Discovery and Preliminary Structure-Activity
Investigation of
3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro
Activity towards Methicillin-Resistant Staphylococcus
aureus

Steven A Li, Rebecca J Zheng, Kenneth Sue, Marie-Lise Bourguet-Kondracki, Azza Troudi, Jean Michel Brunel, Brent R Copp, Melissa M Cadelis

► To cite this version:

Steven A Li, Rebecca J Zheng, Kenneth Sue, Marie-Lise Bourguet-Kondracki, Azza Troudi, et al. Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus. Antibiotics, 2022, 11 (10), pp.1450. 10.3390/antibiotics11101450. [https://doi.org/10.3390/antibiotics11101450](https://doi.org/10.3390/antibiotics11101450)

HAL Id: hal-03833103

https://hal.science/hal-03833103

Submitted on 28 Oct 2022

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_2.png" /></figure>

Article

# Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant *Staphylococcus aureus*

Steven A. Li <fnref n="1" />, Rebecca J. Zheng<fnref n="1" />, Kenneth Sue<fnref n="1" />, Marie-Lise Bourguet-Kondracki<fnref n="2" />, Azza Troudi<fnref n="3" />, Jean Michel Brunel <fnref n="3" /> and Brent R. Copp <fnref n="1" />,<fnref n="2" /> and Melissa M. Cadelis <fnref n="1" />,<fnref n="4" />,*

<figure><img src="image_3.png" /></figure>

check for
updates

**Citation:** Li, S.A.; Zheng, R.J.; Sue, K.; Bourguet-Kondracki, M.-L.; Troudi, A.; Brunel, J.M.; Copp, B.R.; Cadelis, M.M. Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant *Staphylococcus aureus*. *Antibiotics* **2022**, *11*, 1450. https://doi.org/10.3390/antibiotics11101450

Academic Editor: Marc Maresca

Received: 10 October 2022

Accepted: 20 October 2022

Published: 21 October 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

<figure><img src="image_4.png" /></figure>

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

**Abstract:** Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a desperate need for antibiotics with new mechanisms of action. As part of our search for new antimicrobials we have screened an in-house library of compounds and identified two 3-substituted-1H-imidazol-5-yl-1H-indoles as weak growth inhibitors (MIC 16 µg/mL) against methicillin-resistant *Staphylococcus aureus* (MRSA). An extensive library of analogues was prepared using the Van Leusen three-component reaction, biological evaluation of which led to the identification of two analogues (26 and 32) with favorable anti-MRSA activity (MIC ≤ 0.25 µg/mL) which also lacked cytotoxic or hemolytic properties. The screening campaign also identified two derivatives, a phenethyl-indole-imidazole 57 and a 5-phenyl-1H-imidazole 111 that were non-toxic selective antifungals towards *Cryptococcus neoformans*. These results have identified 3-substituted-1H-imidazol-5-yl-1H-indoles and 5-phenyl-1H-imidazoles as new structural scaffolds for further investigation as anti-MRSA and anti-C. *neoformans* agents, respectively.

**Keywords:** MRSA; antimicrobial; imidazole; antifungal

## 1. Introduction

New Zealand has a growing problem with *Staphylococcus aureus* infection, experiencing higher levels of incidence than other developed countries, with incidences of *S. aureus*-related hospitalizations highest in the under-five and over 75 year age groups [1–7]. Over the ten-year period of 2001–2011, the incidence of methicillin-susceptible *S. aureus* infections increased to 361 per 100,000, with MRSA infection (covering non-multidrug resistant MRSA and multidrug resistant MRSA) accounting for an additional 12% of cases. In the case of children under the age of 15, annual average hospitalization rates for *S. aureus* skin and soft tissue infection (SSTI) increased to 522 per 100,000 population (2011), with sub-population analysis identifying Māori and Pacific children with rates of 1488 and 1215 per 100,000 population, respectively [1–7].

Front-line treatments for SSTI in New Zealand are the topical antimicrobials fusidic acid and mupirocin. During the 1993-2012 timeframe, community prescribing rates for fusidic acid increased dramatically (likely due to the drug becoming a Government-subsidized treatment option) and this was matched with a corresponding increase in fusidic acid-resistant MRSA [8,9]. Unfortunately, the widespread, and largely unregulated,

<footnote n="1">¹ School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand</footnote>

<footnote n="2">² Laboratoire Molécules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, 57 rue Cuvier (C.P. 54), 75005 Paris, France</footnote>

<footnote n="3">³ UMR MD1 "Membranes et Cibles Thérapeutiques", U1261 INSERM, Faculté de Pharmacie, Aix-Marseille Universite, 27 bd Jean Moulin, 13385 Marseille, France</footnote>

<footnote n="4">⁴ School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand</footnote>

<footnote>* Correspondence: m.cadelis@auckland.ac.nz</footnote>
use of this valuable topical antimicrobial resource will ultimately lead to the need for more
treatment options.

We have recently screened an in-house library of natural products and synthetic com-
pounds against a panel of bacterial and fungal pathogens [10,11] which led to the discovery
of a compound class (Figure 1) that exhibited activity exclusively against methicillin-
resistant *Staphylococcus aureus* (MRSA). Of the compounds screened, 3-substituted-1H-
imidazol-5-yl-1H-indole (“indole-imidazole”) compounds 1 and 2 were found to weakly
inhibit the growth of MRSA with MIC of 16 µg/mL (Table 1) while a closely related 5-fluoro
analogue 3 (Supplementary Figures S1–S3) was devoid of activity.

<figure><img src="image_5.png" /></figure>

$$
\text{1 R}_1 = \text{R}_2 = \text{R}_3 = \text{H}
$$

$$
\text{2 R}_1 = \text{H}, \text{R}_2 = \text{Cl}, \text{R}_3 = \text{OMe}
$$

$$
\text{3 R}_1 = \text{F}, \text{R}_2 = \text{R}_3 = \text{H}
$$

<caption>**Figure 1.** Structures of indole-imidazole compounds 1–3.</caption>

Similarly functionalized 1H-imidazol-5-yl-1H-indoles have been recently reported as active towards crop-related fungi [12] and as 5-HT<sub>7</sub> serotonin receptor agonists [13]. Variants with increased substitution such as the marine natural products topsentins [14,15] and nortopsentins [16,17] have been shown to exhibit cytotoxic, antiviral and antifungal activities while analogues of the natural product meridianin exhibit antibiotic adjuvant properties [18]. Additionally, 1-benzenesulfonyl-1H-indoles have been reported as 5-HT<sub>6</sub> receptor agonists [19]. With this relatively limited literature on 3-substituted 1H-imidazol-5-yl-1H-indoles, we undertook a study to further explore the antimicrobial properties of this class of molecule by preparing a more diverse array of analogues that explored the influence of the imidazole N-substituent and indole halogen substitution on biological activity. Herein we report on the synthesis and biological evaluation of a diverse set of analogues of hit compounds 1 and 2.

**2. Results and Discussion**

A set of 39 new analogues were prepared (4–42) (Figure 2 and Supplementary Materials
Figures S4–S42) utilizing the Van Leusen three-component reaction [20]. This two-step,
one-pot reaction starts with in situ generation of an imine by condensation of an indole-3-
carbaldehyde with an amine, followed by reaction with *p*-toluenesulfonylmethyl isocyanide
(TosMIC) and K<sub>2</sub>CO<sub>3</sub> at 60 °C for 24 h (Schemes 1 and 2).
<figure><img src="image_6.png" /></figure>

4 R₁ = R₂ = H, R₃ = a

5 R₁ = F, R₂ = H, R₃ = a

6 R₁ = H, R₂ = F, R₃ = a

7 R₁ = Cl, R₂ = H, R₃ = a

8 R₁ = H, R₂ = Cl, R₃ = a

9 R₁ = Br, R₂ = H, R₃ = a

10 R₁ = H, R₂ = Br, R₃ = a

11 R₁ = R₂ = H, R₃ = b

12 R₁ = F, R₂ = H, R₃ = b

13 R₁ = H, R₂ = F, R₃ = b

14 R₁ = Cl, R₂ = H, R₃ = b

15 R₁ = H, R₂ = Cl, R₃ = b

16 R₁ = Br, R₂ = H, R₃ = b

17 R₁ = H, R₂ = Br, R₃ = b

18 R₁ = H, R₂ = F, R₃ = c

19 R₁ = Cl, R₂ = H, R₃ = c

20 R₁ = H, R₂ = Cl, R₃ = c

21 R₁ = Br, R₂ = H, R₃ = c

22 R₁ = H, R₂ = Br, R₃ = c

23 R₁ = R₂ = H, R₃ = d

24 R₁ = F, R₂ = H, R₃ = d

25 R₁ = H, R₂ = F, R₃ = d

26 R₁ = Cl, R₂ = H, R₃ = d

27 R₁ = Br, R₂ = H, R₃ = d

28 R₁ = H, R₂ = Br, R₃ = d

29 R₁ = R₂ = H, R₃ = e

30 R₁ = F, R₂ = H, R₃ = e

31 R₁ = H, R₂ = F, R₃ = e

32 R₁ = Cl, R₂ = H, R₃ = e

33 R₁ = H, R₂ = Cl, R₃ = e

34 R₁ = Br, R₂ = H, R₃ = e

35 R₁ = H, R₂ = Br, R₃ = e

36 R₁ = R₂ = H, R₃ = f

37 R₁ = F, R₂ = H, R₃ = f

38 R₁ = H, R₂ = F, R₃ = f

39 R₁ = Cl, R₂ = H, R₃ = f

40 R₁ = H, R₂ = Cl, R₃ = f

41 R₁ = Br, R₂ = H, R₃ = f

42 R₁ = H, R₂ = Br, R₃ = f

<figure><img src="image_7.png" /><figcaption>**Scheme 1.** Synthetic route to 3-substituted-1H-imidazol-5-yl-1H-indoles 4–42. Reagents and conditions: (i) DMF, 3 h, then (ii) TOSMIC, K2CO3, 60 °C, 24 h.</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**Scheme 2.** Proposed reaction mechanism of Van Leusen three-component reaction.</figcaption></figure>
The set of analogues included the indole fragment bearing 5- and 6- halogen substituents of bromine, chlorine, and fluorine, as well as an unsubstituted indole. The differently substituted indoles offer an opportunity to probe the effect of the electronics of the indole ring against antimicrobial activity. Six amines were used to introduce variation at the R₃ position (Figure 2). These included oxygenated amines such as *p*-methoxybenzylamine, *p*-methoxyphenethylamine, 2,5-dimethoxyphenethylamine and homopiperonylamine probe for hydrogen bond interactions. The phenethylamines explore an increased alkyl chain length between the aromatic group of the amine and the imidazole linker while *p*-iodobenzylamine can be used to directly compare with *p*-methoxybenzylamine the difference in bioactivity in the presence of a bulky halogen.

The antimicrobial activities of compounds **4–42** were determined against a panel of bacterial (Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii) and two fungal (Candida albicans and Cryptococcus neoformans) pathogens. The results are summarized in Table 1. Antimicrobial selectivity was observed towards the Gram-positive bacteria S. aureus and S. aureus MRSA, with MIC values ranging from ≤0.25 µg/mL to >200 µg/mL. None of the compounds exhibited activity against the Gram-negative bacteria P. aeruginosa, E. coli, A. baumannii or K. pneumoniae or the fungus C. albicans at a single dose of 32 µg/mL. Of the compound set, only **9** exhibited (weak, MIC 16 µg/mL) activity towards the fungus C. neoformans.

The more active anti-MRSA compounds were found to contain halogen substitution on the indole, with the 5- position analogues typically being more active than their 6-substituted counterparts, and the presence of an *N*-phenethyl substituent on the imidazole ring, e.g., **26** (MIC ≤ 0.25 µg/mL), **27** (8 µg/mL) and **32** (4 µg/mL). The set of compounds were also evaluated for cytotoxicity against a human embryonic kidney cell line (HEK293) and for hemolytic activity towards human red blood cells (Table 1). Of the compounds tested, none exhibited hemolytic activity at a single dose of 32 µg/mL but quite a few were identified as exhibiting some degree of cytotoxicity. Of note however was the lack of cytotoxicity observed for the two more active anti-MRSA compounds **26** and **32**.

<table><caption>**Table 1.** Antimicrobial (MIC, µg/mL), cytotoxic (µg/mL) and hemolytic (µg/mL) activities of selected compounds.</caption><thead><tr><th rowspan="2">Compound</th><th colspan="3">MIC (µg/mL)</th><th rowspan="2">HEK293 CC<sub>50</sub> (µg/mL)<sup>d</sup></th><th rowspan="2">HC<sub>10</sub> (µg/mL)<sup>e</sup></th></tr><tr><th>S. a<sup>a</sup></th><th>MRSA<sup>b</sup></th><th>C. n<sup>c</sup></th></tr></thead><tbody><tr><td>1</td><td>>200</td><td>16</td><td>>32</td><td>19.3</td><td>>32</td></tr><tr><td>2</td><td>>200</td><td>16</td><td>32</td><td>22.5</td><td>>32</td></tr><tr><td>6</td><td>6.25</td><td>>32</td><td>32</td><td>15.6</td><td>>32</td></tr><tr><td>9</td><td>>200</td><td>16</td><td>16</td><td>5.1</td><td>>32</td></tr><tr><td>11</td><td>>200</td><td>32</td><td>>32</td><td>25.6</td><td>>32</td></tr><tr><td>17</td><td>25</td><td>32</td><td>32</td><td>11.1</td><td>>32</td></tr><tr><td>18</td><td>25</td><td>32</td><td>>32</td><td>16.3<sup>c</sup></td><td>>32<sup>c</sup></td></tr><tr><td>19</td><td>12.5</td><td>16</td><td>>32</td><td>17.3</td><td>>32</td></tr><tr><td>21</td><td>6.25</td><td>16</td><td>32</td><td>10.6</td><td>>32</td></tr><tr><td>22</td><td>12.5</td><td>16</td><td>32</td><td>12.7</td><td>>32</td></tr><tr><td>23</td><td>100</td><td>32</td><td>>32</td><td>24.5</td><td>>32</td></tr><tr><td>25</td><td>100</td><td>16</td><td>>32</td><td>27.0</td><td>>32</td></tr><tr><td>26</td><td>>200</td><td>≤0.25</td><td>>32</td><td>>32</td><td>>32</td></tr><tr><td>27</td><td>12.5</td><td>8</td><td>>32</td><td>16.0</td><td>>32</td></tr><tr><td>28</td><td>12.5</td><td>32</td><td>32</td><td>15.6</td><td>>32</td></tr></tbody></table>
<table><caption>**Table 1.** *Cont.*</caption><thead><tr><th rowspan="2">Compound</th><th colspan="3">MIC (µg/mL)</th><th rowspan="2">HEK293 CC<sub>50</sub> (µg/mL) <sup>d</sup></th><th rowspan="2">HC<sub>10</sub> (µg/mL) <sup>e</sup></th></tr><tr><th>S. a <sup>a</sup></th><th>MRSA <sup>b</sup></th><th>C. n <sup>c</sup></th></tr></thead><tbody><tr><td><b>29</b></td><td>&gt;200</td><td>32</td><td>&gt;32</td><td>11.5</td><td>&gt;32</td></tr><tr><td><b>32</b></td><td>100</td><td>4</td><td>&gt;32</td><td>&gt;32</td><td>&gt;32</td></tr><tr><td><b>34</b></td><td>25</td><td>16</td><td>&gt;32</td><td>6.2</td><td>&gt;32</td></tr><tr><td><b>42</b></td><td>12.5</td><td>16</td><td>32</td><td>16.1</td><td>&gt;32</td></tr><tr><td><b>57</b></td><td>&gt;200</td><td>&gt;32</td><td>≤0.25</td><td>&gt;32</td><td>&gt;32</td></tr><tr><td><b>111</b></td><td>50</td><td>16</td><td>≤0.25</td><td>&gt;32</td><td>&gt;32</td></tr></tbody></table>

A further, more-expansive set of analogues was prepared (Figures 3 and 4) that explored the influence of 4- and 7- halogen or 5/6-methoxy substituted indoles bearing benzyl, 2-phenethyl or 3-phenylpropyl (compounds **43–72**) or indolemethylene or indole-ethyl (**73–88**) and *n*-pentyl (**89–96**) side chains. In addition, analogues **97–102** were prepared that retained a common 5-chloroindole fragment, identified as being associated with activity in set 1, but with a wider variation in R<sub>3</sub> fragment (Figure 3), while analogues **103–116** explored replacement of the indole fragment with a phenyl or *p*-methoxyphenyl group (Figure 4). A total of 74 compounds (**43–116**) were prepared in this library (Figures S43–S116).

Analogues **43–116** were evaluated for biological activity in the same manner as the earlier compound sets. Surprisingly, from the 74 analogues tested, none were considered active towards MRSA (MIC 32 µg/mL or greater). This result suggests that the structural requirements for activity of the indole-imidazole scaffold towards MRSA is very precise/narrow, with halogenation on 5- position of the indole and a methoxy phenethyl sidechain, making it difficult to identify ways forward in further optimizing the structure. Of note from this set of compounds was the observation of potent antifungal activity against *C. neoformans* (MIC values of ≤0.25 µg/mL) for both 6-methoxy-phenethyl-indole-imidazole **57** and 5-phenyl-1*H*-imidazole **111** (Table 1): the lack of cytotoxicity and hemolytic activity for these two compounds identifies them as selective hits and worthy of further investigation.

Currently, the mechanism of antimicrobial action of this compound class is unknown. Thus, we sought to investigate the mechanism of action of this compound class against *S. aureus* using compound **6**, which exhibited strong activity against *S. aureus*. In a preliminary investigation, compound **6** exhibited only very weak membrane depolarization of *S. aureus*, suggesting the cellular target in bacteria is not membrane-related. Further investigation to improve the antimicrobial and antifungal activity and identify the mechanism of action of these compounds is underway.

<footnote><sup>a</sup> *Staphylococcus aureus* ATCC25923 with streptomycin (MIC 12.5 µg/mL) and chloramphenicol (MIC 0.5–1 µg/mL) used as positive controls and values presented as the mean (n = 3); <sup>b</sup> *Staphylococcus aureus* ATCC43300 (MRSA) with vancomycin (MIC 1 µg/mL) used as a positive control and values presented as the mean (n = 2); <sup>c</sup> *Cryptococcus neoformans* ATCC208821 with fluconazole (MIC 8 µg/mL) as a positive control and values presented as the mean (n = 2); <sup>d</sup> Concentration of compound at 50% cytotoxicity on HEK293 human embryonic kidney cells and values presented as the mean (n = 2). Tamoxifen was the positive control (IC<sub>50</sub> 9 µg/mL); <sup>e</sup> Concentration of compound at 10% hemolytic activity on human red blood cells and values presented as the mean (n = 2). Melittin was the positive control (HC<sub>10</sub> 2.7 µg/mL).</footnote>
<figure><img src="image_9.png" /></figure>

43 R₁ = F, R₂ = R₃ = R₄ = R₅ = H, n = 1

44 R₄ = F, R₁ = R₂ = R₃ = R₅ = H, n = 1

45 R₁ = Cl, R₂ = R₃ = R₄ = R₅ = H, n = 1

46 R₂ = Cl, R₁ = R₃ = R₄ = R₅ = H, n = 1

47 R₄ = Cl, R₁ = R₂ = R₃ = R₄ = R₅ = H, n = 1

48 R₁ = Br, R₂ = R₃ = R₄ = R₅ = H, n = 1

49 R₂ = OMe, R₁ = R₃ = R₄ = R₅ = H, n = 1

50 R₃ = OMe, R₁ = R₂ = R₄ = R₅ = H, n = 1

51 R₁ = F, R₂ = R₃ = R₄ = R₅ = H, n = 2

52 R₄ = F, R₁ = R₂ = R₃ = R₄ = H, n = 2

53 R₁ = Cl, R₂ = R₃ = R₄ = R₅ = H, n = 2

54 R₄ = Cl, R₁ = R₂ = R₃ = R₄ = H, n = 2

55 R₁ = Br, R₂ = R₃ = R₄ = R₅ = H, n = 2

56 R₂ = OMe, R₁ = R₃ = R₄ = R₅ = H, n = 2

57 R₃ = OMe, R₁ = R₂ = R₄ = R₅ = H, n = 2

58 R₂ = Cl, R₁ = R₃ = R₄ = R₅ = H, n = 3

59 R₁ = F, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 1

60 R₄ = F, R₁ = R₂ = R₃ = H, R₅ = OMe, n = 1

61 R₁ = Cl, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 1

62 R₄ = Cl, R₁ = R₂ = R₃ = H, R₅ = OMe, n = 1

63 R₁ = Br, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 1

64 R₂ = R₅ = OMe, R₁ = R₃ = R₄ = H, n = 1

65 R₃ = R₅ = OMe, R₁ = R₂ = R₄ = H, n = 1

66 R₁ = F, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 2

67 R₄ = F, R₁ = R₂ = R₃ = H, R₅ = OMe, n = 2

68 R₁ = Cl, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 2

69 R₄ = Cl, R₁ = R₂ = R₃ = H, R₅ = OMe, n = 2

70 R₁ = Br, R₂ = R₃ = R₄ = H, R₅ = OMe, n = 2

71 R₂ = R₅ = OMe, R₁ = R₃ = R₄ = H, n = 2

72 R₃ = R₅ = OMe, R₁ = R₂ = R₄ = H, n = 2

<figure><img src="image_10.png" /></figure>

73 R₁ = F, R₂ = R₃ = R₄ = H, n = 1

74 R₄ = F, R₁ = R₂ = R₃ = H, n = 1

75 R₁ = Cl, R₂ = R₃ = R₄ = H, n = 1

76 R₂ = Cl, R₁ = R₃ = R₄ = H, n = 1

77 R₄ = Cl, R₁ = R₂ = R₃ = H, n = 1

78 R₁ = Br, R₂ = R₃ = R₄ = H, n = 1

79 R₂ = OMe, R₁ = R₃ = R₄ = H, n = 1

80 R₃ = OMe, R₁ = R₂ = R₄ = H, n = 1

81 R₁ = F, R₂ = R₃ = R₄ = H, n = 2

82 R₄ = F, R₁ = R₂ = R₃ = H, n = 2

83 R₁ = Cl, R₂ = R₃ = R₄ = H, n = 2

84 R₂ = Cl, R₁ = R₃ = R₄ = H, n = 2

85 R₄ = Cl, R₁ = R₂ = R₃ = H, n = 2

86 R₁ = Br, R₂ = R₃ = R₄ = H, n = 2

87 R₂ = OMe, R₁ = R₃ = R₄ = H, n = 2

88 R₃ = OMe, R₁ = R₂ = R₄ = H, n = 2

<figure><img src="image_11.png" /></figure>

89 R₁ = F, R₂ = R₃ = R₄ = H

90 R₄ = F, R₁ = R₂ = R₃ = H

91 R₁ = Cl, R₂ = R₃ = R₄ = H

92 R₂ = Cl, R₁ = R₃ = R₄ = H

93 R₄ = Cl, R₁ = R₂ = R₃ = H

94 R₁ = Br, R₂ = R₃ = R₄ = H

95 R₂ = OMe, R₁ = R₃ = R₄ = H

96 R₃ = OMe, R₁ = R₂ = R₄ = H

<figure><img src="image_12.png" /></figure>

97

<figure><img src="image_13.png" /></figure>

98

<figure><img src="image_14.png" /></figure>

99

<figure><img src="image_15.png" /></figure>

100 R = OH

101 R = NHBoc

102 R = NH₂

<caption>**Figure 3.** Structures of substituted indole-imidazoles **43–102**.</caption>
<figure><img src="image_16.png" /><figcaption>**Figure 4.** Structures of substituted 5-phenyl-1H-imidazoles **103–116**.</figcaption></figure>

**3. Materials and Methods**

**3.1. General Experimental Procedures**

High-resolution mass spectra were recorded using a MicrOTOF-QII mass spectrometer (Bruker Daltonics, Bremen, Germany). Melting points were determined on a Reichert-Hofler block and are uncorrected. Infra-red spectra were recorded on a Perkin Elmer Spectrum 100 Fourier Transform infrared spectrometer equipped with a universal ATR accessory. NMR spectra were recorded using a Bruker Avance 400 MHz or Avance III-HD 500 spectrometer operating at 400 or 500 MHz for ¹H nuclei and 100 or 125 MHz for ¹³C nuclei. Proto-deutero solvents signals were use as internal references (DMSO-d₆: δH 2.50, δC 39.52; CDCl₃: δH 7.26, δC 77.16). For ¹H NMR, the data are quoted as position (δ), relative integral, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, dd = doublet of doublets, ddd = doublet of doublet of doublets, tt = triplet of triplets, br = broad), coupling constant (J, Hz), and assignment to the atom. The ¹³C NMR data are quoted as position (δ), and assignment to the atom. Standard Bruker pulse sequences were utilized. Pressurized (flash) column chromatography was carried out with Kieselgel 60 0.063–0.200 mesh (Merck, Darmstadt, Germany). Analytical thin layer chromatography (TLC) was carried out on 0.2 mm thick plates of Kieselgel F₂₅₄ or DC-Kieselgel 60 RP-18 F₂₅₄S (Merck). All samples were determined to >95% purity.

**3.2. Synthesis**

**3.2.1. General Procedure**

A solution of aldehyde (1 eq.) and amine (1 eq.) in DMF (1 mL) was stirred for 3 h under N₂ atmosphere. To the stirred solution was added solid K₂CO₃ (1 eq.) and *p*-toluenesulfonylmethyl isocyanide (1 eq.) before heating to 60 °C for 18 h. The reaction mixture was cooled to room temperature and quenched with H₂O (30 mL). The aqueous layer was extracted with EtOAc (30 mL), and the organic layer was washed with H₂O (3 × 30 mL) then brine (3 × 30 mL), dried over anhydrous MgSO₄ and concentrated under reduced pressure.

**3.2.2. 3-(1-Phenethyl-1H-imidazol-5-yl)-1H-indole (1)**

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.135 g, 47%). R_f = 0.60 (CH₂Cl₂/MeOH, 9:1); m.p 69–70 °C; IR (ATR)
$v_{\text{max}}$ 3350, 2355, 1641, 1511, 1298, 907, 841, 742 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.47 (1H, s, NH-8), 7.63 (1H, s, H-2), 7.52–7.47 (3H, m, H-7, H-9, H-12), 7.24–7.17 (2H, m, 2H-5'), 7.17–7.15 (2H, m, H-10, H-6'), 7.07 (1H, dd, *J* = 7.3 Hz, 7.3 Hz, H-11), 7.01 (1H, s, H-4), 7.00 (2H, d, *J* = 7.3 Hz, 2H-4'), 4.23 (2H, t, *J* = 7.4 Hz, H₂-1'), 2.86 (2H, t, *J* = 7.4 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 138.3 (C-8a), 138.0 (C-3'), 136.5 (C-2), 128.9 (2C-4'), 128.7 (2C-5'), 127.4 (C-6'), 127.0 (C-12a), 126.8 (C-4), 126.4 (C-5), 124.8 (C-7), 122.1 (C-10), 120.0 (C-11), 119.1 (C-12), 112.2 (C-9), 104.0 (C-6), 46.4 (C-1'), 36.6 (C-2'); (+)-HRESIMS *m/z* 288.1497 [M+H]⁺ (calcd for C₁₉H₁₈N₃, 288.1495)

### 3.2.3. 6-Chloro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (2)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a yellow solid (0.214 g, 61%). R_f = 0.57 (CH₂Cl₂/MeOH, 9:1); m.p 165–166 °C; IR (ATR) $v_{\text{max}}$ 2777, 1611, 1511, 1449, 1245, 1112, 909, 827, 810 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.55 (1H, br s, NH-8), 7.60 (1H, d, *J* = 1.0 Hz, H-2), 7.51 (1H, d, *J* = 2.7 Hz, H-7), 7.49 (1H, d, *J* = 2.0 Hz, H-9), 7.46 (1H, d, *J* = 8.6 Hz, H-12), 7.06 (1H, dd, *J* = 8.6, 2.0 Hz, H-11), 6.98 (1H, d, *J* = 1.0 Hz, H-4), 6.89 (2H, d, *J* = 8.8 Hz, 2H-4'), 6.76 (2H, d, *J* = 8.8 Hz, 2H-5'), 4.16 (2H, t, *J* = 7.3 Hz, H₂-1'), 3.68 (3H, s, OMe), 2.77 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.8 (C-6'), 137.8 (C-2), 136.4 (C-8a), 129.8 (C-3'), 129.5 (2C-4'), 127.5 (C-4), 126.4 (C-10), 125.3 (C-12a), 125.2 (C-7), 125.1 (C-5), 120.2 (C-12), 119.9 (C-11), 113.7 (2C-5'), 111.4 (C-9), 104.2 (C-6), 54.9 (OMe), 46.1 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 374.1033 [M+Na]⁺ (calcd for C₂₀H₁₈³CIN₃NaO, 374.1031), *m/z* 376.0999 [M+Na]⁺ (calcd for C₂₀H₁₈³CIN₃NaO, 374.1008).

### 3.2.4. 5-Fluoro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (3)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.210 g, 69%). R_f = 0.63 (CH₂Cl₂/MeOH, 9:1); m.p 127–130 °C; IR (ATR) $v_{\text{max}}$ 3053, 1581, 1473, 1216, 1106, 932, 848, 786 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.54 (1H, br s, NH-8), 7.62 (1H, d, *J* = 1.0 Hz, H-2), 7.56 (1H, d, *J* = 2.7 Hz, H-7), 7.46 (1H, dd, *J* = 8.8, 4.5 Hz, H-9), 7.24–7.18 (2H, m, 2H-5'), 7.18–7.15 (2H, m, H-12, H-6'), 7.04–6.98 (4H, m, H-4, H-10, 2H-4'), 4.20 (2H, t, *J* = 7.4 Hz, H₂-1'), 2.84 (2H, t, *J* = 7.4 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆), δ 157.4 (d, ¹J<sub>CF</sub> = 231.8 Hz, C-11), 138.0 (C-3'), 137.7 (C-2), 132.7 (C-8a), 128.5 (2C-4'), 128.3 (2C-5'), 127.4 (C-6'), 126.8 (C-12a), 126.4 (C-4/C-7), 126.3 (C-4/C-7), 125.2 (C-5), 112.9 (d, ³J<sub>CF</sub> = 9.5 Hz, C-9), 109.9 (d, ²J<sub>CF</sub> = 25.5, C-10), 104.0 (d, ⁴J<sub>CF</sub> = 4.8 Hz, C-6), 103.4 (d, ²J<sub>CF</sub> = 24.7, C-12), 45.8 (C-1'), 36.2 (C-2'); (+)-HRESIMS *m/z* 328.1215 [M+Na]⁺ (calcd for C₁₉H₁₆FN₃Na, 328.1220).

### 3.2.5. 3-(1-(4-Iodobenzyl)-1H-imidazol-5-yl)-1H-indole (4)

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale yellow solid (0.023 g, 6%). R_f = 0.77 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) $v_{\text{max}}$ 2981, 1611, 1450, 1403, 1230, 1118, 917, 795 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.31 (1H, br s, NH-8), 7.81 (1H, s, H-2), 7.62 (2H, d, *J* = 8.3 Hz, 2H-4'), 7.51 (1H, d, *J* = 7.6 Hz, H-12), 7.41 (1H, d, *J* = 7.6 Hz, H-9), 7.25 (1H, d, *J* = 2.4 Hz, H-7), 7.14 (1H, ddd, *J* = 14.9, 7.6, 0.8 Hz, H-10), 7.12 (1H, s, H-4), 7.05 (1H, ddd, *J* = 14.9, 7.6, 0.8 Hz, H-11), 6.75 (2H, d, *J* = 8.3 Hz, 2H-3'), 5.25 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) δ 138.3 (C-2), 137.9 (C-2'), 137.3 (2C-4'), 135.9 (C-8a), 128.6 (2C-3'), 127.4 (C-4), 126.3 (C-5/C-12a), 126.2 (C-5/C-12a), 123.8 (C-7), 121.7 (C-10), 119.6 (C-11),
118.8 (C-12), 111.7 (C-9), 103.4 (C-6), 93.2 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 400.0305 [M+H]$^+$ (calcd for C₁₈H₁₅IN₃, 400.0301).

