Convenient Synthesis of 11‐Substituted 11

DOI: 10.1002/ejoc.201700913

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Palladium-Catalysed Cyclizations

Convenient Synthesis of 11-Substituted 11H-Indolo[3,2-c]quinolines by Sequential Chemoselective Suzuki Reaction/Double C–N Coupling Ngo Nghia Pham,[a,b,c] Sophie Janke,[a,b] Ghazwan Ali Salman,[a,d] Tuan Thanh Dang,[a] Thanh Son Le,[c] Anke Spannenberg,[b] Peter Ehlers,[a,b] and Peter Langer*[a,b] Abstract: A pathway to access 11-substituted 11H-indolo[3,2c]quinolines is described. The protocol features a chemoselective Suzuki reaction of o-dihaloquinolines with o-bromophenylboronic acid, followed by double C–N coupling with primary

amines. The molecular structure of a representative product is exemplified, and demonstrates well-defined π-stacking interactions in the molecular network.

Introduction Among the repertoire of heterocycles, indole and quinoline belong to a class with profound medicinal importance. Thus, they have been broadly utilized in studies related to drug research and development.[1] Consequently, a number of important drugs involving these structures have been explored for the treatment of life-threatening diseases. For example, a quinoline derivative named chloroquine was employed as an antimalarial drug in the middle of the 20th century, helping to save thousands of human lives (Figure 1).[2] As another example, the drug delavirdine, which incorporates the indole skeleton, has been employed for the treatment of HIV (Figure 1).[3] Given the medicinal importance of indole and quinoline, it is not surprising that heterocycles derived from their fusion have attracted the attention of scientists. In this regard, 11H-indolo[3,2-c]quinolines have been discovered to act as potential inhibitors of DYRK1A[4] and NQ01.[5] Other derivatives of 11H-indolo[3,2-c]quinolines have been reported to interact with DNA or to possess antimalarial[6] and anti-tumour[7] activities. A representative example of an 11H-indolo[3,2-c]quinoline with anti-tumour activity is IQDMA, illustrated in Figure 1.[8] Often medicinal research requires a large product library of heterocycles for screening purposes. Therefore, a convenient access to these heterocycles is highly desired. 11H-Indolo[3,2-c]-

[a] Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany E-mail: [email protected] https://www.langer.chemie.uni-rostock.de/ [b] Leibniz Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany [c] Faculty of Chemistry, VNU University of Science Hanoi (VNU-HUS), 19 Le Thanh Tong, Hoan Kiem, Hanoi, Vietnam [d] Department of Chemistry, College of Science, University Al-Mustansiriyah, Palestine St, Mustansiriya, Baghdad, Iraq Supporting information and ORCID(s) from the author(s) for this article are available on the WWW under https://doi.org/10.1002/ejoc.201700913. Eur. J. Org. Chem. 2017, 5554–5565

Figure 1. Examples of indole- and quinoline-derived structures with medicinal importance.

quinolines can be obtained by classic syntheses, including the Fischer indole synthesis,[9] Pictet–Sprengler cyclization[10] and Curtius rearrangement.[11] Transition-metal-catalysed cross-coupling reactions have more recently offered additional synthetic pathways, for example, Suzuki,[12] Sonogashira,[13] C–N coupling/C–H activation,[14] isocyanide insertion[15] and carbonylative cyclization[16] (Scheme 1). Unfortunately, despite these developments, the synthesis of 11-substituted 11H-indolo[3,2-c]quinolines remains a challenge. Current synthetic tools allow the preparation of 11-unsubstituted 11H-indolo[3,2-c]quinolones that can undergo regioselective methylation at the 11-position.[17] With other substituents, the nitrogen atom of the quinoline ring reacts as a nucleophile, resulting in unwanted side-reactions. Herein, we describe what is, to the best of our knowledge, a new and convenient synthesis of 11-substituted 11H-indolo[3,2c]quinolines (Scheme 2). In our approach, the substituents located at the 11-position are installed directly, thereby avoiding the problem of selectivity in the alkylation of the 11-unsubsti-

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Scheme 1. Previously documented palladium-catalysed synthesis of 11-unsubstituted 11H-indolo[3,2-c]quinolines.

tuted heterocycle. Our methodology is based on chemoselective Suzuki reactions of 3,4-dihalo-2-methylquinolines with obromophenylboronic acid.[18]

Scheme 3. Synthesis of 3,4-dihalo-2-methylquinolines 1a,b. Scheme 2. Synthesis of 11-substituted 11H-indolo[3,2-c]quinolines in this study.

Results and Discussion Our starting point was to find the best conditions for the chemoselective Suzuki reaction of 3,4-dihalo-2-methylquinolines 1a,b with o-bromophenylboronic acid. First, quinolines 1a,b were prepared according to a reported procedure (Scheme 3).[14c,19] 3-Bromo-4-chloro-2-methylquinoline (1a) was then used in the Suzuki reaction, but failed to deliver satisfying yields of products. The desired product 2 was formed, but only in 23 % yield (Scheme 4). The poor performance of 3-bromo-4chloro-2-methylquinoline (1a) might be due to the insufficient reactivity of the bromine atom during the palladium-catalysed reaction. Hence, 4-chloro-3-iodo-2-methylquinoline (1b) was employed instead. In comparison with 3-bromo-4-chloro-2methylquinoline (1a), 4-chloro-3-iodo-2-methylquinoline (1b) was expected to give rise to a higher yield of 3-(2-bromophenyl)-4-chloro-2-methylquinoline (2), because iodine is considered to be more reactive in palladium-catalysed reactions. As expected, we obtained the product 2 in better yield (42 %; Scheme 4), which allowed us to continue to study the following double C–N coupling reaction. To optimize the subsequent double C–N coupling reaction, 3-(2-bromophenyl)-4-chloro-2-methylquinoline (2) and 4-methylaniline were chosen as model substrates. The influence of several phosphine ligands in the presence of the palladium source [Pd2dba3] and the base NaOtBu in toluene was monitored. During the optimization, PtBu3·HBF4 was identified as the best ligand for the reaction, affording the desired indoloquinoline 3a in nearly quantitative yield (entry 2, Table 1). Eur. J. Org. Chem. 2017, 5554–5565

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Scheme 4. Chemoselective Suzuki reaction of 3,4-dihalo-2-methylquinolines 2a,b.

Table 1. Optimization for the synthesis of indoloquinoline 3a.[a]

Entry 1 2 3 4

Ligand

Yield [%][b]

SPhos PtBu3·HBF4 dppf (S)-BINAP

56 95 63 78

[a] Reaction conditions: 2 (0.10 mmol), aniline (0.15 mmol), [Pd2dba3] (0.005 mmol), ligand (0.02 mmol for monodentate and 0.01 mmol for bidentate ligand), NaOtBu (0.24 mmol), toluene (2 mL), 100 °C, 24 h. [b] Isolated yields.

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Full Paper Our optimized conditions were then applied to the reaction of 3-(2-bromophenyl)-4-chloro-2-methylquinoline (2) with various electron-neutral and -rich arylamines (Table 2). The yields varied from good to excellent. Sterically hindered amines also worked effectively, giving the corresponding indoloquinolines 3i and 3k in yields of 89 and 85 %, respectively. The reaction of 3-(2-bromophenyl)-4-chloro-2-methylquinoline (2) with electron-poor amines resulted in lower yields. Hence, further ligand screening using 4-fluoroaniline as the model amine was conducted (Table 3). The bidentate phosphine ligand (S)-BINAP was found to be more suitable for this chemical transformation. By applying the catalyst system

[Pd2dba3]/(S)-BINAP with the base NaOtBu in toluene, indoloquinoline 3o was obtained in 95 % yield (entry 4, Table 3). Conducting further reactions under these conditions, indoloquinolines 3p and 3q were prepared in yields of 77 and 93 %, respectively. Furthermore, we found that (S)-BINAP could be successfully applied to the reaction of 3-(2-bromophenyl)-4-chloro2-methylquinoline (2) with benzylic and aliphatic amines, giving indoloquinolines 3r–t in yields of up to 96 % (Table 4). Having prepared a series of 11-substituted 11H-indolo[3,2c]quinolines (3a–t), we attempted to carry out the chemoselective Suzuki reaction followed by a double C–N coupling reaction to obtain 11H-indolo[3,2-c]quinolines without a methyl

Table 2. Synthesis of indolo[3,2-c]quinolines 3a–n.[a]

[a] Reaction conditions: 2 (0.150 mmol), aniline (0.225 mmol), [Pd2dba3] (0.0075 mmol), PtBu3·HBF4 (0.015 mmol), NaOtBu (0.36 mmol), toluene (3 mL), 100 °C, 24 h. Isolated yields are given. Eur. J. Org. Chem. 2017, 5554–5565

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Full Paper Table 3. Optimization of the synthesis of indolo[3,2-c]quinoline 3o.[a]

Scheme 5. Chemoselective Suzuki reactions of 4-bromo-3-iodoquinoline (4). Entry 1 2 3 4

Ligand

Yield [%][b]

SPhos PtBu3·HBF4 dppf (S)-BINAP

73 67 59 95

[a] Reaction conditions: 2 (0.10 mmol), aniline (0.15 mmol), [Pd2dba3] (0.005 mmol), ligand (0.005 mmol for monodentate or 0.010 mmol for bidentate ligands), NaOtBu (0.24 mmol), toluene (2 mL), 100 °C, 14 h. [b] Isolated yields.

group at the 6-position. Thus, 4-bromo-3-iodoquinoline (4), prepared according to the literature,[14c,19] was treated with different bromophenylboronic acids to obtain 3-(2-bromophenyl)-4bromoquinoline derivatives 5a–c (Scheme 5). Under the optimized conditions stated above, the scope of the double C–N coupling was examined by using different primary amines ranging from alkylamines to electron-rich and -poor aniline derivatives (Table 5). The yields of indoloquinolines 6a–k varied from good to excellent.

Thus, both series of 11-substituted 11H-indolo[3,2-c]quinolines, 3a–t and 6a–k, can be synthesized in good-to-excellent yields by chemoselective Suzuki reaction followed by double C–N coupling under the developed reaction conditions, with the highest yields being obtained with electron-rich anilines. The bidentate phosphine ligand (S)-BINAP was found to be more suited to benzylic and aliphatic amines as well as electron-poor anilines. The molecular structure of indoloquinoline 3g was independently confirmed by X-ray crystal structure analysis. The asymmetric unit of 3g is comprised of three molecules, and a representative structure is illustrated in Figure 2. The core indoloquinoline ring is planar with the substituent at the 11position of the three indoloquinoline molecules twisted out of the aromatic plane with angles of 63.53, 87.13 and 78.84°. π–π stacking interactions between the aromatic rings of the indolo-

Table 4. Synthesis of indolo[3,2-c]quinolines from electron-poor and aliphatic amines.[a]

[a] Reaction conditions: 2 (0.150 mmol), amine (0.225 mmol), [Pd2dba3] (0.0075 mmol), (S)-BINAP (0.0075 mmol), NaOtBu (0.36 mmol), toluene (3 mL), 100 °C, 24 h. Isolated yields are given. Eur. J. Org. Chem. 2017, 5554–5565

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Full Paper Table 5. Synthesis of indolo[3,2-c]quinolines 6a–k.[a]

[a] Reaction conditions: 5a–c (0.150 mmol), amine (0.225 mmol), [Pd2dba3] (0.0075 mmol), PtBu3·HBF4 (0.015 mmol) or (S)-BINAP (0.0075 mmol), NaOtBu (0.36 mmol), toluene (3 mL), 100 °C, 24 h. Isolated yields are given.

quinoline unit are observed in the crystal (Figure 3). The shortest distance between the ring centroids is 3.638 Å.

