Visible Light-Mediated Direct C-H Aroylation and Alkylation of Heteroarenes.

Herein, we describe the photocatalytic generation of nucleophilic aroyl radicals from simple aroyl chlorides as a universal and efficient cross-coupling strategy for the direct aroylation of heteroarenes. Furthermore, visible light-mediated direct alkylation of heteroarenes has also been achieved using unactivated bromoalkanes as radical precursors. These two strategies feature high functional group tolerance, exclusive regioselectivity for reaction at the more electrophilic position of heteroarenes, easily accessible substrates, and mild reaction conditions. Moreover, mechanism studies of two reactions are carried out to support our hypotheses.

Introduction

Heteroarenes are essential substructures of a large proportion of small-molecule drugs, functionalization of which is of paramount importance for the design and synthesis of pharmaceutical targets[1] and natural products.[2] Pioneering work by Minisci, known as Minisci reactions, realized the direct C–H acylation and alkylation of heteroarenes with aldehydes[3f] and carboxylic acids,[3g] respectively (Scheme A). With the development of radical chemistry and photoredox catalysis, Minisci reaction has undergone a remarkable renaissance in the past decade, offering increasingly powerful methods for synthesizing heteroarene-based organic building blocks.[4,5] Acyl radicals are one of the most important elements;[6] they are conventionally generated by aldehydes to realize Minisci acylation via oxidative cross-dehydrogenative coupling (CDC) in recent years. However, heating at temperature about 100 °C in the presence of peroxy compounds becomes a major drawback of this strategy.[4c−4h] Recently, Antonchick reported that PhI(OCOCF3)2/TMSN3 can efficiently mediate the oxidative CDC of a wide range of N-heterocycles with diverse aldehydes at room temperature (Scheme B).[4h] Our group is interested in photoredox catalysis,[7] and we recently employed abundant and inexpensive aroyl chlorides for the first time as novel acyl radical precursors in visible-light photocatalysis.[7f,7g] This method featured with easy available substrates, mild reaction conditions, and convenient operation procedure. Moreover, inspired by the properties of tris(trimethylsilyl)silane (TTMSS)[8] and the work of MacMillan,[9] photoredox catalysis or heat can induce radical initiators to generate silyl radical intermediates, which are able to abstract halogen atoms from alkyl Csp-halide bonds to form the strong Si-halogen bond. We expected that the sulfate radical anion, which is readily generated from single-electron transfer (SET) between the photocatalyst and persulfate, could also abstract a hydrogen atom from TTMSS to produce the silyl radical. We believe this novel approach could be utilized in Minisci alkylation. Specifically, we herein report two novel methods for Minisci aroylation and alkylation mediated by photoredox catalysis, where commercial available aroyl chlorides and bromoalkanes are used as radical precursors, respectively (Scheme C). Simultaneously, reaction mechanisms were studied at full length to support our hypotheses.

Scheme 1

Minisci Aroylation and Alkylation of Heteroarenes

Results and Discussion

Our studies of the Minisci aroylation were initiated with the reaction of isoquinoline 1a and benzoyl chloride 2a (Table ). The reaction was irradiated for 48 h with blue light-emitting diode (LED) strips using Ir(ppy)3 as the photocatalyst (Table , entry 4). Surprisingly, the desired product 3a was obtained in 32% yield in MeCN. Screening of the photocatalysts showed that less reducing systems were not effective (entries 1–3). Moreover, it was found that the presence of an acid additive, which was essential in traditional Minisci reaction, decreased the reaction efficiency (entry 5), although the yield could be recovered by extending the reaction time to 72 h (entry 6). Furthermore, the excess amount of benzoyl chloride (up to 10 equiv) had a significant influence on the reaction outcome, delivering the desired product up to 88% yield (entries 7 and 8). It was confirmed that both the photocatalyst and light were required for the reaction by control experiments (entries 9 and 10).

Table 1

Initial Studies of the Minisci Aroylation Reactiona

entry	Catalyst	1a/2a	time (h)	yield (%)b
1	Ru(bpy)3Cl2	1:2	48	NR
2	Ir(ppy)2(dtbbpy)PF6	1:2	48	NR
3	eosin Y	1:2	48	NR
4	fac-Ir(ppy)3	1:2	48	32
5c	fac-Ir(ppy)3	1:2	48	20
6	fac-Ir(ppy)3	1:2	72	35
7	fac-Ir(ppy)3	1:6	72	74
8	fac-Ir(ppy)3	1:10	72	88
9	None	1:10	72	NR
10d	fac-Ir(ppy)3	1:10	72	NR

Unless otherwise noted, reaction conditions are as follows: substrate 1a (0.2 mmol), 2a (2–10 equiv), photocatalyst (0.004 mmol), MeCN (anhydrous, 2 mL), 25 W blue LED strips, room temperature, and under the N2 atmosphere.

Isolated yield.

With additive of TFA (0.2 mmol).

In the dark.

With the reaction conditions optimized, we next performed a series of experiments to determine the scope of the substrates. As shown in Table , a variety of heteroarenes were readily aroylated with a range of aroyl chlorides in moderate to excellent yields. First, the scope of aryl chlorides was investigated using isoquinoline as the heteroarene substrate. To our delight, electron-donating/withdrawing groups substituted in different sites of aroyl chlorides were well-tolerated. More specifically, monosubstituted benzoyl chlorides bearing halogen, trifluoromethyl, methyl, and tert-butyl groups provided the corresponding products in 42–78% yields under the standard conditions (3b to 3k), and disubstituted benzoyl chlorides were also well tolerated, delivering the desired products in 57–80% yields (3l and 3m). The scope of the reaction was further extended to 2-naphthoyl chloride (3n) and 2-thiophenecarbonyl chloride (3o).

Table 2

Scope of Substrates toward Minisci Aroylation Reactiona

Unless otherwise noted, reaction conditions are as follows: 1 (0.2 mmol), 2 (2.0 mmol), fac-Ir(ppy)3 (0.004 mmol), MeCN (anhydrous, 2 mL), 25 W blue LED strips, room temperature, under the N2 atmosphere, and 72 h. All yields are isolated yields.

Next, the scope of the heteroarenes was investigated using benzoyl chloride as the radical source. Monosubstituted quinolines served as suitable substrates, generating the corresponding acylated products as single regioisomers at the C1 position in good yields (3p–3r). The reaction using quinoxaline delivered mono- (3s) and diaroylated (3s′) products in 35 and 60% yields, respectively. Furthermore, C2-substituted quinoxalines could also be aroylated at the C3 position in good yields (3t and 3u). Other heteroarenes, such as quinazoline (3v), acridine (3w), 4-cyano-pyridine (3x), benzothiazole (3y), and 2,3-diphenylpyrido[3,4-b]pyrazine (3z), were monoaroylated smoothly at the most electrophilic position.

Based on the previous works of our group[7f,7g] and mechanism studies, a possible mechanism for the visible light-mediated aroylation of heteroarenes was proposed as depicted in Scheme . Under irradiation of blue LEDs, the photocatalyst fac-IrIII(ppy)3 was excited to form the strong reductant *fac-IrIII(ppy)3 (E1/2IV/*III = −1.73 V vs SCE),[10] which reduced benzoyl chloride (Ep/2 = −1.35 V vs SCE)[11] via SET to deliver fac-IrIV(ppy)3 and radical anion IV. After dechloridation, the key aroyl radical V was added to the heteroarene to provide VI. Upon deprotonation, oxidation of the fac-IrIV(ppy)3 (E1/2IV/III = +0.77 V vs SCE) through SET from VII furnished the desired product VIII.