### 3.2.6. 5-Fluoro-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (5)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.124 g, 30%). R_f = 0.63 (CH₂Cl₂/MeOH, 9:1); m.p 187–188 °C; IR (ATR) νmax 3046, 2777, 1630, 1583, 1507, 1468, 1229, 1118, 847, 794 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.42 (1H, br s, NH-8), 7.83 (1H, d, *J* = 1.0 Hz, H-2), 7.62 (2H, d, *J* = 8.5 Hz, 2H-4'), 7.41 (1H, dd, *J* = 9.0, 4.6 Hz, H-9), 7.34 (1H, d, *J* = 2.7 Hz, H-7), 7.17 (1H, dd, *J* = 9.5, 2.4 Hz, H-12), 7.12 (1H, d, *J* = 1.0 Hz, H-4), 6.98 (1H, ddd, *J* = 9.5, 9.0, 2.5 Hz, H-11), 6.74 (2H, d, *J* = 8.5 Hz, 2H-3'), 5.24 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.4 (d, ¹J₄F = 234.0 Hz, C-11), 138.5 (C-2), 138.8 (C-2'), 137.3 (2C-4'), 132.5 (C-8a), 128.6 (2C-3'), 127.5 (C-4), 126.6 (d, ³J₄F = 10.4 Hz, C-12a), 125.9 (C-7), 125.8 (C-5), 112.8 (d, ³J₄F = 9.6 Hz, C-9), 110.0 (d, ²J₄F = 25.7 Hz, C-10), 103.7 (C-6), 103.5 (d, ²J₄F = 23.4 Hz, C-12), 93.2 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 440.0024 [M+Na]⁺ (calcd for C₁₈H₁₃FIN₃Na, 440.0030).

### 3.2.7. 6-Fluoro-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (6)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a light brown powder (0.119 g, 29%). R_f = 0.74 (CH₂Cl₂/MeOH, 9:1); m.p 191–192 °C; IR (ATR) νmax 3081, 2996, 2807, 1627, 1508, 1458, 1231, 1115, 837, 793 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.37 (1H, br s, NH-8), 7.82 (1H, d, *J* = 0.8 Hz, H-2), 7.62 (2H, d, *J* = 8.4 Hz, 2H-4'), 7.48 (1H, dd, *J* = 8.8, 5.4 Hz, H-12), 7.26 (1H, d, *J* = 2.5 Hz, H-7), 7.18 (1H, dd, *J* = 10.0, 2.5 Hz, H-9), 7.13 (1H, d, *J* = 0.8 Hz, H-4), 6.89 (1H, ddd, *J* = 9.8, 8.8, 2.5 Hz, H-11), 6.74 (2H, d, *J* = 8.4 Hz, 2H-3'), 5.24 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) δ 159.0 (d, ¹J₄F = 235.0 Hz, C-10), 138.4 (C-2), 137.8 (C-2'), 137.3 (2C-4'), 135.7 (d, ³J₄F = 12.7 Hz, C-8a), 128.6 (2C-3'), 127.6 (C-4), 125.8 (C-5), 124.3 (C-7), 123.1 (C-12a), 119.9 (d, ³J₄F = 10.6 Hz, C-12), 108.1 (d, ²J₄F = 24.7 Hz, C-11), 103.7 (C-6), 97.6 (d, ²J₄F = 25.3, C-9), 93.2 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 440.0030 [M+Na]⁺ (calcd for C₁₈H₁₃FIN₃Na, 440.0023).

### 3.2.8. 5-Chloro-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (7)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a pale yellow solid (0.033 g, 9%). R_f = 0.58 (CH₂Cl₂/MeOH, 9:1); m.p >200 °C; IR (ATR) νmax 3032, 2917, 2849, 1461, 1404, 1115, 1007, 886, 802, 792, 757 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.52 (1H, br s, NH-8), 7.85 (1H, br s, H-2), 7.61 (2H, d, *J* = 8.3 Hz, 2H-4'), 7.42 (1H, d, *J* = 8.6 Hz, H-9), 7.37 (1H, d, *J* = 2.1 Hz, H-12), 7.36 (1H, d, *J* = 2.6 Hz, H-7), 7.13 (1H, dd, *J* = 8.6, 2.1 Hz, H-10), 7.12 (1H, br s, H-4), 6.73 (2H, d, *J* = 8.3 Hz, 2H-3'), 5.22 (2H, s, H₂-1'), ¹³C NMR (100 MHz, DMSO-d₆) δ 138.6 (C-2), 137.8 (C-2'), 137.3 (2C-4'), 134.3 (C-8a), 128.6 (2C-3'), 127.8 (C-12a), 127.5 (C-4), 125.8 (C-11), 125.4 (C-5), 124.3 (C-7), 121.8 (C-10), 117.9 (C-12), 113.3 (C-9), 103.3 (C-6), 93.3 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 433.9912 [M+H]⁺ (calcd for C₁₈H₁₄³⁵CIIN₃, 433.9915), *m/z* 435.9888 [M+H]⁺ (calcd for C₁₈H₁₄³⁷CIIN₃, 435.9891).
### 3.2.9. 6-Chloro-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (8)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a brown solid (0.079 g, 18%). Rf = 0.68 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 2775, 1610, 1594, 1512, 1300, 1240, 1112, 828, 796 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.44 (1H, br s, NH-8), 7.83 (1H, d, *J* = 1.0 Hz, H-2), 7.61 (2H, d, *J* = 8.5 Hz, 2H-4'), 7.49 (1H, d, *J* = 8.5 Hz, H-12), 7.45 (1H, d, *J* = 2.0 Hz, H-9), 7.31 (1H, d, *J* = 2.7 Hz, H-7), 7.12 (1H, d, *J* = 1.0 Hz, H-4), 7.05 (1H, dd, *J* = 8.5, 2.0 Hz, H-11), 6.74 (2H, d, *J* = 8.5 Hz, 2H-3'), 5.24 (2H, s, H₂-1'), ¹³C NMR (100 MHz, DMSO-d₆) δ 138.5 (C-2), 137.7 (C-2'), 137.3 (2C-4'), 136.2 (C-8a), 128.6 (2C-3'), 127.7 (C-4), 126.4 (C-10), 125.6 (C-12a), 125.1 (C-5), 124.9 (C-7), 120.3 (C-12), 119.9 (C-11), 111.3 (C-9), 103.8 (C-6), 93.2 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 455.9728 [M+Na]⁺ (calcd for C₁₈H₁₃³⁵ClIN₃Na, 455.9735), *m/z* 457.9711 [M+Na]⁺ (calcd for C₁₈H₁₃³⁷ClIN₃Na, 457.9711).

### 3.2.10. 5-Bromo-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (9)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as an orange solid (0.014 g, 3%). Rf = 0.51 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 3031, 283, 2720, 1623, 1588, 1456, 1238, 1116, 879, 792 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.53 (1H, br s, NH-8), 7.85 (1H, d, *J* = 1.0 Hz, H-2), 7.61 (2H, d, *J* = 8.5 Hz, 2H-4'), 7.48 (1H, d, *J* = 2.0 Hz, H-12), 7.38 (1H, d, *J* = 8.5 Hz, H-9), 7.34 (1H, d, *J* = 1.0 Hz, H-7), 7.24 (1H, dd, *J* = 8.5, 2.0 Hz, H-10), 7.11 (1H, d, *J* = 1.0 Hz, H-4), 6.73 (2H, d, *J* = 8.5 Hz, 2H-3'), 5.21 (2H, d, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) δ 138.6 (C-2), 137.7 (C-2'), 137.2 (2C-4'), 134.5 (C-8a), 128.5 (2C-3'), 128.2 (C-4), 127.9 (C-12a), 125.7 (C-5), 124.2 (C-10), 120.9 (C-12), 113.8 (C-9), 112.2 (C-11), 103.1 (C-6), 93.3 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 477.9411 [M+H]⁺ (calcd for C₁₈H₁₄⁷⁹BrIN₃, 477.9411), *m/z* 479.9391 [M+H]⁺ (calcd for C₁₈H₁₄⁸¹BrIN₃, 479.9392).

### 3.2.11. 6-Bromo-3-(1-(4-iodobenzyl)-1H-imidazol-5-yl)-1H-indole (10)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-iodobenzylamine (0.233 g, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a light brown powder (0.177 g, 37%). Rf = 0.71 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 2831, 1621, 1589, 1484, 1456, 1432, 1225, 1116, 982, 794 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.44 (1H, br s, NH-8), 7.83 (1H, d, *J* = 0.8 Hz, H-2), 7.61 (2H, d, *J* = 8.3 Hz, 2H-4'), 7.60 (1H, d, *J* = 1.8 Hz, H-9), 7.44 (1H, d, *J* = 8.7 Hz, H-12), 7.30 (1H, d, *J* = 2.5 Hz, H-7), 7.16 (1H, dd, *J* = 8.6, 1.8 Hz, H-11), 7.12 (1H, d, *J* = 0.8 Hz, H-4), 6.73 (2H, d, *J* = 8.3 Hz, 2H-3'), 5.24 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) δ 138.5 (C-2'), 137.7 (C-2), 137.2 (2C-4'), 136.7 (C-8a), 128.6 (2C-3'), 127.7 (C-4), 125.5 (C-5), 125.3 (C-12a), 124.8 (C-7), 122.5 (C-11), 120.6 (C-12), 114.4 (C-10), 114.3 (C-9), 103.8 (C-6), 93.2 (C-5'), 47.2 (C-1'); (+)-HRESIMS *m/z* 499.9211 [M+Na]⁺ (calcd for C₁₈H₁₃⁷⁹BrIN₃Na, 499.9230), *m/z* 501.9211 [M+Na]⁺ (calcd for C₁₈H₁₃⁸¹BrIN₃Na, 501.9211).

### 3.2.12. 3-(1-(4-Methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (11)

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.043 g, 14%). Rf = 0.42 (CH₂Cl₂/MeOH, 9:1); m.p 159–160 °C; IR (ATR) νmax 3411, 2959, 1640, 1512, 1298, 1255, 1030, 909, 842, 784 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.37 (1H, br s, NH-8), 7.78 (1H, d, *J* = 0.9 Hz, H-2), 7.54 (1H,
d, *J* = 8.0 Hz, H-12), 7.43 (1H, d, *J* = 8.0 Hz, H-9), 7.32 (1H, d, *J* = 2.7 Hz, H-7), 7.15 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-10), 7.11 (1H, d, *J* = 0.9 Hz, H-4), 7.06 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-11), 6.92 (2H, d, *J* = 8.7 Hz, 2H-3'), 6.82 (2H, d, *J* = 8.7 Hz, 2H-4'), 5.20 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.5 (C-5'), 138.1 (C-2), 136.0 (C-8a), 129.8 (C-2'), 127.9 (2C-3'), 127.2 (C-4, C-5), 126.3 (C-12a), 123.9 (C-7), 121.7 (C-10), 119.6 (C-11), 118.9 (C-12), 114.0 (2C-4'), 111.8 (C-9), 103.7 (C-6), 55.0 (OMe), 47.3 (C-1'); (+)-HRESIMS *m/z* 304.1436 [M+H]⁺ (calcd for C₁₉H₁₈N₃O, 304.1444).

### 3.2.13. 5-Fluoro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (12)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a yellow powder (0.090 g, 28%). R_f = 0.54 (CH₂Cl₂/MeOH, 9:1); m.p 181–182 °C; IR (ATR) νmax 3155, 2835, 2661 cm⁻¹ 1610, 1583, 1509, 1347, 1240, 1032, 970, 837, 790 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.39 (1H, br s, NH-8), 7.77 (1H, d, *J* = 1.0 Hz, H-2), 7.49 (1H, dd, *J* = 8.9, 5.5 Hz, H-9), 7.31 (1H, d, *J* = 2.5 Hz, H-7), 7.20 (1H, dd, *J* = 10.0, 2.5 Hz, H-12), 7.10 (1H, d, *J* = 1.0 Hz, H-4), 6.93–6.88 (3H, m, H-10, 2H-3'), 6.82 (2H, d, *J* = 8.8 Hz, 2H-4'), 5.18 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.9 (d, ¹J₄F = 236.3 Hz, C-11), 158.5 (C-5'), 138.2 (C-2), 135.8 (d, ³J₄F = 12.5 Hz, C-12a), 129.7 (C-2'), 127.8 (2C-3'), 127.4 (C-4), 125.8 (C-5), 124.4 (C-7), 123.1 (C-8a), 120.0 (d, ³J₄F = 10.1 Hz, C-9), 113.9 (2C-4'), 108.1 (d, ²J₄F = 24.6 Hz, C-10), 103.9 (C-6), 97.7 (d, ²J₄F = 25.3 Hz, C-12), 55.0 (OMe), 47.2 (C-1'); (+)-HRESIMS *m/z* 322.1350 [M+H]⁺ (calcd for C₁₉H₁₇FN₃O, 322.1350).

### 3.2.14. 6-Fluoro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (13)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.224 g, 70%). R_f = 0.22 (CH₂Cl₂/MeOH, 9:1); m.p 181–182 °C; IR (ATR) νmax 3045, 2927, 2834, 1739, 1628, 1584, 1510, 1348, 1232, 1032, 837, 771 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.44 (1H, br s, NH-8), 7.80 (1H, d, *J* = 0.63 Hz, H-2), 7.51 (1H, dd, *J* = 8.8, 5.6 Hz, H-12), 7.33 (1H, d, *J* = 2.5 Hz, H-7), 7.22 (1H, dd, *J* = 9.9, 2.3 Hz, H-9), 7.13 (1H, d, *J* = 0.63 Hz, H-4), 6.94–6.89 (3H, m, H-11, 2H-3'), 6.82 (2H, d, *J* = 8.6 Hz, 2H-4'), 5.20 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 159 (d, ¹J₄F = 235.7 Hz, C-10), 158.5 (C-5'), 138.2 (C-2), 135.9 (d, ³J₄F = 12.9 Hz, C-8a), 129.7 (C-2'), 127.8 (2C-3'), 127.4 (C-4), 125.8 (C-5), 124.4 (C-7), 123.3 (C-12a), 120.1 (d, ³J₄F = 10.3 Hz, C-12), 113.9 (2C-4'), 108.2 (d, ²J₄F = 24.4 Hz, C-11), 103.9 (C-6), 97.7 (d, ²J₄F = 25.6 Hz, C-9), 54.9 (OMe), 47.3 (C-1'); (+)-HRESIMS *m/z* 322.1348 [M+H]⁺ (calcd for C₁₉H₁₇FN₃O, 322.1350).

### 3.2.15. 5-Chloro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (14)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale brown solid (0.156 g, 46%). R_f = 0.49 (CH₂Cl₂/MeOH, 9:1); m.p 193–194 °C; IR (ATR) νmax 3073, 3018, 2843, 1609, 1510, 1458, 1433, 1360, 1246, 1117, 1030, 893, 807, 764 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.56 (1H, br s, NH-8), 7.80 (1H, d, *J* = 0.9 Hz, H-2), 7.44 (1H, d, *J* = 8.7 Hz, H-9), 7.40 (1H, d, *J* = 2.9 Hz, H-7), 7.39 (1H, d, *J* = 2.2 Hz, H-12), 7.14 (1H, dd, *J* = 8.7, 2.2 Hz, H-10), 7.10 (1H, d, *J* = 0.9 Hz, H-4), 6.89 (2H, d, *J* = 8.5 Hz, 2H-3'), 6.81 (2H, d, *J* = 8.5 Hz, 2H-4'), 5.17 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.5 (C-5'), 138.3 (C-2), 134.4 (C-8a), 129.6 (C-2'), 127.8 (2C-3'), 127.6 (C-4), 127.4 (C-12a), 125.8 (C-7),
125.4 (C-5), 124.3 (C-11), 121.7 (C-10), 113.9 (2C-4'), 113.3 (C-9), 103.5 (C-6), 55.0 (OMe), 47.2 (C-1'); (+)-HRESIMS *m/z* 338.1056 [M+H]⁺ (calcd for C₁₉H₁₇³⁵ClN₃O, 388.1055), *m/z* 340.1039 [M+H]⁺ (calcd for C₁₉H₁₇³⁷ClN₃O, 340.1031).

### 3.2.16. 6-Chloro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (15)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.183 g, 54%). R_f = 0.64 (CH₂Cl₂/MeOH, 9:1); m.p 178–179 °C; IR (ATR) νmax 3080, 2835, 1612, 1588, 1512, 1456, 1248, 1230, 918, 795 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.46 (1H, br s, NH-8), 7.78 (1H, d, *J* = 0.9 Hz, H-2), 7.50 (1H, d, *J* = 8.7 Hz, H-12), 7.46 (1H, d, *J* = 2.0 Hz, H-9), 7.36 (1H, d, *J* = 2.5 Hz, H-7), 7.10 (1H, d, *J* = 0.9 Hz, H-4), 7.05 (1H, dd, *J* = 8.7, 2.0 Hz, H-11), 6.90 (2H, d, *J* = 9.0 Hz, 2H-3'), 6.81 (2H, d, *J* = 9.0 Hz, 2H-4'), 5.18 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.5 (C-5'), 138.3 (C-11), 136.3 (C-8a), 129.7 (C-2'), 127.9 (2C-3'), 127.5 (C-4), 126.4 (C-10), 125.6 (C-5), 125.1 (C-12a), 124.9 (C-7), 120.3 (C-12), 119.9 (C-11), 114.0 (2C-4'), 111.3 (C-9), 104.0 (C-6), 55.0 (OMe), 47.3 (C-1'); (+)-HRESIMS *m/z* 388.1050 [M+H]⁺ (calcd for C₁₉H₁₇³⁵ClN₃O, 388.1055), *m/z* 340.1033 [M+H]⁺ (calcd for C₁₉H₁₇³⁷ClN₃O, 340.1031).

### 3.2.17. 5-Bromo-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (16)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a white powder (0.025 g, 7%). R_f = 0.66 (CH₂Cl₂/MeOH, 9:1); m.p 197–198 °C; IR (ATR) νmax 2999, 2837, 1610, 1509, 1454, 1248, 1106, 915, 803 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 111.55 (1H, br s, NH-8), 7.80 (1H, d, *J* = 1.0 Hz, H-2), 7.51 (1H, d, *J* = 1.9 Hz, H-12), 7.39 (1H, d, *J* = 8.7 Hz, H-9), 7.38 (1H, s, H-7), 7.25 (1H, dd, *J* = 8.7, 1.9 Hz, H-10), 7.08 (1H, d, *J* = 1.0 Hz, H-4), 6.89 (2H, d, *J* = 8.7 Hz, 2H-3'), 6.80 (2H, d, *J* = 8.7 Hz, 2H-4'), 5.16 (2H, s, H₂-1'), 3.70 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.5 (C-5'), 138.3 (C-2), 134.6 (C-8a), 129.6 (C-2'), 128.3 (C-12a), 127.9 (2C-3'), 127.7 (C-4), 125.7 (C-7), 125.3 (C-5), 124.2 (C-10), 121.0 (C-12), 113.9 (2C-4'), 113.8 (C-9), 112.2 (C-11), 103.4 (C-6), 55.0 (OMe), 47.2 (C-1'); (+)-HRESIMS *m/z* 404.0356 [M+Na]⁺ (calcd for C₁₉H₁₇⁷BrN₃NaO, 404.0369), *m/z* 406.0322 [M+Na]⁺ (calcd for C₁₉H₁₆⁸BrN₃NaO, 406.0350).

### 3.2.18. 6-Bromo-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (17)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-methoxybenzylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a light brown powder (0.120 g, 32%). R_f = 0.65 (CH₂Cl₂/MeOH, 9:1); m.p 188–189 °C; IR (ATR) νmax 3081, 3023, 2834, 2646, 1612, 1588, 1213, 1454, 1224, 1249, 1225, 842, 788 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.47 (1H, br s, NH-8), 7.78 (1H, s, H-2), 7.60 (1H, d, *J* = 1.8 Hz, H-9), 7.45 (1H, d, *J* = 8.6 Hz, H-12), 7.35 (1H, d, *J* = 2.6 Hz, H-7), 7.17 (1H, dd, *J* = 8.6, 1.8 Hz, H-11), 7.10 (1H, s, H-4), 6.90 (2H, d, *J* = 8.7 Hz, 2H-3'), 6.81 (2H, d, *J* = 8.7 Hz, 2H-4'), 5.18 (2H, s, H₂-1'), 3.68 (3H, s, OMe); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.4 (C-5'), 138.3 (C-2), 136.7 (C-8a), 129.6 (C-2'), 127.8 (2C-3'), 127.5 (C-4), 125.5 (C-5), 125.4 (C-12a), 124.9 (C-7), 122.4 (C-11), 120.7 (C-12), 114.4 (C-10), 114.3 (C-9), 113.9 (2C-4'), 104.0 (C-6), 55.0 (OMe), 47.2 (C-1'); (+)-HRESIMS *m/z* 404.0369 [M+Na]⁺ (calcd for C₁₉H₁₆⁷BrN₃NaO, 404.0357), *m/z* 406.0332 [M+Na]⁺ (calcd for C₁₉H₁₆⁸BrN₃NaO, 406.0350).
### 3.2.19. 6-Fluoro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (18)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (163.0 mg, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown oil (0.053 g, 17%). R_f = 0.63 (CH₂Cl₂/MeOH, 9:1); IR (ATR) νmax 3083, 2901, 1628, 1588, 1506, 1452, 1344, 1228, 1149, 1112, 800, 751 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.49 (1H, br s, NH-8), 7.60 (1H, s, H-2), 7.48 (1H, d, *J* = 2.5 Hz, H-7), 7.46 (1H, dd, *J* = 8.8, 5.3 Hz, H-12), 7.25–7.19 (3H, m, H-9, 2H-5'), 7.19–7.16 (1H, m, H-6'), 7.01 (1H, s, H-4), 6.99 (2H, dd, *J* = 6.8, 1.5 Hz, 2H-4'), 6.92 (1H, ddd, *J* = 9.9, 8.8, 2.3 Hz, H-11), 4.20 (2H, t, *J* = 7.5 Hz, H₂-1'), 2.83 (2H, t, *J* = 7.5 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 158.9 (d, ¹J<sub>CF</sub> = 235.9, C-10), 138.0 (C-3'), 137.8 (C-2), 135.8 (d, ³J<sub>CF</sub> = 12.6 Hz, C-8a), 128.5 (2C-4'), 128.3 (2C-5'), 127.4 (C-4), 126.4 (C-6'), 125.3 (C-5), 124.8 (C-7), 123.3 (C-12a), 119.9 (d, ³J<sub>CF</sub> = 10.8 Hz, C-12), 108.1 (d, ²J<sub>CF</sub> = 24.6, C-11), 104.0 (C-6), 97.7 (d, ²J<sub>CF</sub> = 25.3, C-9), 45.8 (C-1'), 36.2 (C-2'); (+)-HRESIMS *m/z* 306.1390 [M+Na]⁺ (calcd for C₁₉H₂₉FNaO, 306.1395).

### 3.2.20. 5-Chloro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (19)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale yellow powder (0.149 g, 46%). R_f = 0.62 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 3016, 2831, 1628, 1481, 1436, 1227, 1111, 921, 886, 793 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.63 (1H, br s, NH-8), 7.63 (1H, s, H-2), 7.56, (1H, d, *J* = 2.5 Hz, H-7), 7.48 (1H, d, *J* = 8.3 Hz, H-9), 7.42 (1H, d, *J* = 1.8 Hz, H-12), 7.23–7.19 (3H, m, 2H-5', H-6'), 7.19–7.15 (1H, m, H-10), 6.99–6.97 (3H, m, H-4, 2H-4'), 4.20 (2H, t, *J* = 7.6 Hz, H₂-1'), 2.83 (2H, t, *J* = 7.6 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.9 (C-3'), 137.8 (C-2), 134.4 (C-8a), 128.5 (2C-5'), 128.3 (2C-4'), 127.7 (C-12a), 127.5 (C-7), 126.4 (C-6'), 126.1 (C-4), 124.9 (C-5), 124.3 (C-11), 121.7 (C-10), 117.8 (C-12), 113.4 (C-9), 103.6 (C-6), 45.7 (C-1'), 36.2 (C-2'); (+)-HRESIMS *m/z* 344.0925 [M+Na]⁺ (calcd for C₁₉H₁₆³⁵ClN₃Na, 344.0925), *m/z* 346.0893 [M+Na]⁺ (calcd for C₁₉H₁₆³⁷ClN₃Na, 346.0893).

### 3.2.21. 6-Chloro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (20)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a dark brown solid (0.145 g, 45%). R_f = 0.69 (CH₂Cl₂/MeOH, 9:1); m.p 91–92 °C; IR (ATR) νmax 3136, 2829, 2629, 1610, 1509, 1440, 1241, 1131, 823, 793 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.56 (1H, br s, NH-8), 7.61 (1H, s, H-2), 7.52 (1H, d, *J* = 2.6 Hz, H-7), 7.50 (1H, d, *J* = 1.9 Hz, H-9), 7.47 (1H, d, *J* = 8.7 Hz, H-12), 7.24–7.20 (2H, m, 2H-5'), 7.20–7.16 (1H, m, H-6'), 7.07 (1H, dd, *J* = 8.9, 1.9 Hz, H-11), 7.00–6.99 (3H, m, 2H-4', H-4), 4.20 (2H, t, *J* = 7.4 Hz, H₂-1'), 2.83 (2H, t, *J* = 7.6 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 138.0 (C-3'), 137.8 (C-2), 136.4 (C-8a), 128.5 (2C-4'), 128.3 (2C-5'), 127.5 (C-4), 126.4 (C-6', C-10), 125.4 (C-12a), 125.3 (C-7), 125.1 (C-5), 120.2 (C-12), 119.9 (C-11), 104.1 (C-6), 45.8 (C-1'), 36.2 (C-2'); (+)-HRESIMS *m/z* 322.1114 [M+H]⁺ (calcd for C₁₉H₁₇³⁵ClN₃, 322.1106), *m/z* 324.1085 [M+H]⁺ (calcd for C₁₉H₁₇³⁷ClN₃, 324.1082).

### 3.2.22. 5-Bromo-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (21)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.092 g, 25%). R_f = 0.41 (CH₂Cl₂/MeOH, 9:1); m.p
110–111 °C; IR (ATR) $v_{max}$ 3404, 2921, 2256, 1627, 1507, 1453, 816, 791 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.70 (1H, s, NH-8), 7.65 (1H, s, H-2), 7.59 (1H, d, $J = 1.6$ Hz, H-12), 7.55 (1H, d, $J = 1.9$ Hz, H-7), 7.45 (1H, d, $J = 8.5$ Hz, H-9), 7.28 (1H, dd, $J = 8.5$, 1.6 Hz, H-10), 7.22–7.15 (3H, m, 2H-5', H-6'), 7.02 (1H, s, H-4), 6.98 (2H, d, $J = 7.4$ Hz, 2H-4'), 4.20 (2H, t, $J = 7.2$ Hz, H$_2$-1'), 2.84 (2H, t, $J = 7.2$ Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 137.9 (C-2/C-3), 137.8 (C-2/C-3'), 134.7 (C-8a), 128.5 (2C-4'), 128.4 (C-12a), 128.3 (2C-5'), 127.6 (C-4), 126.4 (C-6'), 126.0 (C-7), 124.9 (C-5), 124.2 (C-10), 121.0 (C-12), 113.8 (C-9), 112.2 (C-11), 103.5 (C-6), 45.8 (C-1'), 36.2 (C-2'); (+)-HRESIMS *m/z* 366.0599 [M+H]$^+$ (calcd for C$_{19}$H$_{17}$$^{79}$BrN$_3$, 366.0600), *m/z* 368.0576 [M+H]$^+$ (calcd for C$_{19}$H$_{17}$$^{81}$BrN$_3$, 368.0576).

### 3.2.23. 6-Bromo-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (22)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with phenethylamine (0.12 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title compound as an brown oil (0.158 g, 43%). $R_f = 0.56$ (CH$_2$Cl$_2$/MeOH, 9:1); IR (ATR) $v_{max}$ 3086, 2247, 1595, 1453, 1332, 1108, 894, 727 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.56 (1H, br s, NH-8), 7.64 (1H, d, $J = 1.4$ Hz, H-9), 7.61 (1H, d, $J = 0.7$ Hz, H-2), 7.51 (1H, d, $J = 2.7$ Hz, H-7), 7.43 (1H, d, $J = 8.5$ Hz, H-12), 7.24–7.19 (2H, m, 2H-4'), 7.18–7.16 (2H, m, H-11, H-6'), 7.00–6.98 (3H, m, H-4, 2H-5'), 4.20 (2H, t, $J = 7.2$ Hz, H$_2$-1'), 2.82 (2H, $J = 7.2$ Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 138.0 (C-2), 137.8 (C-3'), 136.8 (C-8a), 128.5 (2C-4'), 128.3 (2C-5'), 127.5 (C-7), 126.4 (C-9), 125.6 (C-5), 125.2 (C-4), 125.0 (C-12a), 122.5 (C-11), 120.6 (C-12), 114.4 (C-10), 114.3 (C-6'), 104.1 (C-6), 45.8 (C-1'), 36.1 (C-2'); (+)-HRESIMS *m/z* 388.0422 [M+Na]$^+$ (calcd for C$_{19}$H$_{16}$$^{79}$BrN$_3$Na, 388.0420), *m/z* 390.0400 [M+Na]$^+$ (calcd for C$_{19}$H$_{16}$$^{81}$BrN$_3$Na, 390.0401).

### 3.2.24. 3-(1-(4-Methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (23)

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with 4-methoxy-phenethylamine (0.15 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.146 g, 46%). $R_f = 0.59$ (CH$_2$Cl$_2$/MeOH, 9:1); m.p 158–159 °C; IR (ATR) $v_{max}$ 3402, 2835, 1612, 1511, 1244, 1025, 916, 746 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.46 (1H, s, NH-8), 7.60 (1H, s, H-2), 7.51–7.46 (3H, m, H-7, H-9, H-12), 7.17 (1H, ddd, $J = 7.4$, 7.4, 1.1 Hz, H-10), 7.07 (1H, ddd, $J = 7.4$, 7.4, 0.9 Hz, H-11), 7.00 (1H, s, H-4), 6.90 (2H, d, $J = 8.7$ Hz, 2H-4'), 6.77 (2H, d, $J = 8.7$ Hz, 2H-5'), 4.17 (2H, t, $J = 7.5$ Hz, H$_2$-1'), 3.68 (3H, s, OMe), 2.78 (2H, t, $J = 7.5$ Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 157.8 (C-6'), 137.6 (C-2), 136.0 (C-8a), 129.8 (C-3'), 129.5 (2C-4'), 127.2 (C-4), 126.5 (C-12a), 125.7 (C-5), 124.2 (C-7), 121.7 (C-10), 119.5 (C-11), 118.8 (C-12), 113.7 (2C-5'), 111.8 (C-9), 103.8 (C-6), 54.9 (OMe), 46.1 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 318.1599 [M+H]$^+$ (calcd for C$_{20}$H$_{20}$N$_3$O, 318.1601).

### 3.2.25. 5-Fluoro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (24)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title compound as a yellow solid (0.255 g, 76%). $R_f = 0.70$ (CH$_2$Cl$_2$/MeOH, 9:1); m.p 152–153 °C; IR (ATR) $v_{max}$ 3137, 2993, 2833, 1632, 1509, 1464, 1237, 1114, 849, 794 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.53 (1H, br s, NH-8), 7.60 (1H, d, $J = 1.0$ Hz, H-2), 7.55 (1H, d, $J = 2.4$ Hz, H-7), 7.45 (1H, dd, $J = 9.0$, 4.7 Hz, H-9), 7.16 (1H, dd, $J = 9.5$, 2.7 Hz, H-12), 7.01 (1H, ddd, $J = 9.5$, 9.0, 2.7 Hz, H-10), 6.98 (1H, s, H-4), 6.89 (2H, d, $J = 8.9$ Hz, 2H-4'), 6.76 (2H, d, $J = 8.9$ Hz, 2H-5'), 4.15 (2H, t, $J = 7.2$ Hz, H$_2$-1'), 3.68 (3H, s, OMe), 2.77 (2H, t, $J = 7.2$ Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 157.8 (C-6'), 157.4 (d,
$^1J_{CF} = 230.8$ Hz, C-11), 137.7 (C-2), 132.6 (C-8a), 129.8 (C-3'), 129.5 (2C-4'), 127.3 (C-4), 126.8 (d, $^3J_{CF} = 10.5$ Hz, C-12a), 126.2 (C-7), 125.2 (C-5), 113.7 (2C-5'), 112.9 (d, $^3J_{CF} = 10.4$ Hz, C-9), 109.9 (d, $^2J_{CF} = 26.4$ Hz, C-10), 104.1 (d, $^4J_{CF} = 5.0$ Hz, C-6), 103.4 (d, $^2J_{CF} = 23.9$ Hz, C-12), 54.9 (OMe), 46.0 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 358.1334 [M+Na]$^+$ (calcd for C$_20$H$_{18}$FN$_3$NaO, 358.1326).