Conclusions A convenient and modular synthesis of 11-substituted 11H-indolo[3,2-c]quinolines by sequential chemoselective Suzuki reaction and double C–N coupling has been developed. The crystal structure of a representative product (3g) has been studied in detail, the structure showing well-defined π–π stacking interactions. The modularity and effectiveness of the method are suitable for the synthesis of a large library of products for further biological and physical applications.

Experimental Section

Figure 2. Crystal structure of 11H-indolo[3,2-c]quinoline 3g. Eur. J. Org. Chem. 2017, 5554–5565

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Unless otherwise stated, the employed chemicals were purchased from commercial sources without further purification. Solvents used for work-up and purification were distilled according to standard 5558


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Figure 3. π–π stacking interactions in the crystal of 11H-indolo[3,2-c]quinoline 3g.

procedures. Column chromatography was performed with silica gel (particle sizes 0.006–0.043 mm). Melting points were determined with a Micro-Hot-Stage Galen TM III Cambridge Instrument. NMR spectra were recorded with Bruker AVANCE 250 II (built 2006), AVANCE 300 III (built 2007) and AVANCE 500 (built 2001). NMR peaks were calibrated by reference to standard peaks of chloroform at 7.260 ppm for 1H and 77.160 ppm for 13C. For peak descriptions, the following abbreviations have been used: s (singlet), d (doublet), t (triplet), dd (doublet of doublets), td (triplet of doublets), dt (doublet of triplets), pt (pseudo-triplet), ddd (double of doublets of doublets). IR spectra were recorded with a Nicolet 380 FT-IR spectrometer using the ATR sampling technique. For peak descriptions, the following abbreviations have been used: w (weak), m (medium), s (strong). GC–MS analyses were performed with a Finnigan MAT 95-XP instrument using a HP-5 capillary column with helium as carrier gas and the electron ionization (EI) scan technique at 70 eV. For HRMS, a Finnigan MAT 95 XP spectrometer was employed. Only signals with a deviation of less than ±2 mDa were counted as correct. Crystallographic data were collected with a Bruker Kappa APEX II Duo diffractometer. The structure of 3g was solved by direct methods[20] and refined by full-matrix least-squares procedures.[21] XP (Bruker AXS) and Mercury[22] were used for molecular graphics.[23] General Synthetic Procedures: 3-Bromo-4-chloro-2-methylquinoline (1a), 4-chloro-3-iodo-2-methylquinoline (1b) and 4-bromo-3iodoquinoline (4) were obtained according to known procedures.[14c,19] General Procedure for the Synthesis of 3-(2-Bromophenyl)-4chloro-2-methylquinoline (2) and 3-(2-Bromophenyl)-4-bromoquinoline Derivatives 5a–c by Chemoselective Suzuki Reaction of 3,4-Dihaloquinolines 1a,b and 4: 3,4-Dihaloquinoline 1a,b or 4 (3.0 mmol), the corresponding boronic acid (4.2 mmol), [Pd(PPh3)4](0.15 mmol) and Na2CO3 (6.0 mmol) were added to a dried glass pressure tube. The tube was evacuated and backfilled three times with argon. The solids were solved in DMF (10.0 mL) and distilled water (1.0 mL). The tube was sealed with a Teflon cap and heated at 100 °C for 24 h. After the reaction was complete (monitored by TLC), the mixture was cooled to room temperature. Na2SO4 was added and the mixture diluted with ethyl acetate and filtered. The solvent was removed under reduced pressure. The crude oil was purified by column chromatography (heptane/ethyl acetate). 3-(2-Bromophenyl)-4-chloro-2-methylquinoline (2): Colourless oil. 1H NMR (250 MHz, CDCl3): δ = 8.26 (ddd, 3J = 8.4, 4J = 1.5, 5J = 0.7 Hz, 1 H, CHAr), 8.15 (d, 3J = 8.6 Hz, 1 H, CHAr), 7.85–7.73 (m, 2 H, CHAr), 7.64 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.3 Hz, 1 H, CHAr), 7.48 (td, Eur. J. Org. Chem. 2017, 5554–5565

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3

J = 7.5, 4J = 1.3 Hz, 1 H, CHAr), 7.43–7.28 (m, 1 H, CHAr), 7.26 (dd, J = 7.5, 4J = 1.9 Hz, 1 H, CHAr), 2.48 (s, 3 H, CH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 158.0 (CAr), 147.4 (CAr), 142.1 (CAr), 138.3 (CAr), 133.4 (CAr), 133.2 (CHAr), 130.9 (CHAr), 130.8 (CHAr), 130.2 (CHAr), 128.8 (CHAr), 128.1 (CHAr), 127.3 (CHAr), 125.1 (CAr), 124.8 (CHAr), 123.8 (CAr), 24.7 (CH3) ppm. IR (ATR): ν˜ = 3660 (w), 3399 (w), 3060 (m), 2998 (w), 2954 (w), 2919 (w), 2848 (w), 1613 (m), 1581 (m), 1555 (m), 1475 (m), 1433 (m), 1394 (m), 1345 (s), 1253 (w), 1057 (m), 1026 (m), 924 (m), 840 (m), 751 (s), 638 (m), 592 (m) cm–1. MS (EI, 70 eV): m/z (%) = 335 (29), 334 (18), 333 (100) [M]+, 331 (71), 298 (12), 296 (11), 254 (16), 253 (12), 252 (43), 251 (10), 176 (45), 175 (14), 174 (10), 150 (15), 126 (13), 109 (10), 88 (14), 87 (14), 75 (15). HRMS (EI): calcd. for C16H11NBrCl [M]+ 330.97579; found 330.97625; calcd. for C16H11N81BrCl [M]+ 332.97374; found 332.97349; calcd. for C16H11NBr37Cl [M]+ 332.97284; found 332.97349; calcd. for C16H11N81Br37Cl [M]+ 334.97079; found 334.97103. 3

3-(2-Bromophenyl)-4-bromoquinoline (5a): White solid, m.p. 94– 96 °C. 1H NMR (300 MHz, CDCl3): δ = 8.70 (s, 1 H, CHAr), 8.33 (dd, 3 J = 8.4, 4J = 0.9 Hz, 1 H, CHAr), 8.21 (dd, 3J = 8.4, 4J = 0.7 Hz, 1 H, CHAr), 7.82 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.77–7.68 (m, 2 H, CHAr), 7.50–7.32 (m, 1 H, CHAr), 7.39–7.28 (m, 2 H, CHAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.4 (CHAr), 147.7 (CAr), 139.2 (CAr), 136.0 (CAr), 135.2 (CAr), 133.1 (CHAr), 131.6 (CHAr), 130.7 (CHAr), 130.4 (CHAr), 129.7 (CHAr), 128.5 (CHAr), 127.9 (CAr), 127.6 (CHAr), 127.5 (CHAr), 123.9 (CAr) ppm. IR (ATR): ν˜ = 3060 (w), 2924 (w), 2852 (w), 1551 (m), 1479 (m), 1429 (m), 1338 (m), 1254 (w), 1024 (m), 864 (m), 808 (m), 754 (s), 717 (m), 657 (m), 640 (m), 572 (m), 553 (m) cm–1. MS (EI, 70 eV): m/z (%) = 365 (16) [M]+, 363 (36) [M]+, 361 (21) [M]+, 284 (29), 282 (41), 204 (22), 203 (100), 202 (14), 176 (38), 175 (14), 150 (20), 110 (10), 101 (10), 99 (15), 98 (17), 88 (31), 87 (16), 75 (21), 74 (26), 63 (18), 62 (14), 51 (23), 50 (29), 39 (27). HRMS (EI): calcd. for C15H9NBr2 [M]+ 360.90963; found 360.90906; calcd. for C15H9NBr81Br [M]+ 362.90758; found 362.90699; calcd. for C15H9N81Br2 [M]+ 364.90553; found 364.90526. 3-(2-Bromo-4,5-dimethylphenyl)-4-bromoquinoline (5b): Pink solid, m.p. 102–104 °C. 1H NMR (250 MHz, CDCl3): δ = 8.69 (s, 1 H, CHAr), 8.32–8.27 (m, 1 H, CHAr), 8.20–8.14 (m, 1 H, CHAr), 7.76 (ddd, 3 J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.65 (ddd, 3J = 8.3, 3J = 6.7, 4J = 1.3 Hz, 1 H, CHAr), 7.49 (s, 1 H, CHAr), 7.11 (s, 1 H, CHAr), 2.30 (s, 3 H, CH3), 2.26 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.9 (CHAr), 147.9 (CAr), 139.2 (CAr), 136.4 (CAr), 136.1 (CAr), 135.9 (CAr), 134.7 (CAr), 133.5 (CHAr), 132.3 (CHAr), 130.2 (CHAr), 129.8 (CHAr), 128.1 (CHAr), 127.7 (CAr), 127.4 (CHAr), 120.2 (CAr), 19.5 (CH3), 19.4 (CH3) ppm. IR (ATR): ν˜ = 3065 (w), 2966 (w), 2941 (w), 2917 (w), 2856 (w), 1551 (m), 1481 (m), 1442 (m), 1331 (m), 933 (m), 841 (m), 752 (s), 683 (m), 644 (m) cm–1. MS (EI, 70 eV): m/z (%) = 394 (10), 393 (43) [M]+, 392 (13), 391 (100) [M]+, 390 (15), 389 (49) [M]+, 313 (25), 312 (46), 311 (16), 310 (25), 295 (11), 231 (90), 230 (37), 228 (17), 216 (48), 214 (20), 203 (24), 202 (70), 201 (15), 200 (15), 189 (29), 176 (15), 162 (13), 151 (19), 127 (20), 126 (18), 115 (24), 101