Scheme 2

Proposed Mechanism for Minisci Aroylation Reaction

Having completed our studies of Minisci aroylation, we next turned our attention to Minisci alkylation as another part of this work. As mentioned in the introduction, we hypothesized that persulfate and TTMSS will facilitate the generation of alkyl radicals from bromoalkanes under photoredox conditions. Our study thus started with isoquinoline, bromocyclohexane, TTMSS, trifluoroacetic acid (TFA), and a series of photocatalysts and oxidants. To our delight, the desired alkylated product 6a was obtained in 17% yield using Ir(ppy)2(dtbbpy)PF6 in combination with DTBP as the oxidant in dimethyl sulfoxide (DMSO) under the irradiation of 25 W blue LED strips. Finally, we promoted the yield to 90% by screening the kind and the loading of photocatalysts, oxidants, and solvents.[12]

With the reaction conditions optimized, we next explored the scope of this photoinduced Minisci-type C–H alkylation by investigating the reactions between N-heteroarenes and various bromoalkanes. First, the scope of bromoalkanes was investigated. As summarized in Table , in addition to the model substrate, four- and five-membered cyclic systems were also tolerated, albeit with reduced yields (6b and 6c). Both acyclic primary and secondary alkyl halides reacted efficiently with isoquinoline to generate the corresponding products (6d to 6k) in moderate to good yields. Notably, unsaturated bromohydrocarbons containing a phenyl (6l to 6n) or alkenyl (6o to 6q) group were also shown to be competent substrates. Lastly, ethyl 5-bromopentanoate, bearing an ester group, was found to react with isoquinoline readily in a synthetically useful yield (6r, 56%).

Table 3

Scope of Substrates toward Minisci Alkylation Reactiona

Unless otherwise noted, reaction conditions are as follows: 4 (0.2 mmol), 5 (0.4 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.002 mmol), TFA (0.4 mmol), K2S2O8 (0.4 mmol), TTMSS (0.4 mmol), DMSO (anhydrous, 1 mL), 25 W blue LED strips, room temperature, under the N2 atmosphere, and 12 h. All yields are isolated yields.

To further demonstrate the functional group tolerance and applicability of this method, we examined the scope of this reaction with different electron-deficient heteroarenes (Table ). Both quinolines and isoquinolines were well tolerated (6s to 6w). Quinolines substituted at C4 and C2 positions gave C2 and C4 alkylated products, respectively (6s to 6u). Other heterocycles such as quinoxalines (6x and 6y), benzothiazole (6z), 2,3-diphenylpyrido[3,4-b]pyrazine (6aa), 6-chloroimidazo[1,2-b]pyridazine (6ab), and 4-cyanopyridine (6ac) were also proved to be suitable substrates for this Minisci-type alkylation protocol. For quinazoline, both mono- and double-alkylated products were obtained with the monoalkylation product as the major product (6ad and 6ad′).

Mechanism studies were also carried out. According to the results of fluorescence quenching experiments, the excited photocatalyst X was quenched by isoquinoline instead of potassium persulfate. Moreover, giving the results of cyclic voltammetry (CV) experiments and literature reports, we supposed that isoquinoline and other heteroarenes might act as both substrates and electron transfer agents.[13] Taken together, these observations indicated an oxidative quenching pathway, wherein direct reduction of persulfate by heterocyclic compound intermediate XIX was a viable electron transfer pathway. Radical trapping experiments clearly showed a radical mechanistic pathway. Quantum yield measurements (Φ = 9.3) suggested that radical propagation was involved in the reaction.

Based on the literature and our studies, a plausible mechanism for the visible light-mediated alkylation of heteroarenes was proposed and illustrated in Scheme . Photoexcitation of the Ir[dF(CF3)ppy]2(dtbbpy)PF6 photocatalyst with blue LEDs produced a long-lived excited state, *Ir[dF(CF3)ppy]2(dtbbpy)PF6. The resulting *IrIII species X, as a reductant (E1/2*III/IV = −0.89 V vs SCE),[14] should be able to reduce electron transfer agent XVIII (Ep/2red = −1.08 V vs SCE) to afford the oxidized iridium species XI and radical intermediate XIX. The SET process between persulfate and XIX delivered sulfate anion radical XII. In addition, XII could also be formed by the thermolysis of persulfate.[16] The generated sulfate radical anion underwent a hydrogen-atom transfer process with TTMSS to afford silyl radical XIII, which abstracted a bromine atom from the bromoalkane to afford the key alkyl radical XIV. The alkyl radical XIV was then added to the electron-deficient heteroarene to provide XV. Upon deprotonation, reduction of XVI (E1/2ox = −0.92 to −1.12 V vs SCE)[15] through a SET process with XI (E1/2IV/III = +1.69 V vs SCE)[14] furnished the desired product. Alternatively, the persulfate anion could act as a chain carrier, which oxidized XVI to provide the alkylated heteroarene XVII.

Scheme 3

Proposed Mechanism for Minisci Alkylation Reaction

Conclusions

In summary, we have developed photoredox-catalyzed Minisci alkylation and aroylation using bromoalkanes and aroyl chlorides as the radical precursors, respectively. These methods enabled the rapid synthesis of a series of Minisci-type adducts using commercially available starting materials under mild reaction conditions with easy operation. We expect that these new versions of the Minisci reaction will find more applications in organic synthesis.

Experimental Section

General Information

All glassware was thoroughly oven-dried. Chemicals and solvents were either purchased from commercial suppliers or purified by standard techniques. Analytical high-performance thin-layer chromatography was performed on silica gel glass plates with the F-254 indicator, and compounds were visualized by exposure to ultraviolet light and/or staining with phosphomolybdic acid followed by heating on a hot plate. Flash chromatography was carried out using silica gel (200–300 mesh). 1H NMR and 13C NMR spectra were recorded on a Bruker AM-400 spectrometer (400 MHz 1H, 100 MHz 13C) using CDCl3 as a solvent for deuterium locking with a temperature of 298 K. Chemical shifts are given in ppm with TMS as an internal reference. J values are given in Hertz. High-resolution mass spectrometry (HRMS) were performed on a Bruker Apex II mass instrument (ESI). All fluorescence spectra were surveyed on a PE-LS55 fluorescence spectrophotometer and equipped with a 1 cm quartz cell. All CV curves were measured on a CHI660E electrochemical workstation. During the study of quantum yield, the reaction was irradiated in a Parallel Light Reactor (WP-TEC-1020), and the yield was determined by gas chromatography–mass spectrometry (EI).

General Procedure for the Synthesis of Aroylated Heteroarenes

A mixture of fac-Ir(ppy)3 (2.6 mg, 0.004 mmol, 0.02 equiv), heteroarenes 1 (0.2 mmol, 1.0 equiv), aroyl chloride 2 (2.0 mmol, 10.0 equiv), and MeCN (2 mL) was degassed by three cycles of freeze–pump–thaw. The mixture was stirred under nitrogen atmosphere at room temperature while irradiated by blue LEDs for 72 h. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified by flash chromatography (petroleum ether/ethyl acetate) on silica gel to afford the aroylated products 3.

General Procedure for the Synthesis of Alkylated Heteroarenes

A mixture of Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %), heteroarenes 4 (0.2 mmol, 1.0 equiv), TFA (30 μL, 0.4 mmol, 2.0 equiv), bromoalkane 5 (0.4 mmol, 2.0 equiv), K2S2O8 (108 mg, 0.4 mmol, 2.0 equiv), TTMSS (120 μL, 0.4 mmol, 2.0 equiv), and DMSO (1 mL) was degassed by three cycles of freeze–pump–thaw. The mixture was stirred under the nitrogen atmosphere at room temperature while irradiated by blue LEDs for 12 h. After completion of the reaction, the reaction mixture was neutralized with NaHCO3 and diluted with 25 mL ethyl acetate; the organic layer was washed with brine (30 mL × 3), dried over Na2SO4, and then concentrated in vacuo. Purification of the crude product by flash chromatography (petroleum ether/ethyl acetate) on silica gel was carried out to afford the alkylated product 6.