### 3.2.26. 6-Fluoro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (25)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title compound as a brown oil (0.050 g, 15%). $R_f = 0.60$ (CH$_2$Cl$_2$/MeOH, 9:1); IR (ATR) $\nu_{max}$ 3083, 2929, 2254, 1627, 1612, 1509, 1453, 1241, 1026, 820, 795 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.49 (1H, br s, NH-8), 7.60 (1H, s, H-2), 7.48 (1H, d, *J* = 1.5 Hz, H-7), 7.46 (1H, dd, *J* = 8.5, 5.3 Hz, H-12), 7.24 (1H, d, *J* = 10.0 Hz, H-9), 7.00 (1H, s, H-4), 6.93 (1H, d, *J* = 8.5 Hz, H-11), 6.90 (2H, d, *J* = 8.3 Hz, 2H-4'), 6.77 (2H, d, *J* = 8.3 Hz, 2H-5'), 4.16 (2H, t, *J* = 7.4 Hz, H$_2$-1'), 3.68 (3H, s, OMe), 2.77 (2H, t, *J* = 7.4 Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 159.0 (d, $^1J_{CF} = 229.0$ Hz, C-10), 157.8 (C-6'), 137.8 (C-2), 135.9 (d, $^3J_{CF} = 12.7$ Hz, C-8a), 129.8 (C-3'), 129.5 (2C-4'), 127.4 (C-4), 125.3 (C-5), 124.7 (C-7), 123.4 (C-12a), 119.9 (d, $^3J_{CF} = 10.2$ Hz, C-12), 113.7 (2C-5'), 108.1 (d, $^2J_{CF} = 25.0$ Hz, C-11), 104.1 (C-6), 97.7 (d, $^2J_{CF} = 25.5$ Hz, H-9), 54.9 (OMe), 46.1 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 358.1336 [M+Na]$^+$ (calcd for C$_20$H$_{18}$FN$_3$NaO, 358.1326).

### 3.2.27. 5-Chloro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (26)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title as a brown oil compound (0.038 g, 7%). $R_f = 0.56$ (CH$_2$Cl$_2$/MeOH, 9:1); IR (ATR) $\nu_{max}$ 3136, 2253, 1656, 1612, 1511, 1459, 1244, 1110, 1024, 894, 797 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.63 (1H, br s, NH-8), 7.61 (1H, d, *J* = 1.0 Hz, H-2), 7.55 (1H, d, *J* = 2.9 Hz, H-7), 7.48 (1H, d, *J* = 8.5 Hz, H-9), 7.42 (1H, d, *J* = 2.0 Hz, H-12), 7.16 (1H, dd, *J* = 8.5, 2.0 Hz, H-10), 6.99 (1H, d, *J* = 1.0 Hz, H-4), 6.89 (2H, d, *J* = 8.7 Hz, 2H-4'), 6.75 (2H, *J* = 8.7 Hz, 2H-5'), 4.15 (2H, t, *J* = 7.5 Hz, H$_2$-1'), 3.68 (3H, s, OMe), 2.77 (2H, d, *J* = 7.5 Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$), $\delta$ 157.8 (C-6'), 137.8 (C-2), 134.5 (C-8a), 129.8 (C-3'), 129.5 (2C-4'), 127.7 (C-4), 127.5 (C-12a), 126.1 (C-7), 125.0 (C-5), 124.3 (C-11), 121.7 (C-10), 117.9 (C-12), 113.7 (2C-5'), 113.4 (C-9), 103.7 (C-6), 54.9 (OMe), 46.0 (C-1'), 35.4 (C-2'); (+)-HRESIMS *m/z* 374.1021 [M+Na]$^+$, (calcd for C$_20$H$_{18}$$^{35}$ClN$_3$NaO, 374.1031), *m/z* 376.1002 [M+Na]$^+$, (calcd for C$_20$H$_{18}$$^{37}$ClN$_3$NaO, 376.1008).

### 3.2.28. 5-Bromo-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (27)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K$_2$CO$_3$ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH$_2$Cl$_2$/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.192 g, 49%). $R_f = 0.76$ (CH$_2$Cl$_2$/MeOH, 9:1); m.p 157–158 °C; IR (ATR) $\nu_{max}$ 3136, 2830, 1611, 1587, 1509, 1453, 1241, 1132, 1032, 824, 793 cm$^{-1}$; $^1$H NMR (400 MHz, DMSO-d$_6$) $\delta$ 11.64 (1H, br s, NH-8), 7.62 (1H, d, *J* = 1.0 Hz, H-2), 7.56 (1H, d, *J* = 2.0 Hz, H-12), 7.53 (1H, d, *J* = 2.7 Hz, H-7), 7.43 (1H, d, *J* = 8.8 Hz, H-9), 7.28 (1H, dd, *J* = 8.8, 2.0 Hz, H-10), 6.98 (1H, d, *J* = 1.0 Hz, H-4), 6.89 (2H, d, *J* = 8.4 Hz, 2H-4'), 6.76 (2H, d, *J* = 8.4 Hz, 2H-5'), 4.15 (2H, t, *J* = 7.3 Hz, H$_2$-1'), 3.68 (3H, s, OMe), 2.76 (2H, t, *J* = 7.3 Hz, H$_2$-2'); $^{13}$C NMR (100 MHz, DMSO-d$_6$) $\delta$ 157.8 (C-6'), 137.8 (C-2), 134.6 (C-8a), 129.7 (C-3'), 129.5 (2C-4'), 128.4 (C-12a), 127.5 (C-4), 125.9 (C-7), 124.9 (C-5), 124.2 (C-10), 120.8 (C-12), 113.8 (C-9), 113.7 (2C-5'), 112.2 (C-11), 103.5 (C-6), 54.9 (OMe),
46.0 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 418.0513 [M+Na]⁺ (calcd for C₂₀H₁₈⁷⁹BrN₃NaO, 418.0525), *m/z* 420.0491 [M+Na]⁺ (calcd for C₂₀H₁₈⁸¹BrN₃NaO, 420.0507).

### 3.2.29. 6-Bromo-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (28)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 4-methoxyphenethylamine (0.15 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a yellow solid (0.187 g, 47%). R_f = 0.40 (CH₂Cl₂/MeOH, 9:1); m.p 184–185 °C; IR (ATR) νmax 2775, 1610, 1511, 1440, 1243, 1112, 827, 806 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.55 (1H, br s, NH-8), 7.64 (1H, d, *J* = 1.8 Hz, H-9), 7.60 (1H, d, *J* = 1.0 Hz, H-2), 7.50 (1H, d, *J* = 2.6 Hz, H-7), 7.42 (1H, d, *J* = 8.6 Hz, H-12), 7.18 (1H, dd, *J* = 8.6, 1.8 Hz, H-11), 6.97 (1H, d, *J* = 1.0 Hz, H-4), 6.89 (2H, d, *J* = 8.3 Hz, 2H-4'), 6.76 (2H, d, *J* = 8.3 Hz, 2H-5'), 4.15 (2H, t, *J* = 7.3 Hz, H₂-1'), 3.68 (3H, s, OMe), 2.75 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.8 (C-6'), 137.8 (C-2), 136.8 (C-8a), 129.7 (C-3'), 129.4 (2C-4'), 127.4 (C-4), 125.5 (C-12a), 125.1 (C-7), 125.0 (C-5), 122.4 (C-11), 120.6 (C-12), 114.4 (C-9), 114.3 (C-10), 113.6 (2C-5'), 104.1 (C-6), 54.9 (OMe), 46.0 (C-1'), 35.3 (C-2'); (+)-HRESIMS *m/z* 396.0718 [M+H]⁺ (calcd for C₂₀H₁₈⁷⁹BrN₃O, 396.0706), *m/z* 398.0700 [M+H]⁺ (calcd for C₂₀H₁₈⁸¹BrN₃O, 398.0688).

### 3.2.30. 3-(1-(2,5-Dimethoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (29)

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown oil (0.138 g, 40%). R_f = 0.38 (CH₂Cl₂/MeOH, 9:1); IR (ATR) νmax 3401, 2916, 1644, 1592, 1498, 1223, 823, 796 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.49 (1H, br s, NH-8), 7.65 (1H, s, H-2), 7.51 (1H, d, *J* = 7.8 Hz, H-12), 7.51 (1H, s, H-7), 7.48 (1H, d, *J* = 7.8 Hz, H-9), 7.17 (1H, ddd, *J* = 14.9, 7.8, 1.1 Hz, H-10), 7.07 (1H, ddd, *J* = 14.9, 7.8, 1.1 Hz, H-11), 7.01 (1H, d, *J* = 0.9 Hz, H-4), 6.79 (1H, d, *J* = 8.7 Hz, H-5'), 6.70 (1H, dd, *J* = 8.7, 2.9 Hz, H-6'), 6.53 (1H, d, *J* = 2.9 Hz, H-8'), 4.16 (2H, t, *J* = 7.4 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.58 (3H, s, 4'-OMe), 2.82 (2H, t, *J* = 7.4 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 153.1 (C-7'), 151.3 (C-4'), 137.6 (C-2), 136.1 (C-8a), 127.0 (C-4), 126.7 (C-3'), 126.5 (C-12a), 125.9 (C-5), 124.1 (C-7), 121.6 (C-10), 119.5 (C-11), 119.0 (C-12), 116.3 (C-8'), 112.1 (C-6'), 111.7 (C-9), 111.5 (C-5'), 103.8 (C-6), 55.5 (4'-OMe), 55.2 (7'-OMe), 44.3 (C-1'), 31.9 (C-2'); (+)-HRESIMS *m/z* 348.1712 [M+H]⁺ (calcd for C₂₁H₂₂N₃O₂, 348.1707).

### 3.2.31. 3-(1-(2,5-Dimethoxyphenethyl)-1H-imidazol-5-yl)-5-fluoro-1H-indole (30)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.171 g, 47%). R_f = 0.43 (CH₂Cl₂/MeOH, 9:1); m.p 150–151 °C; IR (ATR) νmax 3027, 230, 1610, 1499, 1454, 1222, 1130, 1032, 821, 791 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.56 (1H, br s, NH-8), 7.65 (1H, s, H-2), 7.56 (1H, d, *J* = 2.6 Hz, H-7), 7.46 (1H, dd, *J* = 8.9, 4.7 Hz, H-9), 7.16 (1H, dd, *J* = 9.8, 2.3 Hz, H-12), 7.01 (1H, ddd, *J* = 9.8, 8.9, 2.5 Hz, H-10), 6.98 (1H, s, H-4), 6.77 (1H, d, *J* = 8.8 Hz, H-5'), 6.68 (1H, dd, *J* = 8.8, 2.9 Hz, H-6'), 6.51 (1H, d, *J* = 2.9 Hz, H-8'), 4.14 (2H, t, *J* = 7.7 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.56 (3H, s, 4'-OMe), 2.80 (2H, t, *J* = 7.7 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.4 (d, ¹J<sub>FC</sub> = 236.3, C-11), 152.9 (C-7'), 151.2 (C-4'), 137.7 (C-2), 132.7 (C-8a), 127.1 (C-3'), 126.8 (d, ³J<sub>FC</sub> = 10.0, C-12a), 126.6 (C-4), 126.1 (C-7), 125.4 (C-5), 116.3 (C-8'), 112.8 (d, ⁵J<sub>FC</sub> = 9.8 Hz, C-9), 112.1 (C-6'), 111.5 (C-5'), 109.8 (d, ²J<sub>FC</sub> = 26.4, C-10), 104.1 (d, ⁴J<sub>FC</sub> = 4.7 Hz, C-6), 103.5 (d, ²J<sub>FC</sub> = 24.7, C-12), 55.5 (4'-OMe), 55.2 (7'-OMe), 44.2 (C-1'), 32.0 (C-2'); (+)-HRESIMS *m/z* 388.1433 [M+Na]⁺ (calcd for C₂₁H₂₀FN₃NaO₂, 388.1432).
### 3.2.32. 3-(1-(2,5-Dimethoxyphenethyl)-1H-imidazol-5-yl)-6-fluoro-1H-indole (31)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as an orange solid (0.156 g, 43%). R_f = 0.60 (CH₂Cl₂/MeOH, 9:1); m.p 130–131 °C; IR (ATR) νmax 2990, 2827, 1632, 1605, 1590, 1499, 1217, 1122, 834, 788 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.52 (1H, br s, NH-8), 7.65 (1H, d, *J* = 1.1 Hz, H-2), 7.49 (1H, d, *J* = 2.6 Hz, H-7), 7.46 (1H, dd, *J* = 8.6, 5.5 Hz, H-12), 7.23 (1H, dd, *J* = 9.9, 2.3 Hz, H-9), 6.99 (1H, d, *J* = 1.1 Hz, H-4), 6.92 (1H, ddd, *J* = 11.9, 8.6, 2.3 Hz, H-11), 6.80 (1H, d, *J* = 9.0 Hz, H-5'), 6.70 (1H, dd, *J* = 9.0, 3.1 Hz, H-6'), 6.51 (1H, d, *J* = 3.1 Hz, H-8'), 4.14 (2H, t, *J* = 7.3 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.58 (3H, s, 4'-OMe), 2.80 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 159.0 (d, ¹JFC = 242.0, C-10), 152.8 (C-7'), 151.2 (C-4'), 137.7 (C-2), 135.8 (d, ³JFC = 12.7, C-8a), 127.1 (C-4), 126.8 (C-3'), 124.5 (C-5), 123.3 (C-12a), 120.0 (d, ³JFC = 11.4 Hz, C-12), 116.2 (C-8'), 112.1 (C-6'), 108.0 (d, ²JFC = 23.9 Hz, C-11), 104.0 (C-6), 97.6 (d, ²JFC = 26.0, C-9), 55.5 (4'-OMe), 55.2 (7'-OMe), 44.2 (C-1'), 31.9 (C-2'); (+)-HRESIMS *m/z* 388.1432 [M+Na]⁺ (calcd for C₂₁H₂₀FN₃NaO₂, 388.1418).

### 3.2.33. 5-Chloro-3-(1-(2,5-dimethoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (32)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown oil (0.198 g, 52%). R_f = 0.49 (CH₂Cl₂/MeOH, 9:1); IR (ATR) νmax 3116, 2833, 1592, 1500, 1457, 1222, 110, 1046, 89, 796 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.66 (1H, br s, NH-8), 7.66 (1H, d, *J* = 0.8 Hz, H-2), 7.55 (1H, d, *J* = 1.5 Hz, H-7), 7.48 (1H, d, *J* = 8.6 Hz, H-9), 7.40 (1H, d, *J* = 2.0 Hz, H-12), 7.16 (1H, dd, *J* = 8.6, 2.0 Hz, H-10), 6.98 (1H, s, H-4), 6.75 (1H, d, *J* = 8.7 Hz, H-5'), 6.68 (1H, dd, *J* = 8.7, 2.9 Hz, H-6'), 6.49 (1H, d, *J* = 2.9 Hz, H-8'), 4.14 (2H, t, *J* = 7.6 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.55 (3H, s, 4'-OMe), 2.78 (2H, t, *J* = 7.6 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆), δ 152.8 (C-7'), 151.2 (C-4'), 137.8 (C-2), 134.5 (C-8a), 127.7 (C-12a), 127.3 (C-7), 126.6 (C-3'), 125.9 (C-4), 125.1 (C-5), 124.2 (C-11), 121.6 (C-10), 117.9 (C-12), 116.2 (C-8'), 113.3 (C-9), 112.1 (C-6'), 111.4 (C-5'), 103.6 (C-6), 55.4 (4'-OMe), 55.2 (7'-OMe), 44.2 (C-1'), 32.0 (C-2'); (+)-HRESIMS *m/z* 404.1129 [M+Na]⁺ (calcd for C₂₁H₂₀³⁵ClN₃NaO₂, 404.1136), *m/z* 406.1107 [M+Na]⁺ (calcd for C₂₁H₂₀³⁷ClN₃NaO₂, 406.1115).

### 3.2.34. 6-Chloro-3-(1-(2,5-dimethoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (33)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale yellow solid (0.044 g, 12%). R_f = 0.57 (CH₂Cl₂/MeOH, 9:1); m.p 80–81 °C; IR (ATR) νmax 3534, 3157, 2966, 1501, 1457, 1220, 1024, 872, 789, 715 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.58 (1H, br s, NH-8), 7.66 (1H, d, *J* = 0.6 Hz, H-2), 7.53 (1H, d, *J* = 2.5 Hz, H-7), 7.50 (1H, d, *J* = 2.0 Hz, H-9), 7.47 (1H, d, *J* = 8.5 Hz, H-12), 7.07 (1H, dd, *J* = 8.5, 2.0 Hz, H-10), 6.99 (1H, d, *J* = 0.6 Hz, H-4), 6.79 (1H, d, *J* = 9.0 Hz, H-5'), 6.69 (1H, dd, *J* = 9.0, 3.0 Hz, H-6'), 6.50 (1H, d, *J* = 3.0 Hz, H-8'), 4.14 (2H, t, *J* = 7.5 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.57 (3H, s, 4'-OMe), 2.79 (2H, t, *J* = 7.5 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 152.9 (C-7'), 151.2 (C-4'), 137.8 (C-2), 136.4 (C-8a), 127.2 (C-4), 126.6 (C-3'), 126.3 (C-10), 125.3 (C-12a), 125.2 (C-5), 125.1 (C-7), 120.3 (C-12), 119.8 (C-11), 116.3 (C-8'), 112.1 (C-6'), 111.5 (C-5'), 111.3 (C-9), 104.1 (C-6), 55.5 (4'-OMe), 55.2 (7'-OMe), 44.3 (C-1'), 31.9 (C-2'); (+)-HRESIMS *m/z* 382.1305 [M+H]⁺ (calcd for C₂₁H₂₁³⁵ClN₃O₂, 382.1317), *m/z* 384.1280 [M+H]⁺ (calcd for C₂₁H₂₁³⁷ClN₃O₂, 384.1295).
### 3.2.35. 5-Bromo-3-(1-(2,5-dimethoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (34)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a light brown powder (0.010 g, 3%). Rf = 0.45 (CH₂Cl₂/MeOH, 9:1); m.p 141–142 °C; IR (ATR) νmax 3124, 2836, 2161, 1619, 1593, 1495, 1455, 1226, 1121, 1030, 918, 884, 782 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.66 (1H, br s, NH-8), 7.65 (1H, d, *J* = 0.9 Hz, H-2), 7.54 (1H, s, H-12), 7.53 (1H, s, H-7), 7.43 (1H, d, *J* = 8.6 Hz, H-9), 7.27 (1H, dd, *J* = 8.6, 1.9 Hz, H-10), 6.98 (1H, d, *J* = 0.9 Hz, H-4), 6.75 (1H, d, *J* = 8.6 Hz, H-5'), 6.68 (1H, dd, *J* = 8.6, 2.9 Hz, H-6'), 6.48 (1H, d, *J* = 2.9 Hz, H-8'), 4.14 (2H, t, *J* = 7.7 Hz, H₂-1'), 3.62 (3H, s, 4'-OMe), 3.54 (3H, s, 7'-OMe), 2.77 (2H, t, *J* = 7.7 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 152.8 (C-7'), 151.1 (C-4'), 137.8 (C-2), 134.7 (C-8a), 128.4 (C-12a), 127.3 (C-4), 125.7 (C-7), 125.0 (C-5), 124.1 (C-10), 120.9 (C-12), 116.2 (C-8'), 113.7 (C-9), 112.1 (C-11), 112.0 (C-6'), 111.4 (C-5'), 103.5 (C-6), 55.4 (7'-OMe), 55.2 (4'-OMe), 44.1 (C-1'), 32.0 (C-2'); (+)-HRESIMS m/z 426.0820 [M+H]⁺ (calcd for C₂₁H₂₁⁷⁹BrN₃O₂, 426.0812), m/z 428.0801 [M+H]⁺ (calcd for C₂₁H₂₁⁸¹BrN₃O₂, 428.0794).

### 3.2.36. 6-Bromo-3-(1-(2,5-dimethoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (35)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with 2,5-dimethoxyphenethylamine (0.17 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale white powder (0.088 g, 21%). Rf = 0.71 (CH₂Cl₂/MeOH, 9:1); m.p 133–134 °C; IR (ATR) νmax 2100, 1590, 1497, 1457, 1269, 1219, 795 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.59 (1H, br s, NH-8), 7.65 (1H, d, *J* = 1.0 Hz, H-2), 7.64 (1H, d, *J* = 1.7 Hz, H-9), 7.51 (1H, d, *J* = 2.1 Hz, H-6), 7.42 (1H, d, *J* = 8.5 Hz, H-12), 7.19 (1H, dd, *J* = 8.5, 1.7 Hz, H-11), 6.98 (1H, d, *J* = 1.0 Hz, H-4), 6.79 (1H, d, *J* = 8.8 Hz, H-5'), 6.69 (1H, dd, *J* = 8.8, 3.0 Hz, H-6'), 6.50 (1H, d, *J* = 3.0 Hz, H-8'), 4.14 (2H, t, *J* = 7.7 Hz, H₂-1'), 3.62 (3H, s, 7'-OMe), 3.57 (3H, s, 4'-OMe), 2.78 (2H, t, *J* = 7.7 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 152.8 (C-7'), 151.2 (C-4'), 137.8 (C-2), 136.8 (C-8a), 127.2 (C-4), 126.6 (C-5), 125.5 (C-12a), 125.1 (C-3'), 125.0 (C-7), 122.3 (C-11), 120.6 (C-12), 116.2 (C-8'), 114.3 (C-10), 114.2 (C-9), 112.1 (C-6'), 111.5 (C-5'), 104.1 (C-6), 55.5 (4'-OMe), 55.2 (7'-OMe), 44.2 (C-1'), 31.9 (C-2'); (+)-HRESIMS m/z 448.0622 [M+Na]⁺ (calcd for C₂₁H₂₀⁷⁹BrN₃NaO₂, 448.0631), m/z 450.0613 [M+Na]⁺ (calcd for C₂₁H₂₀⁸¹BrN₃NaO₂, 450.0613).

### 3.2.37. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-1H-indole (36)

Using the general procedure, reaction of 1H-indole-3-carbaldehyde (0.145 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as white crystals (0.075 g, 46%). Rf = 0.51 (CH₂Cl₂/MeOH, 9:1); m.p 195–196 °C; IR (ATR) νmax 2862, 1626, 1500, 1487, 1246, 1117, 819, 799, 737 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.41 (1H, br s, NH-8), 7.59 (1H, d, *J* = 1.0 Hz, H-2), 7.49 (1H, s, H-7), 7.47 (1H, d, *J* = 7.4 Hz, H-12), 7.45 (1H, d, *J* = 7.4 Hz, H-9), 7.17 (1H, ddd, *J* = 7.4, 7.4, 1.0 Hz, H-10), 7.06 (1H, ddd, *J* = 7.4, 7.4, 1.0 Hz, H-4), 6.97 (1H, d, *J* = 1.0 Hz, H-4), 6.73 (1H, d, *J* = 8.1 Hz, H-8'), 6.55 (1H, d, *J* = 1.7 Hz, H-4'), 6.43 (1H, dd, *J* = 8.1, 1.7 Hz, H-9'), 5.93 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.6 Hz, H₂-1'), 2.74 (2H, t, *J* = 7.6 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 147.1 (C-4a'), 145.5 (C-7a'), 137.6 (C-2), 136.0 (C-8a), 131.7 (C-3'), 127.3 (C-4), 126.5 (C-12a), 125.7 (C-5), 124.2 (C-7), 121.7 (C-10), 121.5 (C-9'), 119.5 (C-11), 118.8 (C-12), 111.8 (C-9), 108.8 (C-4'), 108.0 (C-8'), 103.8 (C-6), 100.7 (C-6'), 46.0 (C-1'), 35.9 (C-2'); (+)-HRESIMS m/z 332.1398 [M+H]⁺ (calcd for C₂₀H₁₈N₃O₂, 332.1394)
### 3.2.38. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-5-fluoro-1H-indole (37)

Using the general procedure, reaction of 5-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1%–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a pale yellow powder (0.137 g, 39%). Rf = 0.49 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 3137, 3105, 2834, 2784, 1583, 1502, 1238, 1115, 1033, 940, 807, 789 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.53 (1H, br s, NH-8), 7.62 (1H, s, H-2), 7.56 (1H, d, *J* = 2.6 Hz, H-7), 7.45 (1H, dd, *J* = 8.9, 4.6 Hz, H-9), 7.15 (1H, dd, *J* = 9.8, 2.5 Hz, H-12), 7.00 (1H, ddd, *J* = 9.3, 8.9, 2.5 Hz, H-10), 6.97 (1H, s, H-4), 6.72 (1H, s, *J* = 8.1 Hz, H-8'), 6.54 (1H, d, *J* = 1.3 Hz, H-4'), 6.42 (1H, dd, *J* = 8.1, 1.3 Hz, H-9'), 5.92 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.3 Hz, H₂-1'), 2.75 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.4 (d, ¹J<sub>CF</sub> = 230.6 Hz, C-11), 147.1 (C-4a'), 145.7 (C-7a'), 137.7 (C-2), 132.6 (C-8a), 131.7 (C-3'), 127.4 (C-7), 126.8 (d, ³J<sub>CF</sub> = 10.2 Hz, C-12a), 126.2 (C-4), 125.3 (C-5), 121.5 (C-9'), 112.9 (d, ³J<sub>CF</sub> = 9.5 Hz, C-9), 109.9 (d, ²J<sub>CF</sub> = 26.0 Hz, C-10), 108.8 (C-4'), 108.0 (C-8'), 104.1 (d, ⁴J<sub>CF</sub> = 4.8 Hz, C-6), 103.4 (d, ²J<sub>CF</sub> = 23.5 Hz, H-12), 100.7 (C-6'), 45.9 (C-1'), 35.9 (C-2'); (+)-HRESIMS *m/z* 350.1307 [M+H]⁺ (calcd for C₂₀H₁₇FN₃O₂, 350.1299).

### 3.2.39. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-6-fluoro-1H-indole (38)

Using the general procedure, reaction of 6-fluoro-1H-indole-3-carbaldehyde (0.163 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a pale white powder (0.089 g, 26%). Rf = 0.69 (CH₂Cl₂/MeOH, 9:1); m.p 188–189 °C; IR (ATR) νmax 2785, 1605, 1490, 1445, 1502, 1345, 1248, 806, 796 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.48 (1H, br s, NH-8), 7.61 (1H, s, H-2), 7.49 (1H, d, *J* = 2.5 Hz, H-7), 7.45 (1H, dd, *J* = 8.8, 5.5 Hz, H-12), 7.23 (1H, dd, *J* = 10.0, 2.5 Hz, H-9), 6.98 (1H, d, *J* = 1.1 Hz, H-4), 6.92 (1H, ddd, *J* = 12.2, 8.5, 2.2 Hz, H-11), 6.72 (1H, d, *J* = 7.9 Hz, H-8'), 6.55 (1H, d, *J* = 1.6 Hz, H-4'), 6.42 (1H, dd, *J* = 7.9, 1.6 Hz, H-9'), 5.93 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.2 Hz, H₂-1'), 2.75 (2H, t, *J* = 7.2 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 159.0 (d, ¹J<sub>CF</sub> = 235.3 Hz, C-10), 147.1 (C-4a'), 145.7 (C-7a'), 137.7 (C-2), 135.8 (C-8a), 131.6 (C-3'), 127.3 (C-4), 125.3 (C-5), 124.7 (C-7), 123.3 (C-12a), 121.5 (C-9'), 119.9 (d, ³J<sub>CF</sub> = 10.3 Hz, C-12), 108.8 (C-4'), 108.0 (d, ²J<sub>CF</sub> = 25.2, C-11, C-8'), 104.0 (C-6), 100.6 (C-6'), 97.7 (d, ²J<sub>CF</sub> = 25.2, C-9), 46.0 (C-1'), 35.9 (C-2'); (+)-HRESIMS *m/z* 350.1299 [M+H]⁺ (calcd for C₂₀H₁₇FN₃O₂, 350.1287).

### 3.2.40. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-5-chloro-1H-indole (39)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from EtOAc afforded the title compound as a white powder (0.146 g, 40%). Rf = 0.62 (CH₂Cl₂/MeOH, 9:1); m.p > 200 °C; IR (ATR) νmax 3137, 2784, 1632, 1584, 1509, 1463, 1439, 1239, 1123, 1114, 940, 794 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.62 (1H, br s, NH-8), 7.63 (1H, s, H-2), 7.57 (1H, d, *J* = 2.5 Hz, H-7), 7.47 (1H, d, *J* = 8.5 Hz, H-9), 7.41 (1H, d, *J* = 2.0 Hz, H-12), 7.16 (1H, dd, *J* = 8.5, 2.0 Hz, H-10), 6.98 (1H, s, H-4), 6.71 (1H, d, *J* = 8.0 Hz, H-8'), 6.53 (1H, d, *J* = 1.5 Hz, H-4'), 6.41 (1H, dd, *J* = 8.0, 1.5 Hz, H-9'), 5.92 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.2 Hz, H₂-1'), 2.74 (2H, t, *J* = 7.2 Hz, H₂-2'), ¹³C NMR (100 MHz, DMSO-d₆) δ 147.1 (C-4a'), 145.7 (C-7a'), 137.8 (C-2), 134.4 (C-8a), 131.6 (C-3'), 127.7 (C-12a), 127.5 (C-4), 126.0 (C-7), 124.9 (C-5), 124.2 (C-11), 121.7 (C-9'), 121.4 (C-10), 117.8 (C-12), 113.4 (C-9), 108.9 (C-4'), 108.0 (C-8'), 103.6 (C-6'), 100.6 (C-6'), 45.9 (C-1'), 35.9 (C-2'); (+)-HRESIMS *m/z* 388.0812 [M+Na]⁺ (calcd for C₂₀H₁₆³⁵ClN₃NaO₂, 388.0823), *m/z* 390.0794 [M+Na]⁺ (calcd for C₂₀H₁₆³⁷ClN₃NaO₂, 390.0801).
### 3.2.41. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-6-chloro-1H-indole (40)

Using the general procedure, reaction of 6-chloro-1H-indole-3-carbaldehyde (0.179 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification by trituration from CH₂Cl₂ afforded the title compound as a light brown solid (0.106 g, 29%). Rf = 0.49 (CH₂Cl₂/MeOH, 9:1); m.p 180–181 °C; IR (ATR) νmax 3014, 2900, 1737, 1504, 1487, 1251, 1042, 910, 809 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.55 (1H, br s, NH-8), 7.61 (1H, d, *J* = 0.8 Hz, H-2), 7.54 (1H, d, *J* = 2.6 Hz, H-7), 7.49 (1H, d, *J* = 2.0 Hz, H-9), 7.46 (1H, d, *J* = 8.5 Hz, H-12), 7.07 (1H, dd, *J* = 8.5, 2.0 Hz, H-11), 6.98 (1H, s, H-4), 6.72 (1H, d, *J* = 7.8 Hz, H-8'), 6.54 (1H, d, *J* = 2.0 Hz, H-4'), 6.41 (1H, dd, *J* = 7.8, 2.0 Hz, H-9'), 5.92 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.1 Hz, H₂-1'), 2.74 (2H, t, *J* = 7.1 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 147.1 (C-4a'), 145.7 (C-7a'), 137.8 (C-2), 136.3 (C-8a), 131.6 (C-3'), 127.5 (C-4), 126.4 (C-10), 125.3 (C-12a), 125.2 (C-7), 125.1 (C-5), 121.5 (C-9'), 120.2 (C-12), 119.9 (C-11), 111.3 (C-9), 108.8 (C-4'), 108.0 (C-8'), 104.1 (C-6), 100.7 (C-6'), 46.0 (C-1'), 35.9 (C-2'); (+)-HRESIMS m/z 388.0836 [M+Na]⁺ (calcd for C₂₀H₁₆³⁵ClN₃NaO₂, 388.0823), m/z 390.0820 [M+Na]⁺ (calcd for C₂₀H₁₆³⁷ClN₃NaO₂, 390.0801).

### 3.2.42. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-5-bromo-1H-indole (41)

Using the general procedure, reaction of 5-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a brown solid (0.164 g, 40%). Rf = 0.41 (CH₂Cl₂/MeOH, 9:1); m.p 176–177 °C; IR (ATR) νmax 3150, 2854, 1499, 1456, 1241, 865, 795 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.65 (1H, br s, NH-8), 7.63 (1H, d, *J* = 1.0 Hz, H-2), 7.55 (1H, d, *J* = 1.6 Hz, H-7), 7.55 (1H, d, *J* = 1.6 Hz, H-12), 7.43 (1H, d, *J* = 8.5 Hz, H-9), 7.27 (1H, dd, *J* = 8.5, 1.6 Hz, H-10), 6.98 (1H, d, *J* = 1.0 Hz, H-4), 6.70 (1H, d, *J* = 8.2 Hz, H-8'), 6.53 (1H, d, *J* = 1.6 Hz, H-4'), 6.40 (1H, dd, *J* = 8.2, 1.6 Hz, H-9'), 5.92 (2H, s, H₂-6'), 4.15 (2H, t, *J* = 7.3 Hz, H₂-1'), 2.74 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 147.1 (C-4a'), 145.7 (C-7a'), 137.8 (C-2), 134.7 (C-8a), 131.6 (C-3'), 128.4 (C-12a), 127.5 (C-4), 125.8 (C-7), 124.9 (C-5), 124.2 (C-10), 121.4 (C-9'), 120.8 (C-12), 113.8 (C-9), 112.2 (C-11), 108.8 (C-4'), 108.1 (C-8'), 103.5 (C-6), 100.6 (C-6'), 45.9 (C-1'), 35.9 (C-2'); (+)-HRESIMS m/z 432.0327 [M+Na]⁺ (calcd for C₂₀H₁₆⁷⁹BrN₃NaO₂, 432.0318), m/z 434.0304 [M+Na]⁺ (calcd for C₂₀H₁₆⁸¹BrN₃NaO₂, 434.0300).