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Full Paper (45). HRMS (EI): calcd. for C17H13NBr2 [M]+ 388.94093; found 388.94076; calcd. for C17H13NBr81Br [M]+ 390.93888; found 390.93918. 3-(2-Bromo-4,5-dimethoxyphenyl)-4-bromoquinoline (5c): Yellow solid, m.p. 120–122 °C. 1H NMR (250 MHz, CDCl3): δ = 8.68 (s, 1 H, CHAr), 8.28–8.22 (m, 1 H, CHAr), 8.15–8.10 (m, 1 H, CHAr), 7.73 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.62 (ddd, 3J = 8.3, 3 J = 6.9, 4J = 1.3 Hz, 1 H, CHAr), 7.14 (s, 1 H, CHAr), 6.82 (s, 1 H, CHAr), 3.90 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 151.0 (CHAr), 149.8 (CAr), 148.3 (CAr), 147.8 (CAr), 135.7 (CAr), 135.0 (CAr), 131.0 (CAr), 130.3 (CHAr), 129.7 (CHAr), 128.2 (CHAr), 127.6 (CAr), 127.4 (CHAr), 115.3 (CHAr), 113.9 (CHAr), 113.9 (CAr), 56.2 (OCH3), 56.1 (OCH3) ppm. IR (ATR): ν˜ = 3057 (w), 3011 (w), 2957 (w), 2935 (w), 2904 (w), 2833 (w), 1603 (m), 1589 (m), 1549 (m), 1512 (m), 1499 (m), 1460 (m), 1437 (m), 1385 (m), 1331 (s), 1244 (w), 1209 (m), 1175 (m), 1032 (m), 785 (m), 752 (s), 675 (m), 584 (m) cm–1. MS (EI, 70 eV): m/z (%) = 426 (16), 425 (48) [M]+, 424 (22), 423 (100) [M]+, 421 (56) [M]+, 382 (11), 380 (15), 301 (21), 299 (20), 248 (19), 220 (19), 219 (25), 205 (17), 191 (11), 190 (20), 177 (48), 176 (17), 165 (13), 163 (16), 150 (36), 149 (11), 123 (12), 111 (22). HRMS (EI): calcd. for C17H13O2NBr2 [M]+ 420.93076; found 420.93051; calcd. for C17H13O2NBr81Br [M]+ 422.92871; found 422.92869; calcd. for C17H13O2N81Br2 [M]+ 424.92666; found 424.92697. General Procedure for the Synthesis of Indoloquinolines 3a–t and 6a–k: Quinoline 2 or 5a–c (0.15 mmol), the corresponding amine (0.225 mmol), [Pd2dba3] (0.0075 mmol), PtBu3·HBF4 (0.015 mmol) or (S)-BINAP (0.0075 mmol) and NaOtBu (0.36 mmol) were added to a dried glass pressure tube. The tube was evacuated and backfilled three times with argon. Dried toluene (2.0 mL) was added to this tube. The mixture was then heated at 100 °C for 14 h. After the reaction was complete (monitored by TLC), the mixture was cooled to room temperature. The solvent was removed under reduced pressure and the crude oil was purified by column chromatography (heptane/ethyl acetate). 6-Methyl-11-(4-tolyl)-11H-indolo[3,2-c]quinoline (3a): Yellow oil. H NMR (300 MHz, CDCl3): δ = 8.32–8.27 (m, 1 H, CHAr), 8.21 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.60 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.48 (d, 3J = 7.7 Hz, 2 H, CHAr), 7.44 (dd, 3J = 6.1, 4J = 3.2 Hz, 2 H, CHAr), 7.40 (d, 3J = 8.2 Hz, 2 H, CHAr), 7.36 (ddd, 3J = 8.4, 4J = 1.5, 5J = 0.6 Hz, 1 H, CHAr), 7.25–7.18 (m, 2 H, CHAr), 3.28 (s, 3 H, CH3), 2.58 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.9 (CAr), 146.1 (CAr), 142.1 (CAr), 140.2 (CAr), 139.7 (CAr), 135.9 (CAr), 131.0 (2 CHAr), 129.2 (CHAr), 128.7 (2 CHAr), 127.9 (CHAr), 125.3 (CHAr), 124.5 (CHAr), 122.4 (CAr), 121.9 (CHAr), 121.7 (CHAr), 121.6 (CHAr), 116.7 (CAr), 114.3 (CAr), 110.8 (CHAr), 25.0 (CH3,quinoline), 21.5 (CH3,Ar) ppm. IR (ATR): ν˜ = 3057 (w), 3035 (w), 2951 (w), 2918 (w), 2852 (w), 1560 (w), 1509 (m), 1428 (m), 1365 (m), 1197 (w), 1118 (w), 740 (s), 507 (m) cm–1. MS (EI, 70 eV): m/z (%) = 323 (27), 322 (100) [M]+, 321 (24), 306 (8), 153 (10). HRMS (ESI): calcd. for C23H18N2 [M + H]+ 323.15428; found 323.15462. 1

11-(3,5-Dimethylphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3b): Yellow solid, m.p. 182–183 °C. 1H NMR (300 MHz, CDCl3): δ = 8.34–8.30 (m, 1 H, CHAr), 8.23 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.63 (ddd, 3 J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.49–7.44 (m, 2 H, CHAr), 7.40 (dd, 3J = 8.4, 5J = 0.8 Hz, 1 H, CHAr), 7.32 (s, 1 H, CHAr), 7.29– 7.22 (m, 2 H, CHAr), 7.16 (s, 2 H, CHAr), 3.30 (s, 3 H, CH3,quinoline), 2.47 (s, 6 H, CH3,Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.9 (CAr), 146.1 (CAr), 142.0 (2 CAr), 140.2 (CAr), 140.1 (CAr), 138.4 (CAr), 131.2 (CHAr), 129.2 (CHAr), 127.8 (CHAr), 126.4 (2 CHAr), 125.2 (CHAr), 124.5 (CHAr), 122.3 (CAr), 122.1 (CHAr), 121.7 (CHAr), 121.5 (CHAr), 116.7 (CAr), 114.2 (CAr), 110.9 (CHAr), 25.0 (CH3,quinoline), 21.4 (2 CH3,Ar) ppm. IR (ATR): ν˜ = 3038 (w), 2995 (w), 2960 (w), 2916 (w), 2855 (w), 1595 (w), 1560 Eur. J. Org. Chem. 2017, 5554–5565

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(m), 1506 (m), 1470 (m), 1363 (m), 1244 (m), 1181 (w), 1023 (w), 858 (m), 744 (s), 726 (m) cm–1. MS (EI, 70 eV): m/z (%) = 337 (28), 336 (100) [M] + , 160 (8). HRMS (ESI): calcd. for C 2 4 H 20 N 2 [M + H] + 337.16993; found 337.1701. 11-(2,3-Dihydro-1H-inden-5-yl)-6-methyl-11H-indolo[3,2-c]quinoline (3c): White solid, m.p. 185–186 °C. 1H NMR (250 MHz, CDCl3): δ = 8.33–8.27 (m, 1 H, CHAr), 8.22 (dd, 3J = 8.6, 4J = 1.4 Hz, 1 H, CHAr), 7.61 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.50 (d, 3 J = 8.0 Hz, 1 H, CHAr), 7.47–7.42 (m, 2 H, CHAr), 7.39 (d, 3J = 7.5 Hz, 1 H, CHAr), 7.34 (s, 1 H, CHAr), 7.30–7.19 (m, 3 H, CHAr), 3.29 (s, 3 H, CH3,quinoline), 3.19–2.99 (m, 4 H, CH2,aliphatic), 2.34–2.19 (m, 2 H, CH2,aliphatic) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.9 (CAr), 146.9 (CAr), 146.1 (CAr), 146.0 (CAr), 142.2 (CAr), 140.3 (CAr), 136.4 (CAr), 129.0 (CHAr), 128.0 (CHAr), 126.7 (CHAr), 125.9 (CHAr), 125.2 (CHAr), 124.7 (CHAr), 124.5 (CHAr), 122.3 (CAr), 122.0 (CHAr), 121.6 (CHAr), 121.6 (CHAr), 116.7 (CAr), 114.2 (CAr), 110.9 (CHAr), 33.0 (CH2), 32.8 (CH2), 25.6 (CH2), 24.9 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3039 (w), 3004 (w), 2946 (m), 2841 (m), 1561 (m), 1493 (m), 1428 (m), 1361 (m), 1238 (m), 1154 (m), 838 (w), 734 (s), 627 (w), 429 (m) cm–1. MS (EI, 70 eV): m/z (%) = 349 (30), 348 (100) [M]+, 347 (25), 160 (7). HRMS (EI): calcd. for C25H20N2 [M]+ 348.16210; found 348.16164. 11-[4-(tert-Butyl)phenyl]-6-methyl-11H-indolo[3,2-c]quinoline (3d): Yellow solid, m.p. 137–138 °C. 1H NMR (250 MHz, CDCl3): δ = 8.33–8.28 (m, 1 H, CHAr), 8.23 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.69 (d, 3J = 8.7 Hz, 2 H, CHAr), 7.60 (ddd, 3J = 8.4, 3J = 6.8, 4J = 1.6 Hz, 1 H, CHAr), 7.48–7.40 (m, 4 H, CHAr), 7.32 (ddd, 3J = 8.4, 4J = 1.6, 5J = 0.6 Hz, 1 H, CHAr), 7.25–7.17 (m, 2 H, CHAr), 3.29 (s, 3 H, CH3,quinoline), 1.49 (s, 9 H, CH3,tBu) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.8 (CAr), 152.9 (CAr), 145.9 (CAr), 142.1 (CAr), 140.2 (CAr), 135.7 (CAr), 129.0 (CHAr), 128.3 (2 CHAr), 127.9 (CHAr), 127.2 (2 CHAr), 125.3 (CHAr), 124.6 (CHAr), 122.3 (CHAr), 121.9 (CHAr), 121.6 (CHAr), 116.7 (CAr), 114.2 (C Ar ), 112.9 (C Ar ), 110.9 (CH Ar ), 35.0 (C tBu ), 31.5 (3 CH 3,tBu ), 25.0 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3393 (w), 3064 (w), 3045 (w), 2956 (m), 2903 (w), 2866 (w), 1561 (m), 1506 (m), 1458 (m), 1429 (m), 1323 (m), 1239 (m), 1199 (m), 1116 (m), 740 (s), 629 (m) cm–1. MS (EI, 70 eV): m/z (%) = 364 (100) [M]+, 349 (52), 307 (8), 160 (11). HRMS (ESI): calcd. for C 2 6 H 2 4 N 2 [M + H] + 365.20123; found 365.20144. 6-Methyl-11-phenyl-11H-indolo[3,2-c]quinoline (3e): Yellow solid, m.p. 195–196 °C. 1H NMR (300 MHz, CDCl3): δ = 8.30 (ddd, 3 J = 6.2, 4J = 3.1, 5J = 0.8 Hz, 1 H, CHAr), 8.22 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.73–7.66 (m, 3 H, CHAr), 7.60 (ddd, 3J = 8.4, 3J = 6.8, 4J = 1.6 Hz, 1 H, CHAr), 7.56–7.51 (m, 2 H, CHAr), 7.45 (dd, 3J = 6.2, 4J = 3.1 Hz, 2 H, CHAr), 7.29 (dd, 3J = 8.4, 4J = 1.0 Hz, 1 H, CHAr), 7.23– 7.17 (m, 2 H, CHAr), 3.28 (s, 3 H, CH3,quinoline) ppm. 13C NMR (75 MHz, CDCl3): δ = 155.0 (CAr), 146.2 (CAr), 142.1 (CAr), 140.2 (CAr), 138.7 (CAr), 130.5 (2 CHPh), 129.8 (CHAr), 129.4 (CHAr), 129.1 (2 CHPh), 128.0 (CHAr), 125.5 (CHAr), 124.7 (CHAr), 122.5 (CAr), 121.9 (CHAr), 121.9 (CH Ar ), 121.8 (CH Ar ), 116.7 (C Ar ), 114.5 (C Ar ), 110.8 (CH Ar ), 25.1 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3055 (w), 2992 (w), 2947 (w), 2912 (w), 2848 (w), 1591 (w), 1559 (m), 1502 (m), 1455 (m), 1435 (m), 1368 (m), 1235 (m), 1197 (m), 1917 (m), 736 (s), 701 (m), 625 (m) cm–1. MS (EI, 70 eV): m/z (%) = 309 (22), 308 (100) [M]+, 307 (30), 153 (5). HRMS (ESI): calcd. for C22H16N2 [M + H]+ 309.13862; found 309.13876. 6-Methyl-11-[4-(methylthio)phenyl]-11H-indolo[3,2-c]quinoline (3f): Yellow solid, m.p. 170–171 °C. 1H NMR (250 MHz, CDCl3): δ = 8.32–8.26 (m, 1 H, CHAr), 8.21 (d, 3J = 8.0 Hz, 1 H, CHAr), 7.61 (ddd, 3 J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.51 (d, 3J = 8.7 Hz, 2 H, CHAr), 7.47–7.37 (m, 5 H, CHAr), 7.28–7.23 (m, 1 H, CHAr), 7.23–7.17 (m, 1 H, CHAr), 3.26 (s, 3 H, CH3,quinoline), 2.64 (s, 3 H, SCH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.8 (CAr), 146.0 (CAr), 142.0 (CAr), 140.9