Trapping Experiments with TEMPO

The trapping experiment for Minisci aroylation was conducted as follows: isoquinoline 1a (0.2 mmol), benzoyl chloride 2a (2.0 mmol), TEMPO (2.0 mmol.), Ir(ppy)3 (0.004 mmol), MeCN (anhydrous, 2 mL), 25 W blue LED strips, room temperature, under the N2 atmosphere, and 72 h. The TEMPO-trapped compound 7 was detected by HRMS techniques. HRMS (ESI): for C16H23NO2 [M + H]+ calcd, 262.1807; found, 262.1803.

Trapping experiments for Minisci alkylation were conducted as follows: isoquinoline 1a (0.2 mmol), bromocyclohexane 5a (0.4 mmol), TEMPO (0.4 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (0.002 mmol), TFA (0.4 mmol), oxidant (0.4 mmol), TTMSS (0.4 mmol), DMSO (anhydrous, 1 mL), room temperature, under the N2 atmosphere, and 12 h. One was irradiated with blue LEDs, and the other one reacted in the dark. The TEMPO-trapped compound 8 was detected in both reactions by HRMS techniques. HRMS (ESI): for C16H23NO2 [M + H]+ calcd, 240.2327; found, 240.2324.

Fluorescence Quenching Experiments

As for Minisci aroylation, Stern–Volmer fluorescence quenching experiments were run with freshly prepared solutions of 0.1 mM Ir(ppy)3 and substrates with the concentration gradient from 0.2 to 1.0 mM in degassed dry MeCN at room temperature. The solutions were irradiated at 376 nm, and the fluorescence was measured from 400 to 700 nm.

As for Minisci alkylation, Stern–Volmer fluorescence quenching experiments were run with freshly prepared solutions of 0.1 mM Ir[dF(CF3)ppy]2(dtbbpy)PF6 and substrates/additives with the concentration gradient from 0.2 to 1.0 mM in degassed dry DMSO at room temperature. The solutions were irradiated at 336 nm, and the fluorescence was measured from 300 to 700 nm.

CV Experiments

Electrolyte solution was prepared by dissolving substrates (0.2 mmol, 0.01 M) and tetrabutylammonium tetrafluoroborate (658 mg, 2.0 mmol, 0.1 M) in MeCN (20 mL). Measurements were performed in a three-compartment electrochemical cell, in which the glassy carbon electrode was used as a working electrode, AgNO3/Ag electrode as the reference electrode, and Pt wire as the counter electrode. Scan rates were 100 mV/s, and the CV curves were thus obtained.

Isoquinolin-1-yl(phenyl)methanone (3a)

It was obtained as a yellow solid; 41.0 mg, 88% yield; Rf = 0.27 (PE/EA = 10:1); mp 62–64 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 7.99–7.93 (m, 2H), 7.91 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 1H), 7.77–7.70 (m, 1H), 7.64–7.57 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.7, 156.4, 141.1, 136.7, 136.6, 133.6, 130.7, 130.6, 128.4, 128.3, 127.0, 126.4, 126.1, 122.5; HRMS (ESI): for C16H11NO [M + H]+ calcd, 234.0919; found, 234.0912.

(4-Fluorophenyl)(isoquinolin-1-yl)methanone (3b)

It was obtained as a white solid; 30.6 mg, 61% yield; Rf = 0.25 (PE/EA = 10:1); mp 64–66 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.24 (dd, J = 8.5, 0.8 Hz, 1H), 8.04–7.98 (m, 2H), 7.93 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 5.6 Hz, 1H), 7.78–7.73 (m, 1H), 7.66–7.63 (m, 1H), 7.19–7.11 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.0, 167.3, 164.8, 155.9, 141.0, 136.7, 133.5, 133.4, 132.9, 130.7, 128.4, 127.1, 126.3, 126.0, 122.7, 115.7, 115.5; HRMS (ESI): for C16H10FNO [M + H]+ calcd, 252.0825; found, 252.0818.

(4-Chlorophenyl)(isoquinolin-1-yl)methanone (3c)

It was obtained as colorless oil; 39.6 mg, 74% yield; Rf = 0.32 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.26 (dd, J = 8.6, 0.8 Hz, 1H), 7.96–7.89 (m, 3H), 7.83 (d, J = 5.6 Hz, 1H), 7.79–7.73 (m, 1H), 7.67–7.62 (m, 1H), 7.48–7.43 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.3, 155.5, 141.0, 140.1, 136.7, 134.9, 132.1, 130.7, 128.7, 128.5, 127.1, 126.4, 126.0, 122.9; HRMS (ESI): for C16H10ClNO [M + H]+ calcd, 268.0529; found, 268.0528.

(4-Bromophenyl)(isoquinolin-1-yl)methanone (3d)

It was obtained as colorless oil; 26.2 mg, 42% yield; Rf = 0.31 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.26 (dd, J = 8.4, 0.8 Hz, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.85 (t, J = 1.9 Hz, 1H), 7.83 (t, J = 2.5 Hz, 2H), 7.79–7.73 (m, 1H), 7.67–7.64 (m, 1H), 7.64–7.60 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.5, 155.5, 141.0, 136.7, 135.4, 132.2, 131.7, 130.8, 128.9, 128.5, 127.1, 126.4, 126.0, 122.9; HRMS (ESI): for C16H10BrNO [M + H]+ calcd, 312.0024; found, 312.0028.

Isoquinolin-1-yl(4-(trifluoromethyl)phenyl)methanone (3e)

It was obtained as a white solid; 31.4 mg, 52% yield; Rf = 0.34 (PE/EA = 10:1); mp 78–80 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.61 (d, J = 5.6 Hz, 1H), 8.36 (dd, J = 8.4, 0.8 Hz 1H), 8.08 (d, J = 8.1 Hz, 2H), 7.96 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 5.3 Hz, 1H), 7.82–7.72 (m, 3H), 7.71–7.65 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.4, 154.8, 141.0, 139.7, 136.8, 134.6, 134.3, 131.0, 130.8, 128.7, 127.2, 126.6, 125.9, 125.4, 125.4, 125.3, 125.3, 124.9, 123.4, 122.2; HRMS (ESI): for C17H10F3NO [M + H]+ calcd, 302.0793; found, 302.0788.

Isoquinolin-1-yl(p-tolyl)methanone (3f)

It was obtained as colorless oil; 36.1 mg, 73% yield; Rf = 0.25 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.59 (d, J = 5.7 Hz, 1H), 8.19 (dd, J = 8.8, 0.8, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.79 (d, J = 5.6 Hz, 1H), 7.75–7.70 (m, 1H), 7.63–7.57 (m, 1H), 7.27 (d, J = 7.8 Hz, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.4, 156.7, 144.6, 141.1, 136.6, 130.8, 130.6, 129.1, 128.1, 127.0, 126.3, 126.1, 122.3, 21.7; HRMS (ESI): for C17H13NO [M + H]+ calcd, 248.1075; found, 248.1069.

(4-(tert-Butyl)phenyl)(isoquinolin-1-yl)methanone (3g)

It was obtained as colorless oil; 34.1 mg, 59% yield; Rf = 0.33 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 7.95–7.86 (m, 3H), 7.80 (d, J = 5.6 Hz, 1H), 7.77–7.70 (m, 1H), 7.63–7.58 (m, 1H), 7.53–7.46 (m, 2H), 1.34 (s, 9H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.3, 157.5, 156.7, 141.1, 136.6, 133.9, 130.7, 130.6, 128.1, 127.0, 126.3, 126.2, 125.4, 122.3, 35.1, 31.0; HRMS (ESI): for C20H19NO [M + H]+ calcd, 290.1545; found, 290.1538.