### 3.2.43. 3-(1-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1H-imidazol-5-yl)-6-bromo-1H-indole (42)

Using the general procedure, reaction of 6-bromo-1H-indole-3-carbaldehyde (0.224 g, 1.0 mmol) with homopiperonylamine (0.13 mL, 1.0 mmol), K₂CO₃ (0.138 g, 1.0 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.195 g, 1.0 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (1–10% CH₂Cl₂/MeOH, 99:1→9:1) afforded the title compound as a light brown powder (0.230 g, 56%). Rf = 0.62 (CH₂Cl₂/MeOH, 9:1); m.p 194–195 °C; IR (ATR) νmax 2781, 1596, 1504, 1487, 1253, 1110, 1042, 845, 806, 815 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.55 (1H, br s, NH-8), 7.63 (1H, d, *J* = 1.8 Hz, H-9), 7.61 (1H, d, *J* = 1.0 Hz, H-2), 7.52 (1H, d, *J* = 2.6 Hz, H-7), 7.41 (1H, d, *J* = 8.5 Hz, H-12), 7.18 (1H, dd, *J* = 8.5, 1.8 Hz, H-11), 6.97 (1H, d, *J* = 1.0 Hz, H-4), 6.72 (1H, d, *J* = 7.7 Hz, H-8'), 6.54 (1H, d, *J* = 1.5 Hz, H-4'), 6.41 (1H, dd, *J* = 7.7, 1.5 Hz, H-9'), 5.92 (2H, s, H₂-6'), 4.16 (2H, t, *J* = 7.3 Hz, H₂-1'), 2.73 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 147.1 (C-4a'), 145.7 (C-7a'), 137.8 (C-2), 136.8 (C-8a), 131.6 (C-3'), 127.5 (C-4), 125.5 (C-5), 125.1 (C-7), 125.0 (C-12a), 122.4 (C-11), 121.5 (C-9'), 120.6 (C-12), 114.4 (C-10), 114.3 (C-9), 108.8 (C-4'), 108.0 (C-8'), 100.7 (C-6'), 46.0 (C-1'), 35.9 (C-2'); (+)-HRESIMS m/z 432.0311 [M+Na]⁺ (calcd for C₂₀H₁₆⁷⁹BrN₃NaO₂, 432.0318), m/z 434.0287 [M+Na]⁺ (calcd for C₂₀H₁₆⁸¹BrN₃NaO₂, 434.0300).
### 3.2.44. 3-(1-Benzyl-1H-imidazol-5-yl)-4-fluoro-1H-indole (43)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.028 g, 0.172 mmol) with benzylamine (19 µL, 0.172 mmol), K₂CO₃ (0.024 g, 0.172 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.172 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.028 g, 56%). R_f = 0.50 (CH₂Cl₂:MeOH, 9:1); m.p. 177–178 °C; IR (ATR) ν_max 3115, 2932, 2858, 1497, 1227, 1109, 716 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.08 (1H, br s, NH-8), 7.57 (1H, d, *J* = 1.0 Hz, H-2), 7.25–7.18 (4H, m, H-9, 2H-4', H-5'), 7.15 (1H, ddd, *J* = 7.8, 7.8, 4.8 Hz, H-10), 7.14 (1H, br s, H-4), 7.04 (1H, d, *J* = 2.5 Hz, H-7), 7.00–6.96 (2H, m, 2H-3'), 6.82 (1H, ddd, *J* = 11.0, 7.5, 1.0 Hz, H-11), 5.10 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 156.6 (d, ¹J₄F = 247.7 Hz, C-12), 139.0 (d, ³J₄F = 10.2 Hz, C-8a), 138.0 (C-2), 137.0 (C-2'), 129.2 (C-4), 128.8 (2C-4'), 127.9 (C-5'), 127.3 (2C-3'), 126.6 (C-5), 125.3 (C-7), 123.3 (d, ³J₄F = 8.0 Hz, C-10), 116.2 (d, ²J₄F = 18.9 Hz, C-12a), 107.8 (d, ⁴J₄F = 3.8 Hz, C-8a), 105.8 (d, ²J₄F = 19.1 Hz, C-11), 102.8 (C-6), 49.0 (C-1'); (-)-HRESIMS *m/z* 290.1095 [M–H]⁻ (calcd for C₁₈H₁₃FN₃, 290.1099).

### 3.2.45. 3-(1-Benzyl-1H-imidazol-5-yl)-7-fluoro-1H-indole (44)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.028 g, 0.172 mmol) with benzylamine (19 µL, 0.172 mmol), K₂CO₃ (0.024 g, 0.172 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.172 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow solid (0.019 g, 38%). R_f = 0.49 (CH₂Cl₂:MeOH, 9:1); m.p. 179–180 °C; IR (ATR) ν_max 3074, 2917, 2849, 1454, 1234, 1110, 733 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.93 (1H, br s, NH-8), 7.65 (1H, br s, H-2), 7.35 (1H, d, *J* = 7.9 Hz, H-12), 7.31–7.25 (4H, m, H-4, 2H-4', H-5'), 7.07 (1H, ddd, *J* = 7.9, 7.9, 4.9 Hz, H-11), 7.01–6.97 (2H, m, 2H-3'), 6.96 (1H, dd, *J* = 11.0, 7.9 Hz, H-10), 5.13 (2H, s, H₂-1'); ¹³C NMR (125 MHz, CDCl₃) δ 149.7 (d, ¹J₄F = 244.2 Hz, C-9), 138.4 (C-2), 137.2 (C-2'), 131.0 (d, ³J₄F = 4.8 Hz, C-12a), 129.07 (C-4), 129.05 (2C-4'), 128.0 (C-5'), 126.7 (2C-3'), 126.0 (C-5), 124.6 (d, ²J₄F = 13.7 Hz, C-8a), 124.4 (C-7), 121.0 (d, ³J₄F = 5.9 Hz, C-11), 115.4 (d, ⁴J₄F = 3.7 Hz, C-12), 107.7 (d, ²J₄F = 15.8 Hz, C-10), 106.1 (d, ⁴J₄F = 2.5 Hz, C-6), 48.8 (C-1'); (-)-HRESIMS *m/z* 290.1099 [M–H]⁻ (calcd for C₁₈H₁₃FN₃, 290.1099).

### 3.2.46. 3-(1-Benzyl-1H-imidazol-5-yl)-4-chloro-1H-indole (45)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.029 g, 0.162 mmol) with benzylamine (18 µL, 0.162 mmol), K₂CO₃ (0.023 g, 0.162 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.162 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a light brown solid (0.020 g, 40%). R_f(CH₂Cl₂:MeOH, 9:1) 0.40; m.p. 198–199 °C; IR (ATR) ν_max 3110, 2924, 2856, 1486, 1108, 777 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.70 (1H, br s, NH-8), 7.60 (1H, d, *J* = 1.0 Hz, H-2), 7.36–7.31 (1H, m, H-9), 7.24–7.18 (3H, m, 2H-4', H-5'), 7.15–7.10 (2H, m, H-10, H-11), 7.10 (1H, d, *J* = 1.0 Hz, H-4), 7.09 (1H, d, *J* = 2.6 Hz, H-2), 6.96–6.92 (2H, m, 2H-3'), 4.98 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 137.5 (C-8a), 137.4 (C-2), 136.8 (C-2'), 129.8 (C-4), 128.7 (2C-4'), 127.9 (C-5'), 127.6 (2C-3'), 127.5 (C-7), 126.3 (C-5), 125.9 (C-12), 124.8 (C-12a), 123.2 (C-10), 121.3 (C-11), 110.7 (C-9), 103.7 (C-6), 49.3 (C-1'); (-)-HRESIMS *m/z* 306.0809 [M–H]⁻ (calcd for C₁₈H₁₃³⁵ClN₃, 306.0803), *m/z* 308.0782 [M–H]⁻ (calcd for C₁₈H₁₃³⁷ClN₃, 308.0779).

### 3.2.47. 3-(1-Benzyl-1H-imidazol-5-yl)-5-chloro-1H-indole (46)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.029 g, 0.162 mmol) with benzylamine (18 µL, 0.162 mmol), K₂CO₃ (0.023 g, 0.162 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.162 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a light brown solid (0.020 g, 40%). R_f = 0.49 (CH₂Cl₂:MeOH, 9:1); m.p. 78–79 °C; IR (ATR) ν_max 3121, 2923, 2855, 1455, 1109, 800 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.63 (1H, br s, NH-8), 7.65
(1H, d, *J* = 1.0 Hz, H-2), 7.50 (1H, d, *J* = 2.0 Hz, H-12), 7.32 (1H, d, *J* = 8.8 Hz, H-9), 7.31–7.26 (3H, m, 2H-4', H-5'), 7.22 (1H, d, *J* = 1.0 Hz, H-4), 7.19 (1H, dd, *J* = 8.8, 2.0 Hz, H-10), 7.00–6.95 (3H, m, H-7, 2H-3'), 5.11 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 138.4 (C-2), 137.1 (C-2'), 134.4 (C-8a), 129.1 (C-4), 129.0 (2C-4'), 128.5 (C-12a), 128.0 (C-5'), 126.7 (2C-3'), 126.6 (C-11), 125.9 (C-5), 125.1 (C-7), 123.4 (C-10), 119.2 (C-12), 112.5 (C-9), 105.0 (C-6), 48.8 (C-1'); (+)-HRESIMS *m/z* 308.0951 [M+H]⁺ (calcd for C₁₈H₁₅³⁵ClN₃, 308.0949), *m/z* 310.0916 [M+H]⁺ (calcd for C₁₈H₁₅³⁷ClN₃, 310.0925).

### 3.2.48. 3-(1-Benzyl-1H-imidazol-5-yl)-7-chloro-1H-indole (47)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.029 g, 0.162 mmol) with benzylamine (18 µL, 0.162 mmol), K₂CO₃ (0.023 g, 0.162 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.162 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.012 g, 24%). R_f = 0.51 (CH₂Cl₂:MeOH, 9:1); m.p. 179–180 °C; IR (ATR) ν_max 3088, 2919, 2853, 1436, 1111, 736 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.92 (1H, br s, NH-8), 7.65 (1H, d, *J* = 1.0 Hz, H-2), 7.48 (1H, dd, *J* = 8.0, 1.0 Hz, H-12), 7.32–7.22 (5H, m, H-4, H-10, 2H-4', H-5'), 7.09 (1H, dd, *J* = 8.0, 7.4 Hz, H-11), 7.02 (1H, d, *J* = 2.0 Hz, H-7), 7.01–6.97 (2H, m, 2H-3'), 5.12 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 138.4 (C-2), 137.2 (C-2'), 133.4 (C-8a), 129.1 (C-4), 129.0 (2C-4'), 128.8 (C-12a), 128.0 (C-5'), 126.7 (2C-3'), 126.0 (C-5), 124.3 (C-7), 122.3 (C-10), 121.4 (C-11), 118.4 (C-12), 117.0 (C-9), 106.3 (C-6), 48.8 (C-1'); (-)-HRESIMS *m/z* 306.0814 (calcd for C₁₈H₁₃³⁵ClN₃, 306.0803), *m/z* 308.0791 [M–H]⁻ (calcd for C₁₈H₁₃³⁷ClN₃, 308.0779).

### 3.2.49. 3-(1-Benzyl-1H-imidazol-5-yl)-4-bromo-1H-indole (48)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.032 g, 0.142 mmol) with benzylamine (16 µL, 0.142 mmol), K₂CO₃ (0.020 g, 0.142 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.142 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow solid (0.025 g, 50%). R_f = 0.41 (CH₂Cl₂:MeOH, 9:1); m.p. 201–202 °C; IR (ATR) ν_max 3109, 3033, 2926, 2856, 1484, 1108, 775 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.85 (1H, br s, NH-8), 7.61 (1H, d, *J* = 0.9 Hz, H-2), 7.40 (1H, dd, *J* = 7.8, 0.9 Hz, H-9), 7.32 (1H, dd, *J* = 7.8, 0.9 Hz, H-11), 7.24–7.19 (3H, m, 2H-4', H-5'), 7.11–7.09 (2H, m, H-4, H-7), 7.07 (1H, dd, *J* = 7.8, 7.8 Hz, H-10), 6.97–6.93 (2H, m, 2H-3'), 4.95 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 137.3 (C-2), 137.2 (C-8a), 136.7 (C-2'), 130.4 (C-4), 128.7 (2C-4'), 127.90 (C-7/C-5'), 127.86 (C-7/C-5'), 127.6 (2C-3'), 126.3 (C-12a), 125.7 (C-5), 124.7 (C-11), 123.5 (C-10), 113.8 (C-12), 111.3 (C-9), 104.5 (C-6), 49.4 (C-1'); (-)-HRESIMS *m/z* 350.0304 [M–H]⁻ (calcd for C₁₈H₁₃⁷BrN₃, 350.0298), *m/z* 352.0289 [M–H]⁻ (calcd for C₁₈H₁₃⁸BrN₃, 352.0279).

### 3.2.50. 3-(1-Benzyl-1H-imidazol-5-yl)-5-methoxy-1H-indole (49)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.029 g, 0.165 mmol) with benzylamine (18 µL, 0.165 mmol), K₂CO₃ (0.022 g, 0.165 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.165 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.008 g, 16%). R_f(CH₂Cl₂:MeOH, 9:1) 0.50; m.p. 65–66 °C; IR (ATR) ν_max 3124, 2956, 2930, 2859, 1482, 1115, 765 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.43 (1H, br s, NH-8), 7.65 (1H, br s, H-2), 7.32–7.22 (5H, m, H-4, H-9, 2H-4', H-5'), 7.01 (2H, dd, *J* = 7.9, 1.5 Hz, 2H-3'), 6.96 (2H, d, *J* = 2.4 Hz, H-7, H-12), 6.89 (1H, dd, *J* = 8.8, 2.4 Hz, H-10), 5.12 (2H, s, H₂-1'), 3.75 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 155.0 (C-11), 138.2 (C-2), 137.4 (C-2'), 131.0 (C-8a), 129.0 (2C-4'), 128.7 (C-4, C-12a), 127.9 (C-5'), 126.7 (C-5, 2C-3'), 124.5 (C-7), 113.6 (C-10), 112.3 (C-9), 105.0 (C-6), 100.9 (C-12), 55.9 (OMe), 48.7 (C-1'); (-)-HRESIMS *m/z* 302.1293 [M–H]⁻ (calcd for C₁₉H₁₆N₃O, 302.1299).
### 3.2.51. 3-(1-Benzyl-1H-imidazol-5-yl)-6-methoxy-1H-indole (50)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.029 g, 0.165 mmol) with benzylamine (18 µL, 0.165 mmol), K₂CO₃ (0.022 g, 0.165 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.165 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.010 g, 20%). R_f = 0.49 (CH₂Cl₂:MeOH, 9:1); m.p. 66–67 °C; IR (ATR) ν_max 3122, 2960, 2930, 2861, 1454, 1111, 764 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (1H, br s, NH-8), 7.62 (1H, br s, H-2), 7.46 (1H, d, *J* = 8.8 Hz, H-12), 7.32–7.22 (4H, m, H-4, 2H-4', H-5'), 7.00 (2H, dd, *J* = 8.3, 1.9 Hz, 2H-3'), 6.88 (1H, d, *J* = 2.4 Hz, H-9), 6.87 (1H, d, *J* = 2.5 Hz, H-7), 6.83 (1H, dd, *J* = 8.8, 2.4 Hz, H-11), 5.14 (2H, s, H₂-1'), 3.85 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 157.1 (C-10), 138.1 (C-2), 137.3 (C-2'), 136.8 (C-8a), 129.0 (2C-4'), 128.5 (C-4), 127.9 (C-5'), 126.8 (C-5), 126.7 (2C-3'), 122.4 (C-7), 121.6 (C-12a), 120.3 (C-12), 110.7 (C-11), 105.2 (C-6), 94.8 (C-9), 55.8 (OMe), 48.8 (C-1'); (-)-HRESIMS *m/z* 302.1304 [M–H]⁻ (calcd for C₁₉H₁₆N₃O, 302.1299).

### 3.2.52. 4-Fluoro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (51)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.027 g, 0.164 mmol) was reacted with phenethylamine (21 µL, 0.164 mmol), K₂CO₃ (0.023 g, 0.164 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.164 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.049 g, 98%). R_f = 0.47 (CH₂Cl₂:MeOH, 9:1); m.p. 181–182 °C; IR (ATR) ν_max 3115, 2930, 2855, 1495, 1226, 736 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.43 (1H, br s, NH-8), 7.45 (1H, d, *J* = 1.0 Hz, H-2), 7.23 (1H, d, *J* = 8.0 Hz, H-9), 7.21–7.15 (3H, m, 2H-5', H-6'), 7.15 (1H, ddd, *J* = 8.0, 8.0, 5.0 Hz, H-10), 7.06 (1H, d, *J* = 1.0 Hz, H-4), 7.03 (1H, s, H-7), 6.90–6.86 (2H, m, 2H-4'), 6.81 (1H, ddd, *J* = 11.0, 8.0, 0.9 Hz, H-11), 4.15 (2H, t, *J* = 7.2 Hz, H₂-1'), 2.86 (2H, t, *J* = 7.2 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 156.6 (d, ¹J₄F = 248.2 Hz, C-12), 139.1 (d, ³J₄F = 10.6 Hz, C-8a), 137.9 (C-3'), 137.6 (C-2), 129.0 (C-4), 128.8 (2C-4'), 128.7 (2C-5'), 126.8 (C-6'), 126.1 (C-5), 125.3 (C-7), 123.2 (d, ³J₄F = 8.4 Hz, C-10), 116.2 (d, ²J₄F = 19.8 Hz, C-12a), 108.0 (d, ⁴J₄F = 3.7 Hz, C-9), 105.7 (d, ²J₄F = 19.2 Hz, C-11), 102.6 (C-6), 46.8 (C-1'), 37.3 (C-2'); (-)-HRESIMS *m/z* 304.1262 [M–H]⁻ (calcd for C₁₉H₁₅FN₃, 304.1255).

### 3.2.53. 7-Fluoro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (52)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.027 g, 0.164 mmol) was reacted with phenethylamine (21 µL, 0.164 mmol), K₂CO₃ (0.023 g, 0.164 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.164 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a light brown solid (0.031 g, 62%). R_f = 0.47 (CH₂Cl₂:MeOH, 9:1); m.p. 45–46 °C; IR (ATR) ν_max 3122, 2930, 2859, 1454, 1233, 783 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.57 (1H, br s, NH-8), 7.49 (1H, d, *J* = 1.0 Hz, H-2), 7.30 (1H, d, *J* = 8.0 Hz, H-12), 7.23–7.16 (3H, m, 2H-5', H-6'), 7.15 (1H, d, *J* = 1.0 Hz, H-4), 7.08 (1H, s, H-7), 7.07 (1H, ddd, *J* = 8.0, 8.0, 4.6 Hz, H-11), 6.97 (1H, ddd, *J* = 11.0, 8.0, 1.0 Hz, H-10), 6.91–6.87 (2H, m, 2H-4'), 4.15 (2H, t, *J* = 7.0 Hz, H₂-1'), 2.87 (2H, t, *J* = 7.0 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 149.8 (d, ¹J₄F = 244.9 Hz, C-9), 137.8 (C-2), 137.6 (C-3'), 131.0 (d, ³J₄F = 5.3 Hz, C-12a), 129.0 (C-4), 128.8 (2C-5'), 128.7 (2C-4'), 127.0 (C-6'), 125.5 (C-5), 124.71 (d, ²J₄F = 14.0 Hz, C-8a), 124.70 (C-7), 120.8 (d, ³J₄F = 6.0 Hz, C-11), 115.4 (d, ⁴J₄F = 3.2 Hz, C-12), 107.6 (d, ²J₄F = 16.2 Hz, C-10), 106.0 (d, ⁴J₄F = 2.9 Hz, C-6), 46.9 (C-1'), 37.6 (C-2'); (-)-HRESIMS *m/z* 304.1259 [M–H]⁻ (calcd for C₁₉H₁₅FN₃, 304.1255).

### 3.2.54. 4-Chloro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (53)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.028 g, 0.155 mmol) was reacted with phenethylamine (20 µL, 0.155 mmol), K₂CO₃ (0.022 g, 0.155 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.155 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound
as a light brown solid (0.034 g, 68%). R<sub>f</sub> = 0.46 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 73–74 °C; IR (ATR) ν<sub>max</sub> 3105, 2922, 2858, 1490, 1193, 741 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.99 (1H, br s, NH-8), 7.49 (1H, d, *J* = 1.0 Hz, H-2), 7.36 (1H, dd, *J* = 7.5, 1.5 Hz, H-8), 7.22–7.16 (3H, m, 2H-5', H-6'), 7.14 (1H, dd, *J* = 7.5, 7.4 Hz, H-10), 7.10 (1H, dd, *J* = 7.4, 1.5 Hz, H-11), 7.05 (1H, d, *J* = 1.0 Hz, H-4), 7.03 (1H, d, *J* = 2.1 Hz, H-7), 6.88–6.84 (2H, m, 2H-4'), 4.07 (2H, t, *J* = 7.2 Hz, H<sub>2</sub>-1'), 2.85 (2H, t, *J* = 7.2 Hz, H<sub>2</sub>-2'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 138.0 (C-3'), 137.6 (C-8a), 137.1 (C-2), 129.7 (C-4), 128.8 (2C-5'), 128.7 (2C-4'), 127.3 (C-7), 126.8 (C-6'), 125.9 (C-5, C-12), 124.8 (C-12a), 123.1 (C-10), 121.2 (C-11), 110.7 (C-9), 103.8 (C-6), 46.9 (C-1'), 37.3 (C-2'); (-)-HRESIMS *m/z* 320.0954 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>35</sup>ClN<sub>3</sub>, 320.0960), *m/z* 322.0931 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>37</sup>ClN<sub>3</sub>, 322.0936).

### 3.2.55. 7-Chloro-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (54)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.028 g, 0.155 mmol) was reacted with phenethylamine (20 µL, 0.155 mmol), K<sub>2</sub>CO<sub>3</sub> (0.022 g, 0.155 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.155 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a light brown solid (0.023 g, 46%). R<sub>f</sub> = 0.51 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 47–48 °C; IR (ATR) ν<sub>max</sub> 3102, 2923, 2853, 1494, 1110, 738 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.43 (1H, br s, NH-8), 7.48 (1H, d, *J* = 1.0 Hz, H-2), 7.43 (1H, dd, *J* = 8.0, 1.0 Hz, H-12), 7.26 (1H, d, *J* = 7.6 Hz, H-10), 7.23–7.16 (3H, m, 2H-5', H-6'), 7.14 (1H, d, *J* = 1.0 Hz, H-4), 7.10 (1H, s, H-7), 7.10 (1H, dd, *J* = 8.0, 7.6 Hz, H-11), 6.90–6.86 (2H, m, 2H-4'), 4.14 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-1'), 2.86 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-2'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 137.8 (C-2), 137.6 (C-3'), 133.5 (C-8a), 129.1 (C-4), 128.9 (C-12a), 128.8 (2C-5'), 128.7 (2C-4'), 127.0 (C-6'), 125.4 (C-5), 124.6 (C-7), 122.2 (C-10), 121.4 (C-11), 118.3 (C-12), 117.1 (C-9), 106.3 (C-6), 46.8 (C-1'), 37.6 (C-2'); (-)-HRESIMS *m/z* 320.0959 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>35</sup>ClN<sub>3</sub>, 320.0960), *m/z* 322.0936 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>37</sup>ClN<sub>3</sub>, 322.0936).

### 3.2.56. 4-Bromo-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (55)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.031 g, 0.136 mmol) with phenethylamine (17 µL, 0.136 mmol), K<sub>2</sub>CO<sub>3</sub> (0.019 g, 0.136 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.027 g, 0.136 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.039 g, 78%). R<sub>f</sub> = 0.46 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 204–205 °C; IR (ATR) ν<sub>max</sub> 3109, 2919, 2848, 1490, 1110, 743 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.29 (1H, br s, NH-8), 7.52 (1H, d, *J* = 1.0 Hz, H-2), 7.40 (1H, dd, *J* = 8.0, 1.0 Hz, H-9), 7.30 (1H, dd, *J* = 7.6, 1.0 Hz, H-11), 7.23–7.16 (3H, m, 2H-5', H-6'), 7.08 (1H, dd, *J* = 8.0, 7.6 Hz, H-10), 7.03 (1H, d, *J* = 1.0 Hz, H-4), 7.00 (1H, d, *J* = 2.5 Hz, H-7), 6.88–6.84 (2H, m, 2H-4'), 4.02 (2H, t, *J* = 7.0 Hz, H<sub>2</sub>-1'), 2.87 (2H, t, *J* = 7.0 Hz, H<sub>2</sub>-2'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 138.1 (C-3'), 137.1 (C-8a), 137.0 (C-2), 130.3 (C-4), 128.8 (2C-5'), 128.7 (2C-4'), 127.4 (C-7), 126.8 (C-6'), 126.2 (C-12a), 125.1 (C-5), 124.8 (C-11), 123.6 (C-10), 113.9 (C-12), 111.1 (C-9), 105.0 (C-6), 46.9 (C-1'), 37.4 (C-2'); (-)-HRESIMS *m/z* 364.0452 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>79</sup>BrN<sub>3</sub>, 364.0455), *m/z* 366.0436 [M–H]<sup>−</sup> (calcd for C<sub>19</sub>H<sub>15</sub><sup>81</sup>BrN<sub>3</sub>, 366.0436).

### 3.2.57. 5-Methoxy-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (56)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.028 g, 0.157 mmol) with phenethylamine (20 µL, 0.157 mmol), K<sub>2</sub>CO<sub>3</sub> (0.023 g, 0.157 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.031 g, 0.157 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.014 g, 28%). R<sub>f</sub> = 0.49 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 51–52 °C; IR (ATR) ν<sub>max</sub> 3181, 2933, 2833, 1480, 1247, 812 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 8.57 (1H, br s, NH-8), 7.46 (1H, d, *J* = 1.0 Hz, H-2), 7.33 (1H, d, *J* = 8.6 Hz, H-9), 7.24–7.17 (3H, m, 2H-5', H-6'), 7.14 (1H, br s, H-4), 7.04 (1H, d, *J* = 2.5 Hz, H-7), 6.97 (1H, d, *J* = 2.5 Hz, H-12), 6.92 (1H, dd, *J* = 8.6, 2.5 Hz, H-10), 6.91–6.89 (2H, m, 2H-4'), 4.15 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-1'), 3.81 (3H, s, OMe), 2.88 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-2'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 155.0 (C-11), 137.74 (C-3'), 137.69 (C-2),
131.1 (C-8a), 128.9 (C-4), 128.79 (2C-5'), 128.76 (2C-4'), 128.0 (C-12a), 126.9 (C-6'), 126.0 (C-5), 124.4 (C-7), 113.5 (C-10), 112.3 (C-9), 105.2 (C-6), 101.0 (C-12), 56.0 (OMe), 46.8 (C-1'), 37.7 (C-2'); (-)-HRESIMS *m/z* 316.1452 [M−H]⁻ (calcd for C₂₀H₁₈N₃O, 316.1455).

### 3.2.58. 6-Methoxy-3-(1-phenethyl-1H-imidazol-5-yl)-1H-indole (57)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.028 g, 0.157 mmol) with phenethylamine (20 µL, 0.157 mmol), K₂CO₃ (0.023 g, 0.157 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.031 g, 0.157 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.015 g, 30%). Rf = 0.49 (CH₂Cl₂:MeOH, 9:1); m.p. 48–49 °C; IR (ATR) νmax 3209, 2918, 2835, 1513, 1247, 812 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (1H, br s, NH-8), 7.44 (1H, d, *J* = 1.0 Hz, H-2), 7.41 (1H, d, *J* = 8.7 Hz, H-12), 7.24–7.17 (3H, m, 2H-5', H-6'), 7.12 (1H, d, *J* = 1.0 Hz, H-4), 6.98 (1H, d, *J* = 2.5 Hz, H-7), 6.92 (1H, d, *J* = 2.5 Hz, H-9), 6.92–6.89 (2H, m, 2H-4'), 6.84 (1H, dd, *J* = 8.7, 2.5 Hz, H-11), 4.15 (2H, t, *J* = 7.0 Hz, H₂-1'), 3.86 (3H, s, OMe), 2.87 (2H, t, *J* = 7.0 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 157.1 (C-10), 137.7 (C-3'), 137.6 (C-2), 136.9 (C-8a), 128.82 (C-4), 128.77 (2C-4', 2C-5'), 126.9 (C-6'), 126.1 (C-5), 122.5 (C-7), 121.7 (C-12a), 120.3 (C-12), 110.7 (C-11), 105.4 (C-6), 94.9 (C-9), 55.8 (OMe), 46.9 (C-1'), 37.6 (C-2'); (-)-HRESIMS *m/z* 316.1448 [M−H]⁻ (calcd for C₂₀H₁₈N₃O, 316.1455).

### 3.2.59. 5-Chloro-3-(1-(3-phenylpropyl)-1H-imidazol-5-yl)-1H-indole (58)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with phenylpropylamine (0.040 mL, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a white oil (0.012 g, 13%). Rf = 0.08 (EtOAc); IR (ATR) νmax 3027, 2929, 1603, 1456, 1226, 1110, 922, 889, 800, 750 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.59 (1H, s, NH-8), 7.79 (1H, s, H-2), 7.55 (1H, d, *J* = 8.5 Hz, H-7), 7.47 (1H, d, *J* = 8.5 Hz, H-9), 7.43 (1H, d, *J* = 2.1 Hz, H-12), 7.19–7.09 (4H, m, H-10, 2H-6', H-7'), 7.02–7.00 (3H, m, H-4, 2H-5'), 3.97 (2H, t, *J* = 7.5 Hz, H₂-1'), 2.43 (2H, t, *J* = 7.5 Hz, H₂-3'), 1.84 (2H, tt, *J* = 7.5, 7.5 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 140.8 (C-4'), 137.9 (C-2), 134.5 (C-8a), 128.2 (2C-6'), 128.0 (2C-5'), 127.8 (C-12a), 127.6 (C-4), 126.1 (C-7), 125.8 (C-5, C-7'), 124.3 (C-11), 121.7 (C-10), 117.8 (C-12), 113.4 (C-9), 103.6 (C-6), 44.1 (C-1'), 31.9 (C-3'), 31.7 (C-2'); (+)-HRESIMS *m/z* 336.1261 [M+H]⁺ (calcd for C₂₀H₁₉ClN₃, 336.1262).

### 3.2.60. 4-Fluoro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (59)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.025 g, 0.156 mmol) with *p*-methoxybenzylamine (20 µL, 0.156 mmol), K₂CO₃ (0.022 g, 0.156 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.156 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.036 g, 72%). Rf = 0.51 (CH₂Cl₂:MeOH, 9:1); m.p. 66–67 °C; IR (ATR) νmax 3120, 2930, 2841, 1513, 1250, 736 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.40 (1H, br s, NH-8), 7.55 (1H, d, *J* = 1.0 Hz, H-2), 7.22 (1H, d, *J* = 8.0 Hz, H-9), 7.14 (1H, ddd, *J* = 8.0, 7.4, 4.5 Hz, H-10), 7.12 (1H, br s, H-4), 7.06 (1H, d, *J* = 2.5 Hz, H-7), 6.95–6.90 (2H, m, 2H-3'), 6.81 (1H, ddd, *J* = 10.9, 7.4, 1.0 Hz, H-11), 6.79–6.74 (2H, m, 2H-4'), 5.00 (2H, s, H₂-1'), 3.75 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.3 (C-5'), 156.6 (d, ¹JCF = 247.6 Hz, C-12), 139.1 (d, ²JCF = 10.7 Hz, C-8a), 137.7 (C-2), 128.9 (2C-3'), 128.72 (C-2'), 128.70 (C-4), 126.6 (C-5), 125.4 (C-7), 123.3 (d, ³JCF = 8.0 Hz, C-10), 116.2 (d, ²JCF = 19.0 Hz, C-12a), 114.2 (2C-4'), 108.0 (d, ⁴JCF = 3.8 Hz, C-9), 105.7 (d, ²JCF = 19.5 Hz, C-11), 102.5 (C-6), 55.4 (OMe), 48.6 (C-1'); (-)-HRESIMS *m/z* 320.1210 [M−H]⁻ (calcd for C₁₉H₁₅FN₃O, 320.1205).