5560


Full Paper (CAr), 140.1 (CAr), 135.1 (CAr), 129.2 (2 CHAr), 127.9 (CHAr), 127.3 (2 CHAr), 125.4 (CHAr), 124.7 (CHAr), 122.4 (CAr), 121.8 (2 CHAr), 121.7 (2 CHAr), 116.6 (CAr), 114.3 (CAr), 110.7 (CHAr), 25.0 (CH3,quinoline), 15.4 (SCH3) ppm. IR (ATR): ν˜ = 3054 (w), 2948 (w), 2918 (w), 1560 (w), 1496 (m), 1432 (m), 1363 (m), 1198 (m), 1087 (m), 737 (s), 626 (m), 511 (m) cm–1. MS (EI, 70 eV): m/z (%) = 355 (27), 354 (100) [M]+, 306 (10), 153 (6). HRMS (EI): calcd. for C23H18N2S [M]+ 354.11852; found 354.11843. 11-(4-Methoxyphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3g): Yellow solid, m.p. 234–236 °C. 1H NMR (250 MHz, CDCl3): δ = 8.54 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.32–8.28 (m, 1 H, CHAr), 7.68 (ddd, 3 J = 8.4, 3J = 6.6, 4J = 1.7 Hz, 1 H, CHAr), 7.51 (d, 3J = 8.9 Hz, 2 H, CHAr), 7.45 (d, 3J = 8.9 Hz, 2 H, CHAr), 7.38 (ddd, 3J = 8.4, 4J = 1.7, 5 J = 0.7 Hz, 1 H, CHAr), 7.32 (dd, 3J = 6.7, 4J = 1.3 Hz, 1 H, CHAr), 7.25–7.17 (m, 3 H, CH A r ), 4.00 (s, 3 H, OCH 3 ), 3.42 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 160.4 (CArOCH3), 154.5 (CAr), 144.9 (CAr), 142.4 (CAr), 140.5 (CAr), 130.7 (CAr), 129.9 (2 CHAr), 128.3 (CHAr), 125.6 (CHAr), 124.9 (CHAr), 122.2 (CHAr), 121.9 (CHAr), 121.9 (CAr), 121.7 (CHAr), 116.5 (CAr), 115.6 (2 CHAr), 114.1 (CHAr), 113.9 (CAr), 110.9 (CHAr), 55.7 (OCH3), 24.2 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3398 (w), 3056 (m), 3004 (w), 2958 (w), 2933 (m), 2837 (m), 2546 (m), 2198 (m), 2056 (w), 1891 (w), 1635 (m), 1606 (m), 1508 (s), 1435 (s), 1368 (m), 1296 (m), 1248 (s), 1198 (m), 1026 (m), 908 (m), 842 (m), 723 (s), 526 (m) cm–1. MS (EI, 70 eV): m/z (%) = 338 (100) [M]+, 323 (10), 294 (21), 147 (14). HRMS (EI): calcd. for C23H18ON2 [M]+ 338.14136; found 338.14096. 11-(3-Methoxyphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3h): Yellow solid, m.p. 206–207 °C. 1H NMR (300 MHz, CDCl3): δ = 8.32–8.28 (m, 1 H, CHAr), 8.22 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.64–7.60 (m, 1 H, CHAr), 7.60–7.56 (m, 1 H, CHAr), 7.50–7.41 (m, 2 H, CHAr), 7.38 (ddd, 3J = 8.4, 4J = 1.5, 5J = 0.6 Hz, 1 H, CHAr), 7.28–7.20 (m, 3 H, CHAr), 7.13 (ddd, 3J = 7.7, 4J = 1.9, 5J = 1.0 Hz, 1 H, CHAr), 7.05 (t, 4 J = 2 . 2 H z , 1 H , C H A r ) , 3 . 8 5 ( s , 3 H , O C H 3 ) , 3 . 2 8 ( s , 3 H, CH3,quinoline) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.1 (CArOCH3), 154.8 (CAr), 146.0 (CAr), 141.9 (CAr), 140.0 (CAr), 139.6 (CAr), 131.1 (CHAr), 129.2 (CHAr), 128.0 (CHAr), 125.4 (CHAr), 124.7 (CHAr), 122.4 (CHAr), 122.0 (CAr), 121.7 (2 CHAr), 121.1 (CHAr), 116.6 (CAr), 115.7 (CH Ar ), 114.3 (C Ar ), 114.2 (CH Ar ), 110.8 (CH Ar ), 55.6 (OCH 3 ), 25.0 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3037 (w), 3008 (w), 2967 (w), 2837 (w), 1594 (m), 1494 (m), 1427 (m), 1364 (m), 1243 (m), 1029 (m), 860 (m), 793 (m), 737 (s), 709 (m), 635 (m) cm–1. MS (EI, 70 eV): m/z (%) = 339 (25), 338 (100) [M]+, 323 (6), 294 (12). HRMS (ESI): calcd. for C23H18N2O [M + H]+ 339.14919; found 339.14961. 11-(2-Methoxyphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3i): Brown oil. 1H NMR (300 MHz, CDCl3): δ = 8.36–8.25 (m, 2 H, CHAr), 7.73–7.59 (m, 2 H, CHAr), 7.52 (dd, 3J = 7.7, 4J = 1.7 Hz, 1 H, CHAr), 7.49–7.45 (m, 2 H, CHAr), 7.39 (ddd, 3J = 8.4, 4J = 1.5, 5J = 0.6 Hz, 1 H, CHAr), 7.31–7.15 (m, 4 H, CHAr), 3.60 (s, 3 H, OCH3), 3.33 (s, 3 H, CH3,quinoline) ppm. 13C NMR (75 MHz, CDCl3): δ = 156.5 (C Ar OCH 3 ), 154.6 (C Ar ), 145.2 (C Ar ), 141.6 (C Ar ), 140.6 (C Ar ), 131.3 (CHAr), 130.4 (CHAr), 128.6 (CHAr), 128.1 (CHAr), 126.8 (CAr), 125.4 (CHAr), 124.8 (CHAr), 122.5 (CAr), 121.7 (CHAr), 121.7 (CHAr), 121.6 (CH Ar ), 121.2 (CH Ar ), 117.0 (C Ar ), 114.3 (C Ar ), 112.8 (CH Ar ), 110.7 (CHAr), 55.8 (OCH3), 24.5 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3358 (m), 3056 (m), 3011 (m), 2939 (m), 2839 (m), 2563 (w), 1596 (m), 1559 (m), 1502 (s), 1455 (m), 1432 (m), 1366 (m), 1244 (m), 1118 (m), 1019 (m), 741 (s), 626 (m) cm–1. MS (EI, 70 eV): m/z (%) = 338 (100) [M]+, 323 (12), 293 (10). HRMS (EI): calcd. for C23H18ON2 [M]+ 338.14136; found 338.14102. 11-(3,5-Dimethoxyphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3j): Yellow solid, m.p. 203–204 °C. 1H NMR (250 MHz, CDCl3): δ = 8.33–8.27 (m, 1 H, CHAr), 8.22 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.63 (ddd, Eur. J. Org. Chem. 2017, 5554–5565