Isoquinolin-1-yl(o-tolyl)methanone (3h)

It was obtained as colorless oil; 38.5 mg, 78% yield; Rf = 0.27 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 1H), 7.79–7.69 (m, 3H), 7.62 (t, J = 7.7 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 195.0, 156.6, 141.1, 138.2, 136.6, 134.5, 131.0, 130.6, 128.3, 128.2, 128.0, 127.0, 126.3, 126.1, 122.4, 21.3; HRMS (ESI): for C17H13NO [M + H]+ calcd, 248.1075; found, 248.1069.

(2-Chlorophenyl)(isoquinolin-1-yl)methanone (3i)

It was obtained as colorless oil; 39.7 mg, 74% yield; Rf = 0.25 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.74 (d, J = 8.3 Hz, 1H), 8.53 (d, J = 5.6 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H), 7.80 (d, J = 5.5 Hz, 1H), 7.79–7.68 (m, 3H), 7.48–7.37 (m, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 196.0, 154.4, 141.2, 139.0, 136.9, 132.4, 132.2, 130.9, 130.5, 130.0, 128.9, 127.0, 126.8, 126.3, 126.3, 123.8; HRMS (ESI): for C16H10ClNO [M + H]+ calcd, 268.0529; found, 268.0525.

Isoquinolin-1-yl(m-tolyl)methanone (3j)

It was obtained as colorless oil; 30.2 mg, 61% yield; Rf = 0.27 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.6 Hz, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 1H), 7.78–7.70 (m, 3H), 7.63–7.58 (m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.9, 156.6, 141.1, 138.2, 136.6, 136.6, 134.4, 130.9, 130.6, 128.3, 128.2, 128.0, 127.0, 126.3, 126.1, 122.4, 21.2; HRMS (ESI): for C17H13NO [M + H]+ calcd, 248.1075; found, 248.1071.

(3-Chlorophenyl)(isoquinolin-1-yl)methanone (3k)

It was obtained as a white solid; 39.1 mg, 73% yield; Rf = 0.29 (PE/EA = 10:1); mp 80–82 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.61 (d, J = 5.6 Hz, 1H), 8.27 (dq, J = 8.5, 0.9 Hz, 1H), 7.97–7.91 (m, 2H), 7.86–7.81 (m, 2H), 7.79–7.74 (m, 1H), 7.68–7.63 (m, 1H), 7.60–7.56 (m, 1H), 7.42 (t, J = 7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.2, 155.3, 141.1, 138.3, 136.8, 130.8, 130.6, 129.7, 128.9, 128.5, 127.1, 126.5, 126.0, 123.0; HRMS (ESI): for C16H10ClNO [M + H]+ calcd, 268.0529; found, 268.0524.

(3,5-Dimethylphenyl)(isoquinolin-1-yl)methanone (3l)

It was obtained as colorless oil; 41.7 mg, 80% yield; Rf = 0.27 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.60 (d, J = 5.7 Hz, 1H), 8.23–8.12 (m, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 1H), 7.76–7.71 (m, 1H), 7.63–7.58 (m, 1H), 7.54 (s, 2H), 7.24 (s, 1H), 2.33 (s, 6H); 13C NMR (100 MHz, CDCl3): δ (ppm) 195.2, 156.9, 141.1, 138.1, 136.6, 136.6, 135.4, 130.6, 128.3, 128.1, 127.0, 126.2, 126.1, 122.3, 21.1; HRMS (ESI): for C18H15NO [M + H]+ calcd, 262.1232; found, 262.1226.

(3,4-Dichlorophenyl)(isoquinolin-1-yl)methanone (3m)

It was obtained as a white solid; 34.4 mg, 57% yield; Rf = 0.36 (PE/EA = 10:1); mp 128–130 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.61 (d, J = 5.6 Hz, 1H), 8.30 (dd, J = 8.4, 0.8 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.95 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 5.5 Hz, 1H), 7.82 (dd, J = 8.4, 2.0 Hz, 1H), 7.80–7.75 (m, 1H), 7.67 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 192.1, 154.6, 141.0, 138.0, 136.8, 136.3, 133.0, 132.6, 130.8, 130.4, 129.7, 128.7, 127.2, 126.5, 125.9, 123.3; HRMS (ESI): for C16H9Cl2NO [M + H]+ calcd, 302.0139; found, 302.0135.

Isoquinolin-1-yl(naphthalen-2-yl)methanone (3n)

It was obtained as a white solid; 11.9 mg, 21% yield; Rf = 0.21 (PE/EA = 10:1); mp 98–100 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.65 (d, J = 5.6 Hz, 1H), 8.34 (s, 1H), 8.25 (dd, J = 8.4, 0.8 Hz, 1H), 8.15 (dd, J = 8.6, 1.7 Hz, 1H), 7.96 (dd, J = 8.4, 3.6 Hz, 2H), 7.93–7.82 (m, 3H), 7.81–7.73 (m, 1H), 7.68–7.56 (m, 2H), 7.56–7.46 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.7, 156.7, 141.2, 136.7, 135.9, 133.9, 133.7, 132.3, 130.7, 129.8, 128.8, 128.4, 128.3, 127.7, 126.6, 126.4, 126.2, 125.2, 122.5; HRMS (ESI): for C20H13NO [M + H]+ calcd, 284.1075; found, 284.1069.

Isoquinolin-1-yl(thiophen-2-yl)methanone (3o)

It was obtained as a yellow solid; 20.5 mg, 43% yield; Rf = 0.26 (PE/EA = 10:1); mp 72–74 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.66 (d, J = 5.6 Hz, 1H), 8.58 (d, J = 8.5 Hz, 1H), 7.97–7.91 (m, 2H), 7.86 (d, J = 5.6 Hz, 1H), 7.81–7.78 (m, 1H), 7.78–7.74 (m, 1H), 7.71–7.66 (m, 1H), 7.21–7.16 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 186.0, 154.6, 142.5, 140.8, 136.9, 136.5, 135.9, 130.6, 128.6, 128.0, 127.0, 126.4, 126.2, 123.5; HRMS (ESI): for C14H9NOS [M + H]+ calcd, 240.0483; found, 240.0479.

(5-Bromoisoquinolin-1-yl)(phenyl)methanone (3p)

It was obtained as a white solid; 51.0 mg, 82% yield; Rf = 0.42 (PE/EA = 10:1); mp 94–96 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.70 (d, J = 5.9 Hz, 1H), 8.19–8.15 (m, 2H), 8.01 (dd, J = 7.5, 0.8 Hz, 1H), 7.95–7.90 (m, 2H), 7.63–7.58 (m, 1H), 7.50–7.41 (m, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.1, 156.8, 142.5, 136.3, 135.7, 134.3, 133.8, 130.6, 128.5, 128.4, 127.3, 125.8, 121.9, 121.3; HRMS (ESI): for C16H10BrNO [M + H]+ calcd, 312.0024; found, 312.0019.

(4-Bromoisoquinolin-1-yl)(phenyl)methanone (3q)

It was obtained as a white solid; 50.0 mg, 80% yield; Rf = 0.27 (PE/EA = 10:1); mp 96–98 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.80 (s, 1H), 8.27 (d, J = 8.5 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 7.94 (dd, J = 8.2, 1.1 Hz, 2H), 7.88–7.83 (m, 1H), 7.70–7.66 m, 1H), 7.65–7.58 (m, 1H), 7.48 (t, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.8, 155.6, 142.8, 136.2, 133.8, 131.9, 130.6, 129.1, 128.4, 127.4, 126.5, 126.3, 121.7; HRMS (ESI): for C16H10BrNO [M + H]+ calcd, 312.0024; found, 312.0022.