### 3.2.61. 7-Fluoro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (60)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.025 g, 0.156 mmol) with *p*-methoxybenzylamine (20 µL, 0.156 mmol), K₂CO₃ (0.022 g, 0.156 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.156 mmol) followed by purification
using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.018 g, 36%). R_f = 0.56 (CH₂Cl₂:MeOH, 9:1); m.p. 179–180 °C; IR (ATR) ν_max 3122, 2918, 2851, 1514, 1250, 785 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.68 (1H, br s, NH-8), 7.64 (1H, d, *J* = 1.0 Hz, H-2), 7.33 (1H, d, *J* = 8.0 Hz, H-12), 7.23 (1H, d, *J* = 1.0 Hz, H-4), 7.07 (1H, ddd, *J* = 8.0, 8.0, 5.0 Hz, H-11), 7.03 (1H, d, *J* = 2.5 Hz, H-7), 6.96 (1H, ddd, *J* = 10.9, 8.0, 1.0 Hz, H-10), 6.94–6.90 (2H, m, 2H-3'), 6.83–6.78 (2H, m, 2H-4'), 5.05 (2H, s, H₂-1'), 3.77 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.4 (C-5'), 149.7 (d, ¹J₄F = 244.6 Hz, C-10), 138.1 (C-2), 130.9 (d, ²J₄F = 5.3 Hz, C-8a), 128.9 (C-9), 128.8 (C-4), 128.2 (2C-3'), 126.0 (C-5), 124.6 (d, ²J₄F = 13.7 Hz, C-12a), 124.5 (C-7), 121.0 (d, ³J₄F = 6.3 Hz, C-11), 115.5 (d, ⁴J₄F = 3.5 Hz, C-12), 114.4 (2C-4'), 107.7 (d, ²J₄F = 15.9 Hz, C-10), 106.1 (d, ⁴J₄F = 2.5 Hz, C-6), 55.4 (OMe), 48.5 (C-1'); (-)-HRESIMS *m/z* 320.1205 [M–H]⁻ (calcd for C₁₉H₁₅FN₃O, 320.1205).

### 3.2.62. 4-Chloro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (61)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.027 g, 0.148 mmol) with *p*-methoxybenzylamine (19 µL, 0.148 mmol), K₂CO₃ (0.020 g, 0.148 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.148 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.034 g, 68%). R_f = 0.57 (CH₂Cl₂:MeOH, 9:1); m.p. 74–75 °C; IR (ATR) ν_max 3115, 2925, 2838, 1514, 1251, 740 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.93 (1H, br s, NH-8), 7.56 (1H, d, *J* = 1.0 Hz, H-2), 7.38–7.35 (1H, m, H-9), 7.14–7.10 (3H, m, H-7, H-10, H-11), 7.09 (1H, d, *J* = 1.0 Hz, H-4), 6.91–6.87 (2H, m, 2H-3'), 6.77–6.72 (2H, m, 2H-4'), 4.89 (2H, s, H₂-1'), 3.74 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.3 (C-5'), 137.6 (C-8a), 137.1 (C-2), 129.4 (C-4), 129.2 (2C-3'), 128.5 (C-2'), 127.5 (C-7), 126.3 (C-5), 125.8 (C-12), 124.8 (C-12a), 123.1 (C-10), 121.2 (C-11), 114.1 (2C-4'), 110.8 (C-9), 103.6 (C-6), 55.4 (OMe), 48.9 (C-1'); (-)-HRESIMS *m/z* 336.0899 [M–H]⁻ (calcd for C₁₉H₁₅₃⁵ClN₃O, 336.0909), *m/z* 338.0879 [M–H]⁻ (calcd for C₁₉H₁₅₃⁷ClN₃O, 338.0886).

### 3.2.63. 7-Chloro-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (62)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.027 g, 0.148 mmol) with *p*-methoxybenzylamine (19 µL, 0.148 mmol), K₂CO₃ (0.020 g, 0.148 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.148 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a white solid (0.011 g, 22%). R_f = 0.56 (CH₂Cl₂:MeOH, 9:1); m.p. 220–221 °C; IR (ATR) ν_max 2920, 2853, 1514, 1250, 1116, 743 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (1H, br s, NH-8), 7.64 (1H, br s, H-2), 7.48 (1H, d, *J* = 8.0 Hz, H-12), 7.26 (1H, dd, *J* = 7.8, 0.9 Hz, H-10), 7.23 (1H, d, *J* = 1.0 Hz, H-4), 7.10 (1H, dd, *J* = 8.0, 7.8 Hz, H-11), 7.05 (1H, d, *J* = 2.5 Hz, H-2), 6.95–6.90 (2H, m, 2H-3'), 6.84–6.79 (2H, m, 2H-4'), 5.05 (2H, s, H₂-1'), 3.78 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.4 (C-5'), 138.3 (C-2), 133.4 (C-8a), 129.2 (C-4), 129.0 (C-12a/C-2'), 128.8 (C-12a/C-2'), 128.2 (2C-3'), 125.8 (C-5), 124.3 (C-7), 122.3 (C-10), 121.5 (C-11), 118.5 (C-12), 117.0 (C-9), 114.4 (2C-4'), 106.6 (C-6), 55.4 (OMe), 48.4 (C-1'); (-)-HRESIMS *m/z* 336.0904 [M–H]⁻ (calcd for C₁₉H₁₅₃⁵ClN₃O, 336.0909), *m/z* 338.0876 [M–H]⁻ (calcd for C₁₉H₁₅₃⁷ClN₃O, 338.0886).

### 3.2.64. 4-Bromo-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (63)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.029 g, 0.131 mmol) with *p*-methoxybenzylamine (17 µL, 0.131 mmol), K₂CO₃ (0.018 g, 0.131 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.026 g, 0.131 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.023 g, 46%). R_f = 0.50 (CH₂Cl₂:MeOH, 9:1); m.p. 92–93 °C; IR (ATR) ν_max 3128, 2920, 2853, 1514, 1250, 1176, 740 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.74 (1H, br s, NH-8), 7.59 (1H, d, *J* = 1.0 Hz, H-2), 7.42 (1H, dd, *J* = 8.0, 1.0 Hz, H-9), 7.32 (1H, dd, *J* = 7.6, 1.0 Hz, H-11), 7.13 (1H, d, *J* = 2.5 Hz, H-7), 7.08 (1H, d, *J* = 1.0 Hz, H-4), 7.07 (1H, dd, *J* = 8.0, 7.6 Hz, H-10), 6.93–6.87 (2H, m, 2H-3'), 6.77–6.73 (2H, m, 2H-4'), 4.86 (1H, dd, *J* = 7.6, 1.0 Hz, H-11), 7.13 (1H, d, *J* = 2.5 Hz, H-7), 7.08 (1H, d, *J* = 1.0 Hz, H-4), 7.07 (1H, dd, *J* = 8.0, 7.6 Hz, H-10), 6.93–6.87 (2H, m, 2H-3'), 6.77–6.73 (2H, m, 2H-4'), 4.86 (1H, dd, *J* = 7.6, 1.0 Hz, H-11), 7.13 (1H, d, *J* = 2.5 Hz, H-7), 7.08 (1H, d, *J* = 1.0 Hz, H-4),
(2H, s, H₂-1'), 3.75 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.4 (C-5'), 137.2 (C-8a), 137.0 (C-2), 129.9 (C-4), 129.3 (2C-3'), 128.4 (C-2'), 127.8 (C-7), 126.2 (C-12a), 125.7 (C-5), 124.7 (C-11), 123.5 (C-10), 114.1 (2C-4'), 113.8 (C-12), 111.3 (C-9), 104.4 (C-6), 55.4 (OMe), 49.1 (C-1'); (-)-HRESIMS *m/z* 380.0408 [M-H]⁻ (calcd for C₁₉H₁₅⁷⁹BrN₃O, 380.0404), *m/z* 382.0389 [M-H]⁻ (calcd for C₁₉H₁₅⁸¹BrN₃O, 382.0385).

### 3.2.65. 5-Methoxy-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (64)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.026 g, 0.150 mmol) with *p*-methoxybenzylamine (20 µL, 0.150 mmol), K₂CO₃ (0.021 g, 0.150 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.150 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.009 g, 18%). R_f = 0.54 (CH₂Cl₂:MeOH, 9:1); m.p. 67–68 °C; IR (ATR) ν_max 3316, 2929, 2838, 1250, 809 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.44 (1H, br s, NH-8), 7.62 (1H, d, *J* = 1.0 Hz, H-2), 7.30 (1H, d, *J* = 8.7 Hz, H-9), 7.22 (1H, d, *J* = 1.0 Hz, H-4), 7.00 (1H, d, *J* = 2.5 Hz, H-7), 6.96 (1H, d, *J* = 2.5 Hz, H-12), 6.95–6.91 (2H, m, 2H-3'), 6.90 (1H, dd, *J* = 8.7, 2.5 Hz, H-10), 6.83–6.78 (2H, m, 2H-4'), 5.04 (2H, s, H₂-1'), 3.77 (6H, s, 11-OMe, 5'-OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.3 (C-5'), 155.0 (C-11), 138.0 (C-2), 131.0 (C-8a), 129.2 (C-2'), 128.6 (C-4), 128.3 (2C-3'), 127.9 (C-12a), 126.6 (C-5), 124.6 (C-7), 114.4 (2C-4'), 113.5 (C-10), 112.3 (C-9), 105.0 (C-6), 100.9 (C-12), 55.9 (11-OMe), 55.4 (5'-OMe), 48.3 (C-1'); (-)-HRESIMS *m/z* 332.1398 [M-H]⁻ (calcd for C₂₀H₁₈N₃O₂, 332.1405).

### 3.2.66. 6-Methoxy-3-(1-(4-methoxybenzyl)-1H-imidazol-5-yl)-1H-indole (65)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.026 g, 0.150 mmol) with *p*-methoxybenzylamine (20 µL, 0.150 mmol), K₂CO₃ (0.021 g, 0.150 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.150 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.008 g, 16%). R_f = 0.54 (CH₂Cl₂:MeOH, 9:1); m.p. 65–66 °C; IR (ATR) ν_max 3332, 2917, 2848, 1612, 1250, 816 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.41 (1H, br s, NH-8), 7.59 (1H, d, *J* = 1.0 Hz, H-2), 7.45 (1H, d, *J* = 8.8 Hz, H-12), 7.21 (1H, d, *J* = 1.0 Hz, H-4), 6.96–6.91 (2H, m, 2H-3'), 6.91 (1H, d, *J* = 2.5 Hz, H-7), 6.89 (1H, d, *J* = 2.2 Hz, H-9), 6.83 (1H, dd, *J* = 8.8, 2.2 Hz, H-11), 6.82–6.78 (2H, m, 2H-4'), 5.05 (2H, s, H₂-1'), 3.85 (3H, s, 10-OMe), 3.77 (3H, s, 5'-OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.3 (C-5'), 157.1 (C-10), 137.9 (C-2), 136.9 (C-8a), 129.1 (C-2'), 128.33 (C-4), 128.29 (2C-3'), 126.7 (C-5), 122.5 (C-7), 121.6 (C-12a), 120.4 (C-12), 114.4 (2C-4'), 110.7 (C-11), 105.2 (C-6), 94.9 (C-9), 55.8 (10-OMe), 55.4 (5'-OMe), 48.4 (C-1'); (-)-HRESIMS *m/z* 332.1400 [M-H]⁻ (calcd for C₂₀H₁₈N₃O₂, 332.1405).

### 3.2.67. 4-Fluoro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (66)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.024 g, 0.149 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.028 g, 0.149 mmol), K₂CO₃ (0.020 g, 0.149 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.149 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.047 g, 94%). R_f = 0.39 (CH₂Cl₂:MeOH, 9:1); m.p. 56–57 °C; IR (ATR) ν_max 3116, 2929, 2851, 1512, 1247, 781 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 10.23 (1H, br s, NH-8), 7.43 (1H, d, *J* = 1.0 Hz, H-2), 7.23 (1H, d, *J* = 8.0 Hz, H-9), 7.14 (1H, ddd, *J* = 8.0, 8.0, 5.0 Hz, H-10), 7.08 (1H, br s, H-4), 7.08 (1H, d, *J* = 2.5 Hz, H-7), 6.81–6.76 (2H, m, 2H-4'), 6.79 (1H, dd, *J* = 10.8, 8.0 Hz, H-11), 6.74–6.69 (2H, m, 2H-5'), 4.12 (2H, t, *J* = 7.0 Hz, H₂-1'), 3.72 (3H, s, OMe), 2.79 (2H, t, *J* = 7.0 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 158.5 (C-6'), 156.5 (d, ¹J₄F = 247.0 Hz, C-12), 139.4 (d, ³J₄F = 11.0 Hz, C-8a), 137.5 (C-2), 129.9 (C-3'), 129.7 (2C-4'), 128.8 (C-4), 126.4 (C-5), 125.5 (C-7), 123.0 (d, ³J₄F = 7.9 Hz, C-10), 116.1 (d, ²J₄F = 18.8 Hz, C-12a), 114.1 (2C-5'), 108.1 (d, ⁴J₄F = 3.8 Hz, C-9), 105.5 (d, ²J₄F = 19.2 Hz, C-11), 102.2 (C-6), 55.3 (OMe), 47.0 (C-1'), 36.3 (C-2'); (-)-HRESIMS *m/z* 334.1360 [M-H]⁻ (calcd for C₂₀H₁₇FN₃O, 334.1361).
### 3.2.68. 7-Fluoro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (67)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.024 g, 0.149 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.028 g, 0.149 mmol), $K_2CO_3$ (0.020 g, 0.149 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.149 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.009 g, 18%). $R_f = 0.43$ ($CH_2Cl_2$:MeOH, 9:1); m.p. 175–176 °C; IR (ATR) $ν_{max}$ 3121, 2927, 2852, 1513, 1236, 784 cm$^{-1}$; $^1$H NMR (400 MHz, $CDCl_3$) $δ$ 8.87 (1H, br s, NH-8), 7.48 (1H, br s, H-2), 7.29 (1H, d, $J = 8.0$ Hz, H-12), 7.13 (1H, br s, H-4), 7.09 (1H, d, $J = 2.5$ Hz, H-7), 7.07 (1H, ddd, $J = 8.0, 8.0, 4.8$ Hz, H-11), 6.98 (1H, ddd, $J = 11.2, 8.0, 1.0$ Hz, H-10), 6.82–6.77 (2H, m, 2H-4'), 6.76–6.71 (2H, m, 2H-5'), 4.11 (2H, t, $J = 7.2$ Hz, H-2-1'), 3.75 (3H, s, OMe), 2.81 (2H, t, $J = 7.2$ Hz, H-2-2'); $^{13}$C NMR (100 MHz, $CDCl_3$) $δ$ 158.6 (C-6'), 149.7 (d, $^1J_{CF} = 245.1$ Hz, C-9), 137.9 (C-2), 131.0 (d, $^3J_{CF} = 5.3$ Hz, C-12a), 129.7 (2C-4'), 129.6 (C-3'), 129.1 (C-4), 125.3 (C-5), 124.6 (d, $^2J_{CF} = 14.2$ Hz, C-8a), 124.4 (C-7), 121.0 (d, $^3J_{CF} = 5.9$ Hz, C-11), 115.5 (d, $^4J_{CF} = 3.3$ Hz, C-12), 114.2 (2C-5'), 107.7 (d, $^2J_{CF} = 16.2$ Hz, C-10), 106.4 (d, $^4J_{CF} = 2.9$ Hz, C-6), 55.4 (OMe), 47.1 (C-1'), 36.8 (C-2'); (-)-HRESIMS *m/z* 334.1356 [M–H]⁻ (calcd for $C_{20}H_{17}FN_3O$, 334.1361).

### 3.2.69. 4-Chloro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (68)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.026 g, 0.142 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.027 g, 0.142 mmol), $K_2CO_3$ (0.020 g, 0.142 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.142 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.038 g, 76%). $R_f = 0.43$ ($CH_2Cl_2$:MeOH, 9:1); m.p. 76–77 °C; IR (ATR) $ν_{max}$ 3107, 2925, 2853, 1512, 1247, 823 cm$^{-1}$; $^1$H NMR (400 MHz, $CDCl_3$) $δ$ 10.31 (1H, br s, NH-8), 7.48 (1H, d, $J = 1.0$ Hz, H-2), 7.36 (1H, dd, $J = 7.5, 1.5$ Hz, H-9), 7.13 (1H, dd, $J = 7.5, 7.5$ Hz, H-10), 7.10 (1H, dd, $J = 7.5, 1.5$ Hz, H-11), 7.09 (1H, d, $J = 2.5$ Hz, H-7), 7.06 (1H, d, $J = 1.0$ Hz, H-4), 6.80–6.75 (2H, m, 2H-4'), 6.75–6.70 (2H, m, 2H-5'), 4.03 (2H, t, $J = 7.1$ Hz, H-2-1'), 3.73 (3H, s, OMe), 2.79 (2H, t, $J = 7.1$ Hz, H-2-2'); $^{13}$C NMR (100 MHz, $CDCl_3$) $δ$ 158.5 (C-6'), 137.7 (C-8a), 137.1 (C-2), 130.0 (C-3'), 129.8 (2C-4'), 129.6 (C-4), 127.4 (C-7), 126.0 (C-5/C-12), 125.8 (C-5/C-12), 124.8 (C-12a), 123.0 (C-10), 121.1 (C-11), 114.1 (2C-5'), 110.8 (C-9), 103.6 (C-6), 55.3 (OMe), 47.1 (C-1'), 36.4 (C-2'); (-)-HRESIMS *m/z* 350.1061 [M–H]⁻ (calcd for $C_{20}H_{17}^{35}ClN_3O$, 350.1066), *m/z* 352.1036 [M–H]⁻ (calcd for $C_{20}H_{17}^{37}ClN_3O$, 352.1043).

### 3.2.70. 7-Chloro-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (69)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.026 g, 0.142 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.027 g, 0.142 mmol), $K_2CO_3$ (0.020 g, 0.142 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.142 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.018 g, 36%). $R_f = 0.49$ ($CH_2Cl_2$:MeOH, 9:1); m.p. 59–60 °C; IR (ATR) $ν_{max}$ 3112, 2921, 2835, 1512, 1247, 821 cm$^{-1}$; $^1$H NMR (400 MHz, $CDCl_3$) $δ$ 8.95 (1H, br s, NH-8), 7.47 (1H, d, $J = 1.0$ Hz, H-2), 7.43 (1H, d, $J = 8.0$ Hz, H-12), 7.27 (1H, dd, $J = 7.5, 1.0$ Hz, H-10), 7.13 (1H, d, $J = 1.0$ Hz, H-4), 7.11 (1H, d, $J = 2.5$ Hz, H-7), 7.10 (1H, dd, $J = 8.0, 7.5$ Hz, H-11), 6.82–6.77 (2H, m, 2H-4'), 6.76–6.71 (2H, m, 2H-5'), 4.11 (2H, t, $J = 7.0$ Hz, H-2-1'), 3.75 (3H, s, OMe), 2.81 (2H, t, $J = 7.0$ Hz, H-2-2'); $^{13}$C NMR (100 MHz, $CDCl_3$) $δ$ 158.6 (C-6'), 137.9 (C-2), 133.4 (C-8a), 129.7 (2C-4'), 129.6 (C-3'), 129.2 (C-4), 128.9 (C-12a), 125.3 (C-5), 124.3 (C-7), 122.3 (C-10), 121.4 (C-11), 118.4 (C-12), 117.1 (C-9), 114.2 (2C-5'), 106.7 (C-6), 55.4 (OMe), 47.0 (C-1'), 36.8 (C-2'); (-)-HRESIMS *m/z* 350.1068 [M–H]⁻ (calcd for $C_{20}H_{17}^{35}ClN_3O$, 350.1066), *m/z* 352.1050 [M–H]⁻ (calcd for $C_{20}H_{17}^{37}ClN_3O$, 352.1043).

### 3.2.71. 4-Bromo-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (70)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.028 g, 0.126 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.024 g, 0.126 mmol), $K_2CO_3$ (0.018 g, 0.126 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.025 g, 0.126 mmol)
followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.042 g, 84%). $R_f = 0.44$ (CH₂Cl₂:MeOH, 9:1); m.p. 83–84 °C; IR (ATR) $ν_{max}$ 3107, 2927, 2833, 1513, 1247, 822 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) $δ$ 9.82 (1H, br s, NH-8), 7.50 (1H, d, $J = 1.0$ Hz, H-2), 7.41 (1H, dd, $J = 8.1, 1.0$ Hz, H-9), 7.30 (1H, dd, $J = 7.7, 1.0$ Hz, H-11), 7.08 (1H, d, $J = 2.5$ Hz, H-7), 7.07 (1H, dd, $J = 8.1, 7.7$ Hz, H-10), 7.05 (1H, d, $J = 1.0$ Hz, H-4), 6.80–6.75 (2H, m, 2H-4'), 6.75–6.70 (2H, m, 2H-5'), 4.00 (2H, t, $J = 7.1$ Hz, H₂-1'), 3.74 (3H, s, OMe), 2.80 (2H, $J = 7.1$ Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) $δ$ 158.5 (C-6'), 137.3 (C-8a), 137.0 (C-2), 130.2 (C-4), 130.1 (C-3'), 129.8 (2C-4'), 127.6 (C-7), 126.2 (C-12a), 125.3 (C-5), 124.7 (C-11), 123.4 (C-10), 114.1 (2C-5'), 113.8 (C-12), 111.2 (C-9), 104.7 (C-6), 55.4 (OMe), 47.4 (C-1'), 36.4 (C-2'); (-)-HRESIMS *m/z* 394.0548 [M–H]⁻ (calcd for C₂₀H₁₇⁷BrN₃O, 394.0560), *m/z* 396.0530 [M–H]⁻ (calcd for C₂₀H₁₇⁸BrN₃O, 396.0542).

### 3.2.72. 5-Methoxy-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (71)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.025 g, 0.144 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.027 g, 0.144 mmol), K₂CO₃ (0.020 g, 0.144 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.144 mmol) followed by purification using silica gel chromatography (EtOAc) afforded the title compound as a yellow solid (0.026 g, 52%). $R_f = 0.44$ (CH₂Cl₂:MeOH, 9:1); m.p. 48–49 °C; IR (ATR) $ν_{max}$ 3221, 2932, 2835, 1454, 1248, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) $δ$ 8.85 (1H, br s, NH-8), 7.45 (1H, d, $J = 1.0$ Hz, H-2), 7.32 (1H, d, $J = 8.5$ Hz, H-9), 7.14 (1H, d, $J = 1.0$ Hz, H-4), 7.07 (1H, d, $J = 2.5$ Hz, H-7), 6.97 (1H, d, $J = 2.5$ Hz, H-12), 6.92 (1H, dd, $J = 8.5, 2.5$ Hz, H-10), 6.83–6.78 (2H, m, 2H-4'), 6.76–6.71 (2H, m, 2H-5'), 4.11 (2H, t, $J = 7.2$ Hz, H₂-1'), 3.81 (3H, s, 11-OMe), 3.74 (3H, s, 6'-OMe), 2.81 (2H, t, $J = 7.2$ Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) $δ$ 158.6 (C-6'), 155.0 (C-11), 137.7 (C-2), 131.2 (C-8a), 129.7 (C-3', 2C-4'), 128.8 (C-4), 128.0 (C-12a), 126.0 (C-5), 124.5 (C-7), 114.2 (2C-5'), 113.4 (C-10), 112.4 (C-9), 105.1 (C-6), 100.9 (C-12), 56.0 (11-OMe), 55.3 (6'-OMe), 47.0 (C-1'), 36.7 (C-2'); (-)-HRESIMS *m/z* 346.1548 [M–H]⁻ (calcd for C₂₁H₂₀N₃O₂, 346.1561).

### 3.2.73. 6-Methoxy-3-(1-(4-methoxyphenethyl)-1H-imidazol-5-yl)-1H-indole (72)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.025 g, 0.144 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.027 g, 0.144 mmol), K₂CO₃ (0.020 g, 0.144 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.144 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.040 g, 80%). $R_f = 0.43$ (CH₂Cl₂:MeOH, 9:1); m.p. 45–46 °C; IR (ATR) $ν_{max}$ 3115, 2929, 2834, 1512, 1245, 809 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) $δ$ 8.95 (1H, br s, NH-8), 7.42 (1H, d, $J = 1.0$ Hz, H-2), 7.41 (1H, d, $J = 8.8$ Hz, H-12), 7.13 (1H, d, $J = 1.0$ Hz, H-4), 7.00 (1H, d, $J = 2.5$ Hz, H-7), 6.92 (1H, d, $J = 2.5$ Hz, H-9), 6.84 (1H, dd, $J = 8.8, 2.5$ Hz, H-11), 6.83–6.78 (2H, m, 2H-4'), 6.76–6.71 (2H, m, 2H-5'), 4.12 (2H, t, $J = 7.1$ Hz, H₂-1'), 3.86 (3H, s, 10-OMe), 3.73 (3H, s, 6'-OMe), 2.81 (2H, t, $J = 7.1$ Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) $δ$ 158.5 (C-6'), 157.0 (C-10), 137.6 (C-2), 137.0 (C-8a), 129.7 (C-3', 2C-4'), 128.6 (C-4), 126.2 (C-5), 122.5 (C-7), 121.7 (C-12a), 120.3 (C-12), 114.1 (2C-5'), 110.6 (C-11), 105.3 (C-6), 95.0 (C-9), 55.8 (10-OMe), 55.3 (6'-OMe), 47.1 (C-1'), 36.6 (C-2'); (-)-HRESIMS *m/z* 346.1554 [M–H]⁻ (calcd for C₂₁H₂₀N₃O₂, 346.1561).

### 3.2.74. 3-(1-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-4-fluoro-1H-indole (73)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.025 g, 0.151 mmol) was reacted with (1H-indol-3-yl)methanamine (0.022 g, 0.151 mmol), K₂CO₃ (0.021 g, 0.151 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.151 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.040 g, 80%). $R_f = 0.34$ (CH₂Cl₂:MeOH, 9:1); m.p. 164–165 °C; IR (ATR) $ν_{max}$ 3404, 3132, 2923, 1108, 738 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) $δ$ 11.74 (1H, br s, NH-8), 11.00 (1H, br s, NH-4'), 7.65 (1H, d, $J = 1.0$ Hz, H-2), 7.45 (1H, d, $J = 2.5$ Hz, H-7), 7.32 (2H, d, $J = 7.9$ Hz, H-9, H-11), 7.21 (1H, d, $J = 7.9$ Hz, H-8'), 7.14 (1H, ddd, $J = 7.9, 7.9, 5.0$ Hz, H-10), 7.05 (1H, ddd, $J = 7.9, 7.0, 1.0$ Hz, H-6'), 6.99 (1H, d, $J = 2.5$ Hz, H-3'), 6.90
(1H, br s, H-4), 6.90 (1H, ddd, *J* = 7.9, 7.0, 1.0 Hz, H-7'), 6.84 (1H, dd, *J* = 11.5, 7.9 Hz, H-5'), 5.23 (2H, br s, H₂-1'); ¹³C NMR (100 MHz, DMSO-*d*₆) δ 155.8 (d, ¹*J*<sub>CF</sub> = 244.9 Hz, C-12), 139.1 (d, ³*J*<sub>CF</sub> = 10.8 Hz, C-8a), 137.4 (C-2), 136.1 (C-4a'), 128.0 (C-4), 126.2 (C-7), 125.93 (C-5), 125.89 (C-8a'), 124.4 (C-3'), 122.2 (d, ³*J*<sub>CF</sub> = 7.8 Hz, C-10), 121.3 (C-6'), 118.8 (C-7'), 117.9 (C-8'), 115.3 (d, ²*J*<sub>CF</sub> = 18.3 Hz, C-12a), 111.6 (C-5'), 110.4 (C-2'), 108.5 (d, ⁴*J*<sub>CF</sub> = 3.8 Hz, C-9), 104.6 (d, ²*J*<sub>CF</sub> = 19.5 Hz, C-11), 101.3 (C-6), 40.0 (C-1'); (-)-HRESIMS *m/z* 329.1207 [M–H]⁻ (calcd for C₂₀H₁₄FN₄, 329.1208).

### 3.2.75. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-7-fluoro-1H-indole (74)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.025 g, 0.151 mmol) was reacted with (1H-indol-3-yl)methanamine (0.022 g, 0.151 mmol), K₂CO₃ (0.021 g, 0.151 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.151 mmol) followed by purification by trituration with CH₂Cl₂ afforded the title compound as a light brown solid (0.026 g, 52%). R<sub>f</sub> = 0.41 (CH₂Cl₂:MeOH, 9:1); m.p. 186–187 °C; IR (ATR) ν<sub>max</sub> 3405, 3120, 2923, 1108, 741 cm<sup>-1</sup>; ¹H NMR (400 MHz, DMSO-*d*₆) δ 11.94 (1H, br s, NH-8), 11.02 (1H, br s, NH-4'), 7.73 (1H, s, H-2), 7.58 (1H, s, H-7), 7.39 (1H, d, *J* = 7.5 Hz, H-4'), 7.34 (1H, d, *J* = 8.0 Hz, H-5'), 7.28 (1H, d, *J* = 8.0 Hz, H-8'), 7.09–7.03 (2H, m, H-4, H-6'), 7.06–7.01 (1H, m, H-11), 7.03–6.96 (2H, m, H-10, H-3'), 6.92 (1H, dd, *J* = 8.0, 7.5 Hz, H-7'), 5.37 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-*d*₆) δ 149.3 (d, ¹*J*<sub>FC</sub> = 243.7 Hz, C-9), 137.9 (C-2), 136.2 (C-4a'), 130.4 (d, ³*J*<sub>CF</sub> = 5.9 Hz, C-12a), 127.3 (C-4), 125.8 (C-8a'), 125.6 (C-5), 125.3 (C-7), 124.2 (C-3'), 124.0 (d, ²*J*<sub>CF</sub> = 13.9 Hz, C-8a), 121.4 (C-6'), 119.9 (d, ³*J*<sub>CF</sub> = 6.3 Hz, C-11), 118.9 (C-7'), 118.0 (C-8'), 115.2 (d, ⁴*J*<sub>CF</sub> = 3.0 Hz, C-12), 111.6 (C-5'), 110.5 (C-2'), 106.5 (d, ²*J*<sub>CF</sub> = 16.1 Hz, C-10), 105.2 (d, ⁴*J*<sub>CF</sub> = 2.2 Hz, C-6), 40.5 (C-1'); (-)-HRESIMS *m/z* 329.1205 [M–H]⁻ (calcd for C₂₀H₁₄FN₄, 329.1208).

### 3.2.76. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-4-chloro-1H-indole (75)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.026 g, 0.144 mmol) was reacted with (1H-indol-3-yl)methanamine (0.021 g, 0.144 mmol), K₂CO₃ (0.020 g, 0.144 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.144 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a light brown solid (0.032 g, 64%). R<sub>f</sub> = 0.37 (CH₂Cl₂:MeOH, 9:1); m.p. 195–196 °C; IR (ATR) ν<sub>max</sub> 3412, 3109, 2923, 1487, 1106, 740 cm<sup>-1</sup>; ¹H NMR (400 MHz, DMSO-*d*₆) δ 11.77 (1H, d, *J* = 2.5 Hz, NH-8), 11.00 (1H, br s, NH-4'), 7.64 (1H, br s, H-2), 7.48 (1H, dd, *J* = 8.0, 1.0 Hz, H-9), 7.44 (1H, d, *J* = 2.5 Hz, H-7), 7.32 (1H, d, *J* = 8.0 Hz, H-5'), 7.20 (1H, d, *J* = 8.0 Hz, H-8'), 7.16 (1H, dd, *J* = 8.0, 7.5 Hz, H-10), 7.11 (1H, dd, *J* = 7.5, 1.0 Hz, H-11), 7.05 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-6'), 6.97 (1H, d, *J* = 2.6 Hz, H-3'), 6.91 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-7'), 6.84 (1H, br s, H-4), 5.06 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-*d*₆) δ 137.6 (C-8a), 137.0 (C-2), 136.1 (C-4a'), 128.9 (C-4), 128.4 (C-7), 126.0 (C-8a'), 125.3 (C-5), 124.6 (C-3'), 124.2 (C-4/C-12a), 124.1 (C-4/C-12a), 122.4 (C-10), 121.3 (C-6'), 120.2 (C-11), 118.8 (C-7'), 117.9 (C-8'), 111.5 (C-5'), 111.3 (C-9), 110.1 (C-2'), 102.6 (C-6), 40.0 (C-1'); (-)-HRESIMS *m/z* 345.0919 [M–H]⁻ (calcd for C₂₀H₁₄₃ClN₄, 345.0912), *m/z* 347.0886 [M–H]⁻ (calcd for C₂₀H₁₄₃ClN₄, 347.0889).