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3

J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.53–7.43 (m, 3 H, CHAr), 7.34–7.24 (m, 2 H, CHAr), 6.77 (t, 4J = 2.3 Hz, 1 H, CHAr), 6.68 (d, 4J = 2.3 Hz, 2 H, CHAr), 3.83 (s, 6 H, OCH3), 3.28 (s, 3 H, CH3,quinoline) ppm. 13 C NMR (63 MHz, CDCl3): δ = 162.0 (2 CArOCH3), 154.8 (CAr), 146.1 (CAr), 141.7 (CAr), 140.1 (CAr), 139.9 (CAr), 129.2 (CHAr), 127.9 (CHAr), 125.4 (CHAr), 124.7 (CHAr), 122.4 (CAr), 122.1 (CHAr), 121.7 (2 CHAr), 116.5 (CAr), 114.3 (CAr), 110.8 (CHAr), 106.9 (2 CHAr), 101.9 (CHAr), 55.7 (2 OCH3), 25.0 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3004 (m), 2966 (m), 2939 (m), 2858 (m), 1607 (m), 1582 (m), 1422 (m), 1192 (m), 1151 (s), 1060 (m), 989 (m), 854 (m), 745 (s), 724 (m), 633 (m) cm–1. MS (EI, 70 eV): m/z (%) = 369 (27), 368 (100) [M]+, 309 (7). HRMS (EI): calcd. for C24H20O2N2 [M]+ 368.15193; found 368.15148. 11-(2,4-Dimethoxyphenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3k): White solid, m.p. 137–138 °C. 1H NMR (250 MHz, CDCl3): δ = 8.33–8.26 (m, 1 H, CHAr), 8.22 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.60 (ddd, 3 J = 8.4, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.49–7.41 (m, 3 H, CHAr), 7.39 (dd, 3J = 8.0, 5J = 0.9 Hz, 1 H, CHAr), 7.24 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.3 Hz, 1 H, CHAr), 7.19–7.13 (m, 1 H, CHAr), 6.74 (d, 3J = 8.0 Hz, 2 H, CHAr), 3.98 (s, 3 H, OCH3), 3.56 (s, 3 H, OCH3), 3.28 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 161.8 (CArOCH3), 157.4 (CArOCH3), 154.8 (CAr), 145.7 (CAr), 141.9 (CAr), 140.6 (CAr), 130.8 (CHAr), 128.9 (CHAr), 127.8 (CHAr), 125.2 (CHAr), 124.6 (CAr), 122.4 (CAr), 121.6 (CAr), 121.5 (CHAr), 121.2 (CAr), 119.8 (CAr), 117.2 (CHAr), 114.2 (CHAr), 110.6 (CHAr), 105.1 (CHAr), 100.2 (CHAr), 55.8 (OCH3), 55.7 (OCH3), 24.8 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3369 (w), 3057 (w), 3011 (w), 2930 (w), 2838 (w), 2573 (w), 1605 (w), 1587 (m), 1510 (m), 1368 (m), 1285 (m), 1208 (m), 1159 (m), 1021 (m), 835 (m), 744 (s), 547 (m) cm–1. MS (EI, 70 eV): m/z (%) = 369 (26), 368 (100) [M]+, 293 (5), 281 (9), 147 (5). HRMS (EI): calcd. for C24H20O2N2 [M]+ 368.15193; found 368.15197. 6-Methyl-11-(3,4,5-trimethoxyphenyl)-11H-indolo[3,2-c]quinoline (3l): White solid, m.p. 201–202 °C. 1H NMR (250 MHz, CDCl3): δ = 8.33–8.28 (m, 1 H, CHAr), 8.24 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.63 (ddd, 3J = 8.4, 3J = 6.8, 4J = 1.5 Hz, 1 H, CHAr), 7.51–7.45 (m, 2 H, CHAr), 7.43 (ddd, 3J = 8.4, 4J = 1.5, 5J = 0.6 Hz, 1 H, CHAr), 7.34– 7.28 (m, 2 H, CHAr), 6.76 (s, 2 H, CHAr), 4.06 (s, 3 H, OCH3), 3.84 (s, 6 H, OCH3), 3.29 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.8 (CAr), 154.6 (2 CArOCH3), 145.8 (CAr), 142.0 (CAr), 140.1 (CAr), 138.8 (CAr), 133.8 (CAr), 129.0 (CHAr), 128.1 (CHAr), 125.5 (CHAr), 124.9 (CHAr), 122.3 (CAr), 121.9 (CHAr), 121.8 (CHAr ), 121.7 (CH Ar ), 116.5 (CAr), 114.1 (CAr), 110.8 (CHAr), 106.0 (2 CHAr), 61.2 (OCH3), 56.4 (2 OCH3), 24.8 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3049 (w), 2993 (w), 2939 (w), 2827 (w), 2454 (w), 1591 (m), 1503 (m), 1346 (w), 1227 (m), 1118 (s), 1000 (m), 747 (s) cm–1. MS (EI, 70 eV): m/z (%) = 398 (100) [M]+, 383 (22), 297 (8). HRMS (EI): calcd. for C25H22O3N2 [M]+ 398.16249; found 398.16215. 6-Methyl-11-(1-naphthyl)-11H-indolo[3,2-c]quinoline (3m): Red solid, m.p. 197–198 °C. 1H NMR (250 MHz, CDCl3): δ = 8.38 (ddd, 3 J = 8.0, 4J = 1.2, 5J = 0.7 Hz, 1 H, CHAr), 8.20 (d, 3J = 8.4 Hz, 2 H, CHAr), 8.07 (d, 3J = 8.3 Hz, 1 H, CHAr), 7.82–7.66 (m, 2 H, CHAr), 7.58– 7.54 (m, 1 H, CHAr), 7.53–7.49 (m, 1 H, CHAr), 7.49–7.43 (m, 1 H, CHAr), 7.38 (ddd, 3J = 8.3, 3J = 7.2, 4J = 1.3 Hz, 1 H, CHAr), 7.27 (ddd, 3 J = 8.2, 3J = 6.8, 4J = 1.2 Hz, 1 H, CHAr), 7.10 (d, 3J = 8.5 Hz, 1 H, CHAr), 7.02–6.99 (m, 1 H, CHAr), 6.99–6.94 (m, 2 H, CHAr), 3.35 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 155.0 (CAr), 146.1 (CAr), 142.2 (CAr), 140.8 (CAr), 135.0 (CAr), 134.7 (CAr), 131.1 (CAr), 130.2 (CHAr), 129.1 (CHAr), 128.5 (CHAr), 127.9 (CHAr), 127.8 (CHAr), 127.2 (CHAr), 127.2 (CHAr), 126.0 (CHAr), 125.5 (CHAr), 124.7 (CHAr), 122.8 (CHAr), 122.5 (CHAr), 121.8 (CHAr), 121.5 (CHAr), 116.6 (CAr), 114.4 (CAr), 111.0 (CHAr), 100.0 (CAr), 25.1 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3047 (m), 2889 (w), 2915 (w), 2849 (w), 1595 (w), 1560 (m), 1508 (m), 1433 (m), 1364 (m), 1240 (m), 1117 (m), 776 (m), 738 (s), 638

5561


Full Paper (m) cm–1. MS (EI, 70 eV): m/z (%) = 359 (30), 358 (100) [M]+, 357 (20), 178 (5). HRMS (ESI): calcd. for C26H18N2 [M + H]+ 359.15428; found 359.15493.

(m), 1228 (m), 1198 (m), 1117 (w), 733 (s), 626 (m), 547 (m) cm–1. MS (EI, 70 eV): m/z (%) = 334 (23), 333 (100) [M]+, 331 (23). HRMS (EI): calcd. for C23H15N3 [M]+ 333.12605; found 333.12566.

11-(2-Anthryl)-6-methyl-11H-indolo[3,2-c]quinoline (3n): Yellow solid, m.p. 290–291 °C. 1H NMR (250 MHz, CDCl3): δ = 8.66 (d, 4J = 1.3 Hz, 1 H, CHAr), 8.54 (d, 4J = 1.1 Hz, 1 H, CHAr), 8.39–8.26 (m, 4 H, CHAr), 8.17–8.02 (m, 2 H, CHAr), 7.64–7.55 (m, 3 H, CHAr), 7.53–7.40 (m, 4 H, CHAr), 7.36–7.28 (m, 1 H, CHAr), 7.11 (ddd, 3J = 8.4, 3J = 6.9, 4 J = 1.3 Hz, 1 H, CHAr), 3.35 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.7 (CAr), 142.1 (CAr), 140.3 (CAr), 135.1 (CAr), 132.6 (CAr), 132.4 (CAr), 131.3 (CAr), 131.2 (CHAr), 131.0 (CAr), 128.3 (CHAr), 128.2 (2 CHAr), 127.9 (2 CHAr), 127.2 (CHAr), 126.9 (2 CHAr), 126.4 (2 CHAr), 125.7 (CAr), 125.6 (CHAr), 124.9 (CHAr), 122.5 (CAr), 122.0 (2 CHAr), 121.8 (CHAr), 116.6 (CAr), 114.5 (CAr), 110.9 (CHAr), 24.6 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3046 (w), 2911 (w), 1672 (m), 1582 (m), 1558 (m), 1430 (m), 1364 (m), 1289 (m), 736 (s), 636 (m), 468 (s) cm–1. MS (EI, 70 eV): m/z (%) = 409 (32), 408 (100) [M]+, 407 (54), 204 (11). HRMS (EI): calcd. for C30H20N2 [M]+ 408.16210; found 408.16132.

11-Benzyl-6-methyl-11H-indolo[3,2-c]quinoline (3r): Yellow oil. 1 H NMR (250 MHz, CDCl3): δ = 8.32–8.23 (m, 2 H, CHAr), 8.15 (ddd, 3 J = 8.4, 4J = 1.3, 5J = 0.6 Hz, 1 H, CHAr), 7.64 (ddd, 3J = 8.4, 3J = 7.0, 4J = 1.3 Hz, 1 H, CHAr), 7.55–7.52 (m, 1 H, CHAr), 7.52–7.51 (m, 1 H, CHAr), 7.50–7.44 (m, 1 H, CHAr), 7.39 (ddd, 3J = 8.6, 3J = 7.1, 4J = 1.5 Hz, 1 H, CHAr), 7.33–7.28 (m, 3 H, CHAr), 7.19–7.14 (m, 2 H, CHAr), 5.95 (s, 2 H, CH2,aliphatic), 3.23 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.7 (CAr), 145.9 (CAr), 140.8 (CAr), 140.0 (CAr), 136.2 (CHAr), 129.3 (CHAr), 129.2 (2 CHAr), 128.0 (CHAr), 127.8 (CHAr), 125.8 (2 CHAr), 125.6 (CHAr), 125.1 (CHAr), 122.5 (CHAr), 122.0 (CHAr), 121.7 (CHAr), 121.7 (CHAr), 116.6 (CAr), 114.3 (CAr), 109.7 (CHAr), 49.4 (CH2), 24.8 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3031 (m), 2921 (m), 2852 (m), 1561 (m), 1513 (m), 1441 (m), 1350 (m), 1239 (m), 1122 (m), 738 (s), 724 (s), 689 (m), 470 (m) cm–1. MS (EI, 70 eV): m/z (%) = 323 (16), 322 (63) [M]+, 231 (15), 204 (7), 91 (100), 65 (12). HRMS (EI): calcd. for C23H18N2 [M]+ 322.14645; found 322.14659.