(6-Methylisoquinolin-1-yl)(phenyl)methanone (3r)

It was obtained as colorless oil; 31.6 mg, 64% yield; Rf = 0.22 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.55 (d, J = 5.6 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 7.98–7.92 (m, 2H), 7.72 (d, J = 5.6 Hz, 1H), 7.69 (s, 1H), 7.63–7.57 (m, 1H), 7.51–7.42 (m, 3H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.8, 156.0, 141.2, 137.0, 133.5, 130.7, 130.6, 128.4, 125.8, 124.8, 122.0, 21.9; HRMS (ESI): for C17H13NO [M + H]+ calcd, 248.1075: found, 248.1071.

Phenyl(quinoxalin-2-yl)methanone (3s)

It was obtained as a white solid; 16.3 mg, 35% yield; Rf = 0.28 (PE/EA = 10:1); mp 62–64 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 9.50 (s, 1H), 8.25 (d, J = 7.6 Hz, 2H), 8.21 (d, J = 8.4 Hz, 2H), 7.96–7.83 (m, 2H), 7.67 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 192.3, 148.6, 145.3, 143.1, 140.4, 135.5, 133.6, 132.0, 131.2, 130.4, 128.3; HRMS (ESI): for C15H10N2O [M + H]+ calcd, 235.0871; found, 235.0868.

Quinoxaline-2,3-diylbis(phenylmethanone) (3s′)

It was obtained as a white solid; 40.5 mg, 60% yield; Rf = 0.23 (PE/EA = 10:1); mp 154–156 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.22 (dt, J = 6.5, 3.3 Hz, 2H), 8.14–8.09 (m, 4H), 7.93 (dt, J = 6.4, 3.2 Hz, 2H), 7.68–7.61 (m, 2H), 7.52 (t, J = 7.7 Hz, 4H); 13C NMR (100 MHz, CDCl3): δ (ppm) 192.5, 151.9, 140.1, 135.0, 133.9, 132.1, 130.9, 129.8, 128.5; HRMS (ESI): for C22H14N2O2 [M + H]+ calcd, 339.1134; found, 339.1133.

(3-Methylquinoxalin-2-yl)(phenyl)methanone (3t)

It was obtained as a yellow solid; 40.2 mg, 81% yield; Rf = 0.27 (PE/EA = 10:1); mp 66–68 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.10 (d, J = 8.5 Hz, 2H), 8.00–7.94 (m, 2H), 7.87–7.81 (m, 1H), 7.80–7.73 (m, 1H), 7.66 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 2.81 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 194.0, 152.2, 150.7, 142.0, 139.3, 135.4, 134.1, 131.2, 130.6, 129.7, 129.4, 128.6, 128.5, 22.7; HRMS (ESI): for C16H12N2O [M + H]+ calcd, 249.1028; found, 249.1024.

(3-Chloroquinoxalin-2-yl)(phenyl)methanone (3u)

It was obtained as a white solid; 46.6 mg, 87% yield; Rf = 0.36 (PE/EA = 10:1); mp 122–124 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.19–8.09 (m, 2H), 7.96–7.83 (m, 4H), 7.68 (tt, J = 7.2, 1.3 Hz, 1H), 7.56–7.49 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 191.2, 150.2, 143.9, 142.0, 139.6, 134.6, 134.6, 132.2, 130.9, 130.4, 129.4, 128.8, 128.4; HRMS (ESI): for C15H9ClN2O [M + H]+ calcd, 269.0482; found, 269.0483.

Phenyl(quinazolin-4-yl)methanone (3v)

It was obtained as colorless oil; 25.2 mg, 54% yield; Rf = 0.32 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 9.44 (s, 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 8.04–7.93 (m, 3H), 7.72–7.63 (m, 2H), 7.51 (t, J = 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 192.9, 164.0, 153.8, 151.2, 135.2, 134.6, 134.4, 130.6, 129.0, 128.7, 125.8, 122.0; HRMS (ESI): for C15H10N2O [M + H]+ calcd, 235.0871; found, 235.0866.

Acridin-9-yl(phenyl)methanone (3w)

It was obtained as a yellow solid; 28.3 mg, 50% yield; Rf = 0.34 (PE/EA = 4:1); mp 140–142 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.31 (d, J = 8.8 Hz, 2H), 7.85–7.76 (m, 4H), 7.73 (d, J = 8.6 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.52–7.41 (m, 4H); 13C NMR (100 MHz, CDCl3): δ (ppm) 197.6, 148.6, 143.5, 137.1, 134.6, 130.3, 129.9, 129.0, 126.7, 125.3; HRMS (ESI): for C20H13NO [M + H]+ calcd, 284.1075; found, 284.1072.

2-Benzoylisonicotinonitrile (3x)

It was obtained as colorless oil; 9.1 mg, 22% yield; Rf = 0.42 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.91 (d, J = 4.8 Hz, 1H), 8.28 (s, 1H), 8.08 (d, J = 7.3 Hz, 2H), 7.72 (d, J = 4.9 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 191.5, 156.1, 149.4, 135.1, 133.5, 131.0, 128.3, 127.2, 126.3, 121.9, 115.8; HRMS (ESI): for C13H8N2O [M + H]+ calcd, 209.0715; found, 209.0709.

Benzo[d]thiazol-2-yl(phenyl)methanone (3y)

It was obtained as a white solid; 33.9 mg, 71% yield; Rf = 0.60 (PE/EA = 10:1); mp 88–90 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.56 (d, J = 7.3 Hz, 2H), 8.24 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.67 (t, J = 7.4 Hz, 1H), 7.62–7.51 (m, 4H); 13C NMR (100 MHz, CDCl3): δ (ppm) 185.3, 167.1, 153.8, 137.0, 134.9, 133.8, 131.2, 128.4, 127.5, 126.8, 125.7, 122.1; HRMS (ESI): for C14H9NOS [M + H]+ calcd, 240.0483; found, 240.0482.

(2,3-Diphenylpyrido[3,4-b]pyrazin-5-yl)(phenyl)methanone (3z)

It was obtained as a white solid; 42.7 mg, 55% yield; Rf = 0.57 (PE/EA = 2:1); mp 142–144 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.87 (d, J = 5.7 Hz, 1H), 8.11 (d, J = 5.7 Hz, 1H), 7.94 (d, J = 7.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.58–7.53 (m, 2H), 7.48 (t, J = 7.7 Hz, 2H), 7.44–7.34 (m, 5H), 7.32 (t, J = 7.4 Hz, 1H), 7.25 (d, J = 3.4 Hz, 1H), 7.22 (d, J = 7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 193.9, 159.3, 158.1, 155.0, 146.0, 143.6, 138.2, 137.6, 136.4, 134.8, 133.7, 130.3, 130.0, 129.8, 129.7, 129.5, 128.4, 128.4, 128.1, 122.7; HRMS (ESI): for C26H17N3O [M + H]+ calcd, 388.1450; found, 388.1444.

1-Cyclohexylisoquinoline (6a)

It was obtained as colorless oil; 38.0 mg, 90% yield; Rf = 0.38 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.48 (d, J = 5.7 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.68–7.61 (m, 1H), 7.60–7.55 (m, 1H), 7.47 (d, J = 5.7 Hz, 1H), 3.56 (tt, J = 11.7, 3.2 Hz, 1H), 2.03–1.89 (m, 4H), 1.89–1.75 (m, 3H), 1.59–1.48 (m, 2H), 1.40 (tt, J = 12.7, 3.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 165.6, 141.8, 136.3, 129.4, 127.5, 126.7, 126.2, 124.6, 118.8, 41.4, 32.5, 26.8, 26.2; HRMS (ESI): for C15H17N [M + H]+ calcd, 212.1439; found, 212.1432.