### 3.2.77. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-5-chloro-1H-indole (76)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.026 g, 0.144 mmol) was reacted with (1H-indol-3-yl)methanamine (0.021 g, 0.144 mmol), K₂CO₃ (0.020 g, 0.144 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.144 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.027 g, 54%). R<sub>f</sub> = 0.41 (CH₂Cl₂:MeOH, 9:1); m.p. 107–108 °C; IR (ATR) ν<sub>max</sub> 3404, 3227, 2929, 1660, 1458, 744 cm<sup>-1</sup>; ¹H NMR (400 MHz, DMSO-*d*₆) δ 11.62 (1H, br s, NH-8), 11.60 (1H, br s, NH-4'), 7.72 (1H, d, *J* = 1.0 Hz, H-2), 7.60 (1H, d, *J* = 2.5 Hz, H-7), 7.49 (1H, d, *J* = 2.0 Hz, H-12), 7.47 (1H, d, *J* = 8.8 Hz, H-9), 7.33 (1H, d, *J* = 8.2 Hz, H-5'), 7.27 (1H, d, *J* = 8.1 Hz, H-8'), 7.16 (1H, dd, *J* = 8.8, 2.0 Hz, H-10), 7.06 (1H, d, *J* = 1.0 Hz, H-4), 7.06 (1H, ddd, *J* = 8.2, 7.0, 1.0 Hz, H-6'), 6.98 (1H, d, *J* = 2.5 Hz,
H-3'), 6.91 (1H, ddd, *J* = 8.1, 7.0, 1.0 Hz, H-7'), 5.34 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) *δ* 137.9 (C-2), 136.1 (C-4a'), 134.5 (C-8a), 127.6 (C-12a), 127.2 (C-4), 126.0 (C-7), 125.8 (C-8a'), 125.4 (C-5), 124.3 (C-11), 124.2 (C-3'), 121.7 (C-10), 121.4 (C-6'), 118.9 (C-7'), 118.02 (C-12/C-8'), 117.99 (C-12/C-8'), 113.4 (C-9), 111.6 (C-5'), 110.5 (C-2'), 103.9 (C-6), 40.4 (C-1'); (-)-HRESIMS *m/z* 345.0910 [M-H]⁻ (calcd for C₂₀H₁₄³⁵ClN₄, 345.0912), *m/z* 347.0881 [M-H]⁻ (calcd for C₂₀H₁₄³⁷ClN₄, 347.0889).

### 3.2.78. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-7-chloro-1H-indole (77)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.026 g, 0.144 mmol) was reacted with (1H-indol-3-yl)methanamine (0.021 g, 0.144 mmol), K₂CO₃ (0.020 g, 0.144 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.144 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a pale yellow solid (0.023 g, 46%). R_f = 0.46 (CH₂Cl₂:MeOH, 9:1); m.p. 165-166 °C; IR (ATR) ν_max 3412, 3116, 2921, 1108, 741 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) *δ* 11.80 (1H, br s, NH-8), 11.01 (1H, br s, NH-4'), 7.74 (1H, d, *J* = 1.0 Hz, H-2), 7.58 (1H, s, H-7), 7.54 (1H, dd, *J* = 8.0, 1.0 Hz, H-12), 7.34 (1H, d, *J* = 8.5 Hz, H-5'), 7.29 (1H, d, *J* = 8.0 Hz, H-8'), 7.26 (1H, dd, *J* = 7.5, 1.0 Hz, H-10), 7.08 (1H, d, *J* = 1.0 Hz, H-4), 7.08 (1H, dd, *J* = 8.5, 7.0 Hz, H-11), 7.07 (1H, ddd, *J* = 8.5, 7.2, 1.0 Hz, H-6'), 6.98 (1H, d, *J* = 2.5 Hz, H-3'), 6.92 (1H, ddd, *J* = 8.0, 7.2, 1.0 Hz, H-7'), 5.37 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) *δ* 137.9 (C-2), 136.2 (C-4a'), 132.9 (C-8a), 128.4 (C-12a), 127.3 (C-4), 125.8 (C-8a'), 125.5 (C-5), 125.4 (C-7), 124.1 (C-3'), 121.4 (C-6'), 121.3 (C-10), 120.6 (C-11), 118.9 (C-7'), 118.1 (C-12/C-8'), 118.0 (C-12/C-8'), 116.2 (C-9), 111.6 (C-5'), 110.5 (C-2'), 105.4 (C-6), 40.5 (C-1'); (-)-HRESIMS *m/z* 345.0919 [M-H]⁻ (calcd for C₂₀H₁₄³⁵ClN₄, 345.0912), *m/z* 347.0894 [M-H]⁻ (calcd for C₂₀H₁₄³⁷ClN₄, 347.0889).

### 3.2.79. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-4-bromo-1H-indole (78)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.029 g, 0.128 mmol) was reacted with (1H-indol-3-yl)methanamine (0.019 g, 0.128 mmol), K₂CO₃ (0.018 g, 0.128 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.025 g, 0.128 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.036 g, 72%). R_f = 0.37 (CH₂Cl₂:MeOH, 9:1); m.p. 201-202 °C; IR (ATR) ν_max 3410, 3110, 2922, 1489, 1107, 740 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) *δ* 11.78 (1H, br s, NH-8), 11.01 (1H, br s, NH-4'), 7.66 (1H, br s, H-2), 7.53 (1H, d, *J* = 7.9 Hz, H-9), 7.45 (1H, d, *J* = 2.5 Hz, H-7), 7.33 (1H, d, *J* = 8.0 Hz, H-5'), 7.28 (1H, d, *J* = 7.5 Hz, H-12), 7.23 (1H, d, *J* = 8.0 Hz, H-8'), 7.10 (1H, dd, *J* = 7.9, 7.5 Hz, H-10), 7.06 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-6'), 6.98 (1H, d, *J* = 2.5 Hz, H-3'), 6.92 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-7'), 6.85 (1H, br s, H-4), 5.02 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) *δ* 137.2 (C-8a), 136.9 (C-2), 136.1 (C-4a'), 129.3 (C-4), 128.7 (C-7), 126.0 (C-8a'), 125.6 (C-12a), 124.8 (C-5), 124.6 (C-3'), 123.5 (C-11), 122.7 (C-10), 121.3 (C-6'), 118.8 (C-7'), 118.0 (C-8'), 112.5 (C-12), 111.8 (C-9), 111.5 (C-5'), 110.0 (C-2'), 103.4 (C-6), 40.1 (C-1'); (-)-HRESIMS *m/z* 389.0412 [M-H]⁻ (calcd for C₂₀H₁₄⁷BrN₄, 389.0407), *m/z* 391.0394 [M-H]⁻ (calcd for C₂₀H₁₄⁸BrN₄, 391.0389).

### 3.2.80. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-5-methoxy-1H-indole (79)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.026 g, 0.146 mmol) was reacted with (1H-indol-3-yl)methanamine (0.021 g, 0.146 mmol), K₂CO₃ (0.020 g, 0.146 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.146 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a light brown solid (0.019 g, 38%). R_f = 0.37 (CH₂Cl₂:MeOH, 9:1); m.p. 97-98 °C; IR (ATR) ν_max 3402, 3116, 2926, 1481, 1212, 744 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) *δ* 8.57 (1H, br s, NH-8), 8.49 (1H, br s, NH-4'), 7.64 (1H, d, *J* = 1.0 Hz, H-2), 7.37 (1H, d, *J* = 7.7 Hz, H-8'), 7.35 (1H, d, *J* = 8.0 Hz, H-5'), 7.29 (1H, d, *J* = 8.9 Hz, H-9), 7.23 (1H, d, *J* = 1.0 Hz, H-4), 7.19 (1H, ddd, *J* = 8.0, 7.0, 1.0 Hz, H-6'), 7.11 (1H, d, *J* = 2.5 Hz, H-7), 7.07 (1H, ddd, *J* = 7.7, 7.0, 1.0 Hz, H-7'), 7.04 (1H, d, *J* = 2.5 Hz, H-12), 6.90 (1H, dd, *J* = 8.9, 2.5 Hz, H-10), 6.83 (1H, d, *J* = 1.0 Hz, H-3'), 5.26 (2H, s, H₂-1'), 3.75 (3H, s, OMe); ¹³C
NMR (100 MHz, CDCl₃) δ 155.0 (C-11), 138.0 (C-2), 136.5 (C-4a'), 131.1 (C-8a), 128.4 (C-4), 127.9 (C-12a), 126.5 (C-5), 126.0 (C-8a'), 124.4 (C-7), 123.2 (C-3'), 122.8 (C-6'), 120.3 (C-7'), 118.6 (C-8'), 113.5 (C-10), 112.3 (C-9), 112.2 (C-2'), 111.6 (C-5'), 105.4 (C-6), 101.1 (C-12), 55.9 (OMe), 41.3 (C-1'); (+)-HRESIMS *m/z* 343.1540 [M+H]⁺ (calcd for C₂₁H₁₉N₄O, 343.1553).

### 3.2.81. 3-((1H-Indol-3-yl)methyl)-1H-imidazol-5-yl)-6-methoxy-1H-indole (80)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.026 g, 0.146 mmol) was reacted with (1H-indol-3-yl)methanamine (0.021 g, 0.146 mmol), K₂CO₃ (0.020 g, 0.146 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.029 g, 0.146 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown solid (0.018 g, 36%). R<sub>f</sub> = 0.43 (CH₂Cl₂:MeOH, 9:1); m.p. 95–96 °C; IR (ATR) ν<sub>max</sub> 3399, 3214, 2921, 1457, 744 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.41 (2H, br s, NH-8, NH-4'), 7.60 (1H, d, *J* = 1.0 Hz, H-2), 7.53 (1H, d, *J* = 8.6 Hz, H-12), 7.38 (1H, d, *J* = 8.0 Hz, H-8'), 7.35 (1H, d, *J* = 8.0 Hz, H-5'), 7.23 (1H, d, *J* = 1.0 Hz, H-4), 7.20 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-6'), 7.08 (1H, ddd, *J* = 8.0, 7.5, 1.0 Hz, H-7'), 7.02 (1H, d, *J* = 2.5 Hz, H-7), 6.89 (1H, d, *J* = 2.5 Hz, H-9), 6.85 (1H, dd, *J* = 8.6, 2.5 Hz, H-11), 6.84 (1H, d, *J* = 2.4 Hz, H-3'), 5.27 (2H, s, H₂-1'), 3.85 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 157.1 (C-10), 137.9 (C-2), 136.9 (C-8a), 136.5 (C-4a'), 128.2 (C-4), 126.6 (C-5), 126.0 (C-8a'), 123.2 (C-3'), 122.8 (C-6'), 122.3 (C-7), 121.6 (C-12a), 120.5 (C-12), 120.2 (C-7'), 118.5 (C-8'), 112.1 (C-2'), 111.6 (C-5'), 110.7 (C-11), 105.6 (C-6), 94.9 (C-9), 55.9 (OMe), 41.3 (C-1'); (+)-HRESIMS *m/z* 343.1556 [M+H]⁺ (calcd for C₂₁H₁₉N₄O, 343.1553).

### 3.2.82. 3-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-4-fluoro-1H-indole (81)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.024 g, 0.145 mmol) with tryptamine (0.023 g, 0.145 mmol), K₂CO₃ (0.020 g, 0.145 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.145 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow solid (0.036 g, 72%). R<sub>f</sub> = 0.27 (CH₂Cl₂:MeOH, 9:1); m.p. > 230 °C; IR (ATR) ν<sub>max</sub> 3409, 3138, 2927, 1227, 738 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.76 (1H, br s, NH-8), 10.78 (1H, br s, NH-5'), 7.68 (1H, br s, H-2), 7.47 (1H, d, *J* = 2.5 Hz, H-7), 7.34 (1H, d, *J* = 8.0 Hz, H-9), 7.27 (1H, d, *J* = 8.2 Hz, H-6'), 7.14 (1H, ddd, *J* = 8.0, 8.0, 5.2 Hz, H-10), 6.99 (1H, ddd, *J* = 8.2, 6.9, 0.9 Hz, H-7'), 6.94 (1H, d, *J* = 2.2 Hz, H-4'), 6.91 (1H, br s, H-4), 6.84 (1H, d, *J* = 7.9 Hz, H-9'), 6.79 (1H, dd, *J* = 11.7, 8.0 Hz, H-11), 6.76 (1H, ddd, *J* = 7.9, 6.9, 0.9 Hz, H-8'), 4.12 (2H, t, *J* = 7.8 Hz, H₂-1'), 2.90 (2H, t, *J* = 7.8 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 155.7 (d, ¹J<sub>CF</sub> = 243.9 Hz, C-12), 139.1 (d, ³J<sub>CF</sub> = 10.8 Hz, C-8a), 137.5 (C-2), 136.0 (C-5a'), 128.3 (C-4), 126.7 (C-9a'), 126.4 (C-7), 125.5 (C-5), 122.9 (C-4'), 122.2 (d, ³J<sub>CF</sub> = 7.7 Hz, C-10), 120.9 (C-7'), 118.2 (C-8'), 117.7 (C-9'), 115.4 (d, ²J<sub>CF</sub> = 18.1 Hz, C-12a), 111.3 (C-6'), 110.3 (C-3'), 108.5 (d, ⁴J<sub>CF</sub> = 2.9 Hz, C-9), 104.5 (d, ²J<sub>CF</sub> = 19.1 Hz, C-11), 101.1 (C-6), 45.2 (C-1'), 26.5 (C-2'); (-)-HRESIMS *m/z* 343.1359 [M−H]⁻ (calcd for C₂₁H₁₆FN₄, 343.1364).

### 3.2.83. 3-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-7-fluoro-1H-indole (82)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.024 g, 0.145 mmol) with tryptamine (0.023 g, 0.145 mmol), K₂CO₃ (0.020 g, 0.145 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.145 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as an off-white solid (0.020 g, 40%). R<sub>f</sub> = 0.30 (CH₂Cl₂:MeOH, 9:1); m.p. > 230 °C; IR (ATR) ν<sub>max</sub> 3417, 3135, 2927, 2856, 1234, 739 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.97 (1H, br s, NH-8), 10.80 (1H, br s, NH-5'), 7.71 (1H, d, *J* = 1.0 Hz, H-2), 7.58 (1H, d, *J* = 2.5 Hz, H-7), 7.32–7.29 (1H, m, H-12), 7.29 (1H, d, *J* = 8.0 Hz, H-6'), 7.06–7.00 (4H, m, H-10, H-11, H-7', H-9'), 7.02 (1H, d, *J* = 1.0 Hz, H-4), 6.96 (1H, d, *J* = 2.4 Hz, H-4'), 6.84 (1H, ddd, *J* = 8.0, 7.0, 1.0 Hz, H-8'), 4.22 (2H, t, *J* = 7.9 Hz, H₂-1'), 2.93 (2H, t, *J* = 7.9 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 149.3 (d, ¹J<sub>CF</sub> = 243.9 Hz, C-9), 137.9 (C-2), 136.0 (C-5a'), 130.6 (d, ³J<sub>CF</sub> = 5.9 Hz, C-12a), 127.7 (C-4), 126.8 (C-9a'), 125.6 (C-7), 125.0 (C-5), 124.0 (d, ²J<sub>CF</sub> = 13.8 Hz, C-8a),
122.9 (C-4'), 120.9 (C-7'), 120.0 (d, $ ^{3}J_{CF} = 6.2 \text{ Hz, C-11}$), 118.2 (C-8'), 117.9 (C-9'), 115.1 (d, $ ^{4}J_{CF} = 2.9 \text{ Hz, C-12}$), 111.3 (C-6'), 110.3 (C-3'), 106.5 (d, $ ^{2}J_{CF} = 15.9 \text{ Hz, C-10}$), 105.0 (d, $ ^{4}J_{CF} = 2.4 \text{ Hz, C-6}$), 45.4 (C-1'), 26.6 (C-2'); (-)-HRESIMS *m/z* 343.1350 [M–H]⁻ (calcd for C₂₁H₁₆FN₄, 343.1364).

### 3.2.84. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-4-chloro-1H-indole (83)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.025 g, 0.139 mmol) with tryptamine (0.023 g, 0.139 mmol), K₂CO₃ (0.019 g, 0.139 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.027 g, 0.139 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.022 g, 44%). R_f = 0.33 (CH₂Cl₂:MeOH, 9:1); m.p. > 230 °C; IR (ATR) ν_max 3399, 3173, 2924, 1490, 1194, 741 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.81 (1H, d, *J* = 2.2 Hz, NH-8), 10.75 (1H, br s, NH-5'), 7.71 (1H, d, *J* = 1.0 Hz, H-2), 7.51 (1H, d, *J* = 2.2 Hz, H-7), 7.50 (1H, d, *J* = 7.9 Hz, H-9), 7.26 (1H, d, *J* = 8.2 Hz, H-6'), 7.15 (1H, dd, *J* = 7.9, 7.9 Hz, H-10), 7.05 (1H, d, *J* = 7.9 Hz, H-11), 6.97 (1H, dd, *J* = 8.2, 7.9 Hz, H-7'), 6.94 (1H, br s, H-4'), 6.88 (1H, d, *J* = 1.0 Hz, H-4), 6.69 (1H, dd, *J* = 7.9, 7.9 Hz, H-8'), 6.63 (1H, d, *J* = 7.9 Hz, H-9'), 3.99 (2H, t, *J* = 7.9 Hz, H₂-1'), 2.89 (2H, t, *J* = 7.9 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.6 (C-8a), 137.2 (C-2), 136.0 (C-5a'), 129.2 (C-4), 128.4 (C-7), 126.6 (C-9a'), 125.0 (C-5), 124.2 (C-12/C-12a), 124.1 (C-12/C-12a), 122.9 (C-10), 122.4 (C-4'), 120.8 (C-7'), 120.2 (C-11), 118.1 (C-8'), 117.5 (C-9'), 111.28 (C-9/C-6'), 111.25 (C-9/C-6'), 110.2 (C-3'), 102.6 (C-6), 45.3 (C-1'), 26.6 (C-2'); (-)-HRESIMS *m/z* 359.1068 [M–H]⁻ (calcd for C₂₁H₁₆**³⁵**ClN₄, 359.1069), *m/z* 361.1046 [M–H]⁻ (calcd for C₂₁H₁₆**³⁷**ClN₄, 361.1047).

### 3.2.85. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-5-chloro-1H-indole (84)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.025 g, 0.139 mmol) with tryptamine (0.023 g, 0.139 mmol), K₂CO₃ (0.019 g, 0.139 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.027 g, 0.139 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.028 g, 56%). R_f = 0.44 (CH₂Cl₂:MeOH, 9:1); m.p. 70–71 °C; IR (ATR) ν_max 3401, 3172, 2922, 1457, 744 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.66 (1H, br s, NH-8), 10.80 (1H, br s, NH-5'), 7.70 (1H, d, *J* = 1.0 Hz, H-2), 7.60 (1H, d, *J* = 2.0 Hz, H-7), 7.50 (1H, d, *J* = 8.3 Hz, H-9), 7.45 (1H, d, *J* = 2.0 Hz, H-12), 7.29 (1H, d, *J* = 8.3 Hz, H-6'), 7.18 (1H, dd, *J* = 8.3, 2.0 Hz, H-10), 7.05 (1H, d, *J* = 7.9 Hz, H-9'), 7.04–6.99 (1H, m, H-7'), 7.01 (1H, d, *J* = 1.0 Hz, H-4), 6.97 (1H, d, *J* = 2.5 Hz, H-4'), 6.84 (1H, ddd, *J* = 7.9, 6.9, 1.0 Hz, H-8'), 4.21 (2H, t, *J* = 7.6 Hz, H₂-1'), 2.93 (2H, t, *J* = 7.6 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.9 (C-2), 136.0 (C-5a'), 134.5 (C-8a), 127.8 (C-12a), 127.6 (C-4), 126.8 (C-9a'), 126.2 (C-7), 124.9 (C-5), 124.3 (C-11), 122.9 (C-4'), 121.7 (C-10), 120.9 (C-7'), 118.2 (C-8'), 117.9 (C-12, C-9'), 113.4 (C-9), 111.3 (C-6'), 110.2 (C-3'), 103.7 (C-6), 45.3 (C-1'), 26.6 (C-2'); (+)-HRESIMS *m/z* 361.1206 [M+H]⁺ (calcd for C₂₁H₁₈**³⁵**ClN₄, 361.1215), *m/z* 363.1168 [M+H]⁺ (calcd for C₂₁H₁₈**³⁷**ClN₄, 363.1192).

### 3.2.86. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-7-chloro-1H-indole (85)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.025 g, 0.139 mmol) with tryptamine (0.023 g, 0.139 mmol), K₂CO₃ (0.019 g, 0.139 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.027 g, 0.139 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as an off-white solid (0.023 g, 46%). R_f = 0.31 (CH₂Cl₂:MeOH, 9:1); m.p. 226–227 °C; IR (ATR) ν_max 3408, 3130, 2919, 1435, 1110, 740 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.85 (1H, br s, NH-8), 10.80 (1H, br s, NH-5'), 7.73 (1H, d, *J* = 1.0 Hz, H-2), 7.60 (1H, d, *J* = 2.4 Hz, H-7), 7.46 (1H, d, *J* = 7.9 Hz, H-12), 7.29 (1H, d, *J* = 8.0 Hz, H-6'), 7.26 (1H, dd, *J* = 7.9, 0.9 Hz, H-10), 7.07 (1H, dd, *J* = 7.9, 7.9 Hz, H-11), 7.04–7.01 (1H, m, H-7'), 7.03 (1H, d, *J* = 1.0 Hz, H-4), 7.00 (1H, d, *J* = 7.8 Hz, H-9'), 6.97 (1H, d, *J* = 2.5 Hz, H-4'), 6.84 (1H, ddd, *J* = 7.8, 6.9, 1.0 Hz, H-8'), 4.22 (2H, t, *J* = 7.5 Hz, H₂-1'), 2.93 (2H, t, *J* = 7.5 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.9 (C-2), 136.0 (C-5a'), 132.9 (C-8a), 128.6 (C-12a), 127.8 (C-4),
126.7 (C-9a'), 125.7 (C-7), 124.9 (C-5), 122.9 (C-4'), 121.3 (C-10), 120.9 (C-7'), 120.6 (C-11), 118.2 (C-8'), 118.0 (C-12/C-9'), 117.9 (C-12/C-9'), 116.2 (C-9), 111.3 (C-6'), 110.2 (C-3'), 105.2 (C-6), 45.4 (C-1'), 26.6 (C-2'); (-)-HRESIMS *m/z* 359.1066 [M-H]⁻ (calcd for C₂₁H₁₆³⁵ClN₄, 359.1069), *m/z* 361.1049 [M-H]⁻ (calcd for C₂₁H₁₆³⁷ClN₄, 361.1047).

### 3.2.87. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-4-bromo-1H-indole (86)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.028 g, 0.123 mmol) with tryptamine (0.020 g, 0.123 mmol), K₂CO₃ (0.017 g, 0.123 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.024 g, 0.123 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as an off white solid (0.021 g, 42%). R_f = 0.34 (CH₂Cl₂:MeOH, 9:1); m.p. > 230 °C; IR (ATR) νmax 3422, 3111, 2919, 1456, 1192, 742 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.82 (1H, d, *J* = 2.5 Hz, NH-8), 10.75 (1H, br s, NH-5'), 7.73 (1H, br s, H-2), 7.55 (1H, dd, *J* = 7.8, 1.0 Hz, H-9), 7.52 (1H, d, *J* = 2.5 Hz, H-7), 7.25 (1H, d, *J* = 7.9 Hz, H-6'), 7.22 (1H, dd, *J* = 7.8, 1.0 Hz, H-11), 7.08 (1H, dd, *J* = 7.8, 7.8 Hz, H-10), 6.99–6.94 (2H, m, H-4', H-7'), 6.88 (1H, d, *J* = 0.9 Hz, H-4), 6.69 (1H, ddd, *J* = 7.8, 6.9, 1.0 Hz, H-8'), 6.61 (1H, d, *J* = 7.8 Hz, H-9'), 3.95 (2H, t, *J* = 7.8 Hz, H₂-1'), 2.90 (2H, t, *J* = 7.8 Hz, H₂-2'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.3 (C-8a), 137.1 (C-2), 136.0 (C-5a'), 129.6 (C-4), 128.7 (C-7), 126.6 (C-9a'), 125.5 (C-12a), 124.5 (C-5), 123.5 (C-11), 122.9 (C-10/C-4'), 122.7 (C-10/C-4'), 120.8 (C-7'), 118.1 (C-8'), 117.5 (C-9'), 112.5 (C-12), 111.7 (C-9), 111.3 (C-6'), 110.3 (C-3'), 103.4 (C-6), 45.5 (C-1'), 26.7 (C-2'); (-)-HRESIMS *m/z* 403.0565 [M-H]⁻ (calcd for C₂₁H₁₆⁷⁹BrN₄, 403.0564), *m/z* 405.0545 [M-H]⁻ (calcd for C₂₁H₁₆⁸¹BrN₄, 405.0546).

### 3.2.88. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-5-methoxy-1H-indole (87)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.049 g, 0.280 mmol) with tryptamine (0.045 g, 0.280 mmol), K₂CO₃ (0.039 g, 0.280 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.055 g, 0.280 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as an orange solid (0.095 g, 95%). R_f = 0.36 (CH₂Cl₂:MeOH, 9:1); m.p. 152–153 °C; IR (ATR) νmax 3411, 3115, 2929, 1481, 1211 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.47 (1H, br s, NH-8), 8.10 (1H, br s, NH-5'), 7.48 (1H, d, *J* = 0.9 Hz, H-2), 7.32 (1H, d, *J* = 8.9 Hz, H-9), 7.30 (1H, dd, *J* = 7.9, 1.0 Hz, H-6'), 7.17–7.12 (3H, m, H-4, H-7', H-9'), 7.03 (1H, d, *J* = 2.5 Hz, H-7), 7.02–7.00 (1H, m, H-8'), 7.00–6.98 (1H, m, H-12), 6.93 (1H, dd, *J* = 8.9, 2.5 Hz, H-10), 6.71 (1H, d, *J* = 2.5 Hz, H-4'), 4.21 (2H, t, *J* = 7.2 Hz, H₂-1'), 3.79 (3H, s, OMe), 3.03 (2H, t, *J* = 7.2 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 155.1 (C-11), 137.9 (C-2), 136.3 (C-5a'), 131.2 (C-8a), 128.8 (C-4), 128.0 (C-12a), 127.0 (C-9a'), 126.0 (C-5), 124.5 (C-7), 122.4 (C-4'/C-7'), 122.3 (C-4'/C-7'), 119.6 (C-8'), 118.3 (C-9'), 113.5 (C-10), 112.3 (C-9), 111.7 (C-3'), 111.4 (C-6'), 105.3 (C-6), 101.0 (C-12), 56.0 (OMe), 45.9 (C-1'), 27.5 (C-2'); (-)-HRESIMS *m/z* 355.1575 [M-H]⁻ (calcd for C₂₂H₁₉N₄O, 355.1564).

### 3.2.89. 3-(1-(2-(1H-Indol-3-yl)ethyl)-1H-imidazol-5-yl)-6-methoxy-1H-indole (88)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.025 g, 0.140 mmol) with tryptamine (0.023 g, 0.140 mmol), K₂CO₃ (0.020 g, 0.140 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.028 g, 0.140 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as brown solid (0.011 g, 22%). R_f = 0.43 (CH₂Cl₂:MeOH, 9:1); m.p. 81–82 °C; IR (ATR) νmax 3301, 2932, 2841, 1456, 1161, 738 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.54 (1H, br s, NH-8), 8.19 (1H, br s, NH-5'), 7.43 (1H, d, *J* = 8.8 Hz, H-12), 7.42 (1H, d, *J* = 1.5 Hz, H-2), 7.29 (1H, dd, *J* = 7.8, 1.0 Hz, H-6'), 7.19–7.13 (2H, m, H-7', H-9'), 7.13 (1H, d, *J* = 1.5 Hz, H-4), 7.01 (1H, ddd, *J* = 7.8, 7.0, 1.0 Hz, H-8'), 6.96 (1H, d, *J* = 2.5 Hz, H-7), 6.91 (1H, d, *J* = 2.0 Hz, H-9), 6.83 (1H, dd, *J* = 8.8, 2.0 Hz, H-11), 6.67 (1H, d, *J* = 2.5 Hz, H-4'), 4.20 (2H, t, *J* = 7.2 Hz, H₂-1'), 3.86 (3H, s, OMe), 3.00 (2H, t, *J* = 7.2 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 157.2 (C-10), 137.9 (C-2), 136.9 (C-8a), 136.3 (C-5a'), 128.8 (C-4), 127.0 (C-9a'), 126.0 (C-5), 122.5 (C-4'/C-7'), 122.4 (C-4'/C-7'), 122.33 (C-12a), 122.27 (C-7), 120.4 (C-12), 119.6 (C-8'), 118.4 (C-6').
(C-9'), 111.8 (C-3'), 111.4 (C-6'), 110.7 (C-11), 105.7 (C-6), 94.5 (C-9), 55.9 (OMe), 45.9 (C-1'), 27.4 (C-2'); (-)-HRESIMS *m/z* 355.1570 [M-H]⁻ (calcd for C₂₂H₁₉N₄O, 355.1564).

### 3.2.90. 4-Fluoro-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (89)

Using the general procedure, reaction of 4-fluoro-1H-indole-3-carbaldehyde (0.030 g, 0.184 mmol) with pentylamine (21 µL, 0.184 mmol), K₂CO₃ (0.026 g, 0.184 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.036 g, 0.184 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.043 g, 86%). Rf = 0.44 (CH₂Cl₂:MeOH, 9:1); m.p. 147–148 °C; IR (ATR) νmax 3118, 2955, 2930, 2859, 1228, 734 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.32 (1H, br s, NH-8), 7.63 (1H, br s, H-2), 7.24 (1H, d, *J* = 7.9 Hz, H-9), 7.20 (1H, d, *J* = 2.5 Hz, H-7), 7.15 (1H, ddd, *J* = 7.9, 7.9, 5.0 Hz, H-10), 7.07 (1H, br s, H-4), 6.80 (1H, ddd, *J* = 11.1, 7.9, 1.0 Hz, H-11), 3.90 (2H, t, *J* = 7.2 Hz, H₂-1'), 1.61 (2H, p, *J* = 7.2 Hz, H₂-2'), 1.22–1.12 (4H, m, H₂-3', H₂-4'), 0.78 (3H, t, *J* = 6.9 Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) δ 156.6 (d, ¹JCF = 248.0 Hz, C-4), 139.1 (d, ³JCF = 10.7 Hz, C-8a), 137.5 (C-2), 128.9 (C-4), 126.3 (C-5), 125.2 (C-7), 123.2 (d, ³JCF = 7.9 Hz, C-10), 116.3 (d, ²JCF = 19.1 Hz, C-12a), 107.9 (d, ⁴JCF = 3.7 Hz, C-9), 105.7 (d, ²JCF = 19.4 Hz, C-11), 103.1 (C-6), 45.3 (C-1'), 30.4 (C-2'), 28.7 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS *m/z* 270.1406 [M-H]⁻ (calcd for C₁₆H₁₇FN₃, 270.1412).

### 3.2.91. 7-Fluoro-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (90)

Using the general procedure, reaction of 7-fluoro-1H-indole-3-carbaldehyde (0.030 g, 0.184 mmol) with pentylamine (21 µL, 0.184 mmol), K₂CO₃ (0.026 g, 0.184 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.036 g, 0.184 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.030 g, 60%). Rf = 0.44 (CH₂Cl₂:MeOH, 9:1); m.p. 164–165 °C; IR (ATR) νmax 3072, 2957, 2930, 2859, 1234, 1110, 783 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.48 (1H, br s, NH-8), 7.68 (1H, d, *J* = 1.0 Hz, H-2), 7.30 (1H, d, *J* = 7.8 Hz, H-12), 7.29 (1H, d, *J* = 2.4 Hz, H-7), 7.16 (1H, d, *J* = 1.0 Hz, H-4), 7.07 (1H, ddd, *J* = 7.8, 7.8, 4.9 Hz, H-11), 6.97 (1H, ddd, *J* = 11.4, 7.8, 1.0 Hz, H-10), 3.91 (2H, t, *J* = 7.4 Hz, H₂-1'), 1.63 (2H, p, *J* = 7.4 Hz, H₂-2'), 1.23–1.13 (4H, m, H₂-3', H₂-4'), 0.79 (3H, t, *J* = 6.8 Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) δ 149.8 (d, ¹JCF = 244.6 Hz, C-9), 137.6 (C-2), 131.1 (d, ³JCF = 5.2 Hz, C-12a), 128.7 (C-4), 125.6 (C-5), 124.7 (d, ²JCF = 14.0 Hz, C-8a), 124.6 (C-7), 120.8 (d, ³JCF = 6.2 Hz, C-11), 115.4 (d, ⁴JCF = 3.4 Hz, C-12), 107.6 (d, ²JCF = 16.1 Hz, C-10), 106.3 (d, ⁴JCF = 3.0 Hz, C-6), 45.5 (C-1'), 30.7 (C-2'), 28.7 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS *m/z* 270.1414 [M-H]⁻ (calcd for C₁₆H₁₇FN₃, 270.1412).