11-(4-Fluorophenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3o): Orange solid, m.p. 226–227 °C. 1H NMR (250 MHz, CDCl3): δ = 8.38 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.32–8.24 (m, 1 H, CHAr), 7.64 (dt, 3J = 8.4, 4J = 4.3 Hz, 1 H, CHAr), 7.57–7.46 (m, 4 H, CHAr), 7.45–7.36 (m, 2 H, CHAr), 7.27 (m, 2 H, CHAr), 7.22–7.15 (m, 1 H, CHAr), 3.32 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 163.1 (d, 1JCF = 250.8 Hz, CArF), 154.3 (CAr), 144.2 (CAr), 142.2 (CAr), 140.5 (CAr), 134.1 (d, 4JCF = 3.5 Hz, CAr), 130.7 (d, 3JCF = 8.8 Hz, 2 CHAr), 128.7 (CHAr), 128.0 (CHAr), 126.0 (CHAr), 125.3 (CHAr), 122.4 (CHAr), 122.3 (C Ar ), 121.8 (CHAr), 121.6 (CHAr), 117.7 (d, 2JCF = 22.8 Hz, 2 CHAr), 116.2 (C Ar ), 114.2 (C Ar ), 110.8 (CH Ar ), 23.8 (CH 3,quinoline ) ppm. 19 F NMR (235 MHz, CDCl3): δ = –110.0 (CArF) ppm. IR (ATR): ν˜ = 3060 (w), 2465 (w), 2426 (w), 1886 (w), 1636 (w), 1585 (w), 1506 (m), 1436 (m), 1370 (m), 1220 (m), 1198 (m), 845 (m), 756 (m), 738 (m), 521 (m) cm–1. MS (EI, 70 eV): m/z (%) = 327 (23), 326 (100) [M]+, 325 (28). HRMS (EI): calcd. for C22H15N2F [M]+ 326.12138; found 326.12098.

11-(4-Methoxybenzyl)-6-methyl-11H-indolo[3,2-c]quinoline (3s): Yellow solid, m.p. 168–169 °C. 1H NMR (250 MHz, CDCl3): δ = 8.29 (dt, 3J = 7.7, 4J = 1.0 Hz, 2 H, CHAr), 8.20 (ddd, 3J = 8.5, 4J = 1.4, 5J = 0.6 Hz, 1 H, CHAr), 7.66 (ddd, 3J = 8.4, 3J = 7.0, 4J = 1.3 Hz, 1 H, CHAr), 7.57–7.52 (m, 2 H, CHAr), 7.50–7.38 (m, 2 H, CHAr), 7.09 (m, 2 H, CH A r ), 6.84 (d, 3 J = 8.7 Hz, 2 H, CH A r ), 5.93 (s, 2 H, CH2,aliphatic), 3.74 (s, 3 H, OCH3), 3.26 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 159.2 (CArOCH3), 154.5 (CAr), 145.5 (CAr), 140.8 (CAr), 140.0 (CAr), 129.0 (CHAr), 128.1 (CHAr), 128.0 (CAr), 127.0 (2 CHAr), 125.6 (CHAr), 125.3 (CHAr), 122.4 (CAr), 122.0 (CHAr), 121.8 (CHAr), 121.7 (CHAr), 116.6 (CAr), 114.6 (2 CHAr), 114.2 (CAr), 109.8 (CHAr), 55.3 (OCH3), 48.9 (CH2), 24.6 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3059 (w), 3002 (w), 2962 (w), 2936 (w), 2907 (w), 2830 (w), 2641 (w), 1613 (w), 1560 (w), 1511 (m), 1439 (m), 1242 (m), 1164 (w), 1024 (m), 808 (m), 741 (s), 506 (m) cm–1. MS (EI, 70 eV): m/z (%) = 352 (25) [M]+, 122 (12), 121 (100), 95 (5), 78 (8). HRMS (EI): calcd. for C24H20ON2 [M]+ 352.15701; found 352.15643.

11-(4-Chlorophenyl)-6-methyl-11H-indolo[3,2-c]quinoline (3p): Yellow solid, m.p. 261–262 °C. 1H NMR (250 MHz, CDCl3): δ = 8.59 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.34–8.24 (m, 1 H, CHAr), 7.76–7.66 (m, 3 H, CHAr), 7.58–7.47 (m, 4 H, CHAr), 7.38–7.32 (m, 2 H, CHAr), 7.24– 7.17 (m, 1 H, CHAr), 3.43 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 153.8 (CAr), 149.7 (CAr), 146.0 (CAr), 142.2 (CHAr), 140.7 (CAr), 136.3 (CAr), 136.2 (CAr), 131.0 (2 CHAr), 130.1 (2 CHAr), 129.5 (CHAr), 126.6 (CHAr), 126.1 (CHAr), 123.0 (CHAr), 122.2 (CAr), 121.9 (CH Ar ), 121.7 (CH Ar ), 115.8 (C Ar ), 114.2 (C Ar ), 111.0 (CH Ar ), 22.8 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3050 (w), 2453 (m), 1876 (w), 1584 (w), 1493 (m), 1433 (m), 1368 (m), 1198 (m), 1085 (m), 1013 (m), 843 (m), 740 (s), 626 (m), 508 (m) cm–1. MS (EI, 70 eV): m/z (%) = 342 (100) [M]+, 306 (8), 153 (14). HRMS (EI): calcd. for C22H15N2Cl [M] + 342.09183; found 342.09087; calcd. for C 22 H 15 N 2 37 Cl [M] + 344.08888; found 344.08934. 4-(6-Methyl-11H-indolo[3,2-c]quinolin-11-yl)benzonitrile (3q): White solid, m.p. 221–222 °C. 1H NMR (250 MHz, CDCl3): δ = 8.35– 8.26 (m, 1 H, CHAr), 8.22 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.01 (d, 3J = 8.7 Hz, 2 H, CHAr), 7.70 (d, 3J = 8.7 Hz, 2 H, CHAr), 7.62 (ddd, 3J = 8.4, 3J = 6.6, 4J = 1.8 Hz, 1 H, CHAr), 7.53–7.44 (m, 2 H, CHAr), 7.30– 7.13 (m, 3 H, CHAr), 3.25 (s, 3 H, CH3,quinoline) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.9 (CAr), 146.0 (CAr), 142.8 (CAr), 141.3 (CAr), 139.7 (CAr), 134.3 (2 CHAr), 130.0 (2 CHAr), 129.5 (CHAr), 128.3 (CHAr), 125.9 (CHAr), 125.0 (CHAr), 122.8 (CAr), 122.4 (CHAr), 122.1 (CHAr), 121.3 (CHAr), 117.8 (CAr), 116.1 (CAr), 115.0 (CAr), 113.6 (CAr), 110.2 (CHAr), 24.9 (CH3,quinoline) ppm. IR (ATR): ν˜ = 3033 (w), 2992 (w), 2919 (w), 2654 (w), 2475 (w), 2226 (w), 1602 (w), 1561 (m), 1431 (m), 1363 Eur. J. Org. Chem. 2017, 5554–5565

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6-Methyl-11-pentyl-11H-indolo[3,2-c]quinoline (3t): Yellow oil. 1 H NMR (250 MHz, CDCl3): δ = 8.35 (dd, 3J = 8.4, 4J = 1.0 Hz, 1 H, CHAr), 8.28 (dd, 3J = 8.4, 4J = 1.2 Hz, 1 H, CHAr), 8.23 (dt, 3J = 8.0, 4 J = 1.0 Hz, 1 H, CHAr), 7.71 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.4 Hz, 1 H, CHAr), 7.63–7.51 (m, 3 H, CHAr), 7.42 (ddd, 3J = 8.0, 3J = 6.0, 4J = 2.2 Hz, 1 H, CH Ar ), 4.74–4.60 (m, 2 H, CH 2,aliphatic ), 3.18 (s, 3 H, CH3,quinoline), 2.03 (p, 3J = 7.7 Hz, 2 H, CH2,aliphatic), 1.60–1.34 (m, 4 H, CH2,aliphatic), 0.94 (t, 3J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 154.7 (CAr), 145.9 (CAr), 140.1 (CAr), 139.1 (CAr), 129.6 (CHAr), 127.7 (CHAr), 125.1 (CHAr), 125.0 (CHAr), 122.2 (CHAr), 121.9 (CAr), 121.5 (CHAr), 121.1 (CHAr), 116.9 (CAr), 114.1 (CAr), 109.4 (CHAr), 45.7 (CH2), 29.4 (CH2), 29.1 (CH2), 24.8 (CH3,quinoline), 22.4 (CH2), 14.0 (CH3) ppm. IR (ATR): ν˜ = 3054 (w), 2950 (m), 2923 (m), 2853 (w), 1560 (m), 1439 (m), 1364 (m), 1251 (m), 1161 (m), 1111 (m), 1029 (w), 736 (s), 621 (m) cm–1. MS (EI, 70 eV): m/z (%) = 303 (13), 302 (52) [M]+, 246 (19), 245 (100), 204 (10). HRMS (EI): calcd. for C21H22N2 [M]+ 302.17775; found 302.17686. 11-(4-Tolyl)-11H-indolo[3,2-c]quinoline (6a): Yellow solid, m.p. 195–197 °C. 1H NMR (250 MHz, CDCl3): δ = 9.63 (s, 1 H, CHAr), 8.32– 8.21 (m, 2 H, CHAr), 7.62 (ddd, 3J = 8.4, 3J = 6.9, 4J = 1.4 Hz, 1 H, CHAr), 7.50–7.37 (m, 7 H, CHAr), 7.31–7.26 (m, 1 H, CHAr), 7.22–7.17 (m, 1 H, CHAr), 2.58 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 146.8 (CAr), 144.6 (CHAr), 142.1 (CAr), 140.1 (CAr), 139.8 (CAr), 135.9 (CAr), 131.1 (2 CHAr), 130.3 (CHAr), 128.6 (2 CHAr), 127.8 (CHAr), 125.9 (CHAr), 125.4 (CHAr), 122.1 (CHAr), 121.9 (CAr), 121.8 (CHAr), 119.7 (CHAr), 117.8 (CAr), 115.5 (CAr), 110.9 (CHAr), 21.6 (CH3) ppm. IR (ATR):

