Ar), 7.51 (d, J = 4.4 Hz, 1H, H–Ar), 7.59–7.63 (m, 1H, H–Ar), 7.74–7.78 (m, 1H, H–Ar), 7.88 (d, J = 8.0 Hz, 1H, H–Ar), 8.08 (d, J = 8.0 Hz, 1H, H–Ar), 8.47 (s, 1H, H–Ar). \(^{13}\hbox {C}\) NMR (100 MHz, \(\hbox {CDCl}_{3}\)): \(\delta \) = 30.3, 31.5, 31.9, 54.5, 56.8, 112.9, 117.9, 127.7, 128.3, 128.4, 128.6, 128.8, 129.6, 131.4, 136.9, 142.0, 146.9, 147.4, 149.7. MS: m/z (%) = 376 (27) [M]\(^{+}\), 319 (43), 263 (100), 135 (71), 113 (47), 57 (38).Anal. Calcd for \(\hbox {C}_{22}\hbox {H}_{24}\hbox {N}_{4}\)S: C, 70.18; H, 6.43; N, 14.88. Found: C, 70.22; H, 6.35; N, 14.98.