### 3.2.92. 4-Chloro-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (91)

Using the general procedure, reaction of 4-chloro-1H-indole-3-carbaldehyde (0.031 g, 0.174 mmol) with pentylamine (20 µL, 0.174 mmol), K₂CO₃ (0.024 g, 0.174 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.174 mmol) followed by purification by trituration with CH₂Cl₂ afforded the title compound as a yellow solid (0.019 g, 38%). Rf = 0.43 (CH₂Cl₂:MeOH, 9:1); m.p. 188–189 °C; IR (ATR) νmax 3107, 2960, 2930, 2861, 1491, 1191, 739 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.98 (1H, br s, NH-8), 7.63 (1H, br s, H-2), 7.36 (1H, dd, *J* = 7.8, 1.5 Hz, H-9), 7.26 (1H, d, *J* = 2.4 Hz, H-7), 7.16 (1H, dd, *J* = 7.8, 7.5 Hz, H-10), 7.12 (1H, dd, *J* = 7.5, 1.5 Hz, H-11), 7.04 (1H, br s, H-4), 3.80 (2H, t, *J* = 7.4 Hz, H₂-1'), 1.58 (2H, p, *J* = 7.4 Hz, H₂-2'), 1.22–1.12 (4H, m, H₂-3', H₂-4'), 0.78 (3H, t, *J* = 7.0 Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) δ 137.4 (C-8a), 137.2 (C-2), 130.0 (C-4), 126.9 (C-7), 126.3 (C-12), 125.5 (C-5), 124.9 (C-12a), 123.3 (C-10), 121.4 (C-11), 110.5 (C-9), 104.8 (C-6), 45.5 (C-1'), 30.3 (C-2'), 28.8 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS *m/z* 286.1114 [M-H]⁻ (calcd for C₁₆H₁₇³⁵ClN₃, 286.1116), *m/z* 288.1095 [M-H]⁻ (calcd for C₁₆H₁₇³⁷ClN₃, 288.1091).

### 3.2.93. 5-Chloro-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (92)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.031 g, 0.174 mmol) with pentylamine (20 µL, 0.174 mmol), K₂CO₃ (0.024 g, 0.174 mmol) and
*p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.17 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a brown gum (0.026 g, 52%). R<sub>f</sub> = 0.45 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); IR (ATR) ν<sub>max</sub> 3129, 2929, 2873, 1458, 1109, 799 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.84 (1H, br s, NH-8), 7.66 (1H, br s, H-2), 7.51 (1H, d, *J* = 2.0 Hz, H-12), 7.37 (1H, d, *J* = 8.5 Hz, H-9), 7.29 (1H, d, *J* = 2.4 Hz, H-7), 7.20 (1H, dd, *J* = 8.5, 2.0 Hz, H-10), 7.14 (1H, br s, H-4), 3.91 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-1'), 1.63 (2H, p, *J* = 7.3 Hz, H<sub>2</sub>-2'), 1.23–1.13 (4H, m, H<sub>2</sub>-3', H<sub>2</sub>-4'), 0.80 (3H, t, *J* = 6.8 Hz, H<sub>3</sub>-5'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 137.6 (C-2), 134.7 (C-8a), 128.7 (C-4), 128.6 (C-12a), 126.3 (C-11), 125.7 (C-5), 125.4 (C-7), 123.1 (C-10), 119.0 (C-12), 112.8 (C-9), 105.0 (C-6), 45.5 (C-1'), 30.7 (C-2'), 28.7 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (+)-HRESIMS *m/z* 288.1261 [M+H]<sup>+</sup> (calcd for C<sub>16</sub>H<sub>19</sub><sup>35</sup>ClN<sub>3</sub>, 288.1262), *m/z* 290.1227 [M+H]<sup>+</sup> (calcd for C<sub>16</sub>H<sub>19</sub><sup>37</sup>ClN<sub>3</sub>, 290.1237).

### 3.2.94. 7-Chloro-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (93)

Using the general procedure, reaction of 7-chloro-1H-indole-3-carbaldehyde (0.031 g, 0.174 mmol) with pentylamine (20 µL, 0.174 mmol), K<sub>2</sub>CO<sub>3</sub> (0.024 g, 0.174 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.174 mmol) followed by purification using silica gel column chromatography (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.041 g, 82%). R<sub>f</sub> = 0.36 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 122–123 °C; IR (ATR) ν<sub>max</sub> 3097, 2956, 2929, 2858, 1436, 1110, 737 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 8.96 (1H, br s, NH-8), 7.64 (1H, d, *J* = 1.0 Hz, H-2), 7.45 (1H, dd, *J* = 8.0, 1.0 Hz, H-12), 7.31 (1H, d, *J* = 2.5 Hz, H-7), 7.27 (1H, dd, *J* = 8.0, 7.5 Hz, H-10), 7.14 (1H, d, *J* = 1.0 Hz, H-4), 7.11 (1H, dd, *J* = 7.5, 1.0 Hz, H-11), 3.90 (2H, t, *J* = 7.2 Hz, H<sub>2</sub>-1'), 1.63 (2H, p, *J* = 7.2 Hz, H<sub>2</sub>-2'), 1.23–1.13 (4H, m, H<sub>2</sub>-3', H<sub>2</sub>-4'), 0.79 (3H, t, *J* = 7.0 Hz, H<sub>3</sub>-5'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 137.8 (C-2), 133.5 (C-8a), 129.1 (C-4), 128.9 (C-12a), 125.4 (C-5), 124.3 (C-7), 122.3 (C-10), 121.4 (C-11), 118.4 (C-12), 117.1 (C-9), 106.8 (C-6), 45.4 (C-1'), 30.7 (C-2'), 28.7 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS *m/z* 286.1112 [M−H]<sup>−</sup> (calcd for C<sub>16</sub>H<sub>17</sub><sup>35</sup>ClN<sub>3</sub>, 286.1116), *m/z* 288.1091 [M−H]<sup>−</sup> (calcd for C<sub>16</sub>H<sub>17</sub><sup>37</sup>ClN<sub>3</sub>, 288.1091).

### 3.2.95. 4-Bromo-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (94)

Using the general procedure, reaction of 4-bromo-1H-indole-3-carbaldehyde (0.034 g, 0.150 mmol) with pentylamine (17 µL, 0.150 mmol), K<sub>2</sub>CO<sub>3</sub> (0.021 g, 0.150 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.030 g, 0.150 mmol) followed by purification by trituration with CH<sub>2</sub>Cl<sub>2</sub> afforded the title compound as a yellow solid (0.026 g, 52%). R<sub>f</sub> = 0.46 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); m.p. 207–208 °C; IR (ATR) ν<sub>max</sub> 3140, 2930, 2861, 1337, 1110, 741 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.11 (1H, br s, NH-8), 7.64 (1H, d, *J* = 1.0 Hz, H-2), 7.42 (1H, dd, *J* = 8.3, 1.0 Hz, H-9), 7.31 (1H, dd, *J* = 7.9, 1.0 Hz, H-11), 7.29 (1H, d, *J* = 2.7 Hz, H-7), 7.08 (1H, dd, *J* = 8.3, 7.9 Hz, H-10), 7.05 (1H, d, *J* = 1.0 Hz, H-4), 3.78 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-1'), 1.59 (2H, p, *J* = 7.3 Hz, H<sub>2</sub>-2'), 1.22–1.12 (4H, m, H<sub>2</sub>-3', H<sub>2</sub>-4'), 0.79 (3H, t, *J* = 6.8 Hz, H<sub>3</sub>-5'); <sup>13</sup>C NMR (100 MHz, CDCl<sub>3</sub>) δ 137.14 (C-8a), 137.08 (C-2), 130.5 (C-4), 127.2 (C-7), 126.3 (C-12a), 125.0 (C-5), 124.8 (C-11), 123.6 (C-10), 114.1 (C-4), 111.0 (C-9), 105.5 (C-6), 45.6 (C-1'), 30.3 (C-2'), 28.9 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS *m/z* 330.0618 [M−H]<sup>−</sup> (calcd for C<sub>16</sub>H<sub>17</sub><sup>79</sup>BrN<sub>3</sub>, 330.0611), *m/z* 332.0596 [M−H]<sup>−</sup> (calcd for C<sub>16</sub>H<sub>17</sub><sup>81</sup>BrN<sub>3</sub>, 332.0592).

### 3.2.96. 5-Methoxy-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (95)

Using the general procedure, reaction of 5-methoxy-1H-indole-3-carbaldehyde (0.031 g, 0.176 mmol) with pentylamine (20 µL, 0.176 mmol), K<sub>2</sub>CO<sub>3</sub> (0.025 g, 0.176 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.035 g, 0.176 mmol) followed by purification using silica gel column chromatography (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 1:0→9:1) afforded the title compound as a brown gum (0.021 g, 42%). R<sub>f</sub> = 0.33 (CH<sub>2</sub>Cl<sub>2</sub>:MeOH, 9:1); IR (ATR) ν<sub>max</sub> 3183, 2957, 2858, 1485, 1212, 803 cm<sup>-1</sup>; <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 8.97 (1H, br s, NH-8), 7.65 (1H, br s, H-2), 7.33 (1H, d, *J* = 8.8 Hz, H-9), 7.22 (1H, d, *J* = 2.5 Hz, H-7), 7.15 (1H, br s, H-4), 6.96 (1H, d, *J* = 2.4 Hz, H-12), 6.91 (1H, dd, *J* = 8.8, 2.4 Hz, H-10), 3.90 (2H, t, *J* = 7.3 Hz, H<sub>2</sub>-1'), 3.81 (3H, s, OMe), 1.64 (2H, p, *J* = 7.3 Hz, H<sub>2</sub>-2'), 1.24–1.14 (4H, m, H<sub>2</sub>-3', H<sub>2</sub>-4'), 0.80 (3H,
$t$, $J = 6.8$ Hz, $H_3-5'$); ¹³C NMR (100 MHz, CDCl₃) $δ$ 154.9 (C-11), 137.4 (C-2), 131.2 (C-8a), 128.5 (C-4), 128.0 (C-12a), 126.3 (C-5), 124.5 (C-7), 113.4 (C-10), 112.4 (C-9), 105.2 (C-6), 100.9 (C-12), 56.0 (OMe), 45.4 (C-1'), 30.8 (C-2'), 28.8 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS $m/z$ 282.1601 [M-H]⁻ (calcd for C₁₇H₂₀N₃O, 282.1612).

### 3.2.97. 6-Methoxy-3-(1-pentyl-1H-imidazol-5-yl)-1H-indole (96)

Using the general procedure, reaction of 6-methoxy-1H-indole-3-carbaldehyde (0.031 g, 0.176 mmol) with pentylamine (20 µL, 0.176 mmol), K₂CO₃ (0.025 g, 0.176 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.035 g, 0.176 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown gum (0.016 g, 32%). $R_f = 0.33$ (CH₂Cl₂:MeOH, 9:1); IR (ATR) $ν_{max}$ 3191, 2930, 2861, 1457, 1163, 805 $cm^{-1}$; ¹H NMR (400 MHz, CDCl₃) $δ$ 8.87 (1H, br s, NH-8), 7.62 (1H, d, $J = 1.0$ Hz, H-2), 7.41 (1H, d, $J = 8.8$ Hz, H-12), 7.13 (1H, br s, H-4), 7.12 (1H, d, $J = 2.4$ Hz, H-7), 6.92 (1H, d, $J = 2.2$ Hz, H-9), 6.83 (1H, dd, $J = 8.8, 2.2$ Hz, H-11), 3.91 (2H, t, $J = 7.4$ Hz, H₂-1'), 3.85 (3H, s, OMe), 1.63 (2H, p, $J = 7.4$ Hz, H₂-2'), 1.24–1.14 (4H, m, H₂-3', H₂-4'), 0.80 (3H, t, $J = 6.8$ Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) $δ$ 157.0 (C-10), 137.4 (C-2), 137.0 (C-8a), 128.4 (C-4), 126.3 (C-5), 122.5 (C-7), 121.8 (C-12a), 120.3 (C-12), 110.6 (C-11), 105.5 (C-6), 94.9 (C-9), 55.8 (OMe), 45.4 (C-1'), 30.7 (C-2'), 28.8 (C-3'), 22.2 (C-4'), 13.9 (C-5'); (-)-HRESIMS $m/z$ 282.1603 [M-H]⁻ (calcd for C₁₇H₂₀N₃O, 282.1612).

### 3.2.98. 3-(1-(Benzo[d][1,3]dioxol-5-ylmethyl)-1H-imidazol-5-yl)-5-chloro-1H-indole (97)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with piperonylamine (0.035 mL, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a pale brown solid (0.040 g, 41%). $R_f = 0.30$ (EtOAc); IR (ATR) $ν_{max}$ 3401, 1664, 1504, 1491, 1447, 1250, 1110, 1025, 1005, 923, 894, 762 $cm^{-1}$; ¹H NMR (400 MHz, DMSO-d₆) $δ$ 11.56 (1H, br s, NH-8), 7.82 (1H, br s, H-2), 7.44 (1H, d, $J = 8.6$ Hz, H-9), 7.42 (1H, d, $J = 2.7$ Hz, H-7), 7.38 (1H, d, $J = 2.0$ Hz, H-12), 7.14 (1H, dd, $J = 8.6, 2.1$ Hz, H-10), 7.09 (1H, br s, H-4), 6.77 (1H, d, $J = 8.0$ Hz, H-7'), 6.52 (1H, d, $J = 1.6$ Hz, H-3'), 6.40 (1H, dd, $J = 8.1, 1.5$ Hz, H-8'), 5.94 (2H, s, H₂-5'), 5.13 (2H, s, H₂-1'); ¹³C NMR (100 MHz, DMSO-d₆) $δ$ 147.4 (C-3a'), 146.5 (C-6a'), 138.4 (C-2), 134.4 (C-8a), 131.6 (C-2'), 127.7 (C-12a), 127.6 (C-4), 125.9 (C-7), 125.4 (C-5), 124.3 (C-11), 121.7 (C-10), 119.9 (C-8'), 117.9 (C-12), 113.3 (C-9), 108.2 (C-7'), 107.1 (C-3'), 103.4 (C-6), 101.0 (C-5'), 47.5 (C-1'); (+)-HRESIMS $m/z$ 352.0841 [M+H]⁺ (calcd for C₁₉H₁₅³ClN₃O₂, 352.0847), $m/z$ 354.0815 [M+H]⁺ (calcd for C₁₉H₁₅³ClN₃O₂, 354.0824).

### 3.2.99. 5-Chloro-3-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-5-yl)-1H-indole (98)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with aminomethyl pyrrolidine (0.038 mL, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel flash chromatography (EtOAc) afforded the title compound as an orange oil (0.048 g, 55%). $R_f = 0.03$ (EtOAc); IR (ATR) $ν_{max}$ 3118, 2964, 2803, 1625, 1457, 1338, 1110, 921, 894, 800 $cm^{-1}$; ¹H NMR (400 MHz, DMSO-d₆) $δ$ 11.63 (1H, s, NH-8), 7.78 (1H, br s, H-2), 7.63 (1H, d, $J = 2.6$ Hz, H-7), 7.47 (1H, d, $J = 8.6$ Hz, H-9), 7.44 (1H, d, $J = 2.0$ Hz, H-12), 7.16 (1H, dd, $J = 8.6, 2.1$ Hz, H-10), 6.99 (1H, br s, H-4), 4.05 (2H, t, $J = 6.7$ Hz, H₂-1'), 2.58 (2H, t, $J = 6.7$ Hz, H₂-2'), 2.31–2.28 (4H, m, 2H₂-4'), 1.59–1.55 (4H, m, 2H₂-5'); ¹³C NMR (100 MHz, DMSO-d₆) $δ$ 138.1 (C-2), 134.5 (C-8a), 127.8 (C-12a), 127.3 (C-4), 126.2 (C-7), 125.1 (C-5), 124.3 (C-11), 121.7 (C-10), 117.9 (C-12), 113.4 (C-9), 103.7 (C-6), 55.7 (C-2'), 53.4 (2C-4'), 43.6 (C-1'), 23.0 (2C-5'); (+)-HRESIMS $m/z$ 315.1371 [M+H]⁺ (calcd for C₁₇H₂₀ClN₄, 315.1371).
### 3.2.100. (E)-5-Chloro-3-(1-(3,7-dimethylocta-2,6-dien-1-yl)-1H-imidazol-5-yl)-1H-indole (99)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with geranylamine (0.051 mL, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) to afford the title product as a yellow oil (0.029 g, 29%). R_f = 0.62 (EtOAc); IR (ATR) νmax 2918, 1625, 1458, 1377, 1281, 1220, 1109, 921, 893, 799 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.62 (1H, s, NH-8), 7.70 (1H, br s, H-2), 7.57 (1H, d, *J* = 2.5 Hz, H-7), 7.46 (1H, d, *J* = 8.6 Hz, H-9), 7.43 (1H, d, *J* = 1.8 Hz, H-12), 7.15 (1H, dd, *J* = 8.6, 2.0 Hz, H-10), 7.03 (1H, br s, H-4), 5.17 (1H, t, *J* = 6.7 Hz, H-2'), 4.97–4.95 (1H, m, H-6'), 4.55 (2H, d, *J* = 6.7 Hz, H₂-1'), 1.95–1.88 (4H, m, H₂-4', H₂-5'), 1.58 (3H, s, H₃-10'), 1.49 (3H, s, H₃-8'), 1.47 (3H, s, H₃-9'); ¹³C NMR (100 MHz, DMSO-d₆) δ 139.1 (C-3'), 137.4 (C-2), 134.5 (C-8a), 131.0 (C-7'), 127.8 (C-12a), 127.5 (C-4), 126.2 (C-7), 125.1 (C-5), 124.3 (C-11), 123.7 (C-6'), 121.7 (C-10), 120.1 (C-2'), 117.9 (C-12), 113.3 (C-9), 103.7 (C-6), 42.6 (C-1'), 38.7 (C-4'), 25.6 (C-10'), 25.4 (C-5'), 17.5 (C-8'), 15.8 (C-9'); (+)-HRESIMS m/z 354.1735 [M+H]⁺ (calcd for C₂₁H₂₅₃⁵ClN₃, 354.1732), m/z 356.1706 [M+H]⁺ (calcd for C₂₁H₂₅₃⁷ClN₃, 356.1709).

### 3.2.101. 6-(5-(5-Chloro-1H-indol-3-yl)-1H-imidazol-1-yl)hexan-1-ol (100)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with aminohexanol (0.037 g, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) to afford the title compound as a yellow oil (0.068 g, 77%). R_f = 0.03 (EtOAc); IR (ATR) νmax 3220, 2932, 2859, 1626, 1458, 1226, 1111, 1050, 1024, 1004, 922, 894, 801, 760 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.65 (1H, br s, NH-8), 7.76 (1H, br s, H-2), 7.61 (1H, d, *J* = 2.5 Hz, H-7), 7.48 (1H, d, *J* = 8.6 Hz, H-9), 7.43 (1H, d, *J* = 2.0 Hz, H-12), 7.16 (1H, dd, *J* = 8.6, 2.1 Hz, H-10), 7.02 (1H, br s, H-4), 4.31 (1H, br s, OH), 3.95 (2H, t, *J* = 7.0 Hz, H₂-1'), 3.28 (2H, t, *J* = 6.6 Hz, H₂-6'), 1.52 (2H, tt, *J* = 7.3, 7.0 Hz, H₂-2'), 1.27 (2H, tt, *J* = 7.0, 6.6 Hz, H₂-5'), 1.18–1.05 (4H, m, H₂-3', H₂-4'); ¹³C NMR (100 MHz, DMSO-d₆) δ 137.9 (C-2), 134.5 (C-8a), 127.8 (C-12a), 127.6 (C-4), 126.0 (C-7), 125.1 (C-5), 124.3 (C-11), 121.7 (C-10), 117.9 (C-12), 113.4 (C-9), 103.8 (C-6), 60.5 (C-6'), 44.4 (C-1'), 32.3 (C-5'), 30.2 (C-2'), 25.7 (C-4'), 24.9 (C-3'); (+)-HRESIMS m/z 318.1365 [M+H]⁺ (calcd for C₁₇H₂₁ClN₃O, 318.1368).

### 3.2.102. Tert-Butyl (6-(5-(5-chloro-1H-indol-3-yl)-1H-imidazol-1-yl)hexyl)carbamate (101)

Using the general procedure, reaction of 5-chloro-1H-indole-3-carbaldehyde (0.050 g, 0.278 mmol) with N-Boc-1,6-hexanediamine (0.062 mL, 0.278 mmol), K₂CO₃ (0.038 g, 0.278 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.054 g, 0.278 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) to afford the title product as an orange oil (0.099 g, 85%). R_f = 0.03 (EtOAc); IR (ATR) νmax 3228, 2932, 2860, 1684, 1512, 1457, 1366, 1337, 1276, 1166, 1109, 1028, 894, 799, 786, 703 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 11.61 (1H, d, *J* = 1.5 Hz, NH-8), 7.75 (1H, br s, H-2), 7.60 (1H, d, *J* = 2.5 Hz, H-7), 7.47 (1H, d, *J* = 1.9 Hz, H-9), 7.42 (1H, d, *J* = 1.9 Hz, H-12), 7.16 (1H, dd, *J* = 8.7, 2.1 Hz, H-10), 7.00 (1H, br s, H-7), 6.68 (1H, t, *J* = 5.4 Hz, NH-7'), 3.95 (2H, t, *J* = 7.1 Hz, H₂-1'), 2.80 (2H, q, *J* = 6.5 Hz, H₂-6'), 1.54–1.48 (2H, m, H₂-2'), 1.34 (9H, s, 3H₃-11'), 1.26–1.20 (2H, m, H₂-5'), 1.11–1.08 (4H, m, H₂-3', H₂-4'); ¹³C NMR (100 MHz, DMSO-d₆) δ 155.5 (C-8'), 137.9 (C-2), 134.5 (C-8a), 127.7 (C-12a), 127.5 (C-4), 126.0 (C-7), 125.0 (C-5), 124.3 (C-11), 121.7 (C-10), 117.8 (C-12), 113.4 (C-9) 103.7 (C-6), 77.2 (C-10'), 44.3 (C-1'), 39.6 (C-6'), 30.1 (C-2'), 29.2 (C-5'), 28.2 (3C-11'), 25.7 (C-4'), 25.5 (C-3'); (+)-HRESIMS m/z 417.2034 [M+H]⁺ (calcd for C₂₂H₃₀³⁵ClN₄O₂, 417.2041), m/z 419.2012 [M+H]⁺ (calcd for C₂₂H₃₀³⁷ClN₄O₂, 419.2020).
### 3.2.103. 6-(5-(5-Chloro-1H-indol-3-yl)-1H-imidazol-1-yl)hexan-1-aminium 2,2,2-trifluoroacetate (102)

A solution of *tert*-butyl (6-(5-(5-chloro-1H-indol-3-yl)-1H-imidazol-1-yl)hexyl)carbamate (101) (0.022 g, 0.0528 mmol) in CH₂Cl₂:TFA (10:1, 2.2 ml) was stirred for 2 h at r.t. under N₂ atmosphere. The resulting solution was dried under reduced pressure and subjected to C₈ reverse-phased column chromatography eluting with 3:1 H₂O:MeOH (+0.05% TFA) to afford the title compound as an orange oil in quantitative yield as the TFA salt. R_f = 0.71 (70% MeOH/30% 1M HCl, C₁₈); IR (ATR) νmax 3116, 2938, 1674, 1201, 1132, 1050, 1026, 1006, 896, 831, 800, 721 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 12.05 (1H, d, *J* = 1.9 Hz, NH-8), 9.27 (1H, s, H-2), 7.89 (1H, s, H-4), 7.87 (1H, d, *J* = 2.7 Hz, H-7), 7.72 (3H, br s, NH₃-7'), 7.58 (1H, d, *J* = 1.9 Hz, H-12), 7.55 (1H, d, *J* = 8.7 Hz, H-9), 7.23 (1H, dd, *J* = 8.8, 2.0 Hz, H-10), 4.16 (2H, t, *J* = 7.3 Hz, H₂-1'), 2.73–2.64 (2H, m, H₂-6'), 1.66–1.59 (2H, m, H₂-2'), 1.45–1.38 (2H, m, H₂-5'), 1.17–1.15 (4H, m, H₂-3', H₂-4'); ¹³C NMR (100 MHz, DMSO-d₆) δ 135.5 (C-2), 134.5 (C-8a), 128.5 (C-5), 127.5 (C-12a), 127.3 (C-7), 125.1 (C-11), 122.4 (C-10), 118.2 (C-4), 117.7 (C-12), 113.9 (C-9), 99.4 (C-6), 46.6 (C-1'), 38.6 (C-6'), 28.7 (C-2'), 26.7 (C-5'), 25.1 (C-3'), 25.0 (C-4'); (+)-HRESIMS *m/z* 317.1526 [M+H]⁺ (calcd for C₁₇H₂₂ClN₄ 317.1528).

### 3.2.104. 1-Benzyl-5-phenyl-1H-imidazole (103)

Using the general procedure, reaction of benzaldehyde (46 µL, 0.417 mmol) with benzylamine (48 µL, 0.417 mmol), K₂CO₃ (0.060 g, 0.417 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.084 g, 0.417 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as an off-white solid (0.013 g, 13%). R_f = 0.60 (CH₂Cl₂:MeOH, 9:1); m.p. 99–100 °C; IR (ATR) νmax 3373, 3084, 2919, 2851, 1109, 725 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.56 (1H, d, *J* = 1.0 Hz, H-2), 7.39–7.31 (3H, m, 2H-8, H-9), 7.31–7.25 (5H, m, 2H-7, 2H-4', H-5'), 7.14 (1H, d, *J* = 1.0 Hz, H-4), 7.03–6.99 (2H, m, 2H-3'), 5.15 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 138.8 (C-2), 136.9 (C-2'), 133.6 (C-5), 129.8 (C-6), 129.0 (2C-8, 2C-4'), 128.8 (2C-7), 128.3 (C-9/C-5'), 128.2 (C-9/C-5'), 128.1 (C-4), 126.8 (2C-3'), 48.9 (C-1'); (+)-HRESIMS *m/z* 235.1233 [M+H]⁺ (calcd for C₁₆H₁₅N₂, 235.1230).

### 3.2.105. 1-Benzyl-5-(4-methoxyphenyl)-1H-imidazole (104)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (23 µL, 0.189 mmol) with benzylamine (21 µL, 0.189 mmol), K₂CO₃ (0.026 g, 0.189 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.037 g, 0.189 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow solid (0.025 g, 50%). R_f = 0.60 (CH₂Cl₂:MeOH, 9:1); m.p. 83–84 °C; IR (ATR) νmax 3351, 2920, 2851, 1251, 730 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.54 (1H, d, *J* = 1.0 Hz, H-2), 7.33–7.24 (3H, m, 2H-4', H-5'), 7.21–7.16 (2H, m, 2H-7), 7.07 (1H, d, *J* = 1.0 Hz, H-4), 7.02–6.98 (2H, m, 2H-3'), 6.91–6.86 (2H, m, 2H-8'), 5.10 (2H, s, H₂-1'), 3.80 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.7 (C-9), 138.4 (C-2), 137.0 (C-2'), 133.3 (C-5), 130.5 (2C-7), 129.0 (2C-4'), 128.0 (C-5'), 127.9 (C-4), 126.8 (2C-3'), 122.1 (C-6), 114.2 (2C-8), 55.4 (OMe), 48.7 (C-1'); (+)-HRESIMS *m/z* 265.1333 [M+H]⁺ (calcd for C₁₇H₁₇N₂O, 265.1335).

### 3.2.106. 1-Phenethyl-5-phenyl-1H-imidazole (105)

Using the general procedure, reaction of benzaldehyde (21 µL, 0.201 mmol) was reacted with phenethylamine (25 µL, 0.201 mmol), K₂CO₃ (0.028 g, 0.201 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.039 g, 0.201 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow oil (0.029 g, 58%). R_f = 0.53 (CH₂Cl₂:MeOH, 9:1); IR (ATR) νmax 3376, 3029, 2932, 2856, 1484, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.45–7.35 (3H, m, 2H-8, H-9), 7.38 (1H, d, *J* = 1.0 Hz, H-2), 7.33–7.28 (2H, m, 2H-7), 7.26–7.16 (3H, m, 2H-5', H-6'), 7.04 (1H, d, *J* = 1.0 Hz, H-4), 6.95–6.90 (2H, m, 2H-4'), 4.19 (2H, t, *J* = 7.3 Hz, H₂-1'), 2.85 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 138.2 (C-2), 137.4 (C-3'), 132.9 (C-5), 130.2 (C-6), 129.0 (2C-8), 128.9 (2C-5'), 128.8 (2C-4'), 128.7 (2C-7), 128.4 (C-4), 128.2 (C-9), 127.0 (C-6'), 46.9 (C-1'), 37.5 (C-2'); (+)-HRESIMS *m/z* 249.1390 [M+H]⁺ (calcd for C₁₇H₁₇N₂, 249.1386).
### 3.2.107. 5-(4-Methoxyphenyl)-1-phenethyl-1H-imidazole (106)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (22 µL, 0.180 mmol) was reacted with phenethylamine (23 µL, 0.180 mmol), K₂CO₃ (0.025 g, 0.180 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.035 g, 0.180 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow oil (0.033 g, 66%). R_f = 0.47 (CH₂Cl₂:MeOH, 9:1); IR (ATR) ν_max 3079, 3028, 2835, 1454, 1248, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.36 (1H, d, *J* = 1.0 Hz, H-2), 7.27-7.21 (2H, m, 2H-5'), 7.23-7.18 (3H, m, 2H-7, H-6'), 6.98 (1H, d, *J* = 1.0 Hz, H-4), 6.97-6.92 (4H, 2H-8, 2H-4'), 4.14 (2H, t, *J* = 7.3 Hz, H₂-1'), 3.85 (3H, s, OMe), 2.85 (2H, t, *J* = 7.3 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 159.7 (C-9), 137.8 (C-2), 137.5 (C-3'), 132.7 (C-5), 130.4 (2C-7), 128.8 (2C-5'), 128.7 (2C-4'), 127.9 (C-4), 127.0 (C-6'), 122.5 (C-6), 114.3 (2C-8), 55.5 (OMe), 46.8 (C-1'), 37.5 (C-2'); (+)-HRESIMS *m/z* 279.1494 [M+H]⁺ (calcd for C₁₈H₁₉N₂O, 279.1492).

### 3.2.108. 1-(4-Methoxybenzyl)-5-phenyl-1H-imidazole (107)

Using the general procedure, reaction of benzaldehyde (17 µL, 0.170 mmol) with *p*-methoxybenzylamine (22 µL, 0.170 mmol), K₂CO₃ (0.024 g, 0.170 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.033 g, 0.170 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a clear oil (0.006 g, 13%). R_f = 0.60 (CH₂Cl₂:MeOH, 9:1); IR (ATR) ν_max 3392, 2933, 2837, 1513, 1249, 769 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.53 (1H, d, *J* = 1.0 Hz, H-2), 7.40-7.33 (3H, m, 2H-8, H-9), 7.32-7.28 (2H, m, 2H-7), 7.12 (1H, d, *J* = 1.0 Hz, H-4), 6.98-6.93 (2H, m, 2H-3'), 6.85-6.80 (2H, m, 2H-4'), 5.08 (2H, s, H₂-1'), 3.78 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.4 (C-5'), 138.6 (C-2), 133.5 (C-5), 130.0 (C-6), 129.1 (2C-7), 128.80 (2C-8), 128.79 (C-2'), 128.4 (C-4/C-9), 128.3 (2C-3'), 128.2 (C-4/C-9), 114.4 (2C-4'), 55.4 (OMe), 48.5 (C-1'); (+)-HRESIMS *m/z* 265.1342 [M+H]⁺ (calcd for C₁₇H₁₇N₂O, 265.1335).