1-Cyclopentylisoquinoline (6b)

It was obtained as colorless oil; 29.1 mg, 74% yield; Rf = 0.49 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.46 (d, J = 5.7 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.68–7.61 (m, 1H), 7.60–7.56 (m, 1H), 7.48 (d, J = 5.7 Hz, 1H), 4.02 (p, J = 8.3 Hz, 1H), 2.22–2.02 (m, 4H), 1.97–1.85 (m, 2H), 1.83–1.70 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 164.6, 141.6, 136.2, 129.5, 127.3, 127.1, 126.7, 125.2, 118.9, 42.9, 26.0; HRMS (ESI): for C14H15N [M + H]+ calcd, 198.1282; found, 198.1274.

1-Cyclobutylisoquinoline (6c)

It was obtained as colorless oil; 21.2 mg, 58% yield; Rf = 0.40 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.49 (d, J = 5.7 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.68–7.61 (m, 1H), 7.58–7.53 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 4.37 (p, J = 8.7 Hz, 1H), 2.63 (pd, J = 9.2, 2.4 Hz, 2H), 2.55–2.45 (m, 2H), 2.25–2.12 (m, 1H), 2.04–1.90 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 163.4, 141.7, 136.0, 129.6, 127.2, 126.7, 126.3, 125.1, 118.9, 39.3, 27.6, 18.5; HRMS (ESI): for C13H13N [M + H]+ calcd, 184.1126; found, 184.1118.

1-Butylisoquinoline (6d)

It was obtained as colorless oil; 21.4 mg, 58% yield; Rf = 0.24 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.65 (t, J = 7.4 Hz, 1H), 7.58 (t, J = 7.3 Hz, 1H), 7.49 (d, J = 5.6 Hz, 1H), 3.34–3.25 (m, 2H), 1.85 (p, J = 7.7 Hz, 2H), 1.50 (h, J = 7.4 Hz, 2H), 0.99 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 162.4, 141.8, 136.2, 129.6, 127.3, 126.9, 126.8, 125.3, 119.0, 35.2, 31.9, 22.9, 13.9; HRMS (ESI): for C13H15N [M + H]+ calcd, 186.1282; found, 186.1275.

1-Pentylisoquinoline (6e)

It was obtained as colorless oil; 25.9 mg, 65% yield; Rf = 0.49 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.65 (t, J = 7.1 Hz, 1H), 7.62–7.55 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 3.32–3.25 (m, 2H), 1.91–1.81 (m, 2H), 1.51–1.33 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 162.4, 141.8, 136.2, 129.7, 127.3, 126.8, 119.0, 35.4, 32.0, 29.4, 22.5, 14.0; HRMS (ESI): for C14H17N [M + H]+ calcd, 200.1439; found, 200.1432.

1-Hexylisoquinoline (6f)

It was obtained as colorless oil; 27.3 mg, 64% yield; Rf = 0.22 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.69–7.62 (m, 1H), 7.60–7.56 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 3.32–3.25 (m, 2H), 1.90–1.81 (m, 2H), 1.48 (p, J = 7.3 Hz, 2H), 1.34 (dqt, J = 12.5, 7.8, 3.6 Hz, 4H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 162.4, 141.8, 136.2, 129.6, 127.3, 125.3, 119.0, 35.5, 31.7, 29.7, 29.5, 22.5, 14.0; HRMS (ESI): for C15H19N [M + H]+ calcd, 214.1595; found, 214.1588.

1-Decylisoquinoline (6g)

It was obtained as colorless oil; 35.0 mg, 65% yield; Rf = 0.30 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.69–7.61 (m, 1H), 7.61–7.54 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 3.32–3.25 (m, 2H), 1.86 (p, J = 7.7 Hz, 2H), 1.47 (p, J = 6.9 Hz, 2H), 1.42–1.18 (m, 12H), 0.87 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 162.4, 141.8, 136.2, 129.6, 127.3, 126.8, 125.3, 35.5, 31.8, 29.9, 29.8, 29.5, 29.5, 29.5, 29.3, 22.6, 14.0; HRMS (ESI): for C19H27N [M + H]+ calcd, 270.2221; found, 270.2217.

1-Isobutylisoquinoline (6h)

It was obtained as colorless oil; 19.2 mg, 52% yield; Rf = 0.41 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.45 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.67–7.63 (m, 1H), 7.60–7.55 (m, 1H), 7.50 (d, J = 5.7 Hz, 1H), 3.17 (d, J = 7.3 Hz, 2H), 2.37–2.22 (m, 1H), 1.00 (d, J = 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ (ppm) 161.6, 141.7, 136.2, 129.6, 127.3, 126.7, 125.5, 119.0, 44.1, 29.5, 22.8; HRMS (ESI): for C13H15N [M + H]+ calcd, 186.1282; found, 186.1274.

1-Isopropylisoquinoline (6i)

It was obtained as colorless oil; 24.6 mg, 72% yield; Rf = 0.43 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.49 (d, J = 5.7 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.69–7.62 (m, 1H), 7.61–7.56 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 3.96 (hept, J = 6.9 Hz, 1H), 1.45 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ (ppm) 166.2, 141.7, 136.3, 129.5, 127.5, 126.8, 126.1, 124.7, 118.9, 30.9, 22.1; HRMS (ESI): for C12H13N [M + H]+ calcd, 172.1126; found, 172.1118.

1-(sec-Butyl)isoquinoline (6j)

It was obtained as colorless oil; 20.0 mg, 54% yield; Rf = 0.43 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.50 (d, J = 5.7 Hz, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.69–7.63 (m, 1H), 7.61–7.56 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 3.72 (h, J = 6.9 Hz, 1H), 2.10–1.97 (m, 1H), 1.83–1.71 (m, 1H), 1.41 (d, J = 6.8 Hz, 3H), 0.90 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 165.8, 141.9, 136.3, 129.5, 127.5, 126.9, 126.7, 124.7, 118.7, 37.7, 29.6, 20.1, 12.3; HRMS (ESI): for C13H15N [M + H]+ calcd, 186.1282; found, 186.1274.

1-(2-Cyclohexylethyl)isoquinoline (6k)

It was obtained as colorless oil; 27.7 mg, 58% yield; Rf = 0.25 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.42 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.67–7.62 (m, 1H), 7.60–7.55 (m, 1H), 7.48 (d, J = 5.7 Hz, 1H), 3.34–3.26 (m, 2H), 1.92–1.82 (m, 2H), 1.79–1.70 (m, 4H), 1.70–1.62 (m, 1H), 1.49–1.38 (m, 1H), 1.33–1.12 (m, 3H), 1.10–0.96 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 141.9, 136.2, 129.7, 127.3, 126.8, 119.0, 38.1, 37.4, 33.3, 33.1, 26.6, 26.3; HRMS (ESI): for C17H21N [M + H]+ calcd, 240.1752; found, 240.1748.

1-Benzylisoquinoline (6l)

It was obtained as colorless oil; 10.1 mg, 23% yield; Rf = 0.35 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.50 (d, J = 5.8 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.66–7.61 (m, 1H), 7.56 (d, J = 5.8 Hz, 1H), 7.53–7.50 (m, 1H), 7.29–7.23 (m, 4H), 7.19–7.14 (m, 1H), 4.68 (s, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 160.1, 141.9, 136.5, 129.8, 128.5, 128.5, 127.3, 127.2, 126.2, 125.8, 119.8, 42.0; HRMS (ESI): for C16H13N [M + H]+ calcd, 220.1126; found, 220.1121.