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Full Paper ν˜ = 3051 (w), 3034 (w), 2962 (w), 2918 (w), 2858 (w), 1562 (m), 1510 (m), 1435 (m), 1360 (m), 1269 (m), 1221 (m), 1107 (m), 918 (m), 823 (m), 758 (m), 735 (s), 706 (m), 621 (m), 559 (m) cm–1. MS (EI, 70 eV): m/z (%) = 309 (24), 308 (100) [M]+, 307 (31), 305 (10), 293 (15), 292 (17), 147 (11), 91 (10), 89 (16), 65 (19), 39 (11). HRMS (EI): calcd. for C22H16N2 [M]+ 308.13080; found 308.13087. 11-[4-(tert-Butyl)phenyl]-11H-indolo[3,2-c]quinoline (6b): Yellow solid, m.p. 249–251 °C. 1H NMR (250 MHz, CDCl3): δ = 9.52 (s, 1 H, CHAr), 8.20–8.10 (m, 2 H, CHAr), 7.55 (dd, 3J = 8.5, 4J = 1.9 Hz, 2 H, CHAr), 7.49 (dd, 3J = 6.9, 4J = 1.5 Hz, 1 H, CHAr), 7.35–7.25 (m, 5 H, CHAr), 7.16 (dd, 3J = 8.4, 4J = 1.4 Hz, 1 H, CHAr), 7.12–7.07 (m, 1 H, CHAr), 1.37 (s, 9 H, CH3,tBu) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.9 (CAr), 146.7 (CAr), 144.5 (CHAr), 142.0 (CAr), 140.0 (CAr), 135.7 (CAr), 130.3 (CHAr), 128.5 (2 CHAr), 127.7 (CHAr), 127.2 (2 CHAr), 125.8 (CHAr), 125.3 (CHAr), 122.0 (CHAr), 121.8 (CAr), 121.6 (CHAr ), 119.6 (CH Ar ), 117.7 (CAr), 115.4 (CAr), 110.9 (CHAr), 35.0 (CtBu), 31.5 (3 CH3,tBu) ppm. IR (ATR): ν˜ = 3051 (w), 2960 (w), 2903 (w), 2868 (w), 1560 (m), 1510 (m), 1462 (m), 1435 (m), 1412 (m), 1358 (m), 1269 (m), 1225 (m), 1014 (m), 926 (m), 741 (s), 625 (m), 552 (m) cm–1. MS (EI, 70 eV): m/z (%) = 351 (35), 350 (100) [M]+, 336 (25), 335 (73), 319 (11), 317 (12), 305 (10), 293 (37), 292 (14), 291 (12), 153 (21), 152 (20), 115 (11), 57 (24), 41 (18), 39 (16). HRMS (EI): calcd. for C25H22N2 [M]+ 350.17775; found 350.17742. 11-(4-Methoxyphenyl)-11H-indolo[3,2-c]quinoline (6c): Yellow solid, m.p. 165–167 °C. 1H NMR (250 MHz, CDCl3): δ = 9.52 (s, 1 H, CHAr), 8.21–8.13 (m, 2 H, CHAr), 7.53 (ddd, 3J = 8.4, 3J = 5.6, 4J = 1.5 Hz, 1 H, CHAr), 7.36–7.30 (m, 5 H, CHAr), 7.20 (dd, 3J = 6.9, 4J = 1.3 Hz, 1 H, CHAr), 7.12–7.05 (m, 3 H, CHAr), 3.88 (s, 3 H, OCH3) ppm. 13 C NMR (63 MHz, CDCl3): δ = 160.3 (COCH3), 146.6 (CAr), 144.4 (CH Ar ), 142.2 (C Ar ), 140.2 (C Ar ), 130.9 (CAr), 130.2 (CHAr), 130.0 (2 CHAr), 127.8 (CHAr), 125.9 (CHAr), 125.4 (CHAr), 121.9 (CHAr), 121.8 (CAr), 121.7 (CHAr), 119.6 (CHAr), 117.7 (CAr), 115.5 (2 CHAr), 115.3 (CAr), 110.8 (CHAr), 55.7 (OCH3) ppm. IR (ATR): ν˜ = 3051 (w), 3007 (w), 2960 (w), 2935 (w), 2839 (w), 1562 (m), 1510 (m), 1433 (m), 1358 (m), 1246 (m), 1223 (m), 1024 (m), 764 (m), 739 (s), 621 (m), 602 (m), 563 (m) cm–1. MS (EI, 70 eV): m/z (%) = 325 (27), 324 (100) [M]+, 309 (12), 281 (14), 180 (41), 279 (25), 140 (18), 63 (10). HRMS (EI): calcd. for C22H16ON2 [M]+ 324.12571; found 324.12568. 11-(4-Fluorophenyl)-11H-indolo[3,2-c]quinoline (6d): Brown solid, m.p. 223–225 °C. 1H NMR (250 MHz, CDCl3): δ = 9.60 (s, 1 H, CHAr), 8.28 (d, 3J = 5.4 Hz, 1 H, CHAr), 8.25 (d, 3J = 5.2 Hz, 1 H, CHAr), 7.67–7.49 (m, 1 H, CHAr), 7.55–7.48 (m, 2 H, CHAr), 7.47–7.40 (m, 3 H, CHAr), 7.38 (s, 1 H, CHAr), 7.35–7.25 (m, 2 H, CHAr), 7.19–7.13 (m, 1 H, CHAr) ppm. 13C NMR (63 MHz, CDCl3): δ = 161.9 (d, 1JCF = 250.3 Hz, CArF), 145.6 (CAr), 143.3 (CHAr), 140.9 (CAr), 138.9 (CAr), 133.4 (d, 4JCF = 3.4 Hz, CAr), 129.7 (d, 3JCF = 8.8 Hz, 2 CHAr), 129.3 (CHAr), 126.7 (CHAr), 125.0 (CHAr), 124.5 (CHAr), 120.9 (CHAr), 120.8 (CAr), 120.6 (CHAr), 118.7 (CHAr), 116.4 (d, 2JCF = 22.8 Hz, 2 CHAr), 116.4 (CAr), 114.4 (CAr), 109.5 (CHAr) ppm. 19F NMR (235 MHz, CDCl3): δ = –110.5 (CArF) ppm. IR (ATR): ν˜ = 3061 (w), 3038 (w), 2953 (w), 2922 (w), 2852 (w), 1562 (w), 1504 (m), 1433 (m), 1360 (m), 1221 (m), 1151 (m), 1090 (m), 816 (m), 758 (m), 737 (s), 619 (m), 561 (m) cm–1. MS (EI, 70 eV): m/z (%) = 313 (23), 312 (100) [M]+, 311 (55), 310 (14), 156 (9), 95 (9), 75 (16). HRMS (EI): calcd. for C21H13N2F [M]+ 312.10573; found 312.10532. 11-(4-Chlorophenyl)-11H-indolo[3,2-c]quinoline (6e): Yellow solid, m.p. 235–237 °C. 1H NMR (250 MHz, CDCl3): δ = 9.59 (s, 1 H, CHAr), 8.31–8.21 (m, 2 H, CHAr), 7.69–7.60 (m, 3 H, CHAr), 7.51–7.41 (m, 4 H, CH A r ), 7.40–7.27 (m, 2 H, CH A r ), 7.20–7.14 (m, 1 H, CHAr) ppm. 13C NMR (63 MHz, CDCl3): δ = 146.6 (CAr), 144.4 (CHAr), 141.7 (CAr), 139.8 (CAr), 137.0 (CAr), 135.6 (CAr), 130.7 (2 CHAr), 130.4 (CHAr), 130.2 (2 CHAr), 128.0 (CHAr), 126.1 (CHAr), 125.6 (CHAr), 122.0 Eur. J. Org. Chem. 2017, 5554–5565

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(CHAr), 121.9 (CAr), 121.7 (CHAr), 119.8 (CHAr), 117.4 (CAr), 115.6 (CAr), 110.5 (CHAr) ppm. IR (ATR): ν˜ = 3055 (w), 3034 (w), 1614 (w), 1562 (m), 1493 (m), 1433 (m), 1360 (m), 1269 (m), 1223 (m), 1086 (m), 760 (m), 737 (s), 716 (m), 617 (m) cm–1. MS (EI, 70 eV): m/z (%) = 330 (25), 329 (32), 328 (100) [M]+, 327 (27), 292 (20), 291 (10), 147 (20), 146 (14), 75 (27). HRMS (EI): calcd. for C 2 1 H 13 N 2 Cl [M] + 328.07618; found 328.07519; calcd. for C21H13N237Cl [M]+ 330.07323; found 330.07272. 11-(3-Methoxybenzyl)-11H-indolo[3,2-c]quinoline (6f): Yellow solid, m.p. 132–134 °C. 1H NMR (250 MHz, CDCl3): δ = 9.47 (s, 1 H, CHAr), 8.17 (dd, 3J = 11.0, 3J = 8.1 Hz, 2 H, CHAr), 8.08 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.55 (dd, 3J = 7.4 Hz, 1 H, CHAr), 7.43–7.27 (m, 4 H, CHAr), 7.12 (dd, 3J = 8.4 Hz, 1 H, CHAr), 6.70 (dd, 3J = 8.3, 3J = 8.3 Hz, 1 H, CH Ar ), 6.66–6.59 (m, 2 H, CH Ar ), 5.78 (s, 2 H, CH 2 ), 3.57 (s, 3 H, OCH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 160.3 (C-OCH3), 146.7 (CAr), 144.3 (CHAr), 140.8 (CAr), 139.8 (CAr), 138.0 (CAr), 130.4 (CHAr), 130.3 (CHAr), 127.8 (CHAr), 126.1 (CHAr), 125.8 (CHAr), 121.9 (C Ar ), 121.8 (CHAr), 121.6 (CHAr), 119.8 (CHAr), 118.0 (CHAr), 117.7 (C Ar ), 115.4 (CAr), 112.7 (CHAr), 111.9 (CHAr), 109.7 (CHAr), 55.2 (OCH3), 49.2 (CH2) ppm. IR (ATR): ν˜ = 3061 (w), 3001 (w), 2958 (w), 2930 (w), 2833 (w), 1597 (m), 1491 (m), 1458 (m), 1427 (m), 1333 (m), 1286 (m), 1256 (m), 1196 (m), 1157 (m), 1040 (m), 912 (m), 854 (m), 775 (m), 741 (s), 689 (m), 596 (m), 561 (m) cm–1. MS (EI, 70 eV): m/z (%) = 339 (10), 338 (51) [M]+, 217 (23), 216 (10), 190 (13), 121 (100), 91 (39), 78 (23), 77 (24), 65 (10). HRMS (EI): calcd. for C23H18ON2 [M]+ 338.14136; found 338.14129. 11-(n-Hexyl)-11H-indolo[3,2-c]quinoline (6g): Yellow solid, m.p. 69–71 °C. 1H NMR (250 MHz, CDCl3): δ = 9.53 (s, 1 H, CHAr), 8.39 (dd, 3J = 8.5, 4J = 1.2 Hz, 1 H, CHAr), 8.34 (dd, 3J = 8.4, 4J = 1.3 Hz, 1 H, CHAr), 8.22 (dt, 3J = 7.7, 4J = 0.9 Hz, 1 H, CHAr), 7.73 (ddd, 3J = 8.4, 3J = 7.0, 4J = 1.5 Hz, 1 H, CHAr), 7.64 (ddd, 3J = 8.3, 3J = 7.0, 4J = 1.5 Hz, 1 H, CHAr), 7.57–7.54 (m, 2 H, CHAr), 7.40 (ddd, 3J = 8.0, 3J = 5.3, 4J = 2.8 Hz, 1 H, CHAr), 4.71 (t, 3J = 7.7 Hz, 2 H, CH2), 2.03 (p, 3 J = 7.6 Hz, 2 H, CH2), 1.61–1.46 (m, 2 H, CH2), 1.44–1.30 (m, 4 H, CH2), 0.90 (t, 3J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 146.3 (CAr), 144.0 (CHAr), 140.2 (CAr), 139.0 (CAr), 130.4 (CHAr), 127.7 (CHAr), 125.8 (CHAr), 125.7 (CHAr), 121.7 (CAr ), 121.6 (CH Ar ), 121.2 (CHAr), 119.8 (CHAr), 117.8 (CAr), 115.2 (CAr), 109.6 (CHAr), 45.8 (CH2), 31.5 (CH2), 29.7 (CH2), 26.7 (CH2), 22.5 (CH2), 14.0 (CH3) ppm. IR (ATR): ν˜ = 3053 (w), 2958 (w), 2937 (w), 2922 (w), 2852 (w), 1560 (m), 1514 (m), 1466 (m), 1441 (m), 1352 (m), 1333 (m), 1223 (m), 928 (m), 743 (s), 596 (m) cm–1. MS (EI, 70 eV): m/z (%) = 303 (12), 302 (47) [M]+, 232 (17), 231 (100), 218 (15), 190 (10), 43 (23), 41 (25), 29 (34). HRMS (EI): calcd. for C21H22N2 [M]+ 302.17775; found 302.17791. 11-[4-(tert-Butyl)phenyl]-8,9-dimethyl-11H-indolo[3,2-c]quinoline (6h): Yellow solid, m.p. 237–239 °C. 1H NMR (250 MHz, CDCl3): δ = 9.52 (s, 1 H, CHAr), 8.30 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.07 (s, 1 H, CHAr), 7.72 (d, 3J = 8.6 Hz, 2 H, CHAr), 7.64 (dd, 3J = 7.0 Hz, 1 H, CHAr), 7.47 (dd, 3J = 8.6 Hz, 2 H, CHAr), 7.39 (d, 3J = 8.1 Hz, 1 H, CHAr), 7.32–7.26 (m, 1 H, CHAr), 7.02 (s, 1 H, CHAr), 2.52 (s, 3 H, CH3), 2.43 (s, 3 H, CH3), 1.54 (s, 9 H, CH3,tBu) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.7 (CAr), 146.2 (CAr), 144.1 (CHAr), 141.1 (CAr), 139.8 (CAr), 135.9 (CAr), 135.4 (CAr), 130.6 (CAr), 130.0 (CHAr), 128.2 (2 CHAr), 127.5 (CHAr), 127.2 (2 CHAr), 125.2 (CHAr), 121.9 (CHAr), 119.9 (CAr), 119.8 (CHAr), 117.8 (CAr), 115.4 (CAr), 111.3 (CHAr), 35.0 (CtBu), 31.5 (3 CH3,tBu), 20.8 (CH3), 20.1 (CH3) ppm. IR (ATR): ν˜ = 3061 (w), 3034 (w), 2958 (w), 2858 (w), 1558 (m), 1510 (m), 1433 (m), 1352 (m), 1327 (m), 1263 (m), 1238 (m), 1182 (m), 1022 (m), 872 (m), 754 (s), 692 (m), 642 (m), 611 (m), 561 (m) cm–1. MS (EI, 70 eV): m/z (%) = 379 (34), 378 (100) [M]+, 364 (13), 363 (45), 348 (11), 347 (13), 335 (12), 333 (10), 244 (10), 243 (10), 229 (11), 160 (15), 159 (11), 115 (13), 91