### 3.2.109. 1-(4-Methoxybenzyl)-5-(4-methoxyphenyl)-1H-imidazole (108)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (21 µL, 0.170 mmol) with *p*-methoxybenzylamine (22 µL, 0.170 mmol), K₂CO₃ (0.024 g, 0.170 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.033 g, 0.170 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow oil (0.022 g, 44%). R_f = 0.56 (CH₂Cl₂:MeOH, 9:1); IR (ATR) ν_max 3371, 2934, 2836, 1512, 1246, 818 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.51 (1H, d, *J* = 1.0 Hz, H-2), 7.22-7.18 (2H, m, 2H-7), 7.05 (1H, d, *J* = 1.0 Hz, H-4), 6.97-6.92 (2H, m, 2H-3'), 6.92-6.88 (2H, m, 2H-8), 6.84-6.80 (2H, m, 2H-4'), 5.03 (2H, s, H₂-1'), 3.82 (3H, s, 9-OMe), 3.78 (3H, s, 5'-OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.7 (C-9), 159.4 (C-5'), 138.2 (C-2), 133.2 (C-5), 130.5 (2C-7), 128.9 (C-2'), 128.3 (2C-3'), 127.9 (C-4), 122.3 (C-6), 114.4 (2C-4'), 114.2 (2C-8), 55.43 (9-OMe), 55.42 (5'-OMe), 48.3 (C-1'); (+)-HRESIMS *m/z* 295.1448 [M+H]⁺ (calcd for C₁₈H₁₉N₂O₂, 295.1441).

### 3.2.110. 1-(4-Methoxyphenethyl)-5-phenyl-1H-imidazole (109)

Using the general procedure, reaction of benzaldehyde (36 µL, 0.358 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.064 g, 0.358 mmol), K₂CO₃ (0.050 g, 0.358 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.070 g, 0.358 mmol) followed by purification using a combination of silica gel column chromatography (EtOAc) and reversed-phase C₈ column chromatography (H₂O:MeOH, 1:0→0:1) afforded the title compound as a yellow gum (0.005 g, 5%). R_f = 0.54 (CH₂Cl₂:MeOH, 9:1); IR (ATR) ν_max 3367, 3061, 2932, 1513, 1247, 763 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.45-7.35 (4H, m, H-2, 2H-8, H-9), 7.33-7.29 (2H, m, 2H-7), 7.05 (1H, br s, H-4), 6.86-6.80 (2H, m, 2H-4'), 6.79-6.73 (2H, m, 2H-5'), 4.16 (2H, t, *J* = 7.4 Hz, H₂-1'), 3.77 (3H, s, OMe), 2.79 (2H, t, *J* = 7.4 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 158.7 (C-6'), 138.3 (C-2), 133.0 (C-5), 130.2 (C-6), 129.7 (2C-4'), 129.4 (C-3'), 129.0 (2C-8), 128.9 (2C-7), 128.2 (C-4, C-9), 114.3 (2C-5'), 55.4 (OMe), 47.2 (C-1'), 36.6 (C-2'); (+)-HRESIMS *m/z* 279.1499 [M+H]⁺ (calcd for C₁₈H₁₉N₂O, 279.1492).
### 3.2.111. 1-(4-Methoxyphenethyl)-5-(4-methoxyphenyl)-1H-imidazole (110)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (20 µL, 0.162 mmol) was reacted with *p*-methoxyphenethylamine hydrochloride (0.030 g, 0.162 mmol), K₂CO₃ (0.023 g, 0.162 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.162 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow gum (0.006 g, 12%). R_f = 0.54 (CH₂Cl₂:MeOH, 9:1); IR (ATR) νmax 3116, 2930, 2839, 1513, 1248, 821 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.35 (1H, br s, H-2), 7.24–7.20 (2H, m, 2H-7), 6.98 (1H, br s, H-4), 6.97–6.94 (2H, m, 2H-8), 6.87–6.84 (2H, m, 2H-4'), 6.80–6.75 (2H, m, 2H-5'), 4.11 (2H, t, *J* = 7.0 Hz, H₂-1'), 3.86 (3H, s, 9-OMe), 3.77 (3H, s, 6'-OMe), 2.79 (2H, t, *J* = 7.0 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 159.7 (C-9), 158.7 (C-6'), 137.9 (C-2), 132.7 (C-5), 130.4 (2C-7), 129.7 (2C-4'), 129.5 (C-3'), 128.0 (C-4), 122.6 (C-6), 114.3 (2C-8/2C-5'), 114.2 (2C-8/2C-5'), 55.5 (9-OMe), 55.4 (6'-OMe), 47.0 (C-1'), 36.7 (C-2'); (+)-HRESIMS *m/z* 309.1602 [M+H]⁺ (calcd for C₁₉H₂₁N₂O₂, 309.1598).

### 3.2.112. 3-((5-Phenyl-1H-imidazol-1-yl)methyl)-1H-indole (111)

Using the general procedure, reaction of benzaldehyde (19 µL, 0.183 mmol) was reacted with (1H-indol-3-yl)methanamine (0.027 g, 0.183 mmol), K₂CO₃ (0.025 g, 0.183 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.036 g, 0.183 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.014 g, 28%). R_f = 0.49 (CH₂Cl₂:MeOH, 9:1); m.p. 57–58 °C; IR (ATR) νmax 3412, 2924, 2849, 1110, 744 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.69 (1H, br s, NH-4'), 7.56 (1H, d, *J* = 1.0 Hz, H-2), 7.44–7.39 (5H, m, 2H-7, 2H-8, H-9), 7.38–7.33 (2H, m, H-5', H-8'), 7.20 (1H, ddd, *J* = 8.3, 7.0, 1.0 Hz, H-6'), 7.13 (1H, d, *J* = 1.0 Hz, H-4), 7.09 (1H, ddd, *J* = 8.0, 7.0, 1.0 Hz, H-7'), 6.91 (1H, d, *J* = 2.5 Hz, H-3'), 5.30 (2H, s, H₂-1'); ¹³C NMR (100 MHz, CDCl₃) δ 138.5 (C-2), 136.6 (C-4a'), 133.4 (C-5), 130.2 (C-6), 129.0 (2C-8), 128.9 (2C-7), 128.1 (C-4/C-9), 128.0 (C-4/C-9), 126.0 (C-8a'), 123.5 (C-3'), 122.8 (C-6'), 120.3 (C-7'), 118.4 (C-8'), 111.6 (C-5'), 111.5 (C-2'), 41.5 (C-1'); (+)-HRESIMS *m/z* 274.1339 [M+H]⁺ (calcd for C₁₈H₁₆N₃, 274.1339).

### 3.2.113. 3-((5-(4-Methoxyphenyl)-1H-imidazol-1-yl)methyl)-1H-indole (112)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (20 µL, 0.165 mmol) with (1H-indol-3-yl)methanamine (0.024 g, 0.165 mmol), K₂CO₃ (0.023 g, 0.165 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.032 g, 0.165 mmol) in DMF (1 mL) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow solid (0.026 g, 52%). R_f = 0.47 (CH₂Cl₂:MeOH, 9:1); m.p. 152–153 °C; IR (ATR) νmax 3417, 3105, 2925, 1250, 744 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.38 (1H, br s, NH-4'), 7.55 (1H, s, H-2), 7.37 (1H, dd, *J* = 8.3, 1.0 Hz, H-5'), 7.36 (1H, d, *J* = 8.3 Hz, H-8'), 7.34–7.30 (2H, m, 2H-7), 7.21 (1H, ddd, *J* = 8.3, 7.2, 1.0 Hz, H-6'), 7.10 (1H, ddd, *J* = 8.3, 7.2, 1.0 Hz, H-7'), 7.06 (1H, d, *J* = 1.0 Hz, H-4), 6.91 (1H, d, *J* = 2.5 Hz, H-3'), 5.27 (2H, s, H₂-1'), 3.83 (3H, s, OMe); ¹³C NMR (100 MHz, CDCl₃) δ 159.6 (C-9), 138.2 (C-2), 136.5 (C-4a'), 133.1 (C-5), 130.4 (2C-7), 127.6 (C-4), 126.0 (C-8a'), 123.3 (C-3'), 122.8 (C-6'), 122.6 (C-6), 120.3 (C-7'), 118.5 (C-8'), 114.3 (2C-8), 111.9 (C-2'), 111.6 (C-5'), 55.5 (OMe), 41.3 (C-1'); (+)-HRESIMS *m/z* 304.1444 [M+H]⁺ (calcd for C₁₉H₁₈N₃O, 304.1444).

### 3.2.114. 3-(2-(5-Phenyl-1H-imidazol-1-yl)ethyl)-1H-indole (113)

Using the general procedure, reaction of benzaldehyde (17 µL, 0.174 mmol) with tryptamine (0.028 g, 0.174 mmol), K₂CO₃ (0.024 g, 0.174 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.034 g, 0.174 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a brown solid (0.023 g, 46%). R_f = 0.40 (CH₂Cl₂:MeOH, 9:1); m.p. 155–156 °C; IR (ATR) νmax 3417, 3170, 2921, 1482, 1221, 742 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.27 (1H, br s, NH-5'), 7.43–7.35 (4H, m, H-4, 2H-7, H-9), 7.35–7.30 (3H, m, 2H-8, H-6'), 7.28 (1H, dd, *J* = 7.8, 0.9 Hz, H-9'), 7.18 (1H, ddd, *J* = 6.9, 6.9, 0.9 Hz, H-7'), 7.06 (1H, d, *J* = 1.5 Hz, H-4), 7.06 (1H, ddd, *J* = 7.8, 6.9, 1.0 Hz, H-8'), 6.73 (1H, d, *J* = 2.2 Hz, H-4'), 4.25 (2H, t, *J* = 7.1 Hz, H₂-1'), 3.02 (2H, t, *J* = 7.1 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 138.5 (C-2), 136.4 (C-5a'), 133.0 (C-5), 130.3 (C-6),
129.0 (2C-8), 128.9 (2C-7), 128.3 (C-4/C-9), 128.2 (C-4/C-9), 127.0 (C-9a'), 122.5 (C-7'), 122.3 (C-4'), 119.7 (C-8'), 118.3 (C-9'), 111.5 (C-3', C-6'), 46.0 (C-1'), 27.3 (C-2'); (-)-HRESIMS *m/z* 286.1351 [M–H]⁻ (calcd for C₁₉H₁₆N₃, 286.1350).

### 3.2.115. 3-(2-(5-(4-Methoxyphenyl)-1H-imidazol-1-yl)ethyl)-1H-indole (114)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (19 µL, 0.157 mmol) with tryptamine (0.025 g, 0.157 mmol), K₂CO₃ (0.022 g, 0.157 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.031 g, 0.157 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow solid (0.030 g, 60%). R_f = 0.40 (CH₂Cl₂:MeOH, 9:1); m.p. 169–170 °C; IR (ATR) νmax 3412, 3163, 2929, 1488, 1250, 744 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.31 (1H, br s, NH-5'), 7.36 (1H, d, *J* = 1.0 Hz, H-2), 7.33 (1H, d, *J* = 8.3 Hz, H-6'), 7.28 (1H, d, *J* = 8.3 Hz, H-9'), 7.22 (2H, d, *J* = 8.8 Hz, 2H-7), 7.18 (1H, ddd, *J* = 8.3, 7.0, 1.0 Hz, H-7'), 7.06 (1H, ddd, *J* = 8.3, 7.0, 1.0 Hz, H-8'), 7.00 (1H, d, *J* = 1.0 Hz, H-4), 6.92 (2H, d, *J* = 8.8 Hz, 2H-8), 6.73 (1H, d, *J* = 2.5 Hz, H-4'), 4.21 (2H, t, *J* = 7.2 Hz, H₂-1'), 3.85 (3H, s, OMe), 3.01 (2H, t, *J* = 7.2 Hz, H₂-2'); ¹³C NMR (100 MHz, CDCl₃) δ 159.7 (C-9), 138.0 (C-2), 136.4 (C-5a'), 132.8 (C-5), 130.5 (2C-7), 127.8 (C-4), 127.0 (C-9a'), 122.6 (C-6), 122.5 (C-4'/C-7'), 122.3 (C-4'/C-7'), 119.6 (C-8'), 118.3 (C-9'), 114.3 (2C-8), 111.51 (C-3'), 111.47 (C-6'), 55.5 (OMe), 45.8 (C-1'), 27.4 (C-2'); (-)-HRESIMS *m/z* 316.1452 [M–H]⁻ (calcd for C₂₀H₁₈N₃O, 316.1455).

### 3.2.116. 1-Pentyl-5-phenyl-1H-imidazole (115)

Using the general procedure, reaction of benzaldehyde (24 µL, 0.233 mmol) with pentylamine (27 µL, 0.233 mmol), K₂CO₃ (0.032 g, 0.233 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.046 g, 0.233 mmol) followed by purification using silica gel column chromatography (EtOAc) afforded the title compound as a yellow gum (0.015 g, 30%). R_f = 0.53 (CH₂Cl₂:MeOH, 9:1); IR (ATR) νmax 3221, 2957, 2930, 2859, 1481, 1114, 764 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.55 (1H, br s, H-2), 7.46–7.40 (2H, m, 2H-8), 7.40–7.36 (3H, m, 2H-7, H-9), 7.06 (1H, br s, H-4), 3.95 (2H, t, *J* = 7.3 Hz, H₂-1'), 1.62 (2H, p, *J* = 7.3 Hz, H₂-2'), 1.28–1.12 (4H, m, H₂-3', H₂-4'), 0.82 (3H, t, *J* = 6.9 Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) δ 138.2 (C-2), 133.1 (C-5), 130.4 (C-6), 128.9 (2C-8), 128.8 (2C-7), 128.3 (C-4), 128.1 (C-9), 45.5 (C-1'), 30.7 (C-2'), 28.7 (C-3'), 22.1 (C-4'), 13.9 (C-5'); (+)-HRESIMS *m/z* 215.1549 [M+H]⁺ (calcd for C₁₄H₁₉N₂, 215.1543).

### 3.2.117. 5-(4-Methoxyphenyl)-1-pentyl-1H-imidazole (116)

Using the general procedure, reaction of *p*-methoxybenzaldehyde (25 µL, 0.205 mmol) with pentylamine (24 µL, 0.205 mmol), K₂CO₃ (0.028 g, 0.205 mmol) and *p*-toluenesulfonylmethyl isocyanide (0.040 g, 0.205 mmol) followed by purification using silica gel column chromatography (CH₂Cl₂:MeOH, 1:0→9:1) afforded the title compound as a yellow gum (0.028 g, 56%). R_f = 0.54 (CH₂Cl₂:MeOH, 9:1); IR (ATR) νmax 3237, 2957, 2930, 2860, 1482, 1249, 763 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.52 (1H, br s, H-2), 7.28–7.25 (2H, m, 2H-7), 6.99 (1H, br s, H-4), 6.98–6.93 (2H, m, 2H-8), 3.90 (2H, t, *J* = 7.2 Hz, H₂-1'), 3.85 (3H, s, OMe), 1.61 (2H, p, *J* = 7.2 Hz, H₂-2'), 1.28–1.12 (2H, m, H₂-3', H₂-4'), 0.83 (3H, t, *J* = 6.8 Hz, H₃-5'); ¹³C NMR (100 MHz, CDCl₃) δ 159.5 (C-9), 137.7 (C-2), 132.8 (C-5), 130.3 (C-7), 127.8 (C-4), 122.6 (C-6), 114.2 (C-8), 55.4 (OMe), 45.3 (C-1'), 30.7 (C-2'), 28.7 (C-3'), 22.1 (C-4'), 13.9 (C-5'); (+)-HRESIMS *m/z* 245.1653 [M+H]⁺ (calcd for C₁₅H₂₁N₂O, 245.1648).

## 3.3. Biological Evaluation

### 3.3.1. Antimicrobial Assays

The susceptibility of *S. aureus* (ATCC25923) to antibiotics and compounds was determined in microplates using the standard broth dilution method in accordance with the recommendations of the Comité de l'AntibioGramme de la Société Française de Microbiology (CA-SFM) as previously described. Briefly, the minimal inhibitory concentrations (MICs) were determined with an inoculum of 10⁵ CFU in 200 µL of Mueller-Hinton broth (MHB) containing two-fold serial dilutions of each drug. The MIC was defined as the
lowest concentration of drug that completely inhibited visible growth after incubation for 18 h at 37 °C. To determine all MICs, the measurements were independently repeated in triplicate [21].

Additional antimicrobial evaluation against *Staphylococcus aureus* MRSA (ATCC43300), *Pseudomonas aeruginosa* (ATCC27853), *Escherichia coli* (ATCC25922), *Klebsiella pneumoniae* (ATCC700603), *Acinetobacter baumannii* (ATCC19606), *Candida albicans* (ATCC90028), and *Cryptococcus neoformans* (ATCC208821) was undertaken at the Community for Open Antimicrobial Drug Discovery at The University of Queensland (Australia) according to their standard protocols [22]. For antimicrobial assays, the tested strains were cultured in either Luria broth (LB) (In Vitro Technologies, USB75852, Noble Park North, Australia), nutrient broth (NB) (Becton Dickinson, 234000, Macquarie Park, Australia), or cation-adjusted MHB at 37 °C overnight. A sample of culture was then diluted 40-fold in fresh MHB and incubated at 37 °C for 1.5–2 h. The compounds were serially diluted 2-fold across the wells of 96-well plates (Corning 3641, Tewksbury, MA, USA, nonbinding surface), with compound concentrations ranging from 0.015 to 64 µg/mL, plated in duplicate. The resultant mid log phase cultures were diluted to the final concentration of 1 × 10⁶ CFU/mL; then, 50 µL was added to each well of the compound containing plates giving a final compound concentration range of 0.008 to 32 µg/mL and a cell density of 5 × 10⁵ CFU/mL. All plates were then covered and incubated at 37 °C for 18 h. Resazurin was added at 0.001% final concentration to each well and incubated for 2 h before MICs were read by eye.

For the antifungal assay, fungi strains were cultured for 3 days on yeast extract-peptone dextrose (YPD) agar at 30 °C. A yeast suspension of 1 × 10⁶ to 5 × 10⁶ CFU/mL was prepared from five colonies. These stock suspensions were diluted with yeast nitrogen base (YNB) (Becton Dickinson, 233520) broth to a final concentration of 2.5 × 10³ CFU/mL. The compounds were serially diluted 2-fold across the wells of 96-well plates (Corning 3641, nonbinding surface), with compound concentrations ranging from 0.015 to 64 µg/mL and final volumes of 50 µL, plated in duplicate. Then, 50 µL of the fungi suspension that was previously prepared in YNB broth to the final concentration of 2.5 × 10³ CFU/mL was added to each well of the compound-containing plates, giving a final compound concentration range of 0.008 to 32 µg/mL. Plates were covered and incubated at 35 °C for 36 h without shaking. *C. albicans* MICs were determined by measuring the absorbance at OD₅₃₀. For *C. neoformans*, resazurin was added at 0.006% final concentration to each well and incubated for a further 3 h before MICs were determined by measuring the absorbance at OD₅₇₀-600.

Colistin and vancomycin were used as positive bacterial inhibitor standards for Gram-negative and Gram-positive bacteria, respectively. Fluconazole was used as a positive fungal inhibitor standard for *C. albicans* and *C. neoformans*. The antibiotics were provided in 4 concentrations, with 2 above and 2 below its MIC value, and plated into the first 8 wells of column 23 of the 384-well NBS plates. The quality control (QC) of the assays was determined by the antimicrobial controls and the Z'-factor (using positive and negative controls). Each plate was deemed to fulfil the quality criteria (pass QC), if the Z'-factor was above 0.4, and the antimicrobial standards showed full range of activity, with full growth inhibition at their highest concentration, and no growth inhibition at their lowest concentration.

### 3.3.2. Cytotoxicity Assays

For the HEK293 cytotoxicity assay, cells were counted manually in a Neubauer hemocytometer and plated at a density of 5000 cells/well into each well of the 384-well plates containing the 25× (2 µL) concentrated compounds. The medium used was Dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS). Cells were incubated together with the compounds for 20 h at 37 °C, 5% CO₂. To measure cytotoxicity, 5 µL (equals 100 µM final) of resazurin was added to each well after incubation, and incubated for further 3 h at 37 °C with 5% CO₂. After final incubation fluorescence intensity was measured as Fex 560/10 nm, em 590/10 nm (F₅₆₀/₅₉₀) using a Tecan M1000 Pro monochromator plate reader. CC₅₀ values (concentration at 50% cytotoxi-
city) were calculated by normalizing the fluorescence readout, with 74 µg/mL tamoxifen as negative control (0%) and normal cell growth as positive control (100%). The concentration-dependent percentage cytotoxicity was fitted to a dose response function (using Pipeline Pilot) and CC₅₀ values determined [22].

### 3.3.3. Hemolytic Assay

Human whole blood was washed three times with 3 volumes of 0.9% NaCl and then resuspended in same to a concentration of 0.5 × 10⁸ cells/mL, as determined by manual cell count in a Neubauer hemocytometer. The washed cells were then added to the 384-well compound-containing plates for a final volume of 50 µL. After a 10 min shake on a plate shaker the plates were then incubated for 1 h at 37 °C. After incubation, the plates were centrifuged at 1000 g for 10 min to pellet cells and debris, 25 µL of the supernatant was then transferred to a polystyrene 384-well assay plate. Hemolysis was determined by measuring the supernatant absorbance at 405 nm (OD₄₀₅). The absorbance was measured using a Tecan M1000 Pro monochromator plate reader. HC₁₀ and HC₅₀ (concentration at 10% and 50% hemolysis, respectively) were calculated by curve fitting the inhibition values vs. log(concentration) using a sigmoidal dose-response function with variable fitting values for top, bottom and slope [22].

### 3.3.4. Membrane Depolarization Assay

S. aureus (ATCC25923) was grown in MH II broth for 24 h at 37 °C. After reaching an OD₆₀₀ nm of 0.5, cells were centrifuged (3600 × g for 20 min at 20 °C) and washed twice with buffered sucrose solution (250 mM), magnesium sulfate solution (25 mM) and Hepes (5 mM) (pH = 7.2). The fluorescent dye 3,3'-diethylthiacarbocyanine iodide DiSC₃(5) was added to a final concentration of 5 µM and was incubated with the suspensions for 5 min at 37 °C to allow the dye incorporation into the polarized membranes. 10 µL of compound was then added to 90 µL of the fluorescent suspensions at different concentrations ranging from 200 µM to 25 µM. Fluorescence measurements were recorded for 20 minutes (excitation wavelength 622 nm, emission wavelength 690 nm).

The difference in the relative fluorescence values (RFU) from the control containing only buffer and the control containing bacteria treated only with cetyltrimethylammonium bromide (CTAB 1%) is taken as the maximum level of depolarization. Assays were performed in three independent experiments. Blank determined by using no compound. Maximum RFU determined by using CTAB 0.1%

Equation used:

$$ \frac{(\text{RFU of the compound} - \text{RFU of the blank}) \times 100}{\text{RFU of the maximum}} $$

## 4. Conclusions

In a bid to combat the surging increase of antibiotic-resistant bacteria a screening programme of a library of natural products, semi-synthetics and synthetic compounds was initiated targeting a subset of the ESKAPE pathogens. Following our discovery of weak anti-MRSA activity associated with two 3-substituted-1H-imidazol-5-yl-1H-indoles we have synthesized a further 99 analogues as well as 14 examples of structurally related 5-phenyl-1H-imidazoles. Surprisingly few examples from the extended set of analogues exhibited antimicrobial properties, with only two examples (26 and 32) identified as being promising non-toxic selective anti-MRSA compounds. Of note was the identification of two analogues, 57 (a phenethyl-indole-imidazole) and 111 (a 5-phenyl-1H-imidazole) as being non-toxic selective antifungals towards C. neoformans. Further elaboration of these anti-MRSA and antifungal compounds will be the subject of future research.
**Supplementary Materials:** The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/antibiotics11101450/s1, Figures S1–S116: NMR spectra of compounds 1–116.

**Author Contributions:** Conceptualization and methodology, M.M.C.; validation, formal analysis, investigation, data curation S.A.L., R.J.Z., K.S. and A.T.; writing—original draft preparation, M.M.C. and B.R.C.; funding acquisition, writing—review and editing, M.M.C., B.R.C., J.M.B. and M.-L.B.-K.; supervision, M.M.C. and B.R.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Catalyst: Seeding Dumont d'Urville NZ-France Science & Technology Support Programme (19-UOA-057-DDU) provided by the New Zealand Ministry of Business, Innovation and Employment and administered by the Royal Society Te Apārangi.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We thank Michael Schmitz, Tony Chen and Mansa Nair for their assistance with NMR and mass spectrometric data. Some of the antimicrobial screening was performed by CO-ADD (The Community for Antimicrobial Drug Discovery), funded by the Wellcome Trust (UK) and The University of Queensland (Australia).

**Conflicts of Interest:** The authors declare no conflict of interest.

## References

1. Williamson, D.A.; Lim, A.; Thomas, M.G.; Baker, M.G.; Roberts, S.A.; Fraser, J.D.; Ritchie, S.R. Incidence, Trends and Demographics of Staphylococcus Aureus Infections in Auckland, New Zealand, 2001–2011. *BMC Infect. Dis.* **2013**, *13*, 569. [CrossRef]

2. Baker, M.G.; Barnard, L.T.; Kvalsvig, A.; Verrall, A.; Zhang, J.; Keall, M.; Wilson, N.; Wall, T.; Howden-Chapman, P. Increasing incidence of serious infectious diseases and inequalities in New Zealand: A national epidemiological study. *Lancet* **2015**, *379*, 1112–1119. [CrossRef]

3. Williamson, D.A.; Roberts, S.A.; Ritchie, S.R.; Coombs, G.W.; Fraser, D.A.; Heffernan, H. Clinical and molecular epidemiology of methicillin-resistant *Staphylococcus aureus* in New Zealand: Rapid emergence of sequence type 5 (ST5)-SCCmec-IV as the dominant community-associated MRSA clone. *PLoS ONE* **2013**, *8*, e62020. [CrossRef] [PubMed]

4. Williamson, D.A.; Lim, A.; Wiles, S.; Roberts, S.A.; Freeman, J.T. Population-based incidence and comparative demographics of community-associated and healthcare-associated *Escherichia coli* bloodstream infection in Auckland, New Zealand, 2005–2011. *BMC Infect. Dis.* **2013**, *13*, 385. [CrossRef]

5. O'Sullivan, C.; Baker, M.G. Skin infections in children in a New Zealand primary care setting: Exploring beneath the tip of the iceberg. *N. Z. Med. J.* **2015**, *125*, 70–79.

6. Williamson, D.A.; Ritchie, S.R.; Roberts, S.A.; Coombs, G.W.; Thomas, M.G.; Hannaford, O.; Baker, M.G.; Lennon, D.; Fraser, J.D. Clinical and molecular epidemiology of community-onset invasive *Staphylococcus aureus* infection in New Zealand children. *Epidemiol. Infect.* **2014**, *142*, 1713–1721. [CrossRef] [PubMed]

7. Heffernan, H.; Bakker, S. *Annual Survey of Methicillin-Resistant Staphylococcus aureus (MRSA)*, 2015; ESR: Wellington, New Zealand, 2016.

8. Williamson, D.A.; Monecke, S.; Heffernan, H.; Ritchie, S.R.; Roberts, S.A.; Upton, A.; Thomas, M.G.; Fraser, J.D. High Usage of Topical Fusidic Acid and Rapid Clonal Expansion of Fusidic Acid–Resistant *Staphylococcus Aureus*: A Cautionary Tale. *Clin. Infect. Dis.* **2014**, *59*, 1451–1454. [CrossRef] [PubMed]

9. Thomas, M.; Smith, A.; Tilyard, M. Rising antimicrobial resistance: A strong reason to reduce excessive antimicrobial consumption in New Zealand. *N. Z. Med. J.* **2014**, *127*, 72–84. [PubMed]

10. Li, S.A.; Cadelis, M.M.; Sue, K.; Blanchet, M.; Vidal, N.; Brunel, J.M.; Bourguet-Kondracki, M.-L.; Copp, B.R. 6-Bromoindolglyoxylamido Derivatives as Antimicrobial Agents and Antibiotic Enhancers. *Bioorganic Med. Chem.* **2019**, *27*, 2090–2099. [CrossRef] [PubMed]

11. Li, S.A.; Cadelis, M.M.; Deed, R.C.; Douafer, H.; Bourguet-Kondracki, M.-L.; Michel Brunel, J.; Copp, B.R. Valorisation of the Diterpene Podocarpic Acid—Antibiotic and Antibiotic Enhancing Activities of Polyamine Conjugates. *Bioorganic Med. Chem.* **2022**, *64*, 116762. [CrossRef] [PubMed]

12. Gao, Y.; Huang, D.-C.; Liu, C.; Song, Z.-L.; Liu, J.-R.; Guo, S.-K.; Tan, J.-Y.; Qiu, R.-L.; Jin, B.; Zhang, H.; et al. Streptochlorin Analogues as Potential Antifungal Agents: Design, Synthesis, Antifungal Activity and Molecular Docking Study. *Bioorganic Med. Chem.* **2021**, *35*, 116073. [CrossRef]
13. Hogendorf, A.S.; Hogendorf, A.; Popiołek-Barczyk, K.; Ciechanowska, A.; Mika, J.; Satała, G.; Walczak, M.; Latacz, G.; Handzlik, J.; Kieć-Kononowicz, K.; et al. Fluorinated Indole-Imidazole Conjugates: Selective Orally Bioavailable 5-HT7 Receptor Low-Basicity Agonists, Potential Neuropathic Painkillers. *Eur. J. Med. Chem.* **2019**, *170*, 261–275. [CrossRef]

14. Bartik, K.; Braekman, J.-C.; Daloze, D.; Stoller, C.; Huysecom, J.; Vandevyver, G.; Ottinger, R. Topsentins, New Toxic Bis-Indole Alkaloids from the Marine Sponge *Topsentia Genitrix*. *Can. J. Chem.* **1987**, *65*, 2118–2121. [CrossRef]

15. Tsujii, S.; Rinehart, K.L.; Gunasekera, S.P.; Kashman, Y.; Cross, S.S.; Lui, M.S.; Pomponi, S.A.; Diaz, M.C. Topsentin, Bromotopsentin, and Dihydrodeoxybromotopsentin: Antiviral and Antitumor Bis(Indolyl)Imidazoles from Caribbean Deep-Sea Sponges of the Family Halichondriidae. Structural and Synthetic Studies. *J. Org. Chem.* **1988**, *53*, 5446–5453. [CrossRef]

16. Sakemi, S.; Sun, H.H. Topsentins, A, B, and C. Cytotoxic and Antifungal Imidazolediylbis[Indoles] from the Sponge Spongosorites Ruetzleri. *J. Org. Chem.* **1991**, *56*, 4304–4307. [CrossRef]

17. Oh, K.-B.; Mar, W.; Kim, S.; Kim, J.-Y.; Lee, T.-H.; Kim, J.-G.; Shin, D.; Sim, C.J.; Shin, J. Antimicrobial Activity and Cytotoxicity of Bis(Indole) Alkaloids from the Sponge *Spongosorites* sp. *Biol. Pharm. Bull.* **2006**, *29*, 570–573. [CrossRef]

18. Huggins, W.M.; Barker, W.T.; Baker, J.T.; Hahn, N.A.; Melander, R.J.; Melander, C. Meridianin D Analogues Display Antibiofilm Activity against MRSA and Increase Colistin Efficacy in Gram-Negative Bacteria. *ACS Med. Chem. Lett.* **2018**, *9*, 702–707. [CrossRef] [PubMed]

19. Hogendorf, A.S.; Hogendorf, A.; Kurczab, R.; Kalinowska-Tłuścik, J.; Popik, P.; Nikiforuk, A.; Krawczyk, M.; Satała, G.; Lenda, T.; Knutelska, J.; et al. 2-Aminoimidazole-Based Antagonists of the 5-HT6 Receptor—A New Concept in Aminergic GPCR Ligand Design. *Eur. J. Med. Chem.* **2019**, *179*, 1–15. [CrossRef] [PubMed]

20. Van Leusen, A.M.; Wildeman, J.; Oldenziel, O.H. Chemistry of Sulfonylmethyl Isocyanides. 12. Base-Induced Cycloaddition of Sulfonylmethyl Isocyanides to Carbon, Nitrogen Double Bonds. Synthesis of 1,5-Disubstituted and 1,4,5-Trisubstituted Imidazoles from Aldimines and Imidoyl Chlorides. *J. Org. Chem.* **1977**, *42*, 1153–1159. [CrossRef]

21. Pieri, C.; Borselli, D.; Di Giorgio, C.; De Méo, M.; Bolla, J.-M.; Vidal, N.; Combes, S.; Brunel, J.M. New Ianthelliformisamine Derivatives as Antibiotic Enhancers against Resistant Gram-Negative Bacteria. *J. Med. Chem.* **2014**, *57*, 4263–4272. [CrossRef] [PubMed]

22. Blaskovich, M.A.T.; Zuegg, J.; Elliott, A.G.; Cooper, M.A. Helping Chemists Discover New Antibiotics. *ACS Infect. Dis.* **2015**, *1*, 285–287. [CrossRef] [PubMed]