1-Phenethylisoquinoline (6m)

It was obtained as yellow oil; 31.2 mg, 67% yield; Rf = 0.40 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.47 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.68–7.63 (m, 1H), 7.60–7.53 (m, 1H), 7.52 (d, J = 5.7 Hz, 1H), 7.31 (d, J = 4.5 Hz, 4H), 7.25–7.19 (m, 1H), 3.63–3.57 (m, 2H), 3.23–3.17 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 160.9, 141.8, 136.2, 129.8, 128.4, 128.4, 127.3, 127.0, 126.8, 126.0, 125.0, 119.4, 37.1, 35.4; HRMS (ESI): for C17H15N [M + H]+ calcd, 234.1282; found, 234.1275.

1-(3-Phenylpropyl)isoquinoline (6n)

It was obtained as colorless oil; 22.7 mg, 46% yield; Rf = 0.33 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.44 (d, J = 5.7 Hz, 1H), 8.08–7.99 (m, 1H), 7.79 (s, 1H), 7.67–7.62 (m, 1H), 7.58–7.52 (m, 1H), 7.50 (d, J = 5.7 Hz, 1H), 7.32–7.14 (m, 5H), 3.36–3.29 (m, 2H), 2.81 (t, J = 7.7 Hz, 2H), 2.27–2.16 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 161.8, 142.0, 141.8, 136.2, 129.7, 128.5, 128.3, 127.3, 126.9, 126.9, 125.8, 125.2, 119.2, 35.9, 34.8, 31.0; HRMS (ESI): for C18H17N [M + H]+ calcd, 248.1439; found, 248.1435.

1-(But-3-en-1-yl)isoquinoline (6o)

It was obtained as colorless oil; 15.4 mg, 42% yield; Rf = 0.41 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.44 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.2 Hz, 1H), 7.71–7.64 (m, 1H), 7.62–7.57 (m, 1H), 7.51 (d, J = 5.7 Hz, 1H), 6.05–5.94 (m, 1H), 5.15–5.09 (m, 1H), 5.08–4.97 (m, 1H), 3.45–3.35 (m, 2H), 2.70–2.60 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 161.2, 141.8, 137.9, 136.2, 129.7, 127.4, 127.0, 126.9, 125.1, 119.2, 115.0, 34.6, 33.4; HRMS (ESI): for C13H13N [M + H]+ calcd, 184.1126; found, 184.1121.

1-(Pent-4-en-1-yl)isoquinoline (6p)

It was obtained as colorless oil; 24.4 mg, 62% yield; Rf = 0.20 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.44 (d, J = 5.8 Hz, 1H), 8.16 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.72–7.65 (m, 1H), 7.63–7.58 (m, 1H), 7.53 (d, J = 5.8 Hz, 1H), 5.95–5.84 (m, 1H), 5.11–4.97 (m, 2H), 3.37–3.28 (m, 2H), 2.25 (q, J = 7.2 Hz, 2H), 2.03–1.93 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 161.9, 141.8, 138.3, 136.2, 129.7, 127.3, 126.9, 126.9, 125.2, 119.1, 114.9, 34.7, 33.7, 28.7; HRMS (ESI): for C14H15N [M + H]+ calcd, 198.1282; found, 198.1276.

1-(Hept-6-en-1-yl)isoquinoline (6q)

It was obtained as colorless oil; 22.0 mg, 49% yield; Rf = 0.27 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.69–7.63 (m, 1H), 7.61–7.55 (m, 1H), 7.49 (d, J = 5.7 Hz, 1H), 5.87–5.76 (m, 1H), 5.02–4.96 (m, 1H), 4.95–4.90 (m, 1H), 3.33–3.25 (m, 2H), 2.07 (q, J = 6.3, 5.6 Hz, 2H), 1.88 (p, J = 7.6 Hz, 2H), 1.55–1.43 (m, 4H); 13C NMR (100 MHz, CDCl3): δ (ppm) 162.2, 141.8, 138.9, 136.2, 129.7, 127.3, 126.9, 126.8, 125.3, 114.2, 35.4, 33.6, 29.5, 29.3, 28.7; HRMS (ESI): for C16H19N [M + H]+ calcd, 226.1595; found, 226.1588.

Ethyl 5-(Isoquinolin-1-yl)pentanoate (6r)

It was obtained as colorless oil; 28.8 mg, 56% yield; Rf = 0.31 (PE/EA = 2:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.69–7.63 (m, 1H), 7.61–7.55 (m, 1H), 7.50 (d, J = 5.7 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.38–3.27 (m, 2H), 2.39 (t, J = 7.4 Hz, 2H), 1.99–1.87 (m, 2H), 1.92–1.83 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 173.5, 161.5, 141.8, 136.1, 129.7, 127.3, 126.9, 126.8, 125.1, 119.2, 77.3, 77.0, 76.6, 34.9, 34.1, 28.8, 25.0, 14.1; HRMS (ESI): for C16H19NO2 [M + H]+ calcd, 258.1494; found, 258.1491.

2-Cyclohexyl-4-methylquinoline (6s)

It was obtained as colorless oil; 34.6 mg, 77% yield; Rf = 0.45 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.05 (d, J = 8.4 Hz, 1H), 7.96–7.90 (m, 1H), 7.69–7.63 (m, 1H), 7.51–7.46 (m, 1H), 7.16 (s, 1H), 2.92–2.84 (m, 1H), 2.70–2.64 (m, 3H), 2.06–1.96 (m, 2H), 1.92–1.86 (m, 2H), 1.82–1.74 (m, 1H), 1.68–1.57 (m, 2H), 1.52–1.41 (m, 2H), 1.39–1.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 166.4, 147.5, 129.3, 128.9, 126.9, 125.3, 123.5, 120.1, 47.5, 32.7, 26.5, 26.0, 18.8; HRMS (ESI): for C16H19N [M + H]+ calcd, 226.1595; found, 226.1588.

4-Chloro-2-cyclohexylquinoline (6t)

It was obtained as colorless oil; 40.2 mg, 82% yield; Rf = 0.68 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.21–8.15 (m, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.75–7.70 (m, 1H), 7.59–7.54 (m, 1H), 7.42 (s, 1H), 2.93–2.85 (m, 1H), 2.08–1.96 (m, 2H), 2.05–1.87 (m, 2H), 1.84–1.74 (m, 1H), 1.67–1.55 (m, 2H), 1.52–1.40 (m, 2H), 1.38–1.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 166.7, 148.6, 142.5, 130.1, 129.2, 126.5, 125.1, 123.8, 119.7, 47.3, 32.6, 26.4, 25.9; HRMS (ESI): for C15H16ClN [M + H]+ calcd, 246.1049; found, 246.1043.

4-Cyclohexyl-2-methylquinoline (6u)

It was obtained as colorless oil; 24.7 mg, 55% yield; Rf = 0.32 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.03 (d, J = 8.5 Hz, 2H), 7.70–7.60 (m, 1H), 7.52–7.45 (m, 1H), 7.17 (s, 1H), 3.33–3.26 (m, 1H), 2.72 (s, 3H), 2.04–1.87 (m, 4H), 1.85–1.80 (m, 1H), 1.62–1.47 (m, 4H), 1.41–1.28 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 158.7, 153.2, 148.1, 129.5, 128.7, 125.2, 125.1, 122.8, 118.2, 38.7, 33.5, 26.9, 26.3, 25.5; HRMS (ESI): for C16H19N [M + H]+ calcd, 226.1595; found, 226.1590.