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Full Paper (11), 57 (42), 41 (27), 39 (16). HRMS (EI): calcd. for C27H26N2 [M]+ 378.20905; found 378.20893. 11-[4-(tert-Butyl)phenyl]-8,9-dimethoxy-11H-indolo[3,2-c]quinoline (6i): Yellow solid, m.p. 210–212 °C. 1H NMR (250 MHz, CDCl3): δ = 9.53 (s, 1 H, CHAr), 8.24 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.71–7.64 (m, 3 H, CHAr), 7.57 (ddd, 3J = 8.4, 3J = 6.3, 4J = 2.0 Hz, 1 H, CHAr), 7.44 (d, 3J = 8.6 Hz, 2 H, CHAr), 7.30–7.19 (m, 2 H, CHAr), 6.65 (s, 1 H, CHAr), 4.07 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 1.49 (s, 9 H, CH3,tBu) ppm. 13 C NMR (75 MHz, CDCl3): δ = 152.9 (CAr), 149.7 (CAr), 146.4 (CAr), 145.6 (CAr), 143.6 (CHAr), 139.3 (CAr), 136.8 (CAr), 135.8 (CAr), 130.0 (CHAr), 128.2 (2 CHAr), 127.3 (2 CHAr), 127.2 (CHAr), 125.2 (CHAr), 121.5 (CHAr), 117.8 (CAr), 115.6 (CAr), 114.0 (CAr), 101.3 (CHAr), 94.2 (CHAr), 56.6 (OCH3), 56.4 (OCH3), 35.1 (CtBu), 31.5 (3 CH3,tBu) ppm. IR (ATR): ν˜ = 3059 (w), 3005 (w), 2960 (w), 2904 (w), 2868 (w), 2829 (w), 1713 (w), 1512 (m), 1479 (m), 1454 (m), 1427 (m), 1356 (m), 1335 (m), 1311 (m), 1263 (m), 1196 (m), 1138 (m), 1076 (m), 1020 (m), 906 (m), 843 (m), 756 (s), 662 (m), 581 (m) cm–1. MS (EI, 70 eV): m/z (%) = 411 (26), 410 (100) [M]+, 395 (14), 367 (13), 337 (18), 309 (14), 307 (10), 184 (11), 153 (12), 117 (10), 115 (12), 90 (10), 57 (22), 41 (34), 39 (10), 29 (17). HRMS (EI): calcd. for C 2 7 H 2 6 O 2 N 2 [M] + 410.19888; found 410.19947. 11-(4-Fluorophenyl)-8,9-dimethyl-11H-indolo[3,2-c]quinoline (6j): Yellow solid, m.p. 204–206 °C. 1H NMR (250 MHz, CDCl3): δ = 9.56 (s, 1 H, CHAr), 8.27 (d, 3J = 8.4 Hz, 1 H, CHAr), 8.02 (s, 1 H, CHAr), 7.61 (ddd, 3J = 8.4, 3J = 6.5, 4J = 1.8 Hz, 1 H, CHAr), 7.51 (ddd, 3J = 9.7, 3J = 4.9, 4J = 2.5 Hz, 2 H, CHAr), 7.39 (dd, 3J = 8.5 Hz, 2 H, CHAr), 7.33–7.27 (m, 2 H, CHAr), 6.93 (s, 1 H, CHAr), 2.48 (s, 3 H, CH3), 2.40 (s, 3 H, CH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 162.9 (d, 1JCF = 250.1 Hz, CArF), 146.2 (CAr), 144.1 (CHAr), 141.0 (CAr), 139.7 (CAr), 135.7 (CAr), 134.7 (d, 4JCF = 3.3 Hz, CAr), 130.9 (CAr), 130.7 (d, 3JCF = 8.8 Hz, 2 CHAr), 130.2 (CHAr), 127.6 (CHAr), 125.4 (CHAr), 121.5 (CHAr), 120.0 (CHAr), 119.9 (CAr), 117.6 (CAr), 117.4 (d, 2JCF = 22.8 Hz, 2 CHAr), 115.5 (C Ar ), 111.0 (CH Ar ), 20.8 (CH 3 ), 20.1 (CH 3 ) ppm. 19 F NMR (235 MHz, CDCl3): δ = –110.8 (CArF) ppm. IR (ATR): ν˜ = 3061 (w), 2964 (w), 2916 (w), 2854 (w), 1558 (w), 1506 (m), 1435 (m), 1354 (m), 1223 (m), 1146 (m), 1086 (m), 1013 (m), 924 (m), 870 (m), 851 (m), 833 (m), 812 (m), 760 (s), 717 (m), 692 (m), 648 (m), 609 (m), 592 (m), 552 (m) cm–1. MS (EI, 70 eV): m/z (%) = 341 (19), 340 (100) [M]+, 339 (19), 325 (18), 324 (11), 162 (20), 75 (17). HRMS (EI): calcd. for C23H17N2F [M]+ 340.13703; found 340.13706. 11-(4-Fluorophenyl)-8,9-dimethoxy-11H-indolo[3,2-c]quinoline (6k): Yellow solid, m.p. 175–177 °C. 1H NMR (250 MHz, CDCl3): δ = 9.42 (s, 1 H, CHAr), 8.16 (d, 3J = 8.4 Hz, 1 H, CHAr), 7.57 (s, 1 H, CHAr), 7.51 (dd, 3J = 8.4, 3J = 6.5 Hz, 1 H, CHAr), 7.45 (dd, 3J = 8.9, 4J = 4.8 Hz, 2 H, CHAr), 7.31 (pt, 3J = 8.5 Hz, 2 H, CHAr), 7.20–7.16 (m, 2 H, CH A r ), 6.50 (s, 1 H, CH Ar ), 3.98 (s, 3 H, OCH 3 ), 3.78 (s, 3 H, OCH3) ppm. 13C NMR (63 MHz, CDCl3): δ = 163.0 (d, 1JCF = 250.4 Hz, CArF), 149.8 (CAr), 146.5 (CAr), 145.7 (CAr), 143.7 (CHAr), 139.1 (CAr), 136.7 (CAr), 134.6 (d, 4JCF = 3.3 Hz, CAr), 130.8 (d, 3JCF = 8.8 Hz, 2 CHAr), 130.2 (CHAr), 127.3 (CHAr), 125.4 (CHAr), 121.1 (CHAr), 117.6 (d, 2 JCF = 22.8 Hz, 2 CHAr), 117.5 (CAr), 115.7 (CAr), 114.0 (CAr), 101.4 (CH A r ), 93.7 (CH A r ), 56.6 (OCH 3 ), 56.3 (OCH 3 ) ppm. 1 9 F NMR (235 MHz, CDCl3): δ = –110.4 (CArF) ppm. IR (ATR): ν˜ = 3063 (w), 2980 (w), 2958 (w), 2930 (w), 2825 (w), 1626 (w), 1556 (w), 1506 (m), 1464 (m), 1412 (m), 1337 (m), 1313 (m), 1229 (m), 1198 (m), 1157 (m), 1136 (m), 1092 (m), 1011 (m), 864 (m), 814 (m), 750 (s), 650 (m), 538 (m) cm–1. MS (EI, 70 eV): m/z (%) = 373 (22), 372 (100) [M]+, 358 (26), 357 (25), 330 (13), 329 (32), 314 (13), 299 (12), 297 (14), 286 (17), 285 (16), 284 (25), 231 (14), 186 (36), 165 (12), 157 (13), 137 (10), 128 (10), 107 (10). HRMS (EI): calcd. for C23H17O2N2F [M]+ 372.12686; found 372.12669. Eur. J. Org. Chem. 2017, 5554–5565

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Acknowledgments Financial support by the State of Iraq (scholarship for G. A. S.), by the Deutscher Akademischer Austauschdienst (DAAD) (scholarship for N. N. P.) and the State of Mecklenburg-Vorpommern is gratefully acknowledged. Keywords: Cross-coupling · Fused-ring systems · Nitrogen heterocycles · Regioselectivity · Synthetic methods

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Received: June 27, 2017

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