5-Bromo-1-cyclohexylisoquinoline (6v)

It was obtained as colorless oil; 27.7 mg, 48% yield; Rf = 0.65 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.58 (d, J = 5.9 Hz, 1H), 8.21 (d, J = 8.6 Hz, 1H), 7.96–7.91 (m, 1H), 7.86 (d, J = 5.9 Hz, 1H), 7.46–7.39 (m, 1H), 3.59–3.50 (m, 1H), 2.02–1.89 (m, 4H), 1.88–1.76 (m, 3H), 1.59–1.45 (m, 2H), 1.44–1.32 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 166.0, 143.2, 135.4, 133.3, 127.4, 127.0, 124.4, 122.5, 41.7, 32.6, 26.8, 26.1; HRMS (ESI): for C15H16BrN [M + H]+ calcd, 290.0544; found, 290.0543.

1-Cyclohexyl-6-methylisoquinoline (6w)

It was obtained as colorless oil; 32.0 mg, 71% yield; Rf = 0.47 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.43 (d, J = 5.7 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 7.57 (s, 1H), 7.43–7.36 (m, 2H), 3.56–3.48 (m, 1H), 2.53 (s, 3H), 2.02–1.89 (m, 4H), 1.88–1.73 (m, 3H), 1.62–1.46 (m, 2H), 1.44–1.35 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 165.3, 141.8, 139.7, 136.6, 129.0, 126.4, 124.5, 124.5, 118.4, 41.4, 32.5, 26.8, 26.2, 21.7; HRMS (ESI): for C16H19N [M + H]+ calcd, 226.1595; found, 226.1588.

2-Cyclohexylquinoxaline (6x)

It was obtained as colorless oil; 29.9 mg, 71% yield; Rf = 0.37 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.77 (s, 1H), 8.09–8.02 (m, 2H), 7.77–7.66 (m, 2H), 3.03–2.91 (m, 1H), 2.10–2.00 (m, 2H), 1.96–1.90 (m, 2H), 1.84–1.78 (m, 1H), 1.77–1.66 (m, 2H), 1.54–1.42 (m, 2H), 1.42–1.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 161.1, 144.9, 142.1, 141.3, 129.7, 129.0, 128.9, 128.8, 45.0, 32.3, 26.3, 25.8; HRMS (ESI): for C14H16N2 [M + H]+ calcd, 213.1391; found, 213.1386.

2-Chloro-3-cyclohexylquinoxaline (6y)

It was obtained as a white solid; 20.2 mg, 41% yield; Rf = 0.74 (PE/EA = 10:1); mp 94–96 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.08–8.02 (m, 1H), 8.00–7.94 (m, 1H), 7.76–7.67 (m, 2H), 3.39–3.30 (m, 1H), 2.03 (d, J = 12.4 Hz, 2H), 1.96–1.90 (m, 2H), 1.86–1.77 (m, 1H), 1.77–1.65 (m, 2H), 1.55–1.43 (m, 2H), 1.42–1.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 159.1, 147.4, 141.1, 140.5, 129.8, 128.7, 128.0, 42.5, 31.2, 26.3, 25.9; HRMS (ESI): for C14H15ClN2 [M + H]+ calcd, 247.1002; found, 247.1002.

2-Cyclohexylbenzo[d]thiazole (6z)

It was obtained as colorless oil; 23.4 mg, 54% yield; Rf = 0.59 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 7.97 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.47–7.40 (m, 1H), 7.38–7.29 (m, 1H), 3.15–3.07 (m, 1H), 2.25–2.17 (m, 2H), 1.92–1.86 (m, 2H), 1.82–1.72 (m, 1H), 1.69–1.61 (m, 2H), 1.51–1.39 (m, 2H), 1.38–1.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 177.6, 153.0, 134.5, 125.7, 124.4, 122.5, 121.5, 43.4, 33.4, 26.0, 25.7; HRMS (ESI): for C13H15NS [M + H]+ calcd, 218.1003; found, 218.0998.

5-Cyclohexyl-2,3-diphenylpyrido[3,4-b]pyrazine (6aa)

It was obtained as a white solid; 60.5 mg, 83% yield; Rf = 0.25 (PE/EA = 10:1); mp 142–144 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.74 (d, J = 5.8 Hz, 1H), 7.80 (d, J = 5.8 Hz, 1H), 7.60–7.51 (m, 4H), 7.43–7.32 (m, 6H), 4.30–4.21 (m, 1H), 2.02 (d, J = 13.2 Hz, 2H), 1.97–1.77 (m, 5H), 1.63–1.52 (m, 2H), 1.46–1.34 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 169.4, 156.9, 153.1, 146.3, 143.4, 138.6, 134.0, 129.9, 129.7, 129.3, 128.3, 128.2, 119.2, 39.7, 32.3, 26.6, 26.2; HRMS (ESI): for C25H23N3 [M + H]+ calcd, 366.1970; found, 366.1964.

6-Chloro-7-cyclohexylimidazo[1,2-b]pyridazine (6ab)

It was obtained as colorless oil; 28.2 mg, 60% yield; Rf = 0.44 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 7.89 (d, J = 1.1 Hz, 1H), 7.72 (d, J = 1.1 Hz, 1H), 6.86 (s, 1H), 3.40–3.32 (m, 1H), 2.15–2.02 (m, 2H), 1.90 (dd, J = 9.5, 3.1 Hz, 2H), 1.86–1.77 (m, 1H), 1.61–1.44 (m, 4H), 1.37–1.27 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 148.0, 147.3, 137.9, 133.1, 117.1, 114.5, 38.7, 32.0, 26.2, 25.9; HRMS (ESI): for C12H14ClN3 [M + H]+ calcd, 236.0954; found, 236.0953.

2-Cyclohexylisonicotinonitrile (6ac)

It was obtained as colorless oil; 12.6 mg, 34% yield; Rf = 0.65 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.70 (s, 1H), 7.39 (s, 1H), 7.35–7.33 (m, 1H), 2.81–2.73 (m, 1H), 2.02–1.92 (m, 2H), 1.91–1.85 (m, 2H), 1.81–1.73 (m, 1H), 1.60–1.48 (m, 2H), 1.48–1.36 (m, 2H), 1.34–1.22 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 167.9, 149.9, 122.7, 122.2, 120.4, 116.7, 46.2, 32.4, 26.1, 25.7; HRMS (ESI): for C12H14N2 [M + H]+ calcd, 187.1235; found, 187.1230.

4-Cyclohexylquinazoline (6ad)

It was obtained as colorless oil; 29.9 mg, 46% yield; Rf = 0.41 (PE/EA = 4:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 9.25 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.94–7.81 (m, 1H), 7.73–7.56 (m, 1H), 3.60–3.52 (m, 1H), 2.02–1.92 (m, 4H), 1.88–1.76 (m, 3H), 1.59–1.45 (m, 2H), 1.45–1.33 (m, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 175.0, 154.7, 150.0, 133.2, 129.3, 127.2, 124.1, 123.2, 41.2, 32.0, 26.4, 25.9; HRMS (ESI): for C14H16N2 [M + H]+ calcd, 213.1391; found, 213.1388.

2,4-Dicyclohexylquinazoline (6ad′)

It was obtained as colorless oil; 29.9 mg, 20% yield; Rf = 0.57 (PE/EA = 10:1); 1H NMR (400 MHz, CDCl3): δ (ppm) 8.11 (d, J = 7.9 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.81–7.75 (m, 1H), 7.54–7.49 (m, 1H), 3.54–3.46 (m, 1H), 3.02–2.94 (m, 1H), 2.10–2.01 (m, 2H), 1.98–1.72 (m, 12H), 1.58–1.32 (m, 6H); 13C NMR (100 MHz, CDCl3): δ (ppm) 174.4, 170.1, 150.5, 128.8, 125.9, 123.9, 121.3, 47.9, 41.3, 31.9, 31.9, 29.6, 26.5, 26.3, 26.1, 26.0; HRMS (ESI): for C20H26N2 [M + H]+ calcd, 295.2174; found, 295.2169.